WorldWideScience

Sample records for internally mediated developmental

  1. International adoption: a health and developmental prospective.

    Science.gov (United States)

    Mason, Patrick; Narad, Christine

    2005-02-01

    Adoptions from international countries have become an option for many US families, with over 150,000 children adopted in the past 14 years. Typically, internationally adopted children present with a host of medical and developmental concerns. Issues such as growth stunting, abnormal behaviors, and significant delays in motor, speech, and language development are likely directly related to the prenatal and early postnatal environment experienced prior to adoption. The new family and its health-care team must quickly work to identify and address these issues to aid the child's integration into his or her new family. This article will examine potential issues seen in children who are being adopted, including the impact of early environment on subsequent development. We will summarize early and long-term medical issues and review the extent of developmental delays seen in children adopted internationally. Finally, we will discuss possible mechanisms leading to the observed delays, including the impact of stress on subsequent development. By understanding the extent of expected delays and the mechanisms likely causing the issues, the health-care team will be in a good position to quickly identify and develop intervention protocols that will foster the child's assimilation into his or her new family.

  2. 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.

  3. The law applicable to International Mediation Contracts

    OpenAIRE

    Orejudo Prieto de los Mozos, Patricia

    2011-01-01

    Mediation entails the provision of the services of a professional, the mediator, who holds a legal relationship with the disputants: the mediation contract. Where there are transnational elements in the mediation process, the contract is of an international character. In such situation, the Laws of the diverse States involved could claim to be applicable to the same contract. The determination of the (only) Law applicable is of upmost interest in spite of the high degree of standardization of...

  4. Socioeconomic status and executive function: developmental trajectories and mediation.

    Science.gov (United States)

    Hackman, Daniel A; Gallop, Robert; Evans, Gary W; Farah, Martha J

    2015-09-01

    Childhood socioeconomic status (SES) predicts executive function (EF), but fundamental aspects of this relation remain unknown: the developmental course of the SES disparity, its continued sensitivity to SES changes during that course, and the features of childhood experience responsible for the SES-EF relation. Regarding course, early disparities would be expected to grow during development if caused by accumulating stressors at a given constant level of SES. Alternatively, they would narrow if schooling partly compensates for the effects of earlier deprivation, allowing lower-SES children to 'catch up'. The potential for later childhood SES change to affect EF is also unknown. Regarding mediating factors, previous analyses produced mixed answers, possibly due to correlation amongst candidate mediators. We address these issues with measures of SES, working memory and planning, along with multiple candidate mediators, from the NICHD Study of Early Childcare (n = 1009). Early family income-to-needs and maternal education predicted planning by first grade, and income-to-needs predicted working memory performance at 54 months. Effects of early SES remained consistent through middle childhood, indicating that the relation between early indicators of SES and EF emerges in childhood and persists without narrowing or widening across early and middle childhood. Changes in family income-to-needs were associated with significant changes in planning and trend-level changes in working memory. Mediation analyses supported the role of early childhood home characteristics in explaining the association between SES and EF, while early childhood maternal sensitivity was specifically implicated in the association between maternal education and planning. Early emerging and persistent SES-related differences in EF, partially explained by characteristics of the home and family environment, are thus a potential source of socioeconomic disparities in achievement and health across

  5. 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

  6. 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.

  7. 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.

  8. A Developmental Sequence Model to University Adjustment of International Undergraduate Students

    OpenAIRE

    Chavoshi, Saeid; Wintre, Maxine Gallander; Dentakos, Stella; Wright, Lorna

    2017-01-01

    The current study proposes a Developmental Sequence Model to University Adjustment and uses a multifaceted measure, including academic, social and psychological adjustment, to examine factors predictive of undergraduate international student adjustment. A hierarchic regression model is carried out on the Student Adaptation to College Questionnaire to examine theoretically pertinent predictors arranged in a developmental sequence in determining adjustment outcomes. This model...

  9. Demystifying internalization and socialization: linking conceptions of how development happens to organismic-developmental theory.

    Science.gov (United States)

    Raeff, Catherine

    2014-01-01

    Internalization and socialization are central constructs in developmental psychology for explaining and investigating how development happens through social interaction. There has been and continues to be much debate about how to conceptualize and investigate these processes. The ways in which internalization and socialization promote development have also been difficult to identify. The goal of this chapter is to offer a way of clarifying what happens during internalization and socialization by linking them to a clear conceptualization of development. The chapter first provides an overview of internalization and socialization theory and research. This review indicates that the focus on how development happens through social interaction has taken attention away from specifying the developmental changes that occur through social interaction. It is argued that understanding internalization and socialization can be enhanced by linking them to a clear definition of development, such as the one provided by organismic-developmental theory. According to organismic-developmental theory, developmental change is distinguished from any change that may occur over time. Rather, development is defined in terms of the differentiation and integration of action components in relation to cultural values and expectations for development. After explicating organismic-developmental theory's key claims, some implications of utilizing it for advancing an understanding of internalization and socialization are discussed. The chapter ends with suggestions for future research on internalization, socialization, and development.

  10. 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…

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

    African Journals Online (AJOL)

    Angela

    UN). In this article, we argue that regional organisations have certain charac- teristics that in ... increasingly important role of regional mediation initiatives is described. The empirical part first ..... Terrorism 22 (1): 53-77. Obiozor, George A. et al.

  12. 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

    The ecdysone 20-monooxygenase (E20MO; 20-hydroxylase) is the enzyme that mediates the conversion of ecdysone (E) to the active insect molting hormone, 20-hydroxyecdysone (20E), which coordinates developmental progression. We report the identification and developmental expression of the Halloween...

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

    African Journals Online (AJOL)

    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 to study the advantages and disadvantages of mediation efforts by regionalorganisations, and ...

  14. Internal conversion mediated by specific nuclear motions

    DEFF Research Database (Denmark)

    Klein, Liv Bærenholdt; Sølling, Theis Ivan

    2014-01-01

    To investigate the influence of amine structure on the internal conversion from S2 to S1, three aliphatic amines containing the same number of degrees of freedom, but with different degree of N-substitution, were investigated with femtosecond time-resolved mass spectrometry. As N-substituents low...

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

    OpenAIRE

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

    2017-01-01

    Background: 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. Aim and Objectives: To develop a module for interns in medical ethics (MIME) in patient care, validate it and pilot run the module for standardization. Meth...

  16. 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.

  17. Long-term developmental, behavioral, and attachment outcomes after international adoption.

    Science.gov (United States)

    Weitzman, Carol; Albers, Lisa

    2005-10-01

    Children adopted internationally and their families are a heterogeneous group. Internationally-adopted children have been reported to have a range of developmental and behavioral difficulties. The authors describe the current evidence documenting developmental outcomes for children and common behavioral and mental health concerns including attachment difficulties that may impact children and their families after international adoption. Pediatricians must be thoughtful to individualize the care of adoptive children and not make assumptions shortly after adoption. It is critical to avoid using "standard" parenting advice that may not apply to children who have experienced loss, deprivation, separation, and instability in their early lives. By listening to families, carefully evaluating children, and monitoring progress over time, pediatricians can avoid the pitfall of oversimplifying and underestimating the complexity and challenges that these families face. Instead, pediatric primary care providers can play a key role in maximizing the potential of an internationally adopted child and his or her family.

  18. A Developmental Sequence Model to University Adjustment of International Undergraduate Students

    Science.gov (United States)

    Chavoshi, Saeid; Wintre, Maxine Gallander; Dentakos, Stella; Wright, Lorna

    2017-01-01

    The current study proposes a Developmental Sequence Model to University Adjustment and uses a multifaceted measure, including academic, social and psychological adjustment, to examine factors predictive of undergraduate international student adjustment. A hierarchic regression model is carried out on the Student Adaptation to College Questionnaire…

  19. Comparison of molecular mechanisms mediating cell contact phenomena in model developmental systems: an exploration of universality.

    Science.gov (United States)

    Bowers-Morrow, Vivienne M; Ali, Sinan O; Williams, Keith L

    2004-08-01

    Are there universal molecular mechanisms associated with cell contact phenomena during metazoan ontogenesis? Comparison of adhesion systems in disparate model systems indicates the existence of unifying principles. Requirements for multicellularity are (a) the construction of three-dimensional structures involving a crucial balance between adhesiveness and motility; and (b) the establishment of integration at molecular, cellular, tissue, and organismal levels of organization. Mechanisms for (i) cell-cell and cell-substrate adhesion, (ii) cell movement, (iii) cell-cell communication, (iv) cellular responses, (v) regulation of these processes, and (vi) their integration with patterning, growth, and other developmental processes are all crucial to metazoan development, and must have been present for the emergence and radiation of Metazoa. The principal unifying themes of this review are the dynamics and regulation of cell contact phenomena. Our knowledge of the dynamic molecular mechanisms underlying cell contact phenomena remains fragmentary. Here we examine the molecular bases of cell contact phenomena using extant model developmental systems (representing a wide range of phyla) including the simplest i.e. sponges, and the eukaryotic protist Dictyostelium discoideum, the more complex Drosophila melanogaster, and vertebrate systems. We discuss cell contact phenomena in a broad developmental context. The molecular language of cell contact phenomena is complex; it involves a plethora of structurally and functionally diverse molecules, and diverse modes of intermolecular interactions mediated by protein and/or carbohydrate moieties. Reasons for this are presumably the necessity for a high degree of specificity of intermolecular interactions, the requirement for a multitude of different signals, and the apparent requirement for an increasingly large repertoire of cell contact molecules in more complex developmental systems, such as the developing vertebrate nervous

  20. Transposable Element-Mediated Balancing Selection at Hsp90 Underlies Embryo Developmental Variation.

    Science.gov (United States)

    Chen, Bing; Zhang, Bo; Xu, Lingling; Li, Qing; Jiang, Feng; Yang, Pengcheng; Xu, Yanan; Kang, Le

    2017-05-01

    Understanding the roles of transposable elements (TEs) in the evolution of genome and adaptation is a long-sought goal. Here, we present a new model of TE co-option, in which a TE is harnessed by an essential gene and confers local adaptation through heterozygote advantage. We characterized a human Alu-like TE family, the Lm1 elements, in the genome of the migratory locust Locusta migratoria that harbors 0.7 million copies of the elements. Scanning Lm1 insertions in the natural locust populations revealed the widespread high polymorphism of Lm1. An Lm1 was recruited into the coding region of Heat-shock protein 90 (Hsp90), an important molecular chaperone for diverse signal transduction and developmental pathways. Only heterozygotes of the allele are present in natural populations. Allele frequency increases with decreased latitudes in east coastal China, even increasing up to 76% in southern populations. Regions flanking the Lm1 insertion display clear signatures of a selective sweep linked to Lm1. The Lm1-mediated Hsp90 mutation is consequential for the embryonic development of locust. Heterozygous embryos develop faster than the wild type, particularly when cued by long-day parental photoperiod. The heterozygotes also present a reduced within-population variation in embryonic development, i.e., high developmental synchrony of embryos. The naturally occurring Hsp90 mutation could facilitate multivoltinism and developmental synchronization of the locust in southern tropical region. These results revealed a genetic mechanism behind microevolutionary changes in which balancing selection may have acted to maintain the heterozygote advantage through TE co-option in essential genes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Language and Internalizing and Externalizing Behavioral Adjustment: Developmental Pathways from Childhood to Adolescence

    Science.gov (United States)

    Bornstein, Marc H.; Hahn, Chun-Shin; Suwalsky, Joan T. D.

    2014-01-01

    Two independent prospective longitudinal studies that cumulatively spanned the age interval from 4 years to 14 years used multi-wave designs to investigate developmental associations between language and behavioral adjustment (internalizing and externalizing behavior problems). Altogether 224 children, their mothers, and teachers provided data. Series of nested path analysis models were used to determine the most parsimonious and plausible paths among the three constructs over and above stability in each across age and their covariation at each age. In both studies, children with poorer language skills in early childhood had more internalizing behavior problems in later childhood and in early adolescence. These developmental paths between language and behavioral adjustment held after taking into consideration children’s nonverbal intellectual functioning, maternal verbal intelligence, education, parenting knowledge, and social desirability bias, as well as family socioeconomic status, and they applied equally to girls and boys. PMID:23880396

  2. 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…

  3. 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.

  4. 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.

  5. 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...

  6. Exploiting CD38-mediated endocytosis for immunoliposome internalization.

    Science.gov (United States)

    Orciani, Monia; Cavaletti, Guido; Fino, Vincenzo; Mattioli-Belmonte, Monica; Tredici, Giovanni; Bruni, Paolo; Di Primio, Roberto

    2008-07-01

    CD38 appears to be a promising candidate in antibody therapy; it is upregulated on cell surfaces in many lymphoid tumors and undergoes rapid internalization after interaction with antibodies. The receptor-mediated endocytosis allows conjugating toxins/drugs that promote suicide only of the malignant cells. Here, we describe the preparation of CD38-immunoliposomes and test their functionality by incubating them with CD38+/- cells. Liposomes were prepared by extrusion of a lipid mixture containing a biotinylated polyethylene glycol-phospholipid and loaded with 5(6)-carboxyfluorescein. The anti-CD38 antibody (IB4) was biotinylated and then linked to streptavidin molecules; streptavidin acts like a bridge between the antibody and the biotinylated lipid of the liposomes. CD38+/- cells were incubated either with liposomes or immunoliposomes and analyzed by fluorescence microscopy and cytofluorimetry. The results indicated a specific mechanism of internalization, owing to CD38-mediated endocytosis, where CD38+ cells incubated with immunoliposomes scored top fluorescence levels. This coupling strategy, based on the use of a streptavidin bridge to prepare immunoliposomes, does not interfere with the cellular functionality and its broad potential use represents a great advantage. Here IB4, a murine monoclonal anti-CD38 antibody, was used to simplify the experiments, but the coupling procedure may be suitable also with human antibodies, against CD38 or other human markers.

  7. 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.

  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. 20-Hydroxyecdysone (20E) Primary Response Gene E75 Isoforms Mediate Steroidogenesis Autoregulation and Regulate Developmental Timing in Bombyx*

    Science.gov (United States)

    Li, Kang; Tian, Ling; Guo, Zhongjian; Guo, Sanyou; Zhang, Jianzhen; Gu, Shi-Hong; Palli, Subba R.; Cao, Yang; Li, Sheng

    2016-01-01

    The temporal control mechanisms that precisely control animal development remain largely elusive. The timing of major developmental transitions in insects, including molting and metamorphosis, is coordinated by the steroid hormone 20-hydroxyecdysone (20E). 20E involves feedback loops to maintain pulses of ecdysteroid biosynthesis leading to its upsurge, whereas the underpinning molecular mechanisms are not well understood. Using the silkworm Bombyx mori as a model, we demonstrated that E75, the 20E primary response gene, mediates a regulatory loop between ecdysteroid biosynthesis and 20E signaling. E75 isoforms A and C directly bind to retinoic acid receptor-related response elements in Halloween gene promoter regions to induce gene expression thus promoting ecdysteroid biosynthesis and developmental transition, whereas isoform B antagonizes the transcriptional activity of isoform A/C through physical interaction. As the expression of E75 isoforms is differentially induced by 20E, the E75-mediated regulatory loop represents a fine autoregulation of steroidogenesis, which contributes to the precise control of developmental timing. PMID:27365399

  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. 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...

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

    DEFF Research Database (Denmark)

    Bal-Price, Anna; Crofton, Kevin M.; Leist, Marcel

    2015-01-01

    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...

  13. The Pedagogical Mediation of a Developmental Learner Corpus for Classroom-Based Language Instruction

    Directory of Open Access Journals (Sweden)

    Julie A. Belz

    2008-10-01

    Full Text Available Although corpora have been used in language teaching for some time, few empirical studies explore their impact on learning outcomes. We provide a microgenetic account of learners’ responses to corpus-driven instructional units for German modal particles and pronominal da-compounds. The units are based on developmental corpus data produced by native speakers during interactions with the very learners for whom the units are designed. Thus, we address the issue of authentication in corpus-driven language pedagogy. Finally, we illustrate how an ethnographically supplemented developmental learner corpus may contribute to second language acquisition research via dense documentation of micro-changes in learners’ language use over time.

  14. 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...

  15. 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…

  16. 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…

  17. Developmental Origins of Infant Emotion Regulation: Mediation by Temperamental Negativity and Moderation by Maternal Sensitivity

    Science.gov (United States)

    Thomas, Jenna C.; Letourneau, Nicole; Campbell, Tavis S.; Tomfohr-Madsen, Lianne; Giesbrecht, Gerald F.

    2017-01-01

    Emotion regulation is essential to cognitive, social, and emotional development and difficulties with emotion regulation portend future socioemotional, academic, and behavioral difficulties. There is growing awareness that many developmental outcomes previously thought to begin their development in the postnatal period have their origins in the…

  18. 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

  19. 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.

  20. Neonatal developmental care in infant pain management and internalizing behaviours at 18 months in prematurely born children.

    Science.gov (United States)

    Montirosso, R; Casini, E; Del Prete, A; Zanini, R; Bellù, R; Borgatti, R

    2016-07-01

    Very preterm infants are exposed to adverse stressful experiences, which may result in long-term behavioural outcomes. The developmental care practices, including pain management and environmental support, can minimize the effects of stress exposure. However, developmental care quality levels may vary among Neonatal Intensive Care Units (NICUs) and little is known about how differences in developmental care quality affect long-term behavioural outcomes. The aim of this study was to examine the relation between quality levels NICUs developmental care and behaviour problems at 18 months corrected age in preterm children. The behaviour of 134 preterm children from 22 NICUs and 123 full-term controls was examined using the questionnaire Child Behaviour Checklist 1½-5. We compared the behavioural profile of children by splitting NICUs into units with high- and low quality of developmental care according to two main care factors: (1) infant centered care (ICC) index, and (2) infant pain management (IPM) index. Preterm children from low-care units in IPM group reported higher scores in Internalizing Problems, compared to children from high-care units. No differences were found between preterm children from high-care in IPM and full-term children. No significant IPM effect was found for externalizing problems. No significant ICC effect emerged both for internalizing and externalizing problems. Findings suggest that higher quality of developmental care related to infant pain management can mitigate behavioural problems at 18 months in children born preterm, to such an extent that preterm children exhibit a behavioural profile similar to that displayed by full-term children. © 2016 European Pain Federation - EFIC®

  1. Internalizing Symptoms and Safe Sex Intentions among Adolescents in Mental Health Treatment: Personal Factors as Mediators

    OpenAIRE

    Joppa, Meredith C.; Rizzo, Christie J.; Brown, Larry K.; Hadley, Wendy; Dattadeen, Jodi-Ann; Donenberg, Geri; DiClemente, Ralph

    2014-01-01

    Little is known about why some adolescents with internalizing symptoms engage in sexual behaviors that increase their risk for HIV. This study tested a mediation model of internalizing symptoms and safe sex intentions among adolescents receiving mental health treatment. Self-efficacy for HIV prevention, HIV knowledge, and worry about HIV were hypothesized to mediate associations between internalizing symptoms and safe sex intentions among sexually active and non-active adolescents receiving m...

  2. 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.

  3. Internalizing Symptoms and Safe Sex Intentions among Adolescents in Mental Health Treatment: Personal Factors as Mediators.

    Science.gov (United States)

    Joppa, Meredith C; Rizzo, Christie J; Brown, Larry K; Hadley, Wendy; Dattadeen, Jodi-Ann; Donenberg, Geri; DiClemente, Ralph

    2014-11-01

    Little is known about why some adolescents with internalizing symptoms engage in sexual behaviors that increase their risk for HIV. This study tested a mediation model of internalizing symptoms and safe sex intentions among adolescents receiving mental health treatment. Self-efficacy for HIV prevention, HIV knowledge, and worry about HIV were hypothesized to mediate associations between internalizing symptoms and safe sex intentions among sexually active and non-active adolescents receiving mental health treatment ( N = 893, M age = 14.9). Significant indirect effects from internalizing symptoms to safe sex intentions varied according sexual experience: for sexually non-active adolescents, HIV worry and knowledge mediated this link, whereas for sexually active adolescents, HIV self-efficacy was the significant mediator. Increasing both HIV knowledge and self-efficacy for HIV prevention are important targets for HIV prevention with adolescents with internalizing symptoms, and careful attention should be paid towards targeting these interventions to sexually experienced and inexperienced youth.

  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. Serotonin Mediates Maternal Effects and Directs Developmental and Behavioral Changes in the Progeny of Snails.

    Science.gov (United States)

    Ivashkin, Evgeny; Khabarova, Marina Yu; Melnikova, Victoria; Nezlin, Leonid P; Kharchenko, Olga; Voronezhskaya, Elena E; Adameyko, Igor

    2015-08-18

    Many organisms survive in constantly changing environments, including cycling seasons. Developing embryos show remarkable instant adaptations to the variable environmental challenges they encounter during their adult life, despite having no direct contact with the changing environment until after birth or hatching. The mechanisms by which such non-genetic information is transferred to the developing embryos are largely unknown. Here, we address this question by using a freshwater pond snail (Lymnaea stagnalis) as a model system. This snail normally lives in a seasonal climate, and the seasons define its locomotion, feeding, and reproductive behavior. We discovered that the serotonergic system plays a crucial role in transmitting a non-genetic instructive signal from mother to progeny. This maternal serotonin-based signal functions in embryos during a short time window at exclusively early pre-neural developmental stages and modulates the dynamics of embryonic and juvenile growth, feeding behavior, and locomotion. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Serotonin Mediates Maternal Effects and Directs Developmental and Behavioral Changes in the Progeny of Snails

    Directory of Open Access Journals (Sweden)

    Evgeny Ivashkin

    2015-08-01

    Full Text Available Many organisms survive in constantly changing environments, including cycling seasons. Developing embryos show remarkable instant adaptations to the variable environmental challenges they encounter during their adult life, despite having no direct contact with the changing environment until after birth or hatching. The mechanisms by which such non-genetic information is transferred to the developing embryos are largely unknown. Here, we address this question by using a freshwater pond snail (Lymnaea stagnalis as a model system. This snail normally lives in a seasonal climate, and the seasons define its locomotion, feeding, and reproductive behavior. We discovered that the serotonergic system plays a crucial role in transmitting a non-genetic instructive signal from mother to progeny. This maternal serotonin-based signal functions in embryos during a short time window at exclusively early pre-neural developmental stages and modulates the dynamics of embryonic and juvenile growth, feeding behavior, and locomotion.

  7. The International society for developmental psychobiology 39th annual meeting symposium: Alcohol and development: beyond fetal alcohol syndrome.

    Science.gov (United States)

    Molina, Juan Carlos; Spear, Norman E; Spear, Linda P; Mennella, Julie A; Lewis, Michael J

    2007-04-01

    As has been repeatedly demonstrated, alcohol can exert deleterious morphological and physiological effects during early stages in development. The present review examines nonteratological links existing between alcohol and ontogeny. Human and animal studies are taken into consideration for the analysis of fetal, neonatal, infantile, adolescent, and adult responsiveness to the drug. Sensitivity to alcohol's chemosensory and postabsorptive properties, as well as learning and memory processes mediated by such properties, are examined from this developmental perspective. The studies under discussion indicate that, within each stage in development, we can trace alcohol-related experiences capable of determining or modulating alcohol seeking and intake patterns. (c) 2007 Wiley Periodicals, Inc.

  8. 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.

  9. The Association between Attention Problems and Internalizing and Externalizing Problems: The Mediating Role of Peer Problems

    Science.gov (United States)

    Yip, Vania T.; Ang, Rebecca P.; Ooi, Yoon Phaik; Fung, Daniel S. S.; Mehrotra, Kala; Sung, Min; Lim, Choon Guan

    2013-01-01

    Background: The high prevalence of attention problems in children warrants concern, as it is a risk factor for internalizing and externalizing problems. There lies a need to understand possible factors that may mediate this link so that interventions may be targeted to alleviate these mediators and interrupt the link between attention problems and…

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

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan

    2005-01-01

    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...... to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of (125)I-labeled folate binding protein (FBP) to sections of kidney proximal tubule, known...

  11. Mediating Transnational Spaces: International Students and Intercultural Responsibility

    Science.gov (United States)

    Tran, Ly Thi; Vu, Thao Thi Phuong

    2017-01-01

    Despite the significant body of literature on international students' intercultural development, the core issue of how they see their own responsibility in transnational intercultural spaces is largely neglected. This paper addresses this paucity by examining the intercultural responsibility perceived by international students. It is based on a…

  12. 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

  13. Maternal depressive symptoms, maternal behavior, and toddler internalizing outcomes: a moderated mediation model.

    Science.gov (United States)

    Hummel, Alexandra C; Kiel, Elizabeth J

    2015-02-01

    Maternal depression relates to child internalizing outcomes, but one missing aspect of this association is how variation in depressive symptoms, including mild and moderate symptoms, relates to young children's outcomes. The current study examined a moderated mediation model to investigate how maternal behaviors may mediate this association in the context of child temperament and gender. Mothers and toddlers completed a free-play/clean-up task in the laboratory. Mothers rated their depressive symptoms and their toddlers' temperament and internalizing behaviors. Results indicated a significant indirect effect of maternal warmth on the relation between maternal depressive symptoms and toddler internalizing outcomes for boys with low negative emotionality. Toddler gender and temperament moderated the relation between maternal intrusiveness and toddler internalizing outcomes, but mediation was not supported. Results highlight the important interaction between child and maternal variables in predicting child outcomes, and suggest mechanisms by and conditions under which mild maternal depressive symptomatology can be a risk factor for toddler internalizing outcomes.

  14. Asymmetric developmental potential along the animal-vegetal axis in the anthozoan cnidarian, Nematostella vectensis, is mediated by Dishevelled.

    Science.gov (United States)

    Lee, Patricia N; Kumburegama, Shalika; Marlow, Heather Q; Martindale, Mark Q; Wikramanayake, Athula H

    2007-10-01

    The relationship between egg polarity and the adult body plan is well understood in many bilaterians. However, the evolutionary origins of embryonic polarity are not known. Insight into the evolution of polarity will come from understanding the ontogeny of polarity in non-bilaterian forms, such as cnidarians. We examined how the axial properties of the starlet sea anemone, Nematostella vectensis (Anthozoa, Cnidaria), are established during embryogenesis. Egg-cutting experiments and sperm localization show that Nematostella eggs are only fertilized at the animal pole. Vital marking experiments demonstrate that the egg animal pole corresponds to the sites of first cleavage and gastrulation, and the oral pole of the adult. Embryo separation experiments demonstrate an asymmetric segregation of developmental potential along the animal-vegetal axis prior to the 8-cell stage. We demonstrate that Dishevelled (Dsh) plays an important role in mediating this asymmetric segregation of developmental fate. Although NvDsh mRNA is ubiquitously expressed during embryogenesis, the protein is associated with the female pronucleus at the animal pole in the unfertilized egg, becomes associated with the unipolar first cleavage furrow, and remains enriched in animal pole blastomeres. Our results suggest that at least one mechanism for Dsh enrichment at the animal pole is through its degradation at the vegetal pole. Functional studies reveal that NvDsh is required for specifying embryonic polarity and endoderm by stabilizing beta-catenin in the canonical Wnt signaling pathway. The localization of Dsh to the animal pole in Nematostella and two other anthozoan cnidarians (scleractinian corals) provides a possible explanation for how the site of gastrulation has changed in bilaterian evolution while other axial components of development have remained the same and demonstrates that modifications of the Wnt signaling pathway have been used to pattern a wide variety of metazoan embryos.

  15. GRIN2B mediates susceptibility to intelligence quotient and cognitive impairments in developmental dyslexia.

    Science.gov (United States)

    Mascheretti, Sara; Facoetti, Andrea; Giorda, Roberto; Beri, Silvana; Riva, Valentina; Trezzi, Vittoria; Cellino, Maria R; Marino, Cecilia

    2015-02-01

    Developmental dyslexia (DD) is a complex heritable condition associated with impairments in multiple neurocognitive domains. Substantial heritability has been reported for DD and related phenotypes, and candidate genes have been identified. Recently, a candidate gene for human cognitive processes, that is, GRIN2B, has been found to be associated significantly with working memory in a German DD sample. In this study, we explored the contribution of six GRIN2B markers to DD and key DD-related phenotypes by association analyses in a sample of Italian nuclear families. Moreover, we assessed potential gene-by-environment interactions on DD-related phenotypes. We carried out a family-based association study to determine whether the GRIN2B gene influences both DD as a categorical trait and its related cognitive traits in a large cohort of 466 Italian nuclear families ascertained through a proband affected by DD. Moreover, we tested the role of the selected GRIN2B markers and a set of commonly described environmental moderators using a test for G×E interaction in sib pair-based association analysis of quantitative traits in 178 Italian nuclear families. Evidence for a significant association was found with the categorical diagnosis of DD, performance intelligence quotient, phonemic elision, and auditory short-term memory. No significant gene-by-environment effects were found. Our results add further evidence in support of GRIN2B contributing toward DD and deficits in DD. More specifically, our data support the view that GRIN2B influences DD as a categorical trait and its related quantitative phenotypes, thus shedding further light on the etiologic basis and the phenotypic complexity of this disorder.

  16. 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

    2018-01-18

    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.

  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. 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.

  20. 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

  1. 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.

  2. Developmental plasticity

    Science.gov (United States)

    Lea, Amanda J; Tung, Jenny; Archie, Elizabeth A; Alberts, Susan C

    2017-01-01

    Abstract Early life experiences can have profound and persistent effects on traits expressed throughout the life course, with consequences for later life behavior, disease risk, and mortality rates. The shaping of later life traits by early life environments, known as ‘developmental plasticity’, has been well-documented in humans and non-human animals, and has consequently captured the attention of both evolutionary biologists and researchers studying human health. Importantly, the parallel significance of developmental plasticity across multiple fields presents a timely opportunity to build a comprehensive understanding of this phenomenon. We aim to facilitate this goal by highlighting key outstanding questions shared by both evolutionary and health researchers, and by identifying theory and empirical work from both research traditions that is designed to address these questions. Specifically, we focus on: (i) evolutionary explanations for developmental plasticity, (ii) the genetics of developmental plasticity and (iii) the molecular mechanisms that mediate developmental plasticity. In each section, we emphasize the conceptual gains in human health and evolutionary biology that would follow from filling current knowledge gaps using interdisciplinary approaches. We encourage researchers interested in developmental plasticity to evaluate their own work in light of research from diverse fields, with the ultimate goal of establishing a cross-disciplinary understanding of developmental plasticity. PMID:29424834

  3. 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...

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

    Science.gov (United States)

    2016-06-01

    armed groups in Northern Ireland had decommissioned their arms.230 While the intractable and deeply-rooted political conflict in Northern Ireland still...As a conflict management strategy, mediation has offered a way to abate or resolve conflicts , and it is a solid alternative to escalating hostilities...terrorism conflicts , this thesis explores the styles of international mediation that have been employed in peace processes between states and terrorist

  5. Global society and society in mediatization: a theoretical framework to comprehend international broadcasting

    OpenAIRE

    Santos, Augusto Junior da Silva; Universidade Estadual Paulista "Júlio de Mesquista Filho" - UNESP

    2017-01-01

    This paper aims to identify relations between international broadcasting and the global society and the society in mediatization through a bibliographical research. Technological advancements and economic motivation enhanced the potentiality of the media. Since then, it has reached geographically distant audiences, broadcasting mediatic representation on different realities. Within this context, the presented modality of broadcasting acts as a tool for diplomacy and is connected with the glob...

  6. Mediators of the relationship between acculturative stress and internalization symptoms for immigrant origin youth.

    Science.gov (United States)

    Katsiaficas, Dalal; Suárez-Orozco, Carola; Sirin, Selcuk R; Gupta, Taveeshi

    2013-01-01

    The present study examines the generational differences in the relation between acculturative stress and internalizing symptoms (i.e., anxiety and depression) with a sample of 304 urban residing first- and second-generation immigrant adolescents. In addition, the role of perceptions of social support-a critical element to healthy immigrant adolescent adaptation-is explored as a mediator of this relation. Results indicate that first-generation adolescents report more acculturative stress and internalizing symptoms than do second generation. Employing a moderated mediation framework (Preacher, Rucker, & Hayes, 2007), we find that perceptions of both emotional and academic social support mediate the relation between acculturative stress and internalizing symptoms for the first generation but not for the second. Our findings serve to expand the discourse of the "immigrant paradox" (García Coll & Marks, 2011).

  7. 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

  8. 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

    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......-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; Pstress is an important stimulus for hypercapnic vasodilation of the internal carotid...

  9. 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.

  10. 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.

  11. Internal pudendal artery from type 2 diabetic female rats demonstrate elevated endothelin-1-mediated constriction.

    Science.gov (United States)

    Allahdadi, Kyan J; Hannan, Johanna L; Ergul, Adviye; Tostes, Rita C; Webb, R Clinton

    2011-09-01

    Diabetes is a risk factor for female sexual dysfunction (FSD). FSD has several etiologies, including a vasculogenic component that could be exacerbated in diabetes. The internal pudendal artery supplies blood to the vagina and clitoris and diabetes-associated functional abnormalities in this vascular bed may contribute to FSD. The Goto-Kakizaki (GK) rat is a non-obese model of type 2 diabetes with elevated endothelin-1 (ET-1) activity. We hypothesize that female GK rats have diminished sexual responses and that the internal pudendal arteries demonstrate increased ET-1 constrictor sensitivity. Female Wistar and GK rats were used. Apomorphine (APO)-mediated genital vasocongestive arousal (GVA) was measured. Functional contraction (ET-1 and phenylephrine) and relaxation (acetylcholine, ACh) in the presence or absence of the ETA receptor antagonist (ETA R; atrasentan) or Rho-kinase inhibitor (Y-27632) were assessed in the internal pudendal and mesenteric arteries. Protein expression of ET-1 and RhoA/Rho-kinase signaling pathway was determined in the internal pudendal and mesenteric arteries. APO-mediated GVAs; contraction and relaxation of internal pudendal and mesenteric arteries; ET-1/RhoA/Rho-kinase protein expression. GK rats demonstrated no APO-induced GVAs. Internal pudendal arteries, but not mesenteric arteries, from GK rats exhibited greater contractile sensitivity to ET-1 compared with Wistar arteries. ETA R blockade reduced ET-1-mediated constriction in GK internal pudendal and mesenteric arteries. Rho-kinase inhibition reduced ET-1-mediated constriction of GK internal pudendal but not mesenteric arteries; however, it had no effect on arteries from Wistar rats. RhoA protein expression was elevated in GK internal pudendal arteries. At the highest concentrations, ACh-mediated relaxation was greater in the GK internal pudendal artery; however, no difference was observed in the mesenteric artery. Female GK rats demonstrate decreased sexual responses that may be

  12. International Adoption in the U. S: Traumatic Stress and Normal Developmental Responses

    Science.gov (United States)

    Wolfgang, Jeff Drayton

    2011-01-01

    The purpose of this paper is to present a review of literature on internationally adopted children in the U.S. that provides context, references for normal development, and describes traumatic stress with children. This gives counselors and other professionals who work with young children and families of international adoption a conceptual…

  13. Health Care of Latino Children with Autism and Other Developmental Disabilities: Quality of Provider Interaction Mediates Utilization

    Science.gov (United States)

    Parish, Susan; Magana, Sandra; Rose, Roderick; Timberlake, Maria; Swaine, Jamie G.

    2012-01-01

    This study examines access to, utilization of, and quality of health care for Latino children with autism and other developmental disabilities. We analyze data from the National Survey of Children with Special Health Care Needs (N = 4,414 children with autism and other developmental disabilities). Compared with White children, Latino children with…

  14. 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.

  15. 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

  16. 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.

  17. 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…

  18. 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…

  19. 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…

  20. 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.

  1. 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…

  2. 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

  3. Vision and hearing deficits and associations with parent-reported behavioral and developmental problems in international adoptees.

    Science.gov (United States)

    Eckerle, Judith K; Hill, Lindsay Knauf; Iverson, Sandra; Hellerstedt, Wendy; Gunnar, Megan; Johnson, Dana E

    2014-04-01

    To determine the occurrence of vision and hearing deficits in international adoptees and their associations with emotional, behavioral and cognitive problems. The Minnesota International Adoption Project (MnIAP) was a 556-item survey that was mailed to 2,969 parents who finalized an international adoption in Minnesota (MN) between January 1990 and December 1998 and whose children were between 4 and 18 years-old at the time of the survey. Families returned surveys for 1,906 children (64%); 1,005 had complete data for analyses. The survey included questions about the child's pre-adoption experiences and post-placement medical diagnoses, and the Child Behavior Checklist (CBCL). Multivariate logistic regression assessed associations between hearing and vision problems and problems identified by the CBCL. Information on hearing and vision screening and specific vision and hearing problems was also collected via a telephone survey (HVS) from 96/184 children (52%) seen between June 1999 and December 2000 at the University of Minnesota International Adoption Clinic. In both cohorts, 61% of children had been screened for vision problems and 59% for hearing problems. Among those children screened, vision (MnIAP = 25%, HVS = 31%) and hearing (MnIAP = 12%, HVS = 13%) problems were common. For MnIAP children, such problems were significant independent predictors for T scores >67 for the CBCL social problems and attention subscales and parent-reported, practitioner-diagnosed developmental delay, learning and speech/language problems, and cognitive impairment. Hearing and vision problems are common in international adoptees and screening and correction are available in the immediate post-arrival period. The importance of identifying vision and hearing problems cannot be overstated as they are risk factors for development and behavior problems.

  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. Preventing dentists' involvement in torture: the developmental history of a new international declaration.

    NARCIS (Netherlands)

    Speers, R.D.; Brands, W.G.; Nuzzolese, E.; Smith, D.; Swiss, P.B.; Woensel, M. van; Welie, J.V.M.

    2008-01-01

    BACKGROUND: For more than half a century, the risk of physicians participating in torture has received thoughtful attention in the field of medicine, and a number of international organizations have issued declarations decrying such involvement. Despite publications that provide evidence of

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

    OpenAIRE

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

    2015-01-01

    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 establish...

  7. [Theroretical and methodological aspects of music therapy in children with special reference to international developmental tendencies].

    Science.gov (United States)

    Schwabe, C

    1976-05-01

    Two melodiotherapeutical principles, namely, the isoprinciple and the intermediary principle (Benenzon), are described in the light of results of recent investigations into the communicative function of music (Reinecke). The paper also discusses the difference between methods of musicotherapy used in the treatment of mental disorders in children and adults. Finally, international trends are analyzed and conclusions drawn in respect of the development of a standard methodology of melodiotherapy.

  8. 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

    ) by a hemolymph reductase, and E is subsequently converted to 20E in various peripheral target tissues. Recently, four Drosophila melanogaster P450 enzymes, encoded by specific Halloween genes, were cloned and functionally characterized as mediating the last hydroxylation steps leading to 20E. We extended...... 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...... of the Halloween genes....

  9. Biological effects of mutant ceruloplasmin on hepcidin-mediated internalization of ferroportin.

    Science.gov (United States)

    Kono, Satoshi; Yoshida, Kenichi; Tomosugi, Naohisa; Terada, Tatsuhiro; Hamaya, Yasushi; Kanaoka, Shigeru; Miyajima, Hiroaki

    2010-11-01

    Ceruloplasmin plays an essential role in cellular iron efflux by oxidizing ferrous iron exported from ferroportin. Ferroportin is posttranslationally regulated through internalization triggered by hepcidin binding. Aceruloplasminemia is an autosomal recessive disorder of iron homeostasis resulting from mutations in the ceruloplasmin gene. The present study investigated the biological effects of glycosylphosphatidylinositol (GPI)-linked ceruloplasmin on the hepcidin-mediated internalization of ferroportin. The prevention of hepcidin-mediated ferroportin internalization was observed in the glioma cells lines expressing endogenous ceruloplasmin as well as in the cells transfected with GPI-linked ceruloplasmin under low levels of hepcidin. A decrease in the extracellular ferrous iron by an iron chelator and incubation with purified ceruloplasmin in the culture medium prevented hepcidin-mediated ferroportin internalization, while the reconstitution of apo-ceruloplasmin was not able to prevent ferroportin internalization. The effect of ceruloplasmin on the ferroportin stability was impaired due to three distinct properties of the mutant ceruloplasmin: namely, a decreased ferroxidase activity, the mislocalization in the endoplasmic reticulum, and the failure of copper incorporation into apo-ceruloplasmin. Patients with aceruloplasminemia exhibited low serum hepcidin levels and a decreased ferroportin protein expression in the liver. The in vivo findings supported the notion that under low levels of hepcidin, mutant ceruloplasmin cannot stabilize ferroportin because of a loss-of-function in the ferroxidase activity, which has been reported to play an important role in the stability of ferroportin. The properties of mutant ceruloplasmin regarding the regulation of ferroportin may therefore provide a therapeutic strategy for aceruloplasminemia patients. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. 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...

  11. 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…

  12. 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.

  13. Timing of Developmentally Programmed Excision and Circularization of Paramecium Internal Eliminated Sequences

    Science.gov (United States)

    Bétermier, Mireille; Duharcourt, Sandra; Seitz, Hervé; Meyer, Eric

    2000-01-01

    Paramecium internal eliminated sequences (IESs) are short AT-rich DNA elements that are precisely eliminated from the germ line genome during development of the somatic macronucleus. They are flanked by one 5′-TA-3′ dinucleotide on each side, a single copy of which remains at the donor site after excision. The timing of their excision was examined in synchronized conjugating cells by quantitative PCR. Significant amplification of the germ line genome was observed prior to IES excision, which starts 12 to 14 h after initiation of conjugation and extends over a 2- to 4-h period. Following excision, two IESs were shown to form extrachromosomal circles that can be readily detected on Southern blots of genomic DNA from cells undergoing macronuclear development. On these circular molecules, covalently joined IES ends are separated by one copy of the flanking 5′-TA-3′ repeat. The similar structures of the junctions formed on the excised and donor molecules point to a central role for this dinucleotide in IES excision. PMID:10669733

  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. 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

  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. 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.

  18. Transglutaminase-mediated internal protein labeling with a designed peptide loop.

    Science.gov (United States)

    Mori, Yutaro; Goto, Masahiro; Kamiya, Noriho

    2011-07-15

    Post-translational internal protein labeling was explored through the insertion of a 13-mer peptidyl loop specifically recognized by microbial transglutaminase (MTG). The peptidyl loop included one lysine residue (abbreviated as the K-loop), and was designed and inserted into two different regions of the protein bacterial alkaline phosphatase (BAP). MTG-mediated selective labeling of a lysine residue in the K-loop was achieved with a functional Gln-donor substrate. Internal protein labeling in the vicinity of the active site of BAP (residues 91-93) markedly decreased the activity of the enzyme. Conversely, insertion of the K-loop at a site distal from the active site (residues 219-221) afforded site-specific and covalent internal protein labeling without impairing the activity of the enzyme. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Workgroup Report: Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies

    Science.gov (United States)

    Coecke, Sandra; Goldberg, Alan M; Allen, Sandra; Buzanska, Leonora; Calamandrei, Gemma; Crofton, Kevin; Hareng, Lars; Hartung, Thomas; Knaut, Holger; Honegger, Paul; Jacobs, Miriam; Lein, Pamela; Li, Abby; Mundy, William; Owen, David; Schneider, Steffen; Silbergeld, Ellen; Reum, Torsten; Trnovec, Tomas; Monnet-Tschudi, Florianne; Bal-Price, Anna

    2007-01-01

    This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19–21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by ECVAM, the European Chemical Industry Council, and the Johns Hopkins University Center for Alternatives to Animal Testing. The primary aim of the workshop was to identify and catalog potential methods that could be used to assess how data from in vitro alternative methods could help to predict and identify DNT hazards. Working groups focused on two different aspects: a) details on the science available in the field of DNT, including discussions on the models available to capture the critical DNT mechanisms and processes, and b) policy and strategy aspects to assess the integration of alternative methods in a regulatory framework. This report summarizes these discussions and details the recommendations and priorities for future work. PMID:17589601

  20. 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...

  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. What Is the Impact of Center Variability in a Multicenter International Prospective Observational Study on Developmental Dysplasia of the Hip?

    Science.gov (United States)

    Mulpuri, Kishore; Schaeffer, Emily K; Kelley, Simon P; Castañeda, Pablo; Clarke, Nicholas M P; Herrera-Soto, Jose A; Upasani, Vidyadhar; Narayanan, Unni G; Price, Charles T

    2016-05-01

    Little information exists concerning the variability of presentation and differences in treatment methods for developmental dysplasia of the hip (DDH) in children Hip Dysplasia Institute to establish the need to consider the center as a key variable in multicenter studies. (1) How do patient demographics differ across participating centers at presentation? (2) How do patient diagnoses (severity and laterality) differ across centers? (3) How do initial treatment approaches differ across participating centers? A multicenter prospective hip dysplasia study database was analyzed from 2010 to April 2015. Patients younger than 6 months of age at diagnosis were included if at least one hip was completely dislocated, whereas patients between 6 and 18 months of age at diagnosis were included with any form of DDH. Participating centers (academic, urban, tertiary care hospitals) span five countries across three continents. Baseline data (patient demographics, diagnosis, swaddling history, baseline International Hip Dysplasia Institute classification, and initial treatment) were compared among all nine centers. A total of 496 patients were enrolled with site enrolment ranging from 10 to 117. The proportion of eligible patients who were enrolled and followed at the nine participating centers was 98%. Patient enrollment rates were similar across all sites, and data collection/completeness for relevant variables at initial presentation was comparable. In total, 83% of all patients were female (410 of 496), and the median age at presentation was 2.2 months (range, 0-18 months). Breech presentation occurred more often in younger (Hip Dysplasia Institute classification), which included 58% (51 of 88) of all classified dislocated hips. Splintage was the primary initial treatment of choice at 80% (395 of 496), but was far more likely in younger compared with older patients (94% [309 of 328] versus 18% [17 of 93]; p < 0.001). With the lack of strong prognostic indicators for DDH

  3. 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

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

    Science.gov (United States)

    Rewitz, Kim F; Rybczynski, Robert; Warren, James T; Gilbert, Lawrence I

    2006-03-01

    The insect molting hormone 20-hydroxyecdysone (20E) plays a central role in regulating gene expression during development and metamorphosis. In many Lepidoptera, the pro-hormone 3-dehydroecdysone (3DE), synthesized from cholesterol in the prothoracic gland, is rapidly converted to ecdysone (E) by a hemolymph reductase, and E is subsequently converted to 20E in various peripheral target tissues. Recently, four Drosophila melanogaster P450 enzymes, encoded by specific Halloween genes, were cloned and functionally characterized as mediating the last hydroxylation steps leading to 20E. We extended 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-hydroxylase), expressed predominantly in the prothoracic gland during the fifth (final) larval instar and during pupal-adult development, with fifth instar mRNA levels closely paralleling the hemolymph ecdysteroid titer. The data indicate that transcriptional regulation of phm, dib and sad plays a role 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 of the Halloween genes.

  5. Effect of ultrasound irradiation on bacterial internalization and bacteria-mediated gene transfer to cancer cells.

    Science.gov (United States)

    Ninomiya, Kazuaki; Yamada, Ryuji; Meisaku, Hitomi; Shimizu, Nobuaki

    2014-05-01

    The present study demonstrates that ultrasound irradiation can facilitate bacteria-mediated gene delivery (bactofection). Escherichia coli modified with avidin were employed as a vehicle for delivery of the green fluorescent protein (GFP) gene, a model heterologous gene, into the breast cancer cell line MCF-7. Avidin-mediated binding of E. coli to MCF-7 cells enhanced the internalization of E. coli by approximately 17%, irrespective of the use of ultrasound irradiation. Furthermore, the use of ultrasound irradiation increased the internalization by approximately 5%, irrespective of the presence of avidin on the E. coli cell surface. The percentages of GFP-expressing MCF-7 cells at 24h after bactofection were below 0.5% and 2% for the case with only avidin-modification of E. coli cell surface and only ultrasound irradiation, respectively. However, combining avidin modification with the ultrasound treatment increased this value to 8%. Thus, the use of avidin-modified bacteria in conjunction with ultrasound irradiation has potential as an effective strategy for tumor-targeted bactofection. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. 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

  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. 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…

  9. 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.

  10. CRISPR-Cas9 and CRISPR-Cpf1 mediated targeting of a stomatal developmental gene EPFL9 in rice.

    Science.gov (United States)

    Yin, Xiaojia; Biswal, Akshaya K; Dionora, Jacqueline; Perdigon, Kristel M; Balahadia, Christian P; Mazumdar, Shamik; Chater, Caspar; Lin, Hsiang-Chun; Coe, Robert A; Kretzschmar, Tobias; Gray, Julie E; Quick, Paul W; Bandyopadhyay, Anindya

    2017-05-01

    CRISPR-Cas9/Cpf1 system with its unique gene targeting efficiency, could be an important tool for functional study of early developmental genes through the generation of successful knockout plants. The introduction and utilization of systems biology approaches have identified several genes that are involved in early development of a plant and with such knowledge a robust tool is required for the functional validation of putative candidate genes thus obtained. The development of the CRISPR-Cas9/Cpf1 genome editing system has provided a convenient tool for creating loss of function mutants for genes of interest. The present study utilized CRISPR/Cas9 and CRISPR-Cpf1 technology to knock out an early developmental gene EPFL9 (Epidermal Patterning Factor like-9, a positive regulator of stomatal development in Arabidopsis) orthologue in rice. Germ-line mutants that were generated showed edits that were carried forward into the T2 generation when Cas9-free homozygous mutants were obtained. The homozygous mutant plants showed more than an eightfold reduction in stomatal density on the abaxial leaf surface of the edited rice plants. Potential off-target analysis showed no significant off-target effects. This study also utilized the CRISPR-LbCpf1 (Lachnospiracae bacterium Cpf1) to target the same OsEPFL9 gene to test the activity of this class-2 CRISPR system in rice and found that Cpf1 is also capable of genome editing and edits get transmitted through generations with similar phenotypic changes seen with CRISPR-Cas9. This study demonstrates the application of CRISPR-Cas9/Cpf1 to precisely target genomic locations and develop transgene-free homozygous heritable gene edits and confirms that the loss of function analysis of the candidate genes emerging from different systems biology based approaches, could be performed, and therefore, this system adds value in the validation of gene function studies.

  11. 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.

  12. 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...... 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....... From the perspective of mediatization research, the most important effect of the media stems from their embeddedness in culture and society....

  13. The Phosducin-Like Protein PhnA Is Required for Gβγ-Mediated Signaling for Vegetative Growth, Developmental Control, and Toxin Biosynthesis in Aspergillus nidulans

    Science.gov (United States)

    Seo, Jeong-Ah; Yu, Jae-Hyuk

    2006-01-01

    Phosducin or phosducin-like protein (PhLP) is a positive regulator of Gβγ activity. The Gβ (SfaD) and Gγ (GpgA) subunits function in vegetative growth and developmental control in the model filamentous fungus Aspergillus nidulans. To better understand the nature of Gβγ-mediated signaling, phnA, encoding an A. nidulans PhLP, has been studied. Deletion of phnA resulted in phenotypes almost identical to those caused by deletion of sfaD, i.e., reduced biomass, asexual sporulation in liquid submerged culture, and defective fruiting body formation, suggesting that PhnA is necessary for Gβ function. The requirement for the RGS protein FlbA in asexual sporulation could be bypassed by the ΔphnA mutation, indicating that PhnA functions in FlbA-controlled vegetative growth signaling, primarily mediated by the heterotrimeric G protein composed of FadA (Gα), SfaD, and GpgA. However, whereas deletion of fadA restored both asexual sporulation and the production of sterigmatocystin (ST), deletion of sfaD, gpgA, or phnA failed to restore ST production in the ΔflbA mutant. Further studies revealed that SfaD, GpgA, and PhnA are necessary for the expression of aflR, encoding the transcriptional activator for the ST biosynthetic genes, and subsequent ST biosynthesis. Overexpression of aflR bypassed the need for SfaD in ST production, indicating that the results of SfaD-mediated signaling may include transcriptional activation of aflR. Potential differential roles of FadA, Gβγ, and FlbA in controlling ST biosynthesis are further discussed. PMID:16467480

  14. 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).

  15. The developmental relationship between DHEA and visual attention is mediated by structural plasticity of cortico-amygdalar networks.

    Science.gov (United States)

    Nguyen, Tuong-Vi; Gower, Patricia; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Fonov, Vladimir S; Collins, Louis; Ducharme, Simon; McCracken, James T

    2016-08-01

    Humans and the great apes are the only species demonstrated to exhibit adrenarche, a key developmental event leading to increased production of dehydroepiandrosterone (DHEA), suggesting that this hormone may play an important evolutionary role. Similarly, visual attention networks have been shown to evolve in a human-specific manner, with some anatomical connections and elements of cortical organization exclusive to our species. Existing studies of human brain development support the notion that DHEA shows significant uptake in cortical structures and the amygdala, and as such, could be involved in the bottom-up regulation of visual attention. Here we examined associations between DHEA, structural covariance of the amygdala with whole-brain cortical thickness, and tests of visual attention, in a longitudinal sample of typically developing children and adolescents 6-22 years of age. We found that DHEA predicted covariance between amygdalar volume and the left occipital pole, right somatosensory parietal cortex and right anterior cingulate cortex. Amygdala-occipital covariance predicted visual awareness; amygdala-parietal covariance predicted visuo-motor dexterity and processing speed; amygdala-prefrontal covariance predicted global attentional impairment. Further, effects of DHEA were above and beyond those of age and sex, as well as distinct from those of pubertal stage, estradiol and testosterone. These findings support the notion that DHEA may play a unique role in shaping amygdala-dependent cortical plasticity and in regulating 'bottom-up' visual attention processes from childhood to young adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Barakat, Lamia P; Patterson, Chavis A; Daniel, Lauren C; Dampier, Carlton

    2008-08-09

    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. 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. 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. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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…

  1. The International Society for Developmental Psychobiology annual meeting symposium: Impact of early life experiences on brain and behavioral development.

    Science.gov (United States)

    Sullivan, Regina; Wilson, Donald A; Feldon, Joram; Yee, Benjamin K; Meyer, Urs; Richter-Levin, Gal; Avi, Avital; Michael, Tsoory; Gruss, Michael; Bock, Jörg; Helmeke, Carina; Braun, Katharina

    2006-11-01

    Decades of research in the area of developmental psychobiology have shown that early life experience alters behavioral and brain development, which canalizes development to suit different environments. Recent methodological advances have begun to identify the mechanisms by which early life experiences cause these diverse adult outcomes. Here we present four different research programs that demonstrate the intricacies of early environmental influences on behavioral and brain development in both pathological and normal development. First, an animal model of schizophrenia is presented that suggests prenatal immune stimulation influences the postpubertal emergence of psychosis-related behavior in mice. Second, we describe a research program on infant rats that demonstrates how early odor learning has unique characteristics due to the unique functioning of the infant limbic system. Third, we present work on the rodent Octodon degus, which shows that early paternal and/or maternal deprivation alters development of limbic system synaptic density that corresponds to heightened emotionality. Fourth, a juvenile model of stress is presented that suggests this developmental period is important in determining adulthood emotional well being. The approach of each research program is strikingly different, yet all succeed in delineating a specific aspect of early development and its effects on infant and adult outcome that expands our understanding of the developmental impact of infant experiences on emotional and limbic system development. Together, these research programs suggest that the developing organism's developmental trajectory is influenced by environmental factors beginning in the fetus and extending through adolescence, although the specific timing and nature of the environmental influence has unique impact on adult mental health. (c) 2006 Wiley Periodicals, Inc.

  2. 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.

  3. Modulation of Macropinocytosis-Mediated Internalization Decreases Ocular Toxicity of Antibody-Drug Conjugates.

    Science.gov (United States)

    Zhao, Hui; Atkinson, John; Gulesserian, Sara; Zeng, Zhilan; Nater, Jenny; Ou, Jimmy W; Yang, Peng; Morrison, Karen; Coleman, Jeffrey; Malik, Faisal; Challita-Eid, Pia M; Karki, Sher; Aviña, Hector; Hubert, René S; Capo, Linnette; Snyder, Josh; Moon, Sung-Ju; Luethy, Roland; Mendelsohn, Brian A; Stover, David R; Doñate, Fernando

    2018-01-30

    AGS-16C3F is an antibody-drug conjugate (ADC) against ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) containing the mcMMAF linker-payload currently in development for treatment of metastatic renal cell carcinoma. AGS-16C3F and other ADC have been reported to cause ocular toxicity in patients by unknown mechanisms. To investigate this toxicity, we developed an in vitro assay using human corneal epithelial cells (HCEC) and show that HCEC internalized AGS-16C3F and other ADCs by macropinocytosis, causing inhibition of cell proliferation. We observed the same mechanism for target-independent internalization of AGS-16C3F in fibroblasts and human umbilical vein endothelial cells (HUVEC). Macropinocytosis-mediated intake of macromolecules is facilitated by the presence of positive charges or hydrophobic residues on the surface of the macromolecule. Modification of AGS-16C3F, either by attachment of poly-glutamate peptides, mutation of residue K16 to D on AGS-16C3F (AGS-16C3F(K16D)), or decreasing the overall hydrophobicity via attachment of polyethylene glycol moieties, significantly reduced cytotoxicity against HCEC and other primary cells. Rabbits treated with AGS-16C3F showed significant ocular toxicity, whereas those treated with AGS-16C3F(K16D) presented with less severe and delayed toxicities. Both molecules displayed similar anti-tumor activity in a mouse xenograft model. These findings establish a mechanism of action for target-independent toxicities of AGS-16C3F and ADCs in general, and provide methods to ameliorate these toxicities. Copyright ©2018, American Association for Cancer Research.

  4. 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…

  5. Internal structure-mediated ultrafast energy transfer in self-assembled polymer-blend dots.

    Science.gov (United States)

    Wang, Lei; Wu, Chang-Feng; Wang, Hai-Yu; Wang, Ya-Feng; Chen, Qi-Dai; Han, Wei; Qin, Wei-Ping; McNeill, Jason; Sun, Hong-Bo

    2013-08-21

    Applications of polymeric semiconductors in organic electronics and biosensors depend critically on the nature of energy transfer in these materials. Important questions arise as to how this long-range transport degrades in amorphous condensed solids which are most amenable to low-cost optoelectronic devices and how fast energy transfer could occur. Here, we address these in disordered, densely packed nanoparticles made from green-light-harvesting host polymers (PFBT) and deep-red-emitting dopant polymers (PF-DBT5). By femtosecond selective excitation of donor (BT) units, we study in detail the internal structure-mediated energy transfer to uniformly distributed, seldom acceptor (DBT) units. It has been unambiguously demonstrated that the creation of interchain species is responsible for the limitation of bulk exciton diffusion length in polymer materials. This interchain Förster resonance energy transfer (FRET) becomes a preferred and dominant channel, and near 100% energy transfer efficiency could be achieved at high acceptor concentrations (>10 wt%). Side-chain carboxylic acid groups in functionalized polymer-blend dots slightly slow down the FRET rate, but it could not affect the Förster radius and FRET efficiency. These findings imply that a greater understanding of the role of interchain species could be an efficient approach to improve the cell efficiency.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Estrogen-induced developmental disorders of the rat penis involve both estrogen receptor (ESR)- and androgen receptor (AR)-mediated pathways.

    Science.gov (United States)

    Goyal, H O; Braden, T D; Williams, C S; Williams, J W

    2009-09-01

    This study tested the hypothesis that the estrogen receptor (ESR) pathway, androgen receptor (AR) pathway, or both mediate estrogen-induced developmental penile disorders. Rat pups received diethylstilbestrol (DES), with or without the ESR antagonist ICI 182,780 (ICI) or the AR agonist dihydrotestosterone (DHT) or testosterone (T), from Postnatal Days 1 to 6. Testicular T concentration, penile morphology and morphometry, and/or fertility was determined at age 7, 28, or 150 days. DES treatment alone caused 90% reduction in the neonatal intratesticular T surge; this reduction was prevented by ICI coadministration, but not by DHT or T coadministration. Unlike the T surge, coadministration of ICI and coadministration of DHT or T mitigated penile deformities and loss of fertility. Generally, ICI, DHT, or T treatment alone did not alter penile morphology; however, fertility was 20% that of controls in ICI-treated rats vs. 70%-90% in DHT- or T-treated rats. The lower fertility in the rats treated with ICI alone could be due to altered sexual behavior, as these males did not deposit vaginal plugs. In conclusion, observations that both an ESR antagonist and AR agonists prevent penile deformities and infertility suggest that both pathways are involved in estrogen-induced penile disorders. Observations that coadministration of ICI, but not DHT or T, prevents the DES-induced reduction in the neonatal T surge suggest that, although ICI exerts its mitigating effect both at the level of Leydig cells and penile stromal cells, DHT and T do so only at the level of stromal cells.

  14. Estrogen-Induced Developmental Disorders of the Rat Penis Involve Both Estrogen Receptor (ESR)- and Androgen Receptor (AR)-Mediated Pathways1

    Science.gov (United States)

    Goyal, H.O.; Braden, T.D.; Williams, C.S.; Williams, J.W.

    2009-01-01

    This study tested the hypothesis that the estrogen receptor (ESR) pathway, androgen receptor (AR) pathway, or both mediate estrogen-induced developmental penile disorders. Rat pups received diethylstilbestrol (DES), with or without the ESR antagonist ICI 182,780 (ICI) or the AR agonist dihydrotestosterone (DHT) or testosterone (T), from Postnatal Days 1 to 6. Testicular T concentration, penile morphology and morphometry, and/or fertility was determined at age 7, 28, or 150 days. DES treatment alone caused 90% reduction in the neonatal intratesticular T surge; this reduction was prevented by ICI coadministration, but not by DHT or T coadministration. Unlike the T surge, coadministration of ICI and coadministration of DHT or T mitigated penile deformities and loss of fertility. Generally, ICI, DHT, or T treatment alone did not alter penile morphology; however, fertility was 20% that of controls in ICI-treated rats vs. 70%–90% in DHT- or T-treated rats. The lower fertility in the rats treated with ICI alone could be due to altered sexual behavior, as these males did not deposit vaginal plugs. In conclusion, observations that both an ESR antagonist and AR agonists prevent penile deformities and infertility suggest that both pathways are involved in estrogen-induced penile disorders. Observations that coadministration of ICI, but not DHT or T, prevents the DES-induced reduction in the neonatal T surge suggest that, although ICI exerts its mitigating effect both at the level of Leydig cells and penile stromal cells, DHT and T do so only at the level of stromal cells. PMID:19420389

  15. A developmental window of opportunity for imprinted gene silencing mediated by DNA methylation and the Kcnq1ot1 noncoding RNA.

    Science.gov (United States)

    Green, Kelly; Lewis, Annabelle; Dawson, Claire; Dean, Wendy; Reinhart, Bonnie; Chaillet, J Richard; Reik, Wolf

    2007-01-01

    The Kcnq1 imprinted domain encodes a paternally expressed noncoding RNA Kcnq1ot1 and several paternally repressed protein-coding genes. Transcriptional regulation is controlled by the Kcnq1ot1 gene whose maternal germline methylation imprint overlaps with the Kcnq1ot1 promoter. The domain can be divided into two groups of genes. One group is imprinted in all lineages and is reliant on DNA methylation for its imprinting. The other group contains genes that are imprinted specifically in the placenta and retain their imprinting in the absence of Dnmt1, the primary DNA maintenance methylase. In the placenta paternal Kcnq1ot1 expression is associated with the acquisition of repressive histone modifications throughout the domain. Using the Dnmt1o knockout, we have analyzed the effect of removing DNA maintenance methylation at the eight-cell stage on the Kcnq1 imprinted domain. In the placenta the expression of the normally silent maternal Kcnq1ot1 allele leads to reduced expression of the surrounding maternally expressed genes. This repression is seen in both the placental-specific imprinted genes and the ubiquitously imprinted genes. Conversely, reduction of functional Dnmt1 results solely in reduced expression of the ubiquitously imprinted genes in the placenta. This suggests that Kcnq1ot1 expression can epigenetically silence placentally imprinted genes in the cluster only during a specific developmental window. This highlights the possibility that Kcnq1ot1-mediated repression is temporally regulated leading to epigenetic silencing of placental-specific genes. We show that allele-specific histone modifications are still present in the Dnmt1 ( -/- ) trophoblast at placental-specific imprinted loci and are likely responsible for maintaining the imprinting of these genes in the absence of DNA methylation.

  16. 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.

  17. 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

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

    Science.gov (United States)

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

    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. 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.

  20. The mediating role of perceived peer support in the relation between quality of attachment and internalizing problems in adolescence: a longitudinal perspective.

    Science.gov (United States)

    Pace, Ugo; Zappulla, Carla; Di Maggio, Rosanna

    2016-10-01

    The study was aimed to verify, from a longitudinal perspective, whether perceived peer support would mediate the relationship between attachment and internalizing problems. Longitudinal participants included 482 adolescents (245 boys) aged 14-15 years in Wave 1 and 17-18 years in Wave 2. Participants in Wave 1 completed the Relationship Questionnaire, and those in Wave 2 completed the Social Support Questionnaire and the Youth Self-Report. Results showed that secure attachment positively predicted high levels of perceived peer support and negatively predicted internalizing problems, whereas fearful and preoccupied attachment negatively predicted perceived peer support and positively predicted internalizing problems. The mediation models showed that perceived peer support partially mediated the relationship between secure attachment and internalizing problems as well as between preoccupied attachment and internalizing problems and between fearful attachment and internalizing problems. Our results confirm the role of subjective perception of peer support in contributing to the prediction of internalizing problems beyond attachment styles.

  1. 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.

  2. 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.

  3. “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

  4. 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.

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

    OpenAIRE

    ?witaj, Piotr; Grygiel, Pawe?; Chrostek, Anna; Nowak, Izabela; Wci?rka, Jacek; Anczewska, Marta

    2017-01-01

    Purpose 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). Methods 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 r...

  6. Parental Negative Control Moderates the Shyness-Emotion Regulation Pathway to School-Age Internalizing Symptoms

    Science.gov (United States)

    Feng, Xin; Shaw, Daniel S.; Moilanen, Kristin L.

    2011-01-01

    Models of developmental psychopathology emphasize both mediation and moderation processes among child and caregiving attributes; however, little research has examined both these processes simultaneously on the development of internalizing problems. This study tested a moderated mediation model that related early childhood shyness, emotion…

  7. 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

  8. 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'…

  9. 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

  10. 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

  11. Semiotic mediation: a case study of a blind child with developmental alterations / Mediação semiótica: estudo de caso de uma criança cega, com alterações no desenvolvimento

    Directory of Open Access Journals (Sweden)

    Michelli Alessandra Silva

    2007-01-01

    Full Text Available The case of a 4 year old congenitally blind child, with developmental alterations, was analyzed, according to assumptions of constitutive language (Franchi, 1977 and semiotic mediation (Rodríguez & Moro, 1999. Seven sessions of intervention were transcribed and analyzed, comprising a period of two years. The adaptation of the methodology of Rodríguez & Moro allowed the observation of the following aspects: the acquisition of use of objects (from less conventional uses to more conventional uses, the participation in play activities (eg: nursery rhymes and the appearance of different modes of communication. Different aspects of the adult-child interaction were given significance, expanding the scope of the original proposition in relation to the role of semiotic mediation. The implications of the study to the area of Special Education were discussed.

  12. An E-Cadherin-mediated hitchhiking mechanism for C. elegans germ cell internalization during gastrulation

    OpenAIRE

    Chihara, Daisuke; Nance, Jeremy

    2011-01-01

    Gastrulation movements place endodermal precursors, mesodermal precursors and primordial germ cells (PGCs) into the interior of the embryo. Somatic cell gastrulation movements are regulated by transcription factors that also control cell fate, coupling cell identity and position. By contrast, PGCs in many species are transcriptionally quiescent, suggesting that they might use alternative gastrulation strategies. Here, we show that C. elegans PGCs internalize by attaching to internal endoderma...

  13. Dyadic adjustment and parenting stress in internationally adoptive mothers and fathers: The mediating role of adult attachment dimensions

    Directory of Open Access Journals (Sweden)

    Silvia eSalcuni

    2015-09-01

    Full Text Available Previous research has shown that a positive marital functioning represents a resource in adoptive families, leading to a decrease in parenting stress, but little is known about the factors mediating such a relationship. This study aimed to explore whether adult attachment avoidance and anxiety mediate the effect of dyadic functioning on parenting stress in 90 internationally adoptive couples (mothers and fathers who had adopted a child (aged 3-10 years in the last 36 months. Participants completed self-report measures of dyadic adjustment, adult attachment, and parenting stress. A series of path analyses supported the mediation hypothesis, but differentially for mothers and fathers. Among mothers, there was a direct and negative relationship between dyadic adjustment and parenting stress. In addition, a better dyadic adjustment was related to lower levels of attachment anxiety, which in turn were associated with less parenting stress. Among fathers, increased dyadic adjustment was related to lower levels of attachment avoidance, which in turn were associated with reduced parenting stress. These findings suggest the importance of including both mothers and fathers in adoption research. Adoptive parents could benefit from specific interventions aimed at reducing attachment avoidance and anxiety by supporting parental sense of competence and involvement for mothers and fathers, respectively.

  14. Dyadic adjustment and parenting stress in internationally adoptive mothers and fathers: the mediating role of adult attachment dimensions.

    Science.gov (United States)

    Salcuni, Silvia; Miconi, Diana; Altoè, Gianmarco; Moscardino, Ughetta

    2015-01-01

    Previous research has shown that a positive marital functioning represents a resource in adoptive families, leading to a decrease in parenting stress, but little is known about the factors mediating such a relationship. This study aimed to explore whether adult attachment avoidance and anxiety mediate the effect of dyadic functioning on parenting stress in 90 internationally adoptive couples (mothers and fathers) who had adopted a child (aged 3-10 years) in the last 36 months. Participants completed self-report measures of dyadic adjustment, adult attachment, and parenting stress. A series of path analyses supported the mediation hypothesis, but differentially for mothers and fathers. Among mothers, there was a direct and negative relationship between dyadic adjustment and parenting stress. In addition, a better dyadic adjustment was related to lower levels of attachment anxiety, which in turn were associated with less parenting stress. Among fathers, increased dyadic adjustment was related to lower levels of attachment avoidance, which in turn were associated with reduced parenting stress. These findings suggest the importance of including both mothers and fathers in adoption research. Adoptive parents could benefit from specific interventions aimed at reducing attachment avoidance and anxiety by supporting parental sense of competence and involvement for mothers and fathers, respectively.

  15. 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

  16. 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.

  17. 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 transcriptional......, the ability to stimulate transcription of the serine protease inhibitor 2.1 promoter by the GHR was not affected by the phenylalanine 346 to alanine mutation. These results demonstrate that phenylalanine 346 is essential for GHR internalization and down-regulation but not for transcriptional signaling......, suggesting that ligand-mediated endocytosis is not a prerequisite for GH-induced gene transcription....

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

    OpenAIRE

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

    2013-01-01

    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 Struct...

  19. 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

  20. Cooperative Activity as Mediation in the Social Adjustment of Chinese International Students

    Science.gov (United States)

    Ma, Junqian

    2017-01-01

    Social adjustment is one of the most difficult and long-lasting challenges for international students who study in a new country. This paper uses a case study of cooperative painting activity conducted in Australian setting, in which two Chinese and three other students from different countries participated, in order to assess the efficiency of…

  1. The mediating effects of family on sport in international development contexts

    NARCIS (Netherlands)

    Kay, T.; Spaaij, R.

    2012-01-01

    The role of family in influencing sports behaviour is widely recognized. This article extends this body of knowledge by examining how the family influences young people’s responses to sport programmes operating in international development contexts. Recognizing the central role of the family as a

  2. Distinguishing possible mechanisms for auxin-mediated developmental control in Arabidopsis: models with two Aux/IAA and ARF proteins, and two target gene-sets.

    Science.gov (United States)

    Bridge, L J; Mirams, G R; Kieffer, M L; King, J R; Kepinski, S

    2012-01-01

    New models of gene transcriptional responses to auxin signalling in Arabidopsis are presented. This work extends a previous model of auxin signalling to include networks of gene-sets which may control developmental responses along auxin gradients. Key elements of this new study include models of signalling pathways and networks involving two Aux-IAA proteins (IAAs), auxin response factors (ARFs) and gene targets. Hypotheses for the gene network topologies which may be involved in developmental responses have been tested against experimental observations for root hair growth in particular. In studying these models, we provide a framework for the analysis of auxin signalling with multiple IAAs and ARFs, and discuss the implications of bistability in such systems. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. 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.

  4. 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.

  5. Solvent-mediated internal conversion in diphenoxyethane-(H2O)nclusters, n = 2-4

    International Nuclear Information System (INIS)

    Walsh, Patrick S.; Buchanan, Evan G.; Gord, Joseph R.; Zwier, Timothy S.

    2015-01-01

    1,2-diphenoxyethane (DPOE) is a flexible bichromophore whose excited states come in close-lying pairs whose splitting and vibronic coupling can be modulated by solvent. Building on the ground state infrared spectroscopy of DPOE-(H 2 O) n clusters with n = 2-4 from the adjoining paper [Walsh et al., J. Chem. Phys. 142, 154303 (2015)], the present work focuses on the vibronic and excited state infrared spectroscopies of the clusters. The type and degree of asymmetry of the water cluster binding to DPOE is reflected in the variation in the magnitude of the S 1 /S 2 splitting with cluster size. Excited state resonant ion-dip infrared spectroscopy was performed at the electronic origins of the first two excited states in order to explore how the water clusters’ OH stretch spectra report on the nature of the two excited states, and the interaction of the S 2 state with nearby S 1 vibronic levels mediated by the water clusters. The data set, when taken as a whole, provides a state-to-state view of internal conversion and the role of solvent in mediating conversion of electronic excitation between two chromophores, providing a molecular-scale view of Kasha’s rule

  6. 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

    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...... vasodilatory function and health in humans.NEW & NOTEWORTHY Shear stress dilates the internal carotid artery in humans. This vasodilatory response occurs independent of other physiological factors, as demonstrated by our transient CO2 test, and is strongly correlated to shear area under the curve. Assessing...

  7. SopB-Mediated Recruitment of SNX18 Facilitates Salmonella Typhimurium Internalization by the Host Cell

    Science.gov (United States)

    Liebl, David; Qi, Xiaying; Zhe, Yang; Barnett, Timothy C.; Teasdale, Rohan D.

    2017-01-01

    To invade epithelial cells, Salmonella enterica serovar Typhimurium (S. Typhimurium) induces macropinocytosis through the action of virulence proteins delivered across the host cell membrane via a type III secretion system. We show that after docking at the plasma membrane S. Typhimurium triggers rapid recruitment of cytosolic SNX18, a SH3-PX-BAR domain sorting nexin protein, to the bacteria-induced membrane ruffles and to the nascent Salmonella-containing vacuole. SNX18 recruitment required the inositol-phosphatase activity of the Salmonella effector SopB and an intact phosphoinositide-binding site within the PX domain of SNX18, but occurred independently of Rho-GTPases Rac1 and Cdc42 activation. SNX18 promotes formation of the SCV from the plasma membrane by acting as a scaffold to recruit Dynamin-2 and N-WASP in a process dependent on the SH3 domain of SNX18. Quantification of bacteria uptake revealed that overexpression of SNX18 increased bacteria internalization, whereas a decrease was detected in cells overexpressing the phosphoinositide-binding mutant R303Q, the ΔSH3 mutant, and in cells where endogenous levels of SNX18 were knocked-down. This study identifies SNX18 as a novel target of SopB and suggests a mechanism where S. Typhimurium engages host factors via local manipulation of phosphoinositide composition at the site of invasion to orchestrate the internalization process. PMID:28664153

  8. 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.

  9. Death by over-eating: The Gaucher disease associated gene GBA1, identified in a screen for mediators of autophagic cell death, is necessary for developmental cell death in Drosophila midgut

    Science.gov (United States)

    Schejter, Eyal; Bialik, Shani; Levin-Zaidman, Smadar; Kimchi, Adi

    2017-01-01

    ABSTRACT Autophagy is critical for homeostasis and cell survival during stress, but can also lead to cell death, a little understood process that has been shown to contribute to developmental cell death in lower model organisms, and to human cancer cell death. We recently reported1 on our thorough molecular and morphologic characterization of an autophagic cell death system involving resveratrol treatment of lung carcinoma cells. To gain mechanistic insight into this death program, we performed a signalome-wide RNAi screen for genes whose functions are necessary for resveratrol-induced death. The screen identified GBA1, the gene encoding the lysosomal enzyme glucocerebrosidase, as an important mediator of autophagic cell death. Here we further show the physiological relevance of GBA1 to developmental cell death in midgut regression during Drosophila metamorphosis. We observed a delay in midgut cell death in two independent Gba1a RNAi lines, indicating the critical importance of Gba1a for midgut development. Interestingly, loss-of-function GBA1 mutations lead to Gaucher Disease and are a significant risk factor for Parkinson Disease, which have been associated with defective autophagy. Thus GBA1 is a conserved element critical for maintaining proper levels of autophagy, with high levels leading to autophagic cell death. PMID:28933588

  10. Is lumbar facet joint tropism developmental or secondary to degeneration? An international, large-scale multicenter study by the AOSpine Asia Pacific Research Collaboration Consortium.

    Science.gov (United States)

    Samartzis, Dino; Cheung, Jason Pui Yin; Rajasekaran, Shanmuganathan; Kawaguchi, Yoshiharu; Acharya, Shankar; Kawakami, Mamoru; Satoh, Shigenobu; Chen, Wen-Jer; Park, Chun-Kun; Lee, Chong-Suh; Foocharoen, Thanit; Nagashima, Hideki; Kuh, Sunguk; Zheng, Zhaomin; Condor, Richard; Ito, Manabu; Iwasaki, Motoki; Jeong, Je Hoon; Luk, Keith D K; Prijambodo, Bambang; Rege, Amol; Jahng, Tae-Ahn; Luo, Zhuojing; Tassanawipas, Warat Anant; Acharya, Narayana; Pokharel, Rohit; Shen, Yong; Ito, Takui; Zhang, Zhihai; Aithala P, Janardhana; Kumar, Gomatam Vijay; Jabir, Rahyussalim Ahmad; Basu, Saumyajit; Li, Baojun; Moudgil, Vishal; Goss, Ben; Sham, Phoebe; Williams, Richard

    2016-01-01

    Facet joint tropism is asymmetry in orientation of the bilateral facets. Some studies have shown that tropism may increase the risk of disc degeneration and herniations, as well as degenerative spondylolisthesis (DS). It remains controversial whether tropism is a pre-existing developmental phenomena or secondary to progressive remodeling of the joint structure due to degenerative changes. As such, the following study addressed the occurrence of tropism of the lower lumbar spine (i.e. L3-S1) in a degenerative spondylolisthesis patient model. An international, multi-center cross-sectional study that consisted of 349 patients with single level DS recruited from 33 spine institutes in the Asia Pacific region was performed. Axial MRI/CT from L3-S1 were utilized to assess left and right facet joint sagittal angulation in relation to the coronal plane. The angulation difference between the bilateral facets was obtained. Tropism was noted if there was 8° or greater angulation difference between the facet joints. Tropism was noted at levels of DS and compared to immediate adjacent and distal non-DS levels, if applicable, to the index level. Age, sex-type and body mass index (BMI) were also noted and assessed in relation to tropism. Of the 349 subjects, there were 63.0 % females, the mean age was 61.8 years and the mean BMI was 25.6 kg/m(2). Overall, 9.7, 76.5 and 13.8 % had L3-L4, L4-L5 and L5-S1 DS, respectively. Tropism was present in 47.1, 50.6 and 31.3 % of L3-L4, L4-L5 and L5-S1 of levels with DS, respectively. Tropism involved 33.3 to 50.0 % and 33.3 to 58.8 % of the immediate adjacent and most distal non-DS levels from the DS level, respectively. Patient demographics were not found to be significantly related to tropism at any level (p > 0.05). To the authors' knowledge, this is one of the largest studies conducted, in particular in an Asian population, addressing facet joint tropism. Although levels with DS were noted to have tropism, immediate adjacent

  11. Prolactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity.

    Science.gov (United States)

    Sundaram, Karthik M; Zhang, Yilin; Mitra, Anirban K; Kouadio, Jean-Louis K; Gwin, Katja; Kossiakoff, Anthony A; Roman, Brian B; Lengyel, Ernst; Piccirilli, Joseph A

    2017-04-01

    Poor prognosis of ovarian cancer, the deadliest of the gynecologic malignancies, reflects major limitations associated with detection and diagnosis. Current methods lack high sensitivity to detect small tumors and high specificity to distinguish malignant from benign tissue, both impeding diagnosis of early and metastatic cancer stages and leading to costly and invasive surgeries. Tissue microarray analysis revealed that >98% of ovarian cancers express the prolactin receptor (PRLR), forming the basis of a new molecular imaging strategy. We fused human placental lactogen (hPL), a specific and tight binding PRLR ligand, to magnetic resonance imaging (gadolinium) and near-infrared fluorescence imaging agents. Both in tissue culture and in mouse models, these imaging bioconjugates underwent selective internalization into ovarian cancer cells via PRLR-mediated endocytosis. Compared with current clinical MRI techniques, this targeted approach yielded both enhanced signal-to-noise ratio from accumulation of signal via selective internalization and improved specificity conferred by PRLR upregulation in malignant ovarian cancer. These features endow PRLR-targeted imaging with the potential to transform ovarian cancer detection. Cancer Res; 77(7); 1684-96. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. 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.

  13. 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...

  14. 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

  15. "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

  16. Prolactin receptor-mediated internalization of imaging agents detects epithelial ovarian cancer

    Science.gov (United States)

    Sundaram, Karthik M.

    Epithelial ovarian cancer (EOC) has the highest mortality rate of all gynecologic malignant tumors. Diagnosis of epithelial ovarian cancer (EOC) presents two main challenges. The first challenge is detecting low volume (prolactin receptor (PRLR) - a cell surface tyrosine kinase receptor that is over-expressed in moderate to high levels on > 98% of epithelial ovarian cancers. Upon binding of native ligands to PRLR, the ligand:PRLR complex is internalized by cells. By conjugating gadolinium-chelates, molecules normally used as contrast agents diagnostically, to human placental lactogen (hPL), a native ligand of PRLR, we show that MRI becomes highly sensitive and specific for detecting PRLR (+) tumors in a nude mouse model of EOC. We further establish the adaptability of this approach for fluorescence-based imaging techniques using an hPL conjugated Cy5.5 dye. We conclude that molecular imaging of PRLR with hPL-conjugated imaging agents can address the current challenges that limit EOC diagnosis.

  17. Glucose is a key driver for GLUT1-mediated nanoparticles internalization in breast cancer cells

    Science.gov (United States)

    Venturelli, Leonardo; Nappini, Silvia; Bulfoni, Michela; Gianfranceschi, Giuseppe; Dal Zilio, Simone; Coceano, Giovanna; Del Ben, Fabio; Turetta, Matteo; Scoles, Giacinto; Vaccari, Lisa; Cesselli, Daniela; Cojoc, Dan

    2016-02-01

    The mesenchymal state in cancer is usually associated with poor prognosis due to the metastatic predisposition and the hyper-activated metabolism. Exploiting cell glucose metabolism we propose a new method to detect mesenchymal-like cancer cells. We demonstrate that the uptake of glucose-coated magnetic nanoparticles (MNPs) by mesenchymal-like cells remains constant when the glucose in the medium is increased from low (5.5 mM) to high (25 mM) concentration, while the MNPs uptake by epithelial-like cells is significantly reduced. These findings reveal that the glucose-shell of MNPs plays a major role in recognition of cells with high-metabolic activity. By selectively blocking the glucose transporter 1 channels we showed its involvement in the internalization process of glucose-coated MNPs. Our results suggest that glucose-coated MNPs can be used for metabolic-based assays aimed at detecting cancer cells and that can be used to selectively target cancer cells taking advantage, for instance, of the magnetic-thermotherapy.

  18. 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

  19. 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.

  20. 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…

  1. The Role of Perceived Learning and Communities of Inquiry in Predicting International Students' Course Grades in Computer-Mediated Graduate Courses

    Science.gov (United States)

    Wendt, Jillian L.; Nisbet, Deanna L.

    2017-01-01

    This study examined the predictive relationship among international students' sense of community, perceived learning, and end-of-course grades in computer-mediated, U.S. graduate-level courses. The community of inquiry (CoI) framework served as the theoretical foundation for the study. Step-wise hierarchical multiple regression showed no…

  2. 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…

  3. 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.

  4. Are You Satisfied? Exploring the Mediating Effects of Mentoring Communication Strategies in Predicting Chinese International Graduate Students' Program Satisfaction

    Science.gov (United States)

    Yang, Qinghua; Orrego Dunleavy, Victoria; Phillips, Jasmine Rene

    2016-01-01

    This study examined how mentoring initiation and maintenance strategies mediate the relationship between acculturative stress and intercultural communication competence on Chinese graduate students' program satisfaction. Results supported a partial mediation effect for mentoring maintenance strategies. By specifying the mediating effect, the model…

  5. Examining stress and coping as a mediator for internalizing symptomatology: A comparison between sexual minority and majority first-year college students.

    Science.gov (United States)

    Riley, Tracey J; Kirsch, Alexandra C; Shapiro, Jenna B; Conley, Colleen S

    2016-06-01

    Sexual and gender minority (SGM) adolescents experience unique stressors and elevated internalizing symptoms. This study examines differences in coping styles between SGM and heterosexual adolescents and the potential mediating roles of stress and coping styles. Analyses indicated that SGM (N = 75) adolescents reported higher levels of internalizing symptoms (depression, anxiety, and distress), higher use of maladaptive coping styles (denial and blame), lesser use of adaptive coping styles (reframing and religion), and greater experiences of stress, compared to their heterosexual counterparts (N = 1702). Bootstrapping analyses revealed the relationship between sexual identity and internalizing symptoms measured approximately 3 months later was not mediated by stress and coping, adjusting for gender, age, and baseline symptomatology. Findings suggest that earlier adolescent differences in internalizing symptoms presage increasing symptomatology across the transition to college, and other mediators during the college transition explain the continued increases in internalizing symptoms. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  6. 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.

  7. 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

  8. Developmental Scaffolding

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio

    2015-01-01

    . As this boundary is gradually defined during development, cells enter into new functional relationships, while, at the same time, are relieved from their physical determinism. The resulting constraints can thus become the driving forces that upgrade embryonic scaffolding from the simple molecular signalling...... 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...

  9. 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

    ester (beta-PMA)-induced phosphorylation of NET occurs on serine and threonine residues. Beta-PMA treatment inhibited NE transport, reduced plasma membrane hNET levels, and stimulated hNET phosphorylation in human placental trophoblast cells expressing the WT-hNET. Substance P-mediated activation......Recently, we have demonstrated the phosphorylation- and lipid raft-mediated internalization of the native norepinephrine transporter (NET) following protein kinase C (PKC) activation (Jayanthi, L. D., Samuvel, D. J., and Ramamoorthy, S. (2004) J. Biol. Chem. 279, 19315-19326). Here we tested...

  10. Interoperability Between Coastal Web Atlases Using Semantic Mediation: A Case Study of the International Coastal Atlas Network (ICAN)

    Science.gov (United States)

    Wright, D. J.; Lassoued, Y.; Dwyer, N.; Haddad, T.; Bermudez, L. E.; Dunne, D.

    2009-12-01

    users formulate their requests using a common ontology of metadata terms, called global ontology. A CSW mediator rewrites the user’s request into CSW requests over local CSWs using their own (local) ontologies, collects the results and sends them back to the user. To extend the system, we have recently added global maritime boundaries and are also considering nearshore ocean observing system data. Ongoing work includes adding WFS, error management, and exception handling, enabling Smart Searches, and writing full documentation. This prototype is a central research project of the new International Coastal Atlas Network (ICAN), a group of 30+ organizations from 14 nations (and growing) dedicated to seeking interoperability approaches to CWAs in support of coastal zone management and the translation of coastal science to coastal decision-making.

  11. 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.

  12. 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.

  13. Developmental dyslexia.

    Science.gov (United States)

    Peterson, Robin L; Pennington, Bruce F

    2015-01-01

    This review uses a levels-of-analysis framework to summarize the current understanding of developmental dyslexia's etiology, brain bases, neuropsychology, and social context. Dyslexia is caused by multiple genetic and environmental risk factors as well as their interplay. Several candidate genes have been identified in the past decade. At the brain level, dyslexia is associated with aberrant structure and function, particularly in left hemisphere reading/language networks. The neurocognitive influences on dyslexia are also multifactorial and involve phonological processing deficits as well as weaknesses in other oral language skills and processing speed. We address contextual issues such as how dyslexia manifests across languages and social classes as well as what treatments are best supported. Throughout the review, we highlight exciting new research that cuts across levels of analysis. Such work promises eventually to provide a comprehensive explanation of the disorder as well as its prevention and remediation.

  14. 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 transcriptional...... signaling. When various mutated GHR cDNAs were transfected stably into Chinese hamster ovary cells or transiently into monkey kidney (COS-7) cells, internalization of the GHR was found to be dependent upon a domain located between amino acids 318 and 380. Mutational analysis of aromatic residues...... in this domain revealed that phenylalanine 346 is required for internalization. Receptor down-regulation in transiently transfected COS-7 cells was also dependent upon the phenylalanine 346 residue of the GHR, since no GH-induced down-regulation was observed in cells expressing the F346A GHR mutant. In contrast...

  15. A short sequence immediately upstream of the internal repeat elements is critical for KSHV LANA mediated DNA replication and impacts episome persistence.

    Science.gov (United States)

    De León Vázquez, Erika; Juillard, Franceline; Rosner, Bernard; Kaye, Kenneth M

    2014-01-05

    Kaposi's sarcoma-associated herpesvirus LANA (1162 residues) mediates episomal persistence of viral genomes during latency. LANA mediates viral DNA replication and segregates episomes to daughter nuclei. A 59 residue deletion immediately upstream of the internal repeat elements rendered LANA highly deficient for DNA replication and modestly deficient for the ability to segregate episomes, while smaller deletions did not. The 59 amino acid deletion reduced LANA episome persistence by ~14-fold, while sequentially smaller deletions resulted in ~3-fold, or no deficiency. Three distinct LANA regions reorganized heterochromatin, one of which contains the deleted sequence, but the deletion did not abolish LANA's ability to alter chromatin. Therefore, this work identifies a short internal LANA sequence that is critical for DNA replication, has modest effects on episome segregation, and substantially impacts episome persistence; this region may exert its effects through an interacting host cell protein(s). © 2013 Published by Elsevier Inc.

  16. Interventions for Suicidal Youth: A Review of the Literature and Developmental Considerations

    OpenAIRE

    Daniel, Stephanie S.; Goldston, David B.

    2009-01-01

    Suicidal behavior is developmentally mediated, but the degree to which interventions for suicidal behaviors have been developmentally tailored has varied widely. Published controlled studies of psychosocial treatment interventions for reducing adolescent suicidal behavior are reviewed, with a particular emphasis on the developmental nuances of these interventions. In addition, developmental considerations important in the treatment of suicidal adolescents are discussed. There are insufficient...

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

    Directory of Open Access Journals (Sweden)

    Crepieux Pascale

    2006-06-01

    Full Text Available Abstract 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.

  18. 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.

  19. 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

  20. C-terminal of human histamine H1receptors 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.

  1. 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.

  2. The international society for developmental psychobiology Sackler symposium: early adversity and the maturation of emotion circuits--a cross-species analysis.

    Science.gov (United States)

    Callaghan, Bridget L; Sullivan, Regina M; Howell, Brittany; Tottenham, Nim

    2014-12-01

    Early-life caregiving shapes the architecture and function of the developing brain. The fact that the infant-caregiver relationship is critically important for infant functioning across all altricial species, and that the anatomical circuits supporting emotional functioning are highly preserved across different species, suggests that the results of studies examining the role of early adversity and emotional functioning should be translatable across species. Here we present findings from four different research laboratories, using three different species, which have converged on a similar finding: adversity accelerates the developmental trajectory of amygdala-prefrontal cortex (PFC) development and modifies emotional behaviors. First, a rodent model of attachment learning associated with adversity is presented showing precocial disruption of attachment learning and emergence of heightened fear learning and emotionality. Second, a model of infant-mother separation is presented in which early adversity is shown to accelerate the developmental emergence of adult-like fear retention and extinction. Third, a model of early life adversity in Rhesus monkeys is presented in which a naturally occurring variation in maternal-care (abuse) is shown to alter the functioning of emotion circuits. Finally, a human model of maternal deprivation is presented in which children born into orphanages and then adopted abroad exhibit aberrant development of emotion circuits. The convergence of these cross-species studies on early life adversity suggests that adversity targets the amygdala and PFC and has immediate impact on infant behavior with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations. © 2014 Wiley Periodicals, Inc.

  3. 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...

  4. 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.

  5. Mediação semiótica: estudo de caso de uma criança cega, com alterações no desenvolvimento Semiotic mediation: a case study of a blind child with developmental alterations

    Directory of Open Access Journals (Sweden)

    Michelli Alessandra Silva

    2007-01-01

    Full Text Available É relatado o caso de uma criança cega congênita de quatro anos, com alterações no desenvolvimento, analisado de acordo com as concepções de linguagem constitutiva (Franchi, 1977/1992 e mediação semiótica (Rodríguez & Moro, 1999. Sete sessões de intervenção, compreendendo um intervalo de dois anos, foram transcritas e analisadas. A adaptação da metodologia utilizada por Rodríguez e Moro permitiu que se observassem as aquisições de uso de objetos (desde usos menos convencionais até usos mais convencionais, a participação em brincadeiras (ex: acompanhamento de cantigas infantis e o surgimento de diferentes modos de comunicação. A análise deu significado a diferentes aspectos da interação entre a criança e adultos, expandindo a proposta das autoras, em relação ao papel da mediação semiótica. Discutem-se as implicações do estudo para a área de Educação Especial.The case of a 4 year old congenitally blind child, with developmental alterations, was analyzed, according to assumptions of constitutive language (Franchi, 1977 and semiotic mediation (Rodríguez & Moro, 1999. Seven sessions of intervention were transcribed and analyzed, comprising a period of two years. The adaptation of the methodology of Rodríguez & Moro allowed the observation of the following aspects: the acquisition of use of objects (from less conventional uses to more conventional uses, the participation in play activities (eg: nursery rhymes and the appearance of different modes of communication. Different aspects of the adult-child interaction were given significance, expanding the scope of the original proposition in relation to the role of semiotic mediation. The implications of the study to the area of Special Education were discussed.

  6. 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

  7. 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.)

  8. 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

  9. 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…

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Mental health difficulties and academic attainment: Evidence for gender-specific developmental cascades in middle childhood.

    Science.gov (United States)

    Panayiotou, Margarita; Humphrey, Neil

    2017-07-17

    We present a developmental cascade model of the longitudinal relationships between internalizing symptoms, externalizing problems, and academic performance in middle childhood, utilizing a large sample (N = 1,771) from the United Kingdom in a 3-year, cross-lag design. Three hypotheses were tested: adjustment erosion, academic incompetence, and (cumulative) shared risk. In addition, we sought to examine whether developmental cascade pathways varied across gender, while also statistically exploring indirect, mediation pathways. Structural equation models that accounted for within-time covariance, data nesting, and temporal stability provided evidence of gender-specific effects as follows: externalizing-attainment adjustment erosion pathways were found only in boys, while attainment-internalizing/externalizing academic incompetence pathways were found only in girls. Analysis of mediation pathways provided further support for these gender-specific longitudinal profiles. Protective longitudinal internalizing-externalizing and externalizing-internalizing pathways were found for both boys and girls. Finally, while it improved model fit for both genders, the influence of cumulative shared risk on the aforementioned pathways was relatively meager, substantively affecting only one (externalizing-attainment adjustment erosion pathway in boys). The implications of these findings are discussed, and study limitations noted.

  15. 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.

  16. Mediating Knowledge through Peer-to-Peer Interaction in a Multicultural Online Learning Environment: A Case Study of International Students in the US

    Directory of Open Access Journals (Sweden)

    Gulnara Sadykova

    2014-07-01

    Full Text Available The continuous growth of online learning and its movement towards cross-border and cross-culture education has recently taken a new turn with the epic hype that currently surrounds the development of massive open online courses (MOOCs (Beattie-Moss, 2013. This development brings to focus the experiences of international students who take online courses designed and offered within the paradigm of Western pedagogy. Employing a sociocultural theoretical framework (Vygotsky, 1978; Scollon & Scollon, 2001, this paper examines the mediating roles that peers may play in the context of multicultural online learning environments. This two-stage, mixed methods study explored the experiences of 12 international graduate students who took fully online courses in a large research university in the northeastern region of the United States. The data included a survey, online interviews, as well as a case study that took a close look at the experiences of a female student from China. Findings of the study demonstrated that international students that come from diverse native academic backgrounds and cultures may necessitate a close relationship with peers they meet in the US courses. Peers become invaluable mediators of knowledge for international students who seek peer assistance to compensate for the lack of culture-specific knowledge and skills and to satisfy their interest in the host culture. The study suggests that course developers and facilitators should be proactive when assigning group projects and activities so as to enable close peer-to-peer interaction and opportunities for building personal relationships with other class members.

  17. An anti-HIV-1 gp120 antibody expressed as an endocytotic transmembrane protein mediates internalization of HIV-1

    International Nuclear Information System (INIS)

    Tan, Yee-Joo; Lim, S.-P.; Ting, Anthony E.; Goh, Phuay-Yee; Tan, Y.H.; Lim, Seng Gee; Hong Wanjin

    2003-01-01

    In this study, we used HIV-1 as a model to demonstrate a novel approach for receptor-independent cell entry of virus. The heavy chain of an anti-HIV-1 gp120 antibody was engineered with endocytotic and transmembrane motifs from either the cation-independent mannose 6-phospate receptor or the low-density lipoprotein receptor. Flow cytometry and immunofluorescence studies showed that the chimeric antibodies were expressed on the cell surface and can undergo rapid internalization. Furthermore, one of the chimeric antibodies was able to bind and internalize HIV-1. Using a luciferase reporter HIV-1, we further showed that internalized viruses could undergo replication. Therefore, we have demonstrated a proof-of-principle of a novel method that can be used to internalize virus into cells, without prior knowledge of the cellular receptor for the virus. We propose that this approach would be particularly useful for studying viruses whose cellular receptor(s) is not known

  18. 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

  19. Developmental Dynamics of Rett Syndrome.

    Science.gov (United States)

    Feldman, Danielle; Banerjee, Abhishek; Sur, Mriganka

    2016-01-01

    Rett Syndrome was long considered to be simply a disorder of postnatal development, with phenotypes that manifest only late in development and into adulthood. A variety of recent evidence demonstrates that the phenotypes of Rett Syndrome are present at the earliest stages of brain development, including developmental stages that define neurogenesis, migration, and patterning in addition to stages of synaptic and circuit development and plasticity. These phenotypes arise from the pleotropic effects of MeCP2, which is expressed very early in neuronal progenitors and continues to be expressed into adulthood. The effects of MeCP2 are mediated by diverse signaling, transcriptional, and epigenetic mechanisms. Attempts to reverse the effects of Rett Syndrome need to take into account the developmental dynamics and temporal impact of MeCP2 loss.

  20. 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)

  1. 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.

  2. [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

  3. 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.

  4. 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)

  5. 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.

  6. Interventions for Suicidal Youth: A Review of the Literature and Developmental Considerations

    Science.gov (United States)

    Daniel, Stephanie S.; Goldston, David B.

    2009-01-01

    Suicidal behavior is developmentally mediated, but the degree to which interventions for suicidal behaviors have been developmentally tailored has varied widely. Published controlled studies of psychosocial treatment interventions for reducing adolescent suicidal behavior are reviewed, with a particular emphasis on the developmental nuances of…

  7. 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.

  8. 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

  9. Interoception, emotion and brain: new insights link internal physiology to social behaviour. Commentary on:: "Anterior insular cortex mediates bodily sensibility and social anxiety" by Terasawa et al. (2012).

    Science.gov (United States)

    Garfinkel, Sarah N; Critchley, Hugo D

    2013-03-01

    In this issue, Terasawa and colleagues used functional neuroimaging to test for common neural substrates supporting conscious appraisal of subjective bodily and emotional states and explored how the relationship might account for personality and experience of anxiety symptoms. Their study highlights a role for the same region of anterior insula cortex in appraisal of emotions and bodily physiology. The reactivity of this region also mediated the relationship between 'bodily sensibility' and social fear, translating a cognitive representation of subjective physical state into an individual personality trait that influences social interaction. The task used by Terasawa and colleagues taps into conscious aspects to the expression of this dynamic. These findings add to increasing evidence for the role of anterior insula as the interface between physiologically driven internal motivational states, emotional awareness and interpersonal behaviour.

  10. 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

  11. 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.

  12. 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.

  13. Mental health consequences of international migration for Vietnamese Americans and the mediating effects of physical health and social networks: results from a natural experiment approach.

    Science.gov (United States)

    Fu, Hongyun; VanLandingham, Mark J

    2012-05-01

    Although the existing literature on immigrant mental health is extensive, major substantive and methodological gaps remain. Substantively, there is little population-based research that focuses on the mental health consequences of migration for Vietnamese Americans. More generally, although a wide range of mental health problems among immigrants has been identified, the potential causal or mediating mechanisms underlying these problems remain elusive. This latter substantive shortcoming is related to a key methodological challenge involving the potentially confounding effects of selection on migration-related outcomes. This article addresses these challenges by employing a "natural experiment" design, involving comparisons among three population-based samples of Vietnamese immigrants, never-leavers, and returnees (N=709). Data were collected in Ho Chi Minh City and in New Orleans between 2003 and 2005. The study investigates the long-term impact of international migration on Vietnamese mental health, and the potential mediating effects of social networks and physical health on these migration-related outcomes. The results reveal both mental health advantages and disadvantages among Vietnamese immigrants relative to the two groups of Vietnamese nationals. Selection can be ruled out for some of these differences, and both social networks and physical health are found to play important explanatory roles.

  14. 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.

  15. Anti-Sclerostin antibody inhibits internalization of Sclerostin and Sclerostin-mediated antagonism of Wnt/LRP6 signaling.

    Directory of Open Access Journals (Sweden)

    Maarten van Dinther

    Full Text Available Sclerosteosis is a rare high bone mass disease that is caused by inactivating mutations in the SOST gene. Its gene product, Sclerostin, is a key negative regulator of bone formation and might therefore serve as a target for the anabolic treatment of osteoporosis. The exact molecular mechanism by which Sclerostin exerts its antagonistic effects on Wnt signaling in bone forming osteoblasts remains unclear. Here we show that Wnt3a-induced transcriptional responses and induction of alkaline phosphatase activity, an early marker of osteoblast differentiation, require the Wnt co-receptors LRP5 and LRP6. Unlike Dickkopf1 (DKK1, Sclerostin does not inhibit Wnt-3a-induced phosphorylation of LRP5 at serine 1503 or LRP6 at serine 1490. Affinity labeling of cell surface proteins with [(125I]Sclerostin identified LRP6 as the main specific Sclerostin receptor in multiple mesenchymal cell lines. When cells were challenged with Sclerostin fused to recombinant green fluorescent protein (GFP this was internalized, likely via a Clathrin-dependent process, and subsequently degraded in a temperature and proteasome-dependent manner. Ectopic expression of LRP6 greatly enhanced binding and cellular uptake of Sclerostin-GFP, which was reduced by the addition of an excess of non-GFP-fused Sclerostin. Finally, an anti-Sclerostin antibody inhibited the internalization of Sclerostin-GFP and binding of Sclerostin to LRP6. Moreover, this antibody attenuated the antagonistic activity of Sclerostin on canonical Wnt-induced responses.

  16. 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.

  17. Mediators of trade and taste. Dealing with demand and quality uncertainty in the international art markets of the seventeenth century

    Directory of Open Access Journals (Sweden)

    Claartje Rasterhoff

    2015-12-01

    Full Text Available Early modern Antwerp-based art dealers exported a variety of luxury goods across Europe and beyond. They traded locally and globally in mass-produced and unique goods of fancy, in newly produced and resold items. Our contribution examines the business models of these dealers in order to better understand the extraordinary reach of the early modern international art trade and its cultural ramifications. The Forchondt and Musson art dealing firms serve as a case study to put into context the artistic exchanges between Southern and Northern Netherlands during the second half of the seventeenth century and we reveal how their business strategies (both on a cultural and economic level helped to overcome high levels of quality and demand uncertainty.

  18. Mediating Effects of Social Support and Internalized Homonegativity on the Association Between Population Density and Mental Health Among Gay and Bisexual Men.

    Science.gov (United States)

    Cain, Demetria N; Mirzayi, Chloe; Rendina, H Jonathon; Ventuneac, Ana; Grov, Christian; Parsons, Jeffrey T

    2017-10-01

    Depression negatively impacts the health and well-being of gay and bisexual men (GBM). However, little is known about the contexts in which rural GBM live relative to those living in urban areas and their overall mental health. The aim of this study was to examine associations between population density and depressive symptoms and the role of internalized homonegativity and social support as potential mediators. A nationally representative sample of 1071 GBM (mean age = 40.24) was enrolled. Participants provided their zip codes, which were categorized according to population density and rank-normalized. In a path analysis model adjusted for race/ethnicity, college education, age, and relationship status, higher population density was significantly associated with increased social support (B = 0.11, P = 0.002) and decreased internalized homonegativity (B = -0.06, P mental health outcomes and indicate the need for further support and inclusion of GBM, especially in less inhabited areas.

  19. 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)

    Higgins, Owen; Clancy, Eoin; Cormican, Martin; Boo, Teck Wee; Cunney, Robert; Smith, Terry J

    2018-02-09

    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.

  20. 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.

  1. 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...

  2. [Developmental sequel of prematurity].

    Science.gov (United States)

    Helwich, Ewa

    2003-01-01

    Severe developmental impairment in children born as extremly prematures include cerebral palsy, subnormal cognitive function, deafness and blindness. The rate of severe disabilities range from 5 to 30%. This article reviews what is known about early brain injury and its developmental sequel.

  3. 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.

  4. 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

  5. Among the Periodicals: Developmentally Appropriate Practice

    Science.gov (United States)

    Kohler, Maxie; Christensen, Lois; Kilgo, Jennifer

    2012-01-01

    This article contains a review of eight refereed publications that addressed the topic of developmentally appropriate practice (DAP), as that is a topic presently being discussed widely both nationally and internationally. According to the most recent 2009 NAEYC publication on DAP, recommended practices are those "that result from the process of…

  6. 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.

  7. 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.

  8. 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.

  9. La Autoantigen Induces Ribosome Binding Protein 1 (RRBP1 Expression through Internal Ribosome Entry Site (IRES-Mediated Translation during Cellular Stress Condition

    Directory of Open Access Journals (Sweden)

    Wenqing Gao

    2016-07-01

    Full Text Available The function of ribosome binding protein 1 (RRBP1 is regulating the transportation and secretion of some intracellular proteins in mammalian cells. Transcription of RRBP1 is induced by various cytokines. However, few studies focused on the process of RRPB1 mRNA translation. The RRBP1 mRNA has a long 5′ untranslated region that potentially formed a stable secondary structure. In this study, we show that the 5′ UTR of RRBP1 mRNA contains an internal ribosome entry site (IRES. Moreover, the RRBP1 expression is induced by chemotherapeutic drug paclitaxel or adriamycin in human hepatocellular carcinoma cells and accompanied with the increased expression of La autoantigen (La, which binds to RRBP1 IRES element and facilitates translation initiation. Interestingly, we found IRES-mediated RRBP1 translation is also activated during serum-starvation condition which can induce cytoplasmic localization of La. After mapping the entire RRBP1 5′ UTR, we determine the core IRES activity is located between nt-237 and -58. Furthermore, two apical GARR loops within the functional RRBP1 IRES elements may be important for La binding. These results strongly suggest an important role for IRES-dependent translation of RRBP1 mRNA in hepatocellular carcinoma cells during cellular stress conditions.

  10. 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 ...

  11. Facts about Developmental Disabilities

    Science.gov (United States)

    ... to maternal infections during pregnancy, such as cytomegalovirus (CMV) infection ; complications after birth; and head trauma. Some ... an increased risk for many developmental disabilities. Untreated newborn jaundice (high levels of bilirubin in the blood ...

  12. Developmental reading disorder

    Science.gov (United States)

    ... brain does not properly recognize and process certain symbols. It is also called dyslexia. Causes Developmental reading ... child's early reading skills are based on word recognition. That involves being able to separate out the ...

  13. 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.

  14. 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

  15. 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

  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 Climate: A Cross-level Analysis of Voluntary Turnover and Job Performance

    Science.gov (United States)

    Spell, Hannah B.; Eby, Lillian T.; Vandenberg, Robert J.

    2014-01-01

    This research investigates the influence of shared perceptions of developmental climate on individual-level perceptions of organizational commitment, engagement, and perceived competence, and whether these attitudes mediate the relationship between developmental climate and both individual voluntary turnover and supervisor-rated job performance. Survey data were collected from 361 intact employee-supervisory mentoring dyads and matched with employee turnover data collected one year later to test the proposed framework using multilevel modeling techniques. As expected, shared perceptions of developmental climate were significantly and positively related to all three individual work attitudes. In addition, both organizational commitment and perceived competence were significant mediators of the positive relationship between shared perceptions of developmental climate and voluntary turnover, as well as shared perceptions of developmental climate and supervisor-rated job performance. By contrast, no significant mediating effects were found for engagement. Theoretical implications, limitations, and future research are discussed. PMID:24748681

  18. Developmental Climate: A Cross-level Analysis of Voluntary Turnover and Job Performance.

    Science.gov (United States)

    Spell, Hannah B; Eby, Lillian T; Vandenberg, Robert J

    2014-06-01

    This research investigates the influence of shared perceptions of developmental climate on individual-level perceptions of organizational commitment, engagement, and perceived competence, and whether these attitudes mediate the relationship between developmental climate and both individual voluntary turnover and supervisor-rated job performance. Survey data were collected from 361 intact employee-supervisory mentoring dyads and matched with employee turnover data collected one year later to test the proposed framework using multilevel modeling techniques. As expected, shared perceptions of developmental climate were significantly and positively related to all three individual work attitudes. In addition, both organizational commitment and perceived competence were significant mediators of the positive relationship between shared perceptions of developmental climate and voluntary turnover, as well as shared perceptions of developmental climate and supervisor-rated job performance. By contrast, no significant mediating effects were found for engagement. Theoretical implications, limitations, and future research are discussed.

  19. Developmental Neurotoxicology: History and Outline of ...

    Science.gov (United States)

    The present work provides a brief review of basic concepts in developmental neurotoxicology, as well as current representative testing guidelines for evaluating developmental neurotoxicity (DNT) of xenobiotics. Historically, DNT was initially recognized as a “functional” teratogenicity: the main concern was that prenatal and/or early postnatal exposures to chemicals during critical periods of central nervous system (CNS) development would cause later functional abnormalities of the brain. Current internationally harmonized DNT study guidelines are thus intended to predict adverse effects of test compounds on the developing CNS by observing such postnatal parameters as motor activity, startle response, and learning and memory, as well as neropathological alterations. The reliability of current DNT study guidelines and sensitivity of testing methodologies recommended in these guidelines have been confirmed by retrospective evaluations of the many international and domestic collaborative validation studies in developed nations including Japan. Invited review with brief review of basic concepts in developmental neurotoxicology, as well as current representative testing guidelines for evaluating developmental neurotoxicity (DNT) of xenobiotics.

  20. Reading in developmental prosopagnosia

    DEFF Research Database (Denmark)

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

    2018-01-01

    OBJECTIVE: Recent models suggest that face and word recognition may rely on overlapping cognitive processes and neural regions. In support of this notion, face recognition deficits have been demonstrated in developmental dyslexia. Here we test whether the opposite association can also be found......, 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...

  1. Parental Negative Control Moderates the Shyness–Emotion Regulation Pathway to School-Age Internalizing Symptoms

    Science.gov (United States)

    Shaw, Daniel S.; Moilanen, Kristin L.

    2011-01-01

    Models of developmental psychopathology emphasize both mediation and moderation processes among child and caregiving attributes; however, little research has examined both these processes simultaneously on the development of internalizing problems. This study tested a moderated mediation model that related early childhood shyness, emotion regulation and maternal negative control to school-age internalizing problems among 257 boys from low-income families. Shyness and maternal negative control was assessed at ages 1.5–2, emotion regulation was observed at age 3.5, and internalizing symptoms were assessed by mothers and teachers at age 6 or 7. Results indicated that 1) the active distraction regulation strategy mediated the relations between early shyness and maternal report of internalizing symptoms; 2) the passive/dependent regulation strategy mediated the relations between shyness and teacher report of internalizing symptoms; and 3) both mediation processes were moderated by maternal negative control. The results are discussed in relation to implications for early prevention and intervention. PMID:21107676

  2. 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...

  3. 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…

  4. 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.

  5. 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...

  6. Learning Developmental Coaching

    Science.gov (United States)

    Hunt, James M.; Weintraub, Joseph R.

    2004-01-01

    This article describes an educational intervention designed to promote the ability and willingness of MBA students to lead through coaching. MBA leadership students are trained to serve as coaches for undergraduate business students in a developmental assessment center. In this compelling context, their main source of influence is the ability to…

  7. Alcoholism: A Developmental Disorder.

    Science.gov (United States)

    Tarter, Ralph E.; Vanyukov, Michael

    1994-01-01

    Alcoholism etiology is discussed from developmental behavior genetic perspective. Temperament features that appear to be associated with heightened risk for alcoholism are examined. Their interactions with the environment during course of development are considered within epigenetic framework and, as discussed, have ramifications for improving…

  8. Evolutionary Developmental Psychology.

    Science.gov (United States)

    Geary, David C.; Bjorklund, David F.

    2000-01-01

    Describes evolutionary developmental psychology as the study of the genetic and ecological mechanisms that govern the development of social and cognitive competencies common to all human beings and the epigenetic (gene-environment interactions) processes that adapt these competencies to local conditions. Outlines basic assumptions and domains of…

  9. 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...

  10. Speech and Language Developmental Milestones

    Science.gov (United States)

    ... Health Info » Voice, Speech, and Language Speech and Language Developmental Milestones On this page: How do speech ... and language developmental milestones? How do speech and language develop? The first 3 years of life, when ...

  11. Developmental Milestones of Early Literacy

    Science.gov (United States)

    ... Size Email Print Share Developmental Milestones of Early Literacy Page Content ​In the spirit of making both ... at the well-defined developmental milestones of early literacy. Younger Than 6 Months: Never Too Young Unlike ...

  12. Developmental Purposes of Commercial Games.

    Science.gov (United States)

    Practical Pointers, 1977

    1977-01-01

    Listed are 45 table, target, manipulative, active, and creative games with such developmental purposes as associative learning, tactile discrimination, and visual motor integration. Information includes the name of the item, distributor, price, description, and developmental purpose. (JYC)

  13. Developmental plasticity: Bridging research in evolution and human health.

    Science.gov (United States)

    Lea, Amanda J; Tung, Jenny; Archie, Elizabeth A; Alberts, Susan C

    2017-01-01

    Early life experiences can have profound and persistent effects on traits expressed throughout the life course, with consequences for later life behavior, disease risk, and mortality rates. The shaping of later life traits by early life environments, known as 'developmental plasticity', has been well-documented in humans and non-human animals, and has consequently captured the attention of both evolutionary biologists and researchers studying human health. Importantly, the parallel significance of developmental plasticity across multiple fields presents a timely opportunity to build a comprehensive understanding of this phenomenon. We aim to facilitate this goal by highlighting key outstanding questions shared by both evolutionary and health researchers, and by identifying theory and empirical work from both research traditions that is designed to address these questions. Specifically, we focus on: (i) evolutionary explanations for developmental plasticity, (ii) the genetics of developmental plasticity and (iii) the molecular mechanisms that mediate developmental plasticity. In each section, we emphasize the conceptual gains in human health and evolutionary biology that would follow from filling current knowledge gaps using interdisciplinary approaches. We encourage researchers interested in developmental plasticity to evaluate their own work in light of research from diverse fields, with the ultimate goal of establishing a cross-disciplinary understanding of developmental plasticity.

  14. 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

  15. International study on syncope of uncertain aetiology 3 (ISSUE 3): pacemaker therapy for patients with asystolic neurally-mediated syncope: rationale and study design

    NARCIS (Netherlands)

    Brignole, M.; Andresen, Dietrich; Benditt, David; Blanc, Jean Jacques; Garcia-Civera, Roberto; Khran, Andrew; Menozzi, Carlo; Moya, Angel; Sutton, Richard; Vardas, Panos; Wieling, Wouter

    2007-01-01

    Aim To assess the effectiveness of pacing therapy for preventing syncope recurrence in patients with a high probability of cardio-inhibitory neurally-mediated syncope (NMS). Methods Study design: Multi-centre, prospective, double-blind, randomized placebo-controlled study. Inclusion criteria:

  16. 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…

  17. 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)

  18. Petro-States - Predatory or Developmental?

    International Nuclear Information System (INIS)

    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)

  19. [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.

  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. 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.

  2. 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.

  3. 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%.

  4. 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...

  5. Developmental coordination disorder - literature review

    OpenAIRE

    Kosová, Blanka

    2015-01-01

    Title: Developmental coordination disorder - literature review Objectives: The theoretical part talks about developmental coordination disorder, its diagnosis, investigations, etiology and division during the different ages of the child. The practical part compares the studies relating to atypical development of motor skills in children with developmental coordination disorder. In diploma thesis was often used shortcut CKP and DCD, depending on the source from which it was drawn. DCD is the E...

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. Young Children's Behavioral Inhibition Mediates the Association between Maternal Negative Affectivity and Internalizing Problems: Observations, Parent-Report, and Moderation of Associations by Age

    Science.gov (United States)

    Fang, Haolei; Gagne, Jeffrey Robert

    2018-01-01

    Employing a multi-method approach, we investigated observed and parent-rated child behavioral inhibition (BI) and maternal reports of their own negative affectivity (NA) as predictors of young children's internalizing problems. Participants were 201 children who were siblings between 2.5 and 5.5 years of age (mean = 3.86, standard deviation =…

  17. 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…

  18. [Developmental venous anomaly (DVA)].

    Science.gov (United States)

    Zimmer, A; Hagen, T; Ahlhelm, F; Viera, J; Reith, W; Schulte-Altedorneburg, G

    2007-10-01

    As congenital anatomic variants of venous drainage, developmental venous anomalies (DVA) represent up to 60% of all cerebral vascular malformations. The prior term "venous angioma" is a misnomer implicating an abnormal vascular structure with an increased bleeding risk. They are often found incidentally and are hardly ever symptomatic. Their morphologic characteristics are dilated vessels in the white matter, which converge on a greater collector vein, forming the typical caput medusae. They drain into the superficial or deep venous system. The frequent association with other, potentially bleeding-prone vascular malformations is clinically relevant, in particular cavernous angioma, which might require therapeutic action. Therefore, coincident vascular lesions need to be actively sought by appropriate additional imaging techniques.

  19. 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.

  20. 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 ...

  1. Is Rett Syndrome a Subtype of Pervasive Developmental Disorders?

    Science.gov (United States)

    Tsai, Luke Y.

    1992-01-01

    This paper reviews whether Rett syndrome is a subtype of pervasive developmental disorders (PDD). The paper analyzes internal and external diagnostic validity and discusses whether Rett syndrome is a neurological disorder or a mental disorder. The paper concludes that data support the idea of classifying Rett syndrome as a subtype of PDD.…

  2. 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...

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

    Science.gov (United States)

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

    2011-12-01

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

  4. Charles Darwin and the Origins of Plant Evolutionary Developmental Biology

    Science.gov (United States)

    Friedman, William E.; Diggle, Pamela K.

    2011-01-01

    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. PMID:21515816

  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. 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

  7. 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.

  8. 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.

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

    OpenAIRE

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

    2014-01-01

    IL-33, a relatively new member of the IL-1 cytokine family, plays a crucial role in allergic inflammation and acute lung injury. 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. Here, we demonstrate that glycogen synthase kinase 3β (GSK3β) regulates S...

  10. 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.

  11. Developmental Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

    OpenAIRE

    Portugal, George S.; Wilkinson, Derek S.; Turner, Jill R.; Blendy, Julie A.; Gould, Thomas J.

    2012-01-01

    Pre-adolescence and adolescence are developmental periods associated with increased vulnerability for tobacco addiction, and exposure to tobacco during these periods may lead to long-lasting changes in behavioral and neuronal plasticity. The present study examined the short- and long-term effects of nicotine and nicotine withdrawal on fear conditioning in pre-adolescent, adolescent, and adult mice, and potential underlying substrates that may mediate the developmental effects of nicotine, suc...

  12. Developmental dyslexia and vision

    Directory of Open Access Journals (Sweden)

    Quercia P

    2013-05-01

    Full Text Available Patrick Quercia,1 Léonard Feiss,2 Carine Michel31Department of Ophthalmology, University Hospital, Dijon, France; 2Office of Ophthalmology, Beaune, France; 3University of Burgundy, Dijon, INSERM U1093, Cognition, Action et Plasticité Sensorimotrice, Dijon, FranceAbstract: Developmental dyslexia affects almost 10% of school-aged children and represents a significant public health problem. Its etiology is unknown. The consistent presence of phonological difficulties combined with an inability to manipulate language sounds and the grapheme–phoneme conversion is widely acknowledged. Numerous scientific studies have also documented the presence of eye movement anomalies and deficits of perception of low contrast, low spatial frequency, and high frequency temporal visual information in dyslexics. Anomalies of visual attention with short visual attention spans have also been demonstrated in a large number of cases. Spatial orientation is also affected in dyslexics who manifest a preference for spatial attention to the right. This asymmetry may be so pronounced that it leads to a veritable neglect of space on the left side. The evaluation of treatments proposed to dyslexics whether speech or oriented towards the visual anomalies remains fragmentary. The advent of new explanatory theories, notably cerebellar, magnocellular, or proprioceptive, is an incentive for ophthalmologists to enter the world of multimodal cognition given the importance of the eye's visual input.Keywords: reading, ocular motility, dyslexia, neglect, spatial representation

  13. 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

  14. 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

    2007-10-01

    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.

  15. 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

    eps15R was identified because of its relatedness to eps15, a gene encoding a tyrosine kinase substrate bearing a novel protein-protein interaction domain, called EH. In this paper, we report a biochemical characterization of the eps15R gene product(s). In NIH-3T3 cells, three proteins of 125, 108......, and 76 kDa were specifically recognized by anti-eps15R sera. The 125-kDa species is a bona fide product of the eps15R gene, whereas p108 and p76 are most likely products of alternative splicing events. Eps15R protein(s) are tyrosine-phosphorylated following epidermal growth factor receptor activation...... 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...

  16. 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.

  17. Mediatized Humanitarianism

    DEFF Research Database (Denmark)

    Vestergaard, Anne

    2014-01-01

    The article investigates the implications of mediatization for the legitimation strategies of humanitarian organizations. Based on a (full population) corpus of ~400 pages of brochure material from 1970 to 2007, the micro-textual processes involved in humanitarian organizations' efforts to legiti......The article investigates the implications of mediatization for the legitimation strategies of humanitarian organizations. Based on a (full population) corpus of ~400 pages of brochure material from 1970 to 2007, the micro-textual processes involved in humanitarian organizations' efforts...... legitimation by accountancy, legitimation by institutionalization, and legitimation by compensation. The analysis relates these changes to a problem of trust associated with mediatization through processes of mediation....

  18. Developmental Problems and Dental Morphology

    Science.gov (United States)

    Goodwin, William C., Jr.; Erickson, Marilyn T.

    1973-01-01

    Ninety-five subjects (mean age 55 months) with mental retardation, learning disabilities, and/or minimal brain dysfunction and 47 control subjects (mean age 46 months) were compared to determine the relationship between developmental problems and dental morphology. (Author)

  19. Developmental dysplasia of the hip

    Science.gov (United States)

    ... dislocation of the hip joint; Developmental hip dysplasia; DDH; Congenital dysplasia of the hip; Congenital dislocation of ... during pregnancy can increase a baby's risk of DDH. Other risk factors include: Being the first child ...

  20. Topographic processing in developmental prosopagnosia

    DEFF Research Database (Denmark)

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

    2016-01-01

    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. Participant...

  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...

  2. 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.

  3. 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.

  4. 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

  5. Plant developmental responses to climate change.

    Science.gov (United States)

    Gray, Sharon B; Brady, Siobhan M

    2016-11-01

    Climate change is multi-faceted, and includes changing concentrations of greenhouse gases in the atmosphere, rising temperatures, changes in precipitation patterns, and increasing frequency of extreme weather events. Here, we focus on the effects of rising atmospheric CO 2 concentrations, rising temperature, and drought stress and their interaction on plant developmental processes in leaves, roots, and in reproductive structures. While in some cases these responses are conserved across species, such as decreased root elongation, perturbation of root growth angle and reduced seed yield in response to drought, or an increase in root biomass in shallow soil in response to elevated CO 2 , most responses are variable within and between species and are dependent on developmental stage. These variable responses include species-specific thresholds that arrest development of reproductive structures, reduce root growth rate and the rate of leaf initiation and expansion in response to elevated temperature. Leaf developmental responses to elevated CO 2 vary by cell type and by species. Variability also exists between C 3 and C 4 species in response to elevated CO 2 , especially in terms of growth and seed yield stimulation. At the molecular level, significantly less is understood regarding conservation and variability in molecular mechanisms underlying these traits. Abscisic acid-mediated changes in cell wall expansion likely underlie reductions in growth rate in response to drought, and changes in known regulators of flowering time likely underlie altered reproductive transitions in response to elevated temperature and CO 2 . Genes that underlie most other organ or tissue-level responses have largely only been identified in a single species in response to a single stress and their level of conservation is unknown. We conclude that there is a need for further research regarding the molecular mechanisms of plant developmental responses to climate change factors in general, and

  6. 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…

  7. Hypothesis test of mediation effect in causal mediation model with high-dimensional continuous mediators.

    Science.gov (United States)

    Huang, Yen-Tsung; Pan, Wen-Chi

    2016-06-01

    Causal mediation modeling has become a popular approach for studying the effect of an exposure on an outcome through a mediator. However, current methods are not applicable to the setting with a large number of mediators. We propose a testing procedure for mediation effects of high-dimensional continuous mediators. We characterize the marginal mediation effect, the multivariate component-wise mediation effects, and the L2 norm of the component-wise effects, and develop a Monte-Carlo procedure for evaluating their statistical significance. To accommodate the setting with a large number of mediators and a small sample size, we further propose a transformation model using the spectral decomposition. Under the transformation model, mediation effects can be estimated using a series of regression models with a univariate transformed mediator, and examined by our proposed testing procedure. Extensive simulation studies are conducted to assess the performance of our methods for continuous and dichotomous outcomes. We apply the methods to analyze genomic data investigating the effect of microRNA miR-223 on a dichotomous survival status of patients with glioblastoma multiforme (GBM). We identify nine gene ontology sets with expression values that significantly mediate the effect of miR-223 on GBM survival. © 2015, The International Biometric Society.

  8. 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....

  9. Caspases: An apoptosis mediator

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Palai

    2015-03-01

    Full Text Available The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy - dependent biochemical mechanisms. Apoptosis is a widely conserved phenomenon helping many processes, including normal cell turnover, proper development and functioning of the immune system, hormone dependent atrophy etc. Inappropriate apoptosis (either low level or high level leads to many developmental abnormalities like, neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. To use cells for therapeutic purposes through generating cell lines, it is critical to study the cell cycle machinery and signalling pathways that controls cell death and apoptosis. Apoptotic pathways provide a fundamental protective mechanism that decreases cellular sensitivity to damaging events and allow proper developmental process in multi-cellular organisms. Major mediator of apoptosis is a family of proteins known as caspases. There are mainly fourteen types of caspases but out of them only ten caspasese have got essential role in controlling the process of apoptosis. These ten caspases have been categorized into either initiator caspases (caspase 2, 8, 9, 10 or executioner caspases (caspase 3, 6, 7. Although various types of caspases have been identified so far, the exact mechanisms of action of these groups of proteins is still to be fully understood. The aim of this review is to provide a detail overview of role of different caspases in regulating the process of apoptosis.

  10. Efficient Gene Delivery Mediated by a Helical Polypeptide: Controlling the Membrane Activity via Multivalency and Light-Assisted Photochemical Internalization (PCI).

    Science.gov (United States)

    Xu, Xin; Li, Yongjuan; Liang, Qiujun; Song, Ziyuan; Li, Fangfang; He, Hua; Wang, Jinhui; Zhu, Lipeng; Lin, Zhifeng; Yin, Lichen

    2018-01-10

    The development of robust and nontoxic membrane-penetrating materials is highly demanded for nonviral gene delivery. Herein, a photosensitizer (PS)-embedded, star-shaped helical polypeptide was developed, which combines the advantages of multivalency-enhanced intracellular DNA uptake and light-strengthened endosomal escape to enable highly efficient gene delivery with low toxicity. 5,10,15,20-Tetrakis-(4-aminophenyl) porphyrin as a selected PS initiated ring-opening polymerization of N-carboxyanhydride and yielded a star-shaped helical polypeptide after side-chain functionalization with guanidine groups. The star polypeptide afforded a notably higher transfection efficiency and lower cytotoxicity than those of its linear analogue. Light irradiation caused almost complete (∼90%) endosomal release of the DNA cargo via the photochemical internalization (PCI) mechanism and further led to a 6-8-fold increment of the transfection efficiency in HeLa, B16F10, and RAW 264.7 cells, outperforming commercial reagent 25k PEI by up to 3 orders of magnitude. Because the PS and DNA cargoes were compartmentalized distantly in the core and polypeptide layers, respectively, the generated reactive oxygen species caused minimal damage to DNA molecules to preserve their transfection potency. Such multivalency- and PCI-potentiated gene delivery efficiency was also demonstrated in vivo in melanoma-bearing mice. This study thus provides a promising strategy to overcome the multiple membrane barriers against nonviral gene delivery.

  11. Internalization of appearance ideals mediates the relationship between appearance-related pressures from peers and emotional eating among adolescent boys and girls.

    Science.gov (United States)

    Thompson, Katherine A; Kelly, Nichole R; Schvey, Natasha A; Brady, Sheila M; Courville, Amber B; Tanofsky-Kraff, Marian; Yanovski, Susan Z; Yanovski, Jack A; Shomaker, Lauren B

    2017-01-01

    Appearance-related pressures have been associated with binge eating in previous studies. Yet, it is unclear if these pressures are associated with emotional eating or if specific sources of pressure are differentially associated with emotional eating. We studied the associations between multiple sources of appearance-related pressures, including pressure to be thin and pressure to increase muscularity, and emotional eating in 300 adolescents (M age =15.3, SD=1.4, 60% female). Controlling for age, race, puberty, body mass index (BMI) z-score, and sex, both pressure to be thin and pressure to be more muscular from same-sex peers were positively associated with emotional eating in response to feeling angry/frustrated and unsettled (pseating when depressed (peating in response to anger/frustration (pemotional eating were non-significant. Results considering sex as a moderator of the associations between appearance-related pressures and emotional eating were non-significant. Findings illustrate that both pressure to be thin and muscular from peers are related to more frequent emotional eating among both boys and girls, and these associations are explained through internalization of appearance-related ideals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. 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.

  13. Internalization of Appearance Ideals Mediates the Relationship between Appearance-Related Pressures from Peers and Emotional Eating among Adolescent Boys and Girls

    Science.gov (United States)

    Thompson, Katherine A.; Kelly, Nichole R.; Schvey, Natasha A.; Brady, Sheila M.; Courville, Amber B.; Tanofsky-Kraff, Marian; Yanovski, Susan Z.; Yanovski, Jack A.; Shomaker, Lauren B.

    2016-01-01

    Appearance-related pressures have been associated with binge eating in previous studies. Yet, it is unclear if these pressures are associated with emotional eating or if specific sources of pressure are differentially associated with emotional eating. We studied the associations between multiple sources of appearance-related pressures, including pressure to be thin and pressure to increase muscularity, and emotional eating in 300 adolescents (Mage = 15.3, SD = 1.4, 60% female). Controlling for age, race, puberty, body mass index (BMI) z-score, and sex, both pressure to be thin and pressure to be more muscular from same-sex peers were positively associated with emotional eating in response to feeling angry/frustrated and unsettled (pseating when depressed (peating in response to anger/frustration (pemotional eating were non-significant. Results considering sex as a moderator of the associations between appearance-related pressures and emotional eating were non-significant. Findings illustrate that both pressure to be thin and muscular from peers are related to more frequent emotional eating among both boys and girls, and these associations are explained through internalization of appearance-related ideals. PMID:28038437

  14. 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...

  15. 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.

  16. 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

  17. 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.

  18. The renaissance of developmental biology.

    Science.gov (United States)

    St Johnston, Daniel

    2015-05-01

    Since its heyday in the 1980s and 90s, the field of developmental biology has gone into decline; in part because it has been eclipsed by the rise of genomics and stem cell biology, and in part because it has seemed less pertinent in an era with so much focus on translational impact. In this essay, I argue that recent progress in genome-wide analyses and stem cell research, coupled with technological advances in imaging and genome editing, have created the conditions for the renaissance of a new wave of developmental biology with greater translational relevance.

  19. 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

  20. 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...

  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 agreeme...

  2. The Developmental Psychopathology of Worry

    Science.gov (United States)

    Kertz, Sarah J.; Woodruff-Borden, Janet

    2011-01-01

    Although childhood generalized anxiety disorder is generally understudied, worry, the cardinal feature of GAD, appears to be relatively common in youth. Despite its prevalence, there are few conceptual models of the development of clinical worry in children. The current review provides a framework for integrating the developmental psychopathology…

  3. 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

  4. 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 =…

  5. 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…

  6. 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.

  7. Serving the Developmentally Disabled Aged.

    Science.gov (United States)

    Kallstrom, Lee A.

    Increasing numbers of aging developmentally disabled individuals have led to a recent emphasis being placed on service provision for this population, the education of professionals working with them, and the assessment of current conditions and needs of these individuals. Through the University Affiliated Program, a project of national…

  8. Building a developmental toxicity ontology.

    NARCIS (Netherlands)

    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

    2018-01-01

    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

  9. Vignettes in College Developmental Classes.

    Science.gov (United States)

    Valeri-Gold, Maria T.

    1994-01-01

    Discusses providing developmental learners with the opportunity to hear and respond to vignettes (short, descriptive literary sketches such as those in "The House on Mango Street"). Notes that the activity allowed students to experiment with another writing style and to use figurative language in a creative way. (RS)

  10. Successful Aging: A Developmental Approach.

    Science.gov (United States)

    Ryff, Carol D.

    1982-01-01

    Examines earlier conceptualizations of successful aging and calls for a reformulation that is more responsive to developmental processes and theoretical guidance. Discusses issues of operational definitions, selective sampling, and stage theory. The perspective is illustrated with empirical research in the personality realm. (Author)

  11. 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.

  12. Developmental Entrepreneurship Program : Massachusetts Institute ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Developmental Entrepreneurship Program at the Massachusetts Institute of Technology (MIT) helps researchers, students and practitioner from developing countries to investigate private-sector-driven solutions to health, energy and environmental problems. As a premier institution for technological innovation with an ...

  13. 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.

  14. 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.

  15. 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…

  16. 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…

  17. 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...

  18. 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....

  19. 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....

  20. 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…

  1. Can there be a developmental state in Morocco? Finding the right balance between autonomy and embeddedness

    OpenAIRE

    Bergh, Sylvia

    2008-01-01

    textabstractAbstract This paper draws on Peter Evans’ approach to the developmental state and applies it to examine the scope for state-society synergy at the local level in Morocco. In doing so, it highlights the usefulness of Evans’ concept of ‘embedded autonomy’ for theorizing about the developmental state. The paper studies the internal and interactive capacities of local government and local civil society organizations in Morocco. It argues that there are certain pre-conditions with rega...

  2. Developmental Milestones in Toddlers with Atypical Development

    Science.gov (United States)

    Horovitz, Max; Matson, Johnny L.

    2011-01-01

    The attainment of developmental milestones was examined and compared in 162 infants and toddlers with developmental disabilities, including Down Syndrome (n = 26), Cerebral Palsy (n = 19), Global Developmental Delay (n = 22), Premature birth (n = 66), and Seizure Disorder (n = 29). Toddlers in the Seizures Disorder group began crawling at a…

  3. Neuromuscular NMDA Receptors Modulate Developmental Synapse Elimination.

    Science.gov (United States)

    Personius, Kirkwood E; Slusher, Barbara S; Udin, Susan B

    2016-08-24

    At birth, each mammalian skeletal muscle fiber is innervated by multiple motor neurons, but in a few weeks, all but one of those axons retracts (Redfern, 1970) and differential activity between inputs controls this phenomenon (Personius and Balice-Gordon, 2001; Sanes and Lichtman, 2001; Personius et al., 2007; Favero et al., 2012). Acetylcholine, the primary neuromuscular transmitter, has long been presumed to mediate this activity-dependent process (O'Brien et al., 1978), but glutamatergic transmission also occurs at the neuromuscular junction (Berger et al., 1995; Grozdanovic and Gossrau, 1998; Mays et al., 2009). To test the role of neuromuscular NMDA receptors, we assessed their contribution to muscle calcium fluxes in mice and tested whether they influence removal of excess innervation at the end plate. Developmental synapse pruning was slowed by reduction of NMDA receptor activation or expression and by reduction of glutamate production. Conversely, pruning is accelerated by application of exogenous NMDA. We also found that NMDA induced increased muscle calcium only during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play previously unsuspected roles in neuromuscular activity and synaptic pruning during development. In normal adult muscle, each muscle fiber is innervated by a single axon, but at birth, fibers are multiply innervated. Elimination of excess connections requires neural activity; because the neuromuscular junction (NMJ) is a cholinergic synapse, acetylcholine has been assumed to be the critical mediator of activity. However, glutamate receptors are also expressed at the NMJ. We found that axon removal in mice is slowed by pharmacological and molecular manipulations that decrease signaling through neuromuscular NMDA receptors, whereas application of exogenous NMDA at the NMJ accelerates synapse elimination and increases muscle calcium levels during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play

  4. The Developmental Origins of Osteoporosis

    Science.gov (United States)

    Wood, Claire L; Stenson, Charlotte; Embleton, Nicholas

    2015-01-01

    Osteoporosis is one of the most prevalent skeletal disorders and has enormous public health consequences due to the morbidity and mortality of the resulting fractures. This article discusses the developmental origins of osteoporosis and outlines some of the modifiable and non-modifiable risk factors in both intrauterine and postnatal life that contribute to the later onset of osteoporosis. Evidence for the effects of birth size and early growth in both preterm and term born infants are discussed and the role of epigenetics within the programming hypothesis is highlighted. This review provides compelling evidence for the developmental origins of osteoporosis and highlights the importance of osteoporosis prevention at all stages of the life course. PMID:27018386

  5. DEVELOPMENTAL COORDINATION DISORDER IN CHILDREN

    OpenAIRE

    Saeideh MIRAFKHAMI; Seyyed Hossein FAKHRAEE; Sina MIRAFKHAMI; Mojtaba YOUSEFI; Mona VARZANDEH FAR

    2010-01-01

    ObjectiveIn this article, a motor skill disorder called developmental coordination disorder (DCD), that is usually first diagnosed during childhood, is explained and discussed. In the year 1987, DCD was formally recognized as a distinct disorder in children by the American Psychiatric Association  (APA). DCD is a generalized term for the children who have some degrees of impairment in the development of motor coordination and therefore have difficulties with physical skills which significantl...

  6. Joint Actions of Developmental Toxicants.

    Science.gov (United States)

    1991-06-01

    applications in aquatic toxicology and experimental teratology [2-15]. A standard ASTM (American Society for Testing and Materials) guide for FETAX is nearing...in malformation rates). Incidences of each joint action type have been reported in experimental teratology [211. Recent advances in aquatic toxicology offer...action produced; as has been observed in aquatic toxicology studies. Several developmental toxicants were selected for mixture tests based on their

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.)

  13. Publication patterns in developmental psychology: Trends and social networks.

    Science.gov (United States)

    Dobermann, Darja; Hamilton, Ian S

    2017-08-01

    Interest in publication patterns has been steady. Journals have instituted policies in an effort to curb bias and provide globally representative research. This study aimed to examine if publication patterns were present in two developmental psychology journals. It also explored the social networks of prominent authors and the prevalence of informal author-editor relationships, searching for any potential power groups. Data were taken from empirical articles published between 2005 and 2014 in Child Development (CD) and The International Journal of Early Childhood (IJEC) data points were geographical authorship affiliation, informal author relationships as established by co-publishing, and connections to journal editors via identical affiliation. Results confirmed the previously established North American dominance in published research. In CD a strongly interlinked social network was identified between authors over the 10 years, with 15 chief influentialists binding groups of authors together. Results suggest that patterns are still present in published research in the realm of developmental psychology. To conclude, the potential implications of these patterns within developmental psychology are presented. © 2015 International Union of Psychological Science.

  14. Dscam-Mediated Cell Recognition Regulates Neural Circuit Formation

    OpenAIRE

    Hattori, Daisuke; Millard, S. Sean; Wojtowicz, Woj M.; Zipursky, S. Lawrence

    2008-01-01

    The Dscam family of immunoglobulin cell surface proteins mediates recognition events between neurons that play an essential role in the establishment of neural circuits. The Drosophila Dscam1 locus encodes tens of thousands of cell surface proteins via alternative splicing. These isoforms exhibit exquisite isoform-specific binding in vitro that mediates homophilic repulsion in vivo. These properties provide the molecular basis for self-avoidance, an essential developmental mechanism that allo...

  15. 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.

  16. Developmental regulation of tandem promoters for the major outer membrane protein gene of Chlamydia trachomatis.

    Science.gov (United States)

    Stephens, R S; Wagar, E A; Edman, U

    1988-01-01

    Chlamydia trachomatis has a biphasic developmental cycle which is characterized by qualitative and quantitative changes in protein expression. The molecular mechanisms that mediate these changes are unknown. Evidence for transcriptional regulation of the chlamydial major outer membrane protein gene (omp1) was found by Northern hybridization of RNA isolated sequentially during the chlamydial developmental cycle. Early in the growth cycle a single transcript was detected, which was followed hours later in the cycle by an additional transcript. Mapping of the initiating nucleotide for each transcript suggested that this gene is regulated by differential transcription from tandem promoters. Images PMID:2448291

  17. Developmental evidence for obstetric adaptation of the human female pelvis.

    Science.gov (United States)

    Huseynov, Alik; Zollikofer, Christoph P E; Coudyzer, Walter; Gascho, Dominic; Kellenberger, Christian; Hinzpeter, Ricarda; Ponce de León, Marcia S

    2016-05-10

    The bony pelvis of adult humans exhibits marked sexual dimorphism, which is traditionally interpreted in the framework of the "obstetrical dilemma" hypothesis: Giving birth to large-brained/large-bodied babies requires a wide pelvis, whereas efficient bipedal locomotion requires a narrow pelvis. This hypothesis has been challenged recently on biomechanical, metabolic, and biocultural grounds, so that it remains unclear which factors are responsible for sex-specific differences in adult pelvic morphology. Here we address this issue from a developmental perspective. We use methods of biomedical imaging and geometric morphometrics to analyze changes in pelvic morphology from late fetal stages to adulthood in a known-age/known-sex forensic/clinical sample. Results show that, until puberty, female and male pelves exhibit only moderate sexual dimorphism and follow largely similar developmental trajectories. With the onset of puberty, however, the female trajectory diverges substantially from the common course, resulting in rapid expansion of obstetrically relevant pelvic dimensions up to the age of 25-30 y. From 40 y onward females resume a mode of pelvic development similar to males, resulting in significant reduction of obstetric dimensions. This complex developmental trajectory is likely linked to the pubertal rise and premenopausal fall of estradiol levels and results in the obstetrically most adequate pelvic morphology during the time of maximum female fertility. The evidence that hormones mediate female pelvic development and morphology supports the view that solutions of the obstetrical dilemma depend not only on selection and adaptation but also on developmental plasticity as a response to ecological/nutritional factors during a female's lifetime.

  18. 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.

  19. 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...... 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...

  20. The Developmental Origins of Dehumanization.

    Science.gov (United States)

    McLoughlin, Niamh; Over, Harriet

    2018-01-01

    Dehumanization is a complex social phenomenon, intimately connected to intergroup harm and neglect. However, developmental research has only recently started to investigate this important topic. In this chapter, we review research in areas closely related to dehumanization including children's intergroup preferences, essentialist conceptions of social groups, and understanding of relative status. We then highlight the small number of recent studies that have investigated the development of this social bias more directly. We close by making a series of suggestions for future research that will enable us to better understand the nature and causes of this harmful phenomenon. © 2018 Elsevier Inc. All rights reserved.

  1. Evolutionary developmental biology its roots and characteristics.

    Science.gov (United States)

    Morange, Michel

    2011-09-01

    The rise of evolutionary developmental biology was not the progressive isolation and characterization of developmental genes and gene networks. Many obstacles had to be overcome: the idea that all genes were more or less involved in development; the evidence that developmental processes in insects had nothing in common with those of vertebrates. Different lines of research converged toward the creation of evolutionary developmental biology, giving this field of research its present heterogeneity. This does not prevent all those working in the field from sharing the conviction that a precise characterization of evolutionary variations is required to fully understand the evolutionary process. Some evolutionary developmental biologists directly challenge the Modern Synthesis. I propose some ways to reconcile these apparently opposed visions of evolution. The turbulence seen in evolutionary developmental biology reflects the present entry of history into biology. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. 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.

  3. Childhood Neglect, Internalizing Symptoms and Adolescent Substance Use: Does the Neighborhood Context Matter?

    Science.gov (United States)

    Duprey, Erinn B; Oshri, Assaf; Caughy, Margaret O

    2017-07-01

    Childhood neglect is associated with risk behaviors in adolescence, including substance use. There is evidence that internalizing behaviors may serve as a mechanism linking childhood neglect and substance use; however, further research is needed to examine this developmental pathway. According to developmental and ecological approaches, the neighborhood context and the developmental timing of maltreatment should both be considered when examining the sequelae of childhood neglect. Hence, the present study uses a longitudinal sample of youth (N = 965, 49.1% female, 59.2% African-American) to examine the influence of timing in the relationship between childhood neglect and adolescent psychopathology, and to examine the indirect effects of child neglect on substance use via internalizing symptoms in adolescence. Furthermore, the role of neighborhood disorder in this indirect effect was tested. Five data collection time points were used: Time 1(M age  = 4.557, SD age  = .701), Time 2 (M age  = 6.422, SD age  = .518), Time 3 (M age  = 12.370, SD age  = .443), Time 4 (M age  = 14.359, SD age  = .452), and Time 5 (M age  = 16.316, SD age  = .615). The findings showed that internalizing problems mediated the link between the severity of neglect in early childhood and adolescent substance use, and this pathway was moderated by neighborhood disorder. These results have implications for preventative interventions aimed toward reducing substance use for at-risk adolescents.

  4. Examination of Associations Among Three Distinct Subjective Aging Constructs and Their Relevance for Predicting Developmental Correlates.

    Science.gov (United States)

    Brothers, Allyson; Miche, Martina; Wahl, Hans-Werner; Diehl, Manfred

    2017-07-01

    This study examined (a) the empirical associations among three subjective aging (SA) constructs: felt age, attitudes toward own aging (ATOA), and awareness of age-related change (AARC); (b) the moderating role of chronological age in these associations; and (c) the predictive relevance of the SA constructs with regard to two developmental correlates: functional health and satisfaction with life. Participants were 819 adults aged 40-98 years from the United States and Germany. Parallel multiple mediation, moderated mediation, and hierarchical regression analyses were used. As hypothesized, AARC mediated the association between the global measures of SA (felt age and ATOA) and the developmental correlates. Specifically, more negative global subjective aging predicted more AARC losses, which predicted poorer health and well-being. Furthermore, this mediation pathway was moderated by chronological age, such that, with increasing age, greater AARC was more strongly related to poorer functional health (but not well-being). The multidimensional measure, AARC, accounted for a significant amount of the variance in the developmental correlates over and above the unidimensional SA constructs. A consistent pattern emerged supporting the role of domain specificity and valence. These findings support the need for conceptualizing SA across different behavioral domains and for distinguishing between positive and negative SA. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Troubling Discourse: Basic Writing and Computer-Mediated Technologies

    Science.gov (United States)

    Jonaitis, Leigh A.

    2012-01-01

    Through an examination of literature in the fields of Basic Writing and developmental education, this essay provides some historical perspective and examines the prevalent discourses on the use of computer-mediated technologies in the basic writing classroom. The author uses Bertram Bruce's (1997) framework of various "stances" on…

  6. Neurogenesis and developmental anesthetic neurotoxicity.

    Science.gov (United States)

    Kang, Eunchai; Berg, Daniel A; Furmanski, Orion; Jackson, William M; Ryu, Yun Kyoung; Gray, Christy D; Mintz, C David

    The mechanism by which anesthetics might act on the developing brain in order to cause long term deficits remains incompletely understood. The hippocampus has been identified as a structure that is likely to be involved, as rodent models show numerous deficits in behavioral tasks of learning that are hippocampal-dependent. The hippocampus is an unusual structure in that it is the site of large amounts of neurogenesis postnatally, particularly in the first year of life in humans, and these newly generated neurons are critical to the function of this structure. Intriguingly, neurogenesis is a major developmental event that occurs during postulated windows of vulnerability to developmental anesthetic neurotoxicity across the different species in which it has been studied. In this review, we examine the evidence for anesthetic effects on neurogenesis in the early postnatal period and ask whether neurogenesis should be studied further as a putative mechanism of injury. Multiple anesthetics are considered, and both in vivo and in vitro work is presented. While there is abundant evidence that anesthetics act to suppress neurogenesis at several different phases, evidence of a causal link between these effects and any change in learning behavior remains elusive. Copyright © 2016. Published by Elsevier Inc.

  7. 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.

  8. Adolescent Safety on the Internet: Risks, Coping with Problems and Parental Mediation

    Science.gov (United States)

    Soldatova, Galina Urtanbekovna; Rasskazova, Elena Igorevna

    2016-01-01

    The article examines the opportunities and limitations of the coping behavior of children and teenagers on the Internet and the assistance that they receive from significant adults (parental mediation) in the context of the new developmental social situation, which is mediated by modern information and communication technologies, and in particular…

  9. Developmental cascades: Linking adolescent substance use, affiliation with substance use promoting peers, and academic achievement to adult substance use disorders

    Science.gov (United States)

    Haller, Moira; Handley, Elizabeth; Chassin, Laurie; Bountress, Kaitlin

    2010-01-01

    Using a high-risk community sample (N = 405), the current study examined developmental cascades among substance use, affiliation with substance use promoting peers, and academic achievement over an 18-year period and tested whether these pathways mediated the influence of parental alcoholism on adult alcohol and drug use disorders. Results showed that the influence of parental alcoholism on adult drug disorders was mediated by developmental cascades across all three domains, whereas the influence of parental alcoholism on adult alcohol disorders was mediated through affiliation with substance use promoting peers and persistence in binge drinking. Adolescent drug use had more implications for adult outcomes than did adolescent alcohol use, which was less likely to spill over into other domains of functioning. Findings indicated that adolescent risk factors had indirect rather than unique effects on adult substance use disorders, suggesting that adolescent risk is not immutable and is largely mediated by later influences. PMID:20883589

  10. 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…

  11. Developmental delays at arrival and postmenarcheal Chinese adolescents' adjustment.

    Science.gov (United States)

    Tan, Tony X; Rice, Jessica L; Mahoney, E Emily

    2015-01-01

    Internationally adopted (IA) children often have delays at adoption and undergo massive catch-up after adoption. Before achieving developmental catch-up, however, delays at adoption present a risk for IA children's adjustment, but it remains unknown whether such delays foreshadow IA children's outcomes after catch-up development has completed or ceased. In the current analysis, we utilized menarche as a practical marker to indicate the cessation of developmental catch-up. We investigated how delays at arrival predicted long-term outcomes in 132 postmenarcheal teens (M = 14.2 years, SD = 1.7) who were adopted from China at 16.6 months (SD = 17.1). In 2005, adoptive parents provided data of medical evaluation results on their children's delay status in gross motor skills, fine motor skills, social development, emotional development, and cognitive development. Six years later in 2011, data on parent-child relationship quality were collected from parents, and data on the adoptees' academic competence and internalizing problems were also collected from both parents and adoptees. We found that gross motor delay at arrival predicted academic performance (parent-report: b = -.34, p < .01) and internalizing problems (self-report: b = .26, p < .05; parent-report: b = .33, p < .01). Other delays were not significant in predicting any of the outcomes. The impact of early nutritional deprivation on gross motor development was discussed.

  12. Policy-Relevant Behaviors Predict Heavier Drinking in Both On and Off Premises and Mediate the Relationship Between Heavier Alcohol Consumption and Age, Gender, and Socioeconomic Status-Analysis from the International Alcohol Control Study.

    Science.gov (United States)

    Casswell, Sally; Huckle, Taisia; Wall, Martin; Parker, Karl

    2016-02-01

    Our goal was to investigate the role of behaviors amenable to policy change in mediating the relationship between alcohol consumption in off and on premises, age, and 2 measures of socioeconomic status (education and income). A cross-sectional general population survey was analyzed by using Bayesian path analysis to understand direct and mediating pathways. A total of 1,900 drinkers (past 6 months), aged 18 to 65 years, living in households with landline phones participated in the study. Measures were as follows: typical quantities of alcohol consumed per occasion, frequency of drinking, both off and on premise; gender, age groups; and years of education, personal income, prices paid, time of purchase, and liking for alcohol advertisements. Later times of purchase predicted larger quantities consumed (on and off premise) and more frequent drinking (on premise only). Younger people and males purchased later, and this mediated their heavier consumption. Lower prices paid predicted larger quantities consumed (on premise) and higher frequency of drinking (off premise). Younger and male respondents paid lower prices, and this mediated larger quantities consumed on premise and more frequent drinking off premise. Less well educated paid lower prices, and this mediated drinking more frequently off premise among this group. Liking for alcohol ads predicted drinking larger quantities and higher frequency both off and on premise. Younger and male respondents reported greater liking for ads, and this mediated their consumption of larger quantities and more frequent drinking both on and off premise. Those with higher income drank larger amounts on premise and more frequently on and off, but there were no mediating effects from the policy-relevant variables. Heavier drinking patterns by young people and those less well educated could be ameliorated by attention to alcohol policy. Copyright © 2016 by the Research Society on Alcoholism.

  13. Artificial grammar learning in primary school children with and without developmental dyslexia.

    Science.gov (United States)

    Pavlidou, Elpis V; Williams, Joanne M; Kelly, Louise M

    2009-06-01

    This paper explores implicit learning in typically developing and primary school children (9-12 years old) with developmental dyslexia using an artificial grammar learning (AGL) task. Two experiments were conducted, which differed in time of presentation and nature of the instructional set (experiment 1--implicit instructions vs experiment 2--explicit instructions). Repeated measures analysis of variance (group x grammaticality x chunk strength) showed a group effect only in experiment 1 (implicit instructions), with only the typically developing children showing evidence of AGL. There was a grammaticality effect (adherence to the rules) for both groups in the two experimental situations. We suggest that the typically developing children exhibited intact implicit learning as manifested in AGL performance, whereas children with developmental dyslexia failed to provide such evidence due to possible mediating cognitive developmental factors.

  14. 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.

  15. A semiotic framework for evolutionary and developmental biology.

    Science.gov (United States)

    Andrade, Eugenio

    2007-01-01

    This work aims at constructing a semiotic framework for an expanded evolutionary synthesis grounded on Peirce's universal categories and the six space/time/function relations [Taborsky, E., 2004. The nature of the sign as a WFF--a well-formed formula, SEED J. (Semiosis Evol. Energy Dev.) 4 (4), 5-14] that integrate the Lamarckian (internal/external) and Darwinian (individual/population) cuts. According to these guide lines, it is proposed an attempt to formalize developmental systems theory by using the notion of evolving developing agents (EDA) that provides an internalist model of a general transformative tendency driven by organism's need to cope with environmental uncertainty. Development and evolution are conceived as non-programmed open-ended processes of information increase where EDA reach a functional compromise between: (a) increments of phenotype's uniqueness (stability and specificity) and (b) anticipation to environmental changes. Accordingly, changes in mutual information content between the phenotype/environment drag subsequent changes in mutual information content between genotype/phenotype and genotype/environment at two interwoven scales: individual life cycle (ontogeny) and species time (phylogeny), respectively. Developmental terminal additions along with increment minimization of developmental steps must be positively selected.

  16. 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.

  17. 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.

  18. [White matter in developmental disorders].

    Science.gov (United States)

    Guinea-Hidalgo, Ana; Tirapu-Ustárroz, Javier

    2011-09-16

    The white matter is the main connection between different regions of the brain and helps them to work in a unified, coordinated way. Diffusion tensor imaging is an ideal technique with which to study it in order to detect the degree of integrity of these fibres. Nowadays, they are considered to play a significant role in the development and pathophysiology of different developmental disorders, and the aim of this study was to examine this role. On reviewing disorders such as autism, dyslexia or attention deficit hyperactivity disorder, certain fibres were found to be clearly involved. This was especially the case of the (arcuate) superior longitudinal fasciculus and the temporal-parietal network (related with the regulation of motor and attentional behaviour), the corpus callosum (which ensures the efficient and swift exchange of information between the hemispheres of the brain) and cingulate regions (which would be related with social cognition and self-consciousness).

  19. Environment protection and developmental politics

    International Nuclear Information System (INIS)

    Schusdziarra, I.

    1993-01-01

    Environment protection and development are characterised as two sides of the same medal. The extent of environmental damage in the developing countries is one of the great challenges of our time. Environment protection is therefore one of the main objectives in the current German developmental policy and as a cross-sectional task figures as a standard in all the other sectors of the field. The support offered to developing countries in fulfillment of global agreements for environment protection represents a service rendered in the interest of the world community. In this regard it should be classified under compensation payments rather than under measures of development aid. It is important to strengthen the economic power of and enhance export opportunities for the developing countries because environmentally benign trading is the best aid for a sustainable development. (orig./HSCH) [de

  20. Transgenic mice in developmental toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Woychik, R.P.

    1992-01-01

    Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.

  1. State of the States in Developmental Disabilities

    Science.gov (United States)

    Braddock, David; Hemp, Richard; Rizzolo, Mary Kay

    2008-01-01

    This is the latest edition of the "State of the States in Developmental Disabilities" study--a thorough and the only one of its kind investigation on public spending, revenues, and programmatic trends of intellectual and developmental programs and services within the United States since 1977. Directed by leading researcher, Dr. David…

  2. Static balance and developmental coordination disorder

    NARCIS (Netherlands)

    Geuze, RH

    2003-01-01

    The development of static balance is a basic characteristic of normal motor development. Most of the developmental motor tests include a measure of static balance. Children with a developmental coordination disorder (DCD) often fail this item. Twenty-four children at risk for DCD with balance

  3. 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 ...

  4. Cross-Modal Binding in Developmental Dyslexia

    Science.gov (United States)

    Jones, Manon W.; Branigan, Holly P.; Parra, Mario A.; Logie, Robert H.

    2013-01-01

    The ability to learn visual-phonological associations is a unique predictor of word reading, and individuals with developmental dyslexia show impaired ability in learning these associations. In this study, we compared developmentally dyslexic and nondyslexic adults on their ability to form cross-modal associations (or "bindings") based…

  5. Menstrual suppression for adolescents with developmental disabilities.

    Science.gov (United States)

    Savasi, I; Spitzer, R F; Allen, L M; Ornstein, M P

    2009-06-01

    The approach to menstrual suppression for adolescents with developmental disabilities has evolved considerably over the years due to changing philosophies and evolving treatment options. We review the medical management options available for menstrual suppression with a focus on the needs and treatment of adolescents with developmental disabilities.

  6. 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 ...

  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. 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.

  9. Pleiotropic consequences of misexpression of the developmentally ...

    Indian Academy of Sciences (India)

    The non-coding hsr gene of Drosophila melanogaster is expressed in nearly all cell types and developmental stages. However, in the absence of conventional mutant alleles of this gene, its developmental functions remain largely unknown. In the present study, we used a variety of GAL4 drivers to overexpress or ablate ...

  10. 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

  11. Issues Surrounding Children with Developmental Coordination Disorder

    Science.gov (United States)

    Sugden, David; Kirby, Amanda; Dunford, Carolyn

    2008-01-01

    Like other developmental disorders such as Attention Deficit Hyperactivity Disorder, specific language impairment and dyslexia, there is no shortage of debate surrounding the condition of Developmental Coordination Disorder. The present article takes a global view of many of these debatable issues, starting with definition and terminology, moving…

  12. Variations in Developmental Patterns across Pragmatic Features

    Science.gov (United States)

    Li, Qiong

    2016-01-01

    Drawing on the findings of longitudinal studies in uninstructed contexts over the last two decades, this synthesis explores variations in developmental patterns across second language (L2) pragmatic features. Two synthesis questions were addressed: (a) What are the variations in developmental patterns across pragmatic features?, and (b) What are…

  13. Developmental Cognitive Neuroscience: Origins, Issues, and Prospects

    Science.gov (United States)

    Pennington, Bruce F.; Snyder, Kelly A.; Roberts, Ralph J., Jr.

    2007-01-01

    This commentary explains how the field of developmental cognitive neuroscience (DCN) holds the promise of a much wider interdisciplinary integration across sciences concerned with development: psychology, molecular genetics, neurobiology, and evolutionary developmental biology. First we present a brief history of DCN, including the key theoretical…

  14. 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…

  15. Rethinking developmental toxicity testing: Evolution or revolution?

    OpenAIRE

    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 toxicity testing?

  16. 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 ...

  17. 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 ...

  18. [A Dynamic Developmental Model of Suicide.] Commentary.

    Science.gov (United States)

    van Geert, Paul

    1996-01-01

    Compares differential and developmental approaches to clinical and developmental problems such as suicide. Contends that abstract model variables (such as suicidal tendency), whose meaning depends on the model in which they function, need a translation between the variable and empirical data. Maintains that practitioners need a model allowing for…

  19. 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.

  20. Mediated intimacies

    DEFF Research Database (Denmark)

    Andreassen, Rikke; Petersen, Michael Nebeling; Harrison, Katherine

    Social media, characterized by user-generated content, interactivity, participation and community formation, have gained much research attention in recent years. At the same time, intimacy, affectivity and emotions are increasingly growing as fields of study. While these two areas are often...... interwoven, the actual interconnections are rarely studied in detail. This anthology explores how social media construct new types of intimacies, and how practices of intimacy shape the development and use of new media, offering empirical knowledge, theoretical insights and an international perspective...... on the flourishing field of digital intimacies....

  1. 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.

  2. 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.

  3. E-Social Astuteness Skills for ICT-Supported Equitable Prosperity and a Capable Developmental State in South Africa

    Science.gov (United States)

    Mitrovic, Zoran; Taylor, Wallace; Sharif, Mymoena; Claassen, Walter; Wesso, Harold

    2013-01-01

    Over 350 national and international delegates at the 2nd e-Skills Summit and the International Telecommunication Union (ITU) Global ICT Forum on Human Capital Development have agreed that the e-skilling agenda in South Africa is making a "profound difference" but still not sufficient to build a capable developmental state. The delegates…

  4. Challenges and opportunities in developmental integrative physiology.

    Science.gov (United States)

    Mueller, C A; Eme, J; Burggren, W W; Roghair, R D; Rundle, S D

    2015-06-01

    This review explores challenges and opportunities in developmental physiology outlined by a symposium at the 2014 American Physiological Society Intersociety Meeting: Comparative Approaches to Grand Challenges in Physiology. Across animal taxa, adverse embryonic/fetal environmental conditions can alter morphological and physiological phenotypes in juveniles or adults, and capacities for developmental plasticity are common phenomena. Human neonates with body sizes at the extremes of perinatal growth are at an increased risk of adult disease, particularly hypertension and cardiovascular disease. There are many rewarding areas of current and future research in comparative developmental physiology. We present key mechanisms, models, and experimental designs that can be used across taxa to investigate patterns in, and implications of, the development of animal phenotypes. Intraspecific variation in the timing of developmental events can be increased through developmental plasticity (heterokairy), and could provide the raw material for selection to produce heterochrony--an evolutionary change in the timing of developmental events. Epigenetics and critical windows research recognizes that in ovo or fetal development represent a vulnerable period in the life history of an animal, when the developing organism may be unable to actively mitigate environmental perturbations. 'Critical windows' are periods of susceptibility or vulnerability to environmental or maternal challenges, periods when recovery from challenge is possible, and periods when the phenotype or epigenome has been altered. Developmental plasticity may allow survival in an altered environment, but it also has possible long-term consequences for the animal. "Catch-up growth" in humans after the critical perinatal window has closed elicits adult obesity and exacerbates a programmed hypertensive phenotype (one of many examples of "fetal programing"). Grand challenges for developmental physiology include

  5. Challenges and opportunities in developmental integrative physiology☆

    Science.gov (United States)

    Mueller, C.A.; Eme, J.; Burggren, W.W.; Roghair, R.D.; Rundle, S.D.

    2015-01-01

    This review explores challenges and opportunities in developmental physiology outlined by a symposium at the 2014 American Physiological Society Intersociety Meeting: Comparative Approaches to Grand Challenges in Physiology. Across animal taxa, adverse embryonic/fetal environmental conditions can alter morphological and physiological phenotypes in juveniles or adults, and capacities for developmental plasticity are common phenomena. Human neonates with body sizes at the extremes of perinatal growth are at an increased risk of adult disease, particularly hypertension and cardiovascular disease. There are many rewarding areas of current and future research in comparative developmental physiology. We present key mechanisms, models, and experimental designs that can be used across taxa to investigate patterns in, and implications of, the development of animal phenotypes. Intraspecific variation in the timing of developmental events can be increased through developmental plasticity (heterokairy), and could provide the raw material for selection to produce heterochrony — an evolutionary change in the timing of developmental events. Epigenetics and critical windows research recognizes that in ovo or fetal development represent a vulnerable period in the life history of an animal, when the developing organism may be unable to actively mitigate environmental perturbations. ‘Critical windows’ are periods of susceptibility or vulnerability to environmental or maternal challenges, periods when recovery from challenge is possible, and periods when the phenotype or epigenome has been altered. Developmental plasticity may allow survival in an altered environment, but it also has possible long-term consequences for the animal. “Catch-up growth” in humans after the critical perinatal window has closed elicits adult obesity and exacerbates a programmed hypertensive phenotype (one of many examples of “fetal programing”). Grand challenges for developmental physiology

  6. 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…

  7. The circadian clock-associated gene zea mays gigantea1 affects maize developmental transitions

    Science.gov (United States)

    The circadian clock is the internal timing mechanism that allows plants to make developmental decisions in accordance with environmental conditions. The genes of the maize circadian clock are not well defined. Gigantea (gi) genes are conserved across flowering plants, including maize. In model plant...

  8. Developmental Language Impairment through the Lens of the ICF: An Integrated Account of Children's Functioning

    Science.gov (United States)

    Dempsey, Lynn; Skarakis-Doyle, Elizabeth

    2010-01-01

    The conceptual framework of the World Health Organization's International Classification of Functioning, Disability and Health (ICF) has the potential to advance understanding of developmental language impairment (LI) and enhance clinical practice. The framework provides a systematic way of unifying numerous lines of research, which have linked a…

  9. 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…

  10. Less than human: Dehumanization underlies prejudice toward people with developmental disabilities

    OpenAIRE

    Parker, Laura Ruth Murry

    2015-01-01

    The present research examined the nature of prejudice toward people with developmental disabilities, its underlying root in dehumanization and implication for opposition to social policies, and the efficacy of two strategies for reducing this bias. In Study 1 and Study 2, dehumanization significantly predicted both greater prejudice and greater opposition to social policies benefiting people with Autism and Down Syndrome. Furthermore, prejudice significantly mediated the effect of dehumanizat...

  11. Tracking developmentally regulated post-synthetic processing of homogalacturonan and chitin using reciprocal oligosaccharide probes

    DEFF Research Database (Denmark)

    Mravec, Jozef; Kračun, Stjepan K.; Rydahl, Maja G.

    2014-01-01

    Polysaccharides are major components of extracellular matrices and are often extensively modified post-synthetically to suit local requirements and developmental programmes. However, our current understanding of the spatiotemporal dynamics and functional significance of these modifications...... binding is mediated by the unique stereochemical arrangement of oppositely charged amino and carboxy groups. Conjugation of oligosaccharides to fluorophores or gold nanoparticles enables direct and rapid imaging of homogalacturonan and chitosan with unprecedented precision in diverse plant, fungal...

  12. Developmental trajectories of body mass index and emotional-behavioral functioning of underweight children: A longitudinal study

    OpenAIRE

    Cimino, Silvia; Cerniglia, Luca; Almenara, Carlos A.; Jezek, Stanislav; Erriu, Michela; Tambelli, Renata

    2016-01-01

    Although several studies have addressed developmental trajectories from childhood to adolescence of internalizing/externalizing problems, limited attention has been given to underweight children. Two groups were recruited for this study from a community sample: underweight (Ug, N?=?80, 50% female) and normal weight (NWg, N?=?80, 50% female) to examine the developmental trajectories of body mass index and emotional-behavioral functioning of underweight children from the age two years, and thei...

  13. Developmental Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

    Science.gov (United States)

    Portugal, George S.; Wilkinson, Derek S.; Turner, Jill R.; Blendy, Julie A.; Gould, Thomas J.

    2012-01-01

    Pre-adolescence and adolescence are developmental periods associated with increased vulnerability for tobacco addiction, and exposure to tobacco during these periods may lead to long-lasting changes in behavioral and neuronal plasticity. The present study examined the short- and long-term effects of nicotine and nicotine withdrawal on fear conditioning in pre-adolescent, adolescent, and adult mice, and potential underlying substrates that may mediate the developmental effects of nicotine, such as changes in nicotinic acetylcholine receptor (nAChR) binding, CREB expression, and nicotine metabolism. Age-related differences existed in sensitivity to the effects of acute nicotine, chronic nicotine and nicotine withdrawal on contextual fear conditioning (no changes in cued fear conditioning were seen); younger mice were more sensitive to the acute effects and less sensitive to the effects of nicotine withdrawal 24 hours post treatment cessation. Developmental differences in nAChR binding were associated with the effects of nicotine withdrawal on contextual learning. Developmental differences in nicotine metabolism and CREB expression were also observed, but were not related to the effects of nicotine withdrawal on contextual learning 24 hours post treatment. Chronic nicotine exposure during pre-adolescence or adolescence, however, produced long-lasting impairments in contextual learning that were observed during adulthood, whereas adult chronic nicotine exposure did not. These developmental effects could be related to changes in CREB. Overall, there is a developmental shift in the effects of nicotine on hippocampus-dependent learning and developmental exposure to nicotine results in adult cognitive deficits; these changes in cognition may play an important role in the development and maintenance of nicotine addiction. PMID:22521799

  14. Macroevolutionary developmental biology: Embryos, fossils, and phylogenies.

    Science.gov (United States)

    Organ, Chris L; Cooper, Lisa Noelle; Hieronymus, Tobin L

    2015-10-01

    The field of evolutionary developmental biology is broadly focused on identifying the genetic and developmental mechanisms underlying morphological diversity. Connecting the genotype with the phenotype means that evo-devo research often considers a wide range of evidence, from genetics and morphology to fossils. In this commentary, we provide an overview and framework for integrating fossil ontogenetic data with developmental data using phylogenetic comparative methods to test macroevolutionary hypotheses. We survey the vertebrate fossil record of preserved embryos and discuss how phylogenetic comparative methods can integrate data from developmental genetics and paleontology. Fossil embryos provide limited, yet critical, developmental data from deep time. They help constrain when developmental innovations first appeared during the history of life and also reveal the order in which related morphologies evolved. Phylogenetic comparative methods provide a powerful statistical approach that allows evo-devo researchers to infer the presence of nonpreserved developmental traits in fossil species and to detect discordant evolutionary patterns and processes across levels of biological organization. © 2015 Wiley Periodicals, Inc.

  15. 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.

  16. 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, pmental health difficulties in late adolescence. Interventions that aim to promote resilience in DCD should involve improving social communication skills and self-esteem. © 2017 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

  17. 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.

  18. Specific Developmental Disorders of Scholastic Skills

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2015-07-01

    Full Text Available Several factors contribute to scholastic backwardness in children. Causes include specific developmental disorders of scholastic skills, low intelligence, chronic illnesses, family dysfunction, social problems, attention deficits, and emotional disorders. Children with specific developmental disorders of scholastic skills experience significant impairment in the acquisition of reading, writing and mathematical skills. If not remedied at the earliest, these children are at risk of developing severe stress related disorders. There is high comorbidity of behaviour disorders and emotional disorders in these children. Hence early intensive remedial education is essential in the management of children with specific developmental disorders of scholastic skills.

  19. Is sporadic Alzheimer's disease a developmental disorder?

    Science.gov (United States)

    Arendt, Thomas; Stieler, Jens; Ueberham, Uwe

    2017-11-01

    Alzheimer's disease (AD) is a neurodegenerative disorder of higher age that specifically occurs in human. Its clinical phase, characterized by a decline in physiological, psychological, and social functioning, is preceded by a long clinically silent phase of at least several decades that might perhaps even start very early in life. Overall, key functional abilities in AD patients decline in reverse order of the development of these abilities during normal childhood and adolescence. Early symptoms of AD, thus, typically affect mental functions that have been acquired only during very recent hominid evolution and as such are specific to human. Neurofibrillar degeneration, a typical neuropathological lesion of the disease and one of the most robust pathological correlates of cognitive impairment, is rarely seen in non-primate mammals and even non-human primates hardly develop a pathology comparable to those seen in AD patients. Neurofibrillar degeneration is not randomly distributed throughout the AD brain. It preferentially affects brain areas that become increasingly predominant during the evolutionary process of encephalization. During progression of the disease, it affects cortical areas in a stereotypic sequence that inversely recapitulates ontogenetic brain development. The specific distribution of cortical pathology in AD, moreover, appears to be determined by the modular organization of the cerebral cortex which basically is a structural reflection of its ontogeny. Here, we summarize recent evidence that phylogenetic and ontogenetic dimensions of brain structure and function provide the key to our understanding of AD. More recent molecular biological studies of the potential pathogenetic role of a genomic mosaic in the brains of patients with AD might even provide arguments for a developmental origin of AD. This article is part of a series "Beyond Amyloid". © 2017 International Society for Neurochemistry.

  20. Aging, glucocorticoids and developmental programming.

    Science.gov (United States)

    Zambrano, E; Reyes-Castro, L A; Nathanielsz, P W

    2015-06-01

    Glucocorticoids are pleiotropic regulators of multiple cell types with critical roles in physiological systems that change across the life-course. Although glucocorticoids have been associated with aging, available data on the aging trajectory in basal circulating glucocorticoids are conflicting. A literature search reveals sparse life-course data. We evaluated (1) the profile of basal circulating corticosterone across the life-course from weaning (postnatal day-PND 21), young adult PND 110, adult PND 450, mature adult PND 650 to aged phase PND 850 in a well-characterized homogeneous rat colony to determine existence of significant changes in trajectory in the second half of life; (2) sex differences; and (3) whether developmental programming of offspring by exposure to maternal obesity during development alters the later-life circulating corticosterone trajectory. We identified (1) a fall in corticosterone between PND 450 and 650 in both males and females (p age but from higher levels in male and female offspring of obese mothers. In all four groups studied, there was a second half of life fall in corticosterone. Higher corticosterone levels in offspring of obese mothers may play a role in their shorter life-span, but the age-associated fall occurs at a similar time to control offspring. Although even more life-course time-points would be useful, a five life-course time-point analysis provides important new information on normative and programmed aging of circulating corticosterone.

  1. Developmental dysplasia of the hip

    Directory of Open Access Journals (Sweden)

    Shahryar Noordin

    2010-10-01

    Full Text Available Developmental dysplasia of the hip (DDH is a spectrum of anatomical abnormalities of the hip joint in which the femoral head has an abnormal relationship with the acetabulum. Most studies report an incidence of 1 to 34 cases per 1,000 live births and differences could be due to different diagnostic methods and timing of evaluation. Risk factors include first born status, female sex, positive family history, breech presentation and oligohydramnios. Clinical presentations of DDH depend on the age of the child. Newborns present with hip instability, infants have limited hip abduction on examination, and older children and adolescents present with limping, joint pain, and/or osteoarthritis. Repeated, careful examination of all infants from birth and throughout the first year of life until the child begins walking is important to prevent late cases. Provocative testing includes the Barlow and Ortolani maneuvers. Other signs, such as shorting of the femur with hips and knees flexed (Galeazzi sign, asymmetry of the thigh or gluteal folds, and discrepancy of leg lengths are potential clues. Treatment depends on age at presentation and outcomes are much better when the child is treated early, particularly during the first six months of life.

  2. 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.

  3. Developmental neurotoxicity of industrial chemicals.

    Science.gov (United States)

    Grandjean, P; Landrigan, P J

    2006-12-16

    Neurodevelopmental disorders such as autism, attention deficit disorder, mental retardation, and cerebral palsy are common, costly, and can cause lifelong disability. Their causes are mostly unknown. A few industrial chemicals (eg, lead, methylmercury, polychlorinated biphenyls [PCBs], arsenic, and toluene) are recognised causes of neurodevelopmental disorders and subclinical brain dysfunction. Exposure to these chemicals during early fetal development can cause brain injury at doses much lower than those affecting adult brain function. Recognition of these risks has led to evidence-based programmes of prevention, such as elimination of lead additives in petrol. Although these prevention campaigns are highly successful, most were initiated only after substantial delays. Another 200 chemicals are known to cause clinical neurotoxic effects in adults. Despite an absence of systematic testing, many additional chemicals have been shown to be neurotoxic in laboratory models. The toxic effects of such chemicals in the developing human brain are not known and they are not regulated to protect children. The two main impediments to prevention of neurodevelopmental deficits of chemical origin are the great gaps in testing chemicals for developmental neurotoxicity and the high level of proof required for regulation. New, precautionary approaches that recognise the unique vulnerability of the developing brain are needed for testing and control of chemicals.

  4. Morphological awareness in developmental dyslexia.

    Science.gov (United States)

    Casalis, Séverine; Colé, Pascale; Sopo, Delphine

    2004-06-01

    This study examines morphological awareness in developmental dyslexia. While the poor phonological awareness of dyslexic children has been related to their difficulty in handling the alphabetical principle, less is known about their morphological awareness, which also plays an important part in reading development. The aim of this study was to analyze in more detail the implications of the phonological impairments of dyslexics in dealing with larger units of language such as morphemes. First, the performance of dyslexic children in a series of morphological tasks was compared with the performance of children matched on reading-level and chronological age. In all the tasks, the dyslexic group performed below the chronological age control group, suggesting that morphological awareness cannot be developed entirely independently of reading experience and/or phonological skills. Comparisons with the reading-age control group indicated that, while the dyslexic children were poorer in the morphemic segmentation tasks, they performed normally for their reading level in the sentence completion tasks. Furthermore, they produced more derived words in the production task. This suggests that phonological impairments prevent the explicit segmentation of affixes while allowing the development of productive morphological knowledge. A second study compared dyslexic subgroups defined by their degree of phonological impairment. Our results suggest that dyslexics develop a certain type of morphological knowledge which they use as a compensatory reading strategy.

  5. The mediational role of neurocognition in the behavioral outcomes of a social-emotional prevention program in elementary school students: effects of the PATHS Curriculum.

    Science.gov (United States)

    Riggs, Nathaniel R; Greenberg, Mark T; Kusché, Carol A; Pentz, Mary Ann

    2006-03-01

    Neuropsychology is one field that holds promise in the construction of comprehensive, developmental models for the promotion of social competence and prevention of problem behavior. Neuropsychological models of behavior suggest that children's neurological functioning affects the regulation of strong emotions, as well as performance in social, cognitive, and behavioral spheres. The current study examines the underlying neurocognitive conceptual theory of action of one social-emotional development program. Hypothesized was that inhibitory control and verbal fluency would mediate the relationship between program condition and teacher-reported externalizing and internalizing behavior problems. Participants were 318 regular education students enrolled in the second or third grade. A series of regression analyses provided empirical support for (a) the effectiveness of the PATHS Curriculum in promoting inhibitory control and verbal fluency and (b) a partial mediating role for inhibitory control in the relation between prevention condition and behavioral outcomes. Implications are that programs designed to promote social and emotional development should consider comprehensive models that attend to neurocognitive functioning and development. Lack of consideration of neurocognitive pathways to the promotion of social competence may ignore important mechanisms through which prevention affects youth outcomes. Furthermore, the findings suggest that developers of social-emotional preventions should design curricula to explicitly promote the developmental integration of executive functioning, verbal processing, and emotional awareness. Doing so may enhance prevention outcomes particularly if those preventions are implemented during a time of peak neurocognitive development.

  6. 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.

  7. 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.

  8. 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.

  9. 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

    2015-01-01

    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 eight. 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. 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.

  10. 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

  11. 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

  12. Current status of developmental neurotoxicity: regulatory view

    DEFF Research Database (Denmark)

    Hass, Ulla

    2003-01-01

    . 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...... 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...

  13. Developmental and comparative perspectives of contagious yawning.

    Science.gov (United States)

    Senju, Atsushi

    2010-01-01

    Contagious yawning (i.e. yawning triggered by perceiving others' yawning) is a well-documented phenomenon, but the mechanism underlying it is still unclear. In this chapter, I review the current evidence about: (1) developmental studies with typically and atypically developing populations, and (2) comparative studies in non-human animals. Developmental studies have revealed that contagious yawning is disturbed in individuals with autism spectrum disorders, suggesting that contagious yawning may share a developmental basis with the capacity for theory of mind. Comparative studies have suggested that contagious yawning can be observed in non-primate species, such as domestic dogs. As dogs are known to have exceptional skills in communicating with humans, it has also been suggested that contagious yawning may be related to the capacity for social communication. These results from developmental and comparative studies are consistent with the claim that the mechanism underlying contagious yawning relates to the capacity for empathy. Copyright 2010 S. Karger AG, Basel.

  14. Developmental Competence for Primordial Germ Cell Fate.

    Science.gov (United States)

    Günesdogan, Ufuk; Surani, M Azim

    2016-01-01

    During mammalian embryonic development, the trophectoderm and primitive endoderm give rise to extraembryonic tissues, while the epiblast differentiates into all somatic lineages and the germline. Remarkably, only a few classes of signaling pathways induce the differentiation of these progenitor cells into diverse lineages. Accordingly, the functional outcome of a particular signal depends on the developmental competence of the target cells. Thus, developmental competence can be defined as the ability of a cell to integrate intrinsic and extrinsic cues to execute a specific developmental program toward a specific cell fate. Downstream of signaling, there is the combinatorial activity of transcription factors and their cofactors, which is modulated by the chromatin state of the target cells. Here, we discuss the concept of developmental competence, and the factors that regulate this state with reference to the specification of mammalian primordial germ cells. © 2016 Elsevier Inc. All rights reserved.

  15. 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)

  16. The Redesign of Developmental Education in Virginia

    Science.gov (United States)

    Edgecombe, Nikki

    2016-01-01

    This chapter describes the structure and implementation of a redesign of developmental education in the Virginia Community College System, discusses preliminary descriptive findings from an evaluation of the redesign, and shares lessons for the field.

  17. 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...

  18. MicroRNAs and Developmental Timing

    OpenAIRE

    Ambros, Victor

    2011-01-01

    MicroRNAs regulate temporal transitions in gene expression associated with cell fate progression and differentiation throughout animal development. Genetic analysis of developmental timing in the nematode C. elegans identified two evolutionarily conserved microRNAs, lin-4/mir-125 and let-7, that regulate cell fate progression and differentiation and in C. elegans cell lineages. MicroRNAs perform analogous developmental timing functions in other animals, including mammals. By regulating cell f...

  19. Developmental neurotoxicity of propylthiouracil in rats

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Hansen, Pernille Reimer; Christiansen, Sofie

    2007-01-01

    . The overall aim was to provide detailed knowledge on the relationship between effects on thyroid hormone levels and long-lasting developmental neurotoxicity effects. Groups of 16–18 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/(kg day)) from gestation day 7 to postnatal day (PND) 16...... behaviour and hearing function. This supports that exposure to TDC's in general may cause long-lasting developmental neurotoxicity....

  20. 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.

  1. 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.

  2. 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.

  3. Lehrman's dictum: information and explanation in developmental biology.

    Science.gov (United States)

    Griffiths, Paul E

    2013-01-01

    The integration of concepts from evolutionary developmental biology, such as the homology concept, into developmental psychobiology has great potential. However, evolutionary developmental biology is an attempt to integrate evolutionary and developmental explanation and developmental psychobiology has traditionally been concerned to avoid conflating these two kinds of explanation. This article examines a recent attempt to explain development in terms of "inherited information." The resulting explanation is an evolutionary explanation of development of a kind typical of evolutionary developmental biology. But its proponent mistakes it for an actual developmental explanation. Any integration of evolutionary developmental biology and developmental psychobiology should pay close attention to longstanding concerns about conflating evolutionary and developmental explanations. Copyright © 2012 Wiley Periodicals, Inc.

  4. 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

  5. Predictors of Latino Men's Paternity in Teen Pregnancy: Test of a Mediational Model of Childhood Experiences, Gender Role Attitudes, and Behaviors.

    Science.gov (United States)

    Goodyear, Rodney K.; Newcomb, Michael D.; Allison, Russell D.

    2000-01-01

    Examines the contribution of developmental and psychosocial factors to the number of teen pregnancies for which young Latino men have been responsible. Results indicated that men's involvement in teen pregnancy was mediated not only by sexual activity, but that it was also affected by developmental factors, gender-related attitudes, and…

  6. PREFACE Physical Aspects of Developmental Biology: 21st Century Perspectives 'On Growth and Form' Physical Aspects of Developmental Biology: 21st Century Perspectives 'On Growth and Form'

    Science.gov (United States)

    Hutson, M. Shane

    2008-04-01

    There is a long and circuitous route from an organism_s genome to its steady-state adult form—all of which falls under the wide umbrella of developmental biology. Given this breadth, how does one answer the question: what is the mechanism by which developmental event X takes place? The answer depends strongly on what one considers an acceptable explanation. In some scientific circles, the answer would focus on the regulatory genes involved. In others, the focus would be on the signaling pathways activated, or on the associated cellular movements, or maybe even on the intra- and intercellular forces. In the long term, the goal must be to provide an explanation that connects all of these perspectives. During the last several decades, molecular biology has made enormous progress towards understanding development from the genome-side. Unfortunately, progress has been much slower on the relevant physical biology—which had a huge head start in the late 19th century age of developmental mechanics. It is just a slight exaggeration to claim that we_ve made little progress on the physical side since D_Arcy Thompson_s On Growth and Form in 1917. Hopefully, such statements will be recognized as large exaggerations in years to come as developmental mechanics is now in resurgence. This special issue of Physical Biology brings together current work in developmental mechanics from an international cadre of scientists—including physicists, biologists and engineers. The works include both models and experiments. They span scales from subcellular microrheology to finite element models of entire embryos. I hope that students looking for one of these articles will dive into the rest. The field of developmental mechanics is in the process of training a new generation of students who are comfortable with both the necessary biology and physics. Enormous opportunities are available for those who can work across those traditional disciplinary boundaries.

  7. 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.

  8. The Teaching Portfolio as a Developmental Intervention: Promoting Developmental Stage Growth in Physical Education Teacher Candidates.

    Science.gov (United States)

    Senne, Terry A.; Rikard, G. Linda

    The objectives of this paper are: to briefly describe how teaching portfolios, in tandem with the Teaching/Learning Framework (Sprinthall & Thies-Sprinthall, 1983) can be employed as a developmental intervention to promote stage growth in teacher candidates; to report developmental stage change (moral judgment/principled thinking) results from…

  9. Internal and International Corruption

    Directory of Open Access Journals (Sweden)

    Dr.Sc. Mario Antinucci

    2015-06-01

    Full Text Available This subject, whence the name of this paper originates from, must be addressed with courage and intellectual integrity by all of us, the different parts of the civil society, the public institutions, the entrepreneurs and the legal professionals, the youth and the new generations. All the public policies of the European governments share the belief of a direct correlation between the criminal density connected to corruption of States political and economic protagonists and the lack of availability of investments on young talents, new generations, both in the entrepreneurial and in the professional fields. In most Member States, anticorruption policies have gained an increased prominence in government agendas and the financial crisis has drawn attention to the integrity and accountability of policy-makers. Most Member States that are currently in serious financial difficulties have acknowledged the seriousness of issues related to corruption and have created (or are planning anticorruption programs in order to deal with the risks deriving from this issue and with the diversion of public funds. In some Member States, the economic adjustment programs provide for explicit obligations related to anti-corruption policies. Even when not formally connected to adjustment programs, anticorruption policies complement the adjustment measures, especially in those countries in which corruption is a serious issue.  During the European Semester of economic policy coordination, recommendations for efficiently fighting corruption have been laid out; Among the most vulnerable sectors, urban development and building projects are certainly very exposed to corruption risks and to infiltration of internal and transnational organized crime.

  10. 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

  11. A Review of Intervention Programs to Prevent and Treat Behavioral Problems in Young Children with Developmental Disabilities.

    Science.gov (United States)

    Petrenko, Christie L M

    2013-12-01

    Children with developmental disabilities are at higher risk for internalizing and externalizing behavioral problems than children in the general population. Effective prevention and treatment programs are necessary to reduce the burden of behavioral problems in this population. The current review identified 17 controlled trials of nine intervention programs for young children with developmental disabilities, with parent training the most common type of intervention in this population. Nearly all studies demonstrated medium to large intervention effects on child behavior post-intervention. Preliminary evidence suggests interventions developed for the general population can be effective for children with developmental disabilities and their families. A greater emphasis on the prevention of behavior problems in young children with developmental disabilities prior to the onset of significant symptoms or clinical disorders is needed. Multi-component interventions may be more efficacious for child behavior problems and yield greater benefits for parent and family adjustment. Recommendations for future research directions are provided.

  12. Systems theory and cascades in developmental psychopathology.

    Science.gov (United States)

    Cox, Martha J; Mills-Koonce, Roger; Propper, Cathi; Gariépy, Jean-Louis

    2010-08-01

    In the wake of prominent theoreticians in developmental science, whose contributions we review in this article, many developmental psychologists came to endorse a systems approach to understanding how the individual, as it develops, establishes functional relationships to social ecological contexts that from birth to school entry rapidly increase in complexity. The concept of developmental cascade has been introduced in this context to describe lawful processes by which antecedent conditions may be related with varying probabilities to specified outcomes. These are understood as processes by which function at one level or in one domain of behavior affect the organization of competency in later developing domains of general adaptation. Here we propose a developmental sequence by which the developing child acquires regulative capacities that are key to adjustment to a society that demands considerable control of emotional and cognitive functions early in life. We report empirical evidence showing that the acquisition of regulative capacities may be understood as a cascade of shifts in control parameters induced by the progressive integration of biological, transactional, and socioaffective systems over development. We conclude by suggesting how the developmental process may be accessed for effective intervention in populations deemed "at risk" for later problems of psychosocial adjustment.

  13. 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.

  14. International arbejdsdeling

    DEFF Research Database (Denmark)

    Henten, Anders

    1998-01-01

    Article dealing with the implications of informátion and communication technologies on the international division of labour.......Article dealing with the implications of informátion and communication technologies on the international division of labour....

  15. Bicultural stress, identity formation, and alcohol expectancies and misuse in Hispanic adolescents: a developmental approach.

    Science.gov (United States)

    Oshri, Assaf; Schwartz, Seth J; Unger, Jennifer B; Kwon, Josephine A; Des Rosiers, Sabrina E; Baezconde-Garbanati, Lourdes; Lorenzo-Blanco, Elma I; Córdova, David; Soto, Daniel W; Lizzi, Karina M; Villamar, Juan A; Szapocznik, José

    2014-12-01

    Hispanic immigrant youth engage in increased health risk behaviors, such as alcohol misuse, due in part to being confronted with acculturative stress in addition to facing major normative developmental challenges, such as identity consolidation (Berry et al. in Appl Psychol 55:303-332, 2006). Using a developmental psychopathology framework, in the present study we examined the effect of bicultural stress on alcohol misuse among immigrated Hispanic adolescents, indirectly through trajectories of identity formation and alcohol expectancies. Our sample consisted of 302 recently immigrated Hispanic adolescents (53 % male; Mage = 14.5 at baseline) who were interviewed every 6 months for 3 years. Bivariate growth curve modeling was used to examine the influence of initial early bicultural stress on later alcohol misuse via change in identity development (i.e., coherence and confusion) and subsequent growth in cognitive alcohol expectancies. Findings revealed that initial levels and growth of identity coherence were not significantly associated with either bicultural stress or tension reduction (TR) alcohol expectancies. Multiple mediation analyses indicated that the effect of bicultural stress at time 1 on the frequency of being drunk at time 6 was mediated via high initial levels of identity confusion, followed by growth in risky TR expectancies (T4-T6). A developmental approach to the genesis of alcohol use problems in immigrant youth is discussed.

  16. 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

  17. Developmental Trajectories of Anxiety and Depression in Early Adolescence

    Science.gov (United States)

    McLaughlin, Katie A.; King, Kevin

    2014-01-01

    Adolescence is a period of heightened vulnerability for the onset of internalizing psychopathology. Characterizing developmental patterns of symptom stability, progression, and co-occurrence is important in order to identify adolescents most at risk for persistent problems. We use latent growth curve modeling to characterize developmental trajectories of depressive symptoms and four classes of anxiety symptoms (separation anxiety, social phobia, GAD, and physical anxiety) across early adolescence, prospective associations of depression and anxiety trajectories with one another, and variation in trajectories by gender. A diverse sample of early adolescents (N=1065) was assessed at three time points across a one-year period. All classes of anxiety symptoms declined across the study period and depressive symptoms remained stable. In between-individual analysis, adolescents with high levels of depressive symptoms experienced less decline over time in symptoms of physical, social, and separation anxiety. Consistent associations were observed between depression and anxiety symptom trajectories within-individuals over time, such that adolescents who experienced a higher level of a specific symptom type than would be expected given their overall symptom trajectory were more likely to experience a later deflection from their average trajectory in other symptoms. Within-individual deflections in physical, social, and GAD symptoms predicted later deflections in depressive symptoms, and deflections in depressive symptoms predicted later deflections in separation anxiety and GAD symptoms. Females had higher levels of symptoms than males, but no evidence was found for variation in symptom trajectories or their associations with one another by gender or by age. PMID:24996791

  18. 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.

  19. Developmental trajectories of anxiety and depression in early adolescence.

    Science.gov (United States)

    McLaughlin, Katie A; King, Kevin

    2015-02-01

    Adolescence is a period of heightened vulnerability for the onset of internalizing psychopathology. Characterizing developmental patterns of symptom stability, progression, and co-occurrence is important in order to identify adolescents most at risk for persistent problems. We use latent growth curve modeling to characterize developmental trajectories of depressive symptoms and four classes of anxiety symptoms (GAD, physical symptoms, separation anxiety, and social anxiety) across early adolescence, prospective associations of depression and anxiety trajectories with one another, and variation in trajectories by gender. A diverse sample of early adolescents (N = 1,065) was assessed at three time points across a one-year period. All classes of anxiety symptoms declined across the study period and depressive symptoms remained stable. In between-individual analysis, adolescents with high levels of depressive symptoms experienced less decline over time in symptoms of physical, social, and separation anxiety. Consistent associations were observed between depression and anxiety symptom trajectories within-individuals over time, such that adolescents who experienced a higher level of a specific symptom type than would be expected given their overall symptom trajectory were more likely to experience a later deflection from their average trajectory in other symptoms. Within-individual deflections in GAD, physical, and social symptoms predicted later deflections in depressive symptoms, and deflections in depressive symptoms predicted later deflections in GAD and separation anxiety symptoms. Females had higher levels of symptoms than males, but no evidence was found for variation in symptom trajectories or their associations with one another by gender or by age.

  20. Cardiac developmental onomatology: the real heart of the matter.

    Science.gov (United States)

    Arráez-Aybar, L A; González-Lorrio, F; Marantos-Gamarra, D G; Jiménez-Collado, J

    2003-12-01

    There has been much controversy regarding Cardiac Embryology since the 19th Century; this has brought up contradictions over many studies on Cardiac Development, and stems mainly from semantic differences rather than from scientific observations. In 1998, FCAT published the 1st Edition of Terminologia Anatomica, which did not include Terminologia Embryologica, and to this day, we do not have a thorough compilation of Terminology related to Cardiac Development (O'Rahilly and Müller 1996). In the present study we have reviewed the literature from the 19th and 20th Centuries gathering the terms proposed by those scientists who influenced Prenatal Cardiac Terminology. Our aim is to bring to the attention of clinicians and researchers of cardiac morphogenesis the need to undertake a reform of the Developmental Cardiac Terminology. We believe an International Consensus on the terminology to be used during the developmental stages is urgent; it should be meaningful both to the experimental embryologist and to the cardiologist, without being ambiguous or controversial. We must not forget that a terminology is of value only when it is properly used.

  1. Terminology used in research reports of developmental coordination disorder.

    Science.gov (United States)

    Magalhães, Lívia C; Missiuna, Cheryl; Wong, Shirley

    2006-11-01

    A systematic search was performed of all articles from January 1995 to December 2005 published in peer-reviewed journals on children with developmental coordination disorder (DCD). Criteria were applied to ensure that articles included DCD so 319 articles were included in the analysis. Since the publication of a systematic search conducted in 1994, the number of publications in this field has greatly increased across countries and disciplines. The term DCD was used in 52.7% of the articles. Other terms were used less frequently: clumsy children (7.2%), developmental dyspraxia (3.5%), handwriting problems (3.1%), hand-eye coordination problems (2.8%), sensory integration dysfunction (2.5%), deficits in attention, motor control, and perception (2.5%), minor neurological dysfunction (2.2%), and several other scattered terms (23.5%). The data indicated that progress has been made in the usage of the term DCD, but a standardized approach has not yet been achieved. Without consistent use of the term DCD, there is limited communication of research results internationally, slowed progress in understanding the condition, and limited development of intervention and management programmes for children with DCD.

  2. MARC International

    Directory of Open Access Journals (Sweden)

    Richard E. Coward

    1969-12-01

    Full Text Available The cooperative development of the Library of Congress MARC II Profect and the British National Bibliography MARC II Project is described and presented as the forerunner of an international MARC network. Emphasis is placed on the necessity for a standard MARC record for international exchange and for acceptance of international standards of cataloging.

  3. Internal Communication

    OpenAIRE

    Rathouský, Tomáš

    2015-01-01

    The diploma thesis focuses on characteristics of internal communication, its implementation in various forms in different companies and analysis of the internal communication in one selected company. After the analysis of its current state in the multinational company, the thesis will recommend improvements to the areas of internal communication and human resources, with the main focus of global implementation of these recommendations.

  4. 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....

  5. 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.

  6. Developmental neurotoxicity of succeeding generations of insecticides.

    Science.gov (United States)

    Abreu-Villaça, Yael; Levin, Edward D

    2017-02-01

    Insecticides are by design toxic. They must be toxic to effectively kill target species of insects. Unfortunately, they also have off-target toxic effects that can harm other species, including humans. Developmental neurotoxicity is one of the most prominent off-target toxic risks of insecticides. Over the past seven decades several classes of insecticides have been developed, each with their own mechanisms of effect and toxic side effects. This review covers the developmental neurotoxicity of the succeeding generations of insecticides including organochlorines, organophosphates, pyrethroids, carbamates and neonicotinoids. The goal of new insecticide development is to more effectively kill target species with fewer toxic side effects on non-target species. From the experience with the developmental neurotoxicity caused by the generations of insecticides developed in the past advice is offered how to proceed with future insecticide development to decrease neurotoxic risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Quantifying Nanoparticle Internalization Using a High Throughput Internalization Assay.

    Science.gov (United States)

    Mann, Sarah K; Czuba, Ewa; Selby, Laura I; Such, Georgina K; Johnston, Angus P R

    2016-10-01

    The internalization of nanoparticles into cells is critical for effective nanoparticle mediated drug delivery. To investigate the kinetics and mechanism of internalization of nanoparticles into cells we have developed a DNA molecular sensor, termed the Specific Hybridization Internalization Probe - SHIP. Self-assembling polymeric 'pHlexi' nanoparticles were functionalized with a Fluorescent Internalization Probe (FIP) and the interactions with two different cell lines (3T3 and CEM cells) were studied. The kinetics of internalization were quantified and chemical inhibitors that inhibited energy dependent endocytosis (sodium azide), dynamin dependent endocytosis (Dyngo-4a) and macropinocytosis (5-(N-ethyl-N-isopropyl) amiloride (EIPA)) were used to study the mechanism of internalization. Nanoparticle internalization kinetics were significantly faster in 3T3 cells than CEM cells. We have shown that ~90% of the nanoparticles associated with 3T3 cells were internalized, compared to only 20% of the nanoparticles associated with CEM cells. Nanoparticle uptake was via a dynamin-dependent pathway, and the nanoparticles were trafficked to lysosomal compartments once internalized. SHIP is able to distinguish between nanoparticles that are associated on the outer cell membrane from nanoparticles that are internalized. This study demonstrates the assay can be used to probe the kinetics of nanoparticle internalization and the mechanisms by which the nanoparticles are taken up by cells. This information is fundamental for engineering more effective nanoparticle delivery systems. The SHIP assay is a simple and a high-throughput technique that could have wide application in therapeutic delivery research.

  8. Integrating diverse datasets improves developmental enhancer prediction.

    Directory of Open Access Journals (Sweden)

    Genevieve D Erwin

    2014-06-01

    Full Text Available Gene-regulatory enhancers have been identified using various approaches, including evolutionary conservation, regulatory protein binding, chromatin modifications, and DNA sequence motifs. To integrate these different approaches, we developed EnhancerFinder, a two-step method for distinguishing developmental enhancers from the genomic background and then predicting their tissue specificity. EnhancerFinder uses a multiple kernel learning approach to integrate DNA sequence motifs, evolutionary patterns, and diverse functional genomics datasets from a variety of cell types. In contrast with prediction approaches that define enhancers based on histone marks or p300 sites from a single cell line, we trained EnhancerFinder on hundreds of experimentally verified human developmental enhancers from the VISTA Enhancer Browser. We comprehensively evaluated EnhancerFinder using cross validation and found that our integrative method improves the identification of enhancers over approaches that consider a single type of data, such as sequence motifs, evolutionary conservation, or the binding of enhancer-associated proteins. We find that VISTA enhancers active in embryonic heart are easier to identify than enhancers active in several other embryonic tissues, likely due to their uniquely high GC content. We applied EnhancerFinder to the entire human genome and predicted 84,301 developmental enhancers and their tissue specificity. These predictions provide specific functional annotations for large amounts of human non-coding DNA, and are significantly enriched near genes with annotated roles in their predicted tissues and lead SNPs from genome-wide association studies. We demonstrate the utility of EnhancerFinder predictions through in vivo validation of novel embryonic gene regulatory enhancers from three developmental transcription factor loci. Our genome-wide developmental enhancer predictions are freely available as a UCSC Genome Browser track, which we hope

  9. 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

  10. International law

    CERN Document Server

    Shaw, Malcolm N

    2017-01-01

    International Law is the definitive and authoritative text on the subject, offering Shaw's unbeatable combination of clarity of expression and academic rigour and ensuring both understanding and critical analysis in an engaging and authoritative style. Encompassing the leading principles, practice and cases, and retaining and developing the detailed references which encourage and assist the reader in further study, this new edition motivates and challenges students and professionals while remaining accessible and engaging. Fully updated to reflect recent case law and treaty developments, this edition contains an expanded treatment of the relationship between international and domestic law, the principles of international humanitarian law, and international criminal law alongside additional material on international economic law.

  11. 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.

  12. 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…

  13. 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.)

  14. 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

  15. 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.

  16. Developmental regulation and modulation of apoptotic genes expression in sheep oocytes and embryos cultured in vitro with L-carnitine.

    Science.gov (United States)

    Mishra, A; Reddy, I J; Gupta, Psp; Mondal, S

    2016-12-01

    The objective of this study was to find out the impact of L-carnitine (10 mM) on developmental regulation of preimplantation sheep embryos cultured in vitro when supplemented in maturation medium and post-fertilization medium separately. Subsequent objective was to observe the L-carnitine-mediated alteration in expression of apoptotic genes (Bcl2, Bax, Casp3 and PCNA) in sheep oocytes and developing embryos produced in vitro. Oocytes matured with L-carnitine showed significantly (p embryos cultured with actinomycin D and TNFα showed developmental arrest with significant (p embryo development and supplementation of L-carnitine during IVM altered the expression of apoptotic genes in the developmental stages of embryos. © 2016 Blackwell Verlag GmbH.

  17. Critical thermal limits affected differently by developmental and adult thermal fluctuations

    DEFF Research Database (Denmark)

    Salachan, Paul Vinu; Sørensen, Jesper Givskov

    2017-01-01

    Means and variances of the environmental thermal regime play an important role in determining the fitness of terrestrial ectotherms. Adaptive phenotypic responses induced by heterogeneous temperatures have been shown to be mediated by molecular pathways independent of the classic heat shock...... responses, however, an in-depth understanding of plasticity induced by fluctuating temperatures is still lacking. We investigated high and low temperature acclimation induced by fluctuating thermal regimes at two different mean temperatures, at two different amplitudes of fluctuation and across...... the developmental and adult life stages. For developmental acclimation, we found mildly detrimental effects of high amplitude fluctuations for critical thermal minima, while the critical thermal maxima showed a beneficial response to higher amplitude fluctuations. For adult acclimation involving shifts between...

  18. 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)

  19. 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.

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

    OpenAIRE

    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 literature review has been performed. Two search strings were used to determine the population and the context of work. The ICF was expanded with two subdivisions: one that made the environmental factor...