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Sample records for early developmental cardiomyocytes

  1. Developmental Milestones of Early Literacy

    MedlinePlus

    ... developmental milestones of early literacy. Younger Than 6 Months: Never Too Young Unlike solid foods , it is ... counts, so have fun with it! 6–12 Months: Developing a Taste for Books Whatever babies are ...

  2. Transcriptomics-based identification of developmental toxicants through their interference with cardiomyocyte differentiation of embryonic stem cells

    SciTech Connect

    Dartel, Dorien A.M. van; Pennings, Jeroen L.A.; Schooten, Frederik J. van; Piersma, Aldert H.

    2010-03-15

    The embryonic stem cell test (EST) predicts developmental toxicity based on the inhibition of cardiomyocyte differentiation of embryonic stem cells (ESC). The subjective endpoint, the long culture duration together with the undefined applicability domain and related predictivity need further improvement to facilitate implementation of the EST into regulatory strategies. These aspects may be improved by studying gene expression changes in the ESC differentiation cultures and their modulation by compound exposure using transcriptomics. Here, we tested the developmental toxicants monobutyl phthalate and 6-aminonicotinamide. ESC were allowed to differentiated, and cardiomyocyte differentiation was assessed after 10 days of culture. RNA of solvent controls was collected after 0, 24, 48, 72 and 96 h of exposure, and RNA of developmental-toxicant-exposed cultures was collected after 24 and 96 h. Samples were hybridized to DNA microarrays, and 1355 genes were found differentially expressed among the unexposed experimental groups. These regulated genes were involved in differentiation-related processes, and Principal Component Analysis (PCA) based on these genes showed that the unexposed experimental groups appeared in chronological order in the PCA, which can therefore be regarded as a continuous representation of the differentiation track. The developmental-toxicant-exposed cultures appeared to deviate significantly from this differentiation track, which confirms the compound-modulating effects on the differentiation process. The incorporation of transcriptomics in the EST is expected to provide a more informative and improved endpoint in the EST as compared with morphology, allowing early detection of differentiation modulation. Furthermore, this approach may improve the definition of the applicability domain and predictivity of the EST.

  3. Metabolic Remodeling in early development and cardiomyocyte maturation

    PubMed Central

    Kreipke, Rebecca; Wang, Yuliang; Miklas, Jason Wayne; Mathieu, Julie; Ruohola-Baker, Hannele

    2016-01-01

    Aberrations in metabolism contribute to a large number of diseases, such as diabetes, obesity, cancer, and cardiovascular diseases, that have a substantial impact on the mortality rates and quality of life worldwide. However, the mechanisms leading to these changes in metabolic state – and whether they are conserved between diseases – is not well understood. Changes in metabolism similar to those seen in pathological conditions are observed during normal development in a number of different cell types. This provides hope that understanding the mechanism of these metabolic switches in normal development may provide useful insight in correcting them in pathological cases. Here, we focus on the metabolic remodeling observed both in early stage embryonic stem cells and during the maturation of cardiomyocytes. PMID:26912118

  4. Early Writing: A Developmental Approach.

    ERIC Educational Resources Information Center

    Goetz, Elizabeth; And Others

    This document consists of four papers on the acquisition of writing skills by young children. The first paper provides a historical and developmental perspective on early writing. Children's development of manual dexterity is briefly overviewed and aspects of the educational approaches of Pestalozzi, Montessori, Chomsky, Rogers and Ashton-Warner…

  5. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis.

    PubMed

    Lin, Yan-Ren; Li, Chao-Jui; Syu, Shih-Han; Wen, Cheng-Hao; Buddhakosai, Waradee; Wu, Han-Ping; Hsu Chen, Cheng; Lu, Huai-En; Chen, Wen-Liang

    2016-01-01

    Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n = 20) and control (normal saline, n = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level.

  6. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis

    PubMed Central

    Syu, Shih-Han; Wen, Cheng-Hao; Buddhakosai, Waradee; Hsu Chen, Cheng

    2016-01-01

    Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n = 20) and control (normal saline, n = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level. PMID:28058255

  7. Practitioner Review: Early Adversity and Developmental Disorders

    ERIC Educational Resources Information Center

    Taylor, Eric; Rogers, Jody Warner

    2005-01-01

    Background: Knowledge of genetic influences, on developmental disorders such as autism spectrum, attention deficit/hyperactivity disorder and learning disabilities, has increased the opportunities for understanding the influences of the early environment. Methods: This paper provides a selective, narrative review for clinicians of the effects of…

  8. Developmental Outcomes after Early Prefrontal Cortex Damage

    ERIC Educational Resources Information Center

    Eslinger, Paul J.; Flaherty-Craig, Claire V.; Benton, Arthur L.

    2004-01-01

    The neuropsychological bases of cognitive, social, and moral development are minimally understood, with a seemingly wide chasm between developmental theories and brain maturation models. As one approach to bridging ideas in these areas, we review 10 cases of early prefrontal cortex damage from the clinical literature, highlighting overall clinical…

  9. Developmental genetics and early hominid craniodental evolution.

    PubMed

    McCollum, M A; Sharpe, P T

    2001-06-01

    Although features of the dentition figure prominently in discussions of early hominid phylogeny, remarkably little is known of the developmental basis of the variations in occlusal morphology and dental proportions that are observed among taxa. Recent experiments on tooth development in mice have identified some of the genes involved in dental patterning and the control of tooth specification. These findings provide valuable new insight into dental evolution and underscore the strong developmental links that exist among the teeth and the jaws and cranium. The latter has important implications for cladistic studies that traditionally consider features of the skull independently from the dentition.

  10. Persistent Noggin arrests cardiomyocyte morphogenesis and results in early in utero lethality

    PubMed Central

    Simmons, Olga; Snider, Paige; Wang, Jain; Schwartz, Robert J.; Chen, YiPing; Conway, Simon J.

    2014-01-01

    Background Multiple BMP genes are expressed in the developing heart from the initiation to late-differentiation stages, and play pivotal roles in cardiovascular development. In this study, we investigated the requirement of BMP activity in heart development by transgenic over-expression of extracellular BMP antagonist Noggin. Results Using Nkx2.5-Cre to drive lineage-restricted Noggin within cardiomyocyte progenitors, we show persistent Noggin arrests cardiac development at the linear heart stage. This is coupled with a significantly reduced cell proliferation rate, subsequent cardiomyocyte programmed cell death and reduction of downstream intracellular pSMAD1/5/8 expression. Noggin mutants exhibit reduced heartbeat which likely results in subsequent fully penetrant in utero lethality. Significantly, confocal and electron micrographic examination revealed considerably fewer contractile elements, as well as a lack of maturation of actin-myosin microfilaments. Molecular analysis demonstrated that ectopic Noggin-expressing regions in the early heart’s pacemaker region, failed to express the potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (Hcn4), resulting in an overall decrease in Hcn4 levels. Conclusions Combined, our results reveal a novel role for BMP signaling in the progression of heart development from the tubular heart stage to the looped stage via regulation of proliferation and promotion of maturation of the in utero heart’s contractile apparatus and pacemaker. PMID:25428115

  11. A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes.

    PubMed

    Wei, Hongguang; Jin, J-P

    2014-08-15

    We previously reported a point mutation substituting Cys for Arg(111) in the highly conserved troponin T (TnT)-contacting helix of cardiac troponin I (cTnI) in wild turkey hearts (Biesiadecki et al. J Biol Chem 279: 13825-13832, 2004). This dominantly negative TnI-TnT interface mutation decreases the binding affinity of cTnI for TnT, impairs diastolic function, and blunts the β-adrenergic response of cardiac muscle (Wei et al. J Biol Chem 285: 27806-27816, 2010). Here we further investigate cellular phenotypes of transgenic mouse cardiomyocytes expressing the equivalent mutation cTnI-K118C. Functional studies were performed on single adult cardiomyocytes after recovery in short-term culture from isolation stress. The amplitude of contraction and the velocities of shortening and relengthening were lower in cTnI-K118C cardiomyocytes than wild-type controls. The intracellular Ca(2+) transient was slower in cTnI-K118C cardiomyocytes than wild-type cells. cTnI-K118C cardiomyocytes also showed a weaker β-adrenergic response. The resting length of cTnI-K118C cardiomyocytes was significantly greater than that of age-matched wild-type cells, with no difference in cell width. The resting sarcomere was not longer, but slightly shorter, in cTnI-K118C cardiomyocytes than wild-type cells, indicating longitudinal addition of sarcomeres. More tri- and quadrinuclei cardiomyocytes were found in TnI-K118C than wild-type hearts, suggesting increased nuclear divisions. Whole-genome mRNA array and Western blots detected an increased expression of leukemia inhibitory factor receptor-β in the hearts of 2-mo-old cTnI-K118C mice, suggesting a signaling pathway responsible for the potent effect of cTnI-K118C mutation on early remodeling in cardiomyocytes.

  12. A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes

    PubMed Central

    Wei, Hongguang

    2014-01-01

    We previously reported a point mutation substituting Cys for Arg111 in the highly conserved troponin T (TnT)-contacting helix of cardiac troponin I (cTnI) in wild turkey hearts (Biesiadecki et al. J Biol Chem 279: 13825–13832, 2004). This dominantly negative TnI-TnT interface mutation decreases the binding affinity of cTnI for TnT, impairs diastolic function, and blunts the β-adrenergic response of cardiac muscle (Wei et al. J Biol Chem 285: 27806–27816, 2010). Here we further investigate cellular phenotypes of transgenic mouse cardiomyocytes expressing the equivalent mutation cTnI-K118C. Functional studies were performed on single adult cardiomyocytes after recovery in short-term culture from isolation stress. The amplitude of contraction and the velocities of shortening and relengthening were lower in cTnI-K118C cardiomyocytes than wild-type controls. The intracellular Ca2+ transient was slower in cTnI-K118C cardiomyocytes than wild-type cells. cTnI-K118C cardiomyocytes also showed a weaker β-adrenergic response. The resting length of cTnI-K118C cardiomyocytes was significantly greater than that of age-matched wild-type cells, with no difference in cell width. The resting sarcomere was not longer, but slightly shorter, in cTnI-K118C cardiomyocytes than wild-type cells, indicating longitudinal addition of sarcomeres. More tri- and quadrinuclei cardiomyocytes were found in TnI-K118C than wild-type hearts, suggesting increased nuclear divisions. Whole-genome mRNA array and Western blots detected an increased expression of leukemia inhibitory factor receptor-β in the hearts of 2-mo-old cTnI-K118C mice, suggesting a signaling pathway responsible for the potent effect of cTnI-K118C mutation on early remodeling in cardiomyocytes. PMID:24898585

  13. Developmental Rainbow: Early Childhood Development Profile.

    ERIC Educational Resources Information Center

    Mahoney, Gerald; Mahoney, Frida

    One of the most important skills of professionals who work with young children is the ability to assess developmental functioning through informal observation. This skill serves as the foundation for screening or identifying children in need of developmental services, conducting play-based developmental assessments, and helping parents to…

  14. Early child development and developmental delay in indigenous communities.

    PubMed

    Cappiello, Matthew M; Gahagan, Sheila

    2009-12-01

    Developmental delay is common and often responds to early intervention. As with other health outcomes, the prevalence of developmental delay may be socially determined. Children in many Indigenous communities experience increased risk for developmental delay. This article highlights special conditions in Indigenous communities related to child development. It addresses the challenges of screening and evaluation for developmental delay in the context of Indigenous cultures, and in settings where resources are often inadequate. It is clear that careful research on child development in Indigenous settings is urgently needed. Intervention strategies tied to cultural traditions could enhance interest, acceptability, and ultimately developmental outcomes in children at risk.

  15. A Developmental Approach to Pregnancy Prevention with Early Adolescent Females.

    ERIC Educational Resources Information Center

    Proctor, Susan E.

    1986-01-01

    Traditional pregnancy prevention strategies employed with older teens and adults do not recognize significant developmental differences between early adolescents and other age groups. Methods that compliment, reflect, and are consistent with the developmental needs of the young teen provide the best approaches to teen pregnancy prevention.…

  16. Developmental Trajectories of Early Communication Skills

    ERIC Educational Resources Information Center

    Maatta, Sira; Laakso, Marja-Leena; Tolvanen, Asko; Ahonen, Timo; Aro, Tuija

    2012-01-01

    Purpose: This study focused on developmental trajectories of prelinguistic communication skills and their connections to later parent-reported language difficulties. Method: The participants represent a subset of a community-based sample of 508 children. Data include parent reports of prelinguistic communication skills at 12, 15, 18, and 21 months…

  17. Research on Children's Play: Analysis of Developmental and Early Education Journals from 2005 to 2007

    ERIC Educational Resources Information Center

    Cheng, Mei-Fang; Johnson, James E.

    2010-01-01

    Our review examined four early childhood journals ("Early Child Development and Care," "Early Childhood Education Journal," "Journal of Research in Childhood Education," and "Early Childhood Research Quarterly") and four developmental science journals ("Child Development," "Developmental Psychology," "Journal of Applied Developmental…

  18. Developmental Changes in the Early Child Lexicon in Mandarin Chinese

    ERIC Educational Resources Information Center

    Hao, Meiling; Liu, Youyi; Shu, Hua; Xing, Ailing; Jiang, Ying; Li, Ping

    2015-01-01

    In this paper we report a large-scale developmental study of early productive vocabulary acquisition by 928 Chinese-speaking children aged between 1;0 and 2;6, using the Early Vocabulary Inventory for Mandarin Chinese (Hao, Shu, Xing & Li, 2008). The results show that: (i) social words, especially words for people, are the predominant type of…

  19. Developmental Assessment of Competence from Early Childhood to Middle Adolescence

    ERIC Educational Resources Information Center

    Obradovic, Jelena; van Dulmen, Manfred H. M.; Yates, Tuppett M.; Carlson, Eilzabeth A.; Egeland, Byron

    2006-01-01

    This study represents a developmentally informed, empirically validated examination of competence across multiple domains (Social, Cognitive, Emotional well-being), gender and age (early childhood, middle childhood, early adolescence, middle adolescence). Competence indicators were created and the structure of these domains was tested using…

  20. Merging Policy Initiatives and Developmental Perspectives in Early Intervention

    PubMed Central

    Guralnick, Michael J.

    2015-01-01

    The provision of early intervention services for vulnerable children and their families is now both accepted and expected by the international community. This article considers the importance of a developmental perspective as an essential guide to early intervention service systems. Emphasized in this framework are three critical features: relationship formation, the continuity of interventions, and the comprehensiveness of interventions. Guidance to early intervention systems design with respect to structural and values principles is also discussed. Future advances in early intervention may well depend upon the merging of these perspectives to create policy initiatives to enhance early intervention systems. PMID:26869749

  1. Epigenetic effects of early developmental experiences.

    PubMed

    Gudsnuk, Kathryn M A; Champagne, Frances A

    2011-12-01

    Early-life adversity can affect brain development and behavior. Emerging evidence from studies on both humans and rodents suggests that epigenetic mechanisms may play a critical role in shaping our biology in response to the quality of the environment. This article highlights the research findings suggesting that prenatal maternal stress, postnatal maternal care, and infant neglect/abuse can lead to epigenetic variation, which may have long-term effects on stress responsivity, neuronal plasticity, and behavior.

  2. Sleep Problems and Early Developmental Delay: Implications for Early Intervention Programs

    ERIC Educational Resources Information Center

    Bonuck, Karen; Grant, Roy

    2012-01-01

    Sleep disorders negatively impact behavior, cognition, and growth--the same areas targeted by early intervention. Conversely, developmental delays and disabilities may themselves precipitate sleep disorders. Young children with developmental delays experience sleep disorders at a higher rate than do typically developing children; the most common…

  3. Innervating sympathetic neurons regulate heart size and the timing of cardiomyocyte cell cycle withdrawal.

    PubMed

    Kreipke, R E; Birren, S J

    2015-12-01

    Sympathetic drive to the heart is a key modulator of cardiac function and interactions between heart tissue and innervating sympathetic fibres are established early in development. Significant innervation takes place during postnatal heart development, a period when cardiomyocytes undergo a rapid transition from proliferative to hypertrophic growth. The question of whether these innervating sympathetic fibres play a role in regulating the modes of cardiomyocyte growth was investigated using 6-hydroxydopamine (6-OHDA) to abolish early sympathetic innervation of the heart. Postnatal chemical sympathectomy resulted in rats with smaller hearts, indicating that heart growth is regulated by innervating sympathetic fibres during the postnatal period. In vitro experiments showed that sympathetic interactions resulted in delays in markers of cardiomyocyte maturation, suggesting that changes in the timing of the transition from hyperplastic to hypertrophic growth of cardiomyocytes could underlie changes in heart size in the sympathectomized animals. There was also an increase in the expression of Meis1, which has been linked to cardiomyocyte cell cycle withdrawal, suggesting that sympathetic signalling suppresses cell cycle withdrawal. This signalling involves β-adrenergic activation, which was necessary for sympathetic regulation of cardiomyocyte proliferation and hypertrophy. The effect of β-adrenergic signalling on cardiomyocyte hypertrophy underwent a developmental transition. While young postnatal cardiomyocytes responded to isoproterenol (isoprenaline) with a decrease in cell size, mature cardiomyocytes showed an increase in cell size in response to the drug. Together, these results suggest that early sympathetic effects on proliferation modulate a key transition between proliferative and hypertrophic growth of the heart and contribute to the sympathetic regulation of adult heart size.

  4. A developmental approach to pregnancy prevention with early adolescent females.

    PubMed

    Proctor, S E

    1986-10-01

    Traditional pregnancy prevention strategies employed with adults and older teens do not recognize significant developmental differences between early adolescents and other age groups. Methods that compliment, reflect, and are consistent with developmental needs of the young teen provide cogent approaches to teen pregnancy prevention. Particular emphasis should be placed on interpersonal relationships and their importance in the young woman's life, especially the relationship between the young teen and her parents. Developing and improving all relationships instrumental in positively affecting teen decision-making represent potent approaches to pregnancy prevention. The axioms of Piaget, Erikson, and Mercer are examined in regard to cognitive, social, emotional, and psychosexual development in the 12-14 year old. Young teens' responses to sex education as well as their use of contraception are reviewed in relation to developmental theory.

  5. Engineered early embryonic cardiac tissue increases cardiomyocyte proliferation by cyclic mechanical stretch via p38-MAP kinase phosphorylation.

    PubMed

    Clause, Kelly C; Tinney, Joseph P; Liu, Li J; Keller, Bradley B; Tobita, Kimimasa

    2009-06-01

    Cardiomyocyte (CM) transplantation is one therapeutic option for cardiac repair. Studies suggest that fetal CMs display the best cell type for cardiac repair, which can finitely proliferate, integrate with injured host myocardium, and restore cardiac function. We have recently developed an engineered early embryonic cardiac tissue (EEECT) using embryonic cardiac cells and have shown that EEECT contractile properties and cellular proliferative response to cyclic mechanical stretch stimulation mimic developing fetal myocardium. However, it remains unknown whether cyclic mechanical stretch-mediated high cellular proliferation activity within EEECT reflects CM or non-CM population. Studies have shown that p38-mitogen-activated protein kinase (p38MAPK) plays an important role in both cyclic mechanical stretch stimulation and cellular proliferation. Therefore, in the present study, we tested the hypothesis that cyclic mechanical stretch (0.5 Hz, 5% strain for 48 h) specifically increases EEECT CM proliferation mediated by p38MAPK activity. Cyclic mechanical stretch increased CM, but not non-CM, proliferation and increased p38MAPK phosphorylation. Treatment of EEECT with the p38MAPK inhibitor, SB202190, reduced CM proliferation. The negative CM proliferation effects of SB202190 were not reversed by concurrent stretch stimulation. Results suggest that immature CM proliferation within EEECT can be positively regulated by mechanical stretch and negatively regulated by p38MAPK inhibition.

  6. Developmental and social influences on young girls' early problem behavior.

    PubMed

    Keenan, K; Shaw, D

    1997-01-01

    A developing body of research suggests that there are few sex differences in the rate and severity of problem behavior in early childhood, but clear sex differences emerge at about 4 years of age. The authors explore 2 hypotheses to further the understanding of emerging sex differences in problem behavior across the first 5 years of life. The first posits that the change in girls' problem behavior from infancy to school entry represents a channeling of early problem behavior into predominantly internalizing problems as a result of socialization. The second hypothesis is that the change in girls' early problem behavior during the preschool period results from the more rapid biological, cognitive, and social-emotional development of girls relative to boys. The authors review research on the influence of parents, teachers, and peers on girls' behavior from infancy to preschool regarding the first hypothesis, whereas they review studies of sex differences in developmental processes to test the second. They find moderate support for both hypotheses and present a comprehensive theory of girls' developmental psychopathology that integrates social and developmental influences.

  7. Loss of dystrophin staining in cardiomyocytes: a novel method for detection early myocardial infarction

    PubMed Central

    Hashmi, Satwat; Al-Salam, Suhail

    2013-01-01

    Myocardial infarction (MI) is the most frequent diagnosis made in majority of sudden death cases subjected to clinical and medicolegal autopsies. When sudden death occurs at a very early stage of MI, traditional macroscopic examination, or histological stains cannot easily detect the myocardial changes. For this reason we propose a new method for detecting MI at an early stage. Murine model of MI was used to induce MI through permanent ligation of left anterior descending branch of left coronary artery. Five groups of C57B6/J mice were used for inducing MI, which includes 20 minutes, 30 minutes, one hour, four hours and 24 hours post MI groups. One naïve group and sham-operated groups were used as controls. There is loss of dystrophin membranous staining in cardiac myocytes occurs as early as 20 minutes post myocardial infarction. This can be used as a novel method to diagnose early myocardial infarction in post mortem cases where diagnosis is unclear. In conclusion, evaluation of immunohistochemical expression of dystrophin represents a highly sensitive method for detecting early myocardial infarction due to the loss of staining in the infarcted areas. Dystrophin immunostaining can also be used to assess myocardial architecture. PMID:23330010

  8. Ah Receptor Activation by Dioxin Disrupts Activin, BMP, and WNT Signals During the Early Differentiation of Mouse Embryonic Stem Cells and Inhibits Cardiomyocyte Functions.

    PubMed

    Wang, Qin; Kurita, Hisaka; Carreira, Vinicius; Ko, Chia-I; Fan, Yunxia; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Puga, Alvaro

    2016-02-01

    The AHR is a ligand-activated transcription factor that mediates gene-environment interactions. Genome-wide expression profiling during differentiation of mouse ES cells into cardiomyocytes showed that AHR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin; Dioxin (TCDD), its prototypical ligand, disrupted the expression of multiple homeobox transcription factors and inhibited cardiomyocyte contractility. Here we treated ES cells with TCDD at daily differentiation intervals to investigate whether TCDD-induced loss of contractility had a developmental window of sensitivity. Surprisingly, contractility was an AHR-dependent TCDD target solely between differentiation days 0 and 3 during the period of panmesoderm development, when TCDD also disrupted expression of genes in the TGFβ/BMP2/4 and wingless-type MMTV integration site (WNT)signaling pathways, suppressed the secretion of bone morphogenetic protein (BMP4), WNT3a, and WNT5a and elevated the secretion of Activin A, as determined by ELISA of the secreted proteins in the culture medium. Supplementing the culture medium with BMP4, WNT3a, or WNT5a during the first 3 days of differentiation successfully countered TCDD-induced impairment of contractility, while anti-WNT3a, or anti-WNT5a antibodies or continuous Noggin (a BMP4 antagonist) or Activin A treatment inhibited the contractile phenotype. In Ahr(+/+), but not in Ahr(-) (/) (-) ES cells, TCDD treatment significantly increased mitochondrial copy number, suggestive of mitochondrial stress and remodeling. Sustained AHR activation during ES cell differentiation appears to disrupt the expression of signals critical to the ontogeny of cardiac mesoderm and cause the loss of contractility in the resulting cardiomyocyte lineage.

  9. Ah Receptor Activation by Dioxin Disrupts Activin, BMP, and WNT Signals During the Early Differentiation of Mouse Embryonic Stem Cells and Inhibits Cardiomyocyte Functions

    PubMed Central

    Wang, Qin; Kurita, Hisaka; Carreira, Vinicius; Ko, Chia-I; Fan, Yunxia; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Puga, Alvaro

    2016-01-01

    The AHR is a ligand-activated transcription factor that mediates gene-environment interactions. Genome-wide expression profiling during differentiation of mouse ES cells into cardiomyocytes showed that AHR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin; Dioxin (TCDD), its prototypical ligand, disrupted the expression of multiple homeobox transcription factors and inhibited cardiomyocyte contractility. Here we treated ES cells with TCDD at daily differentiation intervals to investigate whether TCDD-induced loss of contractility had a developmental window of sensitivity. Surprisingly, contractility was an AHR-dependent TCDD target solely between differentiation days 0 and 3 during the period of panmesoderm development, when TCDD also disrupted expression of genes in the TGFβ/BMP2/4 and wingless-type MMTV integration site (WNT)signaling pathways, suppressed the secretion of bone morphogenetic protein (BMP4), WNT3a, and WNT5a and elevated the secretion of Activin A, as determined by ELISA of the secreted proteins in the culture medium. Supplementing the culture medium with BMP4, WNT3a, or WNT5a during the first 3 days of differentiation successfully countered TCDD-induced impairment of contractility, while anti-WNT3a, or anti-WNT5a antibodies or continuous Noggin (a BMP4 antagonist) or Activin A treatment inhibited the contractile phenotype. In Ahr+/+, but not in Ahr−/− ES cells, TCDD treatment significantly increased mitochondrial copy number, suggestive of mitochondrial stress and remodeling. Sustained AHR activation during ES cell differentiation appears to disrupt the expression of signals critical to the ontogeny of cardiac mesoderm and cause the loss of contractility in the resulting cardiomyocyte lineage. PMID:26572662

  10. Early Risk Factors of Overweight Developmental Trajectories during Middle Childhood

    PubMed Central

    Pryor, Laura E.; Brendgen, Mara; Tremblay, Richard E.; Pingault, Jean-Baptiste; Liu, Xuecheng; Dubois, Lise; Touchette, Evelyne; Falissard, Bruno; Boivin, Michel; Côté, Sylvana M.

    2015-01-01

    Background Research is needed to identify early life risk factors associated with different developmental paths leading to overweight by adolescence. Objectives To model heterogeneity in overweight development during middle childhood and identify factors associated with differing overweight trajectories. Methods Data was drawn from the Quebec Longitudinal Study of Child Development (QLSCD; 1998-2010). Trained research assistants measured height and weight according to a standardized protocol and conducted yearly home interviews with the child’s caregiver (mother in 98% of cases). Information on several putative early life risk factors for the development of overweight were obtained, including factors related to the child’s perinatal, early behavioral family and social environment. Group-based trajectories of the probability of overweight (6-12 years) were identified with a semiparametric method (n=1678). Logistic regression analyses were used to identify early risk factors (5 months- 5 years) associated with each trajectory. Results Three trajectories of overweight were identified: “early-onset overweight” (11.0 %), “late-onset overweight” (16.6%) and “never overweight” (72.5%). Multinomial analyses indicated that children in the early and late-onset group, compared to the never overweight group, had 3 common types of risk factors: parental overweight, preschool overweight history, and large size for gestational age. Maternal overprotection (OR= 1.12, CI: 1.01-1.25), short nighttime sleep duration (OR=1.66, CI: 1.07-2.57), and immigrant status (OR=2.01, CI: 1.05-3.84) were factors specific to the early-onset group. Finally, family food insufficiency (OR=1.81, CI: 1.00-3.28) was weakly associated with membership in the late-onset trajectory group. Conclusions The development of overweight in childhood follows two different trajectories, which have common and distinct risk factors that could be the target of early preventive interventions. PMID

  11. Trajectories of Physical Discipline: Early Childhood Antecedents and Developmental Outcomes

    PubMed Central

    Lansford, Jennifer E.; Criss, Michael M.; Dodge, Kenneth A.; Shaw, Daniel S.; Pettit, Gregory S.; Bates, John E.

    2009-01-01

    This study examined childhood antecedents and developmental outcomes associated with trajectories of mild and harsh parental physical discipline. Interview, questionnaire, and observational data were available from 499 children followed from age 5 to 16 and from 258 children in an independent sample followed from age 5 to 15. Analyses indicated distinct physical discipline trajectory groups that varied in frequency of physical discipline and rate of change. In both samples, family ecological disadvantage differentiated the trajectory groups; in the first sample, early child externalizing also differentiated the groups. Controlling for early childhood externalizing, the minimal/ceasing trajectory groups were associated with the lowest levels of subsequent adolescent antisocial behavior in both samples and with parent-adolescent positive relationship quality in the second sample. PMID:19765007

  12. Precursors of Adolescent Substance Use from Early Childhood and Early Adolescence: Testing a Developmental Cascade Model

    PubMed Central

    Sitnick, Stephanie; Shaw, Daniel S.; Hyde, Luke

    2013-01-01

    This study examined developmentally-salient risk and protective factors of adolescent substance use assessed during early childhood and early adolescence using a sample of 310 low-income boys. Child problem behavior and proximal family risk and protective factors (i.e., parenting, maternal depression) during early childhood, as well as child and family factors and peer deviant behavior during adolescence were explored as potential precursors to later substance use during adolescence using structural equation modeling. Results revealed that early childhood risk and protective factors (i.e., child externalizing problems, mothers’ depressive symptomatology, and nurturant parenting) were indirectly related to substance use at the age of 17 via risk and protective factors during early and middle adolescence (i.e., parental knowledge and externalizing problems). The implications of these findings for early prevention and intervention are discussed. PMID:24029248

  13. Precursors of adolescent substance use from early childhood and early adolescence: testing a developmental cascade model.

    PubMed

    Sitnick, Stephanie L; Shaw, Daniel S; Hyde, Luke W

    2014-02-01

    This study examined developmentally salient risk and protective factors of adolescent substance use assessed during early childhood and early adolescence using a sample of 310 low-income boys. Child problem behavior and proximal family risk and protective factors (i.e., parenting and maternal depression) during early childhood, as well as child and family factors and peer deviant behavior during adolescence, were explored as potential precursors to later substance use during adolescence using structural equation modeling. Results revealed that early childhood risk and protective factors (i.e., child externalizing problems, mothers' depressive symptomatology, and nurturant parenting) were indirectly related to substance use at the age of 17 via risk and protective factors during early and middle adolescence (i.e., parental knowledge and externalizing problems). The implications of these findings for early prevention and intervention are discussed.

  14. Developmental plasticity and disparity in early dipnoan (lungfish) dentitions.

    PubMed

    Ahlberg, Per Erik; Smith, Moya M; Johanson, Zerina

    2006-01-01

    Although the lungfish (Dipnoi) belong within the Osteichthyes, their dentitions are radically different from other osteichthyans. Lungfish dentitions also show a uniquely high structural disparity during the early evolution of the group, partly owing to the independent variation of odontogenic and odontoclastic processes that are tightly and stereotypically coordinated in other osteichthyans. We present a phylogenetic analysis of early lungfishes incorporating a novel approach to coding these process characters in preference to the resultant adult dental morphology. The results only partially resolve the interrelationships of Devonian dipnoans, but show that the widely discussed hypothesis of separate tooth-plated, dentine-plated, and denticulated lineages is unlikely to be true. The dipnoan status of Diabolepis is corroborated. Lungfish dentitions seem to have undergone extensive and nonparsimonious evolution during the early history of the group, but much of the resulting disparity can be explained by a modest number of evolutionary steps in the underlying developmental processes, those for dental formation (odontogenic) and those for the remodeling of dentine tissue (odontoclastic). Later in lungfish evolution, this disparity was lost as the group settled to a pattern of dental development that is just as stereotypic as, but completely different from, that of other osteichthyans.

  15. Early Developmental Program Shapes Colony Morphology in Bacteria

    PubMed Central

    Mamou, Gideon; Malli Mohan, Ganesh Babu; Rouvinski, Alex; Rosenberg, Alex; Ben-Yehuda, Sigal

    2016-01-01

    Summary When grown on a solid surface, bacteria form highly organized colonies, yet little is known about the earliest stages of colony establishment. Following Bacillus subtilis colony development from a single progenitor cell, a sequence of highly ordered spatiotemporal events was revealed. Colony was initiated by the formation of leading-cell chains, deriving from the colony center and extending in multiple directions, typically in a “Y-shaped” structure. By eradicating particular cells during these early stages, we could influence the shape of the resulting colony and demonstrate that Y-arm extension defines colony size. A mutant in ymdB encoding a phosphodiesterase displayed unordered developmental patterns, indicating a role in guiding these initial events. Finally, we provide evidence that intercellular nanotubes contribute to proper colony formation. In summary, we reveal a “construction plan” for building a colony and provide the initial molecular basis for this process. PMID:26904951

  16. Early pharmacological treatment of autism: a rationale for developmental treatment

    PubMed Central

    Bethea, Terrence C.; Sikich, Linmarie

    2007-01-01

    Autism is a dynamic neurodevelopmental syndrome in which disabilities emerge during the first three postnatal years and continue to evolve with ongoing development. We briefly review research in autism describing subtle changes in molecules important in brain development and neurotransmission, in morphology of specific neurons, brain connections and in brain size. We then provide a general schema of how these processes may interact with particular emphasis on neurotransmission. In this context, we present a rationale for utilizing pharmacologic treatments aimed at modifying key neurodevelopmental processes in young children with autism. Early treatment with selective serotonin reuptake inhibitors (SSRIs) is presented as a model for pharmacologic interventions because there is evidence in autistic children for reduced brain serotonin synthesis during periods of peak synaptogenesis; serotonin is known to enhance synapse refinement; and exploratory studies with these agents in autistic children exist. Additional hypothetical developmental interventions and relevant published clinical data are described. Finally, we discuss the importance of exploring early pharmacologic interventions within multiple experimental settings in order to develop effective treatments as quickly as possible while minimizing risks. PMID:17276749

  17. Punishment Insensitivity in Early Childhood: A Developmental, Dimensional Approach.

    PubMed

    Nichols, Sara R; Briggs-Gowan, Margaret J; Estabrook, Ryne; Burns, James L; Kestler, Jacqueline; Berman, Grace; Henry, David B; Wakschlag, Lauren S

    2015-08-01

    Impairment in learning from punishment ("punishment insensitivity") is an established feature of severe antisocial behavior in adults and youth but it has not been well studied as a developmental phenomenon. In early childhood, differentiating a normal: abnormal spectrum of punishment insensitivity is key for distinguishing normative misbehavior from atypical manifestations. This study employed a novel measure, the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB), to examine the distribution, dimensionality, and external validity of punishment insensitivity in a large, demographically diverse community sample of preschoolers (3-5 years) recruited from pediatric clinics (N = 1,855). Caregivers completed surveys from which a seven-item Punishment Insensitivity scale was derived. Findings indicated that Punishment Insensitivity behaviors are relatively common in young children, with at least 50 % of preschoolers exhibiting them sometimes. Item response theory analyses revealed a Punishment Insensitivity spectrum. Items varied along a severity continuum: most items needed to occur "Often" in order to be severe and behaviors that were qualitatively atypical or intense were more severe. Although there were item-level differences across sociodemographic groups, these were small. Construct, convergent, and divergent validity were demonstrated via association to low concern for others and noncompliance, motivational regulation, and a disruptive family context. Incremental clinical utility was demonstrated in relation to impairment. Early childhood punishment insensitivity varies along a severity continuum and is atypical when it predominates. Implications for understanding the phenomenology of emergent disruptive behavior are discussed.

  18. Punishment insensitivity in early childhood: A developmental, dimensional approach

    PubMed Central

    Nichols, Sara R.; Briggs-Gowan, Margaret; Estabrook, Ryne; Burns, James; Kestler, Jacqueline; Berman, Grace; Henry, David; Wakschlag, Lauren

    2014-01-01

    Impairment in learning from punishment ("punishment insensitivity") is an established feature of severe antisocial behavior in adults and youth but it has not been well studied as a developmental phenomenon. In early childhood, differentiating a normal:abnormal spectrum of punishment insensitivity is key for distinguishing normative misbehavior from atypical manifestations. This study employed a novel measure, the Multidimensional Assessment Profile of Disruptive Behavior (MAPDB), to examine the distribution, dimensionality, and external validity of punishment insensitivity in a large, demographically diverse community sample of preschoolers (three-five years) recruited from pediatric clinics (N=1,855). Caregivers completed surveys from which a seven-item Punishment Insensitivity scale was derived. Findings indicated that Punishment Insensitivity behaviors are relatively common in young children, with at least 50% of preschoolers exhibiting them sometimes. Item response theory analyses revealed a Punishment Insensitivity spectrum. Items varied along a severity continuum: most items needed to occur "Often" in order to be severe and behaviors that were qualitatively atypical or intense were more severe. Although there were item-level differences across sociodemographic groups, these were small. Construct, convergent, and divergent validity were demonstrated via association to low concern for others and noncompliance, motivational regulation, and a disruptive family context. Incremental clinical utility was demonstrated in relation to impairment. Early childhood punishment insensitivity varies along a severity continuum and is atypical when it predominates. Implications for understanding the phenomenology of emergent disruptive behavior are discussed. PMID:25425187

  19. Developmentally Appropriate Practice in Early Elementary Grade Schools in Bangkok, Thailand

    ERIC Educational Resources Information Center

    Saifah, Yotsawee

    2012-01-01

    The purposes of this study were (a) to examine early elementary grade teachers' developmentally appropriate beliefs and their teaching practices in public schools in Bangkok, (b) to explore the functioning of developmentally appropriate practice in the two chosen early elementary schools, and (c) to determine the factors that influence the…

  20. Depression and Anxiety Symptoms: Onset, Developmental Course and Risk Factors during Early Childhood

    ERIC Educational Resources Information Center

    Cote, Sylvana M.; Boivin, Michel; Liu, Xuecheng; Nagin, Daniel S.; Zoccolillo, Mark; Tremblay, Richard E.

    2009-01-01

    Background: Depressive and anxiety disorders are among the top ten leading causes of disabilities. We know little, however, about the onset, developmental course and early risk factors for depressive and anxiety symptoms (DAS). Objective: Model the developmental trajectories of DAS during early childhood and to identify risk factors for atypically…

  1. Developmental programming: variations in early growth and adult disease.

    PubMed

    Gallo, Linda A; Tran, Melanie; Moritz, Karen M; Wlodek, Mary E

    2013-11-01

    Suboptimal conditions in utero are associated with the development of adult-onset diseases in offspring. Uteroplacental insufficiency in rats is a well-established animal model used to mimic and study the effects of developmental insults relevant to countries of abundant nutrient supply. However, wide-ranging outcomes for the offspring are apparent between the different investigators that use this model and also between cohorts generated in our laboratory. We aimed to explore the reasons for variability in rat models of uteroplacental insufficiency between different investigators and also between our own animal cohorts. We suggest differences in growth and disease development reflect uniqueness in susceptibility and highlight the complexity of interactions between genetic potential and environmental exposures. The impact of adverse exposures in utero has been described as having far-reaching effects that extend well beyond the first, directly exposed generation. However, the resulting phenotypes are not consistent between generations. This suggests that programmed effects are established de novo in each generation and challenges the prediction of disease. Characterization of growth and disease in the numerous rat models has led to our understanding of the impact of early life experiences on adult health. In order to drive the development of preventative and/or treatment strategies, future studies should focus on identifying the initial cause(s) of uteroplacental insufficiency, including genetic origins and the influence of poor diets.

  2. Children’s early helping in action: Piagetian developmental theory and early prosocial behavior

    PubMed Central

    Hammond, Stuart I.

    2014-01-01

    After a brief overview of recent research on early helping, outlining some central problems, and issues, this paper examines children’s early helping through the lens of Piagetian moral and developmental theory, drawing on Piaget’s “Moral Judgment of the Child” (Piaget, 1932/1997), “Play, Dreams, and Imitation in Childhood” (Piaget, 1945/1951), and the “Grasp of Consciousness” (Piaget, 1976). Piaget refers to a level of moral development in action that precedes heteronomous and autonomous moral reasoning. This action level allows children to begin to interact with people and objects. In his later work, Piaget explores the gradual construction of understanding from this activity level. Taken together, these elements of Piagetian theory provide a promising conceptual framework for understanding the development of early helping. PMID:25101027

  3. Children's early helping in action: Piagetian developmental theory and early prosocial behavior.

    PubMed

    Hammond, Stuart I

    2014-01-01

    After a brief overview of recent research on early helping, outlining some central problems, and issues, this paper examines children's early helping through the lens of Piagetian moral and developmental theory, drawing on Piaget's "Moral Judgment of the Child" (Piaget, 1932/1997), "Play, Dreams, and Imitation in Childhood" (Piaget, 1945/1951), and the "Grasp of Consciousness" (Piaget, 1976). Piaget refers to a level of moral development in action that precedes heteronomous and autonomous moral reasoning. This action level allows children to begin to interact with people and objects. In his later work, Piaget explores the gradual construction of understanding from this activity level. Taken together, these elements of Piagetian theory provide a promising conceptual framework for understanding the development of early helping.

  4. Sauchinone augments cardiomyocyte viability by enhancing autophagy proteins -PI3K, ERK(1/2), AMPK and Beclin-1 during early ischemia-reperfusion injury in vitro

    PubMed Central

    Thapalia, Bisharad Anil; Zhou, Zhen; Lin, Xianhe

    2016-01-01

    Background. Sauchinone has proved its anti-oxidant and anti-inflammatory properties in various animal tissues. This study sought to illustrate its regulatory nature on autophagy associated proteins (PI3K, ERK1/2, AMPK, and Beclin-1) during early cardiomyocyte ischemia and subsequent reperfusion. Methods. Cultured cardiomyocytes were subjected to simulated Ischemia/reperfusion with and without Sauchinone pretreatment and also in the presence of autophagy inhibitor (3-MA). Colorimetric analysis of CCK-8, LDH antibody assay as well as Western blot analysis were performed to observe the expressions of LC3B (II) and Beclin-1 protein (markers of autophagy), autophagy proteins (PI3K, ERK1/2 and AMPK) and apoptotic proteins (Bax and Bcl-2) and the results were quantified into their grey values and subjected to statistical analysis. Results. Sauchinone demonstrated cell survival enhancing properties with increase in CCK-8 (SD = 0.553±0.012) and decrease in LDH (SD = 0.183±0.054) expressions, both of which were best observed at test dose of 20 µmol/L. At this dose, there was increment in cellular autophagy as demonstrated by peaking of autophagy markers LC3B-II (p<0.05) and Beclin-1 (p<0.05) with strong correlations (r = 0.99). Similarly, the autophagy proteins, compared to control and I/R model, also showed a significant increased level with PI3K (p<0.0001), total p-ERK1/2 (p<0.0001) and p-AMPKα (p<0.0001). Simultaneously, a decrease in expressions of pro-apoptotic molecules Bax (r = 0.989, p<0.0001) with increment of in the anti-apoptotic protein Bcl-2 (r = 0.996, p<0.0001) was observed. The observed effects on cell density, viability and autophagy was abrogated in presence of 3-MA. Conclusions. Sauchinone enhances cell survival by promoting autophagy and inhibiting apoptosis in cardiomyocytes during early stages of Ischemia/reperfusion injury. PMID:27508047

  5. Early Childhood Developmental Screenings: Predictors of Screening Referral Completion

    ERIC Educational Resources Information Center

    Jennings, Danielle J.

    2012-01-01

    Developmental screening programs identify young children with delayed skill growth or challenging behaviors and refer them to community agencies for evaluation or other services. This research studied the predictive impact of developmental screening results and child and family characteristics on the completion of these referrals for evaluation. A…

  6. Early-life Social Adversity and Developmental Processes in Nonhuman Primates

    PubMed Central

    French, Jeffrey A; Carp, Sarah B

    2015-01-01

    Most primate species produce offspring that are altricial and highly dependent upon caregivers. As a consequence, a host of developmental trajectories can be dramatically altered by variation in early experiences. We review the impact of early social experiences (in both experimental models and natural contexts) on developmental profiles in three species of nonhuman primates: marmosets, squirrel monkeys, and macaques. Graded exposure to early-life social adversity (ELSA) produces short- to long-term effects on multiple developmental outcomes, including affect, social behavior, cognitive and attentional processes, and in the neural substrates that underlie these sociobehavioral traits. PMID:26858971

  7. The molecular and functional identities of atrial cardiomyocytes in health and disease.

    PubMed

    Brandenburg, Sören; Arakel, Eric C; Schwappach, Blanche; Lehnart, Stephan E

    2016-07-01

    Atrial cardiomyocytes are essential for fluid homeostasis, ventricular filling, and survival, yet their cell biology and physiology are incompletely understood. It has become clear that the cell fate of atrial cardiomyocytes depends significantly on transcription programs that might control thousands of differentially expressed genes. Atrial muscle membranes propagate action potentials and activate myofilament force generation, producing overall faster contractions than ventricular muscles. While atria-specific excitation and contractility depend critically on intracellular Ca(2+) signalling, voltage-dependent L-type Ca(2+) channels and ryanodine receptor Ca(2+) release channels are each expressed at high levels similar to ventricles. However, intracellular Ca(2+) transients in atrial cardiomyocytes are markedly heterogeneous and fundamentally different from ventricular cardiomyocytes. In addition, differential atria-specific K(+) channel expression and trafficking confer unique electrophysiological and metabolic properties. Because diseased atria have the propensity to perpetuate fast arrhythmias, we discuss our understanding about the cell-specific mechanisms that lead to metabolic and/or mitochondrial dysfunction in atrial fibrillation. Interestingly, recent work identified potential atria-specific mechanisms that lead to early contractile dysfunction and metabolic remodelling, suggesting highly interdependent metabolic, electrical, and contractile pathomechanisms. Hence, the objective of this review is to provide an integrated model of atrial cardiomyocytes, from tissue-specific cell properties, intracellular metabolism, and excitation-contraction (EC) coupling to early pathological changes, in particular metabolic dysfunction and tissue remodelling due to atrial fibrillation and aging. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes

  8. The Relation of Emotional Maltreatment to Early Adolescent Competence: Developmental Processes in a Prospective Study

    ERIC Educational Resources Information Center

    Shaffer, Anne; Yates, Tuppett M.; Egeland, Byron R.

    2009-01-01

    Objectives: This investigation examined developmental pathways between childhood emotional maltreatment and adaptational outcomes in early adolescence. This study utilized a developmental psychopathology perspective in adopting a multidimensional approach to the assessment of different forms of emotional maltreatment and later adjustment outcomes.…

  9. Including and Supporting Preschool Children with Developmental Delays in Early Childhood Programs.

    ERIC Educational Resources Information Center

    Brown, William H., Ed.; Conroy, Maureen A., Ed.

    Mainstreaming, integrating, and including young children with developmental delays in programs with peers without developmental delays began over 25 years ago and has gained much legal and policy support. This book provides early childhood educators with high-quality and contemporary information that they might need while serving young children…

  10. Priorities for Developmental Areas in Early Childhood Education: A Comparison of Parents' and Teachers' Priorities

    ERIC Educational Resources Information Center

    Sackes, Mesut

    2013-01-01

    The purpose of this study was to examine parents' and early childhood teachers' perceptions of the priorities for developmental areas targeted in the Turkish Early Childhood Education Curriculum for children aged 36-72 months. The sample of this study consisted of 1600 parents and 158 early childhood teachers. The study utilized a survey research…

  11. Erikson and Early Childhood Educators: Looking at Ourselves and Our Profession Developmentally.

    ERIC Educational Resources Information Center

    Gratz, Rene R.; Boulton, Pamla J.

    1996-01-01

    Describes Erikson's theory of developmentally appropriate curriculum and the eight stages of the life cycle. Provides brief descriptions of these stages and some possible professional applications that early childhood educators can use in pursuing professional development. (MOK)

  12. Screening for autism in young children with developmental delay: an evaluation of the developmental behaviour checklist: early screen.

    PubMed

    Gray, K M; Tonge, B J; Sweeney, D J; Einfeld, S L

    2008-07-01

    The ability to identify children who require specialist assessment for the possibility of autism at as early an age as possible has become a growing area of research. A number of measures have been developed as potential screening tools for autism. The reliability and validity of one of these measures for screening for autism in young children with developmental problems was evaluated. The parents of 207 children aged 20-51 months completed the Developmental Checklist-Early Screen (DBC-ES), prior to their child undergoing assessment. Good interrater agreement and internal consistency was found, along with significant correlations with a clinician completed measure of autism symptomatology. High sensitivity was found, with lower specificity for the originally proposed 17-item screening tool and a five-item version.

  13. Child maltreatment and children's developmental trajectories in early to middle childhood.

    PubMed

    Font, Sarah A; Berger, Lawrence M

    2015-01-01

    Associations between experiencing child maltreatment and adverse developmental outcomes are widely studied, yet conclusions regarding the extent to which effects are bidirectional, and whether they are likely causal, remain elusive. This study uses the Fragile Families and Child Wellbeing Study, a birth cohort of 4,898 children followed from birth through age 9. Hierarchical linear modeling and structural equation modeling are employed to estimate associations of maltreatment with cognitive and social-emotional well-being. Results suggest that effects of early childhood maltreatment emerge immediately, though developmental outcomes are also affected by newly occurring maltreatment over time. Additionally, findings indicate that children's early developmental scores predict their subsequent probability of experiencing maltreatment, though to a lesser extent than early maltreatment predicts subsequent developmental outcomes.

  14. Child Maltreatment and Children's Developmental Trajectories in Early- to Middle-Childhood

    PubMed Central

    Font, Sarah A.; Berger, Lawrence M.

    2014-01-01

    Associations between experiencing child maltreatment and adverse developmental outcomes are widely studied, yet conclusions regarding the extent to which effects are bidirectional, and whether they are likely causal, remain elusive. This study uses the Fragile Families and Child Well-Being study, a birth cohort of 4,898 children followed from birth through age 9. Hierarchical linear modeling and structural equation modeling are employed to estimate associations of maltreatment with cognitive and social-emotional well-being. Results suggest that effects of early childhood maltreatment emerge immediately, though developmental outcomes are also affected by newly occurring maltreatment over time. Additionally, findings indicate that children's early developmental scores predict their subsequent probability of experiencing maltreatment, though to a lesser extent than early maltreatment predicts subsequent developmental outcomes. PMID:25521556

  15. Exclusive Breastfeeding and Developmental and Behavioral Status in Early Childhood

    PubMed Central

    Jonsdottir, Olof H.; Thorsdottir, Inga; Gunnlaugsson, Geir; Fewtrell, Mary S.; Hibberd, Patricia L.; Kleinman, Ronald E.

    2013-01-01

    Breastfeeding during infancy may have beneficial effects on various developmental outcomes in childhood. In this study, exclusively breastfed infants were randomly assigned to receive complementary foods from the age of 4 months in addition to breast milk (CF, n = 60), or to exclusively breastfeed to 6 months (EBF, n = 59). At 18 months and again at 30–35 months of age, the children were evaluated with the Parent’s Evaluation of Developmental Status questionnaire (PEDS) and the Brigance Screens-II. The parents completed the PEDS questionnaire at both time intervals and the children underwent the Brigance Screens-II at 30–35 months. At 30–35 months, no significant differences were seen in developmental scores from the Brigance screening test (p = 0.82). However, at 30–35 months a smaller percentage of parents in group CF (2%) had concerns about their children’s gross motor development compared to those in group EBF (19%; p = 0.01), which remained significant when adjusted for differences in pre-randomization characteristics (p = 0.03). No sustained effect of a longer duration of exclusive breastfeeding was seen on selected measures of developmental and behavioral status at 18 months, although at 30–35 months, a smaller percentage of parents of children introduced to complementary foods at four months of age expressed concerns about their gross motor development. PMID:24284608

  16. Then and Now: The Early Years of Developmental Education.

    ERIC Educational Resources Information Center

    Arendale. David R.

    2002-01-01

    Identifies six phases of developmental education in American history, each of which naturally interconnects with social history. States that each succeeding phase includes more student subpopulations, beginning in the mid-1600s with privileged white males, to the present, more diverse era. Explores first three phases--which focused on tutoring and…

  17. Identification of Early Risk Factors for Developmental Delay

    ERIC Educational Resources Information Center

    Delgado, Christine E. F.; Vagi, Sara J.; Scott, Keith G.

    2007-01-01

    Statewide birth certificate and preschool exceptionality records were integrated to identify risk factors for developmental delay (DD). Epidemiological methods were used to investigate both individual-level and population-level risk for DD associated with a number of child and maternal factors. Infants born with very low birth weight were at the…

  18. Responses to Developmental and Family Changes in Early Adolescence.

    ERIC Educational Resources Information Center

    Petersen, Anne C.; And Others

    Research has identified several factors which may be stressful in early adolescence, including school change, puberty, and family changes. This study used a longitudinal cohort sequential design to examine whether stressful changes in early adolescence have impact beyond early adolescence. Of the 335 sixth graders initially sampled, 169 were…

  19. The Role of Maternal Depression in Accessing Early Intervention Services for Children with Developmental Delay

    ERIC Educational Resources Information Center

    Colgan, Siobhan Eileen

    2012-01-01

    This study investigated the relationship between maternal depression and children's access to early intervention services among a sample of children with developmental delay at age two who were determined to be eligible for early intervention services, were full term and of normal birth weight, and were not previously identified with any special…

  20. An Evaluation of a Multicomponent Early Literacy Program for Students with Severe Developmental Disabilities

    ERIC Educational Resources Information Center

    Browder, Diane; Ahlgrim-Delzell, Lynn; Flowers, Claudia; Baker, Joshua

    2012-01-01

    This study evaluated the effectiveness of a multicomponent early literacy curriculum that included phonics and phonemic awareness in comparison to a sight word approach. A total of 93 students with severe developmental disabilities who were enrolled in Grades K through 4 were randomly assigned to either a multicomponent early literacy curriculum…

  1. Evaluation of the Effectiveness of an Early Literacy Program for Students with Significant Developmental Disabilities

    ERIC Educational Resources Information Center

    Browder, Diane M.; Ahlgrim-Delzell, Lynn; Courtade, Ginevra; Gibbs, Susan L.; Flowers, Claudia

    2008-01-01

    This study evaluated the impact of a curriculum called the Early Literacy Skills Builder on the language and early literacy skills of students with significant developmental disabilities. Students in the control group received the ongoing sight word and picture instruction prescribed by their individualized education programs. Results indicate…

  2. Early Mastery Motivation as a Predictor of Executive Function in Young Adults with Developmental Disabilities

    ERIC Educational Resources Information Center

    Hauser-Cram, Penny; Woodman, Ashley Cynthia; Heyman, Miriam

    2014-01-01

    The role of early childhood mastery motivation as a predictor of executive function 20 years later was examined in a sample of 39 individuals who had early diagnosed developmental disabilities. Multilevel modeling was used to analyze predictors of accuracy and response time on a Flanker task measuring executive function. As predicted, participants…

  3. Social geography of developmental health in the early years.

    PubMed

    Hertzman, Clyde

    2010-01-01

    What happens to children in their earliest years is critical for their development throughout the life course. The years from zero to school age are foundational for brain and biological development. Attachment and face recognition; impulse control and regulation of physical aggression; executive function in the prefrontal cortex and focused attention; fine and gross motor functions and coordination; receptive and expressive language; and understandings of quantitative concepts are all established during this time and become embedded in the architecture and function of the brain (Doherty 1997; Kolb 2009; McCain and Mustard 1999). Brain and biological development are in turn expressed through three broad domains of development of the whole child: physical, social-emotional and language-cognitive, which together are the basis of "developmental health" (Keating and Hertzman 1999). Developmental health influences many aspects of well-being, including obesity and stunting, mental health, heart disease, competence in literacy and numeracy, criminality and economic participation throughout life (Irwin et al. 2007). Accordingly, developmental health is the central concern of this article.

  4. Contractile properties of early human embryonic stem cell-derived cardiomyocytes: beta-adrenergic stimulation induces positive chronotropy and lusitropy but not inotropy.

    PubMed

    Pillekamp, Frank; Haustein, Moritz; Khalil, Markus; Emmelheinz, Markus; Nazzal, Rewa; Adelmann, Roland; Nguemo, Filomain; Rubenchyk, Olga; Pfannkuche, Kurt; Matzkies, Matthias; Reppel, Michael; Bloch, Wilhelm; Brockmeier, Konrad; Hescheler, Juergen

    2012-08-10

    Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) provide the unique opportunity to study the very early development of the human heart. The aim of this study was to investigate the effect of calcium and beta-adrenergic stimulation on the contractile properties of early hESC-CMs. Beating clusters containing hESC-CMs were co-cultured in vitro with noncontractile slices of neonatal murine ventricles. After 5-7 days, when beating clusters had integrated morphologically into the damaged tissue, isometric force measurements were performed during spontaneous beating as well as during electrical field stimulation. Spontaneous beating stopped when extracellular calcium ([Ca²⁺](ec)) was removed or after administration of the Ca²⁺ channel blocker nifedipine. During field stimulation at a constant rate, the developed force increased with incremental concentrations of [Ca²⁺](ec). During spontaneous beating, rising [Ca²⁺](ec) increased beating rate and developed force up to a [Ca²⁺](ec) of 2.5 mM. When [Ca²⁺](ec) was increased further, spontaneous beating rate decreased, whereas the developed force continued to increase. The beta-adrenergic agonist isoproterenol induced a dose-dependent increase of the frequency of spontaneous beating; however, it did not significantly change the developed force during spontaneous contractions or during electrical stimulation at a constant rate. Force developed by early hESC-CMs depends on [Ca²⁺](ec) and on the L-type Ca²⁺ channel. The lack of an inotropic reaction despite a pronounced chronotropic response after beta-adrenergic stimulation most likely indicates immaturity of the sarcoplasmic reticulum. For cell-replacement strategies, further maturation of cardiac cells has to be achieved either in vitro before or in vivo after transplantation.

  5. Analysis of cardiomyocyte movement in the developing murine heart

    SciTech Connect

    Hashimoto, Hisayuki; Yuasa, Shinsuke; Tabata, Hidenori; Tohyama, Shugo; Seki, Tomohisa; Egashira, Toru; Hayashiji, Nozomi; Hattori, Fumiyuki; Kusumoto, Dai; Kunitomi, Akira; Takei, Makoto; Kashimura, Shin; Yozu, Gakuto; Shimojima, Masaya; Motoda, Chikaaki; Muraoka, Naoto; Nakajima, Kazunori; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Fukuda, Keiichi

    2015-09-04

    The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.

  6. Developmental Dyslexia: Early Precursors, Neurobehavioral Markers, and Biological Substrates

    ERIC Educational Resources Information Center

    Benasich, April A., Ed.; Fitch, R. Holly, Ed.

    2012-01-01

    Understanding the precursors and early indicators of dyslexia is key to early identification and effective intervention. Now there's a single research volume that brings together the very latest knowledge on the earliest stages of dyslexia and the diverse genetic, neurobiological, and cognitive factors that may contribute to it. Based on findings…

  7. Cerebral lateralization and early speech acquisition: a developmental scenario.

    PubMed

    Minagawa-Kawai, Yasuyo; Cristià, Alejandrina; Dupoux, Emmanuel

    2011-07-01

    During the past ten years, research using Near-infrared Spectroscopy (NIRS) to study the developing brain has provided groundbreaking evidence of brain functions in infants. This paper presents a theoretically oriented review of this wealth of evidence, summarizing recent NIRS data on language processing, without neglecting other neuroimaging or behavioral studies in infancy and adulthood. We review three competing classes of hypotheses (i.e. signal-driven, domain-driven, and learning biases hypotheses) regarding the causes of hemispheric specialization for speech processing. We assess the fit between each of these hypotheses and neuroimaging evidence in speech perception and show that none of the three hypotheses can account for the entire set of observations on its own. However, we argue that they provide a good fit when combined within a developmental perspective. According to our proposed scenario, lateralization for language emerges out of the interaction between pre-existing left-right biases in generic auditory processing (signal-driven hypothesis), and a left-hemisphere predominance of particular learning mechanisms (learning-biases hypothesis). As a result of this completed developmental process, the native language is represented in the left hemisphere predominantly. The integrated scenario enables to link infant and adult data, and points to many empirical avenues that need to be explored more systematically.

  8. Bringing a developmental perspective to early childhood and family interventionists: where to begin.

    PubMed

    Hogan, Anne E; Quay, Herbert C

    2014-01-01

    There is a pressing need to share advances in developmental science with the large, multidisciplinary professional workforce that serves vulnerable infants and toddlers and their families. Foundational knowledge and conceptual frameworks that integrate material regarding the contents and processes of early development and promotion of their use can assist interventionists and the families they serve. This chapter describes an approach that has been developed over the past 10 years and summarizes key contents with sample practical applications. Topic areas include developmental theories, newborn capacities, a model for synthesizing information about early social competence (including self-regulation, early relationships, social skills, and social cognition), and key current topics in developmental psychopathology. Brief considerations of diversity and stigma for work with young children and families are also included.

  9. Transcriptional Control of Early T and B Cell Developmental Choices

    PubMed Central

    Rothenberg, Ellen V.

    2014-01-01

    T and B cells share a common somatic gene rearrangement mechanism for assembling the genes that code for their antigen receptors and developmental pathways with many parallels. Shared usage of basic helix-loop-helix E proteins as transcriptional drivers underlies these common features. However, the transcription factor networks in which these E proteins are embedded are different both in membership and in architecture for T and B cell gene regulatory programs. These differences permit lineage commitment decisions to be made in different hierarchical orders. Furthermore, in a contrast to B-cell gene networks, the T-cell gene network architecture for effector differentiation is sufficiently modular so that E protein inputs can be removed. Complete “T-cell-like” effector differentiation can proceed without T-cell receptor rearrangement or selection when E proteins are neutralized, yielding natural killer and other innate lymphoid cells. PMID:24471430

  10. Early Engineering: A Developmentally Appropriate Curriculum for Young Children

    ERIC Educational Resources Information Center

    Bagiati, Aikaterini

    2011-01-01

    Engineering education for the pre-college years is a developing academic discipline that emanates from the need to understand and improve the ways that engineers are formally educated. To date, there are no curricula available that incorporate engineering at a preschool level. The focus of this study is on the development of an early engineering…

  11. Linking Developmental Working Memory and Early Academic Skills

    ERIC Educational Resources Information Center

    Decker, Janice E.

    2011-01-01

    Brain-based initiatives and school readiness mandates in education have prompted researchers to examine the biological mechanisms associated with learning in the hope that understanding empirical evidence can maximize learning potential. Current research has examined working memory skills in relationship to early learning. The function of working…

  12. Traumatic Brain Injury in Early Childhood: Developmental Effects and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara; Lowenthal, Barbara

    1998-01-01

    Describes the unique effects of traumatic brain injury (TBI) on development in early childhood and offers suggestions for interventions in the cognitive, language, social-emotional, motor, and adaptive domains. Urges more intensive, long-term studies on the immediate and long-term effects of TBI. (Author/DB)

  13. Efficient embryonic culture method for the Japanese striped snake, Elaphe quadrivirgata, and its early developmental stages.

    PubMed

    Matsubara, Yoshiyuki; Sakai, Atsushi; Kuroiwa, Atsushi; Suzuki, Takayuki

    2014-10-01

    The morphogenesis of snake embryos is an elusive yet fascinating research target for developmental biologists. However, few data exist on development of early snake embryo due to limited availability of pregnant snakes, and the need to harvest early stage embryos directly from pregnant snakes before oviposition without knowing the date of fertilization. We established an ex vivo culture method for early snake embryos using the Japanese striped snake, Elaphe quadrivirgata. This method, which we named "sausage-style (SS) culture", allows us to harvest snake embryos at specific stages for each experiment. Using this SS culture system, we calculated somite formation rate at early stages before oviposition. The average somite formation rate between 6/7 and 12/13 somite stages was 145.9 min, between 60/70 and 80/91 somite stages 42.4 min, and between 113-115 and 126/127 somite stages 71 min. Thus, somite formation rate that we observed during early snake embryogenesis was changed over time. We also describe a developmental staging series for E. quadrivirgata. This is the first report of a developmental series of early snake embryogenesis prior to oviposition by full-color images with high-resolution. We propose that the SS culture system is an easy method for treating early snake embryos ex vivo.

  14. Defining the Developmental Parameters of Temper Loss in Early Childhood: Implications for Developmental Psychopathology

    ERIC Educational Resources Information Center

    Wakschlag, Lauren S.; Choi, Seung W.; Carter, Alice S.; Hullsiek, Heide; Burns, James; McCarthy, Kimberly; Leibenluft, Ellen; Briggs-Gowan, Margaret J.

    2012-01-01

    Background: Temper modulation problems are both a hallmark of early childhood and a common mental health concern. Thus, characterizing specific behavioral manifestations of temper loss along a dimension from normative misbehaviors to clinically significant problems is an important step toward identifying clinical thresholds. Methods:…

  15. Developmental rate and behavior of early life stages of bighead carp and silver carp

    USGS Publications Warehouse

    Chapman, Duane C.; George, Amy E.

    2011-01-01

    The early life stages of Asian carp are well described by Yi and others (1988), but since these descriptions are represented by line drawings based only on live individuals and lacked temperature controls, further information on developmental time and stages is of use to expand understanding of early life stages of these species. Bighead carp and silver carp were cultured under two different temperature treatments to the one-chamber gas bladder stage, and a photographic guide is provided for bighead carp and silver carp embryonic and larval development, including notes about egg morphology and larval swimming behavior. Preliminary information on developmental time and hourly thermal units for each stage is also provided. Both carp species developed faster under warmer conditions. Developmental stages and behaviors are generally consistent with earlier works with the exception that strong vertical swimming immediately after hatching was documented in this report.

  16. The Effect of Early Childhood Developmental Program Attendance on Future School Enrollment in Rural North India

    ERIC Educational Resources Information Center

    Hazarika, Gautam; Viren, Vejoya

    2013-01-01

    This paper examines the effect of prior participation in early childhood developmental programs, considered endogenous, upon 7-18 years olds' school enrollment in rural North India. Analyses by age group of data from the World Bank's 1997-98 Survey of Living Conditions in Uttar Pradesh and Bihar reveal that 7-10 year olds, 11-14 year olds, and…

  17. The Effects of Developmental Placement and Early Retention on Children's Later Scores on Standardized Tests.

    ERIC Educational Resources Information Center

    May, Deborah C.; Welch, Edward L.

    1984-01-01

    Examined the relationship between early school retention as a result of preschool and kindergarten developmental testing and children's later academic achievement (N=223). Results showed children who scored as immature on the Gesell Screening Test and who were retained a year had the lowest scores on all measures. (JAC)

  18. Interdisciplinary Early Intervention for Developmentally Delayed Infants and Young Children: A Family-Oriented Approach.

    ERIC Educational Resources Information Center

    Russell, Fay F.; And Others

    Intended to help developers of early intervention programs for children with developmental disabilities, the book provides philosophy, methods, and procedures based on experiences of the Child Development Center of the University of Tennessee Center for Health Sciences. The first section presents a program description including information on…

  19. Similar Developmental Trajectories in Autism and Asperger Syndrome: From Early Childhood to Adolescence

    ERIC Educational Resources Information Center

    Szatmari, Peter; Bryson, Susan; Duku, Eric; Vaccarella, Liezanne; Zwaigenbaum, Lonnie; Bennett, Teresa; Boyle, Michael H.

    2009-01-01

    Objective: The objective of this study was to chart the developmental trajectories of high-functioning children with autism spectrum disorders (ASD) from early childhood to adolescence using the presence and absence of structural language impairment (StrLI) as a way of differentiating autism from Asperger syndrome (AS). Method: Sixty-four…

  20. A Developmental Study of the Relationships between Cognitive Abilities and Early Reading Achievement.

    ERIC Educational Resources Information Center

    Canter, Andrea Sherril

    This study investigated the developmental relationships between a battery of cognitive tasks--including Piagetian operations of conservation, classification, and seriation--and early reading achievement. Subjects were 128 kindergarten through third-grade students at a suburban elementary school. They were administered a battery of cognitive tests…

  1. Developmentally Appropriate Technology Practice: Exploring Myths and Perceptions of Early Childhood and Instructional Technology Professionals

    ERIC Educational Resources Information Center

    Blake, Sally; Winsor, Denise; Burkett, Candice; Allen, Lee

    2011-01-01

    The integration of technology in early childhood classrooms has become a controversial issue among professionals in this field. One issue which may influence technology in these classrooms may be perceptions of what is developmentally appropriate practice (DAP). This article explores perceptions about technology and age appropriate recommendations…

  2. Moving beyond Screen Time: Redefining Developmentally Appropriate Technology Use in Early Childhood Education. Policy Brief

    ERIC Educational Resources Information Center

    Daugherty, Lindsay; Dossani, Rafiq; Johnson, Erin-Elizabeth; Wright, Cameron

    2014-01-01

    Conversations about what constitutes "developmentally appropriate" use of technology in early childhood education have, to date, focused largely on a single, blunt measure--screen time--that fails to capture important nuances, such as what type of media a child is accessing and whether technology use is taking place solo or with peers.…

  3. Social and Developmental Predictors of Optimism from Infancy to Early Adulthood

    ERIC Educational Resources Information Center

    Ek, Ellen; Remes, Jouko; Sovio, Ulla

    2004-01-01

    The positive effects of dispositional optimism on mental and physical health are well documented, but little is known about its developmental origins. The present population-based longitudinal study of young adults (n = 8673) examined predictors of optimism that were related to early childhood family conditions, school achievement in middle…

  4. Parental Divorce and Offspring Depressive Symptoms: Dutch Developmental Trends during Early Adolescence

    ERIC Educational Resources Information Center

    Oldehinkel, Albertine J.; Ormel, Johan; Veenstra, Rene; De Winter, Andrea F.; Verhulst, Frank C.

    2008-01-01

    In this study, we investigated if the association between parental divorce and depressive symptoms changes during early adolescence and if developmental patterns are similar for boys and girls. Data were collected in a prospective population cohort of Dutch adolescents (N = 2,149), aged 10 - 15 years. Outcome variables were self-reported and…

  5. Latent Class Analysis of Early Developmental Trajectory in Baby Siblings of Children with Autism

    ERIC Educational Resources Information Center

    Landa, Rebecca J.; Gross, Alden L.; Stuart, Elizabeth A.; Bauman, Margaret

    2012-01-01

    Background: Siblings of children with autism (sibs-A) are at increased genetic risk for autism spectrum disorders (ASD) and milder impairments. To elucidate diversity and contour of early developmental trajectories exhibited by sibs-A, regardless of diagnostic classification, latent class modeling was used. Methods: Sibs-A (N = 204) were assessed…

  6. Developmental Trajectories of Academic Achievement in Chinese Children: Contributions of Early Social-Behavioral Functioning

    ERIC Educational Resources Information Center

    Fu, Rui; Chen, Xinyin; Wang, Li; Yang, Fan

    2016-01-01

    This study explored the developmental trajectories of academic achievement and the contributions of early social behaviors and problems to these trajectories in Chinese children. Data were collected each year in 5 consecutive years from a sample of elementary schoolchildren in China (initially N = 1,146, 609 boys, initial M [subscript age] = 8.33…

  7. Context Matters: The Interrelatedness of Early Literacy Skills, Developmental Health, and Community Demographics

    ERIC Educational Resources Information Center

    Lesaux, Nonie K.; Vukovic, Rose K.; Hertzman, Clyde; Siegel, Linda S.

    2007-01-01

    Whereas the great majority of literacy research has been focused at the child level, this study examined the relationship between early literacy rates, developmental health of the population, and demographics in 23 school communities. The results showed that school-level literacy scores were related to the physical, social, and emotional maturity…

  8. Developmental Structuralist Approach to the Classification of Adaptive and Pathologic Personality Organizations: Infancy and Early Childhood.

    ERIC Educational Resources Information Center

    Greenspan, Stanley I.; Lourie, Reginald S.

    This paper applies a developmental structuralist approach to the classification of adaptive and pathologic personality organizations and behavior in infancy and early childhood, and it discusses implications of this approach for preventive intervention. In general, as development proceeds, the structural capacity of the developing infant and child…

  9. Persistence of Early Emerging Aberrant Behavior in Children with Developmental Disabilities

    ERIC Educational Resources Information Center

    Green, Vanessa A.; O'Reilly, Mark; Itchon, Jonathan; Sigafoos, Jeff

    2005-01-01

    This study examined the persistence of early emerging aberrant behavior in 13 preschool children with developmental disabilities. The severity of aberrant behavior was assessed every 6 months over a 3-year period. Teachers completed the assessments using the Aberrant Behavior Checklist [Aman, M. G., & Singh, N. N. (1986). "Aberrant…

  10. Kindezi: A Distinctively Africentric Perspective on Early Childhood Education. Developmentally Appropriate Practice.

    ERIC Educational Resources Information Center

    Lowden, Frances Y.

    2000-01-01

    Presents the Kindezian philosophy of early childhood education, a historical developmentally appropriate Africentric worldview. Describes the curriculum as predating Western curriculum development by centuries. Maintains that Kindezi affords children the possibility to develop their full potential and that it provides a framework on which to…

  11. Queering Early Childhood Studies: Challenging the Discourse of Developmentally Appropriate Practice

    ERIC Educational Resources Information Center

    Janmohamed, Zeenat

    2010-01-01

    This article reviews approaches to early childhood training and practice in Ontario and sets it in the wider context of feminist poststructural knowledge production. Through a feminist poststructural reading, this article uncovers dominant assumptions of universality underlying the heteronormative discourse of developmentally appropriate practice…

  12. Developmental and Communication Disorders in Children with Intellectual Disability: The Place Early Intervention for Effective Inclusion

    ERIC Educational Resources Information Center

    Jacob, Udeme Samuel; Olisaemeka, Angela Nneka; Edozie, Isioma Sitamalife

    2015-01-01

    The paper attempts to discuss the place of intervention in the developmental and communication disorders of children with intellectual disability for the purpose of providing effective inclusion programme. The definition of early intervention was stated, areas affected by children communication disorder such as language comprehension, fluency,…

  13. Infancy to Early Childhood: Genetic and Environmental Influences on Developmental Change.

    ERIC Educational Resources Information Center

    Emde, Robert N., Ed.; Hewitt, John K., Ed.

    This book analyzes the MacArthur Longitudinal Twin Study, a collaborative study by leading developmental scientists and behavioral geneticists on the transition from infancy to early childhood. Part 1 of the book describes the twin method and procedures used and introduces the analytic strategies. Parts 2 through 4 present results related to…

  14. Executive Function in Early Childhood: Longitudinal Measurement Invariance and Developmental Change

    ERIC Educational Resources Information Center

    Willoughby, Michael T.; Wirth, R. J.; Blair, Clancy B.

    2012-01-01

    This study tested the longitudinal measurement invariance and developmental changes of a newly developed battery of executive function (EF) tasks for use in early childhood. The battery was administered in the Family Life Project--a prospective longitudinal study (N = 1,292) of families who were oversampled from low-income and African American…

  15. Developmental phenotypes and causal pathways in attention deficit/hyperactivity disorder: potential targets for early intervention?

    PubMed

    Sonuga-Barke, Edmund J S; Halperin, Jeffrey M

    2010-04-01

    Early intervention approaches have rarely been implemented for the prevention of attention deficit/hyperactivity disorder (ADHD). In this paper we explore whether such an approach may represent an important new direction for therapeutic innovation. We propose that such an approach is most likely to be of value when grounded in and informed by developmental models of the dynamic, complex and heterogeneous nature of the condition. First, we set out a rationale for early intervention grounded in the science of ADHD viewed through developmental models. Second, we re-examine the concept of disorder-onset from the perspective of developmental trajectories and phenotypes. Third, we examine potential causal pathways to ADHD with regard to originating risk, pathophysiological mediators, environmental moderators and developmental continuities. Finally, we explore the potential value of strategies for identifying young children at risk for ADHD, and implementing interventions in ways that can target these underlying pathogenic processes. The utility of such an approach represents an important area for future research but still requires 'proof of concept'. Therefore prior to widespread clinical implementation, far greater knowledge is required of (i) developmental pathways into ADHD, (ii) the value of identifying neuropsychological mediators of these pathways, and (iii) the extent to which targeting mediating mechanisms will improve treatment outcomes for children with ADHD.

  16. Fertilisation and early developmental barriers to hybridisation in field crickets

    PubMed Central

    2013-01-01

    Background Post-mating interactions between the reproductive traits and gametes of mating individuals and among their genes within zygotes are invariably complex, providing multiple opportunities for reproduction to go awry. These interactions have the potential to act as barriers to gene flow between species, and may be important in the process of speciation. There are multiple post-mating barriers to interbreeding between the hybridising field crickets Gryllus bimaculatus and G. campestris. Female G. bimaculatus preferentially store sperm from conspecific males when mated to both conspecific and heterospecific partners. Additionally, conspecific males sire an even greater proportion of offspring than would be predicted from their sperm’s representation in the spermatheca. The nature of these post-sperm-storage barriers to hybridisation are unknown. We use a fluorescent staining technique to determine whether barriers occur prior to, or during embryo development. Results We show that eggs laid by G. bimaculatus females mated to G. campestris males are less likely to begin embryogenesis than eggs from conspecific mating pairs. Of the eggs that are successfully fertilised and start to develop, those from heterospecific mating pairs are more likely to arrest early, prior to blastoderm formation. We find evidence for bimodal variation among egg clutches in the number of developing embryos that subsequently arrest, indicating that there is genetic variation for incompatibility between mating individuals. In contrast to the pattern of early embryonic mortality, those hybrids reaching advanced stages of embryogenesis have survival rates equal to that of embryos from conspecific mating pairs. Conclusions Post-sperm-storage barriers to hybridisation show evidence of genetic polymorphism. They are sufficiently large, that if the species interbreed where they are sympatric, these barriers could play a role in the maintenance of reproductive isolation between them. The

  17. Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

    PubMed Central

    Tain, You-Lin; Hsu, Chien-Ning

    2017-01-01

    Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called “developmental programming” or “developmental origins of health and disease” (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease. PMID:28208659

  18. Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

    PubMed

    Tain, You-Lin; Hsu, Chien-Ning

    2017-02-11

    Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called "developmental programming" or "developmental origins of health and disease" (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease.

  19. Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint.

    PubMed

    Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco

    2016-04-01

    Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations.

  20. Developmental commentary: individual and contextual influences on student-teacher relationships and children's early problem behaviors.

    PubMed

    Myers, Sonya S; Pianta, Robert C

    2008-07-01

    Understanding factors associated with children's early behavioral difficulties is of vital importance to children's school success, and to the prevention of future behavior problems. Although biological factors can influence the expression of certain behaviors, the probability of children exhibiting classroom behavior problems is intensified when they are exposed to multiple risk factors, particularly negative student-teacher interactions. Children who exhibit behavior problems during early childhood and the transition to kindergarten, without intervention, can be placed on a developmental trajectory for serious behavior problems in later grades. Using a developmental systems model, this commentary provides a conceptual framework for understanding the contributions of individual and contextual factors to the development of early student-teacher relationships. Parent, teacher, and student characteristics are discussed as they are related to shaping student-teacher interactions and children's adjustment to school.

  1. Gender Differences in the Developmental Links Between Conduct Problems and Depression Across Early Adolescence.

    PubMed

    Klostermann, Susan; Connell, Arin; Stormshak, Beth

    2016-03-01

    Various developmental models have attempted to explain the relationship between antisocial behavior and depressive symptoms in youth, often proposing intermediary processes such as social and academic functioning. However, few studies have tested these developmental models fully, particularly in mixed gender samples. The current study strives to fill this gap in the literature, examining these processes in an early adolescent sample. Results indicated both direct and indirect paths between antisocial behavior and depression. In addition, potentially important gender differences were found. These results underscore the importance of examining direct and indirect links between symptoms of depression and anti-social behavior, and suggest that there may be important developmental differences between girls and boys in the relationship between these symptoms.

  2. Early development of Moniliophthora perniciosa basidiomata and developmentally regulated genes

    PubMed Central

    2009-01-01

    second in basidiomata, confirming their distinctiveness. The number of transcripts of the gene for plerototolysin B increased in reddish-pink mycelium and indicated an activation of the initial basidiomata production even at this culturing stage. Expression of the glucose transporter gene increased in mycelium after the stress, coinciding with a decrease of adenylate cyclase gene transcription. This indicated that nutrient uptake can be an important signal to trigger fruiting in this fungus. Conclusion The identification of genes with increased expression in this phase of the life cycle of M. perniciosa opens up new possibilities of controlling fungus spread as well as of genetic studies of biological processes that lead to basidiomycete fruiting. This is the first comparative morphologic study of the early development both in vivo and in vitro of M. perniciosa basidiomata and the first description of genes expressed at this stage of the fungal life cycle. PMID:19653910

  3. DEVELOPMENTAL CHANGES IN SEROTONIN SIGNALING: IMPLICATIONS FOR EARLY BRAIN FUNCTION, BEHAVIOR AND ADAPTATION

    PubMed Central

    BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.

    2017-01-01

    The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950

  4. Developmental Changes in Sleep Spindle Characteristics and Sigma Power across Early Childhood

    PubMed Central

    McClain, Ian J.; Lustenberger, Caroline; Achermann, Peter; Lassonde, Jonathan M.; Kurth, Salome; LeBourgeois, Monique K.

    2016-01-01

    Sleep spindles, a prominent feature of the non-rapid eye movement (NREM) sleep electroencephalogram (EEG), are linked to cognitive abilities. Early childhood is a time of rapid cognitive and neurophysiological maturation; however, little is known about developmental changes in sleep spindles. In this study, we longitudinally examined trajectories of multiple sleep spindle characteristics (i.e., spindle duration, frequency, integrated spindle amplitude, and density) and power in the sigma frequency range (10–16 Hz) across ages 2, 3, and 5 years (n = 8; 3 males). At each time point, nocturnal sleep EEG was recorded in-home after 13-h of prior wakefulness. Spindle duration, integrated spindle amplitude, and sigma power increased with age across all EEG derivations (C3A2, C4A1, O2A1, and O1A2; all ps < 0.05). We also found a developmental decrease in mean spindle frequency (p < 0.05) but no change in spindle density with increasing age. Thus, sleep spindles increased in duration and amplitude but decreased in frequency across early childhood. Our data characterize early developmental changes in sleep spindles, which may advance understanding of thalamocortical brain connectivity and associated lifelong disease processes. These findings also provide unique insights into spindle ontogenesis in early childhood and may help identify electrophysiological features related to healthy and aberrant brain maturation. PMID:27110405

  5. Methods for in vitro functional analysis of iPSC derived cardiomyocytes - Special focus on analyzing the mechanical beating behavior.

    PubMed

    Laurila, Eeva; Ahola, Antti; Hyttinen, Jari; Aalto-Setälä, Katriina

    2016-07-01

    A rapidly increasing number of papers describing novel iPSC models for cardiac diseases are being published. To be able to understand the disease mechanisms in more detail, we should also take the full advantage of the various methods for analyzing these cell models. The traditionally and commonly used electrophysiological analysis methods have been recently accompanied by novel approaches for analyzing the mechanical beatingbehavior of the cardiomyocytes. In this review, we provide first a concise overview on the methodology for cardiomyocyte functional analysis and then concentrate on the video microscopy, which provides a promise for a new faster yet reliable method for cardiomyocyte functional analysis. We also show how analysis conditions may affect the results. Development of the methodology not only serves the basic research on the disease models, but could also provide the much needed efficient early phase screening method for cardiac safety toxicology. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  6. The GATA transcription factor GtaC regulates early developmental gene expression dynamics in Dictyostelium.

    PubMed

    Santhanam, Balaji; Cai, Huaqing; Devreotes, Peter N; Shaulsky, Gad; Katoh-Kurasawa, Mariko

    2015-07-06

    In many systems, including the social amoeba Dictyostelium discoideum, development is often marked by dynamic morphological and transcriptional changes orchestrated by key transcription factors. However, efforts to examine sequential genome-wide changes of gene regulation in developmental processes have been fairly limited. Here we report the developmental regulatory dynamics of GtaC, a GATA-type zinc-finger transcription factor, through the analyses of serial ChIP- and RNA-sequencing data. GtaC is essential for developmental progression, decoding extracellular cAMP pulses during early development and may play a role in mediating cell-type differentiation at later stages. We find that GtaC exhibits temporally distinctive DNA-binding patterns concordant with each developmental stage. We identify direct GtaC targets and observe cotemporaneous GtaC-binding and developmental expression regulation. Our results suggest that GtaC regulates multiple physiological processes as Dictyostelium transitions from a group of unicellular amoebae to an integrated multicellular organism.

  7. Developmental programming of early brain and behaviour development and mental health: a conceptual framework.

    PubMed

    Van den Bergh, Bea R H

    2011-09-01

    The Developmental Origins of Health and Disease (DOHaD) hypothesis studies the short- and long-term consequences of the conditions of the developmental environment for phenotypic variations in health and disease. Central to this hypothesis is the idea of interdependence of developmental influences, genes, and environment. Developmental programming effects are mediated by alterations in fundamental life functions, and the most enduring effects seem to occur if the main regulatory instances of the organ - the (epi)genome and the brain - are affected. Some new insights in the role of chromatin, in cellular development and differentiation, and neural plasticity from the field of epigenetics are introduced, followed by a section on epigenetics and brain development. It is proposed to extend the DOHaD hypothesis into the 'Developmental Origins of Behaviour, Health, and Disease' (DOBHaD) concept. Pregnancy and the early postnatal period are times of both great opportunity and considerable risk, and their influence can extend over a lifetime. The DOBHaD hypothesis opens fundamental new perspectives on preventing diseases and disorders.

  8. The pea aphid (Acyrthosiphon pisum) genome encodes two divergent early developmental programs.

    PubMed

    Duncan, Elizabeth J; Leask, Megan P; Dearden, Peter K

    2013-05-01

    The pea aphid (Acyrthosiphon pisum) can reproduce either sexually or asexually (parthenogenetically), giving rise, in each case, to almost identical adults. These two modes of reproduction are accompanied by differences in ovarian morphology and the developmental environment of the offspring, with sexual forms producing eggs that are laid, whereas asexual development occurs within the mother. Here we examine the effect each mode of reproduction has on the expression of key maternal and axis patterning genes; orthodenticle (otd), hunchback (hb), caudal (cad) and nanos (nos). We show that three of these genes (Ap-hb, Ap-otd and Ap-cad) are expressed differently between the sexually and asexually produced oocytes and embryos of the pea aphid. We also show, using immunohistochemistry and cytoskeletal inhibitors, that Ap-hb RNA is localized differently between sexually and asexually produced oocytes, and that this is likely due to differences in the 3' untranslated regions of the RNA. Furthermore, Ap-hb and Ap-otd have extensive expression domains in early sexually produced embryos, but are not expressed at equivalent stages in asexually produced embryos. These differences in expression likely correspond with substantial changes in the gene regulatory networks controlling early development in the pea aphid. These data imply that in the evolution of parthenogenesis a new program has evolved to control the development of asexually produced embryos, whilst retaining the existing, sexual, developmental program. The patterns of modification of these developmental processes mirror the changes that we see in developmental processes between species, in that early acting pathways in development are less constrained, and evolve faster, than later ones. We suggest that the evolution of the novel asexual development pathway in aphids is not a simple modification of an ancestral system, but the evolution of two very different developmental mechanisms occurring within a single

  9. Early developmental conditioning of later health and disease: physiology or pathophysiology?

    PubMed

    Hanson, M A; Gluckman, P D

    2014-10-01

    Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention.

  10. Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

    PubMed Central

    Hanson, M. A.; Gluckman, P. D.

    2014-01-01

    Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention. PMID:25287859

  11. First Steps for Early Success: State Strategies to Support Developmental Screening in Early Childhood Settings

    ERIC Educational Resources Information Center

    Johnson-Staub, Christine

    2014-01-01

    Young children's development occurs along a continuum, with milestones reached at ages that vary within an accepted timeframe. Milestones not met within the expected timeframe can raise concerns about developmental delays, health conditions, or other factors contributing negatively to the child's growth and learning. Monitoring children's…

  12. Endocrine and other physiologic modulators of perinatal cardiomyocyte endowment

    PubMed Central

    Jonker, S S; Louey, S

    2015-01-01

    Immature contractile cardiomyocytes proliferate to rapidly increase cell number, establishing cardiomyocyte endowment in the perinatal period. Developmental changes in cellular maturation, size and attrition further contribute to cardiac anatomy. These physiological processes occur concomitant with a changing hormonal environment as the fetus prepares itself for the transition to extrauterine life. There are complex interactions between endocrine, hemodynamic and nutritional regulators of cardiac development. Birth has been long assumed to be the trigger for major differences between the fetal and postnatal cardiomyocyte growth patterns, but investigations in normally growing sheep and rodents suggest this may not be entirely true; in sheep, these differences are initiated before birth, while in rodents they occur after birth. The aim of this review is to draw together our understanding of the temporal regulation of these signals and cardiomyocyte responses relative to birth. Further, we consider how these dynamics are altered in stressed and suboptimal intrauterine environments. PMID:26432905

  13. [Relationship between developmental prognosis and changing picture of postural findings in early infancy among early treated children].

    PubMed

    Yuge, M; Yamori, Y; Kanda, T; Ando, R

    1992-09-01

    We followed 93 infants prospectively who were treated because of moderate and severe grades of cerebral coordination disturbances since less than 6 months of age. They were divided into 3 groups according to developmental prognosis at 4 years of age; normal 44, mental retardation 18, and cerebral palsy 31. We compared the postural findings in supine and prone position, and 7 postural reactions at the first examination with those at discharge about 50 days after the first examination. We assessed the changing pictures of postural findings as improved, not changed or worsened. We analyzed the relationship between the changing pictures of postural findings during the short period in early infancy and the developmental prognosis among the 3 groups. The normal group showed improvement in a larger number of items than the other two groups. The findings of cerebral palsied children showed poor improvement, and more postural reactions changed to be more pathologic than those in the other two groups. Among the cerebral palsied children, ambulatory cases showed better improvement than those who could not crawl. But we found no significant difference between ambulatory and crawling children. This study demonstrated that assessment of changing pictures of postural findings in early infancy was helpful to predict developmental prognosis.

  14. Changes in Developmental Factors and HIV Risk Behaviors among Early Adolescents in Puerto Rico

    PubMed Central

    Fernández Santos, Diana M.; Figueroa-Cosme, Wanda I.; María de los, A. Gómez; Maysonet-Cruz, Johanna; Miranda-Díaz, Christine; Sepúlveda-Santiago, Mario; Ríos-Olivares, Eddy; Hunter-Mellado, Robert F.

    2013-01-01

    Introduction Teenagers are the fastest growing group of newly HIV-infected persons. Consequently, a support model for HIV risk reduction was designed and implemented for early adolescents in Puerto Rico. Objective The purpose of this article is to assess changes in developmental factors and HIV risk behaviors among early adolescents after three years of follow-up of an intervention and a non-intervention group. Methods This prospective cohort study followed 135 early adolescents who were enrolled in the ASUMA (A Supportive Model for HIV Risk Reduction in Early Adolescents) Project. The study was performed in two public and two private junior schools. Baseline and three follow-up self-administered questionnaires were given. We examined sociodemographic factors, HIV risk behavior and developmental factors. Results 48% were in the intervention group and 51.1% were controls. Most adolescents were aged 12 years; 47.4% were males; 75.6% reported not having risk behaviors and 24.4% reported having risk behaviors at anytime in their lifespan. A significant decrease in the HIV risk behaviors median was observed among the intervention group (P<.05), while a non-significant increase was found among adolescents in the control group. At the end of the implementation phase, positive improvement in the developmental factors were observed in the intervention group (P<.05). Conclusions Our study suggests that the ASUMA project curriculum had a positive effect on developmental factors and HIV risk behaviors, as proposed in our conceptual framework. Also, this study illustrates the importance of the creation of culturally appropriate instruments and interventions to reach the goal of HIV/AIDS reduction. PMID:20521399

  15. Expression Analysis of Cathepsin F during Embryogenesis and Early Developmental Stage in Olive Flounder (Paralichthys olivaceus)

    PubMed Central

    Lee, Jang-Wook; Lee, Young Mee; Yang, Hyun; Noh, Jae Koo; Kim, Hyun Chul; Park, Choul-Ji; Park, Jong-Won; Hwang, In Joon; Kim, Sung Yeon; Lee, Jeong-Ho

    2013-01-01

    Cathepsins are members of the multigene family of lysosomal cysteine proteinases and have regulated function in several life processes. The potential role of cathepsin F cysteine gene was expected as protease in the yolk processing mechanism during early developmental stage, but expression analysis was unknown after fertilization. The alignment analysis showed that amino acid sequence of cathepsin F from olive flounder liver expressed sequence tag (EST) homologous to cathepsin F of other known cathepsin F sequences with 87-98% identity. In this study, we examined the gene expression analysis of cathepsin F in various tissues at variety age flounder. Tissue distribution of the cathepsin F mRNA has been shown to be ubiquitous and constitutive pattern regardless of age in each group, although derived from cDNA library using liver sample. The mRNA level of cathepsin F more increased as developmental proceed during embryogenesis and early developmental stage, especially increased in the blastula, hatching stage and 3 days post hatching (dph). As a result, it may suggest that the proteolysis of yolk proteins (YPs) has been implicated as a mechanism for nutrient supply during early larval stages in olive flounder. PMID:25949137

  16. High throughput physiological screening of iPSC-derived cardiomyocytes for drug development.

    PubMed

    Del Álamo, Juan C; Lemons, Derek; Serrano, Ricardo; Savchenko, Alex; Cerignoli, Fabio; Bodmer, Rolf; Mercola, Mark

    2016-07-01

    Cardiac drug discovery is hampered by the reliance on non-human animal and cellular models with inadequate throughput and physiological fidelity to accurately identify new targets and test novel therapeutic strategies. Similarly, adverse drug effects on the heart are challenging to model, contributing to costly failure of drugs during development and even after market launch. Human induced pluripotent stem cell derived cardiac tissue represents a potentially powerful means to model aspects of heart physiology relevant to disease and adverse drug effects, providing both the human context and throughput needed to improve the efficiency of drug development. Here we review emerging technologies for high throughput measurements of cardiomyocyte physiology, and comment on the promises and challenges of using iPSC-derived cardiomyocytes to model disease and introduce the human context into early stages of drug discovery. This article is part of a Special Issue entitled: Cardiomyocyte biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  17. Early mastery motivation as a predictor of executive function in young adults with developmental disabilities.

    PubMed

    Hauser-Cram, Penny; Woodman, Ashley Cynthia; Heyman, Miriam

    2014-11-01

    The role of early childhood mastery motivation as a predictor of executive function 20 years later was examined in a sample of 39 individuals who had early diagnosed developmental disabilities. Multilevel modeling was used to analyze predictors of accuracy and response time on a Flanker task measuring executive function. As predicted, participants had relatively poorer performance on trials requiring inhibition and rule switches. Individuals with Down syndrome, in comparison to other participants, demonstrated longer response times. Young adults who had higher levels of persistence on mastery motivation tasks during early childhood displayed higher levels of accuracy and shorter response times on the executive function task. Possible mechanisms by which early mastery motivation relates to later executive function are discussed.

  18. Revisiting a Progressive Pedagogy. The Developmental-Interaction Approach. SUNY Series, Early Childhood Education: Inquiries and Insights.

    ERIC Educational Resources Information Center

    Nager, Nancy, Ed.; Shapiro, Edna K., Ed.

    This book reviews the history of the developmental-interactive approach, a formulation rooted in developmental psychology and educational practice, progressively informing educational thinking since the early 20th century. The book describes and analyzes key assumptions and assesses the compatibility of new theoretical approaches, focuses on…

  19. Longitudinal Analyses of Geographic Differences in Utilization Rates of Children with Developmental Delays Who Participation in Early Intervention Services

    ERIC Educational Resources Information Center

    Lin, Jin-Ding; Chen, Yong-Chen; Chou, Yu-Ching

    2012-01-01

    The purposes of the present study were to describe the longitudinal utilization rates of participation in early intervention services of children with developmental delays, and to examine the geographical difference of services in this vulnerable population. We analyzed service utilization of the developmentally delayed children based on data of…

  20. Early Developmental Processes and the Continuity of Risk for Underage Drinking and Problem Drinking

    PubMed Central

    Donovan, John E.; Masten, Ann S.; Mattson, Margaret E.; Moss, Howard B.

    2008-01-01

    Developmental pathways to underage drinking emerge before the second decade of life. Nonetheless, many scientists, as well as the general public, continue to focus on proximal influences surrounding the initiation of drinking in adolescence, such as the social, behavioral, and genetic variables relating to availability and ease of acquisition of the drug, social reinforcement for its use, and individual differences in drug response. Over the past 20 years, a considerable body of evidence has accumulated on the early predictors and pathways of youthful alcohol use and abuse, often much earlier than the time of first drink. These early developmental influences involve numerous risk, vulnerability, promotive and protective processes. Some of these factors are not directly related to alcohol use per se, while others involve learning and expectancies about later drug use that are shaped by social experience. The salience of these factors-- identifiable in early childhood-- for understanding the course and development of adult alcohol and other drug use disorders is evident from the large and growing body of findings on their ability to predict these adult clinical outcomes. This review summarizes the evidence on early pathways toward and away from underage drinking, with a particular focus on the risk and protective factors, mediators and moderators of risk for underage drinking that become evident during the preschool and early school years. It is guided by a developmental perspective on the aggregation of risk and protection, and examines the contributions of biological, psychological, and social processes within the context of normal development. Implications of this evidence for policy, intervention, and future research are discussed. PMID:18381493

  1. Developmental cascades: externalizing, internalizing, and academic competence from middle childhood to early adolescence.

    PubMed

    Moilanen, Kristin L; Shaw, Daniel S; Maxwell, Kari L

    2010-08-01

    The current study was initiated to increase understanding of developmental cascades in childhood in a sample of at-risk boys (N = 291; 52% White). Mothers, teachers, and boys reported on boys' externalizing problems, internalizing difficulties, and academic competence. Consistent with hypotheses regarding school-related transitions, high levels of externalizing problems were associated with both low levels of academic competence and high levels of internalizing problems during the early school-age period, and with elevations in internalizing problems during the transition to adolescence. Low levels of academic competence were associated with high levels of internalizing problems in middle childhood, and with high levels of externalizing problems during the transition from elementary school to middle school. Shared risk factors played a minimal role in these developmental cascades. Results suggest that there are cascading effects of externalizing problems and academic competence in childhood and early adolescence, and that some cascading effects are more likely to occur during periods of school-related transitions. Implications of developmental cascade effects for research and intervention are discussed.

  2. Developmental cascades: Externalizing, internalizing, and academic competence from middle childhood to early adolescence

    PubMed Central

    Moilanen, Kristin L.; Shaw, Daniel S.; Maxwell, Kari L.

    2011-01-01

    The current study was initiated to increase understanding of developmental cascades in childhood in a sample of at-risk boys (N = 291; 52% White). Mothers, teachers, and boys reported on boys’ externalizing problems, internalizing difficulties, and academic competence. Consistent with hypotheses regarding school-related transitions, high levels of externalizing problems were associated with both low levels of academic competence and high levels of internalizing problems during the early school-age period, and with elevations in internalizing problems during the transition to adolescence. Low levels of academic competence were associated with high levels of internalizing problems in middle childhood, and with high levels of externalizing problems during the transition from elementary school to middle school. Shared risk factors played a minimal role in these developmental cascades. Results suggest that there are cascading effects of externalizing problems and academic competence in childhood and early adolescence, and that some cascading effects are more likely to occur during periods of school-related transitions. Implications of developmental cascade effects for research and intervention are discussed. PMID:20576184

  3. Emanuel Miller lecture developmental risks (still) associated with early child care.

    PubMed

    Belsky, J

    2001-10-01

    In the mid to late 1980s a major controversy erupted when Belsky's (1986, 1988. 1990) analysis of research produced the conclusion that early and extensive nonmaternal care carried risks in terms of increasing the probability of insecure infant-parent attachment relationships and promoting aggression and noncompliance during the toddler, preschool, and early primary school years. Widespread critiques of Belsky's analysis called attention to problems associated with the Strange Situation procedure for measuring attachment security in the case of day-care reared children and to the failure of much of the cited research to take into consideration child-care quality and control for background factors likely to make children with varying child-care experiences developmentally different in the first place. In this lecture, research concerning the developmental effects of child care and maternal employment initiated in the first year of life that has emerged since the controversy broke is reviewed. Evidence indicating that early, extensive, and continuous nonmaternal care is associated with less harmonious parent-child relations and elevated levels of aggression and noncompliance suggests that concerns raised about early and extensive child care 15 years ago remain valid and that alternative explanations of Belsky's originally controversial conclusion do not account for seemingly adverse effects of routine nonmaternal care that continue to be reported in the literature.

  4. Early developmental gene regulation in Strongylocentrotus purpuratus embryos in response to elevated CO₂ seawater conditions.

    PubMed

    Hammond, LaTisha M; Hofmann, Gretchen E

    2012-07-15

    Ocean acidification, or the increased uptake of CO(2) by the ocean due to elevated atmospheric CO(2) concentrations, may variably impact marine early life history stages, as they may be especially susceptible to changes in ocean chemistry. Investigating the regulatory mechanisms of early development in an environmental context, or ecological development, will contribute to increased understanding of potential organismal responses to such rapid, large-scale environmental changes. We examined transcript-level responses to elevated seawater CO(2) during gastrulation and the initiation of spiculogenesis, two crucial developmental processes in the purple sea urchin, Strongylocentrotus purpuratus. Embryos were reared at the current, accepted oceanic CO(2) concentration of 380 microatmospheres (μatm), and at the elevated levels of 1000 and 1350 μatm, simulating predictions for oceans and upwelling regions, respectively. The seven genes of interest comprised a subset of pathways in the primary mesenchyme cell gene regulatory network (PMC GRN) shown to be necessary for the regulation and execution of gastrulation and spiculogenesis. Of the seven genes, qPCR analysis indicated that elevated CO(2) concentrations only had a significant but subtle effect on two genes, one important for early embryo patterning, Wnt8, and the other an integral component in spiculogenesis and biomineralization, SM30b. Protein levels of another spicule matrix component, SM50, demonstrated significant variable responses to elevated CO(2). These data link the regulation of crucial early developmental processes with the environment that these embryos would be developing within, situating the study of organismal responses to ocean acidification in a developmental context.

  5. Early developmental responses to seedling environment modulate later plasticity to light spectral quality.

    PubMed

    von Wettberg, Eric J B; Stinchcombe, John R; Schmitt, Johanna

    2012-01-01

    Correlations between developmentally plastic traits may constrain the joint evolution of traits. In plants, both seedling de-etiolation and shade avoidance elongation responses to crowding and foliage shade are mediated by partially overlapping developmental pathways, suggesting the possibility of pleiotropic constraints. To test for such constraints, we exposed inbred lines of Impatiens capensis to factorial combinations of leaf litter (which affects de-etiolation) and simulated foliage shade (which affects phytochrome-mediated shade avoidance). Increased elongation of hypocotyls caused by leaf litter phenotypically enhanced subsequent elongation of the first internode in response to low red:far red (R:FR). Trait expression was correlated across litter and shade conditions, suggesting that phenotypic effects of early plasticity on later plasticity may affect variation in elongation traits available to selection in different light environments.

  6. Early augmented language intervention for children with developmental delays: potential secondary motor outcomes.

    PubMed

    Whitmore, Ani S; Romski, Mary Ann; Sevcik, Rose A

    2014-09-01

    This exploratory study examined the potential secondary outcome of an early augmented language intervention that incorporates speech-generating devices (SGD) on motor skill use for children with developmental delays. The data presented are from a longitudinal study by Romski and colleagues. Toddlers in the augmented language interventions were either required (Augmented Communication-Output; AC-O) or not required (Augmented Communication-Input; AC-I) to use the SGD to produce an augmented word. Three standardized assessments and five event-based coding schemes measured the participants' language abilities and motor skills. Toddlers in the AC-O intervention used more developmentally appropriate motor movements and became more accurate when using the SGD to communicate than toddlers in the AC-I intervention. AAC strategies, interventionist/parent support, motor learning opportunities, and physical feedback may all contribute to this secondary benefit of AAC interventions that use devices.

  7. Increasing pre-kindergarten early literacy skills in children with developmental disabilities and delays.

    PubMed

    Pears, Katherine C; Kim, Hyoun K; Fisher, Philip A; Yoerger, Karen

    2016-08-01

    Two hundred and nine children receiving early childhood special education services for developmental disabilities or delays who also had behavioral, social, or attentional difficulties were included in a study of an intervention to increase school readiness, including early literacy skills. Results showed that the intervention had a significant positive effect on children's literacy skills from baseline to the end of summer before the start of kindergarten (d=.14). The intervention also had significant indirect effects on teacher ratings of children's literacy skills during the fall of their kindergarten year (β=.09). Additionally, when scores were compared to standard benchmarks, a greater percentage of the children who received the intervention moved from being at risk for reading difficulties to having low risk. Overall, this study demonstrates that a school readiness intervention delivered prior to the start of kindergarten may help increase children's early literacy skills.

  8. Early postnatal stress suppresses the developmental trajectory of hippocampal pyramidal neurons: the role of CRHR1.

    PubMed

    Liu, Rui; Yang, Xiao-Dun; Liao, Xue-Mei; Xie, Xiao-Meng; Su, Yun-Ai; Li, Ji-Tao; Wang, Xiao-Dong; Si, Tian-Mei

    2016-12-01

    Adverse experiences early in life hamper the development and maturation of the hippocampus, but how early-life stress perturbs the developmental trajectory of the hippocampus across various life stages and the underlying molecular mechanisms remain to be investigated. In this study, we stressed male mice from postnatal day 2 (P2) to P9, and examined the potential role of CRHR1 in postnatal stress-induced structural remodeling of hippocampal CA3 pyramidal neurons directly after stress (P9), in mid-adolescence (P35) and in adulthood (P90). We found that early-life stress exposure significantly reduced apical dendritic arborization and spine density in CA3 neurons on P9 and P90. Moreover, postnatally stressed neurons underwent increased pruning of spines, especially thin spines, between P35 and P90. These stress-induced immediate and long-term structural abnormalities could be abolished by daily systemic administration of the CRHR1 antagonist antalarmin (20 µg/g of body weight) during stress exposure. However, such treatment strategy failed to attenuate the deleterious stress effects in mid-adolescence on P35. We then extended antalarmin treatment until the end of the second postnatal week, and found that prolonged blockade of CRHR1 could prevent the mid-term impact of early postnatal stress on structural remodeling of CA3 neurons. Our study characterized the influences of early-life stress on the developmental trajectory of hippocampal pyramidal neurons, and highlighted the critical role of CRHR1 in modulating these negative outcomes evoked by early-life stress.

  9. Developmental plasticity of growth and digestive efficiency in dependence of early-life food availability.

    PubMed

    Kotrschal, Alexander; Szidat, Sönke; Taborsky, Barbara

    2014-08-01

    Nutrition is a potent mediator of developmental plasticity. If food is scarce, developing organisms may invest into growth to outgrow size-dependent mortality (short-term benefit) and/or into an efficient digestion system (long-term benefit). We investigated this potential trade-off, by determining the influence of food availability on juvenile body and organ growth, and on adult digestive efficiency in the cichlid fish Simochromis pleurospilus. We reared two groups of fish at constant high or low food rations, and we switched four other groups between these two rations at an early and late juvenile period. We measured juvenile growth and organ sizes at different developmental stages and determined adult digestive efficiency. Fish kept at constant, high rations grew considerably faster than low-food fish. Nevertheless, S. pleurospilus partly buffered the negative effects of low food availability by developing heavier digestive organs, and they were therefore more efficient in digesting their food as adults. Results of fish exposed to a ration switch during either the early or late juvenile period suggest (i) that the ability to show compensatory growth after early exposure to low food availability persists during the juvenile period, (ii) that digestive efficiency is influenced by varying juvenile food availability during the late juvenile phase and (iii) that the efficiency of the adult digestive system is correlated with the growth rate during a narrow time window of juvenile period.

  10. Developmental plasticity of growth and digestive efficiency in dependence of early-life food availability

    PubMed Central

    Kotrschal, Alexander; Szidat, Sönke; Taborsky, Barbara

    2014-01-01

    Nutrition is a potent mediator of developmental plasticity. If food is scarce, developing organisms may invest into growth to outgrow size-dependent mortality (short-term benefit) and/or into an efficient digestion system (long-term benefit). We investigated this potential trade-off, by determining the influence of food availability on juvenile body and organ growth, and on adult digestive efficiency in the cichlid fish Simochromis pleurospilus. We reared two groups of fish at constant high or low food rations, and we switched four other groups between these two rations at an early and late juvenile period. We measured juvenile growth and organ sizes at different developmental stages and determined adult digestive efficiency. Fish kept at constant, high rations grew considerably faster than low-food fish. Nevertheless, S. pleurospilus partly buffered the negative effects of low food availability by developing heavier digestive organs, and they were therefore more efficient in digesting their food as adults. Results of fish exposed to a ration switch during either the early or late juvenile period suggest (i) that the ability to show compensatory growth after early exposure to low food availability persists during the juvenile period, (ii) that digestive efficiency is influenced by varying juvenile food availability during the late juvenile phase and (iii) that the efficiency of the adult digestive system is correlated with the growth rate during a narrow time window of juvenile period. PMID:25866430

  11. [Early identification of children with developmental language disorders - when and how?].

    PubMed

    von Suchodoletz, Waldemar

    2011-11-01

    Children with developmental language disorders have a high risk for their cognitive, social, and emotional development. Therefore, they should be identified and treated as early as possible. This paper reviews the possibilities and limits of methods for such early identification. Language screenings during the first 3 years of life are described and appraised with respect to their diagnostic accuracy. The overview indicates that the current stage of language development can be estimated with high reliability by means of parent questionnaires. The possibility of identifying children with developmental language disorders early on is limited. Precursors and first steps of language acquisition correlate with later language abilities, although the relationship is weak and predicting further language development in a individual child is not possible. At the end of the second year of life, however, late talkers can be identified; these children are at risk of language impairment. But not until the end of the third year can sufficient detection of language-impaired children succeed. Parent questionnaires are the most reliable screening instruments for evaluating language abilities during the first 3 years.

  12. Early neural disruption and auditory processing outcomes in rodent models: implications for developmental language disability.

    PubMed

    Fitch, R Holy; Alexander, Michelle L; Threlkeld, Steven W

    2013-10-21

    Most researchers in the field of neural plasticity are familiar with the "Kennard Principle," which purports a positive relationship between age at brain injury and severity of subsequent deficits (plateauing in adulthood). As an example, a child with left hemispherectomy can recover seemingly normal language, while an adult with focal injury to sub-regions of left temporal and/or frontal cortex can suffer dramatic and permanent language loss. Here we present data regarding the impact of early brain injury in rat models as a function of type and timing, measuring long-term behavioral outcomes via auditory discrimination tasks varying in temporal demand. These tasks were created to model (in rodents) aspects of human sensory processing that may correlate-both developmentally and functionally-with typical and atypical language. We found that bilateral focal lesions to the cortical plate in rats during active neuronal migration led to worse auditory outcomes than comparable lesions induced after cortical migration was complete. Conversely, unilateral hypoxic-ischemic (HI) injuries (similar to those seen in premature infants and term infants with birth complications) led to permanent auditory processing deficits when induced at a neurodevelopmental point comparable to human "term," but only transient deficits (undetectable in adulthood) when induced in a "preterm" window. Convergent evidence suggests that regardless of when or how disruption of early neural development occurs, the consequences may be particularly deleterious to rapid auditory processing (RAP) outcomes when they trigger developmental alterations that extend into subcortical structures (i.e., lower sensory processing stations). Collective findings hold implications for the study of behavioral outcomes following early brain injury as well as genetic/environmental disruption, and are relevant to our understanding of the neurologic risk factors underlying developmental language disability in human

  13. Cardiomyocyte proliferation in zebrafish and mammals: lessons for human disease.

    PubMed

    Matrone, Gianfranco; Tucker, Carl S; Denvir, Martin A

    2017-04-01

    Cardiomyocytes proliferate profusely during early development and for a brief period after birth in mammals. Within a month after birth, this proliferative capability is dramatically reduced in mammals unlike lower vertebrates where it persists into adult life. The zebrafish, for example, retains the ability to regenerate the apex of the heart following resection by a mechanism predominantly driven by cardiomyocyte proliferation. Differences in proliferative capacity of cardiomyocytes in adulthood between mammals and lower vertebrates are closely liked to ontogenetic or phylogenetic factors. Elucidation of these factors has the potential to provide enormous benefits if they lead to the development of therapeutic strategies that facilitate cardiomyocyte proliferation. In this review, we highlight the differences between Mammalian and Zebrafish cardiomyocytes, which could explain at least in part the different proliferative capacities in these two species. We discuss the advantages of the zebrafish as a model of cardiomyocyte proliferation, particularly at the embryonic stage. We also identify a number of key molecular pathways with potential to reveal key steps in switching cardiomyocytes from a quiescent to a proliferative phenotype.

  14. Developmental pathways from childhood conduct problems to early adult depression: findings from the ALSPAC cohort

    PubMed Central

    Stringaris, Argyris; Lewis, Glyn; Maughan, Barbara

    2014-01-01

    Background Pathways from early-life conduct problems to young adult depression remain poorly understood. Aims To test developmental pathways from early-life conduct problems to depression at age 18. Method Data (n = 3542) came from the Avon Longitudinal Study of Parents and Children (ALSPAC). Previously derived conduct problem trajectories (ages 4-13 years) were used to examine associations with depression from ages 10 to 18 years, and the role of early childhood factors as potential confounders. Results Over 43% of young adults with depression in the ALSPAC cohort had a history of child or adolescent conduct problems, yielding a population attributable fraction of 0.15 (95% CI 0.08-0.22). The association between conduct problems and depression at age 18 was considerable even after adjusting for prior depression (odds ratio 1.55, 95% CI 1.24-1.94). Early-onset persistent conduct problems carried the highest risk for later depression. Irritability characterised depression for those with a history of conduct problems. Conclusions Early-life conduct problems are robustly associated with later depressive disorder and may be useful targets for early intervention. PMID:24764545

  15. Early developmental exposures shape trade-offs between acquired and innate immunity in humans

    PubMed Central

    Georgiev, Alexander V.; Kuzawa, Christopher W.; McDade, Thomas W.

    2016-01-01

    Background and objectives Life history theory predicts resource allocation trade-offs between competing functions and processes. We test the hypothesis that relative investment towards innate versus acquired immunity in humans is subject to such trade-offs and that three types of early developmental exposures are particularly salient in shaping adult immunophenotype: (i) pathogen exposure, (ii) nutritional resources; and (iii) extrinsic mortality cues. Methodology We quantified one aspect each of innate and acquired immune function, via C-reactive protein and Epstein–Barr virus antibodies, respectively, in a sample of 1248 men and women from the Philippines (ca. 21.5 years old). Early developmental exposures were assessed via long-term data collected prospectively since participants’ birth (1983–4). We calculated a standardized ratio to assess relative bias towards acquired versus innate immune function and examined its relationship to a suite of predictors via multiple regression. Results In partial support of our predictions, some of the measures of higher pathogen exposure, greater availability of nutritional resources, and lower extrinsic mortality cues in early life were associated with a bias toward acquired immunity in both men and women. The immune profile of women, in particular, appeared to be more sensitive to early life pathogen exposures than those of men. Finally, contrary to prediction, women exhibited a greater relative investment toward innate, not acquired, immunity. Conclusions and implications Early environments can exert considerable influence on the development of immunity. They affect trade-offs between innate and acquired immunity, which show adaptive plasticity and may differ in their influence in men and women. PMID:27530543

  16. Gender Differences In Social And Developmental Factors Affecting Puerto Rican Adolescents During The Early Stage

    PubMed Central

    Figueroa-Cosme, Wanda I.; Miranda, Christine; Fernandez, Diana M.; Maysonet, Johanna; Ramon, Raul O.

    2011-01-01

    Background Adolescence is associated with risky behaviors related with social and developmental factors. Objectives were to describe social and developmental factors affecting Puerto Rican early adolescent by gender and type of school at study entry. Methods Cross-sectional study design. The study group was composed by 168 seventh grade adolescents from private and public schools. Descriptive and non-parametric comparisons were performed. Results Significance differences among proportions for gender by type of school were found in the following variables: self-esteem and HIV/AIDS attitudes in public school and peer pressure and sensation seeking in private school Discussion Our study revealed that public school adolescents are characterized by males with higher self-esteem and less attitude for HIV/AIDS, while in private school the males has more peer pressure and seeking sensation than females. Future studies could analyze factors related with changes in developmental factors, this step is important to evaluate the effectiveness of ASUMA interventions. PMID:23875519

  17. Social Competence, Externalizing, and Internalizing Behavioral Adjustment from Early Childhood through Early Adolescence: Developmental Cascades

    PubMed Central

    Bornstein, Marc H.; Hahn, Chun-Shin; Haynes, O. Maurice

    2011-01-01

    This study used a 3-wave longitudinal design to investigate developmental cascades among social competence and externalizing and internalizing behavioral adjustment in a normative sample of 117 children seen at 4, 10, and 14 years. Children, mothers, and teachers provided data. A series of nested path analysis models was used to determine the most parsimonious and plausible cascades across the three constructs over and above their covariation at each age and stability across age. Children with lower social competence at age 4 years exhibited more externalizing and internalizing behaviors at age 10 years and more externalizing behaviors at age 14 years. Children with lower social competence at age 4 years also exhibited more internalizing behaviors at age 10 years and more internalizing behaviors at age 14 years. Children who exhibited more internalizing behaviors at age 4 years exhibited more internalizing behaviors at age 10 years and more externalizing behaviors at age 14 years. These cascades among social competence and behavioral adjustment obtained independent of child intelligence and maternal education and social desirability of responding. PMID:20883577

  18. Early developmental stress negatively affects neuronal recruitment to avian song system nucleus HVC.

    PubMed

    Honarmand, Mariam; Thompson, Christopher K; Schatton, Adriana; Kipper, Silke; Scharff, Constance

    2016-01-01

    Adverse environmental conditions can impact the life history trajectory of animals. Adaptive responses enable individuals to cope with unfavorable conditions, but altered metabolism and resource allocation can bear long-term costs. In songbirds, early developmental stress can cause lifelong changes in learned song, a culturally transmitted trait, and nestlings experiencing developmental stress develop smaller song control nucleus HVCs. We investigated whether nutrition-related developmental stress impacts neurogenesis in HVC, which may explain how poor nutrition leads to smaller HVC volume. We provided different quality diets (LOW and HIGH) by varying the husks-to-seeds ratio to zebra finch families for the first 35 days after the young hatched (PHD). At PHD14-18 and again at nutritional independence (PHD35), juveniles were injected with different cell division markers. To monitor growth, we took body measures at PHD10, 17, and 35. At PHD35 the number of newly recruited neurons in HVC and the rate of proliferation in the adjacent ventricular zone (VZ) were counted. Males raised on the LOW diet for their first weeks of life had significantly fewer new neurons in HVC than males raised on the HIGH diet. At the time when these new HVC neurons were born and labeled in the VZ (PHD17) the birds exposed to the LOW diet had significantly lower body mass. At PHD35 body mass or neuronal proliferation no longer differed. Our study shows that even transitory developmental stress can have negative consequences on the cellular processes underlying the development of neural circuits.

  19. Developmentally Appropriate Practices and Early Childhood Special Education: A Reaction to Johnson and McChesney Johnson.

    ERIC Educational Resources Information Center

    Carta, Judith J.; And Others

    1993-01-01

    As part of a continuing dialog, this response to Johnson and McChesney Johnson (1992) focuses on the many areas of overlap between principles of Developmentally Appropriate Practice and current early childhood special education principles of early intervention. (Author/DB)

  20. Early Blindness Results in Developmental Plasticity for Auditory Motion Processing within Auditory and Occipital Cortex

    PubMed Central

    Jiang, Fang; Stecker, G. Christopher; Boynton, Geoffrey M.; Fine, Ione

    2016-01-01

    Early blind subjects exhibit superior abilities for processing auditory motion, which are accompanied by enhanced BOLD responses to auditory motion within hMT+ and reduced responses within right planum temporale (rPT). Here, by comparing BOLD responses to auditory motion in hMT+ and rPT within sighted controls, early blind, late blind, and sight-recovery individuals, we were able to separately examine the effects of developmental and adult visual deprivation on cortical plasticity within these two areas. We find that both the enhanced auditory motion responses in hMT+ and the reduced functionality in rPT are driven by the absence of visual experience early in life; neither loss nor recovery of vision later in life had a discernable influence on plasticity within these areas. Cortical plasticity as a result of blindness has generally be presumed to be mediated by competition across modalities within a given cortical region. The reduced functionality within rPT as a result of early visual loss implicates an additional mechanism for cross modal plasticity as a result of early blindness—competition across different cortical areas for functional role. PMID:27458357

  1. Segmenting two-phoneme syllables: developmental differences in relation with early reading skills.

    PubMed

    Geudens, Astrid; Sandra, Dominiek; Van den Broeck, Wim

    2004-01-01

    This study explored developmental differences in children's segmentation skills of VC and CV syllables (e.g., /af/ and /fa/) in relation to their early reading abilities. To this end, we followed a subgroup of Dutch speaking prereaders who participated in, and replicated the segmentation task in first grade, at the outset of phonics reading instruction. Reading abilities were assessed after 6 and 9 months. First, we confirmed that VCs offer an easier context to isolate phonemes than CVs. Second, matching analyses showed that this development from VC to CV segmentation posed comparatively increasing difficulties for poor segmenters. Third, this qualitatively different development was reflected in early reading performance. Our data emphasize the importance of phonetic factors and instruction-based experiences in phonological development.

  2. Chromosome Damage and Early Developmental Arrest Caused by the Rex Element of Drosophila Melanogaster

    PubMed Central

    Robbins, L. G.; Pimpinelli, S.

    1994-01-01

    Rex (Ribosomal exchange) is a genetically identified repeated element within the ribosomal DNA (rDNA) of Drosophila melanogaster. Rex has a semidominant maternal effect that promotes exchange between and within rDNA arrays in the first few embryonic mitoses. Several of Rex's genetic properties suggest that its primary effect is rDNA-specific chromosome breakage that is resolved by recombination. We report here that rDNA crossovers are only a small, surviving minority of Rex-induced events. Cytology of embryos produced by Rex-homozygous females reveals obvious chromosome damage in at least a quarter of the embryos within the first three mitotic divisions. More than half of the embryos produced by Rex females die, and the developmental arrest is among the earliest reported for any maternal-effect lethal. The striking lethal phenotype suggests that embryos with early chromosome damage could be particularly fruitful subjects for analysis of the cell biology of early embryos. PMID:7828823

  3. General movements: A window for early identification of children at high risk for developmental disorders.

    PubMed

    Hadders-Algra, Mijna

    2004-08-01

    Detection of children with a developmental disorder, such as cerebral palsy, at an early age is notoriously difficult. Recently, a new form of neuromotor assessment of young infants was developed, based on the assessment of the quality of general movements (GMs). GMs are movements of the fetus and young infant in which all parts of the body participate. The technique of GM assessment is presented and the features of normal, mildly abnormal, and definitely abnormal GMs discussed. Essential to GM assessment is the Gestalt evaluation of movement complexity and variation. The quality of GMs at 2 to 4 months postterm (so-called fidgety GM age) has been found to have the highest predictive value. The presence of definitely abnormal GMs at this age--that is, GMs devoid of complexity and variation--puts a child at very high risk for cerebral palsy. This implies that definitely abnormal GMs at fidgety age are an indication for early physiotherapeutic intervention.

  4. Early acoustic discrimination experience ameliorates auditory processing deficits in male rats with cortical developmental disruption

    PubMed Central

    Threlkeld, Steven W.; Hill, Courtney A.; Rosen, Glenn D.; Fitch, R. Holly

    2014-01-01

    Auditory temporal processing deficits have been suggested to play a causal role in language learning impairments, and evidence of cortical developmental anomalies (microgyria (MG), ectopia) has been reported for language-impaired populations. Rodent models have linked these features, by showing deficits in auditory temporal discrimination for rats with neuronal migration anomalies (MG, ectopia). Since evidence from human studies suggests that training with both speech and non-speech acoustic stimuli may improve language performance in developmentally language-disabled populations, we were interested in whether/how maturation and early experience might influence auditory processing deficits seen in male rats with induced focal cortical MG. Results showed that for both simple (Normal single tone), as well as increasingly complex auditory discrimination tasks (Silent gap in white noise and FM sweep), prior experience significantly improved acoustic discrimination performance -- in fact, beyond improvements seen with maturation only. Further, we replicated evidence that young adult rats with MG were significantly impaired at discriminating FM sweeps compared to shams. However, these MG effects were no longer seen when experienced subjects were retested in adulthood (even though deficits in short duration FM sweep detection were seen for adult MG rats with no early experience). Thus while some improvements in auditory processing were seen with normal maturation, the effects of early experience were even more profound, in fact resulting in amelioration of MG effects seen at earlier ages. These findings support the clinical view that early training intervention with appropriate acoustic stimuli could similarly ameliorate long-term processing impairments seen in some language-impaired children. PMID:19460626

  5. Genetic identification of female Cannabis sativa plants at early developmental stage.

    PubMed

    Techen, Natascha; Chandra, Suman; Lata, Hemant; Elsohly, Mahmoud A; Khan, Ikhlas A

    2010-11-01

    Sequence-characterized amplified region (SCAR) markers were used to identify female plants at an early developmental stage in four different varieties of Cannabis sativa. Using the cetyl trimethylammonium bromide (CTAB) method, DNA was isolated from two-week-old plants of three drug-type varieties (Terbag W1, Terbag K2, and Terbag MX) and one fiber-type variety (Terbag Fedora A7) of C. sativa grown under controlled environmental conditions through seeds. Attempts to use MADC2 (male-associated DNA from Cannabis sativa) primers as a marker to identify the sex of Cannabis sativa plants were successful. Amplification of genomic DNA using MADC2-F and MADC2-R primers produced two distinct fragments, one with a size of approximately 450 bp for female plants and one for male plants with a size of approximately 300 bp. After harvesting the tissues for DNA extraction, plants were subjected to a flowering photoperiod (i.e., 12-h light cycle), and the appearance of flowers was compared with the DNA analysis. The results of the molecular analysis were found to be concordant with the appearance of male or female flowers. The results of this study represent a quick and reliable technique for the identification of sex in Cannabis plants using SCAR markers at a very early developmental stage.

  6. Social Problem-Solving in Early Childhood: Developmental Change and the Influence of Shyness

    PubMed Central

    Walker, Olga L.; Degnan, Kathryn A.; Fox, Nathan A.; Henderson, Heather A.

    2013-01-01

    The purpose of this study was to examine developmental change and the influence of shyness on social problem-solving (SPS). At 24, 36, and 48 months, children (N=570) were observed while interacting with an unfamiliar peer during an SPS task and at 24 months, maternal report of shyness was collected. Results showed that across the full sample, children displayed low but stable levels of withdrawn SPS and increasing levels of SPS competence over development. In addition, results showed that 24-month shyness was associated with high-increasing and high-decreasing withdrawn SPS trajectories compared to the low-increasing withdrawn SPS trajectory. Shyness was also associated with the low-increasing compared to the high-increasing SPS competence trajectory. Findings demonstrate the development of SPS competence over early childhood, as well as the influence of early shyness on this developmental course, with some shy children showing improvement in SPS skills and others continuing to show SPS difficulties over time. PMID:24039325

  7. Extraction of Functional Binding Sites from Unique Regulatory Regions: The Drosophila Early Developmental Enhancers

    PubMed Central

    Papatsenko, Dmitri A.; Makeev, Vsevolod J.; Lifanov, Alex P.; Régnier, Mireille; Nazina, Anna G.; Desplan, Claude

    2002-01-01

    The early developmental enhancers of Drosophila melanogaster comprise one of the most sophisticated regulatory systems in higher eukaryotes. An elaborate code in their DNA sequence translates both maternal and early embryonic regulatory signals into spatial distribution of transcription factors. One of the most striking features of this code is the redundancy of binding sites for these transcription factors (BSTF). Using this redundancy, we explored the possibility of predicting functional binding sites in a single enhancer region without any prior consensus/matrix description or evolutionary sequence comparisons. We developed a conceptually simple algorithm, Scanseq, that employs an original statistical evaluation for identifying the most redundant motifs and locates the position of potential BSTF in a given regulatory region. To estimate the biological relevance of our predictions, we built thorough literature-based annotations for the best-known Drosophila developmental enhancers and we generated detailed distribution maps for the most robust binding sites. The high statistical correlation between the location of BSTF in these experiment-based maps and the location predicted in silico by Scanseq confirmed the relevance of our approach. We also discuss the definition of true binding sites and the possible biological principles that govern patterning of regulatory regions and the distribution of transcriptional signals. PMID:11875036

  8. Early developmental plasticity and integrative responses in arctic charr (Salvelinus alpinus): effects of water velocity on body size and shape.

    PubMed

    Grünbaum, Thomas; Cloutier, Richard; Mabee, Paula M; Le François, Nathalie R

    2007-07-15

    Environmental conditions such as temperature and water velocity may induce changes among alternative developmental pathways, i.e. phenotypic responses, in vertebrates. However, the extent to which the environment induces developmental plasticity and integrated developmental responses during early ontogeny of fishes remains poorly documented. We analyzed the responses of newly hatched Arctic charr (Salvelinus alpinus) to four experimental water velocities during 100 days of development. To our knowledge, this work is the first to analyze developmental plasticity responses of body morphology to an experimental gradient of water velocities during early ontogeny of fish. Arctic charr body size and shape responses show first, that morphometric traits display significant differences between low and high water velocities, thus revealing directional changes in body traits. Secondly, trait variation allows the recognition of critical ontogenetic periods that are most responsive to environmental constraints (40-70 and 80-90 days) and exhibit different levels of developmental plasticity. This is supported by the observation of asynchronous timing of variation peaks among treatments. Third, morphological interaction of traits is developmentally plastic and time-dependent. We suggest that developmental responses of traits plasticity and interaction at critical ontogenetic periods are congruent with specific environmental conditions to maintain the functional integrity of the organism.

  9. Irreversibility of a bad start: early exposure to osmotic stress limits growth and adaptive developmental plasticity.

    PubMed

    Wu, Chi-Shiun; Gomez-Mestre, Ivan; Kam, Yeong-Choy

    2012-05-01

    Harsh environments experienced early in development have immediate effects and potentially long-lasting consequences throughout ontogeny. We examined how salinity fluctuations affected survival, growth and development of Fejervarya limnocharis tadpoles. Specifically, we tested whether initial salinity effects on growth and rates of development were reversible and whether they affected the tadpoles' ability to adaptively accelerate development in response to deteriorating conditions later in development. Tadpoles were initially assigned to either low or high salinity, and then some were switched between salinity levels upon reaching either Gosner stage 30 (early switch) or 38 (late switch). All tadpoles initially experiencing low salinity survived whereas those initially experiencing high salinity had poor survival, even if switched to low salinity. Growth and developmental rates of tadpoles initially assigned to high salinity did not increase after osmotic stress release. Initial low salinity conditions allowed tadpoles to attain a fast pace of development even if exposed to high salinity afterwards. Tadpoles experiencing high salinity only late in development metamorphosed faster and at a smaller size, indicating an adaptive acceleration of development to avoid osmotic stress. Nonetheless, early exposure to high salinity precluded adaptive acceleration of development, always causing delayed metamorphosis relative to those in initially low salinity. Our results thus show that stressful environments experienced early in development can critically impact life history traits, having long-lasting or irreversible effects, and restricting their ability to produce adaptive plastic responses.

  10. Sociodemographic risk, developmental competence, and PTSD symptoms in young children exposed to interpersonal trauma in early life.

    PubMed

    Enlow, Michelle Bosquet; Blood, Emily; Egeland, Byron

    2013-12-01

    Young children are disproportionately exposed to interpersonal trauma (maltreatment, witnessing intimate partner violence [IPV]) and appear particularly susceptible to negative sequelae. Little is known about the factors influencing vulnerability to traumatic stress responses and other negative outcomes in early life. This study examined associations among interpersonal trauma exposure, sociodemographic risk, developmental competence, and posttraumatic stress disorder (PTSD) symptoms in 200 children assessed from birth to first grade via standardized observations, record reviews, and maternal and teacher interviews. More severe PTSD symptoms were predicted by greater trauma exposure (r = .43), greater sociodemographic risk (r = .22), and lower developmental competence (rs=−.31 and −.54 for preschool and school-age developmental competence, respectively). Developmental competence partially mediated the association between trauma exposure and symptoms. Trauma exposure fully mediated the association between sociodemographic risk and symptoms. Neither sociodemographic risk nor developmental competence moderated trauma exposure effects on symptoms. The findings suggest that (a)exposure to maltreatment and IPV has additive effects on posttraumatic stress risk in early life, (b) associations between sociodemographic adversity and poor mental health may be attributable to increased trauma exposure in disadvantaged populations, and (c) early exposures have a negative cascade effect on developmental competence and mental health.

  11. Interpersonal Callousness from Childhood to Adolescence: Developmental Trajectories and Early Risk Factors.

    PubMed

    Byrd, Amy L; Hawes, Samuel W; Loeber, Rolf; Pardini, Dustin A

    2016-04-21

    Youth with a callous interpersonal style, consistent with features of adult psychopathy (e.g., lack of guilt, deceitful), are at risk for exhibiting severe and protracted antisocial behaviors. However, no studies have examined changes that occur in interpersonal callousness (IC) from childhood to adolescence, and little is known about the influence of early child, social, and contextual factors on trajectories of IC. The current study examined distinct patterns of IC across childhood and adolescence and associations with early risk factors. Participants were an at-risk sample of 503 boys (56% African American) assessed annually from around ages 7-15. Analyses examined child (anger dysregulation, fearfulness), social (peer, family, maltreatment), and contextual (psychosocial adversity) factors associated with teacher-reported IC trajectories across childhood and adolescence. Using latent class growth analysis, five trajectories of IC were identified (early-onset chronic, childhood-limited, adolescent-onset, moderate, low). Approximately 10% of boys followed an early-onset chronic trajectory, and a roughly equal percent of youth followed childhood-limited trajectory (10%) or an adolescent-onset trajectory (12%) of IC across development. Specifically, half of the boys with high IC in childhood did not continue to exhibit significant levels of these features into adolescence, whereas an equal proportion of youth with low IC in childhood demonstrated increasing levels during the transition to adolescence. Boys in the early-onset chronic group were characterized by the most risk factors and were differentiated from those with childhood-limited and adolescent-onset IC only by higher conduct problems, fearlessness, and emotional abuse/neglect. Findings are discussed in terms of developmental models of IC and several avenues for early targeted interventions.

  12. Elicitor-Induced Spruce Stress Lignin (Structural Similarity to Early Developmental Lignins).

    PubMed Central

    Lange, B. M.; Lapierre, C.; Sandermann, H.

    1995-01-01

    Suspension cultures of Picea abies (L.) Karst released polymeric material into the culture medium when treated with an elicitor preparation from the spruce needle pathogen Rhizosphaera kalkhoffii. The presence of lignin (about 35%, w/w) was demonstrated by phloroglucinol/HCI reactivity and quantitation with thioglycolic acid. Carbohydrate (about 14%, w/w) and protein (about 32%, w/w) were also detected. Amino acid analysis revealed that hydroxyproline and proline predominated. Thioacidolysis and subsequent Raney nickel desulfurization allowed the analysis of lignin-building units and interunit bonds. Compared with spruce wood lignin, an approximately 20-fold higher relative amount of p-hydroxyphenyl units was determined. A high content of p-hydroxyphenyl units is typical for certain developmental lignins, such as conifer compression wood and middle lamella lignins, as well as all induced cell culture lignins so far analyzed. Cross-linkages of the pinoresinol type ([beta]-[beta]) in the excreted cell culture lignin were markedly increased, whereas [beta]-1 interunit linkages were decreased relative to spruce wood lignin. The amount and nature of cross-linkages were shown to be intermediate between those in wood lignin and in enzymatically prepared lignins. In summary, the elicitor-induced stress lignin was excreted as a lignin-extensin complex that closely resembled early developmental lignins. PMID:12228544

  13. The early embryo response to intracellular reactive oxygen species is developmentally regulated.

    PubMed

    Bain, Nathan T; Madan, Pavneesh; Betts, Dean H

    2011-01-01

    In vitro embryo production (IVP) suffers from excessive developmental failure. Its inefficiency is linked, in part, to reactive oxygen species (ROS) brought on by high ex vivo oxygen (O(2)) tensions. To further delineate the effects of ROS on IVP, the intracellular ROS levels of early bovine embryos were modulated by: (1) varying O(2) tension; (2) exogenous H(2)O(2) treatment; and (3) antioxidant supplementation. Although O(2) tension did not significantly affect blastocyst frequencies (P>0.05), 20% O(2) accelerated the rate of first cleavage division and significantly decreased and increased the proportion of permanently arrested 2- to 4-cell embryos and apoptotic 9- to 16-cell embryos, respectively, compared with embryos cultured in 5% O(2) tension. Treatment with H(2)O(2), when applied separately to oocytes, zygotes, 2- to 4-cell embryos or 9- to 16-cell embryos, resulted in a significant (P<0.05) dose-dependent decrease in blastocyst development in conjunction with a corresponding increase in the induction of either permanent embryo arrest or apoptosis in a stage-dependent manner. Polyethylene glycol-catalase supplementation reduced ROS-induced embryo arrest and/or death, resulting in a significant (P<0.05) increase in blastocyst frequencies under high O(2) culture conditions. Together, these results indicate that intracellular ROS may be signalling molecules that, outside an optimal range, result in various developmentally regulated modes of embryo demise.

  14. DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD DC:0-5: SELECTIVE REVIEWS FROM A NEW NOSOLOGY FOR EARLY CHILDHOOD PSYCHOPATHOLOGY.

    PubMed

    Zeanah, Charles H; Carter, Alice S; Cohen, Julie; Egger, Helen; Gleason, Mary Margaret; Keren, Miri; Lieberman, Alicia; Mulrooney, Kathleen; Oser, Cindy

    2016-09-01

    The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-5; ZERO TO THREE) is scheduled to be published in 2016. The articles in this section are selective reviews that have been undertaken as part of the process of refining and updating the nosology. They provide the rationales for new disorders, for disorders that had not been included previously in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-3R; ZERO TO THREE, 2005), and for changes in how certain types of disorders are conceptualized.

  15. Timing of cardiomyocyte growth, maturation, and attrition in perinatal sheep

    PubMed Central

    Jonker, Sonnet S.; Louey, Samantha; Giraud, George D.; Thornburg, Kent L.; Faber, J. Job

    2015-01-01

    Studies in altricial rodents attribute dramatic changes in perinatal cardiomyocyte growth, maturation, and attrition to stimuli associated with birth. Our purpose was to determine whether birth is a critical trigger controlling perinatal cardiomyocyte growth, maturation and attrition in a precocial large mammal, sheep (Ovis aries). Hearts from 0–61 d postnatal lambs were dissected or enzymatically dissociated. Cardiomyocytes were measured by micromorphometry, cell cycle activity assessed by immunohistochemistry, and nuclear number counted after DNA staining. Integration of this new data with published fetal data from our laboratory demonstrate that a newly appreciated >30% decrease in myocyte number occurred in the last 10 d of gestation (P < 0.0005) concomitant with an increase in cleaved poly (ADP-ribose) polymerase 1 (P < 0.05), indicative of apoptosis. Bisegmental linear regressions show that most changes in myocyte growth kinetics occur before birth (median = 15.2 d; P < 0.05). Right ventricular but not left ventricular cell number increases in the neonate, by 68% between birth and 60 d postnatal (P = 0.028). We conclude that in sheep few developmental changes in cardiomyocytes result from birth, excepting the different postnatal degrees of free wall hypertrophy between the ventricles. Furthermore, myocyte number is reduced in both ventricles immediately before term, but proliferation increases myocyte number in the neonatal right ventricle.—Jonker, S. S., Louey, S., Giraud, G. D., Thornburg, K. L., Faber, J. J. Timing of cardiomyocyte growth, maturation, and attrition in perinatal sheep. PMID:26139099

  16. The Developmental Pathway From Pubertal Timing to Delinquency and Sexual Activity From Early to Late Adolescence

    PubMed Central

    Negriff, Sonya; Elizabeth, J. Susman; Trickett, Penelope K.

    2013-01-01

    There is strong evidence that early pubertal timing is associated with adolescent problem behaviors. However, there has been limited investigation of the mechanisms or developmental relationships. The present study examined longitudinal models incorporating pubertal timing, delinquency, and sexual activity in a sample of 454 adolescents (9–13 years old at enrollment; 47% females). Participants were seen for three assessments approximately 1 year apart. Characteristics of friendship networks (older friends, male friends, older male friends) were examined as mediators. Structural equation modeling was used to test these associations as well as temporal relationships between sexual activity and delinquency. Results showed that early pubertal timing at Time 1 was related to more sexual activity at Time 2, which was related to higher delinquency at Time 3, a trend mediation effect. None of the friendship variables mediated these associations. Gender or maltreatment status did not moderate the meditational pathways. The results also supported the temporal sequence of sexual activity preceding increases in delinquency. These findings reveal that early maturing adolescents may actively seek out opportunities to engage in sexual activity which appears to be risk for subsequent delinquency. PMID:21191640

  17. Pyrosequencing of Haliotis diversicolor Transcriptomes: Insights into Early Developmental Molluscan Gene Expression

    PubMed Central

    Huang, Zi-Xia; Chen, Zhi-Sen; Ke, Cai-Huan; Zhao, Jing; You, Wei-Wei; Zhang, Jie; Dong, Wei-Ting; Chen, Jun

    2012-01-01

    Background The abalone Haliotis diversicolor is a good model for study of the settlement and metamorphosis, which are widespread marine ecological phenomena. However, information on the global gene backgrounds and gene expression profiles for the early development of abalones is lacking. Methodology/Principal Findings In this study, eight non-normalized and multiplex barcode-labeled transcriptomes were sequenced using a 454 GS system to cover the early developmental stages of the abalone H. diversicolor. The assembly generated 35,415 unigenes, of which 7,566 were assigned GO terms. A global gene expression profile containing 636 scaffolds/contigs was constructed and was proven reliable using qPCR evaluation. It indicated that there may be existing dramatic phase transitions. Bioprocesses were proposed, including the ‘lock system’ in mature eggs, the collagen shells of the trochophore larvae and the development of chambered extracellular matrix (ECM) structures within the earliest postlarvae. Conclusion This study globally details the first 454 sequencing data for larval stages of H. diversicolor. A basic analysis of the larval transcriptomes and cluster of the gene expression profile indicates that each stage possesses a batch of specific genes that are indispensable during embryonic development, especially during the two-cell, trochophore and early postlarval stages. These data will provide a fundamental resource for future physiological works on abalones, revealing the mechanisms of settlement and metamorphosis at the molecular level. PMID:23236463

  18. Toxic effects of magnesium oxide nanoparticles on early developmental and larval stages of zebrafish (Danio rerio).

    PubMed

    Ghobadian, Mehdi; Nabiuni, Mohammad; Parivar, Kazem; Fathi, Mojtaba; Pazooki, Jamileh

    2015-12-01

    Magnesium oxide nanoparticles (MgONPs) are used in medicine, manufacturing and food industries. Because of their extensive application in our daily lives, environmental exposure to these nanoparticles is inevitable. The present study examined the effects of MgONPs on zebrafish (Danio rerio) early developmental stages. The results showed that, at different concentrations, MgONPs induced cellular apoptosis and intracellular reactive oxygen species. The hatching rate and survival of embryos decreased in a dose dependent manner. The 96-h LC50 value of MgONPs on zebrafish survival was 428 mg/l and the 48-h EC50 value of MgONPs on zebrafish embryo hatching rate was 175 mg/l. Moreover different types of malformation were observed in exposed embryos. The results demonstrate the toxic effects of MgONPs on zebrafish embryos and emphasize the need for further studies.

  19. Developmental pathways to integrated social skills: the roles of parenting and early intervention.

    PubMed

    Ayoub, Catherine; Vallotton, Claire D; Mastergeorge, Ann M

    2011-01-01

    Dynamic skill theory was utilized to explain the multiple mechanisms and mediating processes influencing development of self-regulatory and language skills in children at 14, 24, and 36 months of age. Relations were found between family risks, parenting-related stresses, and parent-child interactions that contribute either independently or through mediation to the child's acquisition of self-regulatory skills even when accounting for the influence of language development. Variation in impacts between control and Early Head Start (EHS) intervention samples was compared to explore the sequence of developmental mechanisms over time. Findings indicate that EHS protects parenting, child language, and self-regulatory development from the effects of demographic risks and parenting stress, and thus supports parents to raise healthy children.

  20. Retinoic acid is enriched in Hensen's node and is developmentally regulated in the early chicken embryo.

    PubMed Central

    Chen, Y; Huang, L; Russo, A F; Solursh, M

    1992-01-01

    Retinoic acid (RA) has been considered as a potential morphogen in the chicken limb and has also been suggested to be involved in early embryonic development. On the basis of biological activity, previous reports suggest that Hensen's node, the anatomical equivalent in the chicken of the Spemann's organizer, may contain RA. Here, by using a molecular assay system, we demonstrate that Hensen's node contains retinoids in a concentration approximately 20 times more than that in the neighboring tissues. Furthermore, stage 6 Hensen's node contains approximately 3 times more retinoid than that of stage 4 embryos. These endogenous retinoids may establish a concentration gradient from Hensen's node to adjacent tissues and play a role in establishing the primary embryonic axis in the vertebrate. The results also suggest that the retinoid concentration in Hensen's node is developmentally regulated. Images PMID:1438194

  1. Retinoic acid is enriched in Hensen's node and is developmentally regulated in the early chicken embryo.

    PubMed

    Chen, Y; Huang, L; Russo, A F; Solursh, M

    1992-11-01

    Retinoic acid (RA) has been considered as a potential morphogen in the chicken limb and has also been suggested to be involved in early embryonic development. On the basis of biological activity, previous reports suggest that Hensen's node, the anatomical equivalent in the chicken of the Spemann's organizer, may contain RA. Here, by using a molecular assay system, we demonstrate that Hensen's node contains retinoids in a concentration approximately 20 times more than that in the neighboring tissues. Furthermore, stage 6 Hensen's node contains approximately 3 times more retinoid than that of stage 4 embryos. These endogenous retinoids may establish a concentration gradient from Hensen's node to adjacent tissues and play a role in establishing the primary embryonic axis in the vertebrate. The results also suggest that the retinoid concentration in Hensen's node is developmentally regulated.

  2. Analysis of cardiomyocyte movement in the developing murine heart.

    PubMed

    Hashimoto, Hisayuki; Yuasa, Shinsuke; Tabata, Hidenori; Tohyama, Shugo; Seki, Tomohisa; Egashira, Toru; Hayashiji, Nozomi; Hattori, Fumiyuki; Kusumoto, Dai; Kunitomi, Akira; Takei, Makoto; Kashimura, Shin; Yozu, Gakuto; Shimojima, Masaya; Motoda, Chikaaki; Muraoka, Naoto; Nakajima, Kazunori; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Fukuda, Keiichi

    2015-09-04

    The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle.

  3. Analysis of cerebro-spinal fluid protein composition in early developmental stages in chick embryos.

    PubMed

    Gato, A; Martín, P; Alonso, M I; Martín, C; Pulgar, M A; Moro, J A

    2004-04-01

    Foetal cerebro-spinal fluid (CSF) has a very high protein concentration when compared to adult CSF, and in many species five major protein fractions have been described. However, the protein concentration and composition in CSF during early developmental stages remains largely unknown. Our results show that in the earliest stages (18 to 30 H.H.) of chick development there is a progressive increase in CSF protein concentration until foetal values are attained. In addition, by performing electrophoretic separation and high-sensitivity silver staining, we were able to identify a total of 21 different protein fractions in the chick embryo CSF. In accordance with the developmental pattern of their concentration, these can be classified as follows: A: high-concentration fractions which corresponded with the ones described in foetal CSF by other authors; B: low-concentration fractions which remained stable throughout the period studied; C: low-concentration fractions which show changes during this period. The evolution and molecular weight of the latter group suggest the possibility of an important biological role. Our data demonstrate that all the CSF protein fractions are present in embryonic serum; this could mean that the specific transport mechanisms in neuroepithelial cells described in the foetal period evolve in very early stages of development. In conclusion, this paper offers an accurate study of the protein composition of chick embryonic CSF, which will help the understanding of the influences on neuroepithelial stem cells during development and, as a result, the appropriate conditions for the in vitro study of embryonic/foetal nervous tissue cells.

  4. Early motor developmental milestones and schizophrenia: A systematic review and meta-analysis.

    PubMed

    Filatova, S; Koivumaa-Honkanen, H; Hirvonen, N; Freeman, A; Ivandic, I; Hurtig, T; Khandaker, G M; Jones, P B; Moilanen, K; Miettunen, J

    2017-01-25

    The neurodevelopmental hypothesis of schizophrenia proposes that impaired brain development is a cause of the illness. Early motor developmental milestones, such as learning to walk, are predictors of later schizophrenia but studies have not been systematically reviewed. The aim of the present systematic review and meta-analysis was to explore the association between early motor developmental milestones and the risk of adult schizophrenia. In addition, we updated a systematic review on motor function and risk of schizophrenia. The PubMed, PsycINFO and Scopus databases were searched for original research articles published up to July 2015. Motor milestones were measured between ages 0 and 13years. Random effect meta-analysis calculated effect estimates (Hedges' g) for the association between individual motor milestones and schizophrenia risk. An electronic database and selected articles reference list search identified 5990 articles after removing duplicates. Sixty-nine full text articles were assessed for eligibility of which six were included in the review. Five studies provided sufficient data for meta-analyses. The following motor milestones were significantly associated with adult schizophrenia risk: walking unsupported (g=0.46; 95% CI 0.27-0.64; p<0.001), standing unsupported (g=0.28; 0.16-0.40; p<0.001) and sitting unsupported (g=0.18; 0.05-0.31; p=0.007). Results for the milestones 'holding head up' and 'grabbing object' were not statistically significant. Delayed walking, sitting and standing unsupported were associated with adult onset schizophrenia. The findings emphasise the importance of timely achievement of these motor milestones in childhood and can contribute to the identification of individuals at risk of psychosis.

  5. Developmental activation of the capability to undergo checkpoint-induced apoptosis in the early zebrafish embryo.

    PubMed

    Ikegami, R; Hunter, P; Yager, T D

    1999-05-15

    In this study, we demonstrate the developmental activation, in the zebrafish embryo, of a surveillance mechanism which triggers apoptosis to remove damaged cells. We determine the time course of activation of this mechanism by exposing embryos to camptothecin, an agent which specifically inhibits topoisomerase I within the DNA replication complex and which, as a consequence of this inhibition, also produces strand breaks in the genomic DNA. In response to an early (pre-gastrula) treatment with camptothecin, apoptosis is induced at a time corresponding approximately to mid-gastrula stage in controls. This apoptotic response to a block of DNA replication can also be induced by early (pre-MBT) treatment with the DNA synthesis inhibitors hydroxyurea and aphidicolin. After camptothecin treatment, a high proportion of cells in two of the embryo's three mitotic domains (the enveloping and deep cell layers), but not in the remaining domain (the yolk syncytial layer), undergoes apoptosis in a cell-autonomous fashion. The first step in this response is an arrest of the proliferation of all deep- and enveloping-layer cells. These cells continue to increase in nuclear volume and to synthesize DNA. Eventually they become apoptotic, by a stereotypic pathway which involves cell membrane blebbing, "margination" and fragmentation of nuclei, and cleavage of the genomic DNA to produce a nucleosomal ladder. Fragmentation of nuclei can be blocked by the caspase-1,4,5 inhibitor Ac-YVAD-CHO, but not by the caspase-2,3,7[, 1] inhibitor Ac-DEVD-CHO. This suggests a functional requirement for caspase-4 or caspase-5 in the apoptotic response to camptothecin. Recently, Xenopus has been shown to display a developmental activation of the capability for stress- or damaged-induced apoptosis at early gastrula stage. En masse, our experiments suggest that the apoptotic responses in zebrafish and Xenopus are fundamentally similar. Thus, as for mammals, embryos of the lower vertebrates exhibit the

  6. Sociodemographic Risk, Developmental Competence, and PTSD Symptoms in Young Children Exposed to Interpersonal Trauma in Early Life

    PubMed Central

    Enlow, Michelle Bosquet; Blood, Emily; Egeland, Byron

    2014-01-01

    Children under age six years are disproportionately exposed to interpersonal trauma, including maltreatment and witnessing intimate partner violence (IPV), and may be particularly susceptible to negative sequelae. However, young children have generally been neglected from trauma research; thus, little is known about the factors influencing vulnerability to traumatic stress responses and other negative outcomes in early life. This study examined associations among interpersonal trauma exposure, sociodemographic risk, developmental competence, and posttraumatic stress disorder (PTSD) symptoms in 200 children assessed prospectively from birth to 1st grade via home and laboratory observations, record reviews, and maternal and teacher interviews. Greater trauma exposure and sociodemographic risk and lower developmental competence predicted more severe PTSD symptoms. Developmental competence partially mediated the association between exposures and symptoms. Trauma exposure fully mediated the association between sociodemographic risk and symptoms. Neither sociodemographic risk nor developmental competence moderated trauma exposure effects on symptoms. The findings suggest that (a) exposure to maltreatment and IPV has additive effects on posttraumatic stress risk in early life, (b) associations between sociodemographic adversity and poor mental health may be attributable to increased trauma exposure in disadvantaged populations, and (c) early exposures have a negative cascade effect on developmental competence and child mental health. PMID:24490247

  7. Executive function in early childhood: longitudinal measurement invariance and developmental change.

    PubMed

    Willoughby, Michael T; Wirth, R J; Blair, Clancy B

    2012-06-01

    This study tested the longitudinal measurement invariance and developmental changes of a newly developed battery of executive function (EF) tasks for use in early childhood. The battery was administered in the Family Life Project-a prospective longitudinal study (N = 1,292) of families who were oversampled from low-income and African American families at the birth of a new child-at assessments conducted when the child was 3, 4, and 5 years old. All 6 individual EF tasks exhibited strong measurement invariance over time. The EF battery, which was derived from the 6 individual tasks, exhibited partial strong invariance over time. Second-order latent growth curve models revealed individual differences in the levels but not rates of change in latent EF ability. The functional form of change was nonlinear; 60% of the total change in EF ability that was observed between the 3- and 5-year assessments occurred between the Year 3 and Year 4 assessments. Results are discussed with respect to the importance of establishing scalable measures of EF ability prior to investigating experiences that predict or are predicted by changes in EF during early childhood.

  8. Tackling the 'dyslexia paradox': reading brain and behavior for early markers of developmental dyslexiax.

    PubMed

    Ozernov-Palchik, Ola; Gaab, Nadine

    2016-01-01

    Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5-17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in pre-reading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure.

  9. Tackling the ‘dyslexia paradox’: reading brain and behavior for early markers of developmental dyslexia

    PubMed Central

    Ozernov-Palchik, Ola; Gaab, Nadine

    2016-01-01

    Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5–17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in prereading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure. PMID:26836227

  10. Ernest Everett Just (1883-1941)--an early ecological developmental biologist.

    PubMed

    Byrnes, W Malcolm; Eckberg, William R

    2006-08-01

    Ecological developmental biology (Eco-Devo) involves the study of development in its natural environmental context as opposed to the laboratory setting. Ernest E. Just was an early 20th century African-American embryologist who devoted his career to studying the early development of marine invertebrates in the United States and abroad. Through detailed study of the fertilization process, he came to see the cell cortex as playing a central role in development, inheritance, and evolution. This paper, after presenting some of Just's scientific and philosophical contributions, argues that Just was an Eco-Devo biologist. Three lines of evidence are given. First, Just believed that intimate knowledge of the natural history of the marine animal under study--hence, the natural setting in which fertilization occurs--was essential. Second, he stressed the importance of the egg's "normality"--how well its condition in the laboratory corresponds to the natural, fertilizable state. Finally, Just was an organicist, believing that organisms are holistic systems with emergent properties that arise from their organization and complexity. Although other scientists may stand out more clearly as founding architects of Eco-Devo, E. E. Just, with his unwavering insistence on the normality and holistic integrity of the egg cell, was one of its purest adherents.

  11. Screening for Autism Spectrum Disorders in Flemish Day-Care Centres with the Checklist for Early Signs of Developmental Disorders

    ERIC Educational Resources Information Center

    Dereu, Mieke; Warreyn, Petra; Raymaekers, Ruth; Meirsschaut, Mieke; Pattyn, Griet; Schietecatte, Inge; Roeyers, Herbert

    2010-01-01

    A new screening instrument for ASD was developed that can be filled out by child care workers: the Checklist for Early Signs of Developmental Disorders (CESDD). The predictive validity of the CESDD was evaluated in a population of 6,808 children between 3 and 39 months attending day-care centres in Flanders. The CESDD had a sensitivity of 0.80 and…

  12. A Framework for Early Literacy Instruction: Aligning Standards to Developmental Patterns and Student Behaviors. Pre-K through Kindergarten.

    ERIC Educational Resources Information Center

    Bodrova, Elena; Leong, Deborah J.; Paynter, Diane E.; Semenov, Dmitri

    This document is designed to establish consistency in the definition and format to be used in developing early literacy standards and benchmarks. It articulates a set of standards and benchmarks that is based on current national and state standards documents and that reflects the foundational knowledge and developmental differences representative…

  13. Preservice Early Childhood Educators' and Elementary Teachers' Perspectives on Including Young Children with Developmental Disabilities: A Mixed Methods Analysis

    ERIC Educational Resources Information Center

    Frankel, Elaine B.; Hutchinson, Nancy L.; Burbidge, Julie; Minnes, Patricia

    2014-01-01

    This mixed methods study reports on the perspectives of 143 preservice early childhood educators (ECE) and 208 elementary teacher candidates (TC) on teaching children with developmental disabilities and delays (DDD) in inclusive classrooms. A questionnaire was administered which included items on demographic characteristics, experience, knowledge,…

  14. Missing the Boat with Technology Usage in Early Childhood Settings: A 21st Century View of Developmentally Appropriate Practice

    ERIC Educational Resources Information Center

    Parette, Howard P.; Quesenberry, Amanda C.; Blum, Craig

    2010-01-01

    Technology use permeates virtually all aspects of twenty-first century society, though its integration in early childhood settings and recognition as a developmentally appropriate practice remains problematic. A position is taken that education professionals may be "missing the boat" by not embracing technology usage as a developmentally…

  15. Cypriot Pre-Service Kindergarten Teachers' Beliefs about and Practices of Developmentally Appropriate Practices in Early Childhood Education

    ERIC Educational Resources Information Center

    Sakellariou, Maria; Rentzou, Konstantina

    2011-01-01

    Beliefs are said to affect the pedagogical practice one employs. Considering the potentially important influence of teachers' beliefs on their practices, the level of early childhood teachers' beliefs about developmentally appropriate practice (DAP) and the relationship between their beliefs and practices are regarded as important topics of study…

  16. Cardiomyocyte Hypertrophy in Arrhythmogenic Cardiomyopathy.

    PubMed

    Gerçek, Mustafa; Gerçek, Muhammed; Kant, Sebastian; Simsekyilmaz, Sakine; Kassner, Astrid; Milting, Hendrik; Liehn, Elisa A; Leube, Rudolf E; Krusche, Claudia A

    2017-04-01

    Arrhythmogenic cardiomyopathy (AC) is a hereditary disease leading to sudden cardiac death or heart failure. AC pathology is characterized by cardiomyocyte loss and replacement fibrosis. Our goal was to determine whether cardiomyocytes respond to AC progression by pathological hypertrophy. To this end, we examined tissue samples from AC patients with end-stage heart failure and tissue samples that were collected at different disease stages from desmoglein 2-mutant mice, a well characterized AC model. We find that cardiomyocyte diameters are significantly increased in right ventricles of AC patients. Increased mRNA expression of the cardiac stress marker natriuretic peptide B is also observed in the right ventricle of AC patients. Elevated myosin heavy chain 7 mRNA expression is detected in left ventricles. In desmoglein 2-mutant mice, cardiomyocyte diameters are normal during the concealed disease phase but increase significantly after acute disease onset on cardiomyocyte death and fibrotic myocardial remodeling. Hypertrophy progresses further during the chronic disease stage. In parallel, mRNA expression of myosin heavy chain 7 and natriuretic peptide B is up-regulated in both ventricles with right ventricular preference. Calcineurin/nuclear factor of activated T cells (Nfat) signaling, which is linked to pathological hypertrophy, is observed during AC progression, as evidenced by Nfatc2 and Nfatc3 mRNA in cardiomyocytes and increased mRNA of the Nfat target regulator of calcineurin 1. Taken together, we demonstrate that pathological hypertrophy occurs in AC and is secondary to cardiomyocyte loss and cardiac remodeling.

  17. Infant and Early Childhood Mental Health: A Comprehensive Developmental Approach to Assessment and Intervention

    ERIC Educational Resources Information Center

    Greenspan, Stanley I.; Wieder, Serena

    2003-01-01

    This article describes how the "developmental structuralist" theory of emotional development has evolved over 25 years into the developmental-individual difference-relationship (DIR[R]) approach to assessment and intervention. ZERO TO THREE and the Interdisciplinary Council for Developmental and Learning Disorders (ICDL) trace their roots to the…

  18. 14-3-3ε Plays a Role in Cardiac Ventricular Compaction by Regulating the Cardiomyocyte Cell Cycle

    PubMed Central

    Kosaka, Yasuhiro; Cieslik, Katarzyna A.; Li, Ling; Lezin, George; Maguire, Colin T.; Saijoh, Yukio; Toyo-oka, Kazuhito; Gambello, Michael J.; Vatta, Matteo; Wynshaw-Boris, Anthony; Baldini, Antonio; Yost, H. Joseph

    2012-01-01

    Trabecular myocardium accounts for the majority of the ventricles during early cardiogenesis, but compact myocardium is the primary component at later developmental stages. Elucidation of the genes regulating compact myocardium development is essential to increase our understanding of left ventricular noncompaction (LVNC), a cardiomyopathy characterized by increased ratios of trabecular to compact myocardium. 14-3-3ε is an adapter protein expressed in the lateral plate mesoderm, but its in vivo cardiac functions remain to be defined. Here we show that 14-3-3ε is expressed in the developing mouse heart as well as in cardiomyocytes. 14-3-3ε deletion did not appear to induce compensation by other 14-3-3 isoforms but led to ventricular noncompaction, with features similar to LVNC, resulting from a selective reduction in compact myocardium thickness. Abnormal compaction derived from a 50% decrease in cardiac proliferation as a result of a reduced number of cardiomyocytes in G2/M and the accumulation of cardiomyocytes in the G0/G1 phase of the cell cycle. These defects originated from downregulation of cyclin E1 and upregulation of p27Kip1, possibly through both transcriptional and posttranslational mechanisms. Our work shows that 14-3-3ε regulates cardiogenesis and growth of the compact ventricular myocardium by modulating the cardiomyocyte cell cycle via both cyclin E1 and p27Kip1. These data are consistent with the long-held view that human LVNC may result from compaction arrest, and they implicate 14-3-3ε as a new candidate gene in congenital human cardiomyopathies. PMID:23071090

  19. The Role of Developmental Screening Practices in Early Diagnosis of Autism Spectrum Disorders: An Analysis of All-Payer Claims Data in New Hampshire

    ERIC Educational Resources Information Center

    Humphreys, Betsy P.

    2013-01-01

    Universal developmental screening during pediatric well child care detects early delays in development and is a critical gateway to early intervention for young children at risk for Autism Spectrum Disorders (ASD). Developmental screening practices are highly variable, and few studies have examined screening utilization for children at risk for…

  20. Developmental Differences in Early Adolescent Aggression: A Gene × Environment × Intervention Analysis

    PubMed Central

    Cleveland, H. Harrington; Vandenbergh, David J.; Feinberg, Mark E.; Neiderhiser, Jenae M.; Greenberg, Mark T.; Spoth, Richard; Redmond, Cleve

    2015-01-01

    Aggression-related problems such as assault and homicide among adolescents and young adults exact considerable social and economic costs. Although progress has been made, additional research is needed to help combat this persistent problem. Several lines of research indicate that parental hostility is an especially potent predictor of adolescent aggression, although most longitudinal research has focused on clarifying the direction of effects. In this study, we used longitudinal data from the PROSPER project (N = 580; 54.8 % female), a primarily rural Caucasian preventative intervention sample, to examine developmental change in early- to mid-adolescent aggressive behavior problems (age 11–16 years). In addition, we examined maternal hostility as a predictor of developmental change in aggression and the PROSPER preventative intervention, designed to reduce substance use and aggression, as a potential influence on this association. Lastly, several studies indicate that variation in the DRD4 7-repeat gene moderates both parenting and intervention influences on externalizing behavior. Accordingly, we examined the potential moderating role of DRD4. As hypothesized, there was a significant maternal hostility by intervention interaction indicating that the intervention reduced the negative impact of maternal hostility on adolescent change in aggressive behavior problems. DRD4 7-repeat status (7+ vs. 7−) further conditioned this association whereby control group 7+ adolescents with hostile mothers showed increasing aggressive behavior problems. In contrast, aggression decreased for 7+ adolescents with similarly hostile mothers in the intervention. Implications for prevention are discussed as well as current perspectives in candidate gene-by-environment interaction research. PMID:25319639

  1. Improvement of the developmental competence of porcine oocytes collected from early antral follicles by cytoplast fusion

    PubMed Central

    DANG-NGUYEN, Thanh Quang; APPELTANT, Ruth; SOMFAI, Tamas; ISHIHARA, Shinya; MEN, Nguyen Thi; SANTOS, Elisa Caroline da Silva; NOGUCHI, Junko; KANEKO, Hiroyuki; KIKUCHI, Kazuhiro

    2016-01-01

    In the present study, we propose an alternative technique called cytoplast fusion to improve the maturation rate and developmental competence of growing oocytes collected from early antral follicles in pigs. We examined whether the fusion of a growing oocyte with the cytoplast from a fully-grown oocyte (CFR group) could better promote maturation and developmental competence of the growing oocyte compared to germinal vesicle (GV) transfer (GVTR group). After 44 h of in vitro maturation (IVM), most growing oocytes (GR group) were still arrested at the GV stage (64.0 ± 5.1%); this number was significantly higher (P < 0.01) than that of the other groups. No matured oocyte was observed in the GR group. The maturation rate of GVTR oocytes was significantly improved (18.8 ± 3.5%) compared with that of growing oocytes. The proportion of oocytes that reached the metaphase-II (M-II) stage in the CFR group (37.8 ± 2.0%) was significantly higher (P < 0.05) than that in the GVTR group, although still lower than that in the control group (75.2 ± 4.4%). No blastocyst was derived from growing oocytes. Among in vitro fertilized GVTR oocytes, 3.0 ± 1.9% developed into blastocysts; however, this percentage showed an insignificant increase compared with the GR group. On the other hand, the percentage of CFR embryos that developed into blastocysts (12.0 ± 4.3%) was significantly higher than that of GR embryos (0.0%), although still lower than that of control embryos (27.0 ± 5.5%). Total cell number in blastocysts in the GVTR group (23.3 ± 6.9) was significantly lower (P < 0.05) than that in the control group (50.4 ± 5.0). Meanwhile, the total cell number in blastocysts derived from CFR oocytes (36.3 ± 4.8) was comparable to that of the control group. In summary, cytoplast fusion significantly improves maturation rate and developmental competence of growing oocytes compared with GV transfer. PMID:27795465

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

    PubMed

    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.

  3. Early Psychosocial Neglect Adversely Impacts Developmental Trajectories of Brain Oscillations and Their Interactions.

    PubMed

    Stamoulis, Catherine; Vanderwert, Ross E; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A

    2015-12-01

    Rhythmicity is a fundamental property of neural activity at multiple spatiotemporal scales, and associated oscillations represent a critical mechanism for communication and transmission of information across brain regions. During development, these oscillations evolve dynamically as a function of neural maturation and may be modulated by early experiences, positive and/or negative. This study investigated the impact of psychosocial deprivation associated with institutional rearing in early life and the effects of subsequent foster care intervention on developmental trajectories of neural oscillations and their cross-frequency correlations. Longitudinally acquired nontask EEGs from three cohorts of children from the Bucharest Early Intervention Project were analyzed. These included abandoned children initially reared in institutions and subsequently randomized to be placed in foster care or receive care as usual (prolonged institutional rearing) and a group of never-institutionalized children. Oscillation trajectories were estimated from 42 to 96 months, that is, 1-3 years after all children in the intervention arm of the study had been placed in foster care. Significant differences between groups were estimated for the amplitude trajectories of cognitive-related gamma, beta, alpha, and theta oscillations. Similar differences were identified as a function of time spent in institutions, suggesting that increased time spent in psychosocial neglect may have profound and widespread effects on brain activity. Significant group differences in cross-frequency coupling were estimated longitudinally between gamma and lower frequencies as well as alpha and lower frequencies. Lower cross-gamma coupling was estimated at 96 months in the group of children that remained in institutions at that age compared to the other two groups, suggesting potentially impaired communication between local and long-distance brain networks in these children. In contrast, higher cross

  4. Early Developmental Changes in Sleep in Infants: The Impact of Maternal Depression

    PubMed Central

    Armitage, Roseanne; Flynn, Heather; Hoffmann, Robert; Vazquez, Delia; Lopez, Juan; Marcus, Sheila

    2009-01-01

    Objectives: This study evaluated whether sleep over the first 6 months of life was more disturbed in infants born to mothers who were depressed compared with infants from nondepressed mothers. Design: Actigraphy was recorded for 7 consecutive days starting at 2 weeks postpartum and monthly thereafter until 6 months of age. Mothers completed daily sleep/wake diaries. Sleep data at 2 weeks and 6 months postpartum are presented here. Setting: The home environment. Participants: Eighteen healthy, full-term infants, 9 males and 9 females. Seven infants were born to women with no personal or family history of depression; 11 infants were born to women diagnosed with depression or with elevated levels of depression symptoms. Interventions: N/A. Measurements and Results: Total sleep time, sleep latency, sleep efficiency, and number and duration of sleep episodes were computed for nocturnal and daytime sleep in each 24-hour block. Data were coded for risk group (1 = low risk, 2 = high risk), and repeated-measures multivariate analysis of variance contrasted changes in sleep measures at Week 2 and Week 24, between risk groups. The high-risk infants took longer to fall asleep, had lower sleep efficiencies, and had more sleep bouts in the nocturnal sleep period than did low-risk infants. These effects persisted at 6 months postpartum. Conclusions: Maternal depression is associated with significant sleep disturbance in infancy at 2 weeks postpartum that continues through 24 weeks. It remains to be determined if sleep disturbance in infancy confers a greater risk of developing early-onset depression in childhood. Citation: Armitage R; Flynn H; Hoffmann R; Vazquez D; Lopez J; Marcus S. Early developmental changes in sleep in infants: the impact of maternal depression. SLEEP 2009;32(5):693-696. PMID:19480236

  5. Developmental and physiological challenges of octopus (Octopus vulgaris) early life stages under ocean warming.

    PubMed

    Repolho, Tiago; Baptista, Miguel; Pimentel, Marta S; Dionísio, Gisela; Trübenbach, Katja; Lopes, Vanessa M; Lopes, Ana Rita; Calado, Ricardo; Diniz, Mário; Rosa, Rui

    2014-01-01

    The ability to understand and predict the effects of ocean warming (under realistic scenarios) on marine biota is of paramount importance, especially at the most vulnerable early life stages. Here we investigated the impact of predicted environmental warming (+3 °C) on the development, metabolism, heat shock response and antioxidant defense mechanisms of the early stages of the common octopus, Octopus vulgaris. As expected, warming shortened embryonic developmental time by 13 days, from 38 days at 18 °C to 25 days at 21 °C. Concomitantly, survival decreased significantly (~29.9 %). Size at hatching varied inversely with temperature, and the percentage of smaller premature paralarvae increased drastically, from 0 % at 18 °C to 17.8 % at 21 °C. The metabolic costs of the transition from an encapsulated embryo to a free planktonic form increased significantly with warming, and HSP70 concentrations and glutathione S-transferase activity levels were significantly magnified from late embryonic to paralarval stages. Yet, despite the presence of effective antioxidant defense mechanisms, ocean warming led to an augmentation of malondialdehyde levels (an indicative of enhanced ROS action), a process considered to be one of the most frequent cellular injury mechanisms. Thus, the present study provides clues about how the magnitude and rate of ocean warming will challenge the buffering capacities of octopus embryos and hatchlings' physiology. The prediction and understanding of the biochemical and physiological responses to warmer temperatures (under realistic scenarios) is crucial for the management of highly commercial and ecologically important species, such as O. vulgaris.

  6. Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents.

    PubMed

    Murphy, M O; Cohn, D M; Loria, A S

    2017-03-01

    The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood.

  7. Prenatal tobacco exposure and self-regulation in early childhood: Implications for developmental psychopathology.

    PubMed

    Wiebe, Sandra A; Clark, Caron A C; De Jong, Desiree M; Chevalier, Nicolas; Espy, Kimberly Andrews; Wakschlag, Lauren

    2015-05-01

    Prenatal tobacco exposure (PTE) has a well-documented association with disruptive behavior in childhood, but the neurocognitive effects of exposure that underlie this link are not sufficiently understood. The present study was designed to address this gap, through longitudinal follow-up in early childhood of a prospectively enrolled cohort with well-characterized prenatal exposure. Three-year-old children (n = 151) were assessed using a developmentally sensitive battery capturing both cognitive and motivational aspects of self-regulation. PTE was related to motivational self-regulation, where children had to delay approach to attractive rewards, but not cognitive self-regulation, where children had to hold information in mind and inhibit prepotent motor responses. Furthermore, PTE predicted motivational self-regulation more strongly in boys than in girls, and when propensity scores were covaried to control for confounding risk factors, the effect of PTE on motivational self-regulation was significant only in boys. These findings suggest that PTE's impact on neurodevelopment may be greater in boys than in girls, perhaps reflecting vulnerability in neural circuits that subserve reward sensitivity and emotion regulation, and may also help to explain why PTE is more consistently related to disruptive behavior disorders than attention problems.

  8. Developmental Trajectories of Disordered Eating from Early Adolescence to Young Adulthood: A Longitudinal Study

    PubMed Central

    Slane, Jennifer D.; Klump, Kelly L.; McGue, Matthew; Iacono, William G.

    2014-01-01

    Objective Research examining changes in eating disorder symptoms across adolescence suggests an increase in disordered eating from early to late adolescence. However, relevant studies have largely been cross-sectional in nature and most have not examined the changes in the attitudinal symptoms of eating disorders (e.g., weight concerns). This longitudinal study aimed to address gaps in the available data by examining the developmental trajectories of disordered eating in females from preadolescence into young adulthood. Method Participants were 745 same-sex female twins from the Minnesota Twin Family Study. Disordered eating was assessed using the Total Score, Body Dissatisfaction subscale, Weight Preoccupation subscale, and a combined Binge Eating and Compensatory Behavior subscale from the Minnesota Eating Behavior Survey assessed at the ages of 11, 14, 18, 21, and 25. Several latent growth models were fit to the data to identify the trajectory that most accurately captures the changes in disordered eating symptoms from 11 to 25 years. Results The best-fitting models for overall levels of disordered eating, body dissatisfaction, and weight preoccupation showed an increase in from 11 through 25 years. In contrast, bulimic behaviors increased to age of 18 and then stabilized to age of 25. Discussion The findings expanded upon extant research by investigating longitudinal, symptom specific, within-person changes and showing an increase in cognitive symptoms into young adulthood and the stability of disordered eating behaviors past late adolescence. PMID:24995824

  9. Young children who commit crime: epidemiology, developmental origins, risk factors, early interventions, and policy implications.

    PubMed

    Loeber, R; Farrington, D P

    2000-01-01

    An early onset of delinquency prior to age 13 years increases the risk of later serious, violent, and chronic offending by a factor of 2-3. Also child delinquents, compared to juveniles who start offending at a later age, tend to have longer delinquent careers. This article summarizes the report of the Office of Juvenile Justice and Delinquency Prevention's Study Group on Very Young Offenders, chaired by Rolf Loeber and David P. Farrington. The Study Group, consisting of 16 scholars and 23 coauthors, worked for 2 years on preparing a report, undertaking extensive secondary data analyses, and writing chapters in different speciality areas. The report consists of a state of the art review of the developmental background of child delinquents. The report also summarizes risk and protective factors in the individual, family, peer group, school, and neighborhood that affect that development. Lastly, the report renews relevant preventive and remedial interventions in the juvenile justice system, families, peer groups, schools. and neighborhoods, and makes a case for improvement in the integration of services for child delinquents. Policy recommendations are presented to improve methods of dealing with child delinquents by juvenile justice, child welfare, and mental health agencies.

  10. Developmental trajectories of prejudice and tolerance toward immigrants from early to late adolescence.

    PubMed

    van Zalk, Maarten Herman Walter; Kerr, Margaret

    2014-10-01

    Adolescence is an important period for the development of relationships between immigrants and non-immigrants, yet little is known about how problematic personality traits affect adolescents' relationships with and attitudes toward immigrants. This work identified the roles of intergroup relationships and one dimension of problematic personality traits, namely callous-unemotional traits, in the development of adolescents' tolerance and prejudice. Three annual measurements of a large community sample (N = 1,542) of non-immigrant adolescents (M age = 15.31 at first measurement; 50.2% girls) were used to show that tolerance and prejudice toward immigrants represent two dimensions with distinct developmental trajectories from early to late adolescence. Callous-unemotional traits predicted fewer decreases in prejudice toward immigrants, yet were not directly associated with tolerance. Intergroup friendships predicted stronger increases in tolerance, which, in turn, predicted decreases in prejudice toward immigrants. Thus, tolerance and prejudice toward immigrants seem to be differentially influenced by social experiences and problematic personality traits.

  11. Screening for Autism in Young Children with Developmental Delay: An Evaluation of the Developmental Behaviour Checklist--Early Screen

    ERIC Educational Resources Information Center

    Gray, K. M.; Tonge, B. J.; Sweeney, D. J.; Einfeld, S. L.

    2008-01-01

    The ability to identify children who require specialist assessment for the possibility of autism at as early an age as possible has become a growing area of research. A number of measures have been developed as potential screening tools for autism. The reliability and validity of one of these measures for screening for autism in young children…

  12. Effects of early developmental conditions on innate immunity are only evident under favourable adult conditions in zebra finches

    NASA Astrophysics Data System (ADS)

    de Coster, Greet; Verhulst, Simon; Koetsier, Egbert; de Neve, Liesbeth; Briga, Michael; Lens, Luc

    2011-12-01

    Long-term effects of unfavourable conditions during development can be expected to depend on the quality of the environment experienced by the same individuals during adulthood. Yet, in the majority of studies, long-term effects of early developmental conditions have been assessed under favourable adult conditions only. The immune system might be particularly vulnerable to early environmental conditions as its development, maintenance and use are thought to be energetically costly. Here, we studied the interactive effects of favourable and unfavourable conditions during nestling and adult stages on innate immunity (lysis and agglutination scores) of captive male and female zebra finches ( Taeniopygia guttata). Nestling environmental conditions were manipulated by a brood size experiment, while a foraging cost treatment was imposed on the same individuals during adulthood. This combined treatment showed that innate immunity of adult zebra finches is affected by their early developmental conditions and varies between both sexes. Lysis scores, but not agglutination scores, were higher in individuals raised in small broods and in males. However, these effects were only present in birds that experienced low foraging costs. This study shows that the quality of the adult environment may shape the long-term consequences of early developmental conditions on innate immunity, as long-term effects of nestling environment were only evident under favourable adult conditions.

  13. Developmental toxicity of PAH mixtures in fish early life stages. Part II: adverse effects in Japanese medaka.

    PubMed

    Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme

    2014-12-01

    In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development.

  14. Skeletal Morphogenesis of Microbrachis and Hyloplesion (Tetrapoda: Lepospondyli), and Implications for the Developmental Patterns of Extinct, Early Tetrapods

    PubMed Central

    Olori, Jennifer C.

    2015-01-01

    The ontogeny of extant amphibians often is used as a model for that of extinct early tetrapods, despite evidence for a spectrum of developmental modes in temnospondyls and a paucity of ontogenetic data for lepospondyls. I describe the skeletal morphogenesis of the extinct lepospondyls Microbrachis pelikani and Hyloplesion longicostatum using the largest samples examined for either taxon. Nearly all known specimens were re-examined, allowing for substantial anatomical revisions that affect the scoring of characters commonly used in phylogenetic analyses of early tetrapods. The palate of H. longicostatum is re-interpreted and suggested to be more similar to that of M. pelikani, especially in the nature of the contact between the pterygoids. Both taxa possess lateral lines, and M. pelikani additionally exhibits branchial plates. However, early and rapid ossification of the postcranial skeleton, including a well-developed pubis and ossified epipodials, suggests that neither taxon metamorphosed nor were they neotenic in the sense of branchiosaurids and salamanders. Morphogenetic patterns in the foot suggest that digit 5 was developmentally delayed and the final digit to ossify in M. pelikani and H. longicostatum. Overall patterns of postcranial ossification may indicate postaxial dominance in limb and digit formation, but also more developmental variation in early tetrapods than has been appreciated. The phylogenetic position and developmental patterns of M. pelikani and H. longicostatum are congruent with the hypothesis that early tetrapods lacked metamorphosis ancestrally and that stem-amniotes exhibited derived features of development, such as rapid and complete ossification of the skeleton, potentially prior to the evolution of the amniotic egg. PMID:26083733

  15. Developmentally dynamic genome: Evidence of genetic influences on increases and decreases in conduct problems from early childhood to adolescence.

    PubMed

    Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi

    2015-05-06

    The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems' developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact.

  16. Excitation–Contraction Coupling of the Mouse Embryonic Cardiomyocyte

    PubMed Central

    Rapila, Risto; Korhonen, Topi; Tavi, Pasi

    2008-01-01

    In the mammalian embryo, the primitive tubular heart starts beating during the first trimester of gestation. These early heartbeats originate from calcium-induced contractions of the developing heart muscle cells. To explain the initiation of this activity, two ideas have been presented. One hypothesis supports the role of spontaneously activated voltage-gated calcium channels, whereas the other emphasizes the role of Ca2+ release from intracellular stores initiating spontaneous intracellular calcium oscillations. We show with experiments that both of these mechanisms coexist and operate in mouse cardiomyocytes during embryonic days 9–11. Further, we characterize how inositol-3-phosphate receptors regulate the frequency of the sarcoplasmic reticulum calcium oscillations and thus the heartbeats. This study provides a novel view of the regulation of embryonic cardiomyocyte activity, explaining the functional versatility of developing cardiomyocytes and the origin and regulation of the embryonic heartbeat. PMID:18794377

  17. Excitation-contraction coupling of the mouse embryonic cardiomyocyte.

    PubMed

    Rapila, Risto; Korhonen, Topi; Tavi, Pasi

    2008-10-01

    In the mammalian embryo, the primitive tubular heart starts beating during the first trimester of gestation. These early heartbeats originate from calcium-induced contractions of the developing heart muscle cells. To explain the initiation of this activity, two ideas have been presented. One hypothesis supports the role of spontaneously activated voltage-gated calcium channels, whereas the other emphasizes the role of Ca(2+) release from intracellular stores initiating spontaneous intracellular calcium oscillations. We show with experiments that both of these mechanisms coexist and operate in mouse cardiomyocytes during embryonic days 9-11. Further, we characterize how inositol-3-phosphate receptors regulate the frequency of the sarcoplasmic reticulum calcium oscillations and thus the heartbeats. This study provides a novel view of the regulation of embryonic cardiomyocyte activity, explaining the functional versatility of developing cardiomyocytes and the origin and regulation of the embryonic heartbeat.

  18. Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender.

    PubMed

    Cong, Xiaomei; Xu, Wanli; Janton, Susan; Henderson, Wendy A; Matson, Adam; McGrath, Jacqueline M; Maas, Kendra; Graf, Joerg

    2016-01-01

    Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05-0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother's own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion

  19. Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender

    PubMed Central

    Xu, Wanli; Janton, Susan; Henderson, Wendy A.; Matson, Adam; McGrath, Jacqueline M.; Maas, Kendra; Graf, Joerg

    2016-01-01

    Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05–0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother’s own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion

  20. Effects of Substrate Mechanics on Contractility of Cardiomyocytes Generated from Human Pluripotent Stem Cells

    PubMed Central

    Hazeltine, Laurie B.; Simmons, Chelsey S.; Salick, Max R.; Lian, Xiaojun; Badur, Mehmet G.; Han, Wenqing; Delgado, Stephanie M.; Wakatsuki, Tetsuro; Crone, Wendy C.; Pruitt, Beth L.; Palecek, Sean P.

    2012-01-01

    Human pluripotent stem cell (hPSC-) derived cardiomyocytes have potential applications in drug discovery, toxicity testing, developmental studies, and regenerative medicine. Before these cells can be reliably utilized, characterization of their functionality is required to establish their similarity to native cardiomyocytes. We tracked fluorescent beads embedded in 4.4–99.7 kPa polyacrylamide hydrogels beneath contracting neonatal rat cardiomyocytes and cardiomyocytes generated from hPSCs via growth-factor-induced directed differentiation to measure contractile output in response to changes in substrate mechanics. Contraction stress was determined using traction force microscopy, and morphology was characterized by immunocytochemistry for α-actinin and subsequent image analysis. We found that contraction stress of all types of cardiomyocytes increased with substrate stiffness. This effect was not linked to beating rate or morphology. We demonstrated that hPSC-derived cardiomyocyte contractility responded appropriately to isoprenaline and remained stable in culture over a period of 2 months. This study demonstrates that hPSC-derived cardiomyocytes have appropriate functional responses to substrate stiffness and to a pharmaceutical agent, which motivates their use in further applications such as drug evaluation and cardiac therapies. PMID:22649451

  1. Developmental Surveillance and Screening Practices by Pediatric Primary Care Providers: Implications for Early Intervention Professionals

    ERIC Educational Resources Information Center

    Porter, Sallie; Qureshi, Rubab; Caldwell, Barbara Ann; Echevarria, Mercedes; Dubbs, William B.; Sullivan, Margaret W.

    2016-01-01

    This study used a survey approach to investigate current developmental surveillance and developmental screening practices by pediatric primary care providers in a diverse New Jersey county. A total of 217 providers were contacted with a final sample size of 57 pediatric primary care respondents from 13 different municipalities. Most providers…

  2. Biological and Environmental Correlates of Developmental Outcomes of Prematurely Born Infants in Early Adolescence.

    ERIC Educational Resources Information Center

    Levy-Shiff, Rachel; And Others

    1994-01-01

    Examined the role of biological factors, such as perinatal complications, and psychological factors, such as maternal attitudes, in predicting developmental outcomes in preterm children. Findings support the main effects model of biological and environmental factors in explaining developmental psychopathology, but also the interactional model, as…

  3. Developmentally Universal Practice: Visioning Innovative Early Childhood Pedagogy for Meeting the Needs of Diverse Learners

    ERIC Educational Resources Information Center

    Harris, Kathleen I.

    2015-01-01

    Although developmentally appropriate practice (DAP) has strong merits, there are considerations pertaining to its development and implementation which must be raised. In order for educators to include diverse voices of young children, the time has come for a new conversation to unfold introducing developmentally universal practice (DUP). With this…

  4. Examining Parents' Experiences and Information Needs Regarding Early Identification of Developmental Delays: Qualitative Research to Inform a Public Health Campaign

    PubMed Central

    Raspa, Melissa; Levis, Denise M.; Kish-Doto, Julia; Wallace, Ina; Rice, Catherine; Barger, Brian; Green, Katie K.; Wolf, Rebecca B.

    2015-01-01

    Objective The purpose of this study was to assess the approach and materials of Centers for Disease Control and Prevention's “Learn the Signs. Act Early.” (LTSAE) health education campaign, which aims to improve awareness of developmental milestones and early warning signs of developmental delay among parents of young children. Methods We conducted 2 phases of qualitative research. Focus groups assessed the campaign's objectives by exploring the experiences of parents with children who have developmental delays or disabilities to determine facilitators of and barriers to identification. In-depth interviews were conducted with parents of typically developing children, who reviewed campaign materials and provided feedback on appropriateness, appeal, and clarity with regard to the campaign's objectives. Results Phase 1: Parents were typically the first to express concern about their child's development, and most talked with their child's health care provider. Two categories of health care providers emerged: those who proactively asked about a child's development, used tools to facilitate conversations, and made referrals, and those who did not ask about development, told parents to “wait and see,” and did not provide information about services and supports. Few parents knew about special education services before identification. Phase 2: Participants found the campaign materials appealing, but were unclear about how to act early and why acting early was important. Conclusions Results affirmed LTSAE's evidence-based approach to educating parents about child development. Additional campaign considerations include providing more information about how to act early and why acting early is important and enhancing outreach to providers to help them communicate with concerned parents. PMID:26414090

  5. Acute CO2 tolerance during the early developmental stages of four marine teleosts.

    PubMed

    Kikkawa, T; Ishimatsu, A; Kita, J

    2003-12-01

    Ocean sequestration of CO2 is proposed as a possible measure to mitigate climate changes caused by increasing atmospheric concentrations of the gas, but its impact on the marine ecosystem is unknown. We investigated the acute lethal effect of CO2 during the early developmental stages of four marine teleosts: red sea bream (Pagrus major), Japanese whiting (Sillago japonica), Japanese flounder (Paralichthys olivaceus), and eastern little tuna (Euthynnus affinis). The percentages of larvae that hatched and survived were not affected by exposure to water with a PCO2 of 1.0 kPa (= 7.5 mmHg) within 24 h. Median lethal PCO2 values for a 360-min exposure were 1.4 kPa (cleavage), 5.1 kPa (embryo), 7.3 kPa (preflexion), 4.2 kPa (flexion), 4.6 kPa (postflexion), and 2.5 kPa (juvenile) for red sea bream; 2.4 kPa (cleavage), 4.9 kPa (embryo), 5.9 kPa (preflexion), 6.1 kPa (flexion), 4.1 kPa (postflexion), and 2.7 kPa (juvenile) for Japanese whiting; 2.8 kPa (cleavage) and > 7.0 kPa (young) for Japanese flounder; and 11.8 kPa (cleavage) for eastern little tuna. Red sea bream and Japanese whiting of all ontogenetic stages had similar susceptibilities to CO2: the most susceptible stages were cleavage and juvenile, whereas the most tolerant stages were preflexion and flexion.

  6. Detection of differentially expressed genes in the early developmental stage of the mouse mandible.

    PubMed

    Yamaza, H; Matsuo, K; Kiyoshima, T; Shigemura, N; Kobayashi, I; Wada, H; Akamime, A; Sakai, H

    2001-06-01

    We previously examined the development of the mouse mandible, and demonstrated that odontogenesis occurs between embryonic day 10.5 (E10.5) and E12. Based on the histological findings, we performed cDNA subtraction between the E10.5 and E12 mandibles to detect any differentially expressed genes which might be involved in the initiation of odontogenesis. By sequencing, homology search and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), we thus found Pgk-1, Ccte, Hsp86, Nucleolin, Hsc73, Frg1, N-ras, Set alpha and Hsj2 from the E10.5 mandible, and E25, ATPase6, Mum2, Thymosin beta4 and L21 from the E12 mandible to be differentially expressed genes. These genes are functionally related to protein transport, signal transduction, transcription, translation and molecular chaperon activity. In situ hybridization analyses of Set alpha and E25 showed that Set alpha was detected in the tooth germ at E12 and E14.5, thus indicating a close relationship of this gene to odontogenesis. Meanwhile, the in situ signal of E25 was found in the muscular layer of the tongue, thus suggesting E25 to be related to the differentiation of muscular tissue. In conclusion, we found 15 differentially expressed genes in the course of the early developmental stage of the mouse mandible using a combination of the cDNA subtraction and semi-quantitative RT-PCR methods, while in addition, two genes were demonstrated to be related to the initiation and the development of both tooth germ and the tongue according to the in situ hybridization technique.

  7. Evidence for a Critical Role of Catecholamines for Cardiomyocyte Lineage Commitment in Murine Embryonic Stem Cells

    PubMed Central

    Lehmann, Martin; Nguemo, Filomain; Wagh, Vilas; Pfannkuche, Kurt; Hescheler, Jürgen; Reppel, Michael

    2013-01-01

    Catecholamine release is known to modulate cardiac output by increasing heart rate. Although much is known about catecholamine function and regulation in adults, little is known about the presence and role of catecholamines during heart development. The present study aimed therefore to evaluate the effects of different catecholamines on early heart development in an in vitro setting using embryonic stem (ES) cell-derived cardiomyocytes. Effects of catecholamine depletion induced by reserpine were examined in murine ES cells (line D3, αPIG44) during differentiation. Cardiac differentiation was assessed by immunocytochemistry, qRT-PCR, quantification of beating clusters, flow cytometry and pharmacological approaches. Proliferation was analyzed by EB cross-section measurements, while functionality of cardiomyocytes was studied by extracellular field potential (FP) measurements using microelectrode arrays (MEAs). To further differentiate between substance-specific effects of reserpine and catecholamine action via α- and β-receptors we proved the involvement of adrenergic receptors by application of unspecific α- and β-receptor antagonists. Reserpine treatment led to remarkable down-regulation of cardiac-specific genes, proteins and mesodermal marker genes. In more detail, the average ratio of ∼40% spontaneously beating control clusters was significantly reduced by 100%, 91.1% and 20.0% on days 10, 12, and 14, respectively. Flow cytometry revealed a significant reduction (by 71.6%, n = 11) of eGFP positive CMs after reserpine treatment. By contrast, reserpine did not reduce EB growth while number of neuronal cells in reserpine-treated EBs was significantly increased. MEA measurements of reserpine-treated EBs showed lower FP frequencies and weak responsiveness to adrenergic and muscarinic stimulation. Interestingly we found that developmental inhibition after α- and β-adrenergic blocker application mimicked developmental changes with reserpine. Using several

  8. Developmental competence of bovine early embryos depends on the coupled response between oxidative and endoplasmic reticulum stress.

    PubMed

    Yoon, Seung-Bin; Choi, Seon-A; Sim, Bo-Woong; Kim, Ji-Su; Mun, Seong-Eun; Jeong, Pil-Soo; Yang, Hae-Jun; Lee, Youngjeon; Park, Young-Ho; Song, Bong-Seok; Kim, Young-Hyun; Jeong, Kang-Jin; Huh, Jae-Won; Lee, Sang-Rae; Kim, Sun-Uk; Chang, Kyu-Tae

    2014-05-01

    The stress produced by the coupling of reactive oxygen species (ROS) and endoplasmic reticulum (ER) has been explored extensively, but little is known regarding their roles in the early development of mammalian embryos. Here, we demonstrated that the early development of in vitro-produced (IVP) bovine embryos was governed by the cooperative action between ROS and ER stress. Compared with the tension produced by 5% O2, 20% O2 significantly decreased the blastocyst formation rate and cell survival, which was accompanied by increases in ROS and in levels of sXBP-1 transcript, which is an ER stress indicator. In addition, treatment with glutathione (GSH), a ROS scavenger, decreased ROS levels, which resulted in increased blastocyst formation and cell survival rates. Importantly, levels of sXBP-1 and ER stress-associated transcripts were reduced by GSH treatment in developing bovine embryos. Consistent with this observation, tauroursodeoxycholate (TUDCA), an ER stress inhibitor, improved blastocyst developmental rate, trophectoderm proportion, and cell survival. Moreover, ROS and sXBP-1 transcript levels were markedly decreased by supplementation with TUDCA, suggesting a possible mechanism governing the mutual regulation between ROS and ER stress. Interestingly, knockdown of XBP-1 transcripts resulted in both elevation of ROS and decrease of antioxidant transcripts, which ultimately reduced in vitro developmental competence of bovine embryos. Based on these results, in vitro developmental competence of IVP bovine embryos was highly dependent on the coupled response between oxidative and ER stresses. These results increase our understanding of the mechanism(s) governing early embryonic development and may improve strategies for the generation of IVP embryos with high developmental competence.

  9. EMOTIONAL AVAILABILITY IN EARLY MOTHER-CHILD INTERACTIONS FOR CHILDREN WITH AUTISM SPECTRUM DISORDERS, OTHER PSYCHIATRIC DISORDERS, AND DEVELOPMENTAL DELAY.

    PubMed

    Gul, Hesna; Erol, Nese; Akin, Duygu Pamir; Gullu, Belgin Ustun; Akcakin, Melda; Alpas, Başak; Öner, Özgür

    2016-01-01

    Emotional availability (EA) is a method to assess early parent-child dyadic interactions for emotional awareness, perception, experience, and expression between child and parent that describe global relational quality (Z. Biringen & M. Easterbrooks, 2012). The current study aimed to examine the effects of an infant's diagnosis of autism spectrum disorders (ASDs), other psychiatric disorders (OPD), and developmental delay (DD) on the maternal EA Scale (EAS; Z. Biringen & M. Easterbrooks, 2012; Z. Biringen, J.L. Robinson, & R.N. Emde, 2000) scores and the relative contributions of infant's age, gender, diagnosis, developmental level, and maternal education on EAS scores in a clinical Turkish sample. Three hundred forty-five infant-mother dyads participated in this study. Results of the research indicated that EAS adult scores were associated with maternal education and infant's diagnosis whereas child scores were associated with infant's age, diagnosis, and developmental level. Infants' involvement and responsiveness to the mother were lower in the group with ASD. Children with OPD, particularly when their mothers have lower education, might be at increased risk of having problems in parent-child interactions. Young ASD subjects with developmental delay are in greatest need of support to increase reactions toward their mother. These findings underscore the importance of using all of the EA dimensions rather than only one measure on children in high-risk populations.

  10. Early oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca(2+) transporters in HL-1 cardiomyocytes.

    PubMed

    Asensio-López, Mari C; Soler, Fernando; Sánchez-Más, Jesús; Pascual-Figal, Domingo; Fernández-Belda, Francisco; Lax, Antonio

    2016-03-15

    In atrial-derived HL-1 cells, ryanodine receptor and Na(+)/Ca(2+)-exchanger were altered early by 5 μM doxorubicin. The observed effects were an increase of cytosolic Ca(2+) at rest, ensuing ryanodine receptor phosphorylation, and the slowing of Ca(2+) transient decay after caffeine addition. Doxorubicin triggered a linear rise of reactive oxygen species (ROS) with no early effect on mitochondrial inner membrane potential. Doxorubicin and ROS were both detected in mitochondria by colocalization with fluorescence probes and doxorubicin-induced ROS was totally blocked by mitoTEMPO. The NADPH oxidase activity in the mitochondrial fraction was sensitive to inhibition by GKT137831, and doxorubicin-induced ROS decreased gradually as the GKT137831 concentration added in preincubation was increased. When doxorubicin-induced ROS was prevented by GKT137831, the kinetic response revealed a permanent degree of protection that was consistent with mitochondrial NADPH oxidase inhibition. In contrast, the ROS induction by doxorubicin after melatonin preincubation was totally eliminated at first but the effect was completely reversed with time. Limiting the source of ROS production is a better alternative for dealing with oxidative damage than using ROS scavengers. The short-term effect of doxorubicin on Ca(2+) transporters involved in myocardiac contractility was dependent on oxidative damage, and so the impairment was subsequent to ROS production.

  11. Developmental Links Between Children's Working Memory and their Social Relations with Teachers and Peers in the Early School Years.

    PubMed

    de Wilde, Amber; Koot, Hans M; van Lier, Pol A C

    2016-01-01

    This study assessed the developmental links between children's working memory development and their relations with teachers and peers across 2 years of kindergarten and early elementary school. Kindergarten and first grade children, N = 1109, 50% boys, were followed across 2 school-years. Children were assessed across 3 waves, in the fall and spring of the first school-year (within school-year), and finally in the spring of the second school-year. Working memory was assessed using a visuo-spatial working memory task. The developmental links between working memory and child-reported teacher-child relationship quality (warmth and conflict) and peer-nominated likeability and friendedness were assessed using autoregressive cross-lagged models. Lower working memory scores were related to increases in teacher-child conflict and decreases in teacher-child warmth one school-year later, in addition to decreases in likeability by peers within the same school-year. Conversely, teacher-child conflict was negatively associated with the development of working memory across the studied period. Path estimates between working memory and social relational factors were similar for boys and girls. Findings show developmental links between working memory and social-relational factors and vice versa. These results suggest that children's working memory development can be fostered through pro-social relations with teachers in early elementary school children.

  12. Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health.

    PubMed

    Garner, Andrew S; Shonkoff, Jack P

    2012-01-01

    Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.

  13. DEFINING RELATIONAL PATHOLOGY IN EARLY CHILDHOOD: THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD DC:0-5 APPROACH.

    PubMed

    Zeanah, Charles H; Lieberman, Alicia

    2016-09-01

    Infant mental health is explicitly relational in its focus, and therefore a diagnostic classification system for early childhood disorders should include attention not only to within-the-child psychopathology but also between child and caregiver psychopathology. In this article, we begin by providing a review of previous efforts to introduce this approach that date back more than 30 years. Next, we introduce changes proposed in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood DC:0-5 (ZERO TO THREE, in press). In a major change from previous attempts, the DC:0-5 includes an Axis I "Relationship Specific Disorder of Early Childhood." This disorder intends to capture disordered behavior that is limited to one caregiver relationship rather than cross contextually. An axial characterization is continued from the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood DC:0-3R (ZERO TO THREE, 2005), but two major changes are introduced. First, the DC:0-5 proposes to simplify ratings of relationship adaptation/maladaptation, and to expand what is rated so that in addition to characterizing the child's relationship with his or her primary caregiver, there also is a characterization of the network of family relationships in which the child develops. This includes coparenting relationships and the entire network of close relationships that impinge on the young child's development and adaptation.

  14. Emotional Self-Regulation, Peer Rejection, and Antisocial Behavior: Developmental Associations from Early Childhood to Early Adolescence

    ERIC Educational Resources Information Center

    Trentacosta, Christopher J.; Shaw, Daniel S.

    2009-01-01

    This study examined relations among emotional self-regulation, peer rejection, and antisocial behavior in a sample of 122 boys from low-income families who participated in a summer camp and were followed longitudinally from early childhood to early adolescence. Emotional self-regulation strategies were coded in early childhood from a waiting task,…

  15. Promoting the "3Rs" principle in developmental biology with early and convenient diagnosis of pregnancy in mice.

    PubMed

    Seaborn, Tommy; Moulin, Julie-Alexandra; Côté, Mélissa; Tremblay, Yves

    2011-10-01

    The 3Rs stand for Replacement of animals in experiments, Reduction in the number of experimental animals, and Refinement of experiments to minimize animal pain and stress. We propose to address Reduction and Refinement in the use of mice as experimental models in developmental research. This study focuses on the maternal percentage of weight increase at gestational day 8 (%WI(GD8)) to diagnose pregnancy early in BALB/c mice. We documented sensitivity, specificity, false positive and negative rates and probability of pregnancy associated with %WI(GD8). This predictive model of pregnancy allows for significant reduction in the number of mice to be sacrificed in developmental research. Reported observations and literature suggest that this model is independent of litter size and should be applicable to other mice strains. This procedure allows mice pregnancy detection before midgestation and proposes an ethically sound approach to experimental animal use by optimizing the number of mice used and refining animal manipulation.

  16. A Longitudinal Twin Study of Fears From Middle Childhood to Early Adulthood: Evidence for a Developmentally Dynamic Genome

    PubMed Central

    Kendler, Kenneth S.; Gardner, Charles O.; Annas, Peter; Neale, Michael C.; Eaves, Lindon J.; Lichtenstein, Paul

    2009-01-01

    Context While the nature of common fears changes over development, we do not know whether genetic effects on fear-proneness are developmentally stable or developmentally dynamic. Objective To determine the temporal pattern of genetic and environmental effects on the level of intensity of common fears. Design Prospective, 4-wave longitudinal twin study. Structural modeling was performed with Mx. Setting General community. Participants Two thousand four hundred ninety twins and their parents from the Swedish Twin Study of Child and Adolescent Development. Main Outcome Measure The level of parent- and/or self-reported fears obtained at ages 8 to 9, 13 to 14, 16 to 17, and 19 to 20 years. Results Thirteen questionnaire items formed 3 distinct fear factors: situational, animal, and blood/injury. For all 3 fears, the best-fit model revealed developmentally dynamic effects and, in particular, evidence for both genetic attenuation and innovation. That is, genetic factors influencing fear intensity at age 8 to 9 years decline substantially in importance over time. Furthermore, new sets of genetic risk factors impacting fear intensity “come on line” in early adolescence, late adolescence, and early adulthood. As the twins aged, the influence of the shared environment declined and unique environment increased. No sex effects were found for situational fears while for animal and blood/injury fears, genetic factors in males and females were correlated but not identical. Shared environmental factors were both more important and more stable for animal fears than for situational or blood/injury fears. Conclusions Genetic effects on fear are developmentally dynamic from middle childhood to young adulthood. As children age, familial-environmental influences on fears decline in importance. PMID:18391130

  17. The CASA Trauma and Attachment Group (TAG) Program for Children who have Attachment Issues Following Early Developmental Trauma

    PubMed Central

    Ashton, Chandra K.; O’Brien-Langer, Anna; Silverstone, Peter H.

    2016-01-01

    Objective: There is relatively little research about effective therapeutic approaches for children in middle childhood who have attachment related diagnoses as a result of experiencing significant, early developmental trauma. This study describes findings from an intensive, dyad-based intervention, aimed at stabilizing attachment relationships with primary caregivers, increasing caregiver reflective function skills, and reducing children’s trauma-related behavioural sequelae. Method: We analyzed retrospective data from 51 caregiver/child dyads who participated in the Trauma and Attachment Group (TAG) Program from September 2011–December 2014. This data included pre- and post-intervention scores retrieved from the Parenting Relationship Questionnaire (PRQ), the Parent Report of Post-Traumatic Stress Symptoms (PROPS), and the Parental Reflective Functioning Questionnaire (PRFQ-1) Results: The preliminary findings show statistically significant improvements in attachment, communication, discipline practices, involvement, and relational frustration. Additionally there were statistically significant improvements in parental reflective functioning, and a trend towards a reduction in symptoms typical of post-traumatic stress disorder. Conclusion: Poor quality or inconsistent interactions with early caregivers can lead to life-long impairments in physical and mental health. This intensive program shows potential as a way to improve longer-term outcomes for children exposed to early developmental trauma. Longer-term research is required to further substantiate outcomes, appraise cost analysis, as well as to consider evaluation with appropriate comparison groups. PMID:27047555

  18. Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance.

    PubMed

    Gonzalez-Bulnes, Antonio; Astiz, Susana; Ovilo, Cristina; Lopez-Bote, Clemente J; Sanchez-Sanchez, Raul; Perez-Solana, Maria L; Torres-Rovira, Laura; Ayuso, Miriam; Gonzalez, Jorge

    2014-10-01

    Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre- and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity.

  19. Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1

    PubMed Central

    Champhekar, Ameya; Damle, Sagar S.; Freedman, George; Carotta, Sebastian; Nutt, Stephen L.

    2015-01-01

    The ETS family transcription factor PU.1 is essential for the development of several blood lineages, including T cells, but its function in intrathymic T-cell precursors has been poorly defined. In the thymus, high PU.1 expression persists through multiple cell divisions in early stages but then falls sharply during T-cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it has remained unknown how PU.1 activities could contribute positively to T-cell development. Here we employed conditional knockout and modified antagonist PU.1 constructs to perturb PU.1 function stage-specifically in early T cells. We show that PU.1 is needed for full proliferation, restricting access to some non-T fates, and controlling the timing of T-cell developmental progression such that removal or antagonism of endogenous PU.1 allows precocious access to T-cell differentiation. Dominant-negative effects reveal that this repression by PU.1 is mediated indirectly. Genome-wide transcriptome analysis identifies novel targets of PU.1 positive and negative regulation affecting progenitor cell signaling and cell biology and indicating distinct regulatory effects on different subsets of progenitor cell transcription factors. Thus, in addition to supporting early T-cell proliferation, PU.1 regulates the timing of activation of the core T-lineage developmental program. PMID:25846797

  20. Two dimensional electrophysiological characterization of human pluripotent stem cell-derived cardiomyocyte system

    PubMed Central

    Zhu, Huanqi; Scharnhorst, Kelsey S.; Stieg, Adam Z.; Gimzewski, James K.; Minami, Itsunari; Nakatsuji, Norio; Nakano, Haruko; Nakano, Atsushi

    2017-01-01

    Stem cell-derived cardiomyocytes provide a promising tool for human developmental biology, regenerative therapies, disease modeling, and drug discovery. As human pluripotent stem cell-derived cardiomyocytes remain functionally fetal-type, close monitoring of electrophysiological maturation is critical for their further application to biology and translation. However, to date, electrophysiological analyses of stem cell-derived cardiomyocytes has largely been limited by biologically undefined factors including 3D nature of embryoid body, sera from animals, and the feeder cells isolated from mouse. Large variability in the aforementioned systems leads to uncontrollable and irreproducible results, making conclusive studies difficult. In this report, a chemically-defined differentiation regimen and a monolayer cell culture technique was combined with multielectrode arrays for accurate, real-time, and flexible measurement of electrophysiological parameters in translation-ready human cardiomyocytes. Consistent with their natural counterpart, amplitude and dV/dtmax of field potential progressively increased during the course of maturation. Monolayer culture allowed for the identification of pacemaking cells using the multielectrode array platform and thereby the estimation of conduction velocity, which gradually increased during the differentiation of cardiomyocytes. Thus, the electrophysiological maturation of the human pluripotent stem cell-derived cardiomyocytes in our system recapitulates in vivo development. This system provides a versatile biological tool to analyze human heart development, disease mechanisms, and the efficacy/toxicity of chemicals. PMID:28266620

  1. Global Perspective on Early Diagnosis and Intervention for Children with Developmental Delays and Disabilities

    ERIC Educational Resources Information Center

    Scherzer, Alfred L.; Chhagan, Meera; Kauchali, Shuaib; Susser, Ezra

    2012-01-01

    Low- and middle-income countries are experiencing a significant reduction in mortality of children under 5 years of age. This reduction is bringing in its wake large numbers of surviving children with developmental delays and disabilities. Very little attention has been paid to these children, most of whom receive minimal or no support. Thus,…

  2. Early Domain-Specific Knowledge? Nonlinear Developmental Trajectories Further Erode a House of Sand

    ERIC Educational Resources Information Center

    Deak, Gedeon O.

    2011-01-01

    Rakison and Yermolayeva (this issue) argue that domain specificity is difficult to reconcile with U-, N-, or M-shaped developmental trends. They are justified because: (1) There is no compelling evidence that nonlinear trends require mechanisms beyond general, well-known cognitive processes; and (2) epigenetic neuroscience provides no clear…

  3. The Role of Early Childhood Personality in the Developmental Course of Social Adjustment

    ERIC Educational Resources Information Center

    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…

  4. Developmental Trajectories of Perceived Friendship Intimacy, Constructive Problem Solving, and Depression from Early to Late Adolescence

    ERIC Educational Resources Information Center

    Selfhout, M. H. W.; Branje, S. J. T.; Meeus, W. H. J.

    2009-01-01

    This study examined friendship types in developmental trajectories of perceived closeness and balanced relatedness. In addition, differences between friendship types in the development of constructive problem solving and depression were examined. Questionnaire data of five annual waves were used from two adolescent cohorts (cohort 1: M = 12.41…

  5. Developmental Trajectories of Depressive Symptoms from Early Childhood to Late Adolescence: Gender Differences and Adult Outcome

    ERIC Educational Resources Information Center

    Dekker, Marielle C.; Ferdinand, Robert F.; van Lang, Natasja D. J.; Bongers, Ilja L.; van der Ende, Jan; Verhulst, Frank C.

    2007-01-01

    Background: Limited information is available on gender differences and young-adult poor outcome in children and adolescents following distinct developmental trajectories of depressive symptoms. Methods: Parent information on depressive symptoms of 4- to 18-year-olds from an ongoing Dutch community-based longitudinal multiple-cohort study (N =…

  6. Early Intervention for Developmental Functioning: A Quantitative Synthesis of Single-Subject Research.

    ERIC Educational Resources Information Center

    Scruggs, Thomas E.; And Others

    1988-01-01

    Reviewed are 14 studies employing single-subject methodology to investigate the results of interventions to improve developmental functioning in handicapped preschoolers. Interventions included treatments to develop physical responsiveness, increase feeding behavior, and decrease rumination or compulsive vomiting. Knowledge concerning the…

  7. Long-Term Follow-up Study of Children Developmentally Retarded by Early Environmental Deprivation.

    ERIC Educational Resources Information Center

    Fujinaga, Tamotsu; And Others

    This paper reports on a 14-year follow-up study of two developmentally retarded Japanese children, a brother and sister, who had been kept shut up in a small shack before being rescued (at ages 5 and 6 respectively). Following birth they consistently suffered malnutrition, maternal deprivation, social isolation from adults, language deprivation,…

  8. Information Management Strategies in Early Adolescence: Developmental Change in Use and Transactional Associations with Psychological Adjustment

    ERIC Educational Resources Information Center

    Laird, Robert D.; Marrero, Matthew D.; Melching, Jessica A.; Kuhn, Emily S.

    2013-01-01

    Adolescents use various strategies to manage their parents' access to information. This study tested developmental change in strategy use, longitudinal associations between disclosing and concealing strategies, and longitudinal associations linking disclosing and concealing strategies with antisocial behavior and depressive symptoms. Self-report…

  9. Child Maltreatment and Children's Developmental Trajectories in Early to Middle Childhood

    ERIC Educational Resources Information Center

    Font, Sarah A.; Berger, Lawrence M.

    2015-01-01

    Associations between experiencing child maltreatment and adverse developmental outcomes are widely studied, yet conclusions regarding the extent to which effects are bidirectional, and whether they are likely causal, remain elusive. This study uses the Fragile Families and Child Wellbeing Study, a birth cohort of 4,898 children followed from birth…

  10. Early Childhood Predictors of Mothers' and Fathers' Relationships with Adolescents with Developmental Disabilities

    ERIC Educational Resources Information Center

    Mitchell, D. B.; Hauser-Cram, P.

    2010-01-01

    Background: The importance of positive parent-adolescent relationships is stressed in research on adolescents, although very little is known about this relationship when a teen has developmental disabilities (DD). We investigated the relationships of adolescents with disabilities with their mothers and their fathers in order to answer a number of…

  11. Parental Practices and Developmental Challenges of Boys of Color: Opportunities for Early Intervention

    ERIC Educational Resources Information Center

    Barbarin, Oscar A.

    2015-01-01

    The "My Brother's Keeper" Initiative (Obama, 2014) has helped to attract public attention to the vulnerabilities faced by many boys of color (BOC). In this article, I review what is known about the developmental status of BOC, identify key family practices that are critical to their development, and consider the implications of both for…

  12. Comparative study of early childhood high-function autism and developmental mixed receptive-expressive language disorder.

    PubMed

    Yang, Pinchen; Jong, Yuh-Jyh; Hsu, Hsiu-Yi; Chen, Cheng-Sheng

    2004-01-01

    Verbal cognitive profile and general social functioning were compared between two groups of children aged 5 to 7 years, one with high-function autism and the other with developmental mixed receptive-expressive language disorders. The two groups, totaling 50 children, were matched for age and non-verbal IQ (mean, 90). Both groups had impaired verbal cognitive profile and social adaptive functioning, with no statistically significant differences between the two groups. The implications of our findings are discussed. Current preschool and early childhood medical-educational intervention programs in Taiwan must design and implement curricula in which children with language delay, whether autistic or/not, can develop essential social skills.

  13. Local Ca2+ releases enable rapid heart rates in developing cardiomyocytes

    PubMed Central

    Korhonen, Topi; Rapila, Risto; Ronkainen, Veli-Pekka; Koivumäki, Jussi T; Tavi, Pasi

    2010-01-01

    The ability to generate homogeneous intracellular Ca2+ oscillations at high frequency is the basis of the rhythmic contractions of mammalian cardiac myocytes. While the specific mechanisms and structures enabling homogeneous high-frequency Ca2+ signals in adult cardiomyocytes are well characterized, it is not known how these kind of Ca2+ signals are produced in developing cardiomyocytes. Here we investigated the mechanisms reducing spatial and temporal heterogeneity of cytosolic Ca2+ signals in mouse embryonic ventricular cardiomyocytes. We show that in developing cardiomyocytes the propagating Ca2+ signals are amplified in cytosol by local Ca2+ releases. Local releases are based on regular 3-D sarcoplasmic reticulum (SR) structures containing SR Ca2+ uptake ATPases (SERCA) and Ca2+ release channels (ryanodine receptors, RyRs) at regular intervals throughout the cytosol. By evoking [Ca2+]i-induced Ca2+ sparks, the local release sites promote a 3-fold increase in the cytosolic Ca2+ propagation speed. We further demonstrate by mathematical modelling that without these local release sites the developing cardiomyocytes lose their ability to generate homogeneous global Ca2+ signals at a sufficiently high frequency. The mechanism described here is robust and indispensable for normal mammalian cardiomyocyte function from the first heartbeats during the early embryonic phase till terminal differentiation after birth. These results suggest that local cytosolic Ca2+ releases are indispensable for normal cardiomyocyte development and function of developing heart. PMID:20211983

  14. Local Ca2+ releases enable rapid heart rates in developing cardiomyocytes.

    PubMed

    Korhonen, Topi; Rapila, Risto; Ronkainen, Veli-Pekka; Koivumäki, Jussi T; Tavi, Pasi

    2010-05-01

    The ability to generate homogeneous intracellular Ca(2+) oscillations at high frequency is the basis of the rhythmic contractions of mammalian cardiac myocytes. While the specific mechanisms and structures enabling homogeneous high-frequency Ca(2+) signals in adult cardiomyocytes are well characterized, it is not known how these kind of Ca(2+) signals are produced in developing cardiomyocytes. Here we investigated the mechanisms reducing spatial and temporal heterogeneity of cytosolic Ca(2+) signals in mouse embryonic ventricular cardiomyocytes. We show that in developing cardiomyocytes the propagating Ca(2+) signals are amplified in cytosol by local Ca(2+) releases. Local releases are based on regular 3-D sarcoplasmic reticulum (SR) structures containing SR Ca(2+) uptake ATPases (SERCA) and Ca(2+) release channels (ryanodine receptors, RyRs) at regular intervals throughout the cytosol. By evoking [Ca(2+)](i)-induced Ca(2+) sparks, the local release sites promote a 3-fold increase in the cytosolic Ca(2+) propagation speed. We further demonstrate by mathematical modelling that without these local release sites the developing cardiomyocytes lose their ability to generate homogeneous global Ca(2+) signals at a sufficiently high frequency. The mechanism described here is robust and indispensable for normal mammalian cardiomyocyte function from the first heartbeats during the early embryonic phase till terminal differentiation after birth. These results suggest that local cytosolic Ca(2+) releases are indispensable for normal cardiomyocyte development and function of developing heart.

  15. Emotional Self-Regulation, Peer Rejection, and Antisocial Behavior: Developmental Associations from Early Childhood to Early Adolescence

    PubMed Central

    Trentacosta, Christopher J.; Shaw, Daniel S.

    2009-01-01

    This study examined relations among emotional self-regulation, peer rejection, and antisocial behavior in a sample of 122 boys from low-income families who participated in a summer camp and were followed longitudinally from early childhood to early adolescence. Emotional self- regulation strategies were coded in early childhood from a waiting task, measures of peer rejection were collected during middle childhood at the summer camp, and reports of antisocial behavior were obtained during early adolescence. Structural equation modeling was utilized to examine longitudinal relations among these constructs, with results supporting a negative association between use of active distraction and peer rejection and a positive association between peer rejection and antisocial behavior. Furthermore, an indirect effect of active distraction on antisocial behavior was found through peer rejection. Thus, adaptive self-regulation strategy use in early childhood demonstrated direct longitudinal relations with peer rejection and an indirect association with antisocial behavior in early adolescence. Results have implications for early prevention and intervention efforts to foster adaptive self-regulation of emotion and reduce risk for later social problems and delinquency. PMID:20161105

  16. Functional Characterization of Human Stem Cell-Derived Cardiomyocytes

    PubMed Central

    Kirsch, Authors Glenn E.; Obejero-Paz, Carlos A.; Bruening-Wright, Andrew

    2014-01-01

    Cardiac toxicity is a leading contributor to late-stage attrition in the drug discovery process and to withdrawal of approved from the market. In vitro assays that enable earlier and more accurate testing for cardiac risk provide early stage predictive indicators that aid in mitigating risk. Human cardiomyocytes, the most relevant subjects for early stage testing, are severely limited in supply. But human stem cell-derived cardiomyocytes (SC-hCM) are readily available from commercial sources and are increasingly used in academic research, drug discovery and safety pharmacology. As a result, SC-hCM electrophysiology has become a valuable tool to assess cardiac risk associated with drugs. This unit describes techniques for recording individual currents carried by sodium, calcium and potassium ions, as well as single cell action potentials, and impedance recordings from contracting syncytia of thousands of interconnected cells. PMID:25152802

  17. From specialist to generalist: Developmental transformations in the genetic structure of early child abilities.

    PubMed

    Cheung, Amanda K; Harden, K Paige; Tucker-Drob, Elliot M

    2015-07-01

    The heritability of abilities increases substantially over development, and much of heritable variation in abilities is shared with other abilities. No study, however, has formally tested the extent to which developmental increases in heritability occur on shared versus unique variation in child abilities. A transactional perspective predicts that the relative proportion of shared to total genetic variance will increase with age, whereas an endogenous perspective predicts that such proportion will be invariant with age. We tested these competing predictions using data from a sample of 292 twins providing a total of 578 cross-sectional and longitudinal observations between ages 0 and 6 years on measures of Communication, Gross Motor, Fine Motor, Problem-Solving, and Personal-Social abilities. Consistent with predictions of the transactional perspective, developmental increases in heritability were localized to variance shared across abilities.

  18. Generation of a transgenic medaka (Oryzias latipes) strain for visualization of nuclear dynamics in early developmental stages.

    PubMed

    Inoue, Takanobu; Iida, Atsuo; Maegawa, Shingo; Sehara-Fujisawa, Atsuko; Kinoshita, Masato

    2016-12-01

    In this study, we verified nuclear transport activity of an artificial nuclear localization signal (aNLS) in medaka fish (Oryzias latipes). We generated a transgenic medaka strain expresses the aNLS tagged enhanced green fluorescent protein (EGFP) driven by a medaka beta-actin promoter. The aNLS-EGFP was accumulated in the nuclei of somatic tissues and yolk nuclei of oocytes, but undetectable in the spermatozoa. The fluorescent signal was observed from immediately after fertilization by a maternal contribution. Furthermore, male and female pronuclei were visualized in fertilized eggs, and nuclear dynamics of pronuclear fusion and subsequent cleavage were captured by time-lapse imaging. In contrast, SV40NLS exhibited no activity of nuclear transport in early embryos. In conclusion, the aNLS possesses a strong nuclear localization activity and is a useful probe for fluorescent observation of the pronuclei and nuclei in early developmental stage of medaka.

  19. Genes, environments, and developmental research: methods for a multi-site study of early substance abuse.

    PubMed

    Costello, E Jane; Eaves, Lindon; Sullivan, Patrick; Kennedy, Martin; Conway, Kevin; Adkins, Daniel E; Angold, A; Clark, Shaunna L; Erkanli, Alaattin; McClay, Joseph L; Copeland, William; Maes, Hermine H; Liu, Youfang; Patkar, Ashwin A; Silberg, Judy; van den Oord, Edwin

    2013-04-01

    The importance of including developmental and environmental measures in genetic studies of human pathology is widely acknowledged, but few empirical studies have been published. Barriers include the need for longitudinal studies that cover relevant developmental stages and for samples large enough to deal with the challenge of testing gene-environment-development interaction. A solution to some of these problems is to bring together existing data sets that have the necessary characteristics. As part of the National Institute on Drug Abuse-funded Gene-Environment-Development Initiative, our goal is to identify exactly which genes, which environments, and which developmental transitions together predict the development of drug use and misuse. Four data sets were used of which common characteristics include (1) general population samples, including males and females; (2) repeated measures across adolescence and young adulthood; (3) assessment of nicotine, alcohol, and cannabis use and addiction; (4) measures of family and environmental risk; and (5) consent for genotyping DNA from blood or saliva. After quality controls, 2,962 individuals provided over 15,000 total observations. In the first gene-environment analyses, of alcohol misuse and stressful life events, some significant gene-environment and gene-development effects were identified. We conclude that in some circumstances, already collected data sets can be combined for gene-environment and gene-development analyses. This greatly reduces the cost and time needed for this type of research. However, care must be taken to ensure careful matching across studies and variables.

  20. Genes, environments, and developmental GEWIS: Methods for a multi-site study of early substance abuse

    PubMed Central

    Costello, E. J.; Eaves, Lindon; Sullivan, Patrick; Kennedy, Martin; Conway, Kevin; Adkins, Daniel E.; Angold, A.; Clark, Shaunna L; Erkanli, Alaattin; McClay, Joseph L; Copeland, William; Maes, Hermine H.; Liu, Youfang; Patkar, Ashwin A.; Silberg, Judy; van den Oord, Edwin

    2013-01-01

    The importance of including developmental and environmental measures in genetic studies of human pathology is widely acknowledged, but few empirical studies have been published. Barriers include the need for longitudinal studies that cover relevant developmental stages and for samples large enough to deal with the challenge of testing gene-environment-development interaction. A solution to some of these problems is to bring together existing data sets that have the necessary characteristics. As part of the NIDA-funded Gene-Environment-Development Initiative (GEDI) our goal is to identify exactly which genes, which environments, and which developmental transitions together predict the development of drug use and misuse. Four data sets were used whose common characteristics include (1) general population samples including males and females; (2) repeated measures across adolescence and young adulthood; (3) assessment of nicotine, alcohol and cannabis use and addiction; (4) measures of family and environmental risk; and (5) consent for genotyping DNA from blood or saliva. After quality controls, 2,962 individuals provided over 15,000 total observations. In the first gene-environment analyses, of alcohol misuse and stressful life events, some significant gene-environment and gene-development effects were identified. We conclude that in some circumstances, already-collected data sets can be combined for gene-environment and gene-development analyses. This greatly reduces the cost and time needed for this type of research. However, care must be taken to ensure careful matching across studies and variables. PMID:23461817

  1. Developmental Trajectories of Social Skills during Early Childhood and Links to Parenting Practices in a Japanese Sample

    PubMed Central

    Takahashi, Yusuke; Okada, Kensuke; Hoshino, Takahiro; Anme, Tokie

    2015-01-01

    This study used data from a nationwide survey in Japan to model the developmental course of social skills during early childhood. The goals of this study were to identify longitudinal profiles of social skills between 2 and 5 years of age using a group-based trajectory approach, and to investigate whether and to what extent parenting practices at 2 years of age predicted developmental trajectories of social skills during the preschool period. A relatively large sample of boys and girls (N > 1,000) was assessed on three social skill dimensions (Cooperation, Self-control, and Assertion) at four time points (ages 2, 3, 4, and 5), and on four parenting practices (cognitive and emotional involvement, avoidance of restriction and punishment, social stimulation, and social support for parenting) at age 2. The results indicated that for each social skill dimension, group-based trajectory models identified three distinct trajectories: low, moderate, and high. Multinomial regression analysis revealed that parenting practice variables showed differential contributions to development of child social skills. Specifically, Cooperation and Assertion were promoted by cognitive and emotional involvement, Self-control by social stimulation, and Assertion by avoidance of restriction and punishment. Abundant social support for parenting was not associated with higher child social skills trajectories. We found heterogeneity in developmental profiles of social skills during the preschool ages, and we identified parenting practices that contributed to different patterns of social skills development. We discussed the implications of higher-quality parenting practices on the improvement of child social skills across early childhood. PMID:26267439

  2. Developmental exposures to waterborne abused drugs alter physiological function and larval locomotion in early life stages of medaka fish.

    PubMed

    Liao, Pei-Han; Hwang, Chiu-Chu; Chen, Te-Hao; Chen, Pei-Jen

    2015-08-01

    Environmental pollution by neuroactive pharmaceuticals from wastewater discharge is a major threat to aquatic ecosystems. However, the ecotoxicologic effect of waterborne abused drugs remains unclear. Embryos of medaka fish (Oryzias latipes) were exposed to aqueous solutions of 2 hallucinogenic drugs, ketamine (KET) and methamphetamine (MET) (0.004-40μM) to assess developmental toxicity, oxidative stress and behavioral alteration in early life stages. The environmentally relevant concentration (0.004μM) of both KET and MET significantly delayed blood circulation and hatching time in embryos and altered larval swimming behavior (e.g., maximum velocity and relative turn angle). KET and MET induced similar oxidative stress responses in embryos, which were unrecoverable in hatchlings in drug-free solutions. Early life exposure to the 2 drugs conferred distinct patterns in larval locomotion: KET induced hyperactivity and a less tortuous swimming path, but MET-treated larvae showed hypoactivity and a clockwise swimming direction at high doses. The alteration in locomotor responses were generally similar in mammals and zebrafish. We report sensitive biomarkers (e.g., heartbeat, hatching and swimming behavior) by developmental stage of medaka that reflect environmentally relevant exposures of abused drugs. They could be useful for ecological risk assessment of waterborne neuroactive drugs. The toxicity results implicate a potential ecotoxicological impact of controlled or abused drugs on fish development and populations in aquatic environments.

  3. Sex differences in the developmental trajectories of impulse control and sensation-seeking from early adolescence to early adulthood.

    PubMed

    Shulman, Elizabeth P; Harden, K Paige; Chein, Jason M; Steinberg, Laurence

    2015-01-01

    It has been proposed that high rates of risk-taking in adolescence are partly attributable to patterns of neurobiological development that promote an increase in sensation-seeking tendencies at a time when impulse control is still developing. It is not known, however, whether this pattern is the same for males and females. The present study investigates sex differences in the developmental trajectories of self-reported impulse control and sensation-seeking between the ages of 10 and 25 using longitudinal data from the National Longitudinal Study of Youth 1979 Child and Young Adult Survey (N = 8,270; 49% female; 33% Black, 22% Hispanic, 45% Non-Black, Non-Hispanic). Prior work has found that, consistent with the dual-systems model of adolescent neurobiological development, sensation-seeking rises and falls across this age span, whereas impulse control increases into the 20s. In the present study, we find that this same general pattern holds for both males and females, but with some key differences. As expected, males exhibit higher levels of sensation-seeking and lower levels of impulse control than females. Differences also emerged in the shapes of the developmental trajectories. Females reach peak levels of sensation-seeking earlier than males (consistent with the idea that sensation-seeking is linked to pubertal development) and decline in sensation-seeking more rapidly thereafter. Also, males increase in impulse control more gradually than females. Consequently, sex differences in both impulse control and sensation-seeking increase with age. The findings suggest that the window of heightened vulnerability to risk-taking during adolescence may be greater in magnitude and more protracted for males than for females.

  4. Mathematical model of mouse embryonic cardiomyocyte excitation-contraction coupling.

    PubMed

    Korhonen, Topi; Rapila, Risto; Tavi, Pasi

    2008-10-01

    Excitation-contraction (E-C) coupling is the mechanism that connects the electrical excitation with cardiomyocyte contraction. Embryonic cardiomyocytes are not only capable of generating action potential (AP)-induced Ca(2+) signals and contractions (E-C coupling), but they also can induce spontaneous pacemaking activity. The spontaneous activity originates from spontaneous Ca(2+) releases from the sarcoplasmic reticulum (SR), which trigger APs via the Na(+)/Ca(2+) exchanger (NCX). In the AP-driven mode, an external stimulus triggers an AP and activates voltage-activated Ca(2+) intrusion to the cell. These complex and unique features of the embryonic cardiomyocyte pacemaking and E-C coupling have never been assessed with mathematical modeling. Here, we suggest a novel mathematical model explaining how both of these mechanisms can coexist in the same embryonic cardiomyocytes. In addition to experimentally characterized ion currents, the model includes novel heterogeneous cytosolic Ca(2+) dynamics and oscillatory SR Ca(2+) handling. The model reproduces faithfully the experimentally observed fundamental features of both E-C coupling and pacemaking. We further validate our model by simulating the effect of genetic modifications on the hyperpolarization-activated current, NCX, and the SR Ca(2+) buffer protein calreticulin. In these simulations, the model produces a similar functional alteration to that observed previously in the genetically engineered mice, and thus provides mechanistic explanations for the cardiac phenotypes of these animals. In general, this study presents the first model explaining the underlying cellular mechanism for the origin and the regulation of the heartbeat in early embryonic cardiomyocytes.

  5. Mathematical Model of Mouse Embryonic Cardiomyocyte Excitation–Contraction Coupling

    PubMed Central

    Korhonen, Topi; Rapila, Risto; Tavi, Pasi

    2008-01-01

    Excitation–contraction (E–C) coupling is the mechanism that connects the electrical excitation with cardiomyocyte contraction. Embryonic cardiomyocytes are not only capable of generating action potential (AP)-induced Ca2+ signals and contractions (E–C coupling), but they also can induce spontaneous pacemaking activity. The spontaneous activity originates from spontaneous Ca2+ releases from the sarcoplasmic reticulum (SR), which trigger APs via the Na+/Ca2+ exchanger (NCX). In the AP-driven mode, an external stimulus triggers an AP and activates voltage-activated Ca2+ intrusion to the cell. These complex and unique features of the embryonic cardiomyocyte pacemaking and E–C coupling have never been assessed with mathematical modeling. Here, we suggest a novel mathematical model explaining how both of these mechanisms can coexist in the same embryonic cardiomyocytes. In addition to experimentally characterized ion currents, the model includes novel heterogeneous cytosolic Ca2+ dynamics and oscillatory SR Ca2+ handling. The model reproduces faithfully the experimentally observed fundamental features of both E–C coupling and pacemaking. We further validate our model by simulating the effect of genetic modifications on the hyperpolarization-activated current, NCX, and the SR Ca2+ buffer protein calreticulin. In these simulations, the model produces a similar functional alteration to that observed previously in the genetically engineered mice, and thus provides mechanistic explanations for the cardiac phenotypes of these animals. In general, this study presents the first model explaining the underlying cellular mechanism for the origin and the regulation of the heartbeat in early embryonic cardiomyocytes. PMID:18794378

  6. Thermally induced chronic developmental stress in coho salmon: Integrating measures of mortality, early growth and fluctuating asymmetry

    USGS Publications Warehouse

    Campbell, W.B.; Emlen, J.M.; Hershberger, W.K.

    1998-01-01

    Developmental stability, or homeostasis, facilitates the production of consistent phenotypes by buffering against stress. Fluctuating asymmetry is produced by developmental instability and is manifested as small random departures from bilateral symmetry. Increased fluctuating asymmetry is thought to parallel compromised fitness, in part, because stress promotes energy dissipation. Compensatory energy expenditures within the organism are required to complete development, thus promoting instability through reductions in homeostasis. Increased heterozygosity may enhance developmental stability by reducing energy dissipation from stress through increased metabolic efficiency, possibly by providing greater flexibility in metabolic pathways. Traditionally, fluctuating asymmetry has been used as a bioindicator of chronic stress, provided that selective mortality of less fit individuals did not reduce stress-mediated increases in fluctuating asymmetry to background levels produced by natural developmental error, or create data inconsistencies such as higher asymmetry in groups exposed to lower stress. Unfortunately, absence of selective mortality and its effects, while often assumed, can be difficult to substantiate. We integrated measures of early growth, mortality, fluctuating asymmetry (mandibular pores, pectoral finrays, pelvic finrays, and gillrakers on the upper and lower arms of the first branchial arch) and directional asymmetry (branchiostegal rays) to assess chronic thermal stress (fluctuating temperatures as opposed to ambient temperatures) in developing eggs from two different coho salmon (Oncorhynchus kisutch) stocks and their reciprocal hybrids. Hybridization provided insight on the capacity of heterozygosity to reduce stress during development. Although egg losses were consistently higher in crosses exposed to fluctuating temperatures, egg mortality was predominantly a function of maternal stock of origin. Post-hatch losses were higher in crosses exposed to

  7. The Typical Developmental Trajectory of Social and Executive Functions in Late Adolescence and Early Adulthood

    ERIC Educational Resources Information Center

    Taylor, Sophie Jane; Barker, Lynne Ann; Heavey, Lisa; McHale, Sue

    2013-01-01

    Executive functions and social cognition develop through childhood into adolescence and early adulthood and are important for adaptive goal-oriented behavior (Apperly, Samson, & Humphreys, 2009; Blakemore & Choudhury, 2006). These functions are attributed to frontal networks known to undergo protracted maturation into early adulthood…

  8. Embedding Computer Technology in Developmentally Appropriate Practice: Engaging with Early Years Professionals' Beliefs and Values

    ERIC Educational Resources Information Center

    Hall, Elaine; Higgins, Steven

    2002-01-01

    The use of computers in early years has become a contentious issue, with advocates calling for more Information and Communications Technology (ICT), more machines, better software, and more training for professionals, while other groups call for "a moratorium on the further introduction of computers in early childhood and elementary…

  9. Applying Contemporary Developmental and Movement Science Theories and Evidence to Early Intervention Practice

    ERIC Educational Resources Information Center

    Hickman, Robbin; McCoy, Sarah Westcott; Long, Toby M.; Rauh, Mitchell J.

    2011-01-01

    Changes in early childhood science, theory, and best practices for improving outcomes of children with motor delay or dysfunction and their families have evolved rapidly since EI began. Changes in daily early intervention (EI) practice have been more elusive. Closing the gap between knowledge and practice requires EI providers to piece together…

  10. Early adverse experience as a developmental risk factor for later psychopathology: evidence from rodent and primate models.

    PubMed

    Sánchez, M M; Ladd, C O; Plotsky, P M

    2001-01-01

    Increasing evidence supports the view that the interaction of perinatal exposure to adversity with individual genetic liabilities may increase an individual's vulnerability to the expression of psycho- and physiopathology throughout life. The early environment appears to program some aspects of neurobiological development and, in turn, behavioral, emotional, cognitive, and physiological development. Several rodent and primate models of early adverse experience have been analyzed in this review, including those that "model" maternal separation or loss, abuse or neglect, and social deprivation. Accumulating evidence shows that these early traumatic experiences are associated with long-term alterations in coping style, emotional and behavioral regulation. neuroendocrine responsiveness to stress, social "fitness,' cognitive function, brain morphology, neurochemistry, and expression levels of central nervous system genes that have been related to anxiety and mood disorders. Studies are underway to identify important aspects of adverse early experience, such as (a) the existence of "sensitive periods" during development associated with alterations in particular output systems. (b) the presence of "windows of opportunity" during which targeted interventions (e.g., nurturant parenting or supportive-enriching environment) may prevent or reverse dysfunction, (c) the identity of gene polymorphisms contributing to the individual's variability in vulnerability, and (d) a means to translate the timing of these developmental "sensitive periods" across species.

  11. Developmental Risk Signals as a Screening Tool for Early Identification of Sensory Processing Disorders.

    PubMed

    Bolaños, Cristina; Gomez, M Marlene; Ramos, Gregorio; Rios Del Rio, Janina

    2016-06-01

    The main purpose of this research was to determine if the indicators of risk included in the Indicators of Developmental Risk Signals (INDIPCD-R) could differentiate between children at risk of sensory processing disorders (SPDs) from those with normal development and if the SPD indicators correlated with a delay or altered development. A retrospective, descriptive, correlational design was used with a sample of 51 children, 36 referred because of clinical sensory processing indicators and 15 with non-clinical indicators. Participants were assessed with a developmental scale Revised Profile of Developmental Behaviors (PCD-R), the Sensory Profile, play and clinical observations. The INDIPCD-R showed a high correlation with developmental areas of PCD-R and a sensitivity and specificity of 100%, when compared with the Sensory Profile. T-test results for independent samples showed significant differences at p ≤ 0.01 level between the children with SPD indicators and those with no clinical signs in the PCD-R. The Mann-Whitney U-test was conducted for unpaired samples, to verify if there were significant differences between children with apparent SPD indicators and children with no apparent difficulties. The Spearman's rho was used to identify the correlations between the INDIPCD-R, with different areas of development. This study supports the use of the INDIPCD-R as a screening instrument that could be used by occupational therapists to discriminate children with and without indicators of SPD. The limitation of this study was that it did not cover all the ages of the INDIPCD-R. Additional studies are required to determine the utility of this instrument for outcome studies and whether it is valid and reliable to identify children at risk of different pathologies. The INDIPCD-R is a low-cost instrument that allows the occupational therapist to make a quick review of the different components that could be involved in SPD and therefore guide the more in

  12. Human Stem Cell Derived Cardiomyocytes: An Alternative ...

    EPA Pesticide Factsheets

    Chemical spills and associated deaths in the US has increased 2.6-fold and 16-fold from 1983 to 2012, respectfully. In addition, the number of chemicals to which humans are exposed to in the environment has increased almost 10-fold from 2001 to 2013 within the US. Internationally, a WHO report on the global composite impact of chemicals on health reported that 16% of the total burden of cardiovascular disease was attributed to environmental chemical exposure with 2.5 million deaths per year. Clearly, the cardiovascular system, at all its various developmental and life stages, represents a critical target organ system that can be adversely affected by existing and emerging chemicals (e.g., engineered nanomaterials) in a variety of environmental media. The ability to assess chemical cardiac risk and safety is critically needed but extremely challenging due to the number and categories of chemicals in commerce, as indicated. This presentation\\session will evaluate the use of adult human stem cell derived cardiomyocytes, and existing platforms, as an alternative model to evaluate environmental chemical cardiac toxicity as well as provide key information for the development of predictive adverse outcomes pathways associated with environmental chemical exposures. (This abstract does not represent EPA policy) Rapid and translatable chemical safety screening models for cardiotoxicity current status for informing regulatory decisions, a workshop sponsored by the Society

  13. Developmental neurotoxicity of organophosphate flame retardants in early life stages of Japanese medaka (Oryzias latipes).

    PubMed

    Sun, Liwei; Tan, Hana; Peng, Tao; Wang, Sisi; Xu, Wenbin; Qian, Haifeng; Jin, Yuanxiang; Fu, Zhengwei

    2016-12-01

    Because brominated flame retardants are being banned or phased out worldwide, organophosphate flame retardants have been used as alternatives on a large scale and have thus become ubiquitous environmental contaminants; this raises great concerns about their environmental health risk and toxicity. Considering that previous research has identified the nervous system as a sensitive target, Japanese medaka were used as an aquatic organism model to evaluate the developmental neurotoxicity of 4 organophosphate flame retardants: triphenyl phosphate, tri-n-butyl phosphate, tris(2-butoxyethyl) phosphate, and tris(2-chloroethyl) phosphate (TCEP). The embryo toxicity test showed that organophosphate flame retardant exposure could decrease hatchability, delay time to hatching, increase the occurrence of malformations, reduce body length, and slow heart rate. Regarding locomotor behavior, exposure to the tested organophosphate flame retardants (except TCEP) for 96 h resulted in hypoactivity for medaka larvae in both the free-swimming and the dark-to-light photoperiod stimulation test. Changes of acetylcholinesterase activity and transcriptional responses of genes related to the nervous system likely provide a reasonable explanation for the neurobehavioral disruption. Overall, the present study clearly demonstrates the developmental neurotoxicity of various organophosphate flame retardants with very different potency and contribute to the determination of which organophosphate flame retardants are appropriate substitutes, as well as the consideration of whether regulations are reasonable and required. Environ Toxicol Chem 2016;35:2931-2940. © 2016 SETAC.

  14. Long-term follow-up study of children developmentally retarded by early environmental deprivation.

    PubMed

    Fujinaga, T; Kasuga, T; Uchida, N; Saiga, H

    1990-02-01

    In 1972, two children representing a case of severe developmental retardation were discovered and taken into custody. The children, an older sister (referred to as F) and a younger brother (referred to as G), were found to have achieved no more than the physical and mental age level normal to children 1 year of age or less, in spite of their actual respective chronological ages of 6 and 5. Investigation revealed that the children's developmental retardation was due both to extreme social isolation and to complex deprivation. By following their sensorimotor, linguistic, cognitive, and socio-emotional development from the time of discovery to the date of this writing, we have found that their physical and motor development or recovery has proceeded smoothly, whereas their linguistic and cognitive development has continued to show such weaknesses as defective functioning of internal speech (Vygotsky, 1962) and poor ability to deal with abstract, linguistic subjects. F and G have continued to exhibit a tendency toward undersocialization, but this has at times been rather a positive factor in the process of attaining ego identity during adolescence, especially for G, serving to protect him from unreasonable social pressures to conform to group behavior. In combination with other cases of severe deprivation, the case of F and G holds some interesting implications for theories of human development, particularly the notion of critical periods.

  15. Myxococcus xanthus sasS encodes a sensor histidine kinase required for early developmental gene expression.

    PubMed Central

    Yang, C; Kaplan, H B

    1997-01-01

    Initiation of Myxococcus xanthus multicellular development requires integration of information concerning the cells' nutrient status and density. A gain-of-function mutation, sasB7, that bypasses both the starvation and high cell density requirements for developmental expression of the 4521 reporter gene, maps to the sasS gene. The wild-type sasS gene was cloned and sequenced. This gene is predicted to encode a sensor histidine protein kinase that appears to be a key element in the transduction of starvation and cell density inputs. The sasS null mutants express 4521 at a basal level, form defective fruiting bodies, and exhibit reduced sporulation efficiencies. These data indicate that the wild-type sasS gene product functions as a positive regulator of 4521 expression and participates in M. xanthus development. The N terminus of SasS is predicted to contain two transmembrane domains that would locate the protein to the cytoplasmic membrane. The sasB7 mutation, an E139K missense mutation, maps to the predicted N-terminal periplasmic region. The C terminus of SasS contains all of the conserved residues typical of the sensor histidine protein kinases. SasS is predicted to be the sensor protein in a two-component system that integrates information required for M. xanthus developmental gene expression. PMID:9401035

  16. Born early and born poor: An eco-bio-developmental model for poverty and preterm birth.

    PubMed

    Brumberg, H L; Shah, S I

    2015-01-01

    Poverty is associated with adverse long-term cognitive outcomes in children. Poverty is also linked with preterm delivery which, in turn, is associated with adverse cognitive outcomes. However, the extent of the effect of poverty on preterm delivery, as well as proposed mechanisms by which they occur, have not been well described. Further, the impact of poverty on preterm school readiness has not been reviewed. As the childhood poverty level continues to increase in the U.S., we examine the evidence around physiological, neurological, cognitive and learning outcomes associated with prematurity in the context of poverty. We use the evidence gathered to suggest an Eco-Bio-Developmental model, emphasizing poverty as a toxic stress which predisposes preterm birth and which, via epigenetic forces, can continue into the next generation. Continued postnatal social disadvantage for these developmentally high-risk preterm infants is strongly linked with poor neurodevelopmental outcomes, decreased school readiness, and decreased educational attainment which can perpetuate the poverty cycle. We suggest social remedies aimed at decreasing the impact of poverty on mothers, fathers, and children which may be effective in reducing the burden of preterm birth.

  17. The Scottish Centre for Autism preschool treatment programme. I: A developmental approach to early intervention.

    PubMed

    Salt, J; Sellars, V; Shemilt, J; Boyd, S; Coulson, T; McCool, S

    2001-12-01

    Early intervention is an area of intense current interest for parents and professionals. This article describes a mainstream National Health Service (NHS) approach to early intervention, developed at the Scottish Centre for Autism. The aims of treatment are to improve the child's early social communication and social interaction skills, leading to the potential development of play and flexibility of behaviour. This is achieved by 1:1 intensive treatment by trained therapists, and a schedule of parent training. The treatment protocol incorporates a child led approach; the use of imitation as a therapeutic strategy; using language contingent on activities; and the introduction of flexibility into play and social exchanges.

  18. Heart valve cardiomyocytes of mouse embryos express the serotonin transporter SERT

    SciTech Connect

    Pavone, Luigi Michele Spina, Anna; Lo Muto, Roberta; Santoro, Dionea; Mastellone, Vincenzo; Avallone, Luigi

    2008-12-12

    Multiple evidence demonstrate a role for serotonin and its transporter SERT in heart valve development and disease. By utilizing a Cre/loxP system driven by SERT gene expression, we recently demonstrated a regionally restricted distribution of SERT-expressing cells in developing mouse heart. In order to characterize the cell types exhibiting SERT expression within the mouse heart valves at early developmental stages, in this study we performed immunohistochemistry for Islet1 (Isl1) and connexin-43 (Cx-43) on heart sections from SERT{sup Cre/+};ROSA26R embryos previously stained with X-gal. We observed the co-localization of LacZ staining with Isl1 labelling in the outflow tract, the right ventricle and the conal region of E11.5 mouse heart. Cx-43 labelled cells co-localized with LacZ stained cells in the forming atrioventricular valves. These results demonstrate the cardiomyocyte phenotype of SERT-expressing cells in heart valves of the developing mouse heart, thus suggesting an active role of SERT in early heart valve development.

  19. Comparative toxicity of several metal oxide nanoparticle aqueous suspensions to Zebrafish (Danio rerio) early developmental stage.

    PubMed

    Zhu, Xiaoshan; Zhu, Lin; Duan, Zhenghua; Qi, Ruiqi; Li, Yan; Lang, Yupeng

    2008-02-15

    With the emergence of manufactured nanomaterials, it is urgent to carry out researches on their potential environmental impacts and biological effects. To better understand the potential ecotoxicological impacts of metal oxide nanoparticles released to aquatic environments, the zebrafish 96-h embryo-larval bioassay was used to assess and compare the developmental toxicities of nanoscale zinc oxide (nZnO), titanium dioxide (nTiO(2)) and alumina (nAl(2)O(3)) aqueous suspensions. Toxicological endpoints such as zebrafish embryos or larvae survival, hatching rate and malformation were noted and described within 96 h of exposure. Meanwhile, a comparative experiment with their bulk counterparts (i.e., ZnO/bulk, TiO(2)/bulk and Al(2)O(3)/bulk) was conducted to understand the effect of particle size on their toxicities. The results showed that: (i) both nZnO and ZnO/bulk aqueous suspensions delayed zebrafish embryo and larva development, decreased their survival and hatching rates, and caused tissue damage. The 96-h LC(50) of nZnO and ZnO/bulk aqueous suspensions on the zebrafish survival are 1.793 mg/L and 1.550 mg/L respectively; and the 84-h EC(50) on the zebrafish embryo hatching rate are 2.065 mg/L and 2.066 mg/L respectively. Serious tissue ulceration was found on zebrafish larvae exposed to nZnO and ZnO/bulk aqueous suspensions. (ii) In contrast, neither nTiO(2) and TiO(2)/bulk nor nAl(2)O(3) and Al(2)O(3)/bulk showed any toxicity to zebrafish embryos and larvae under the same experimental condition. It revealed that the metal oxide nanoparticles with different chemical composition have different zebrafish developmental toxicities. (iii) Exposures of nTiO(2), nZnO and nAl(2)O(3) produced toxic effects on zebrafish embryos and larvae, which was not different from the effects caused by exposing to their bulk counterparts. This is the first study about the developmental toxicity of metal oxide nanoparticles, and the results demonstrate that nZnO is very toxic to

  20. Association of the use of bacterial cell wall synthesis Inhibitor drugs in early childhood with the Developmental Defects of Enamel

    PubMed Central

    Tariq, Amna; Alam Ansari, Munawar; Owais Ismail, Muhammad; Memon, Zahida

    2014-01-01

    Objective: Our objective of the study was to determine the association between frequent use of Penicillins and Cephalosporins with developmental defects of enamel in pediatric age group. Methods: This is a cross sectional study, conducted at Ziauddin University. A total of 367 children, having the history of either Penicillin or Cephalosporin exposure were included. The parents of children were asked to complete a questionnaire related to disease and drug history. Dental examination was carried out to assess the hypomineralization in tooth enamel based on modified Developmental Defects of Enamel (DDE) index. Results: Out of 367 children, 124 (34%) were males and females were 243(66%). In the study group 22.6% (n= 83) of children were found to be hypomineralized. The maximum type of teeth defects were diffused opacities that was 12.0% (n=44). The statistically significant association (p-value < 0.05) was found between frequency of antibiotic use and hypomineralization for most teeth. Children who were exposed to either Penicillins or Cephalosporin in early childhood showed significant (p-value < 0.002) hypomineralized enamel. Conclusion: This study concludes that frequent use of antibiotics such as penicillins and cephalosporins has positive association with enamel hypomineralization in developing tooth structure. PMID:24772150

  1. The Dictyostelium MAPK ERK1 is phosphorylated in a secondary response to early developmental signaling.

    PubMed

    Schwebs, David J; Hadwiger, Jeffrey A

    2015-01-01

    Previous reports have suggested that the two mitogen-activated protein kinases (MAPKs) in Dictyostelium discoideum, ERK1 and ERK2, can be directly activated in response to external cAMP even though these MAPKs play different roles in the developmental life cycle. To better characterize MAPK regulation, the levels of phosphorylated MAPKs were analyzed in response to external signals. Only ERK2 was rapidly phosphorylated in response to the chemoattractants, cAMP and folate. In contrast, the phosphorylation of ERK1 occurred as a secondary or indirect response to these stimuli and this phosphorylation was enhanced by cell-cell interactions, suggesting that other external signals can activate ERK1. The phosphorylation of ERK1 or ERK2 did not require the function of the other MAPK in these responses. Folate stimulation of a chimeric population of erk1- and gα4- cells revealed that the phosphorylation of ERK1 could be mediated through an intercellular signal other than folate. Loss of ERK1 function suppressed the developmental delay and the deficiency in anterior cell localization associated with gα5- mutants suggesting that ERK1 function can be down regulated through Gα5 subunit-mediated signaling. However, no major changes in the phosphorylation of ERK1 were observed in gα5- cells suggesting that the Gα5 subunit signaling pathway does not regulate the phosphorylation of ERK1. These findings suggest that the activation of ERK1 occurs as a secondary response to chemoattractants and that other cell-cell signaling mechanisms contribute to this activation. Gα5 subunit signaling can down regulate ERK1 function to promote prestalk cell development but not through major changes to the level of phosphorylated ERK1.

  2. Genome-wide identification and analysis of rice genes preferentially expressed in pollen at an early developmental stage.

    PubMed

    Nguyen, Tien Dung; Moon, Sunok; Nguyen, Van Ngoc Tuyet; Gho, Yunsil; Chandran, Anil Kumar Nalini; Soh, Moon-Soo; Song, Jong Tae; An, Gynheung; Oh, Sung Aeong; Park, Soon Ki; Jung, Ki-Hong

    2016-09-01

    Microspore production using endogenous developmental programs has not been well studied. The main limitation is the difficulty in identifying genes preferentially expressed in pollen grains at early stages. To overcome this limitation, we collected transcriptome data from anthers and microspore/pollen and performed meta-expression analysis. Subsequently, we identified 410 genes showing preferential expression patterns in early developing pollen samples of both japonica and indica cultivars. The expression patterns of these genes are distinguishable from genes showing pollen mother cell or tapetum-preferred expression patterns. Gene Ontology enrichment and MapMan analyses indicated that microspores in rice are closely linked with protein degradation, nucleotide metabolism, and DNA biosynthesis and regulation, while the pollen mother cell or tapetum are strongly associated with cell wall metabolism, lipid metabolism, secondary metabolism, and RNA biosynthesis and regulation. We also generated transgenic lines under the control of the promoters of eight microspore-preferred genes and confirmed the preferred expression patterns in plants using the GUS reporting system. Furthermore, cis-regulatory element analysis revealed that pollen specific elements such as POLLEN1LELAT52, and 5659BOXLELAT5659 were commonly identified in the promoter regions of eight rice genes with more frequency than estimation. Our study will provide new sights on early pollen development in rice, a model crop plant.

  3. Preventing high-risk sexual behavior in early adulthood with family interventions in adolescence: outcomes and developmental processes.

    PubMed

    Caruthers, Allison S; Van Ryzin, Mark J; Dishion, Thomas J

    2014-02-01

    Adolescent study participants who engaged in a brief, family-centered intervention (the Family Check-Up, FCU) were later assessed for the intervention's effects on high-risk sexual behavior (HRSB) in early adulthood (age 22). Participants (N = 998 adolescents and their families) were randomly assigned to a family-centered intervention in sixth grade and were offered a gated, multilevel intervention that included (a) a school-based family resource center, (b) the FCU, and (c) more intensive, family-based treatment. All services were voluntary, but high-risk families were actively recruited into the FCU. Approximately 23% of the intervention families engaged in the FCU and approximately 18% engaged in more intensive treatment. Using an intent-to-treat design, we found that the direct effect of the FCU on HRSB was not significant; however, an analysis of the developmental processes indicated that intervention families demonstrated improved family relationship quality when compared to control families, which in turn resulted in lower levels of HRSB in early adulthood. Furthermore, the significant effect of family relationship quality on HRSB was mediated by differences in parental monitoring and early sexual activity, and these effects varied as a function of gender and ethnicity. Indirect effects of the FCU on HRSB were significant via multiple different pathways. The implications of these findings for enhancing the impact of family-centered interventions are discussed.

  4. Thermal tolerance during early ontogeny in the common whelk Buccinum undatum (Linnaeus 1785): Bioenergetics, nurse egg partitioning and developmental success

    NASA Astrophysics Data System (ADS)

    Smith, Kathryn E.; Thatje, Sven; Hauton, Chris

    2013-05-01

    Temperature is arguably the primary factor affecting development in ectotherms and, as a result, may be the driving force behind setting species' geographic limits. The shallow-water gastropod Buccinum undatum is distributed widely throughout the North Atlantic, with an overall annual thermal range of below zero to above 22 °C. In UK waters this species is a winter spawner. Egg masses are laid and develop when sea temperatures are at their coolest (4 to 10 °C) indicating future climate warming may have the potential to cause range shifts in this species. In order to examine the potential impacts of ocean warming, we investigate the effects of temperature on the early ontogeny of B. undatum across a thermal range of 0 to 22 °C. Each egg mass consists of approximately 100 capsules, in which embryos undergo direct development. Successful development was observed at temperatures ranging from 6 to 18 °C. Rates of development increased with temperature, but the proportion of each egg mass developing successfully decreased at the same time. With increasing temperature, the mean early veliger weight increased, but the number of early veligers developing per capsule decreased, suggesting a negative impact on the number of crawl-away juveniles produced per capsule. Elemental analysis showed both carbon (C) and nitrogen (N) to increase with temperature in early veligers but not in hatching juveniles, indicating greater energy reserves are accumulated during early ontogeny to compensate for the higher energetic demands of development at higher temperature. The developmental plasticity observed in B. undatum suggests this species to be capable of adapting to temperatures above those it currently experiences in nature. B. undatum may possess a thermal resilience to ocean warming at its current upper temperature distribution limit. This thermal resilience, however, may come at the cost of a reduced offspring number.

  5. Developmental associations between adolescent change in depressive symptoms and menstrual-cycle-phase-specific negative affect during early adulthood.

    PubMed

    Kiesner, Jeff; Poulin, François

    2012-10-01

    The causal factors associated with increases in depressive symptoms among adolescent girls remain an area of theoretical debate, and the limited research considering a hormonal influence has provided mixed results. The goal of the present study was to test a set of longitudinal associations, that, if found, would provide support for a hormonal contribution to these changes. Specifically, this study tested the hypotheses that changes in depressive symptoms among adolescent girls would be associated with phase-specific symptoms of the menstrual cycle during early adulthood; that these associations would differ across three phases of the menstrual cycle; and that the pattern of associations would differ for changes in depressive symptoms during early- and late-adolescence. The sample consisted of 47 women with longitudinal data from 12 to 21 years old (approximately 91% European Canadian, 4% Middle Eastern Canadian, 2% Haitian Canadian, and 2% Asian Canadian). Consistent with expectations, results showed that early-adolescent increases in depressive symptoms were negatively associated with menstrual-phase negative affect, and positively associated with mid-cycle negative affect, but not associated with premenstrual negative affect; whereas late-adolescent change in depressive symptoms was only associated with depressive symptoms at 20-21 years. Thus, early-adolescent changes in depressive symptoms are longitudinally associated with later mood change across the menstrual cycle, suggesting a common underlying cause, which is hypothesized to be hormonal. Moreover, results suggest that, with respect to variables that are involved in affective development, important differences exist between early- and late-adolescence. The discussion considers menstrual-cycle-related symptoms (e.g., dysmenorrhea) during adolescence, and the need to study their effects on development. It is suggested that focused intervention and prevention efforts may be indicated to interrupt negative

  6. Daily temperature fluctuations unpredictably influence developmental rate and morphology at a critical early larval stage in a frog

    PubMed Central

    2013-01-01

    Background Environmental temperature has profound consequences for early amphibian development and many field and laboratory studies have examined this. Most laboratory studies that have characterized the influence of temperature on development in amphibians have failed to incorporate the realities of diel temperature fluctuations (DTF), which can be considerable for pond-breeding amphibians. Results We evaluated the effects of different ecologically relevant ranges of DTF compared with effects of constant temperatures on development of embryos and larvae of the Korean fire-bellied toad (Bombina orientalis). We constructed thermal reaction norms for developmental stage, snout- vent length, and tail length by fitting a Gompertz-Gaussian function to measurements taken from embryos after 66 hours of development in 12 different constant temperature environments between 14°C and 36°C. We used these reaction norms as null models to test the hypothesis that developmental effects of DTF are more than the sum of average constant temperature effects over the distribution of temperatures experienced. We predicted from these models that growth and differentiation would be positively correlated with average temperature at low levels of DTF but not at higher levels of DTF. We tested our prediction in the laboratory by rearing B. orientalis embryos at three average temperatures (20°C, 24°C, and 28°C) and four levels of thermal variation (0°C, 6°C, 13°C, and 20°C). Several of the observed responses to DTF were significantly different from both predictions of the model and from responses in constant temperature treatments at the same average temperatures. At an average temperature of 24°C, only the highest level of DTF affected differentiation and growth rates, but at both cooler and warmer average temperatures, moderate DTF was enough to slow developmental and tail growth rates. Conclusions These results demonstrate that both the magnitude of DTF range and thermal

  7. Developmental changes in the corpus callosum from infancy to early adulthood: a structural magnetic resonance imaging study.

    PubMed

    Tanaka-Arakawa, Megumi M; Matsui, Mie; Tanaka, Chiaki; Uematsu, Akiko; Uda, Satoshi; Miura, Kayoko; Sakai, Tomoko; Noguchi, Kyo

    2015-01-01

    Previous research has reported on the development trajectory of the corpus callosum morphology. However, there have been only a few studies that have included data on infants. The goal of the present study was to examine the morphology of the corpus callosum in healthy participants of both sexes, from infancy to early adulthood. We sought to characterize normal development of the corpus callosum and possible sex differences in development. We performed a morphometric magnetic resonance imaging (MRI) study of 114 healthy individuals, aged 1 month to 25 years old, measuring the size of the corpus callosum. The corpus callosum was segmented into seven subareas of the rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus and splenium. Locally weighted regression analysis (LOESS) indicated significant non-linear age-related changes regardless of sex, particularly during the first few years of life. After this increase, curve slopes gradually became flat during adolescence and adulthood in both sexes. Age of local maximum for each subarea of the corpus callosum differed across the sexes. Ratios of total corpus callosum and genu, posterior midbody, as well as splenium to the whole brain were significantly higher in females compared with males. The present results demonstrate that the developmental trajectory of the corpus callosum during early life in healthy individuals is non-linear and dynamic. This pattern resembles that found for the cerebral cortex, further suggesting that this period plays a very important role in neural and functional development. In addition, developmental trajectories and changes in growth do show some sex differences.

  8. Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis

    PubMed Central

    Trump, Natalie; McTague, Amy; Brittain, Helen; Papandreou, Apostolos; Meyer, Esther; Ngoh, Adeline; Palmer, Rodger; Morrogh, Deborah; Boustred, Christopher; Hurst, Jane A; Jenkins, Lucy; Kurian, Manju A; Scott, Richard H

    2016-01-01

    Background We sought to investigate the diagnostic yield and mutation spectrum in previously reported genes for early-onset epilepsy and disorders of severe developmental delay. Methods In 400 patients with these disorders with no known underlying aetiology and no major structural brain anomaly, we analysed 46 genes using a combination of targeted sequencing on an Illumina MiSeq platform and targeted, exon-level microarray copy number analysis. Results We identified causative mutations in 71/400 patients (18%). The diagnostic rate was highest among those with seizure onset within the first two months of life (39%), although overall it was similar in those with and without seizures. The most frequently mutated gene was SCN2A (11 patients, 3%). Other recurrently mutated genes included CDKL5, KCNQ2, SCN8A (six patients each), FOXG1, MECP2, SCN1A, STXBP1 (five patients each), KCNT1, PCDH19, TCF4 (three patients each) and ATP1A3, PRRT2 and SLC9A6 (two patients each). Mutations in EHMT1, GABRB3, LGI1, MBD5, PIGA, UBE3A and ZEB2 were each found in single patients. We found mutations in a number of genes in patients where either the electroclinical features or dysmorphic phenotypes were atypical for the identified gene. In only 11 cases (15%) had the clinician sufficient certainty to specify the mutated gene as the likely cause before testing. Conclusions Our data demonstrate the considerable utility of a gene panel approach in the diagnosis of patients with early-onset epilepsy and severe developmental delay disorders., They provide further insights into the phenotypic spectrum and genotype–phenotype correlations for a number of the causative genes and emphasise the value of exon-level copy number testing in their analysis. PMID:26993267

  9. Proteolysis regulates cardiomyocyte maturation and tissue integration

    PubMed Central

    Fukuda, Ryuichi; Gunawan, Felix; Beisaw, Arica; Jimenez-Amilburu, Vanesa; Maischein, Hans-Martin; Kostin, Sawa; Kawakami, Koichi; Stainier, Didier Y. R.

    2017-01-01

    Tissue integrity is critical for organ formation and function. During heart development, cardiomyocytes differentiate and integrate to form a coherent tissue that contracts synchronously. However, the molecular mechanisms regulating cardiac tissue integrity are poorly understood. Here we show that proteolysis, via the E3 ubiquitin ligase ASB2, regulates cardiomyocyte maturation and tissue integrity. Cardiomyocytes in asb2b zebrafish mutants fail to terminally differentiate, resulting in reduced cardiac contractility and output. Mosaic analyses reveal a cell-autonomous requirement for Asb2b in cardiomyocytes for their integration as asb2b mutant cardiomyocytes are unable to meld into wild-type myocardial tissue. In vitro and in vivo data indicate that ASB2 negatively regulates TCF3, a bHLH transcription factor. TCF3 must be degraded for cardiomyocyte maturation, as TCF3 gain-of-function causes a number of phenotypes associated with cardiomyocyte dedifferentiation. Overall, our results show that proteolysis has an important role in cardiomyocyte maturation and the formation of a coherent myocardial tissue. PMID:28211472

  10. Engineering adolescence: maturation of human pluripotent stem cell-derived cardiomyocytes.

    PubMed

    Yang, Xiulan; Pabon, Lil; Murry, Charles E

    2014-01-31

    The discovery of human pluripotent stem cells (hPSCs), including both human embryonic stem cells and human-induced pluripotent stem cells, has opened up novel paths for a wide range of scientific studies. The capability to direct the differentiation of hPSCs into functional cardiomyocytes has provided a platform for regenerative medicine, development, tissue engineering, disease modeling, and drug toxicity testing. Despite exciting progress, achieving the optimal benefits has been hampered by the immature nature of these cardiomyocytes. Cardiac maturation has long been studied in vivo using animal models; however, finding ways to mature hPSC cardiomyocytes is only in its initial stages. In this review, we discuss progress in promoting the maturation of the hPSC cardiomyocytes, in the context of our current knowledge of developmental cardiac maturation and in relation to in vitro model systems such as rodent ventricular myocytes. Promising approaches that have begun to be examined in hPSC cardiomyocytes include long-term culturing, 3-dimensional tissue engineering, mechanical loading, electric stimulation, modulation of substrate stiffness, and treatment with neurohormonal factors. Future studies will benefit from the combinatorial use of different approaches that more closely mimic nature's diverse cues, which may result in broader changes in structure, function, and therapeutic applicability.

  11. Evidence for Cardiomyocyte Renewal in Humans

    SciTech Connect

    Bergmann, O; Bhardwaj, R D; Bernard, S; Zdunek, S; Barnabe-Heider, F; Walsh, S; Zupicich, J; Alkass, K; Buchholz, B A; Druid, H; Jovinge, S; Frisen, J

    2008-10-14

    It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 20 to 0.3% at the age of 75. Less than 50% of cardiomyocytes are exchanged during a normal lifespan. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work towards the development of therapeutic strategies aiming to stimulate this process in cardiac pathologies.

  12. Evidence for cardiomyocyte renewal in humans.

    PubMed

    Bergmann, Olaf; Bhardwaj, Ratan D; Bernard, Samuel; Zdunek, Sofia; Barnabé-Heider, Fanie; Walsh, Stuart; Zupicich, Joel; Alkass, Kanar; Buchholz, Bruce A; Druid, Henrik; Jovinge, Stefan; Frisén, Jonas

    2009-04-03

    It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 25 to 0.45% at the age of 75. Fewer than 50% of cardiomyocytes are exchanged during a normal life span. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work toward the development of therapeutic strategies aimed at stimulating this process in cardiac pathologies.

  13. Developmental Changes in the Relations between Inhibitory Control and Externalizing Problems during Early Childhood

    ERIC Educational Resources Information Center

    Utendale, William T.; Hastings, Paul D.

    2011-01-01

    Deficits in executive function, and in particular, reduced capacity to inhibit a dominant action, are a risk factor for externalizing problems (EP). Inhibitory control (IC) develops in the later preschool and early childhood periods, such that IC might not regulate EP in toddlers and younger preschoolers. Aggression was observed during peer play…

  14. What Makes a Difference: Early Head Start Evaluation Findings in a Developmental Context

    ERIC Educational Resources Information Center

    Love, John M.; Chazan-Cohen, Rachel; Raikes, Helen; Brooks-Gunn, Jeanne

    2013-01-01

    The federal Early Head Start (EHS) program began in 1995, and a randomized trial was conducted to evaluate the efficacy of 17 EHS programs. In all, 3,001 low-income families (35% African American, 24% Hispanic, and 37% White) with a pregnant women or an infant under the age of 12 months were randomly assigned to a treatment or control group (with…

  15. The Developmental Significance of Late Adolescent Substance Use for Early Adult Functioning

    ERIC Educational Resources Information Center

    Englund, Michelle M.; Siebenbruner, Jessica; Oliva, Elizabeth M.; Egeland, Byron; Chung, Chu-Ting; Long, Jeffrey D.

    2013-01-01

    This study examines the predictive significance of late adolescent substance use groups (i.e., abstainers, experimental users, at-risk users, and abusers) for early adult adaptation. Participants (N = 159) were drawn from a prospective longitudinal study of first-born children of low-income mothers. At 17.5 years of age, participants were assigned…

  16. A Developmental Approach to Helping: The Epigenetic Model Applied to the Period of Early Childhood

    ERIC Educational Resources Information Center

    Dawson, Susan H.

    1973-01-01

    The article describes application of the epigenetic model to work with children in the period of early childhood development. The focus is placed on verbal learning. Projects wherein disadvantaged children gain in verbal skills through supervised mother-child interactions are described. The response of families to this approach suggests important…

  17. Developmental Differences in Relations between Episodic Memory and Hippocampal Subregion Volume during Early Childhood

    ERIC Educational Resources Information Center

    Riggins, Tracy; Blankenship, Sarah L.; Mulligan, Elizabeth; Rice, Katherine; Redcay, Elizabeth

    2015-01-01

    Episodic memory shows striking improvement during early childhood. However, neural contributions to these behavioral changes are not well understood. This study examined associations between episodic memory and volume of subregions (head, body, and tail) of the hippocampus--a structure known to support episodic memory in school-aged children and…

  18. Early Childhood Intervention in South Africa in Relation to the Developmental Systems Model

    ERIC Educational Resources Information Center

    Samuels, Alecia M.; Slemming, Wiedaad; Balton, Sadna

    2012-01-01

    As highlighted in recent series in "The Lancet" (2007, 2011), children from low and middle income countries are more likely to be adversely affected by early biological and psychosocial experiences that have their origins in environments characterized by poverty, violence, nutritional deficiencies, HIV infections, substance abuse, and…

  19. Infants' Early Visual Attention and Social Engagement as Developmental Precursors to Joint Attention

    ERIC Educational Resources Information Center

    Salley, Brenda; Sheinkopf, Stephen J.; Neal-Beevers, A. Rebecca; Tenenbaum, Elena J.; Miller-Loncar, Cynthia L.; Tronick, Ed; Lagasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles; Whitaker, Toni; Hammond, Jane; Lester, Barry M.

    2016-01-01

    This study examined infants' early visual attention (at 1 month of age) and social engagement (4 months) as predictors of their later joint attention (12 and 18 months). The sample (n = 325), drawn from the Maternal Lifestyle Study, a longitudinal multicenter project conducted at 4 centers of the National Institute of Child Health and Human…

  20. Early Relationships for Healthy Brains. An interview with Developmental Psychologist Ross Thompson. Perspectives

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2006

    2006-01-01

    Healthy brain development relies on the quality of early relationships. Supportive relationships and parent-child conversations buffer stress; they contribute to the cognitive and emotional stimulation that developing brains need; and the quality of parent-child conversation is important even before young children are good conversational partners.…

  1. Early Childhood Intervention in Portugal: An Overview Based on the Developmental Systems Model

    ERIC Educational Resources Information Center

    Pinto, Ana Isabel; Grande, Catarina; Aguiar, Cecilia; de Almeida, Isabel Chaves; Felgueiras, Isabel; Pimentel, Julia Serpa; Serrano, Ana Maria; Carvalho, Leonor; Brandao, Maria Teresa; Boavida, Tania; Santos, Paula; Lopes-dos-Santos, Pedro

    2012-01-01

    Research studies on early childhood intervention (ECI) in Portugal are diffuse regarding both program components and the geographical area under scrutiny. Since the 1990s, a growing body of knowledge and evidence in ECI is being gathered, based on postgraduate teaching, in-service training, and research. This article draws on the systems theory…

  2. Genetic Moderation of Early Child-Care Effects on Social Functioning Across Childhood: A Developmental Analysis

    ERIC Educational Resources Information Center

    Belsky, Jay; Pluess, Michael

    2013-01-01

    Data from 508 Caucasian children in the NICHD Study of Early Child Care and Youth Development shows that the DRD4 (but not 5-HTTLPR) polymorphism moderates the effect of child-care quality (but not quantity or type) on caregiver-reported externalizing problems at 54 months and in kindergarten and teacher-reported social skills at kindergarten and…

  3. Early Language Impairments and Developmental Pathways of Emotional Problems across Childhood

    ERIC Educational Resources Information Center

    Goh Kok Yew, Shaun; O'Kearney, Richard

    2015-01-01

    Background: Language impairments are associated with an increased likelihood of emotional difficulties later in childhood or adolescence, but little is known about the impact of LI on the growth of emotional problems. Aims: To examine the link between early language status (language impaired (LI), typical language (TL)) and the pattern and…

  4. Elucidating Early Mechanisms of Developmental Psychopathology: The Case of Prenatal Smoking and Disruptive Behavior

    ERIC Educational Resources Information Center

    Wakschlag, Lauren S.; Leventhal, Bennett L.; Pine, Daniel S.; Pickett, Kate E.; Carter, Alice S.

    2006-01-01

    There is a robust association between prenatal smoking and disruptive behavior disorders, but little is known about the emergence of such behaviors in early development. The association of prenatal smoking and hypothesized behavioral precursors to disruptive behavior in toddlers (N=93) was tested. Exposed toddlers demonstrated atypical behavioral…

  5. Developmental Phenotypes and Causal Pathways in Attention Deficit/Hyperactivity Disorder: Potential Targets for Early Intervention?

    ERIC Educational Resources Information Center

    Sonuga-Barke, Edmund J. S.; Halperin, Jeffrey M.

    2010-01-01

    Early intervention approaches have rarely been implemented for the prevention of attention deficit/hyperactivity disorder (ADHD). In this paper we explore whether such an approach may represent an important new direction for therapeutic innovation. We propose that such an approach is most likely to be of value when grounded in and informed by…

  6. Developmental Trends and L1 Effects in Early L2 Learners' Onset Cluster Production

    ERIC Educational Resources Information Center

    Tessier, Anne-Michelle; Duncan, Tamara Sorenson; Paradis, Johanne

    2013-01-01

    This study focuses on English onset cluster production in spontaneous speech samples of 10 children aged 5;04-6;09 from Chinese and Hindi/Punjabi first language (L1) backgrounds, each with less than a year of exposure to English. The results suggest commonalities between early second language (L2) learners and both monolingual and adult L2…

  7. Early Childhood Developmental Status in Low- and Middle-Income Countries: National, Regional, and Global Prevalence Estimates Using Predictive Modeling

    PubMed Central

    McCoy, Dana Charles; Danaei, Goodarz; Black, Maureen M.; Sudfeld, Christopher R.; Fawzi, Wafaie; Fink, Günther

    2016-01-01

    Background The development of cognitive and socioemotional skills early in life influences later health and well-being. Existing estimates of unmet developmental potential in low- and middle-income countries (LMICs) are based on either measures of physical growth or proxy measures such as poverty. In this paper we aim to directly estimate the number of children in LMICs who would be reported by their caregivers to show low cognitive and/or socioemotional development. Methods and Findings The present paper uses Early Childhood Development Index (ECDI) data collected between 2005 and 2015 from 99,222 3- and 4-y-old children living in 35 LMICs as part of the Multiple Indicator Cluster Survey (MICS) and Demographic and Health Surveys (DHS) programs. First, we estimate the prevalence of low cognitive and/or socioemotional ECDI scores within our MICS/DHS sample. Next, we test a series of ordinary least squares regression models predicting low ECDI scores across our MICS/DHS sample countries based on country-level data from the Human Development Index (HDI) and the Nutrition Impact Model Study. We use cross-validation to select the model with the best predictive validity. We then apply this model to all LMICs to generate country-level estimates of the prevalence of low ECDI scores globally, as well as confidence intervals around these estimates. In the pooled MICS and DHS sample, 14.6% of children had low ECDI scores in the cognitive domain, 26.2% had low socioemotional scores, and 36.8% performed poorly in either or both domains. Country-level prevalence of low cognitive and/or socioemotional scores on the ECDI was best represented by a model using the HDI as a predictor. Applying this model to all LMICs, we estimate that 80.8 million children ages 3 and 4 y (95% CI 48.1 million, 113.6 million) in LMICs experienced low cognitive and/or socioemotional development in 2010, with the largest number of affected children in sub-Saharan Africa (29.4.1 million; 43.8% of children

  8. Enamel Defects of Human Primary Dentition as Virtual Memory of Early Developmental Events

    PubMed Central

    Asl Aminabadi, Naser; Ghertasi Oskouei, Sina; Pouralibaba, Firoz; Jamali, Zahra; Pakdel, Farzaneh

    2009-01-01

    Background and aims The objectives of the present study were to investigate the prevalence and the position of enamel defects of primary teeth and hence to estimate the approximate time of an insult. Materials and methods 121 children aged 3 to 5 years were included in the study. The Modified Developmental De-fects of Enamel Index was used to diagnose and classify the defects. The defects were categorized as hypoplasia, hypocalcification or a combination of them. Each tooth was investigated for occlusal/incisal, middle, cervical, incisomiddle, cervicomiddle and complete crown defects. Results 55.37% of the children were affected by enamel defects, 23.96% being categorized as hypocalcification and 22.31% as hypoplasia. The enamel defects were more abundant in maxillary primary incisors and mandibular primary canines. Minimum involvement was seen in maxillary primary second molars and mandibular primary lateral incisors. The prevalence of cervical defects in maxillary primary incisors was significantly more than the middle or incisal defects (P < 0.05). The prevalence of incisal defects in mandibular primary incisors was significantly more than the middle or cervical defects (P < 0.05). Conclusion The results revealed a considerable number of enamel defects which are multiple, symmetric and chrono-logically accordant with the estimated neonatal line in primary teeth of healthy children. PMID:23230497

  9. Maternal high-fat diet prevents developmental programming by early-life stress

    PubMed Central

    Rincel, M; Lépinay, A L; Delage, P; Fioramonti, J; Théodorou, V S; Layé, S; Darnaudéry, M

    2016-01-01

    Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4). Surprisingly, perinatal HFD strongly attenuated the developmental alterations induced by MS. Furthermore, maternal HFD totally prevented the endophenotypes (anxiety, spatial memory, social behavior, hypothalamic–pituitary–adrenal (HPA) axis response to stress, hippocampal neurogenesis and visceral pain) associated with MS at adulthood. Finally, we also demonstrated that HFD intake reduced anxiety and enhanced maternal care in stressed dams. Overall, our data suggest that a HFD restricted to gestation and lactation, which did not lead to overweight in dams, had limited effects in unstressed offspring, highlighting the role of maternal obesity, rather than fat exposure per se, on brain vulnerability during development. PMID:27898075

  10. The Effects of Subchronic Exposure to Terbuthylazine on Early Developmental Stages of Common Carp

    PubMed Central

    Štěpánová, Stanislava; Plhalová, Lucie; Doleželová, Petra; Prokeš, Miroslav; Maršálek, Petr; Škorič, Miša; Svobodová, Zdeňka

    2012-01-01

    The aim of this study was to assess the impact of terbuthylazine in surface waters on fish under experimental conditions. Subchronic toxic effects on embryos and larvae of common carp (Cyprinus carpio) were investigated during a 30-day toxicity test. The exposure to terbuthylazin showed no effect on mortality, but significant differences (P < 0.0001) were revealed on weight and growth parameters at concentrations of 520 and 820 μg/L. The inhibition of specific growth rate at concentrations of 520 and 820 μg/L was 14% compared to the control group. No significant negative effects on total body length and body weight were observed at lower concentrations (0.9 and 160 μg/L). The concentrations 520 and 820 μg/L were associated with a delay in development compared to other experimental groups and controls. On the basis of weight and growth rate evaluation and determination of developmental stages, the No Observed Effect Concentration (NOEC) of terbuthylazine was estimated at 160 μg/L and the Lowest Observed Effect Concentration (LOEC) was 520 μg/L. According to these results, the reported environmental concentration of terbuthylazine in Czech rivers does not impact growth, development, morphology, or histology of carp embryos and larvae. PMID:22629165

  11. Polymorphic core promoter GA-repeats alter gene expression of the early embryonic developmental genes.

    PubMed

    Valipour, E; Kowsari, A; Bayat, H; Banan, M; Kazeminasab, S; Mohammadparast, S; Ohadi, M

    2013-12-01

    Protein complexes that bind to 'GAGA' DNA elements are necessary to replace nucleosomes to create a local chromatin environment that facilitates a variety of site-specific regulatory responses. Three to four elements are required for the disruption of a preassembled nucleosome. We have previously identified human protein-coding gene core promoters that are composed of exceptionally long GA-repeats. The functional implication of those GA-repeats is beginning to emerge in the core promoter of the human SOX5 gene, which is involved in multiple developmental processes. In the current study, we analyze the functional implication of GA-repeats in the core promoter of two additional genes, MECOM and GABRA3, whose expression is largely limited to embryogenesis. We report a significant difference in gene expression as a result of different alleles across those core promoters in the HEK-293 cell line. Across-species homology check for the GABRA3 GA-repeats revealed that those repeats are evolutionary conserved in mouse and primates (p<1 × 10(-8)). The MECOM core promoter GA-repeats are also conserved in numerous species, of which human has the longest repeat and complexity. We propose a novel role for GA-repeat core promoters to regulate gene expression in the genes involved in development and evolution.

  12. Early failure of Pavlik harness treatment for developmental hip dysplasia: clinical and ultrasound predictors.

    PubMed

    Lerman, J A; Emans, J B; Millis, M B; Share, J; Zurakowski, D; Kasser, J R

    2001-01-01

    A cohort of 93 patients with developmental dysplasia of the hip (DDH) treated with a Pavlik harness were evaluated to determine predictors of treatment failure. Failure was defined as failure to achieve or maintain hip reduction in the Pavlik harness. Of 93 patients (137 hips), 17 (26 hips) failed Pavlik harness treatment. Univariate risk factors for failure included bilaterality, initial clinical exam, and initial ultrasound (US) percent coverage. Clinical exam and initial percent coverage were multivariate risk factors for failure. Among initially clinically dislocatable hips, a low initial US alpha angle correlated with an increased likelihood of failure. All (6/6) patients with an initially irreducible hip and an initial coverage of <20% by US eventually failed treatment. Gender, side of pathology, and age at diagnosis and initiation of treatment did not correlate with failure. Irreducibility by physical exam combined with US coverage of <20% identified a patient group that uniformly failed Pavlik harness treatment. These patients may be candidates for alternative bracing, traction, or closed or open reduction.

  13. Information management strategies in early adolescence: developmental change in use and transactional associations with psychological adjustment.

    PubMed

    Laird, Robert D; Marrero, Matthew D; Melching, Jessica A; Kuhn, Emily S

    2013-05-01

    Adolescents use various strategies to manage their parents' access to information. This study tested developmental change in strategy use, longitudinal associations between disclosing and concealing strategies, and longitudinal associations linking disclosing and concealing strategies with antisocial behavior and depressive symptoms. Self-report data (n = 218; 49% female; 49% European American, 47% African American) following Grades 5 (M age = 11 years, 11 months), 6, and 7 show that the use of disclosing strategies (e.g., telling all, telling if asked) following misbehavior declined while use of concealing strategies (e.g., omitting details, keeping secrets, lying) increased over time. Longitudinal links between strategies suggest a transactional process wherein infrequent disclosing is a gateway to concealment but concealment also predicts subsequent rank-order reductions in disclosure. Infrequent disclosing was associated with more subsequent antisocial behavior and depressive symptoms, whereas more antisocial behavior was associated with more subsequent concealment. Although absolute declines in disclosure and increases in concealment are normative, individual differences show that adolescents reporting low levels of disclosure, rather than high levels of concealment, appear to experience the most adjustment problems.

  14. Developmental changes in spontaneous electrocortical activity and network organization from early to late childhood.

    PubMed

    Miskovic, Vladimir; Ma, Xinpei; Chou, Chun-An; Fan, Miaolin; Owens, Max; Sayama, Hiroki; Gibb, Brandon E

    2015-09-01

    We investigated the development of spontaneous (resting state) cerebral electric fields and their network organization from early to late childhood in a large community sample of children. Critically, we examined electrocortical maturation across one-year windows rather than creating aggregate averages that can miss subtle maturational trends. We implemented several novel methodological approaches including a more fine grained examination of spectral features across multiple electrodes, the use of phase-lagged functional connectivity to control for the confounding effects of volume conduction and applying topological network analyses to weighted cortical adjacency matrices. Overall, there were major decreases in absolute EEG spectral density (particularly in the slow wave range) across cortical lobes as a function of age. Moreover, the peak of the alpha frequency increased with chronological age and there was a redistribution of relative spectral density toward the higher frequency ranges, consistent with much of the previous literature. There were age differences in long range functional brain connectivity, particularly in the alpha frequency band, culminating in the most dense and spatially variable networks in the oldest children. We discovered age-related reductions in characteristic path lengths, modularity and homogeneity of alpha-band cortical networks from early to late childhood. In summary, there is evidence of large scale reorganization in endogenous brain electric fields from early to late childhood, suggesting reduced signal amplitudes in the presence of more functionally integrated and band limited coordination of neuronal activity across the cerebral cortex.

  15. Developmental Changes in Spontaneous Electrocortical Activity and Network Organization From Early to Late Childhood

    PubMed Central

    Miskovic, Vladimir; Ma, Xinpei; Chou, Chun-An; Fan, Miaolin; Owens, Max; Sayama, Hiroki; Gibb, Brandon E.

    2015-01-01

    We investigated the development of spontaneous (resting state) cerebral electric fields and their network organization from early to late childhood in a large community sample of children. Critically, we examined electrocortical maturation across one-year windows rather than creating aggregate averages that can miss more subtle maturational trends. We implemented several novel methodological approaches including a more fine grained examination of spectral features across multiple electrodes, the use of phase-lagged functional connectivity to control for the confounding effects of volume conduction and applying topological network analyses to weighted cortical adjacency matrices. Overall, there were major decreases in absolute EEG spectral density (particularly in the slow wave range) across cortical lobes as a function of age. Moreover, the peak of the alpha frequency increased with chronological age and there was a redistribution of relative spectral density towards the higher frequency ranges, consistent with much of the previous literature. There were age differences in long range functional brain connectivity, particularly in the alpha frequency band, culminating in the most dense and spatially variable networks in the oldest children. We discovered age-related reductions in characteristic path lengths, modularity and homogeneity of alpha-band cortical networks from early to late childhood. In summary, there is evidence of large scale reorganization in endogenous brain electric fields from early to late childhood, suggesting reduced signal amplitudes in the presence of more functionally integrated and band limited coordination of neuronal activity across the cerebral cortex. PMID:26057595

  16. Musicians' Enhanced Neural Differentiation of Speech Sounds Arises Early in Life: Developmental Evidence from Ages 3 to 30

    PubMed Central

    Strait, Dana L.; O'Connell, Samantha; Parbery-Clark, Alexandra; Kraus, Nina

    2014-01-01

    The perception and neural representation of acoustically similar speech sounds underlie language development. Music training hones the perception of minute acoustic differences that distinguish sounds; this training may generalize to speech processing given that adult musicians have enhanced neural differentiation of similar speech syllables compared with nonmusicians. Here, we asked whether this neural advantage in musicians is present early in life by assessing musically trained and untrained children as young as age 3. We assessed auditory brainstem responses to the speech syllables /ba/ and /ga/ as well as auditory and visual cognitive abilities in musicians and nonmusicians across 3 developmental time-points: preschoolers, school-aged children, and adults. Cross-phase analyses objectively measured the degree to which subcortical responses differed to these speech syllables in musicians and nonmusicians for each age group. Results reveal that musicians exhibit enhanced neural differentiation of stop consonants early in life and with as little as a few years of training. Furthermore, the extent of subcortical stop consonant distinction correlates with auditory-specific cognitive abilities (i.e., auditory working memory and attention). Results are interpreted according to a corticofugal framework for auditory learning in which subcortical processing enhancements are engendered by strengthened cognitive control over auditory function in musicians. PMID:23599166

  17. Social visual engagement in infants and toddlers with autism: early developmental transitions and a model of pathogenesis.

    PubMed

    Klin, Ami; Shultz, Sarah; Jones, Warren

    2015-03-01

    Efforts to determine and understand the causes of autism are currently hampered by a large disconnect between recent molecular genetics findings that are associated with the condition and the core behavioral symptoms that define the condition. In this perspective piece, we propose a systems biology framework to bridge that gap between genes and symptoms. The framework focuses on basic mechanisms of socialization that are highly-conserved in evolution and are early-emerging in development. By conceiving of these basic mechanisms of socialization as quantitative endophenotypes, we hope to connect genes and behavior in autism through integrative studies of neurodevelopmental, behavioral, and epigenetic changes. These changes both lead to and are led by the accomplishment of specific social adaptive tasks in a typical infant's life. However, based on recent research that indicates that infants later diagnosed with autism fail to accomplish at least some of these tasks, we suggest that a narrow developmental period, spanning critical transitions from reflexive, subcortically-controlled visual behavior to interactional, cortically-controlled and social visual behavior be prioritized for future study. Mapping epigenetic, neural, and behavioral changes that both drive and are driven by these early transitions may shed a bright light on the pathogenesis of autism.

  18. Social visual engagement in infants and toddlers with autism: Early developmental transitions and a model of pathogenesis

    PubMed Central

    Klin, Ami; Shultz, Sarah; Jones, Warren

    2014-01-01

    Efforts to determine and understand the causes of autism are currently hampered by a large disconnect between recent molecular genetics findings that are associated with the condition and the core behavioral symptoms that define the condition. In this perspective piece, we propose a systems biology framework to bridge that gap between genes and symptoms. The framework focuses on basic mechanisms of socialization that are highly-conserved in evolution and are early-emerging in development. By conceiving of these basic mechanisms of socialization as quantitative endophenotypes, we hope to connect genes and behavior in autism through integrative studies of neurodevelopmental, behavioral, and epigenetic changes. These changes both lead to and are led by the accomplishment of specific social adaptive tasks in a typical infant's life. However, based on recent research that indicates that infants later diagnosed with autism fail to accomplish at least some of these tasks, we suggest that a narrow developmental period, spanning critical transitions from reflexive, subcortically-controlled visual behavior to interactional, cortically-controlled and social visual behavior be prioritized for future study. Mapping epigenetic, neural, and behavioral changes that both drive and are driven by these early transitions may shed a bright light on the pathogenesis of autism. PMID:25445180

  19. Developmental Coordination Disorder: Is Clumsy Motor Behavior Caused by a Lesion of the Brain at Early Age?

    PubMed Central

    Hadders-Algra, Mijna

    2003-01-01

    Children presenting with Developmental Coordination Disorder or clumsiness often exhibit signs of minor neurological dysfunction (MND). The data of the Groningen Perinatal Project, a long-term follow-up project .on the relations between prenatal and perinatal adversities and neurological, behavioral, and cognitive development revealed that two basic forms of MND can be distinguished: simple and complex MND. During school age children with simple MND are characterized by the presence of one or two dysfunctional clusters of MND, in adolescence by the presence of choreiform dyskinesia or hypotonia. Probably the major sources of origin of simple MND are genetic constitution and stress during early life. Simple MND might reflect the lower tail of the normal distribution of the quality of non-pathological brain function. In line with this hypothesis is the finding that simple MND is associated with only a moderately increased risk for learning and behavioral problems. Children with complex MND present at school age with at least three dysfunctional clusters of MND, in adolescence with problems in fine manipulation or coordination. Perinatal adversities play an evident etiological role in the development of complex MND, suggesting that it might be attributed to a lesion of the brain at early age. In line with this idea is the finding that complex MND shows .a strong correlation with attention and learning problems. PMID:14640306

  20. Parent-child conflict and early childhood adjustment in two-parent low-income families: parallel developmental processes.

    PubMed

    Weaver, Chelsea M; Shaw, Daniel S; Crossan, Jennifer L; Dishion, Thomas J; Wilson, Melvin N

    2015-02-01

    Parent-child conflict is central to most intervention models focused on reducing child problem behavior, yet few longitudinal studies have examined these processes during early childhood. The current study investigates (1) growth in mother-child and father figure (FF)-child conflict, (2) associations between trajectories of mother-child and FF-child conflict and children's adjustment; and (3) intervention effects in attenuating conflict. Participants are 195 ethnically diverse mother-FF-child triads drawn from a larger parenting intervention study for families with children at risk for developing conduct problems. Mother-child conflict decreased from ages 2 to 4, but decreases were unrelated to changes in children's adjustment problems. In contrast, the slope of FF-child conflict was positively related to the slope of child externalizing behaviors. Random assignment to a family-centered parenting intervention predicted rate of decline in mother-child conflict. Findings are discussed with respect to developmental patterns of parent-child conflict in early childhood and implications for prevention.

  1. Parent–Child Conflict and Early Childhood Adjustment in Two-Parent Low-Income Families: Parallel Developmental Processes

    PubMed Central

    Shaw, Daniel S.; Crossan, Jennifer L.; Dishion, Thomas J.; Wilson, Melvin N.

    2015-01-01

    Parent–child conflict is central to most intervention models focused on reducing child problem behavior, yet few longitudinal studies have examined these processes during early childhood. The current study investigates (1) growth in mother–child and father figure (FF)–child conflict, (2) associations between trajectories of mother–child and FF–child conflict and children’s adjustment; and (3) intervention effects in attenuating conflict. Participants are 195 ethnically diverse mother–FF–child triads drawn from a larger parenting intervention study for families with children at risk for developing conduct problems. Mother–child conflict decreased from ages 2 to 4, but decreases were unrelated to changes in children’s adjustment problems. In contrast, the slope of FF–child conflict was positively related to the slope of child externalizing behaviors. Random assignment to a family-centered parenting intervention predicted rate of decline in mother–child conflict. Findings are discussed with respect to developmental patterns of parent–child conflict in early childhood and implications for prevention. PMID:24610382

  2. The Early Developmental Competencies and School Readiness of Low-Income, Immigrant Children: Influences of Generation, Race/Ethnicity, and National Origins

    ERIC Educational Resources Information Center

    De Feyter, Jessica Johnson; Winsler, Adam

    2009-01-01

    Though much valuable research has been conducted on the academic achievement of school-age immigrant youth, less is known about the early developmental competencies of immigrant children during the preschool years. This study describes the school readiness of 2194 low-income children receiving subsidies to attend child care with emphasis on how…

  3. Sex-Specific Pathways to Early Puberty, Sexual Debut, and Sexual Risk Taking: Tests of an Integrated Evolutionary-Developmental Model

    ERIC Educational Resources Information Center

    James, Jenee; Ellis, Bruce J.; Schlomer, Gabriel L.; Garber, Judy

    2012-01-01

    The current study tested sex-specific pathways to early puberty, sexual debut, and sexual risk taking, as specified by an integrated evolutionary-developmental model of adolescent sexual development and behavior. In a prospective study of 238 adolescents (n = 129 girls and n = 109 boys) followed from approximately 12-18 years of age, we tested for…

  4. The Teacher's Ongoing Role in Creating a Developmentally Appropriate Early Childhood Program: A Self-Study Process for Teachers of Children Ages 5-8.

    ERIC Educational Resources Information Center

    Connecticut State Dept. of Education, Hartford.

    This self-study instrument is designed to support teachers' efforts to implement an early childhood program for children of 5-8 years of age that reflects the qualities of developmentally appropriate programming described in Connecticut's Guide to Program Development for Kindergarten (1988). The contents, which are presented in checklist format,…

  5. An Interpretative Model of Early Indicators of Specific Developmental Dyslexia in Preschool Age: A Comparative Presentation of Three Studies in Greece

    ERIC Educational Resources Information Center

    Zakopoulou, Victoria; Anagnostopoulou, Areti; Christodoulides, Pavlos; Stavrou, Lambros; Sarri, Ioanna; Mavreas, Venetsanos; Tzoufi, Meropi

    2011-01-01

    The detection of specific factors of the developmental dyslexia at an early stage, and the identification of the role of those factors responsible for its manifestation, is a fundamental area of study on dyslexia in the recent literature. The objective of the present study is to clarify that dysfunctions in the following specific domains…

  6. The Study to Explore Early Development (SEED): A Multisite Epidemiologic Study of Autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) Network

    ERIC Educational Resources Information Center

    Schendel, Diana E.; DiGuiseppi, Carolyn; Croen, Lisa A.; Fallin, M. Daniele; Reed, Philip L.; Schieve, Laura A.; Wiggins, Lisa D.; Daniels, Julie; Grether, Judith; Levy, Susan E.; Miller, Lisa; Newschaffer, Craig; Pinto-Martin, Jennifer; Robinson, Cordelia; Windham, Gayle C.; Alexander, Aimee; Aylsworth, Arthur S.; Bernal, Pilar; Bonner, Joseph D.; Blaskey, Lisa; Bradley, Chyrise; Collins, Jack; Ferretti, Casara J.; Farzadegan, Homayoon; Giarelli, Ellen; Harvey, Marques; Hepburn, Susan; Herr, Matthew; Kaparich, Kristina; Landa, Rebecca; Lee, Li-Ching; Levenseller, Brooke; Meyerer, Stacey; Rahbar, Mohammad H.; Ratchford, Andria; Reynolds, Ann; Rosenberg, Steven; Rusyniak, Julie; Shapira, Stuart K.; Smith, Karen; Souders, Margaret; Thompson, Patrick Aaron; Young, Lisa; Yeargin-Allsopp, Marshalyn

    2012-01-01

    The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal,…

  7. Parent-Reported Attention Deficit/Hyperactivity Symptomatology in Preschool-Aged Children: Factor Structure, Developmental Change, and Early Risk Factors

    ERIC Educational Resources Information Center

    Willoughby, Michael T.; Pek, Jolynn; Greenberg, Mark T.

    2012-01-01

    Although Attention Deficit/Hyperactivity Disorder (ADHD) has increasingly been studied in preschool-aged children, relatively few studies have provided a comprehensive evaluation of the factor structure and patterns of developmental changes in parent-reported ADHD symptomatology across the early childhood period. This study used confirmatory…

  8. Effective Connectivity from Early Visual Cortex to Posterior Occipitotemporal Face Areas Supports Face Selectivity and Predicts Developmental Prosopagnosia

    PubMed Central

    Garrido, Lucia; Driver, Jon; Dolan, Raymond J.; Duchaine, Bradley C.; Furl, Nicholas

    2016-01-01

    Face processing is mediated by interactions between functional areas in the occipital and temporal lobe, and the fusiform face area (FFA) and anterior temporal lobe play key roles in the recognition of facial identity. Individuals with developmental prosopagnosia (DP), a lifelong face recognition impairment, have been shown to have structural and functional neuronal alterations in these areas. The present study investigated how face selectivity is generated in participants with normal face processing, and how functional abnormalities associated with DP, arise as a function of network connectivity. Using functional magnetic resonance imaging and dynamic causal modeling, we examined effective connectivity in normal participants by assessing network models that include early visual cortex (EVC) and face-selective areas and then investigated the integrity of this connectivity in participants with DP. Results showed that a feedforward architecture from EVC to the occipital face area, EVC to FFA, and EVC to posterior superior temporal sulcus (pSTS) best explained how face selectivity arises in both controls and participants with DP. In this architecture, the DP group showed reduced connection strengths on feedforward connections carrying face information from EVC to FFA and EVC to pSTS. These altered network dynamics in DP contribute to the diminished face selectivity in the posterior occipitotemporal areas affected in DP. These findings suggest a novel view on the relevance of feedforward projection from EVC to posterior occipitotemporal face areas in generating cortical face selectivity and differences in face recognition ability. SIGNIFICANCE STATEMENT Areas of the human brain showing enhanced activation to faces compared to other objects or places have been extensively studied. However, the factors leading to this face selectively have remained mostly unknown. We show that effective connectivity from early visual cortex to posterior occipitotemporal face areas gives

  9. Effects of a commonly used glyphosate-based herbicide formulation on early developmental stages of two anuran species.

    PubMed

    Wagner, Norman; Müller, Hendrik; Viertel, Bruno

    2017-01-01

    Environmental contamination, especially due to the increasing use of pesticides, is suggested to be one out of six main reasons for the global amphibian decline. Adverse effects of glyphosate-based herbicides on amphibians have been already discussed in several studies with different conclusions, especially regarding sublethal effects at environmentally relevant concentrations. Therefore, we studied the acute toxic effects (mortality, growth, and morphological changes) of the commonly used glyphosate-based herbicide formulation Roundup® UltraMax on early aquatic developmental stages of two anuran species with different larval types (obligate vs. facultative filtrating suspension feeders), the African clawed frog (Xenopus laevis) and the Mediterranean painted frog (Discoglossus pictus). While X. laevis is an established anuran model organism in amphibian toxicological studies, we aim to establish D. pictus as another model for species with facultative filtrating larvae. A special focus of the present study lies on malformations in X. laevis embryos, which were investigated using histological preparations. In general, embryos and larvae of X. laevis reacted more sensitive concerning lethal effects compared to early developmental stages of D. pictus. It was suggested, that especially the different morphology of their filter apparatus and the higher volume of water pumped through the buccopharynx of X. laevis larvae lead to higher exposure to the formulation. The test substance induced similar lethal effects in D. pictus larvae as it does in the teleost standard test organism used in pesticide approval, the rainbow trout (Oncorhynchus mykiss), whereas embryos of both species are apparently more tolerant and, conversely, X. laevis larvae about two times more sensitive. In both species, early larvae always reacted significantly more sensitive than embryos. Exposure to the test substance increased malformation rates in embryos of both species in a concentration

  10. Kisspeptin system in pejerrey fish (Odontesthes bonariensis). Characterization and gene expression pattern during early developmental stages.

    PubMed

    Tovar Bohórquez, M Oswaldo; Mechaly, Alejandro S; Hughes, Lily C; Campanella, Daniela; Ortí, Guillermo; Canosa, Luis F; Somoza, Gustavo M

    2017-02-01

    In vertebrates, kisspeptins and their receptors are known to be related to puberty onset and gonadal maturation, however, there are few studies concerning their role in early development. Here, we characterize the kisspeptin system in the pejerrey, Odontesthes bonariensis, a fish with strong temperature-dependent sex determination. We reconstructed the phylogenetic history of the two ligands (kiss1 and kiss 2) and two receptors (kissr2 and kissr3) in pejerrey in the context of recent classifications of bony fishes, determined their tissue distribution and documented the early expression pattern of these ligands and receptors. Phylogenetic analysis of these gene families clearly resolved the percomorph clade and grouped pejerrey with Beloniformes. Paralogous sets of genes putatively arising from the teleost-specific genome duplication event (3R) were not detected. Kisspeptins and their receptors showed a wide tissue distribution in adult pejerrey, including tissues not related to reproduction. In larvae reared at 24°C, the four kisspeptin elements were expressed in the head from week 1 to week 8 of life, with no differences in transcript levels. Larvae kept at a female-producing temperature (17°C) did not show statistically significant differences in the transcript levels of all analyzed genes during the sex determination/differentiation period; however, in those larvae raised at male producing temperature (29°C), kiss2 levels were increased at week 4 after hatching. These results showed that all members of the kisspeptin system are expressed at this early period, and the increase of kiss2 transcripts at week 4 could be interpreted as it would be related to the differentiation of the brain-pituitary axis in male development.

  11. What makes a difference: Early Head Start evaluation findings in a developmental context.

    PubMed

    Love, John M; Chazan-Cohen, Rachel; Raikes, Helen; Brooks-Gunn, Jeanne

    2013-02-01

    The federal Early Head Start (EHS) program began in 1995, and a randomized trial was conducted to evaluate the efficacy of 17 EHS programs. In all, 3,001 low-income families (35% African American, 24% Hispanic, and 37% White) with a pregnant women or an infant under the age of 12 months were randomly assigned to a treatment or control group (with 91% of the treatment group receiving some services). Data were collected when the children were about 1, 2, and 3 years of age, and at age 5 (2 years after leaving EHS). Research questions examined (1) impacts of EHS at ages 2 and 3 (when services were being offered) and at age 5, and (2) contributions of early education experiences across children's first 5 years of life. Child outcomes included cognition, language, attention, behavior problems, and health; maternal outcomes included parenting, mental health, and employment. Overall impact analyses at ages 2 and 3 indicated that EHS benefited children and families: impacts were seen in all domains, with effect sizes of significant impacts ranging from .10 to .20. At age 5, EHS children had better attention and approaches toward learning as well as fewer behavior problems than the control group, although they did not differ on early school achievement. Subgroup analyses indicated that cognitive impacts were sustained 2 years after the program ended for African American children and language impacts for Hispanic children who spoke Spanish. Some significant family benefits were seen at age 5. Mediated analyses identified which child and family impacts at ages 2 and 3 contributed to the child impacts at age 5 (most relevant were earlier treatment effects on child cognition and on engagement with the parent). Growth curve analyses were also conducted. Although fewer than half the children enrolled in center-based preschool programs between ages 3 and 4, almost 90% participated in the year preceding kindergarten. A higher percentage of EHS than control children were enrolled

  12. Developmental delays at arrival, early intervention enrollment, and adopted Chinese girls' academic performance and internalizing problems in adolescence.

    PubMed

    Tan, Tony Xing

    2014-01-01

    The author investigated the extent of developmental delays in girls adopted from China, their subsequent early intervention (EI) enrollment, and how the delays and EI were related to their academic performance and internalizing problems in adolescence. The sample included 180 adolescent girls (M = 13.4 years, SD = 2.0 years) who were adopted at 3-23.5 months (M = 11.5 months, SD = 3.7 months). Data on the adopted Chinese girls' delays at arrival and EI enrollment in physical therapy (PT) and speech-language therapy (SLT) were collected from the adoptive mothers at the Baseline; data on the adopted Chinese girls' present academic performance and internalizing problems were collected from the adoptive mothers and adopted girls at Wave 4 six years later. Data analyses revealed that 55% of the adoptees had moderate-to-severe delays when first arrived at the adoptive homes. Motor delays significantly increased the odds for PT (odds ratio [OR] = 3.98, 95% CI [2.18, 7.82], p <.001) and SLT (OR = 2.36, 95% CI [1.50-3.72, p <.001). Social-cognitive delays also significantly increased the odds for PT (OR = 1.90, 95% CI [1.36, 2.63], p <.001) and SLT (OR = 1.63, 95% CI [1.22, 2.17], p <.001). Motor delays were negatively associated with academic performance but positively associated with internalizing problems. General linear modeling showed that the adoptees who had developmental delays at arrival and subsequently enrolled in EI scored significantly lower on academic performance than their peers who had delays but did not enroll in EI, as well their peers who had no delays and did not enroll in EI. Implications of these findings are discussed.

  13. Isolation and Culture of Neonatal Mouse Cardiomyocytes

    PubMed Central

    Ehler, Elisabeth; Moore-Morris, Thomas; Lange, Stephan

    2013-01-01

    Cultured neonatal cardiomyocytes have long been used to study myofibrillogenesis and myofibrillar functions. Cultured cardiomyocytes allow for easy investigation and manipulation of biochemical pathways, and their effect on the biomechanical properties of spontaneously beating cardiomyocytes. The following 2-day protocol describes the isolation and culture of neonatal mouse cardiomyocytes. We show how to easily dissect hearts from neonates, dissociate the cardiac tissue and enrich cardiomyocytes from the cardiac cell-population. We discuss the usage of different enzyme mixes for cell-dissociation, and their effects on cell-viability. The isolated cardiomyocytes can be subsequently used for a variety of morphological, electrophysiological, biochemical, cell-biological or biomechanical assays. We optimized the protocol for robustness and reproducibility, by using only commercially available solutions and enzyme mixes that show little lot-to-lot variability. We also address common problems associated with the isolation and culture of cardiomyocytes, and offer a variety of options for the optimization of isolation and culture conditions. PMID:24056408

  14. A Hypothesis About How Early Developmental Methylmercury Exposure Disrupts Behavior in Adulthood

    PubMed Central

    Newland, M. Christopher; Reed, Miranda N.; Rasmussen, Erin

    2015-01-01

    Events that disrupt the early development of the nervous system have lifelong, irreversible behavioral consequences. The environmental contaminant, methylmercury (MeHg), impairs neural development with effects that are manifested well into adulthood and even into aging. Noting the sensitivity of the developing brain to MeHg, the current review advances an argument that one outcome of early MeHg exposure is a distortion in the processing of reinforcing consequences that results in impaired choice, poor inhibition of prepotent responding, and perseveration on discrimination reversals (in the absence of alteration of extradimensional shifts). Neurochemical correlates include increased sensitivity to dopamine agonists and decreased sensitivity to gamma-aminobutyric acid (GABA) agonists. This leads to a hypothesis that the prefrontal cortex or dopamine neurotransmission is especially sensitive to even subtle gestational MeHg exposure and suggests that public health assessments of MeHg based on intellectual performance may underestimate the impact of MeHg in public health. Finally, those interested in modeling neural development may benefit from MeHg as an experimental model. PMID:25795099

  15. Developmental Associations Between Conduct Problems and Expressive Language in Early Childhood: A Population-Based Study.

    PubMed

    Girard, Lisa-Christine; Pingault, Jean-Baptiste; Doyle, Orla; Falissard, Bruno; Tremblay, Richard E

    2016-08-01

    Conduct problems have been associated with poor language development, however the direction of this association in early childhood remains unclear. This study examined the longitudinal directional associations between conduct problems and expressive language ability. Children enrolled in the UK Millennium Cohort Study (N = 14, 004; 50.3 % boys) were assessed at 3 and 5 years of age. Parent reports of conduct problems and standardised assessments of expressive language were analyzed using cross-lagged modeling. Conduct problems at 3 years was associated with poorer expressive language at 5 years and poorer expressive language at 3 years was associated with increased conduct problems by 5 years. The results support reciprocal associations, rather than a specific unidirectional path, which is commonly found with samples of older children. The emergence of problems in either domain can thus negatively impact upon the other over time, albeit the effects were modest. Studies examining the effects of intervention targeting conduct problems and language acquisition prior to school entry may be warranted in testing the efficacy of prevention programmes related to conduct problems and poor language ability early in childhood.

  16. The "early life" origins of obesity-related health disorders: new discoveries regarding the intergenerational transmission of developmentally programmed traits in the global cardiometabolic health crisis.

    PubMed

    Benyshek, Daniel C

    2013-12-01

    Popular media reports concerning the causes of the current global obesity pandemic and its related sequelae-the cardiometabolic syndrome-are often couched in terms of dramatic changes in diet and lifestyle around the world; namely, drastically increasing dietary intakes of high energy foods and plummeting levels of daily physical activity-the hallmarks of the so called "nutrition transition." Far less attention is generally drawn to the important role phenotypic plasticity during early life (i.e., "developmental programming") plays in the cardiometabolic health crisis. Recently, however, researchers working within the field of the developmental origins of health and disease (DOHaD) and epigenetics have extended our understanding of the role played by these developmental processes and capacities in health and disease even further by investigating the transmissible nature of developmentally programmed cardiometabolic traits to subsequent generations. In this review, after briefly revisiting the fundamental discoveries of first-generation DOHaD research, I consider how recent discoveries regarding the transmissibility of developmentally acquired traits are providing new insights into the current global cardiometabolic pandemic, and how a better understanding of developmental programming-including transmissibility-are essential for the conceptualization and implementation of public health initiatives aimed at stemming this global health crisis.

  17. Regulation of cardiomyocyte autophagy by calcium.

    PubMed

    Shaikh, Soni; Troncoso, Rodrigo; Criollo, Alfredo; Bravo-Sagua, Roberto; García, Lorena; Morselli, Eugenia; Cifuentes, Mariana; Quest, Andrew F G; Hill, Joseph A; Lavandero, Sergio

    2016-04-15

    Calcium signaling plays a crucial role in a multitude of events within the cardiomyocyte, including cell cycle control, growth, apoptosis, and autophagy. With respect to calcium-dependent regulation of autophagy, ion channels and exchangers, receptors, and intracellular mediators play fundamental roles. In this review, we discuss calcium-dependent regulation of cardiomyocyte autophagy, a lysosomal mechanism that is often cytoprotective, serving to defend against disease-related stress and nutrient insufficiency. We also highlight the importance of the subcellular distribution of calcium and related proteins, interorganelle communication, and other key signaling events that govern cardiomyocyte autophagy.

  18. Early developmental stages of Ascaris lumbricoides featured by high-resolution mass spectrometry.

    PubMed

    Melo, Carlos Fernando Odir Rodrigues; Esteves, Cibele Zanardi; de Oliveira, Rosimeire Nunes; Guerreiro, Tatiane Melina; de Oliveira, Diogo Noin; Lima, Estela de Oliveira; Miné, Júlio César; Allegretti, Silmara Marques; Catharino, Rodrigo Ramos

    2016-11-01

    Ascaris lumbricoides is responsible for a highly disseminated helminth parasitic disease, ascariosis, a relevant parasitosis that responds for great financial burden on the public health system of developing countries. In this work, metabolic fingerprinting using high-resolution mass spectrometry (HRMS) was employed to identify marker molecules from A. lumbricoides in different development stages. We have identified nine biomarkers, such as pheromones and steroidal prohormones in early stages, among other molecules in late development stages, making up four molecules for fertilized eggs, four marker molecules for first larvae (L1) and one marker molecule for third larvae (L3). Therefore, our findings indicate that this approach is suitable for biochemical characterization of A. lumbricoides development stages. Moreover, the straightforward analytical method employed, with almost no sample preparation from a complex matrix (feces) using high-resolution mass spectrometry, suggests that it is possible to seek for an easier and faster way to study animal molding processes.

  19. Neighborhood poverty and early transition to sexual activity in young adolescents: a developmental ecological approach.

    PubMed

    Dupéré, Véronique; Lacourse, Eric; Willms, J Douglas; Leventhal, Tama; Tremblay, Richard E

    2008-01-01

    This study examined how the link between neighborhood poverty and the timing of sexual initiation varies as a function of age, gender, and background characteristics. A sample of N = 2,596 predominately White Canadian adolescents from the National Longitudinal Survey of Children and Youth was used. Sexual initiations occurring between 12 and 15 years old were considered. Results showed that younger adolescent females who lived in poor neighborhoods and who had a history of conduct problems were more likely to report early sexual activity. Peer characteristics partly accounted for this susceptibility. Among adolescent males, no direct neighborhood effects were found, but those who had combined risks at multiple levels appeared more vulnerable. The theoretical and practical implications of these findings are discussed.

  20. Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas.

    PubMed

    Schroeder, Diane I; Jayashankar, Kartika; Douglas, Kory C; Thirkill, Twanda L; York, Daniel; Dickinson, Pete J; Williams, Lawrence E; Samollow, Paul B; Ross, Pablo J; Bannasch, Danika L; Douglas, Gordon C; LaSalle, Janine M

    2015-08-01

    Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs) and highly methylated domains (HMDs) with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq) analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo.

  1. Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer's-like memory deficits in the Ts65Dn mouse model of Down syndrome.

    PubMed

    Kazim, Syed Faraz; Blanchard, Julie; Bianchi, Riccardo; Iqbal, Khalid

    2017-04-03

    Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer's disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS in utero, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3β) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model.

  2. Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer’s-like memory deficits in the Ts65Dn mouse model of Down syndrome

    PubMed Central

    Kazim, Syed Faraz; Blanchard, Julie; Bianchi, Riccardo; Iqbal, Khalid

    2017-01-01

    Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer’s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS in utero, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3β) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model. PMID:28368015

  3. Biochemical defects of mutant nudel alleles causing early developmental arrest or dorsalization of the Drosophila embryo.

    PubMed Central

    LeMosy, E K; Leclerc, C L; Hashimoto, C

    2000-01-01

    The nudel gene of Drosophila is maternally required both for structural integrity of the egg and for dorsoventral patterning of the embryo. It encodes a structurally modular protein that is secreted by ovarian follicle cells. Genetic and molecular studies have suggested that the Nudel protein is also functionally modular, with a serine protease domain that is specifically required for ventral development. Here we describe biochemical and immunolocalization studies that provide insight into the molecular basis for the distinct phenotypes produced by nudel mutations and for the interactions between these alleles. Mutations causing loss of embryonic dorsoventral polarity result in a failure to activate the protease domain of Nudel. Our analyses support previous findings that catalytic activity of the protease domain is required for dorsoventral patterning and that the Nudel protease is auto-activated and reveal an important role for a region adjacent to the protease domain in Nudel protease function. Mutations causing egg fragility and early embryonic arrest result in a significant decrease in extracellular Nudel protein, due to defects in post-translational processing, stability, or secretion. On the basis of these and other studies of serine proteases, we suggest potential mechanisms for the complementary and antagonistic interactions between the nudel alleles. PMID:10628985

  4. Fungal and algal gene expression in early developmental stages of lichen-symbiosis.

    PubMed

    Joneson, Suzanne; Armaleo, Daniele; Lutzoni, François

    2011-01-01

    How plants and microbes recognize each other and interact to form long-lasting relationships remains one of the central questions in cellular communication. The symbiosis between the filamentous fungus Cladonia grayi and the single-celled green alga Asterochloris sp. was used to determine fungal and algal genes upregulated in vitro in early lichen development. cDNA libraries of upregulated genes were created with suppression subtractive hybridization in the first two stages of lichen development. Quantitative PCR subsequently was used to verify the expression level of 41 and 33 candidate fungal and algal genes respectively. Induced fungal genes showed significant matches to genes putatively encoding proteins involved in self and non-self recognition, lipid metabolism, and negative regulation of glucose repressible genes, as well as to a putative d-arabitol reductase and two dioxygenases. Upregulated algal genes included a chitinase-like protein, an amino acid metabolism protein, a dynein-related protein and a protein arginine methyltransferase. These results also provided the first evidence that extracellular communication without cellular contact can occur between lichen symbionts. Many genes showing slight variation in expression appear to direct the development of the lichen symbiosis. The results of this study highlight future avenues of investigation into the molecular biology of lichen symbiosis.

  5. Developmental trajectories of anxiety symptoms in early adolescence: the influence of anxiety sensitivity.

    PubMed

    Allan, Nicholas P; Capron, Daniel W; Lejuez, Carl W; Reynolds, Elizabeth K; MacPherson, Laura; Schmidt, Norman B

    2014-05-01

    Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity has been identified as an important risk factor in the development of anxiety psychopathology. This study prospectively examined the development of anxiety symptoms in a sample of 277 adolescents (M age = 11.52; 44 % female, 56 % male) over a 3 year period including the influence of anxiety sensitivity on this development. Further, this study investigated whether there were distinct classes of adolescents based on their anxiety symptom trajectories and including anxiety sensitivity as a predictor. Consistent with other reports, findings indicated an overall decline in anxiety symptoms over time in the sample. However, three classes of adolescents were found with distinct anxiety symptom trajectories and anxiety sensitivity was an important predictor of class membership. Adolescents with elevated anxiety sensitivity scores were more likely to be classified as having high and increasing anxiety symptoms over time versus having moderate to low and decreasing anxiety symptoms over time. There are important implications for identification of adolescents and children who are at risk for the development of an anxiety disorder.

  6. Developmental profile and synaptic origin of early network oscillations in the CA1 region of rat neonatal hippocampus

    PubMed Central

    Garaschuk, Olga; Hanse, Eric; Konnerth, Arthur

    1998-01-01

    By applying fura-2-based fluorometric calcium imaging to neonatal rat hippocampal slices we identified a developmentally regulated spontaneous neuronal activity in the CA1 region of the hippocampus. The activity consisted of bursts of intracellular Ca2+ transients recurring synchronously at a slow rate of 0.4–2 min−1 in the entire population of pyramidal neurones and interneurones. These early network oscillations (ENOs) were present during a restricted period of postnatal development. Thus, they were not detected at the day of birth (P0), at P1–P4 they consisted of bursts of large (up to 1.5 μm) Ca2+ transients, gradually transforming into regularly occurring, smaller Ca2+ transients during the subsequent week. Beyond P15–P16 no ENOs were detected. The ENOs were blocked by tetrodotoxin (TTX) and by a reduction in temperature from 33–35°C to 20–22°C. By combining fluorometric imaging with whole-cell current-clamp recordings, we found that each ENO-related Ca2+ transient was associated with a high-frequency (up to 100 Hz) train of action potentials riding on a depolarizing wave. Recordings in the voltage-clamp mode revealed barrages of synaptic currents that were strictly correlated with the ENO-associated Ca2+ transients in neighbouring pyramidal neurones. Perfusing the cells with an intracellular solution that allowed for a discrimination between GABAA and glutamate receptor-mediated currents showed that these barrages of synaptic currents were predominantly of GABAergic origin. The ENOs were totally blocked by the GABAA receptor antagonist bicuculline and they were also substantially reduced by the glutamatergic antagonists d,l-2-amino-5-phosphonovaleric acid (d,l-APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Synaptic stimulation and application of the GABAA receptor agonist muscimol mimicked the spontaneous Ca2+ transients in pyramidal neurones. The efficacy of muscimol in evoking Ca2+ transients decreased during development in parallel

  7. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc.

  8. Internalizing symptoms: effects of a preventive intervention on developmental pathways from early adolescence to young adulthood.

    PubMed

    Trudeau, Linda; Spoth, Richard; Randall, G Kevin; Mason, W Alex; Shin, Chungyeol

    2012-06-01

    This study examined the mediated and moderated effects of a universal family-focused preventive intervention, delivered during young adolescence, on internalizing symptoms assessed in young adulthood. Sixth grade students (N=446; 52% female; 98% White) and their families from 22 rural Midwestern school districts were randomly assigned to the experimental conditions in 1993. Self-report questionnaires were administered at seven time points (pre-test to young adulthood-age 21) to those receiving the Iowa Strengthening Families Program (ISFP) and to the control group. Results showed that growth factors of adolescent internalizing symptoms (grades 6-12) were predicted by ISFP condition and risk status (defined as early substance initiation). Moderation of the condition effect by risk status was found, with higher-risk adolescents benefitting more from the ISFP. Results also supported the hypothesis that the ISFP's effect on internalizing symptoms in young adulthood was mediated through growth factors of adolescents' internalizing symptoms; risk moderation, however, was only marginally significant in young adulthood. The relative reduction rate on clinical or subclinical levels of young adult internalizing symptoms was 28%, indicating that for every 100 young adults displaying clinical or subclinical levels of internalizing symptoms from school districts not offering an intervention, there could be as few as 72 displaying those levels of symptoms in school districts that offered middle school prevention programming. These findings highlight how the positive effects of family-focused universal interventions can extend to non-targeted outcomes and the related potential public-health impact of scaling up these interventions.

  9. Developmental adaptation of withdrawal reflexes to early alteration of peripheral innervation in the rat.

    PubMed

    Holmberg, H; Schouenborg, J

    1996-09-01

    1. In adult decerebrate spinal rats whose plantar nerves (PLN) had been transected at either postnatal day 1 (P1) or P21 the nociceptive withdrawal reflexes (NWR) of musculi extensor digitorum longus (EDL), peroneus longus (PER) and semitendinosus (ST) were characterized with respect to receptive field (RF) organization, magnitude and time course, using electromyography. Thermal (short CO2 laser pulses) and mechanical (calibrated pinch) stimulation were used. The innervation patterns in normal and lesioned adult rats were assessed by acute nerve lesions. 2. The spatial organization of the mean mechano- and thermonociceptive RFs of all the muscles studied was similar to normal in both P1- and P21-lesioned rats, although in some P21-lesioned rats atypical EDL RFs were encountered. 3. In P1-lesioned rats thermo-NWR of PER and EDL had normal magnitudes, while mechano-NWR were reduced. In P21-lesioned rats both thermo- and mechano-NWR of these muscles had reduced magnitudes. Except for thermo-NWR of ST in P1-lesioned rats, which were increased, NWR of ST had normal magnitudes in both P1- and P21-lesioned rats. The time course of thermonociceptive NWR of the muscles studied were near normal in both P1- and P21-lesioned rats. 4. Acute nerve lesions in adult P1-lesioned rats revealed an essentially abolished contribution to NWR from the PLN. Instead, the contribution to NWR from other hindpaw nerves, such as the superficial and deep peroneal nerves, was dramatically increased. By contrast, in P21-lesioned rats, the regenerated PLN contributed significantly to the NWR. 5. It is concluded that despite profound alterations of plantar hindpaw innervation induced by early PLN transection the cutaneous nociceptive input to NWR attained an essentially normal spatial organization. An experience-dependent mechanism is suggested to be instrumental in adapting the reflex connectivity to the peripheral innervation.

  10. Developmental trends in auditory processing can provide early predictions of language acquisition in young infants.

    PubMed

    Chonchaiya, Weerasak; Tardif, Twila; Mai, Xiaoqin; Xu, Lin; Li, Mingyan; Kaciroti, Niko; Kileny, Paul R; Shao, Jie; Lozoff, Betsy

    2013-03-01

    Auditory processing capabilities at the subcortical level have been hypothesized to impact an individual's development of both language and reading abilities. The present study examined whether auditory processing capabilities relate to language development in healthy 9-month-old infants. Participants were 71 infants (31 boys and 40 girls) with both Auditory Brainstem Response (ABR) and language assessments. At 6 weeks and/or 9 months of age, the infants underwent ABR testing using both a standard hearing screening protocol with 30 dB clicks and a second protocol using click pairs separated by 8, 16, and 64-ms intervals presented at 80 dB. We evaluated the effects of interval duration on ABR latency and amplitude elicited by the second click. At 9 months, language development was assessed via parent report on the Chinese Communicative Development Inventory - Putonghua version (CCDI-P). Wave V latency z-scores of the 64-ms condition at 6 weeks showed strong direct relationships with Wave V latency in the same condition at 9 months. More importantly, shorter Wave V latencies at 9 months showed strong relationships with the CCDI-P composite consisting of phrases understood, gestures, and words produced. Likewise, infants who had greater decreases in Wave V latencies from 6 weeks to 9 months had higher CCDI-P composite scores. Females had higher language development scores and shorter Wave V latencies at both ages than males. Interestingly, when the ABR Wave V latencies at both ages were taken into account, the direct effects of gender on language disappeared. In conclusion, these results support the importance of low-level auditory processing capabilities for early language acquisition in a population of typically developing young infants. Moreover, the auditory brainstem response in this paradigm shows promise as an electrophysiological marker to predict individual differences in language development in young children.

  11. Developmental Exposure to Organophosphate Flame Retardants Elicits Overt Toxicity and Alters Behavior in Early Life Stage Zebrafish (Danio rerio)

    PubMed Central

    Dishaw, Laura V.; Hunter, Deborah L.; Padnos, Beth; Padilla, Stephanie; Stapleton, Heather M.

    2014-01-01

    Organophosphate flame retardants (OPFRs) are common replacements for the phased-out polybrominated diphenyl ethers (PBDEs) and have been detected at high concentrations in environmental samples. OPFRs are structurally similar to organophosphate pesticides and may adversely affect the developing nervous system. This study evaluated the overt toxicity, uptake, and neurobehavioral effects of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP) in early life stage zebrafish. Chlorpyrifos was used as a positive control. For overt toxicity and neurobehavioral assessments, zebrafish were exposed from 0 to 5 days postfertilization (dpf). Hatching, death, or malformations were evaluated daily. Teratogenic effects were scored by visual examination on 6 dpf. To evaluate uptake and metabolism, zebrafish were exposed to 1 µM of each organophosphate (OP) flame retardant and collected on 1 and 5 dpf to monitor accumulation. Larval swimming activity was measured in 6 dpf larvae to evaluate neurobehavioral effects of exposures below the acute toxicity threshold. TDBPP elicited the greatest toxicity at >1 µM. TDCPP and chlorpyrifos were overtly toxic at concentrations ≥10 µM, TCEP, and TCPP were not overtly toxic at the doses tested. Tissue concentrations increased with increasing hydrophobicity of the parent chemical after 24 h exposures. TDCPP and TDBPP and their respective metabolites were detected in embryos on 5 dpf. For all chemicals tested, developmental exposures that were not overtly toxic significantly altered larval swimming activity. These data indicate that OPFRs adversely affect development of early life stage zebrafish. PMID:25239634

  12. Developmental exposure to organophosphate flame retardants elicits overt toxicity and alters behavior in early life stage zebrafish (Danio rerio).

    PubMed

    Dishaw, Laura V; Hunter, Deborah L; Padnos, Beth; Padilla, Stephanie; Stapleton, Heather M

    2014-12-01

    Organophosphate flame retardants (OPFRs) are common replacements for the phased-out polybrominated diphenyl ethers (PBDEs) and have been detected at high concentrations in environmental samples. OPFRs are structurally similar to organophosphate pesticides and may adversely affect the developing nervous system. This study evaluated the overt toxicity, uptake, and neurobehavioral effects of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP) in early life stage zebrafish. Chlorpyrifos was used as a positive control. For overt toxicity and neurobehavioral assessments, zebrafish were exposed from 0 to 5 days postfertilization (dpf). Hatching, death, or malformations were evaluated daily. Teratogenic effects were scored by visual examination on 6 dpf. To evaluate uptake and metabolism, zebrafish were exposed to 1 µM of each organophosphate (OP) flame retardant and collected on 1 and 5 dpf to monitor accumulation. Larval swimming activity was measured in 6 dpf larvae to evaluate neurobehavioral effects of exposures below the acute toxicity threshold. TDBPP elicited the greatest toxicity at >1 µM. TDCPP and chlorpyrifos were overtly toxic at concentrations ≥10 µM, TCEP, and TCPP were not overtly toxic at the doses tested. Tissue concentrations increased with increasing hydrophobicity of the parent chemical after 24 h exposures. TDCPP and TDBPP and their respective metabolites were detected in embryos on 5 dpf. For all chemicals tested, developmental exposures that were not overtly toxic significantly altered larval swimming activity. These data indicate that OPFRs adversely affect development of early life stage zebrafish.

  13. Growth Attenuation with Developmental Schedule Progression in Embryos and Early Larvae of Sterechinus neumayeri Raised under Elevated CO2

    PubMed Central

    Yu, Pauline C.; Sewell, Mary A.; Matson, Paul G.; Rivest, Emily B.; Kapsenberg, Lydia; Hofmann, Gretchen E.

    2013-01-01

    The Southern Ocean, a region that will be an ocean acidification hotspot in the near future, is home to a uniquely adapted fauna that includes a diversity of lightly-calcified invertebrates. We exposed the larvae of the echinoid Sterechinus neumayeri to environmental levels of CO2 in McMurdo Sound (control: 410 µatm, Ω = 1.35) and mildly elevated pCO2 levels, both near the level of the aragonite saturation horizon (510 µatm pCO2, Ω = 1.12), and to under-saturating conditions (730 µatm, Ω = 0.82). Early embryological development was normal under these conditions with the exception of the hatching process, which was slightly delayed. Appearance of the initial calcium carbonate (CaCO3) spicule nuclei among the primary mesenchyme cells of the gastrulae was synchronous between control and elevated pCO2 treatments. However, by prism (7 days after the initial appearance of the spicule nucleus), elongating arm rod spicules were already significantly shorter in the highest CO2 treatment. Unfed larvae in the 730 µatm pCO2 treatment remained significantly smaller than unfed control larvae at days 15–30, and larvae in the 510 µatm treatment were significantly smaller at day 20. At day 30, the arm lengths were more differentiated between 730 µatm and control CO2 treatments than were body lengths as components of total length. Arm length is the most plastic morphological aspect of the echinopluteus, and appears to exhibit the greatest response to high pCO2/low pH/low carbonate, even in the absence of food. Thus, while the effects of elevated pCO2 representative of near future climate scenarios are proportionally minor on these early developmental stages, the longer term effects on these long-lived invertebrates is still unknown. PMID:23300974

  14. Substance use changes and social role transitions: proximal developmental effects on ongoing trajectories from late adolescence through early adulthood.

    PubMed

    Staff, Jeremy; Schulenberg, John E; Maslowsky, Julie; Bachman, Jerald G; O'Malley, Patrick M; Maggs, Jennifer L; Johnston, Lloyd D

    2010-11-01

    Substance use changes rapidly during late adolescence and early adulthood. This time in the life course is also dense with social role changes, as role changes provide dynamic context for individual developmental change. Using nationally representative, multiwave longitudinal data from age 18 to 28, we examine proximal links between changes in social roles and changes in substance use during the transition to adulthood. We find that changes in family roles, such as marriage, divorce, and parenthood, have clear and consistent associations with changes in substance use. With some notable exceptions, changes in school and work roles have weaker effects on changes in substance use compared to family roles. Changes in socializing (i.e., nights out for fun and recreation) and in religiosity were found to mediate the relationship of social role transitions to substance use. Two time-invariant covariates, socioeconomic background and heavy adolescent substance use, predicted social role status, but did not moderate associations, as within-person links between social roles and substance use were largely equivalent across groups. This paper adds to the cascading effects literature by considering how, within individuals, more proximal variations in school, work, and family roles relate to variations in substance use, and which roles appear to be most influential in precipitating changes in substance use during the transition to adulthood.

  15. Developmental insights from early mammalian embryos and core signaling pathways that influence human pluripotent cell growth and differentiation.

    PubMed

    Chen, Kevin G; Mallon, Barbara S; Johnson, Kory R; Hamilton, Rebecca S; McKay, Ronald D G; Robey, Pamela G

    2014-05-01

    Human pluripotent stem cells (hPSCs) have two potentially attractive applications: cell replacement-based therapies and drug discovery. Both require the efficient generation of large quantities of clinical-grade stem cells that are free from harmful genomic alterations. The currently employed colony-type culture methods often result in low cell yields, unavoidably heterogeneous cell populations, and substantial chromosomal abnormalities. Here, we shed light on the structural relationship between hPSC colonies/embryoid bodies and early-stage embryos in order to optimize current culture methods based on the insights from developmental biology. We further highlight core signaling pathways that underlie multiple epithelial-to-mesenchymal transitions (EMTs), cellular heterogeneity, and chromosomal instability in hPSCs. We also analyze emerging methods such as non-colony type monolayer (NCM) and suspension culture, which provide alternative growth models for hPSC expansion and differentiation. Furthermore, based on the influence of cell-cell interactions and signaling pathways, we propose concepts, strategies, and solutions for production of clinical-grade hPSCs, stem cell precursors, and miniorganoids, which are pivotal steps needed for future clinical applications.

  16. Vanadate induces necrotic death in neonatal rat cardiomyocytes through mitochondrial membrane depolarization.

    PubMed

    Soares, Sandra Sofia; Henao, Fernando; Aureliano, Manuel; Gutiérrez-Merino, Carlos

    2008-03-01

    Besides the well-known inotropic effects of vanadium in cardiac muscle, previous studies have shown that vanadate can stimulate cell growth or induce cell death. In this work, we studied the toxicity to neonatal rat ventricular myocytes (cardiomyocytes) of two vanadate solutions containing different oligovanadates distribution, decavanadate (containing decameric vanadate, V 10) and metavanadate (containing monomeric vanadate and also di-, tetra-, and pentavanadate). Incubation for 24 h with decavanadate or metavanadate induced necrotic cell death of cardiomyocytes, without significant caspase-3 activation. Only 10 microM total vanadium of either decavanadate (1 microM V 10) or metavanadate (10 microM total vanadium) was needed to produce 50% loss of cell viability after 24 h (assessed with MTT and propidium iodide assays). Atomic absorption spectroscopy showed that vanadium accumulation in cardiomyocytes after 24 h was the same when incubation was done with decavanadate or metavanadate. A decrease of 75% of the rate of mitochondrial superoxide anion generation, monitored with dihydroethidium, and a sustained rise of cytosolic calcium (monitored with Fura-2-loaded cardiomyocytes) was observed after 24 h of incubation of cardiomyocytes with decavanadate or metavanadate concentrations close to those inducing 50% loss of cell viability produced. In addition, mitochondrial membrane depolarization within cardiomyocytes, monitored with tetramethylrhodamine ethyl esther or with 3,3',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide, were observed after only 6 h of incubation with decavanadate or metavanadate. The concentration needed for 50% mitochondrial depolarization was 6.5 +/- 1 microM total vanadium for both decavanadate (0.65 microM V 10) and metavanadate. In conclusion, mitochondrial membrane depolarization was an early event in decavanadate- and monovanadate-induced necrotic cell death of cardiomyocytes.

  17. Diagnostic Classification 0-3: Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood.

    ERIC Educational Resources Information Center

    Zero to Three: National Center for Infants, Toddlers and Families, Washington, DC.

    The diagnostic framework presented in this manual seeks to address the need for a systematic, multi-disciplinary, developmentally based approach to the classification of mental health and developmental difficulties in the first 4 years of life. An introduction discusses clinical approaches to assessment and diagnosis, gives an overview of the…

  18. Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood. Diagnostic Classification: 0-3.

    ERIC Educational Resources Information Center

    Wieder, Serena, Ed.

    The diagnostic framework presented in this manual seeks to address the need for a systematic, multidisciplinary, developmentally based approach to the classification of mental health and developmental difficulties in the first 4 years of life. An introduction discusses clinical approaches to assessment and diagnosis, gives an overview of the…

  19. Annotation: Early Intervention and Prevention of Self-Injurious Behaviour Exhibited by Young Children with Developmental Disabilities

    ERIC Educational Resources Information Center

    Richman, D. M.

    2008-01-01

    The ontogeny of self-injurious behaviour exhibited by young children with developmental delays or disabilities is due to a complex interaction between neurobiological and environmental variables. In this manuscript, the literature on emerging self-injury in the developmental disability population is reviewed with a focus on an operant conceptual…

  20. Setting the Stage: Early Child and Family Characteristics as Predictors of Later Loneliness in Children with Developmental Disabilities

    ERIC Educational Resources Information Center

    Howell, Angela; Hauser-Cram, Penny; Kersh, Joanne E.

    2007-01-01

    Children with developmental disabilities often report having few friends. Researchers have tended to focus on social skill deficits, neglecting other potent predictors of children's feelings of loneliness. In a sample of 82 children with developmental disabilities, we examined characteristics of the child at age 3 (i.e., the conclusion of early…

  1. Getting Ready for College: An Implementation and Early Impacts Study of Eight Texas Developmental Summer Bridge Programs. NCPR Brief

    ERIC Educational Resources Information Center

    Wathington, Heather D.; Barnett, Elisabeth A.; Weissman, Evan; Teres, Jedediah; Pretlow, Joshua; Nakanishi, Aki

    2011-01-01

    In 2009, the National Center for Postsecondary Research (NCPR) launched an evaluation of eight developmental summer bridge programs in Texas to assess whether these programs reduce the need for developmental coursework and improve student outcomes in college. The evaluation uses an experimental design to measure the effects of these programs on…

  2. Developmental Programming of Nonalcoholic Fatty Liver Disease: The Effect of Early Life Nutrition on Susceptibility and Disease Severity in Later Life.

    PubMed

    Li, Minglan; Reynolds, Clare M; Segovia, Stephanie A; Gray, Clint; Vickers, Mark H

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is fast becoming the most common liver disease globally and parallels rising obesity rates. The developmental origins of health and disease hypothesis have linked alterations in the early life environment to an increased risk of metabolic disorders in later life. Altered early life nutrition, in addition to increasing risk for the development of obesity, type 2 diabetes, and cardiovascular disease in offspring, is now associated with an increased risk for the development of NAFLD. This review summarizes emerging research on the developmental programming of NAFLD by both maternal obesity and undernutrition with a particular focus on the possible mechanisms underlying the development of hepatic dysfunction and potential strategies for intervention.

  3. Developmental trajectory from early responses to transgressions to future antisocial behavior: evidence for the role of the parent-child relationship from two longitudinal studies.

    PubMed

    Kim, Sanghag; Kochanska, Grazyna; Boldt, Lea J; Nordling, Jamie Koenig; O'Bleness, Jessica J

    2014-02-01

    Parent-child relationships are critical in development, but much remains to be learned about the mechanisms of their impact. We examined the early parent-child relationship as a moderator of the developmental trajectory from children's affective and behavioral responses to transgressions to future antisocial, externalizing behavior problems in the Family Study (102 community mothers, fathers, and infants, followed through age 8) and the Play Study (186 low-income, diverse mothers and toddlers, followed for 10 months). The relationship quality was indexed by attachment security in the Family Study and maternal responsiveness in the Play Study. Responses to transgressions (tense discomfort and reparation) were observed in laboratory mishaps wherein children believed they had damaged a valued object. Antisocial outcomes were rated by parents. In both studies, early relationships moderated the future developmental trajectory: diminished tense discomfort predicted more antisocial outcomes, but only in insecure or unresponsive relationships. That risk was defused in secure or responsive relationships. Moderated mediation analyses in the Family Study indicated that the links between diminished tense discomfort and future antisocial behavior in insecure parent-child dyads were mediated by stronger discipline pressure from parents. By indirectly influencing future developmental sequelae, early relationships may increase or decrease the probability that the parent-child dyad will embark on a path toward antisocial outcomes.

  4. Automatic classification of gait in children with early-onset ataxia or developmental coordination disorder and controls using inertial sensors.

    PubMed

    Mannini, Andrea; Martinez-Manzanera, Octavio; Lawerman, Tjitske F; Trojaniello, Diana; Croce, Ugo Della; Sival, Deborah A; Maurits, Natasha M; Sabatini, Angelo Maria

    2017-02-01

    Early-Onset Ataxia (EOA) and Developmental Coordination Disorder (DCD) are two conditions that affect coordination in children. Phenotypic identification of impaired coordination plays an important role in their diagnosis. Gait is one of the tests included in rating scales that can be used to assess motor coordination. A practical problem is that the resemblance between EOA and DCD symptoms can hamper their diagnosis. In this study we employed inertial sensors and a supervised classifier to obtain an automatic classification of the condition of participants. Data from shank and waist mounted inertial measurement units were used to extract features during gait in children diagnosed with EOA or DCD and age-matched controls. We defined a set of features from the recorded signals and we obtained the optimal features for classification using a backward sequential approach. We correctly classified 80.0%, 85.7%, and 70.0% of the control, DCD and EOA children, respectively. Overall, the automatic classifier correctly classified 78.4% of the participants, which is slightly better than the phenotypic assessment of gait by two pediatric neurologists (73.0%). These results demonstrate that automatic classification employing signals from inertial sensors obtained during gait maybe used as a support tool in the differential diagnosis of EOA and DCD. Furthermore, future extension of the classifier's test domains may help to further improve the diagnostic accuracy of pediatric coordination impairment. In this sense, this study may provide a first step towards incorporating a clinically objective and viable biomarker for identification of EOA and DCD.

  5. Qualitative Reflections: CASA’s Trauma and Attachment Group (TAG) Program for Youth who have Experienced Early Developmental Trauma

    PubMed Central

    Ashton, Chandra K.; O’Brien-Langer, Anna; Olson, Karin; Silverstone, Peter H.

    2017-01-01

    Objective We demonstrated previously that the Trauma and Attachment Group (TAG) program for youth in middle childhood significantly improved caregiver/child attachment relationships, reduced children’s symptoms of attachment trauma, and increased the caregiver’s ability for self-reflection. Here we examine the perspectives of both those administering and those taking part in this intensive dyad-based group intervention. Methods Utilizing an ethnographic design we collected and analyzed qualitative data obtained through a focus group and interviews with program facilitators, as well as interviews with participating caregivers. Data were collected from six TAG facilitators through a formal focus group interview (n=4), and informal interviews with TAG facilitators unable to attend the focus group (n=2). Four interviews were also carried out with caregivers (three females and one male). Thematic analysis of the focus group and interview transcripts was conducted. Results Three key themes were identified in the focus group and interview data: Relationship as locus of change, Group process, and Psychoeducation-based content. That the TAG program provides psychoeducation about the effects of trauma to caregiver/child dyads in a group setting appears important in supporting the effectiveness of the program. Structured parent-child play and sensory activities together (“kit-time”) were also highly valued. Conclusions This qualitative study suggests that establishment of a healthy and focused caregiver/child relationship may be the key mechanism to promoting change in relationships that have been challenged by adverse effects of early developmental trauma. Further evaluation may help to identify other components that contribute to the success of the program. PMID:28331499

  6. Developmental trends in alcohol use initiation and escalation from early- to middle-adolescence: Prediction by urgency and trait affect

    PubMed Central

    Spillane, Nichea S.; Merrill, Jennifer E.; Jackson, Kristina M.

    2016-01-01

    Studies on adolescent drinking have not always been able to distinguish between initiation and escalation of drinking, because many studies include samples in which initiation has already occurred; hence initiation and escalation are often confounded. The present study draws from a dual-process theoretical framework to investigate: if changes in the likelihood of drinking initiation and escalation are predicted by a tendency towards rash action when experiencing positive and negative emotions (positive and negative urgency); and whether trait positive and negative affect moderate such effects. Alcohol naïve adolescents (n=944; age: M=12.16, SD=.96; 52% female) completed 6 semi-annual assessments of trait urgency and affect (wave-1) and alcohol use (waves 2–6). A two-part random-effects model was used to estimate changes in the likelihood of any alcohol use vs. escalation in the volume of use amongst initiators. Main effects suggest a significant association between positive affect and change in level of alcohol use amongst initiators, such that lower positive affect predicted increased alcohol involvement. This main effect was qualified by a significant interaction between positive urgency and positive affect predicting changes in the escalation of drinking, such that the effect of positive urgency was augmented for those high on trait positive affect, though only at extremely high levels of positive affect. Results suggest risk factors in the development of drinking depend on whether initiation or escalation is investigated. A more nuanced understanding of the early developmental phases of alcohol involvement can inform prevention and intervention efforts. PMID:27031086

  7. Developmental trends in alcohol use initiation and escalation from early to middle adolescence: Prediction by urgency and trait affect.

    PubMed

    Lopez-Vergara, Hector I; Spillane, Nichea S; Merrill, Jennifer E; Jackson, Kristina M

    2016-08-01

    Studies on adolescent drinking have not always been able to distinguish between initiation and escalation of drinking, because many studies include samples in which initiation has already occurred; hence, initiation and escalation are often confounded. The present study draws from a dual-process theoretical framework to investigate: if changes in the likelihood of drinking initiation and escalation are predicted by a tendency toward rash action when experiencing positive and negative emotions (positive and negative urgency) and whether trait positive and negative affect moderate such effects. Alcohol naïve adolescents (n = 944; age M = 12.16, SD = .96; 52% female) completed 6 semiannual assessments of trait urgency and affect (Wave 1) and alcohol use (Waves 2-6). A 2-part random-effects model was used to estimate changes in the likelihood of any alcohol use versus escalation in the volume of use among initiators. Main effects suggest a significant association between positive affect and change in level of alcohol use among initiators, such that lower positive affect predicted increased alcohol involvement. This main effect was qualified by a significant interaction between positive urgency and positive affect predicting changes in the escalation of drinking, such that the effect of positive urgency was augmented for those high on trait positive affect, though only at extremely high levels of positive affect. Results suggest risk factors in the development of drinking depend on whether initiation or escalation is investigated. A more nuanced understanding of the early developmental phases of alcohol involvement can inform prevention and intervention efforts. (PsycINFO Database Record

  8. Childhood and adolescent predictors of heavy drinking and alcohol use disorders in early adulthood: a longitudinal developmental analysis

    PubMed Central

    Englund, Michelle M.; Egeland, Byron; Oliva, Elizabeth M.; Collins, W. Andrew

    2010-01-01

    Aims To identify childhood and adolescent factors differentiating heavy alcohol users in early adulthood from more moderate users or abstainers. Design Low-income participants followed from birth to age 28 years. Participants A total of 178 adults (95 males) who were first-born children of low-income mothers recruited in Minneapolis, Minnesota, during their third trimester of pregnancy. Measurements Maternal hostility (24/42 months), externalizing and internalizing behavior problems (9 years), peer acceptance and academic achievement (12 years), maternal alcohol use and participants’ drinking behavior (16 years), quantity of alcohol use per occasion (19, 23 and 26 years), alcohol use disorders (28 years). Findings For men: (i) higher amounts of alcohol consumption at age 16 increased the odds of being a heavy drinker compared to an abstainer (age 19) and a moderate drinker (ages 23 and 26); (ii) lower achievement scores at age 12 and having a mother who drank more when the participant was age 16 increased the odds of being a heavy drinker compared to moderate drinker (age 26). Higher levels of externalizing behavior problems at age 9 and drinking more when the participants were age 16 increased the odds that men would have a current alcohol use disorder at age 28. For women: (i) drinking more at age 16 increased the odds of being a heavy drinker compared to being either an abstainer or a moderate drinker (age 26); (ii) having higher levels of achievement at age 12 increased the odds of being a heavy drinker compared to an abstainer at age 23. Adolescent alcohol use mediated the relation between externalizing behavior at age 9 and alcohol use at age 26 for women. Conclusions Problem drinking may be the result of a long-term developmental process wherein childhood externalizing behavior problems sets a pathway leading to heavy drinking during and after adolescence. PMID:18426538

  9. Pulse splitter-based nonlinear microscopy for live-cardiomyocyte imaging

    NASA Astrophysics Data System (ADS)

    Wang, Zhonghai; Qin, Wan; Shao, Yonghong; Ma, Siyu; Borg, Thomas K.; Gao, Bruce Z.

    2014-02-01

    Second harmonic generation (SHG) microscopy is a new imaging technique used in sarcomeric-addition studies. However, during the early stage of cell culture in which sarcomeric additions occur, the neonatal cardiomyocytes that we have been working with are very sensitive to photodamage, the resulting high rate of cell death prevents systematic study of sarcomeric addition using a conventional SHG system. To address this challenge, we introduced use of the pulse-splitter system developed by Na Ji et al. in our two photon excitation fluorescence (TPEF) and SHG hybrid microscope. The system dramatically reduced photodamage to neonatal cardiomyocytes in early stages of culture, greatly increasing cell viability. Thus continuous imaging of live cardiomyocytes was achieved with a stronger laser and for a longer period than has been reported in the literature. The pulse splitter-based TPEF-SHG microscope constructed in this study was demonstrated to be an ideal imaging system for sarcomeric addition-related investigations of neonatal cardiomyocytes in early stages of culture.

  10. Early detection of developmental dysplasia of the hip in The Netherlands: the validity of a standardized assessment protocol in infants.

    PubMed Central

    Boere-Boonekamp, M M; Kerkhoff, T H; Schuil, P B; Zielhuis, G A

    1998-01-01

    OBJECTIVES: This study evaluated the validity of the traditionally recommended screening protocol for developmental dysplasia of the hip in infants. METHODS: Study children (n = 1968) underwent a standardized screening examination. RESULTS: The incidence of developmental dysplasia of the hip was 3.7%. The sensitivity of the test protocol was 86%, the specificity was 82%, and the predictive values of positive and negative tests were 16% and 99%, respectively. CONCLUSIONS: The validity of the screening protocol for developmental dysplasia of the hip is disappointingly low. The yield of adding an ultrasonographic examination to current screening activities needs further study. PMID:9491024

  11. Simultaneous Assessment of Cardiomyocyte DNA Synthesis and Ploidy: A Method to Assist Quantification of Cardiomyocyte Regeneration and Turnover

    PubMed Central

    Richardson, Gavin D.

    2016-01-01

    Although it is accepted that the heart has a limited potential to regenerate cardiomyocytes following injury and that low levels of cardiomyocyte turnover occur during normal ageing, quantification of these events remains challenging. This is in part due to the rarity of the process and the fact that multiple cellular sources contribute to myocardial maintenance. Furthermore, DNA duplication within cardiomyocytes often leads to a polyploid cardiomyocyte and only rarely leads to new cardiomyocytes by cellular division. In order to accurately quantify cardiomyocyte turnover discrimination between these processes is essential. The protocol described here employs long term nucleoside labeling in order to label all nuclei which have arisen as a result of DNA replication and cardiomyocyte nuclei identified by utilizing nuclei isolation and subsequent PCM1 immunolabeling. Together this allows the accurate and sensitive identification of the nucleoside labeling of the cardiomyocyte nuclei population. Furthermore, 4′,6-diamidino-2-phenylindole labeling and analysis of nuclei ploidy, enables the discrimination of neo-cardiomyocyte nuclei from nuclei which have incorporated nucleoside during polyploidization. Although this method cannot control for cardiomyocyte binucleation, it allows a rapid and robust quantification of neo-cardiomyocyte nuclei while accounting for polyploidization. This method has a number of downstream applications including assessing the potential therapeutics to enhance cardiomyocyte regeneration or investigating the effects of cardiac disease on cardiomyocyte turnover and ploidy. This technique is also compatible with additional downstream immunohistological techniques, allowing quantification of nucleoside incorporation in all cardiac cell types. PMID:27285379

  12. Role of cardiomyocyte circadian clock in myocardial metabolic adaptation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marked circadian rhythmicities in cardiovascular physiology and pathophysiology exist. The cardiomyocyte circadian clock has recently been linked to circadian rhythms in myocardial gene expression, metabolism, and contractile function. For instance, the cardiomyocyte circadian clock is essential f...

  13. Examining the social determinants of children's developmental health: protocol for building a pan-Canadian population-based monitoring system for early childhood development

    PubMed Central

    Guhn, Martin; Janus, Magdalena; Enns, Jennifer; Brownell, Marni; Forer, Barry; Duku, Eric; Muhajarine, Nazeem; Raos, Rob

    2016-01-01

    Introduction Early childhood is a key period to establish policies and practices that optimise children's health and development, but Canada lacks nationally representative data on social indicators of children's well-being. To address this gap, the Early Development Instrument (EDI), a teacher-administered questionnaire completed for kindergarten-age children, has been implemented across most Canadian provinces over the past 10 years. The purpose of this protocol is to describe the Canadian Neighbourhoods and Early Child Development (CanNECD) Study, the aims of which are to create a pan-Canadian EDI database to monitor trends over time in children's developmental health and to advance research examining the social determinants of health. Methods and analysis Canada-wide EDI records from 2004 to 2014 (representing over 700 000 children) will be linked to Canada Census and Income Taxfiler data. Variables of socioeconomic status derived from these databases will be used to predict neighbourhood-level EDI vulnerability rates by conducting a series of regression analyses and latent variable models at provincial/territorial and national levels. Where data are available, we will measure the neighbourhood-level change in developmental vulnerability rates over time and model the socioeconomic factors associated with those trends. Ethics and dissemination Ethics approval for this study was granted by the Behavioural Research Ethics Board at the University of British Columbia. Study findings will be disseminated to key partners, including provincial and federal ministries, schools and school districts, collaborative community groups and the early childhood development research community. The database created as part of this longitudinal population-level monitoring system will allow researchers to associate practices, programmes and policies at school and community levels with trends in developmental health outcomes. The CanNECD Study will guide future early childhood

  14. The pro-angiogenic cytokine pleiotrophin potentiates cardiomyocyte apoptosis through inhibition of endogenous AKT/PKB activity.

    PubMed

    Li, Jinliang; Wei, Hong; Chesley, Alan; Moon, Chanil; Krawczyk, Melissa; Volkova, Maria; Ziman, Bruce; Margulies, Kenneth B; Talan, Mark; Crow, Michael T; Boheler, Kenneth R

    2007-11-30

    Pleiotrophin is a development-regulated cytokine and growth factor that can promote angiogenesis, cell proliferation, or differentiation, and it has been reported to have neovasculogenic effects in damaged heart. Developmentally, it is prominently expressed in fetal and neonatal hearts, but it is minimally expressed in normal adult heart. Conversely, we show in a rat model of myocardial infarction and in human dilated cardiomyopathy that pleiotrophin is markedly up-regulated. To elucidate the effects of pleiotrophin on cardiac contractile cells, we employed primary cultures of rat neonatal and adult cardiomyocytes. We show that pleiotrophin is released from cardiomyocytes in vitro in response to hypoxia and that the addition of recombinant pleiotrophin promotes caspase-mediated genomic DNA fragmentation in a dose- and time-dependent manner. Functionally, it potentiates the apoptotic response of neonatal cardiomyocytes to hypoxic stress and to ultraviolet irradiation and of adult cardiomyocytes to hypoxia-reoxygenation. Moreover, UV-induced apoptosis in neonatal cardiomyocytes can be partially inhibited by small interfering RNA-mediated knockdown of endogenous pleiotrophin. Mechanistically, pleiotrophin antagonizes IGF-1 associated Ser-473 phosphorylation of AKT/PKB, and it concomitantly decreases both BAD and GSK3beta phosphorylation. Adenoviral expression of constitutively active AKT and lithium chloride-mediated inhibition of GSK3beta reduce the potentiated programmed cell death elicited by pleiotrophin. These latter data indicate that pleiotrophin potentiates cardiomyocyte cell death, at least partially, through inhibition of AKT signaling. In conclusion, we have uncovered a novel function for pleiotrophin on heart cells following injury. It fosters cardiomyocyte programmed cell death in response to pro-apoptotic stress, which may be critical to myocardial injury repair.

  15. In situ mechanical analysis of cardiomyocytes at nano scales

    NASA Astrophysics Data System (ADS)

    Liu, Yuansheng; Feng, Jiantao; Shi, Liang; Niu, Ruibin; Sun, Quanmei; Liu, Hao; Li, Jing; Guo, Jihong; Zhu, Jihong; Han, Dong

    2011-12-01

    Nanomechanical behaviors of single living cardiomyocytes are quantitatively observed using calculated torsions and deflections of an AFM cantilever. The lateral contractions are related to the calcium intensity within rather than the vertical beating power of the cardiomyocytes. Drug-induced nanomechanical changes of cardiomyocytes were further investigated by measuring lateral contractions in real time.

  16. The impact of caffeine on connexin expression in the embryonic chick cardiomyocyte micromass culture system.

    PubMed

    Ahir, Bhavesh K; Pratten, Margaret K

    2016-07-01

    Cardiomyocytes are electrically coupled by gap junctions, defined as clusters of low-resistance multisubunit transmembrane channels composed of connexins (Cxs). The expression of Cx40, Cx43 and Cx45, which are present in cardiomyocytes, is known to be developmentally regulated. This study investigates the premise that alterations in gap junction proteins are one of the mechanisms by which teratogens may act. Specifically, those molecules known to be teratogenic in humans could cause their effects via disruption of cell-to-cell communication pathways, resulting in an inability to co-ordinate tissue development. Caffeine significantly inhibited contractile activity at concentrations above and including 1500 μm (P < 0.05), while not affecting cell viability and total protein, in the embryonic chick cardiomyocyte micromass culture system. The effects of caffeine on key cardiac gap junction protein (Cx40, Cx43 and Cx45) expression were analysed using immunocytochemistry and in-cell Western blotting. The results indicated that caffeine altered the expression pattern of Cx40, Cx43 and Cx45 at non-cytotoxic concentrations (≥2000 μm), i.e., at concentrations that did not affect total cell protein and cell viability. In addition the effects of caffeine on cardiomyocyte formation and function (contractile activity score) were correlated with modulation of Cxs (Cx40, Cx43 and Cx45) expression, at above and including 2000 μm caffeine concentrations (P < 0.05). These experiments provide evidence that embryonic chick cardiomyocyte micromass culture may be a useful in vitro method for mechanistic studies of perturbation of embryonic heart development. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Human Pluripotent Stem Cell-Derived Cardiomyocytes as Research and Therapeutic Tools

    PubMed Central

    Pesl, Martin; Lacampagne, Alain; Dvorak, Petr; Rotrekl, Vladimir; Meli, Albano C.

    2014-01-01

    Human pluripotent stem cells (hPSCs), namely, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), with their ability of indefinite self-renewal and capability to differentiate into cell types derivatives of all three germ layers, represent a powerful research tool in developmental biology, for drug screening, disease modelling, and potentially cell replacement therapy. Efficient differentiation protocols that would result in the cell type of our interest are needed for maximal exploitation of these cells. In the present work, we aim at focusing on the protocols for differentiation of hPSCs into functional cardiomyocytes in vitro as well as achievements in the heart disease modelling and drug testing on the patient-specific iPSC-derived cardiomyocytes (iPSC-CMs). PMID:24800237

  18. Alterations in sarcomere function modify the hyperplastic to hypertrophic transition phase of mammalian cardiomyocyte development

    PubMed Central

    Nixon, Benjamin R.; Williams, Alexandra F.; Glennon, Michael S.; de Feria, Alejandro E.; Sebag, Sara C.; Baldwin, H. Scott; Becker, Jason R.

    2017-01-01

    It remains unclear how perturbations in cardiomyocyte sarcomere function alter postnatal heart development. We utilized murine models that allowed manipulation of cardiac myosin-binding protein C (MYBPC3) expression at critical stages of cardiac ontogeny to study the response of the postnatal heart to disrupted sarcomere function. We discovered that the hyperplastic to hypertrophic transition phase of mammalian heart development was altered in mice lacking MYBPC3 and this was the critical period for subsequent development of cardiomyopathy. Specifically, MYBPC3-null hearts developed evidence of increased cardiomyocyte endoreplication, which was accompanied by enhanced expression of cell cycle stimulatory cyclins and increased phosphorylation of retinoblastoma protein. Interestingly, this response was self-limited at later developmental time points by an upregulation of the cyclin-dependent kinase inhibitor p21. These results provide valuable insights into how alterations in sarcomere protein function modify postnatal heart development and highlight the potential for targeting cell cycle regulatory pathways to counteract cardiomyopathic stimuli. PMID:28239655

  19. Multi-level models of internalizing disorders and translational developmental science: Seeking etiological insights that can inform early intervention strategies

    PubMed Central

    Allen, Nicholas B.; Dahl, Ronald E.

    2015-01-01

    This commentary discusses the articles in this special section with an emphasis on the specific utility of multivariate, multi-level models in developmental psychopathology for ultimately contributing to both etiologic insights and translational advances. These issues are considered not only in terms of the specific papers, but also within a larger set of questions regarding the opportunities (and challenges) currently facing the field. We describe why we believe this an exciting time for integrative team-science approaches to tackle these challenges—a time that holds great promise for rapid advances in integrative developmental science that includes a biological level of mechanistic understanding. In order to facilitate this, we outline a range of approaches within both translational neuroscience and translational developmental science that can be used as frameworks for understanding how such research can provide etiologic insights regarding real-world targets at the level of social, behavioral, and affective processes that can be modified during key developmental windows of opportunity. We conclude that a “construct validity” framework, where biological data form a critical, but not privileged, component of key etiological mechanisms, combined with a developmental perspective on key period of sensitivity to intervention effects, is most likely to provide significant translational outcomes. PMID:25947071

  20. Developmental dynamics of Kranz cell transcriptional specificity in maize leaf reveals early onset of C4-related processes

    PubMed Central

    Tausta, S. Lori; Li, Pinghua; Si, Yaqing; Gandotra, Neeru; Liu, Peng; Sun, Qi; Brutnell, Thomas P.; Nelson, Timothy

    2014-01-01

    The comparison of the cell-specific transcriptomes of bundle sheath (BS) and mesophyll (M) cells from successive developmental stages of maize (Zea mays) leaves reveals that the number of genes preferentially transcribed in one cell type or the other varies considerably from the sink–source transition to mature photosynthetic stages. The number of differentially expressed (DE) genes is maximal at a stage well before full maturity, including those that encode key functions for C4 photosynthesis. The developmental dynamics of BS/M differential expression can be used to identify candidates for other C4-related functions and to simplify the identification of specific pathways members from otherwise complex gene families. A significant portion of the candidates for C4-related transcription factors identified with this developmental DE strategy overlap with those identified in studies using alternative strategies, thus providing independent support for their potential importance. PMID:24790109

  1. The impact of youth, family, peer and neighborhood risk factors on developmental trajectories of risk involvement from early through middle adolescence.

    PubMed

    Wang, Bo; Deveaux, Lynette; Li, Xiaoming; Marshall, Sharon; Chen, Xinguang; Stanton, Bonita

    2014-04-01

    Few studies have analyzed the development course beginning in pre-/early adolescence of overall engagement in health-risk behaviors and associated social risk factors that place individuals in different health-risk trajectories through mid-adolescence. The current longitudinal study identified 1276 adolescents in grade six and followed them for three years to investigate their developmental trajectories of risk behaviors and to examine the association of personal and social risk factors with each trajectory. Group-based trajectory modeling was applied to identify distinctive trajectory patterns of risk behaviors. Multivariate multinomial logistic regression analyses were performed to examine the effects of the personal and social risk factors on adolescents' trajectories. Three gender-specific behavioral trajectories were identified for males (55.3% low-risk, 37.6% moderate-risk, increasing, and 7.1% high-risk, increasing) and females (41.4% no-risk, 53.4% low-risk, increasing and 5.2% moderate to high-risk, increasing). Sensation-seeking, family, peer, and neighborhood factors at baseline predicted following the moderate-risk, increasing trajectory and the high-risk, increasing trajectory in males; these risk factors predicted following the moderate to high-risk, increasing trajectory in females. The presence of all three social risk factors (high-risk neighborhood, high-risk peers and low parental monitoring) had a dramatic impact on increased probability of being in a high-risk trajectory group. These findings highlight the developmental significance of early personal and social risk factors on subsequent risk behaviors in early to middle adolescence. Future adolescent health behavior promotion interventions might consider offering additional prevention resources to pre- and early adolescent youth who are exposed to multiple contextual risk factors (even in the absence of risk behaviors) or youth who are early-starters of delinquency and substance use behaviors

  2. Notch1 signaling stimulates proliferation of immature cardiomyocytes

    PubMed Central

    Collesi, Chiara; Zentilin, Lorena; Sinagra, Gianfranco; Giacca, Mauro

    2008-01-01

    The identification of the molecular mechanisms controlling cardiomyocyte proliferation during the embryonic, fetal, and early neonatal life appears of paramount interest in regard to exploiting this information to promote cardiac regeneration. Here, we show that the proliferative potential of neonatal rat cardiomyocytes is powerfully stimulated by the sustained activation of the Notch pathway. We found that Notch1 is expressed in proliferating ventricular immature cardiac myocytes (ICMs) both in vitro and in vivo, and that the number of Notch1-positive cells in the heart declines with age. Notch1 expression in ICMs paralleled the expression of its Jagged1 ligand on non-myocyte supporting cells. The inhibition of Notch signaling in ICMs blocked their proliferation and induced apoptosis; in contrast, its activation by Jagged1 or by the constitutive expression of its activated form using an adeno-associated virus markedly stimulated proliferative signaling and promoted ICM expansion. Maintenance or reactivation of Notch signaling in cardiac myocytes might represent an interesting target for innovative regenerative therapy. PMID:18824567

  3. SYMPTOM PRESENTATIONS AND CLASSIFICATION OF AUTISM SPECTRUM DISORDER IN EARLY CHILDHOOD: APPLICATION TO THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD (DC:0-5).

    PubMed

    Soto, Timothy; Giserman Kiss, Ivy; Carter, Alice S

    2016-09-01

    Over the past 5 years, a great deal of information about the early course of autism spectrum disorder (ASD) has emerged from longitudinal prospective studies of infants at high risk for developing ASD based on a previously diagnosed older sibling. The current article describes early ASD symptom presentations and outlines the rationale for defining a new disorder, Early Atypical Autism Spectrum Disorder (EA-ASD) to accompany ASD in the new revision of the ZERO TO THREE Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-5) (in press) alternative diagnostic classification manual. EA-ASD is designed to identify children who are 9 to 36 months of age presenting with a minimum of (a) two social-communication symptoms and (b) one repetitive and restricted behavior symptom as well as (c) evidence of impairment, with the intention of providing these children with appropriately tailored services and improving the likelihood of optimizing their development.

  4. Parent-reported Attention Deficit/Hyperactivity symptomatology in preschool-aged children: factor structure, developmental change, and early risk factors.

    PubMed

    Willoughby, Michael T; Pek, Jolynn; Greenberg, Mark T

    2012-11-01

    Although Attention Deficit/Hyperactivity Disorder (ADHD) has increasingly been studied in preschool-aged children, relatively few studies have provided a comprehensive evaluation of the factor structure and patterns of developmental changes in parent-reported ADHD symptomatology across the early childhood period. This study used confirmatory factor analyses to test for longitudinal measurement invariance of ADHD symptoms and semi-parametric finite mixture models to identify prototypic patterns of developmental changes in ADHD symptomatology from 3 to 5 years of age. Participants were 1155 children and their parents who participated in a prospective longitudinal study involving a representative sample of children who resided in six non-metropolitan counties in the United States. Results indicated that (1) ADHD symptomatology was best represented by a single latent factor that exhibited partial measurement invariance from 3 to 5 years of age, (2) 8.5 % of children exhibited sustained high levels of ADHD symptoms from age 3-5 years, and (3) a variety of risk factors differentiated children with sustained high from those with sustained low levels of ADHD, relatively few (most notably caregiver education) were able to differentiate children with sustained high levels of ADHD symptoms from all other groups. Children who exhibit persistent ADHD symptomatology across the early childhood period may define a clinically important group for etiologic research and/or early intervention efforts.

  5. Mothers' Perceived Physical Health during Early and Middle Childhood: Relations with Child Developmental Delay and Behavior Problems

    ERIC Educational Resources Information Center

    Eisenhower, Abbey; Blacher, Jan; Baker, Bruce L.

    2013-01-01

    The self-perceived physical health of mothers raising children with developmental delay (DD; N = 116) or typical development (TD; N = 129) was examined across child ages 3-9 years, revealing three main findings. First, mothers of children with DD experienced poorer self-rated physical health than mothers of children with TD at each age. Latent…

  6. Teaching Early Reading Skills to Children with Intellectual and Developmental Disabilities Using Computer-Delivered Instruction: A Pilot Study

    ERIC Educational Resources Information Center

    Tyler, Emily J.; Hughes, John C.; Wilson, Meadhbh M.; Beverley, Michael; Hastings, Richard P.; Williams, Bethan M.

    2015-01-01

    Many children with Intellectual and Developmental Disabilities (IDD) have considerable difficulty learning basic reading skills. Increasing evidence suggests individuals with IDD may benefit from instruction incorporating components of reading found to be effective for typically developing children. However, little research into reading…

  7. How Does Early Developmental Assessment Predict Academic and Attentional-Behavioural Skills at Group and Individual Levels?

    ERIC Educational Resources Information Center

    Valtonen, Riitta; Ahonen, Timo; Tolvanen, Asko; Lyytinen, Paula

    2009-01-01

    The main aim of the study was to explore the ability of a brief developmental assessment to predict teacher-rated learning and attentional and behavioural skills in the first grade of school at both the group and individual levels. A sample of 394 children (181 males, 213 females) aged 4 years were followed to the age of 6 years, and 283 of the…

  8. Developmental Trajectories of Behavior Problems among Children Who Have Experienced Maltreatment: Heterogeneity during Early Childhood and Ecological Predictors

    ERIC Educational Resources Information Center

    Tabone, Jiyoung K.; Guterman, Neil B.; Litrownik, Alan J.; Dubowitz, Howard; Isbell, Patricia; English, Diana J.; Runyan, Desmond K.; Thompson, Richard

    2011-01-01

    The current study is a longitudinal investigation of unobserved heterogeneity in the developmental trajectories of problem behaviors among children who have experienced maltreatment. The goal of this study is to inform effective intervention plans with respect to behavior problems of maltreated children by examining the different trajectories of…

  9. Early Childhood Developmental Screening: A Compendium of Measures for Children Ages Birth to Five. OPRE Report 2014-11

    ERIC Educational Resources Information Center

    Moodie, Shannon; Daneri, Paula; Goldhagen, Samantha; Halle, Tamara; Green, Katie; LaMonte, Lauren

    2014-01-01

    For children age birth to five, physical, cognitive, linguistic, and social-emotional growth and development occur at a rapid pace. While all children in this age range may not reach developmental milestones (e.g., smiling, saying first words, taking first steps) at the same time, development that does not happen within an expected timeframe can…

  10. Multidimensional Latent Markov Models in a Developmental Study of Inhibitory Control and Attentional Flexibility in Early Childhood

    ERIC Educational Resources Information Center

    Bartolucci, Francesco; Solis-Trapala, Ivonne L.

    2010-01-01

    We demonstrate the use of a multidimensional extension of the latent Markov model to analyse data from studies with repeated binary responses in developmental psychology. In particular, we consider an experiment based on a battery of tests which was administered to pre-school children, at three time periods, in order to measure their inhibitory…

  11. Early Developmental Assessment of Children with Major Non-Cardiac Congenital Anomalies Predicts Development at the Age of 5 Years

    ERIC Educational Resources Information Center

    Mazer, Petra; Gischler, Saskia J.; van der Cammen-van Zijp, Monique H. M.; Tibboel, Dick; Bax, Nicolaas M. A.; Ijsselstijn, Hanneke; van Dijk, Monique; Duivenvoorden, Hugo J.

    2010-01-01

    Aim: The aim of this study was to evaluate cognitive and motor development in children with major congenital anomalies and the predictability of development at age 5 years. Method: A prospective, longitudinal follow-up study was undertaken. The Dutch version of the Bayley Scales of Infant Development--Mental Developmental Index (MDI) and…

  12. Developmental Course of Deprivation-Specific Psychological Patterns: Early Manifestations, Persistence to Age 15, and Clinical Features

    ERIC Educational Resources Information Center

    Kreppner, Jana; Kumsta, Robert; Rutter, Michael; Beckett, Celia; Castle, Jennifer; Stevens, Suzanne; Sonuga-Barke, Edmund J.

    2010-01-01

    In chapter IV, the authors focused on their findings on the developmental course of deprivation-specific psychological patterns (DSPs). The authors rediscussed the syndrome concept in the light of two main considerations. First, the findings indicated substantial overlap among the four postulated DSPs at 15 years including CI and I/O before…

  13. Early Effects of Responsivity Education/Prelinguistic Milieu Teaching for Children with Developmental Delays and Their Parents

    ERIC Educational Resources Information Center

    Fey, Marc E.; Warren, Steven F.; Brady, Nancy; Finestack, Lizbeth H.; Bredin-Oja, Shelley L.; Fairchild, Martha; Sokol, Shari; Yoder, Paul J.

    2006-01-01

    Purpose: To evaluate the efficacy of a 6-month course of responsivity education/prelinguistic milieu teaching (RE/PMT) for children with developmental delay and RE/PMT's effects on parenting stress in a randomized clinical trial. Method: Fifty-one children, age 24-33 months, with no more than 10 expressive words or signs, were randomly assigned to…

  14. Interdyad Differences in Early Mother-Infant Face-to-Face Communication: Real-Time Dynamics and Developmental Pathways

    ERIC Educational Resources Information Center

    Lavelli, Manuela; Fogel, Alan

    2013-01-01

    A microgenetic research design with a multiple case study method and a combination of quantitative and qualitative analyses was used to investigate interdyad differences in real-time dynamics and developmental change processes in mother-infant face-to-face communication over the first 3 months of life. Weekly observations of 24 mother-infant dyads…

  15. Developmentally and Culturally Inappropriate Practice in U.s. Early Childhood Programs, Early Childhood Programs, Kindergarten Programs: Prevalence, Severity, and Its Relationship with Teacher and Administrator Qualifications.

    ERIC Educational Resources Information Center

    Zeng, Guang; Zeng, Liang

    2005-01-01

    In this study, confirmatory factor analyses (CFA) were conducted to facilitate the examination of the status quo of the developmentally and culturally inappropriate practices (DCIP) that may exist in U.S. kindergarten programs given the self-reports and preferences of a nationally representative sample of kindergarten teachers (N=3,047) and…

  16. Improvement of the developmental ability of nuclear transfer embryos by using blastomeres from in vitro fertilized embryos selected according to the early developmental stage and cell division status as donor cells in cattle.

    PubMed

    Goto, Yuji; Matoba, Satoko; Imai, Kei; Geshi, Masaya

    2011-04-01

    This study was conducted to improve the developmental ability of nuclear transfer (NT) embryos by using blastomeres from in vitro fertilized (IVF) embryos with high quality as donor cells. The IVF embryos selected at the 2-cell stage at 24-h postinsemination (hpi) and again at the ≥8-cell stage at 48 hpi (Selected-IVF-embryos) showed the highest blastocyst formation rate among embryos. When blastomeres from the Selected-IVF-embryos (Selected-NT group) or Nonselected-IVF-embryos (Non-selected-NT group) were used as donor cells for NT, the blastocyst formation rate in the Selected-NT group (25.6%) was significantly higher than that in the Non-selected-NT group (13.5%). When blastomeres from the Selected-IVF-embryos at 108 (contained many cells before cell division) and 126 hpi (contained many cells immediately after cell division) were used as donor cells for NT (108- and 126-NT groups, respectively), the 126-NT group showed a significantly higher blastocyst formation rate (32.1%) than the 108-NT group (16.8%). Embryo transfer of blastocysts in the 126-NT group showed that 11 of 23 recipients became pregnant; nine calves were obtained. For the NT embryos reconstructed using in vivo derived embryos, 9 of 20 recipients became pregnant; seven calves were obtained. These results indicate that the blastocyst formation rate of NT embryos can be improved by using blastomeres from IVF embryos selected at the early developmental stage, especially immediately after cell division, and that the resultant NT embryos have a high developmental ability to progress to term that is comparable to NT embryos reconstructed using in vivo derived embryos.

  17. The International Society for Developmental Psychobiology Sackler Symposium: Early adversity and the maturation of emotion circuits - a cross-species analysis

    PubMed Central

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

    2016-01-01

    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 4 different research laboratories, using 3 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 behaviour with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations. PMID:25290865

  18. Fibroblast growth factor receptor-1 is essential for in vitro cardiomyocyte development.

    PubMed

    Dell'Era, Patrizia; Ronca, Roberto; Coco, Laura; Nicoli, Stefania; Metra, Marco; Presta, Marco

    2003-09-05

    Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling plays a crucial role in mesoderm formation and patterning. Heartless mutant studies in Drosophila suggest that FGFR1, among the different FGFRs, may play a role in cardiogenesis. However, fgfr1-/- mice die during gastrulation before heart formation. To establish the contribution of FGFR1 in cardiac development, we investigated the capacity of murine fgfr1+/- and fgfr1-/- embryonic stem (ES) cells to differentiate to cardiomyocytes in vitro. Clusters of pulsating cardiomyocytes were observed in >90% of 3-dimensional embryoid bodies (EBs) originated from fgfr1+/- ES cells at day 9 to 10 of differentiation. In contrast, 10% or less of fgfr1-/- EBs showed beating foci at day 16. Accordingly, fgfr1-/- EBs were characterized by impaired expression of early cardiac transcription factors Nkx2.5 and d-Hand and of late structural cardiac genes myosin heavy chain (MHC)-alpha, MHC-beta, and ventricular myosin light chain. Homozygous fgfr1 mutation resulted also in alterations of the expression of mesoderm-related early genes, including nodal, BMP2, BMP4, T(bra), and sonic hedgehog. Nevertheless, fgfr1+/- and fgfr1-/- EBs similarly express cardiogenic precursor, endothelial, hematopoietic, and skeletal muscle markers, indicating that fgfr1-null mutation exerts a selective effect on cardiomyocyte development in differentiating ES cells. Accordingly, inhibitors of FGFR signaling, including the FGFR1 tyrosine kinase inhibitor SU 5402, the MEK1/2 inhibitor U0126, and the protein kinase C inhibitor GF109 all prevented cardiomyocyte differentiation in fgfr1+/- EBs without affecting the expression of the hematopoietic/endothelial marker flk-1. In conclusion, the data point to a nonredundant role for FGFR1-mediated signaling in cardiomyocyte development.

  19. Stimulation of cardiomyocyte regeneration in neonatal mice and in human myocardium with neuregulin reveals a therapeutic window

    PubMed Central

    Polizzotti, Brian D.; Ganapathy, Balakrishnan; Walsh, Stuart; Choudhury, Sangita; Ammanamanchi, Niyatie; Bennett, David G.; dos Remedios, Cristobal G.; Haubner, Bernhard J.; Penninger, Josef M.; Kuhn, Bernhard

    2015-01-01

    Background Pediatric patients with heart failure are treated with medical therapies that were developed for adult patients. These therapies have been shown to be ineffective in pediatric trials, leading to the recognition that new pediatric-specific therapies must be developed. We have previously shown that administration of the recombinant growth factor neuregulin-1 (rNRG1) stimulates heart muscle cell (cardiomyocyte) regeneration in adult mice. We hypothesized that rNRG1 administration may be more effective in the neonatal period, which could provide a new therapeutic paradigm for treating heart failure in pediatric patients. Methods We used a cryoinjury model to induce myocardial dysfunction and scar formation for evaluating the effectiveness of rNRG1-administration in neonatal mice. We evaluated the ability of rNRG1 to stimulate cardiomyocyte proliferation in intact cultured myocardium from pediatric patients. Results After cryoinjury in neonatal mice, early administration of rNRG1 from birth for 34 days improved myocardial function and reduced the prevalence of transmural scars. In contrast, late administration of rNRG1 from 4 to 34 days after cryoinjury transiently improved myocardial function. The mechanisms of early administration involved cardiomyocyte protection (38%) and proliferation (62%). rNRG1 induced cardiomyocyte proliferation in myocardium from infants with heart disease less than 6 months of age. Conclusion Our results identify a more effective time period within which to execute future clinical trials of rNRG1 for stimulating cardiomyocyte regeneration. PMID:25834111

  20. Developmental milestones record

    MedlinePlus

    ... in the early years is to follow your child's development. Most parents also watch for different milestones. Talk ... child's provider if you have concerns about your child's development. Closely watching a "checklist" or calendar of developmental ...

  1. Developmental Trajectories of Adaptive Behaviors from Early Childhood to Adolescence in a Cohort of 152 Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Baghdadli, Amaria; Assouline, Brigitte; Sonie, Sandrine; Pernon, Eric; Darrou, Celine; Michelon, Cecile; Picot, Marie-Christine; Aussilloux, Charles; Pry, Rene

    2012-01-01

    This study examines change in 152 children over an almost 10-year period (T1: 4.9 (plus or minus 1.3) years; T2: 8.1 (plus or minus 1.3) years; T3: 15(plus or minus 1.6) years) using a group-based, semi-parametric method in order to identify distinct developmental trajectories. Important deficits remain at adolescence in the adaptive abilities of…

  2. Embryonic developmental plasticity of the chick: increased CO(2) during early stages of incubation changes the developmental trajectories during prenatal and postnatal growth.

    PubMed

    De Smit, Lieve; Bruggeman, Veerle; Tona, Jacob K; Debonne, Marianne; Onagbesan, Okanlawon; Arckens, Lut; De Baerdemaeker, Josse; Decuypere, Eddy

    2006-10-01

    This study investigated the effect of non-ventilation of the incubator during the first 10 days of incubation on carbon dioxide (CO(2)) concentrations in the incubator and its effects on the embryonic and post-hatch development of the chicken (Gallus gallus). Two different incubation conditions were created, one incubator was kept at standard conditions, with adequate ventilation (V) and a second incubator was non-ventilated (NV) during the first ten days of incubation, allowing the CO(2) to rise. After the first 10 days, both incubations were continued under standard conditions. The experiment was repeated twice with different ages of the breeders (45 and 60 wks) which resulted in different CO(2) levels at ED10 (1.5 and 1%). The CO(2) concentration in the V incubators remained below 0.1% in these first 10 days. The eggs of the NV incubation showed higher pCO(2) levels in the air cell from ED10 until ED14 compared to the eggs of the V group. The NV embryos had significantly higher absolute and relative (to egg weight) body weights from ED10 until ED18, pointing to an accelerated embryonic growth. At internal pipping, the NV chick embryos had higher plasma corticosterone and T(3) levels and higher pCO(2) in the air cell. Chicks incubated under NV conditions hatched 10 h earlier in the first and 15 h earlier in the second experiment and the spread of hatch was narrower. During the post-hatch period, the NV chickens had a higher body weight compared to the V chickens. From these results, it is clear that higher levels of CO(2) during the first ten days of incubation have persistent (epigenetic) effects during the incubation and early post-hatch period.

  3. TNF-α-induced cardiomyocyte apoptosis contributes to cardiac dysfunction after coronary microembolization in mini-pigs.

    PubMed

    Chen, Zhang-Wei; Qian, Ju-Ying; Ma, Jian-Ying; Chang, Shu-Fu; Yun, Hong; Jin, Hang; Sun, Ai-Jun; Zou, Yun-Zeng; Ge, Jun-Bo

    2014-10-01

    This experimental study was designed to clarify the relationship between cardiomyocyte apoptosis and tumour necrosis factor-alpha (TNF-α) expression, and confirm the effect of TNF-α on cardiac dysfunction after coronary microembolization (CME) in mini-pigs. Nineteen mini-pigs were divided into three groups: sham-operation group (n = 5), CME group (n = 7) and adalimumab pre-treatment group (n = 7; TNF-α antibody, 2 mg/kg intracoronary injection before CME). Magnetic resonance imaging (3.0-T) was performed at baseline, 6th hour and 1 week after procedure. Cardiomyocyte apoptosis was detected by cardiac-TUNEL staining, and caspase-3 and caspase-8 were detected by RT-PCR and immunohistochemistry. Furthermore, serum TNF-α, IL-6 and troponin T were analysed, while myocardial expressions of TNF-α and IL-6 were detected. Both TNF-α expression (serum level and myocardial expression) and average number of apoptotic cardiomyocyte nuclei were significantly increased in CME group compared with the sham-operation group. Six hours after CME, left ventricular end-systolic volume (LVESV) was increased and the left ventricular ejection fraction (LVEF) was decreased in CME group. Pre-treatment with adalimumab not only significantly improved LVEF after CME (6th hour: 54.9 ± 2.3% versus 50.4 ± 3.9%, P = 0.036; 1 week: 56.7 ± 4.2% versus 52.7 ± 2.9%, P = 0.041), but also suppressed cardiomyocyte apoptosis and the expression of caspase-3 and caspase-8. Meanwhile, the average number of apoptotic cardiomyocytes nuclei was inversely correlated with LVEF (r = -0.535, P = 0.022). TNF-α-induced cardiomyocyte apoptosis is likely involved in cardiac dysfunction after CME. TNF-α antibody therapy suppresses cardiomyocyte apoptosis and improves early cardiac function after CME.

  4. Developmental Toxicology##

    EPA Science Inventory

    Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functi...

  5. Atorvastatin protects cardiomyocytes from oxidative stress by inhibiting LOX-1 expression and cardiomyocyte apoptosis.

    PubMed

    Zhang, Lei; Cheng, Linfang; Wang, Qiqi; Zhou, Dongchen; Wu, Zhigang; Shen, Ling; Zhang, Li; Zhu, Jianhua

    2015-03-01

    Coronary artery disease (CAD) is a major health problem worldwide. The most severe form of CAD is acute coronary syndrome (ACS). Recent studies have demonstrated the beneficial role of atorvastatin in ACS; however, the mechanisms underlying this effect have not been fully clarified. Growing evidence indicates that activation of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays an important role in oxidative stress-induced cardiomyocyte apoptosis during ACS. In this study, we examined whether atorvastatin inhibits H2O2-induced LOX-1 expression and H9c2 cardiomyocyte apoptosis, and investigated the underlying signaling pathway. Treatment of H9c2 cardiomyocytes with H2O2 resulted in elevated expression of LOX-1 mRNA and protein, as well as increased caspase-3 and -9 protein expression and cell apoptosis. H2O2-induced LOX-1 expression, caspase protein expression, and cardiomyocyte apoptosis were attenuated by pretreatment with atorvastatin. Atorvastatin activated H2O2-inhibited phosphorylation of Akt in a concentration-dependent manner. The Akt inhibitor, LY294002, inhibited the effect of atorvastatin on inducing Akt phosphorylation and on suppressing H2O2-mediated caspase up-regulation and cell apoptosis. These findings indicate that atorvastatin protects cardiomyocyte from oxidative stress via inhibition of LOX-1 expression and apoptosis, and that activation of H2O2-inhibited phosphorylation of Akt may play an important role in the protective function of atorvastatin.

  6. Elastic interactions synchronize beating in cardiomyocytes.

    PubMed

    Cohen, Ohad; Safran, Samuel A

    2016-07-13

    Motivated by recent experimental results, we study theoretically the synchronization of the beating phase and frequency of two nearby cardiomyocyte cells. Each cell is represented as an oscillating force dipole in an infinite, viscoelastic medium and the propagation of the elastic signal within the medium is predicted. We examine the steady-state beating of two nearby cells, and show that elastic interactions result in forces that synchronize the phase and frequency of beating in a manner that depends on their mutual orientation. The theory predicts both in-phase and anti-phase steady-state beating depending on the relative cell orientations, as well as how synchronized beating varies with substrate elasticity and the inter-cell distance. These results suggest how mechanics plays a role in cardiac efficiency, and may be relevant for the design of cardiomyocyte based micro devices and other biomedical applications.

  7. A Proliferative Burst During Preadolescence Establishes the Final Cardiomyocyte Number

    PubMed Central

    Naqvi, Nawazish; Li, Ming; Calvert, John W.; Tejada, Thor; Lambert, Jonathan P.; Wu, Jianxin; Kesteven, Scott H.; Holman, Sara R.; Matsuda, Torahiro; Lovelock, Joshua D.; Howard, Wesley W.; Iismaa, Siiri E.; Chan, Andrea Y.; Crawford, Brian H.; Wagner, Mary B.; Martin, David I. K.; Lefer, David J.; Graham, Robert M.; Husain, Ahsan

    2014-01-01

    SUMMARY It is widely believed that perinatal cardiomyocyte terminal differentiation blocks cytokinesis, thereby causing binucleation and limiting regenerative repair after injury. This suggests that heart growth should occur entirely by cardiomyocyte hypertrophy during preadolescence when, in mice, cardiac mass increases many-fold over a few weeks. Here we show thata thyroid hormone surge activates the IGF-1/IGF1-R/Akt pathway on postnatal day-15andinitiates a brief but intense proliferative burst of predominantly binuclear cardiomyocytes. This proliferation increases cardiomyocyte numbers by ~40%, causing a major disparity between heart and cardiomyocyte growth. Also, the response to cardiac injury at postnatal day15 is intermediate between that observed at postnatal day-2 and -21, further suggesting persistence of cardiomyocyte proliferative capacity beyond the perinatal period. If replicated in humans, this may allow novel regenerative therapies for heart diseases. PMID:24813607

  8. A proliferative burst during preadolescence establishes the final cardiomyocyte number.

    PubMed

    Naqvi, Nawazish; Li, Ming; Calvert, John W; Tejada, Thor; Lambert, Jonathan P; Wu, Jianxin; Kesteven, Scott H; Holman, Sara R; Matsuda, Torahiro; Lovelock, Joshua D; Howard, Wesley W; Iismaa, Siiri E; Chan, Andrea Y; Crawford, Brian H; Wagner, Mary B; Martin, David I K; Lefer, David J; Graham, Robert M; Husain, Ahsan

    2014-05-08

    It is widely believed that perinatal cardiomyocyte terminal differentiation blocks cytokinesis, thereby causing binucleation and limiting regenerative repair after injury. This suggests that heart growth should occur entirely by cardiomyocyte hypertrophy during preadolescence when, in mice, cardiac mass increases many-fold over a few weeks. Here, we show that a thyroid hormone surge activates the IGF-1/IGF-1-R/Akt pathway on postnatal day 15 and initiates a brief but intense proliferative burst of predominantly binuclear cardiomyocytes. This proliferation increases cardiomyocyte numbers by ~40%, causing a major disparity between heart and cardiomyocyte growth. Also, the response to cardiac injury at postnatal day 15 is intermediate between that observed at postnatal days 2 and 21, further suggesting persistence of cardiomyocyte proliferative capacity beyond the perinatal period. If replicated in humans, this may allow novel regenerative therapies for heart diseases.

  9. Targeted deletion of Tsc1 causes fatal cardiomyocyte hyperplasia independently of afterload.

    PubMed

    Kayyali, Usamah S; Larsen, Christopher G; Bashiruddin, Sarah; Lewandowski, Sara L; Trivedi, Chinmay M; Warburton, Rod R; Parkhitko, Andrey A; Morrison, Tasha A; Henske, Elizabeth P; Chekaluk, Yvonne; Kwiatkowski, David J; Finlay, Geraldine A

    2015-01-01

    Despite high expression levels, the role of Tsc1 in cardiovascular tissue is ill defined. We launched this study to examine the role of Tsc1 in cardiac physiology and pathology. Mice in which Tsc1 was deleted in cardiac tissue and vascular smooth muscle (Tsc1c/cSM22cre(+/-)), developed progressive cardiomegaly and hypertension and died early. Hearts of Tsc1c/cSM22cre(+/-) mice displayed a progressive increase in cardiomyocyte number, and to a lesser extent, size between the ages of 1 and 6 weeks. In addition, compared to control hearts, proliferation markers (phospho-histone 3 and PCNA) were elevated in Tsc1c/cSM22cre(+/-) cardiomyocytes at 0-4 weeks, suggesting that cardiomyocyte proliferation was the predominant mechanism underlying cardiomegaly in Tsc1c/cSM22cre(+/-) mice. To examine the contribution of Tsc1 deletion in peripheral vascular smooth muscle to the cardiac phenotype, Tsc1c/cSM22cre(+/-) mice were treated with the antihypertensive, hydralazine. Prevention of hypertension had no effect on survival, cardiac size, or cardiomyocyte number in these mice. We furthermore generated mice in which Tsc1 was deleted only in vascular smooth muscle but not in cardiac tissue (Tsc1c/cSMAcre-ER(T2+/-)). The Tsc1c/cSMAcre-ER(T2+/-) mice also developed hypertension. However, their survival was normal and no cardiac abnormalities were observed. Our results suggest that loss of Tsc1 in the heart causes cardiomegaly, which is driven by increased cardiomyocyte proliferation that also appears to confer relative resistance to afterload reduction. These findings support a critical role for the Tsc1 gene as gatekeeper in the protection against uncontrolled cardiac growth.

  10. [The influence of fibroblast growth factor (FGF2) on cardiomyocytes differentiation of mesenchymal stem cells of bone marrow ex vivo].

    PubMed

    Lobanok, E S; Kvacheva, Z B; Pinchuk, S V; Volk, M V; Mezhevkina, L M; Fesenko, E E; Volotovski, I D

    2014-01-01

    The influence of FGF2 on the efficiency of cardiomyocytes differentiation of mesenchymal stem cells (MSC) of bone marrow induced by 5-azacetidine (5-aza) was studied. The effect of FGF2 developing by the 14th day after the combined action of a differentiating agent and growth factor was manifested in an increase in Mef2A, Mef2D and gene transcription and a rise of ionized Ca2+ concentration in cytoplasm keeping cell viability and proliferation activity. In the presence of FGF2 this approach provided cardiomyogenesis and the increase in the formation of early precursors of cardiomyocytes.

  11. Is Music an Active Developmental Tool or Simply a Supplement? Early Childhood Preservice Teachers' Beliefs about Music

    ERIC Educational Resources Information Center

    Kim, Hae Kyoung; Kemple, Kristen M.

    2011-01-01

    This study examines early childhood preservice teachers' beliefs about the importance of music in early childhood and explores factors influencing those beliefs. The study found that preservice teachers in this study held relatively strong beliefs about the importance of music, including aesthetic, quality-of-life, and social-emotional benefits.…

  12. Cardiomyocyte death in doxorubicin-induced cardiotoxicity

    PubMed Central

    Zhang, Yi-Wei; Shi, Jianjian; Li, Yuan-Jian; Wei, Lei

    2009-01-01

    SUMMARY Doxorubicin (DOX) is one of the most widely used and successful antitumor drugs, but its cumulative and dose-dependent cardiac toxicity has been the major concern of oncologists in cancer therapeutic practice for decades. With the increasing population of cancer survivals, there is a growing need to develop preventive strategies and effective therapies against DOX-induced cardiotoxicity, in particular, the late onset cardiomyopathy. Although intensive investigations on the DOX-induced cardiotoxicity have been continued for decades, the underlying mechanisms responsible for DOX-induced cardiotoxicity have not been completely elucidated. A rapidly expanding body of evidence supports that cardiomyocyte death by apoptosis and necrosis is a primary mechanism of DOX-induced cardiomyopathy and other types of cell death, such as autophagy and senescence/aging, may participate in this process. In this review, we will focus on the current understanding of molecular mechanisms underlying DOX-induced cardiomyocyte death, including the major primary mechanism of excess production of reactive oxygen species (ROS) and other recently discovered ROS-independent mechanisms. Different sensitivity to DOX-induced cell death signals between adult and young cardiomyocytes will also be discussed. PMID:19866340

  13. Potential for early-life immune insult including developmental immunotoxicity in autism and autism spectrum disorders: focus on critical windows of immune vulnerability.

    PubMed

    Dietert, Rodney R; Dietert, Janice M

    2008-10-01

    Early-life immune insults (ELII) including xenobiotic-induced developmental immunotoxicity (DIT) are important factors in childhood and adult chronic diseases. However, prenatal and perinatal environmentally induced immune alterations have yet to be considered in depth in the context of autism and autism spectrum disorders (ASDs). Numerous factors produce early-life-induced immune dysfunction in offspring, including exposure to xenobiotics, maternal infections, and other prenatal-neonatal stressors. Early life sensitivity to ELII, including DIT, results from the heightened vulnerability of the developing immune system to disruption and the serious nature of the adverse outcomes arising after disruption of one-time immune maturational events. The resulting health risks extend beyond infectious diseases, cancer, allergy, and autoimmunity to include pathologies of the neurological, reproductive, and endocrine systems. Because these changes may include misregulation of resident inflammatory myelomonocytic cells in tissues such as the brain, they are a potential concern in cases of prenatal-neonatal brain pathologies and neurobehavioral deficits. Autism and ASDs are chronic developmental neurobehavioral disorders that are on the rise in the United States with prenatal and perinatal environmental factors suspected as contributors to this increase. Evidence for an association between environmentally associated childhood immune dysfunction and ASDs suggests that ELII and DIT may contribute to these conditions. However, it is not known if this linkage is directly associated with the brain pathologies or represents a separate (or secondary) outcome. This review considers the known features of ELII and DIT and how they may provide important clues to prenatal brain inflammation and the risk of autism and ASDs.

  14. Modulation of cardiomyocyte activity using pulsed laser irradiated gold nanoparticles

    PubMed Central

    Gentemann, Lara; Kalies, Stefan; Coffee, Michelle; Meyer, Heiko; Ripken, Tammo; Heisterkamp, Alexander; Zweigerdt, Robert; Heinemann, Dag

    2016-01-01

    Can photothermal gold nanoparticle mediated laser manipulation be applied to induce cardiac contraction? Based on our previous work, we present a novel concept of cell stimulation. A 532 nm picosecond laser was employed to heat gold nanoparticles on cardiomyocytes. This leads to calcium oscillations in the HL-1 cardiomyocyte cell line. As calcium is connected to the contractility, we aimed to alter the contraction rate of native and stem cell derived cardiomyocytes. A contraction rate increase was particularly observed in calcium containing buffer with neonatal rat cardiomyocytes. Consequently, the study provides conceptual ideas for a light based, nanoparticle mediated stimulation system. PMID:28101410

  15. Migration of cardiomyocytes is essential for heart regeneration in zebrafish.

    PubMed

    Itou, Junji; Oishi, Isao; Kawakami, Hiroko; Glass, Tiffany J; Richter, Jenna; Johnson, Austin; Lund, Troy C; Kawakami, Yasuhiko

    2012-11-01

    Adult zebrafish possess a significant ability to regenerate injured heart tissue through proliferation of pre-existing cardiomyocytes, which contrasts with the inability of mammals to do so after the immediate postnatal period. Zebrafish therefore provide a model system in which to study how an injured heart can be repaired. However, it remains unknown what important processes cardiomyocytes are involved in other than partial de-differentiation and proliferation. Here we show that migration of cardiomyocytes to the injury site is essential for heart regeneration. Ventricular amputation induced expression of cxcl12a and cxcr4b, genes encoding a chemokine ligand and its receptor. We found that cxcl12a was expressed in the epicardial tissue and that Cxcr4 was expressed in cardiomyocytes. We show that pharmacological blocking of Cxcr4 function as well as genetic loss of cxcr4b function causes failure to regenerate the heart after ventricular resection. Cardiomyocyte proliferation was not affected but a large portion of proliferating cardiomyocytes remained localized outside the injury site. A photoconvertible fluorescent reporter-based cardiomyocyte-tracing assay demonstrates that cardiomyocytes migrated into the injury site in control hearts but that migration was inhibited in the Cxcr4-blocked hearts. By contrast, the epicardial cells and vascular endothelial cells were not affected by blocking Cxcr4 function. Our data show that the migration of cardiomyocytes into the injury site is regulated independently of proliferation, and that coordination of both processes is necessary for heart regeneration.

  16. Early Developmental Low-Dose Methylmercury Exposure Alters Learning and Memory in Periadolescent but Not Young Adult Rats

    PubMed Central

    Albores-Garcia, Damaris; Hernandez, Alberto J.; Loera, Miriam J.

    2016-01-01

    Few studies have assessed the effects of developmental methylmercury (MeHg) exposure on learning and memory at different ages. The possibility of the amelioration or worsening of the effects has not been sufficiently investigated. This study aimed to assess whether low-dose MeHg exposure in utero and during suckling induces differential disturbances in learning and memory of periadolescent and young adult rats. Four experimental groups of pregnant Sprague-Dawley rats were orally exposed to MeHg or vehicle from gestational day 5 to weaning: (1) control (vehicle), (2) 250 μg/kg/day MeHg, (3) 500 μg/kg/day MeHg, and (4) vehicle, and treated on the test day with MK-801 (0.15 mg/kg i.p.), an antagonist of the N-methyl D-aspartate receptor. The effects were evaluated in male offspring through the open field test, object recognition test, Morris water maze, and conditioned taste aversion. For each test and stage assessed, different groups of animals were used. MeHg exposure, in a dose-dependent manner, disrupted exploratory behaviour, recognition memory, spatial learning, and acquisition of aversive memories in periadolescent rats, but alterations were not observed in littermates tested in young adulthood. These results suggest that developmental low-dose exposure to MeHg induces age-dependent detrimental effects. The relevance of decreasing exposure to MeHg in humans remains to be determined. PMID:26885512

  17. Investigation into developmental potential and nuclear/mitochondrial function in early wood and plains bison hybrid embryos.

    PubMed

    Seaby, R P; Mackie, P; King, W A; Mastromonaco, G F

    2012-08-01

    Studies to date have shown that bison embryo development in vitro is compromised with few embryos developing to the blastocyst stage. The aim of this study was to use bison-cattle hybrid embryos, an interspecific cross that is known to result in live offspring in vivo, as a model for assessing species-specific differences in embryo development in vitro. Cattle oocytes fertilized with cattle, plains bison and wood bison sperm were assessed for various developmental parameters associated with embryo quality, including cell number, apoptosis and ATP content. Decreased development to the blastocyst stage was observed in hybrid wood bison embryos compared with the other treatment groups. Although both wood bison and plains bison hybrid blastocysts had significantly lower cell numbers than cattle blastocysts, only wood bison hybrid blastocysts had a greater incidence of apoptosis than cattle blastocysts. Among the treatment groups, ATP levels and expression profiles of NRF1, TFAM, MT-CYB, BAX and BCL2 were not significantly different in both 8- to 16-cell stage and blastocyst stage embryos. These data provide evidence of decreased developmental competence in the wood bison hybrid embryos, owing to inadequate culture conditions that have increased apoptotic events.

  18. Early Developmental Low-Dose Methylmercury Exposure Alters Learning and Memory in Periadolescent but Not Young Adult Rats.

    PubMed

    Albores-Garcia, Damaris; Acosta-Saavedra, Leonor C; Hernandez, Alberto J; Loera, Miriam J; Calderón-Aranda, Emma S

    2016-01-01

    Few studies have assessed the effects of developmental methylmercury (MeHg) exposure on learning and memory at different ages. The possibility of the amelioration or worsening of the effects has not been sufficiently investigated. This study aimed to assess whether low-dose MeHg exposure in utero and during suckling induces differential disturbances in learning and memory of periadolescent and young adult rats. Four experimental groups of pregnant Sprague-Dawley rats were orally exposed to MeHg or vehicle from gestational day 5 to weaning: (1) control (vehicle), (2) 250 μg/kg/day MeHg, (3) 500 μg/kg/day MeHg, and (4) vehicle, and treated on the test day with MK-801 (0.15 mg/kg i.p.), an antagonist of the N-methyl D-aspartate receptor. The effects were evaluated in male offspring through the open field test, object recognition test, Morris water maze, and conditioned taste aversion. For each test and stage assessed, different groups of animals were used. MeHg exposure, in a dose-dependent manner, disrupted exploratory behaviour, recognition memory, spatial learning, and acquisition of aversive memories in periadolescent rats, but alterations were not observed in littermates tested in young adulthood. These results suggest that developmental low-dose exposure to MeHg induces age-dependent detrimental effects. The relevance of decreasing exposure to MeHg in humans remains to be determined.

  19. Gender Differences and Developmental Change in Externalizing Disorders From Late Adolescence to Early Adulthood: A Longitudinal Twin Study

    PubMed Central

    Hicks, Brian M.; Blonigen, Daniel M.; Kramer, Mark D.; Krueger, Robert F.; Patrick, Christopher J.; Iacono, William G.; McGue, Matt

    2008-01-01

    Using data from over 1,000 male and female twins participating in the Minnesota Twin Family Study, the authors examined developmental change, gender differences, and genetic and environmental contributions to the symptom levels of four externalizing disorders (adult antisocial behavior, alcohol dependence, nicotine dependence, and drug dependence) from ages 17 to 24. Both men and women increased in symptoms for each externalizing disorder, with men increasing at a greater rate than women, such that a modest gender gap at age 17 widened to a large one at age 24. Additionally, a mean-level gender difference on a latent Externalizing factor could account for the mean-level gender differences for the individual disorders. Biometric analyses revealed increasing genetic variation and heritability for men but a trend toward decreasing genetic variation and increasing environmental effects for women. Results illustrate the importance of gender and developmental context for symptom expression and the utility of structural models to integrate general trends and disorder-specific characteristics. PMID:17696699

  20. Five Developmental Stages of Spelling.

    ERIC Educational Resources Information Center

    Gentry, J. Richard

    1984-01-01

    Precommunicative, semiphonetic, phonetic, transitional, and correct spelling are the developmental stages in the acquisition of spelling competency. Samples of children's early spelling patterns are presented. A system for classifying early spelling strategy is outlined. (DF)

  1. On the nature of facultative and constitutive CAM: environmental and developmental control of CAM expression during early growth of Clusia, Kalanchöe, and Opuntia.

    PubMed

    Winter, Klaus; Garcia, Milton; Holtum, Joseph A M

    2008-01-01

    The capacity to induce crassulacean acid metabolism developmentally (constitutive CAM) and to up-regulate CAM expression in response to drought stress (facultative CAM) was studied in whole shoots of seven species by measuring net CO(2) gas exchange for up to 120 day-night cycles during early growth. In Clusia rosea, CAM was largely induced developmentally. Well-watered seedlings began their life cycle as C(3) plants and developed net dark CO(2) fixation indicative of CAM after the initiation of the fourth leaf pair following the cotyledons. Thereafter, CAM activity increased progressively and drought stress led to only small additional, reversible increases in dark CO(2) fixation. In contrast, CAM expression was overwhelmingly under environmental control in seedlings and mature plants of Clusia pratensis. C(3)-type CO(2) exchange was maintained under well-watered conditions, but upon drought stress, CO(2) exchange shifted, in a fully reversible manner, to a CAM-type pattern. Clusia minor showed CO(2) exchange reponses intermediate to those of C. rosea and C. pratensis. Clusia cretosa operated in the C(3) mode at all times. Notably, reversible stress-induced increases of dark CO(2) fixation were also observed during the developmental progression to pronounced CAM in young Kalanchoë daigremontiana and Kalanchoë pinnata, two species considered constitutive CAM species. Drought-induced up-regulation of CAM was even detected in young cladodes of a cactus, Opuntia ficus-indica, an archetypal constitutive CAM species. Evidently, the defining characteristics of constitutive and facultative CAM are shared, to variable degrees, by all CAM species.

  2. Myc overexpression enhances of epicardial contribution to the developing heart and promotes extensive expansion of the cardiomyocyte population

    PubMed Central

    Villa del Campo, Cristina; Lioux, Ghislaine; Carmona, Rita; Sierra, Rocío; Muñoz-Chápuli, Ramón; Clavería, Cristina; Torres, Miguel

    2016-01-01

    Myc is an essential regulator of cell growth and proliferation. Myc overexpression promotes the homeostatic expansion of cardiomyocyte populations by cell competition, however whether this applies to other cardiac lineages remains unknown. The epicardium contributes signals and cells to the developing and adult injured heart and exploring strategies for modulating its activity is of great interest. Using inducible genetic mosaics, we overexpressed Myc in the epicardium and determined the differential expansion of Myc-overexpressing cells with respect to their wild type counterparts. Myc-overexpressing cells overcolonized all epicardial-derived lineages and showed increased ability to invade the myocardium and populate the vasculature. We also found massive colonization of the myocardium by Wt1Cre-derived Myc-overexpressing cells, with preservation of cardiac development. Detailed analyses showed that this contribution is unlikely to derive from Cre activity in early cardiomyocytes but does not either derive from established epicardial cells, suggesting that early precursors expressing Wt1Cre originate the recombined cardiomyocytes. Myc overexpression does not modify the initial distribution of Wt1Cre-recombined cardiomyocytes, indicating that it does not stimulate the incorporation of early expressing Wt1Cre lineages to the myocardium, but differentially expands this initial population. We propose that strategies using epicardial lineages for heart repair may benefit from promoting cell competitive ability. PMID:27752085

  3. Development of a culturally, theoretically and developmentally based survey instrument for assessing risk behaviors among African-American early adolescents living in urban low-income neighborhoods.

    PubMed

    Stanton, B; Black, M; Feigelman, S; Ricardo, I; Galbraith, J; Li, X; Kaljee, L; Keane, V; Nesbitt, R

    1995-04-01

    The creation of developmentally and culturally appropriate data-gathering instruments is necessary as health researchers and interventionists expand their investigations to community-based minority adolescent populations. The creation of such instruments is a complex process, requiring the integration of multiple data-gathering and analytic approaches. Recent efforts have delineated several issues to be considered in survey design for minority populations: community collaboration; problem conceptualization; application of the presumed model of behavioral change; and dialect and format of delivery. This paper describes the process of creating a culturally and developmentally appropriate, theoretically grounded instrument for use in monitoring the impact of an AIDS educational intervention on the behavior and health outcomes of urban African-American pre-adolescents and early adolescents. Three phases of research were involved: preliminary (and ongoing) ethnographic research including extensive participant observation, as well as, focus group and individual interviews with 65 youths; construction and testing of the preliminary instrument involving two waves of pilot testing (N1 = 57; N2 = 45); and, finalization of the instrument including reliability testing and assessment of tool constructs and selection of the mode of delivery (involving 2 additional waves of pilot testing (N3 = 91; N4 = 351). The essential role played by the community in all phases of instrument development is underscored.

  4. A new hynobiid-like salamander (Amphibia, Urodela) from Inner Mongolia, China, provides a rare case study of developmental features in an Early Cretaceous fossil urodele.

    PubMed

    Jia, Jia; Gao, Ke-Qin

    2016-01-01

    A new fossil salamander, Nuominerpeton aquilonaris (gen. et sp. nov.), is named and described based on specimens from the Lower Cretaceous Guanghua Formation of Inner Mongolia, China. The new discovery documents a far northern occurrence of Early Cretaceous salamanders in China, extending the geographic distribution for the Mesozoic fossil record of the group from the Jehol area (40th-45th parallel north) to near the 49th parallel north. The new salamander is characterized by having the orbitosphenoid semicircular in shape; coracoid plate of the scapulocoracoid greatly expanded with a convex ventral and posterior border; ossification of two centralia in carpus and tarsus; and first digit being about half the length of the second digit in both manus and pes. The new salamander appears to be closely related to hynobiids, although this inferred relationship awaits confirmation by research in progress by us on a morphological and molecular combined analysis of cryptobranchoid relationships. Comparison of adult with larval and postmetamorphic juvenile specimens provides insights into developmental patterns of cranial and postcranial skeletons in this fossil species, especially resorption of the palatine and anterior portions of the palatopterygoid in the palate and the coronoid in the mandible during metamorphosis, and postmetamorphic ossification of the mesopodium in both manus and pes. Thus, this study provides a rare case study of developmental features in a Mesozoic salamander.

  5. A new hynobiid-like salamander (Amphibia, Urodela) from Inner Mongolia, China, provides a rare case study of developmental features in an Early Cretaceous fossil urodele

    PubMed Central

    Jia, Jia

    2016-01-01

    A new fossil salamander, Nuominerpeton aquilonaris (gen. et sp. nov.), is named and described based on specimens from the Lower Cretaceous Guanghua Formation of Inner Mongolia, China. The new discovery documents a far northern occurrence of Early Cretaceous salamanders in China, extending the geographic distribution for the Mesozoic fossil record of the group from the Jehol area (40th–45th parallel north) to near the 49th parallel north. The new salamander is characterized by having the orbitosphenoid semicircular in shape; coracoid plate of the scapulocoracoid greatly expanded with a convex ventral and posterior border; ossification of two centralia in carpus and tarsus; and first digit being about half the length of the second digit in both manus and pes. The new salamander appears to be closely related to hynobiids, although this inferred relationship awaits confirmation by research in progress by us on a morphological and molecular combined analysis of cryptobranchoid relationships. Comparison of adult with larval and postmetamorphic juvenile specimens provides insights into developmental patterns of cranial and postcranial skeletons in this fossil species, especially resorption of the palatine and anterior portions of the palatopterygoid in the palate and the coronoid in the mandible during metamorphosis, and postmetamorphic ossification of the mesopodium in both manus and pes. Thus, this study provides a rare case study of developmental features in a Mesozoic salamander. PMID:27761316

  6. Spontaneously beating cardiomyocytes derived from white mature adipocytes

    PubMed Central

    Jumabay, Medet; Zhang, Rui; Yao, Yucheng; Goldhaber, Joshua I.; Boström, Kristina I.

    2010-01-01

    Aims Adipose stromal cells and dissociated brown adipose tissue have been shown to generate cardiomyocyte-like cells. However, it is not clear whether white mature adipocytes have the same potential, even though a close relationship has been found between adipocytes and vascular endothelial cells, another cardiovascular cell type. The objective of this study was to examine if white adipocytes would be able to supply cardiomyocytes. Methods and results We prepared a highly purified population of lipid-filled adipocytes from mice, 6–7 weeks of age. When allowed to lose lipids, the adipocytes assumed a fibroblast-like morphology, so-called dedifferentiated fat (DFAT) cells. Subsequently, 10–15% of the DFAT cells spontaneously differentiated into cardiomyocyte-like cells, in which the cardiomyocyte phenotype was identified by morphological observations, expression of cardiomyocyte-specific markers, and immunocytochemical staining. In addition, electrophysiological studies revealed pacemaker activity in these cells, and functional studies showed that a β-adrenergic agonist stimulated the beating rate, whereas a β-antagonist reduced it. In vitro treatment of newly isolated adipocytes or DFAT cells with inhibitors of bone morphogenetic proteins (BMP) and Wnt signalling promoted the development of the cardiomyocyte phenotype as determined by the number or beating colonies of cardiomyocyte-like cells and expression of troponin I, a cardiomyocyte-specific marker. Inhibition of BMP was most effective in promoting the cardiomyocyte phenotype in adipocytes, whereas Wnt-inhibition was most effective in DFAT cells. Conclusion White mature adipocytes can differentiate into cardiomyocyte-like cells, suggesting a link between adipocyte and cardiomyocyte differentiation. PMID:19643806

  7. Early developmental stages of a protozoan parasite, Marteilioides chungmuensis (Paramyxea), the causative agent of the ovary enlargement disease in the Pacific oyster, Crassostrea gigas.

    PubMed

    Itoh, Naoki; Komiyama, Hideki; Ueki, Noriyuki; Ogawa, Kazuo

    2004-09-01

    A paramyxea, Marteilioides chungmuensis, causes the irregular enlargement of the ovary in the Pacific oyster, Crassostrea gigas in Korea and Japan. The knowledge about the life cycle of the parasite has been limited to the sporulation stages within the oocyte of oysters. In this study, we used the parasite-specific DNA probes and electron microscopy to experimentally infected oysters in a field and successfully clarified early developmental stages of the parasite. The parasite invaded the oysters through the epithelial tissues of the gills, mantle and labial palps. Extrasporogony repeatedly occurred in the connective tissues by binary fusion. The inner cell of the extrasporogonic stage migrated into the gonadal epithelium, invaded the oocyte to start sporulation.

  8. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice.

    PubMed

    Jonscher, Karen R; Stewart, Michael S; Alfonso-Garcia, Alba; DeFelice, Brian C; Wang, Xiaoxin X; Luo, Yuhuan; Levi, Moshe; Heerwagen, Margaret J R; Janssen, Rachel C; de la Houssaye, Becky A; Wiitala, Ellen; Florey, Garrett; Jonscher, Raleigh L; Potma, Eric O; Fiehn, Oliver; Friedman, Jacob E

    2017-04-01

    Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity or Western-style diet (WD) increases steatosis and oxidative stress in fetal liver and is associated with lifetime disease risk in the offspring. Pyrroloquinoline quinone (PQQ) is a natural antioxidant found in soil, enriched in human breast milk, and essential for development in mammals. We investigated whether a supplemental dose of PQQ, provided prenatally in a mouse model of diet-induced obesity during pregnancy, could protect obese offspring from progression of NAFLD. PQQ treatment given pre- and postnatally in WD-fed offspring had no effect on weight gain but increased metabolic flexibility while reducing body fat and liver lipids, compared with untreated obese offspring. Indices of NAFLD, including hepatic ceramide levels, oxidative stress, and expression of proinflammatory genes (Nos2, Nlrp3, Il6, and Ptgs2), were decreased in WD PQQ-fed mice, concomitant with increased expression of fatty acid oxidation genes and decreased Pparg expression. Notably, these changes persisted even after PQQ withdrawal at weaning. Our results suggest that supplementation with PQQ, particularly during pregnancy and lactation, protects offspring from WD-induced developmental programming of hepatic lipotoxicity and may help slow the advancing epidemic of NAFLD in the next generation.-Jonscher, K. R., Stewart, M. S., Alfonso-Garcia, A., DeFelice, B. C., Wang, X. X., Luo, Y., Levi, M., Heerwagen, M. J. R., Janssen, R. C., de la Houssaye, B. A., Wiitala, E., Florey, G., Jonscher, R. L., Potma, E. O., Fiehn, O. Friedman, J. E. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice.

  9. Effects of Zn Fertilization on Hordein Transcripts at Early Developmental Stage of Barley Grain and Correlation with Increased Zn Concentration in the Mature Grain

    PubMed Central

    Uddin, Mohammad Nasir; Kaczmarczyk, Agnieszka; Vincze, Eva

    2014-01-01

    Zinc deficiency is causing malnutrition for nearly one third of world populations. It is especially relevant in cereal-based diets in which low amounts of mineral and protein are present. In biological systems, Zn is mainly associated with protein. Cereal grains contain the highest Zn concentration during early developmental stage. Although hordeins are the major storage proteins in the mature barley grain and suggested to be involved in Zn binding, very little information is available regarding the Zn fertilization effects of hordein transcripts at early developmental stage and possible incorporation of Zn with hordein protein of matured grain. Zinc fertilization experiments were conducted in a greenhouse with barley cv. Golden Promise. Zn concentration of the matured grain was measured and the results showed that the increasing Zn fertilization increased grain Zn concentration. Quantitative real time PCR showed increased level of total hordein transcripts upon increasing level of Zn fertilization at 10 days after pollination. Among the hordein transcripts the amount of B-hordeins was highly correlated with the Zn concentration of matured grain. In addition, protein content of the matured grain was analysed and a positive linear relationship was found between the percentage of B-hordein and total grain Zn concentration while C-hordein level decreased. Zn sensing dithizone assay was applied to localize Zn in the matured grain. The Zn distribution was not limited to the embryo and aleurone layer but was also present in the outer part of the endosperm (sub-aleurone layers) which known to be rich in proteins including B-hordeins. Increased Zn fertilization enriched Zn even in the endosperm. Therefore, the increased amount of B-hordein and decreased C-hordein content suggested that B-hordein upregulation or difference between B and C hordein could be one of the key factors for Zn biofortification of cereal grains due to the Zn fertilization. PMID:25250985

  10. Effects of Zn fertilization on hordein transcripts at early developmental stage of barley grain and correlation with increased Zn concentration in the mature grain.

    PubMed

    Uddin, Mohammad Nasir; Kaczmarczyk, Agnieszka; Vincze, Eva

    2014-01-01

    Zinc deficiency is causing malnutrition for nearly one third of world populations. It is especially relevant in cereal-based diets in which low amounts of mineral and protein are present. In biological systems, Zn is mainly associated with protein. Cereal grains contain the highest Zn concentration during early developmental stage. Although hordeins are the major storage proteins in the mature barley grain and suggested to be involved in Zn binding, very little information is available regarding the Zn fertilization effects of hordein transcripts at early developmental stage and possible incorporation of Zn with hordein protein of matured grain. Zinc fertilization experiments were conducted in a greenhouse with barley cv. Golden Promise. Zn concentration of the matured grain was measured and the results showed that the increasing Zn fertilization increased grain Zn concentration. Quantitative real time PCR showed increased level of total hordein transcripts upon increasing level of Zn fertilization at 10 days after pollination. Among the hordein transcripts the amount of B-hordeins was highly correlated with the Zn concentration of matured grain. In addition, protein content of the matured grain was analysed and a positive linear relationship was found between the percentage of B-hordein and total grain Zn concentration while C-hordein level decreased. Zn sensing dithizone assay was applied to localize Zn in the matured grain. The Zn distribution was not limited to the embryo and aleurone layer but was also present in the outer part of the endosperm (sub-aleurone layers) which known to be rich in proteins including B-hordeins. Increased Zn fertilization enriched Zn even in the endosperm. Therefore, the increased amount of B-hordein and decreased C-hordein content suggested that B-hordein upregulation or difference between B and C hordein could be one of the key factors for Zn biofortification of cereal grains due to the Zn fertilization.

  11. Developmental pathways from childhood aggression-disruptiveness, chronic peer rejection, and deviant friendships to early-adolescent rule breaking.

    PubMed

    Ettekal, Idean; Ladd, Gary W

    2015-01-01

    Childhood aggression-disruptiveness (AD), chronic peer rejection, and deviant friendships were examined as predictors of early-adolescent rule-breaking behaviors. Using a sample of 383 children (193 girls and 190 boys) who were followed from ages 6 to 14, peer rejection trajectories were identified and incorporated into a series of alternative models to assess how chronic peer rejection and deviant friendships mediate the association between stable childhood AD and early-adolescent rule breaking. There were multiple mediated pathways to rule breaking that included both behavioral and relational risk factors, and findings were consistent for boys and girls. Results have implications for better understanding the influence of multiple social processes in the continuity of antisocial behaviors from middle childhood to early adolescence.

  12. Oxygen consumption rate and Na+/K+-ATPase activity in early developmental stages of the sea urchin Paracentrotus lividus Lam.

    NASA Astrophysics Data System (ADS)

    Tomšić, Sanja; Stanković, Suzana; Lucu, Čedomil

    2011-09-01

    Changes in oxygen consumption rate and Na+/K+-ATPase activity during early development were studied in the sea urchin Paracentrotus lividus Lam. The oxygen consumption rate increased from 0.12 μmol O2 mg protein-1 h-1 in unfertilized eggs to 0.38 μmol O2 mg protein-1 h-1 25 min after fertilization. Specific activity of the Na+/K+-ATPase was significantly stimulated after fertilization, ranging up to 1.07 μmol Pi h-1 mg protein-1 in the late blastula stage and slightly lower values in the early and late pluteus stages.

  13. DEVELOPMENTAL DIVERSITY OF AMPHIBIANS

    PubMed Central

    Elinson, Richard P.; del Pino, Eugenia M.

    2011-01-01

    The current model amphibian, Xenopus laevis, develops rapidly in water to a tadpole which metamorphoses into a frog. Many amphibians deviate from the X. laevis developmental pattern. Among other adaptations, their embryos develop in foam nests on land or in pouches on their mother’s back or on a leaf guarded by a parent. The diversity of developmental patterns includes multinucleated oogenesis, lack of RNA localization, huge non-pigmented eggs, and asynchronous, irregular early cleavages. Variations in patterns of gastrulation highlight the modularity of this critical developmental period. Many species have eliminated the larva or tadpole and directly develop to the adult. The wealth of developmental diversity among amphibians coupled with the wealth of mechanistic information from X. laevis permit comparisons that provide deeper insights into developmental processes. PMID:22662314

  14. Developmental Trajectories of Preschool Early Literacy Skills: A Comparison of Language-Minority and Monolingual-English Children

    ERIC Educational Resources Information Center

    Lonigan, Christopher J.; Farver, JoAnn M.; Nakamoto, Jonathan; Eppe, Stefanie

    2013-01-01

    This study utilized latent growth-curve analyses to determine if the early literacy skills of children who were Spanish-speaking language-minority (LM) followed a similar quantitative growth profile over a preschool year as that of a group of children from a comparable socioeconomic (SES) background but who were not LM. Participants, who ranged in…

  15. Mapping Early Speech: Prescriptive Developmental Profiles for Very Remote Aboriginal Students in the First Two Years of School

    ERIC Educational Resources Information Center

    Kenny, Lawrence

    2011-01-01

    This article examines the issues surrounding the mapping of the oral language development of Standard Australian English (SAE) in the early school years of remote and very remote Aboriginal education in the Northern Territory (NT). Currently, teachers in this context have 2 mandated documents as guides that chart the development of SAE oracy.…

  16. From Lark to Owl: developmental changes in morningness-eveningness from new-borns to early adulthood

    PubMed Central

    Randler, Christoph; Faßl, Corina; Kalb, Nadine

    2017-01-01

    Morningness-eveningness or chronotype changes significantly throughout the life span. This has been reported for the transition during adolescence in some studies, and to a lesser extent in early adulthood. Primary and pre-school children have been under investigation in fewer studies. This is the first comprehensive study covering the age range from very young children until early adulthood (0–30 years) based on the same measurement instrument. Here, we show that the turn towards eveningness starts at an early age in German children. Based on 26,214 cross-sectional data, we further show that at the end of adolescence, morningness-eveningness does not significantly change during early adulthood. Sex differences arise during puberty and remain until 30 years. The breaking point for the turn towards morningness is 15.7 years in girls and 17.2 boys. At the age of 0–1 years, there are about 70% morning types, and about 1% evening types, while at the age of 16 years, only 5% are morning types and 19% are evening types. PMID:28378787

  17. Racial Gaps in Early Childhood: Socio-Emotional Health, Developmental, and Educational Outcomes among African-American Boys. Report

    ERIC Educational Resources Information Center

    Aratani, Yumiko; Wight, Vanessa R.; Cooper, Janice L.

    2011-01-01

    This study uses the Early Childhood Longitudinal Study-Birth Cohort (child-B) data, collected by the National Center for Education Statistics in the U.S. Department of Education. The EC LS-B is a nationally representative longitudinal study of approximately 11,000 children who were born in 2001. The children in the EC LS-B have been followed…

  18. "Dosage" Effects on Developmental Progress during Early Childhood Intervention: Accessible Metrics for Real-Life Research and Advocacy

    ERIC Educational Resources Information Center

    Bagnato, Stephen J.; Suen, Hoi K.; Fevola, Antonio V.

    2011-01-01

    The accountability movement in education, in general, and early childhood intervention (ECI), specifically, have fueled the debate about the quality, benefits, and limitations of various types of publicly funded ECI and human service programs (PEW Charitable Trusts, 2008; National Research Council/National Academy of Sciences, 2009) not only in…

  19. Potential Developmental and Early Life Health Effects of Nanomaterials: Data Gaps and Research Needs for Risk Assessment

    EPA Science Inventory

    Although research examining the toxicology of nanomaterials has been ongoing for many years, early studies largely focus on respiratory effects, and are limited by lack of appropriate dose metrics and a limited understanding of the role of the physicochemical properties of nanoma...

  20. Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophy.

    PubMed

    Putinski, Charis; Abdul-Ghani, Mohammad; Stiles, Rebecca; Brunette, Steve; Dick, Sarah A; Fernando, Pasan; Megeney, Lynn A

    2013-10-22

    Cardiomyocyte hypertrophy is the cellular response that mediates pathologic enlargement of the heart. This maladaptation is also characterized by cell behaviors that are typically associated with apoptosis, including cytoskeletal reorganization and disassembly, altered nuclear morphology, and enhanced protein synthesis/translation. Here, we investigated the requirement of apoptotic caspase pathways in mediating cardiomyocyte hypertrophy. Cardiomyocytes treated with hypertrophy agonists displayed rapid and transient activation of the intrinsic-mediated cell death pathway, characterized by elevated levels of caspase 9, followed by caspase 3 protease activity. Disruption of the intrinsic cell death pathway at multiple junctures led to a significant inhibition of cardiomyocyte hypertrophy during agonist stimulation, with a corresponding reduction in the expression of known hypertrophic markers (atrial natriuretic peptide) and transcription factor activity [myocyte enhancer factor-2, nuclear factor kappa B (NF-κB)]. Similarly, in vivo attenuation of caspase activity via adenoviral expression of the biologic effector caspase inhibitor p35 blunted cardiomyocyte hypertrophy in response to agonist stimulation. Treatment of cardiomyocytes with procaspase 3 activating compound 1, a small-molecule activator of caspase 3, resulted in a robust induction of the hypertrophy response in the absence of any agonist stimulation. These results suggest that caspase-dependent signaling is necessary and sufficient to promote cardiomyocyte hypertrophy. These results also confirm that cell death signal pathways behave as active remodeling agents in cardiomyocytes, independent of inducing an apoptosis response.

  1. Micropost arrays for measuring stem cell-derived cardiomyocyte contractility

    PubMed Central

    Beussman, Kevin M.; Rodriguez, Marita L.; Leonard, Andrea; Taparia, Nikita; Thompson, Curtis R.; Sniadecki, Nathan J.

    2015-01-01

    Stem cell-derived cardiomyocytes have the potential to be used to study heart disease and maturation, screen drug treatments, and restore heart function. Here, we discuss the procedures involved in using micropost arrays to measure the contractile forces generated by stem cell-derived cardiomyocytes. Cardiomyocyte contractility is needed for the heart to pump blood, so measuring the contractile forces of cardiomyocytes is a straightforward way to assess their function. Microfabrication and soft lithography techniques are utilized to create identical arrays of flexible, silicone microposts from a common master. Micropost arrays are functionalized with extracellular matrix protein to allow cardiomyocytes to adhere to the tips of the microposts. Live imaging is used to capture videos of the deflection of microposts caused by the contraction of the cardiomyocytes. Image analysis code provides an accurate means to quantify these deflections. The contractile forces produced by a beating cardiomyocyte are calculated by modeling the microposts as cantilever beams. We have used this assay to assess techniques for improving the maturation and contractile function of stem cell-derived cardiomyocytes. PMID:26344757

  2. A Developmental Shift in Black-White Differences in Depressive Affect across Adolescence and Early Adulthood: The Influence of Early Adult Social Roles and Socio-Economic Status

    ERIC Educational Resources Information Center

    Jager, Justin

    2011-01-01

    This study examined Black-White differences in growth of depressive affect using a longitudinal sample of middle-class, suburban U.S. subjects (n = 956) that spanned from adolescence to early adulthood. Specifically, this study examined whether Black-White differences in growth of depressive affect shift over time, and the extent to which that…

  3. Acoustical sensing of cardiomyocyte cluster beating

    SciTech Connect

    Tymchenko, Nina; Kunze, Angelika; Dahlenborg, Kerstin; Svedhem, Sofia; Steel, Daniella

    2013-06-14

    Highlights: •An example of the application of QCM-D to live cell studies. •Detection of human pluripotent stem cell-derived cardiomyocyte cluster beating. •Clusters were studied in a thin liquid film and in a large liquid volume. •The QCM-D beating profile provides an individual fingerprint of the hPS-CMCs. -- Abstract: Spontaneously beating human pluripotent stem cell-derived cardiomyocytes clusters (CMCs) represent an excellent in vitro tool for studies of human cardiomyocyte function and for pharmacological cardiac safety assessment. Such testing typically requires highly trained operators, precision plating, or large cell quantities, and there is a demand for real-time, label-free monitoring of small cell quantities, especially rare cells and tissue-like structures. Array formats based on sensing of electrical or optical properties of cells are being developed and in use by the pharmaceutical industry. A potential alternative to these techniques is represented by the quartz crystal microbalance with dissipation monitoring (QCM-D) technique, which is an acoustic surface sensitive technique that measures changes in mass and viscoelastic properties close to the sensor surface (from nm to μm). There is an increasing number of studies where QCM-D has successfully been applied to monitor properties of cells and cellular processes. In the present study, we show that spontaneous beating of CMCs on QCM-D sensors can be clearly detected, both in the frequency and the dissipation signals. Beating rates in the range of 66–168 bpm for CMCs were detected and confirmed by simultaneous light microscopy. The QCM-D beating profile was found to provide individual fingerprints of the hPS-CMCs. The presented results point towards acoustical assays for evaluation cardiotoxicity.

  4. Impact of early developmental arsenic exposure on promotor CpG-island methylation of genes involved in neuronal plasticity.

    PubMed

    Martínez, Liborio; Jiménez, Verónica; García-Sepúlveda, Christian; Ceballos, Fátima; Delgado, Juan Manuel; Niño-Moreno, Perla; Doniz, Lesly; Saavedra-Alanís, Víctor; Castillo, Claudia G; Santoyo, Martha E; González-Amaro, Roberto; Jiménez-Capdeville, María E

    2011-04-01

    Epigenetic mechanisms are crucial to regulate the expression of different genes required for neuronal plasticity. Neurotoxic substances such as arsenic, which induces cognitive deficits in exposed children before any other manifestation of toxicity, could interfere with the epigenetic modulation of neuronal gene expression required for learning and memory. This study assessed in Wistar rats the effects that developmental arsenic exposure had on DNA methylation patterns in hippocampus and frontal cortex. Animals were exposed to arsenic in drinking water (3 and 36ppm) from gestation until 4 months of age, and DNA methylation in brain cells was determined by flow cytometry, immunohistochemistry and methylation-specific polymerase chain reaction (PCR) of the promoter regions of reelin (RELN) and protein phosphatase 1 (PP1) at 1, 2, 3 and 4 months of age. Immunoreactivity to 5 methyl-cytosine was significantly higher in the cortex and hippocampus of exposed animals compared to controls at 1 month, and DNA hypomethylation was observed the following months in the cortex at high arsenic exposure. Furthermore, we observed a significant increase in the non-methylated form of PP1 gene promoter at 2 and 3 months of age, either in cortex or hippocampus. In order to determine whether this exposure level is associated with memory deficits, a behavioral test was performed at the same age points, revealing progressive and dose-dependent deficits of fear memory. Our results demonstrate alterations of the methylation pattern of genes involved in neuronal plasticity in an animal model of memory deficit associated with arsenic exposure.

  5. Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease

    PubMed Central

    Gilsbach, Ralf; Preissl, Sebastian; Grüning, Björn A.; Schnick, Tilman; Burger, Lukas; Benes, Vladimir; Würch, Andreas; Bönisch, Ulrike; Günther, Stefan; Backofen, Rolf; Fleischmann, Bernd K.; Schübeler, Dirk; Hein, Lutz

    2014-01-01

    The heart is a highly specialized organ with essential function for the organism throughout life. The significance of DNA methylation in shaping the phenotype of the heart remains only partially known. Here we generate and analyse DNA methylomes from highly purified cardiomyocytes of neonatal, adult healthy and adult failing hearts. We identify large genomic regions that are differentially methylated during cardiomyocyte development and maturation. Demethylation of cardiomyocyte gene bodies correlates strongly with increased gene expression. Silencing of demethylated genes is characterized by the polycomb mark H3K27me3 or by DNA methylation. De novo methylation by DNA methyltransferases 3A/B causes repression of fetal cardiac genes, including essential components of the cardiac sarcomere. Failing cardiomyocytes partially resemble neonatal methylation patterns. This study establishes DNA methylation as a highly dynamic process during postnatal growth of cardiomyocytes and their adaptation to pathological stress in a process tightly linked to gene regulation and activity. PMID:25335909

  6. Pluripotent Stem Cell Derived Cardiomyocytes for Cardiac Repair

    PubMed Central

    Lundy, Scott D.; Gantz, Jay A.; Pagan, Chelsea M.; Filice, Dominic; Laflamme, Michael A.

    2014-01-01

    Opinion Statement The adult mammalian heart has limited capacity for generation, so a major injury such as a myocardial infarction results in the permanent loss of up to one billion cardiomyocytes. The field of cardiac cell therapy aims to replace these lost contractile units with de novo cardiomyocytes to restore lost systolic function and prevent progression to heart failure. Arguably the ideal cell for this application is the human cardiomyocyte itself, which can electromechanically couple with host myocardium and contribute active systolic force. Pluripotent stem cells from both human embryonic or induced pluripotent lineages are attractive sources for cardiomyocytes, and preclinical investigation of these cells is in progress. Recent work has focused on efficient generation and purification of cardiomyocytes, tissue engineering efforts, and examining the consequences of cell transplantation from mechanical, vascular, and electrical standpoints. Here we discuss historical and contemporary aspects of pluripotent stem cell-based cardiac cell therapy, with an emphasis on recent preclinical studies with translational goals. PMID:24838687

  7. Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease.

    PubMed

    Gilsbach, Ralf; Preissl, Sebastian; Grüning, Björn A; Schnick, Tilman; Burger, Lukas; Benes, Vladimir; Würch, Andreas; Bönisch, Ulrike; Günther, Stefan; Backofen, Rolf; Fleischmann, Bernd K; Schübeler, Dirk; Hein, Lutz

    2014-10-22

    The heart is a highly specialized organ with essential function for the organism throughout life. The significance of DNA methylation in shaping the phenotype of the heart remains only partially known. Here we generate and analyse DNA methylomes from highly purified cardiomyocytes of neonatal, adult healthy and adult failing hearts. We identify large genomic regions that are differentially methylated during cardiomyocyte development and maturation. Demethylation of cardiomyocyte gene bodies correlates strongly with increased gene expression. Silencing of demethylated genes is characterized by the polycomb mark H3K27me3 or by DNA methylation. De novo methylation by DNA methyltransferases 3A/B causes repression of fetal cardiac genes, including essential components of the cardiac sarcomere. Failing cardiomyocytes partially resemble neonatal methylation patterns. This study establishes DNA methylation as a highly dynamic process during postnatal growth of cardiomyocytes and their adaptation to pathological stress in a process tightly linked to gene regulation and activity.

  8. Bone morphogenetic protein-4 promotes induction of cardiomyocytes from human embryonic stem cells in serum-based embryoid body development.

    PubMed

    Takei, Shunsuke; Ichikawa, Hinako; Johkura, Kohei; Mogi, Akimi; No, Heesung; Yoshie, Susumu; Tomotsune, Daihachiro; Sasaki, Katsunori

    2009-06-01

    Cardiomyocytes derived from human embryonic stem (ES) cells are a potential source for cell-based therapy for heart diseases. We studied the effect of bone morphogenetic protein (BMP)-4 in the presence of fetal bovine serum (FBS) on cardiac induction from human H1 ES cells during embryoid body (EB) development. Suspension culture for 4 days with 20% FBS produced the best results for the differentiation of early mesoderm and cardiomyocytes. The addition of Noggin reduced the incidence of beating EBs from 23.6% to 5.3%, which indicated the involvement of BMP signaling in the spontaneous cardiac differentiation. In this condition, treatment with 12.5-25 ng/ml BMP-4 during the 4-day suspension optimally promoted the cardiomyocyte differentiation. The incidence of beating EBs at 25 ng/ml BMP-4 reached 95.8% on day 6 of expansion and then plateaued until day 20. In real-time PCR analysis, the cardiac development-related genes MESP1 and Nkx2.5 were upregulated in the EB outgrowths by 25 ng/ml BMP-4. The activation of BMP signaling in EBs was confirmed by the increase in the phosphorylation of Smad1/5/8 and by the nuclear localization of phospho-Smad1/5/8 and Smad4. The addition of 150 ng/ml Noggin considerably decreased the incidence of beating EBs and Nkx2.5 expression, and Noggin alone increased Nestin expression and neural differentiation in EB outgrowths. The cardiomyocytes induced by 25 ng/ml BMP-4 showed proper cell biological characteristics and a course of differentiation as judged from isoproterenol administration, gene expression, protein assay, immunoreactivity, and subcellular structures. No remarkable change in the extent of apoptosis and proliferation in the cardiomyocytes was observed by BMP-4 treatment. These findings showed that BMP-4 in combination with FBS at the appropriate time and concentrations significantly promotes cardiomyocyte induction from human ES cells.

  9. Developmental Seizures Induced by Common Early-Life Insults: Short- and Long-Term Effects on Seizure Susceptibility

    PubMed Central

    Jensen, Frances E.; Baram, Tallie Z.

    2011-01-01

    The immature brain is highly susceptible to seizures induced by a variety of insults, including hypoxia, fever, and trauma. Unlike early life epilepsy associated with congenital dysplasias or genetic abnormalities, insults induce a hyperexcitable state in a previously normal brain. Here we evaluate the epileptogenic effects of seizure-inducing stimuli on the developing brain, and the age and regional specificity of these effects. PMID:11107190

  10. Exorhodopsin and melanopsin systems in the pineal complex and brain at early developmental stages of Atlantic halibut (Hippoglossus hippoglossus).

    PubMed

    Eilertsen, Mariann; Drivenes, Oyvind; Edvardsen, Rolf B; Bradley, Clarrisa A; Ebbesson, Lars O E; Helvik, Jon Vidar

    2014-12-15

    The complexity of the nonvisual photoreception systems in teleosts has just started to be appreciated, with colocalization of multiple photoreceptor types with unresolved functions. Here we describe an intricate expression pattern of melanopsins in early life stages of the marine flat fish Atlantic halibut (Hippoglossus hippoglossus), a period when the unpigmented brain is directly exposed to environmental photons. We show a refined and extensive expression of melanopsins in the halibut brain already at the time of hatching, long before the eyes are functional. We detect melanopsin in the habenula, suprachiasmatic nucleus, dorsal thalamus, and lateral tubular nucleus of first feeding larvae, suggesting conserved functions of the melanopsins in marine teleosts. The complex expression of melanopsins already at larval stages indicates the importance of nonvisual photoreception early in development. Most strikingly, we detect expression of both exorhodopsin and melanopsin in the pineal complex of halibut larvae. Double-fluorescence labeling showed that two clusters of melanopsin-positive cells are located lateral to the central rosette of exorhodopsin-positive cells. The localization of different photopigments in the pineal complex suggests that two parallel photoreceptor systems may be active. Furthermore, the dispersed melanopsin-positive cells in the spinal cord of halibut larvae at the time of hatching may be primary sensory cells or interneurons representing the first example of dispersed high-order photoreceptor cells. The appearance of nonvisual opsins early in the development of halibut provides an alternative model for studying the evolution and functional significance of nonvisual opsins.

  11. Toxicity of road deicing salt (NaCl) and copper (Cu) to fertilization and early developmental stages of Atlantic salmon (Salmo salar).

    PubMed

    Mahrosh, Urma; Kleiven, Merethe; Meland, Sondre; Rosseland, Bjørn Olav; Salbu, Brit; Teien, Hans-Christian

    2014-09-15

    In many countries, salting of ice or snow covered roads may affect aquatic organisms in the catchment directly or indirectly by mobilization of toxic metals. We studied the toxicity of road deicing salt and copper (Cu) on the vulnerable early life stages of Atlantic salmon (Salmo salar), from fertilization till hatching. Controlled episodic exposure to road salt (≥ 5,000 mg/L) during fertilization resulted in reduced swelling and less percent egg survival. Exposure to Cu both during and post fertilization caused delayed hatching. Larval deformities were, however found as an additional effect, when eggs were exposed to high salt concentration (≥ 5,000 mg/L) mixed with Cu (10 μg Cu/L) during fertilization. Thus, it appears that the sensitivity of early developmental stages of Atlantic salmon increased when exposed to these stressors, and road salt application during spawning can pose threat to Atlantic salmon in water bodies receiving road runoff. The study gives insight on assessment and management of risks on Atlantic salmon population posed by road related hazardous chemicals.

  12. Improvement of insulin resistance, blood pressure and interstitial pH in early developmental stage of insulin resistance in OLETF rats by intake of propolis extracts.

    PubMed

    Aoi, Wataru; Hosogi, Shigekuni; Niisato, Naomi; Yokoyama, Noriko; Hayata, Hiroki; Miyazaki, Hiroaki; Kusuzaki, Katsuyuki; Fukuda, Takuya; Fukui, Michiaki; Nakamura, Naoto; Marunaka, Yoshinori

    2013-03-22

    Propolis, a resinous mixture collected from plants by the Apis mellifera bee, contains high level nutrient factors including vitamins, polyphenols, and amino acids that would be expected to improve insulin sensitivity. Insulin resistance would secondarily cause elevation of blood pressure and increase the risk of cardiovascular diseases. The purpose of this study is to investigate the effect of propolis extracts on blood glucose levels and blood pressures in an early developmental stage of insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats (10 weeks old) were divided into three different groups: normal diet, 0.1% propolis diet, and 0.5% propolis diet. After 8 weeks, blood glucose levels, blood pressures, plasma metabolic factors and hormones, and interstitial fluid pH were measured. Casual blood glucose levels were decreased associated with a reduction of plasma insulin levels in both propolis diet groups compared with normal diet group. Propolis decreased systolic blood pressure with no significant changes in plasma aldosterone levels. We also found that interstitial fluid pH in ascites, liver, and skeletal muscle was higher in rats fed propolis diet than rats fed normal diet. These data suggests that dietary propolis improves insulin sensitivity and blood pressures in the early stage of the process in development of insulin resistance, which may be mediated by suppression of metabolic acidosis.

  13. Understanding Early Childhood Teachers' Beliefs and Self-Stated Practices about Social Competence Instructional Strategies in the Context of Developmentally Appropriate Practice: A Comparison of Preservice and In-Service Teachers in the United States

    ERIC Educational Resources Information Center

    Kim, Hae Kyoung; Han, Heejeong Sophia

    2015-01-01

    The current study is an examination of early childhood preservice and in-service teachers' beliefs and self-stated practices about social competence instructional strategies, developmentally appropriate practices (DAP), and the relationship between the two. Teachers in this study generally believed that the social competence instructional…

  14. Developmental defects of enamel in primary teeth and association with early life course events: a study of 6–36 month old children in Manyara, Tanzania

    PubMed Central

    2013-01-01

    Background Children with low birth weight show an increased prevalence of developmental defects of enamel in the primary dentition that subsequently may predispose to early childhood caries (ECC). Focusing 6–36 months old, the purpose of this study was to assess the frequency of enamel defects in the primary dentition and identify influences of early life course factors; socio-demographics, birth weight, child’s early illness episodes and mothers’ perceived size of the child at birth, whilst controlling for more recent life course events in terms of current breastfeeding and oral hygiene. Methods A cross-sectional study was conducted in the high fluoride area of Manyara, northern Tanzania including 1221 child-mother pairs who attended Reproductive and Child Health (RCH) clinics for immunization and/or growth monitoring. After the primary caregivers had completed face to face interviews at the health care facility, children underwent oral clinical examination whereby ECC and developmental defects of enamel were recorded using field criteria. All erupted teeth were examined and the enamel defects were assessed on buccal surfaces according to the modified DDE Index. Results The prevalence of enamel defects was 33.3%. Diffuse opacities were the most common defects identified (23.1%), followed by hypoplasia (7.6%) and demarcated opacities (5.0%). The most frequently affected teeth were the upper central incisors (29.0% - 30.5%), whereas lower central incisors (4.3% to 4.5%) were least frequently affected. Multiple logistic regression analysis, adjusting for confounding the factors revealed that having normal birth weight (equal or more than 2500 g) associated with lower odds of having enamel hypoplasia [OR 0.2 (95% CI 0.1-0.7)]. No statistically significant association occurred between birth weight and diffuse opacities, demarcated opacities or combined DDE. Conclusion Children with the history of low birth weight were more likely than their normal birth weight

  15. Developmental Screening

    MedlinePlus

    Learn More about Your Child’s Development: Developmental Monitoring and Screening Taking a first step, waving “bye-bye,” and pointing to something interesting are all developmental milestones, ...

  16. Developmental Toxicity

    EPA Science Inventory

    This chapter provides an overview the developmental toxicity resulting from exposure to perfluorinated alkyl acids (PFAAs). The majority of studies of PFAA-induced developmental toxicity have examined effects of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) a...

  17. Developmental trajectories of preschool early literacy skills: a comparison of language-minority and monolingual-English children.

    PubMed

    Lonigan, Christopher J; Farver, Joann M; Nakamoto, Jonathan; Eppe, Stefanie

    2013-10-01

    This study utilized latent growth-curve analyses to determine if the early literacy skills of children who were Spanish-speaking language-minority (LM) followed a similar quantitative growth profile over a preschool year as that of a group of children from a comparable socioeconomic (SES) background but who were not LM. Participants, who ranged in age from 37 to 60 months (M = 50.73; SD = 5.04), included 540 Spanish-speaking LM and 408 non-LM children (47% girls) who were enrolled in 30 Head Start classrooms. Scores on a measure of oral language and measures of code-related skills (i.e., phonological awareness, print knowledge) were lower for LM children than for non-LM children. LM children experienced significantly faster growth in oral language skills than did non-LM children. Growth for print knowledge and blending was similar for LM and non-LM children, whereas LM children experienced slightly less growth than non-LM children on elision. The inclusion of child (i.e., initial language scores, age, nonverbal cognitive ability) and family (i.e., maternal/paternal education, 2-parent household, father employment) variables eliminated initial differences between LM and non-LM children on the code-related variables, and the effect was due primarily to children's initial oral language skills. These results indicate that the early risk for reading-related problems experienced by Spanish-speaking LM children is due both to low SES and to their LM status, and they highlight the critical need for the development, evaluation, and deployment of early instructional programs for LM children with limited English oral language proficiency.

  18. Trichloroethylene alters central and peripheral immune function in autoimmune-prone MRL(+/+) mice following continuous developmental and early life exposure.

    PubMed

    Blossom, Sarah J; Doss, Jason C

    2007-04-01

    Trichloroethylene (TCE) is a widespread environmental toxicant known to promote CD4(+) T-lymphocyte activation, IFNgamma production, and autoimmunity in adult MRL(+/+) mice. Because developing tissues may be more sensitive to toxicant exposure, it was hypothesized that continuous TCE exposure beginning at conception might induce even more pronounced CD4(+) T-lymphocyte effects and exacerbate the development of autoimmunity in MRL(+/+) mice. In the current study, MRL(+/+) mice were exposed to occupationally-relevant doses of TCE from conception until adulthood (i.e., 7-8 wk-of-age). The CD4(+) T-lymphocyte effects in the thymus and periphery were evaluated, as well as serum antibody levels. TCE exposure altered the number of thymocyte subsets, and reduced the capacity of the most immature CD4-/CD8- thymocytes to undergo apoptosis in vitro. In the periphery, T-lymphocyte IFN(gamma) production was monitored in the blood prior to sacrifice by intracellular cytokine staining and flow cytometry. TCE induced a dose-dependent increase in T-lymphocyte IFN(gamma) as early as 4-5-week-of-age. However, these effects were transient, and not observed in splenic T-lymphocytes in 7-8-week-old mice. In contrast, the serum levels of anti-histone autoantibodies and total IgG(2a) were significantly elevated in the TCE-exposed offspring. The data illustrated that occupationally-relevant doses of TCE administered throughout development until adulthood affected central and peripheral immune function in association with early signs of autoimmunity. Future studies will address the possibility that early-life exposure to TCE may alter some aspect of self tolerance in the thymus, leading to autoimmune disease later in life.

  19. Effect of synchronization of donor cells in early G1-phase using shake-off method on developmental potential of somatic cell nuclear transfer embryos in cattle.

    PubMed

    Goto, Yuji; Hirayama, Muneyuki; Takeda, Kazuya; Tukamoto, Nobuyuki; Sakata, Osamu; Kaeriyama, Hiroshi; Geshi, Masaya

    2013-08-01

    In this study, we compared the developmental ability of somatic cell nuclear transfer (SCNT) embryos reconstructed with three bovine somatic cells that had been synchronized in G0-phase (G0-SCNT group) or early G1-phase (eG1-SCNT group). Furthermore, we investigated the production efficiency of cloned offspring for NT embryos derived from these donor cells. The G0-phase and eG1-phase cells were synchronized, respectively, using serum starvation and antimitotic reagent treatment combined with shaking of the plate containing the cells (shake-off method). The fusion rate in the G0-SCNT groups (64.2 ± 1.8%) was significantly higher than that of eG1-SCNT groups (39.2 ± 1.9%) (P < 0.05), but the developmental rates to the blastocyst stage of SCNT embryos per fused oocytes were similar for all groups. The overall production efficiency of the clone offspring in eG1-SCNT groups (12.7%) per recipient cow was higher than that in G0-SCNT groups (3%) (P < 0.05). The mean birth weight of cloned calves and the average calving score in the G0-SCNT groups (48.1 ± 3.4 kg and 3.3 ± 0.3, respectively) was significantly higher (P < 0.05) than those of eG1-SCNT groups (37.2 ± 2.1 kg and 2.3 ± 0.2, respectively). Results of this study indicate that synchronization of donor cells in eG1-phase using the shake-off method improved the overall production efficiency of the clone offspring per transferred embryo.

  20. Exposure to Mercury and Aluminum in Early Life: Developmental Vulnerability as a Modifying Factor in Neurologic and Immunologic Effects

    PubMed Central

    Dórea, José G.

    2015-01-01

    Currently, ethylmercury (EtHg) and adjuvant-Al are the dominating interventional exposures encountered by fetuses, newborns, and infants due to immunization with Thimerosal-containing vaccines (TCVs). Despite their long use as active agents of medicines and fungicides, the safety levels of these substances have never been determined, either for animals or for adult humans—much less for fetuses, newborns, infants, and children. I reviewed the literature for papers reporting on outcomes associated with (a) multiple exposures and metabolism of EtHg and Al during early life; (b) physiological and metabolic characteristics of newborns, neonates, and infants relevant to xenobiotic exposure and effects; (c) neurobehavioral, immunological, and inflammatory reactions to Thimerosal and Al-adjuvants resulting from TCV exposure in infancy. Immunological and neurobehavioral effects of Thimerosal-EtHg and Al-adjuvants are not extraordinary; rather, these effects are easily detected in high and low income countries, with co-exposure to methylmercury (MeHg) or other neurotoxicants. Rigorous and replicable studies (in different animal species) have shown evidence of EtHg and Al toxicities. More research attention has been given to EtHg and findings have showed a solid link with neurotoxic effects in humans; however, the potential synergic effect of both toxic agents has not been properly studied. Therefore, early life exposure to both EtHg and Al deserves due consideration. PMID:25625408

  1. AP-1(c-Jun/FosB) mediates xFoxD5b expression in Xenopus early developmental neurogenesis.

    PubMed

    Yoon, Jaeho; Kim, Jung-Ho; Lee, Ok-Joo; Lee, Sung-Young; Lee, Seung-Hwan; Park, Jae-Bong; Lee, Jae-Yong; Kim, Sung-Chan; Kim, Jaebong

    2013-01-01

    AP-1 (activator protein-1) is composed of Jun and Fos proteins and functions in cell proliferation, apoptosis and differentiation. Previous studies have demonstrated that different AP-1 complexes participate in the determination of various cell fates. However, the role of different AP-1 complexes during early vertebrate development is not yet fully understood. In the present study, we demonstrate that AP-1(c-Jun/FosB) regulates neurogenesis via FoxD5b expression. We show that FoxD5 was induced by the inhibition of BMP and that FoxD5b plays roles in neurogenesis. Additionally, we show that the FoxD5b promoter region within -1336 and -1316 contains an AP-1 binding site, which is required for the transcriptional regulation of FoxD5b and is induced by the inhibition of BMP signaling in animal cap explants. Moreover, c-Jun, a component of AP-1, directly binds to the AP-1 binding site of the FoxD5b promoter and induces FoxD5b expression cooperatively with FosB, but not with c-Fos or Fra-1. Altogether, these results suggest that AP-1(c-Jun/FosB) may play a role in neurogenesis via the induction of FoxD5b expression during early vertebrate development.

  2. Urea-based osmoregulation in the developing embryo of oviparous cartilaginous fish (Callorhinchus milii): contribution of the extraembryonic yolk sac during the early developmental period.

    PubMed

    Takagi, Wataru; Kajimura, Makiko; Tanaka, Hironori; Hasegawa, Kumi; Bell, Justin D; Toop, Tes; Donald, John A; Hyodo, Susumu

    2014-04-15

    Marine cartilaginous fish retain a high concentration of urea to maintain the plasma slightly hyperosmotic to the surrounding seawater. In adult fish, urea is produced by hepatic and extrahepatic ornithine urea cycles (OUCs). However, little is known about the urea retention mechanism in developing cartilaginous fish embryos. In order to address the question as to the mechanism of urea-based osmoregulation in developing embryos, the present study examined the gene expression profiles of OUC enzymes in oviparous holocephalan elephant fish (Callorhinchus milii) embryos. We found that the yolk sac membrane (YSM) makes an important contribution to the ureosmotic strategy of the early embryonic period. The expression of OUC enzyme genes was detectable in the embryonic body from at least stage 28, and increased markedly during development to hatching, which is most probably due to growth of the liver. During the early developmental period, however, the expression of OUC enzyme genes was not prominent in the embryonic body. Meanwhile, we found that the mRNA expression of OUC enzymes was detected in the extra-embryonic YSM; the mRNA expression of cmcpsIII in the YSM was much higher than that in the embryonic body during stages 28-31. Significant levels of enzyme activity and the existence of mitochondrial-type cmgs1 transcripts in the YSM supported the mRNA findings. We also found that the cmcpsIII transcript is localized in the vascularized inner layer of the YSM. Taken together, our findings demonstrate for the first time that the YSM is involved in urea-based osmoregulation during the early to mid phase of development in oviparous cartilaginous fish.

  3. Perturbations of heart development and function in cardiomyocytes from human embryonic stem cells with trisomy 21.

    PubMed

    Bosman, Alexis; Letourneau, Audrey; Sartiani, Laura; Del Lungo, Martina; Ronzoni, Flavio; Kuziakiv, Rostyslav; Tohonen, Virpi; Zucchelli, Marco; Santoni, Federico; Guipponi, Michel; Dumevska, Biljana; Hovatta, Outi; Antonarakis, Stylianos E; Jaconi, Marisa E

    2015-05-01

    Congenital heart defects (CHD) occur in approximately 50% of patients with Down syndrome (DS); the mechanisms for this occurrence however remain unknown. In order to understand how these defects evolve in early development in DS, we focused on the earliest stages of cardiogenesis to ascertain perturbations in development leading to CHD. Using a trisomy 21 (T21) sibling human embryonic stem cell (hESC) model of DS, we show that T21-hESC display many significant differences in expression of genes and cell populations associated with mesodermal, and more notably, secondary heart field (SHF) development, in particular a reduced number of ISL1(+) progenitor cells. Furthermore, we provide evidence for two candidate genes located on chromosome 21, ETS2 and ERG, whose overexpression during cardiac commitment likely account for the disruption of SHF development, as revealed by downregulation or overexpression experiments. Additionally, we uncover an abnormal electrophysiological phenotype in functional T21 cardiomyocytes, a result further supported by mRNA expression data acquired using RNA-Seq. These data, in combination, revealed a cardiomyocyte-specific phenotype in T21 cardiomyocytes, likely due to the overexpression of genes such as RYR2, NCX, and L-type Ca(2+) channel. These results contribute to the understanding of the mechanisms involved in the development of CHD. Stem Cells 2015;33:1434-1446.

  4. Regulation of myoglobin in hypertrophied rat cardiomyocytes in experimental pulmonary hypertension.

    PubMed

    Peters, E L; Offringa, C; Kos, D; Van der Laarse, W J; Jaspers, R T

    2016-10-01

    A major problem in chronic heart failure is the inability of hypertrophied cardiomyocytes to maintain the required power output. A Hill-type oxygen diffusion model predicts that oxygen supply is limiting in hypertrophied cardiomyocytes at maximal rates of oxygen consumption and that this limitation can be reduced by increasing the myoglobin (Mb) concentration. We explored how cardiac hypertrophy, oxidative capacity, and Mb expression in right ventricular cardiomyocytes are regulated at the transcriptional and translational levels in an early stage of experimental pulmonary hypertension, in order to identify targets to improve the oxygen supply/demand ratio. Male Wistar rats were injected with monocrotaline to induce pulmonary hypertension (PH) and right ventricular heart failure. The messenger RNA (mRNA) expression levels per nucleus of growth factors insulin-like growth factor-1Ea (IGF-1Ea) and mechano growth factor (MGF) were higher in PH than in healthy controls, consistent with a doubling in cardiomyocyte cross-sectional area (CSA). Succinate dehydrogenase (SDH) activity was unaltered, indicating that oxidative capacity per cell increased. Although the Mb protein concentration was unchanged, Mb mRNA concentration was reduced. However, total RNA per nucleus was about threefold higher in PH rats versus controls, and Mb mRNA content expressed per nucleus was similar in the two groups. The increase in oxidative capacity without an increase in oxygen supply via Mb-facilitated diffusion caused a doubling of the critical extracellular oxygen tension required to prevent hypoxia (PO2crit). We conclude that Mb mRNA expression is not increased during pressure overload-induced right ventricular hypertrophy and that the increase in myoglobin content per myocyte is likely due to increased translation. We conclude that increasing Mb mRNA expression may be beneficial in the treatment of experimental PH.

  5. Microscopic heat pulses induce contraction of cardiomyocytes without calcium transients

    SciTech Connect

    Oyama, Kotaro; Mizuno, Akari; Shintani, Seine A.; Itoh, Hideki; Serizawa, Takahiro; Fukuda, Norio; Suzuki, Madoka

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Infra-red laser beam generates microscopic heat pulses. Black-Right-Pointing-Pointer Heat pulses induce contraction of cardiomyocytes. Black-Right-Pointing-Pointer Ca{sup 2+} transients during the contraction were not detected. Black-Right-Pointing-Pointer Skinned cardiomyocytes in free Ca{sup 2+} solution also contracted. Black-Right-Pointing-Pointer Heat pulses regulated the contractions without Ca{sup 2+} dynamics. -- Abstract: It was recently demonstrated that laser irradiation can control the beating of cardiomyocytes and hearts, however, the precise mechanism remains to be clarified. Among the effects induced by laser irradiation on biological tissues, temperature change is one possible effect which can alter physiological functions. Therefore, we investigated the mechanism by which heat pulses, produced by infra-red laser light under an optical microscope, induce contractions of cardiomyocytes. Here we show that microscopic heat pulses induce contraction of rat adult cardiomyocytes. The temperature increase, {Delta}T, required for inducing contraction of cardiomyocytes was dependent upon the ambient temperature; that is, {Delta}T at physiological temperature was lower than that at room temperature. Ca{sup 2+} transients, which are usually coupled to contraction, were not detected. We confirmed that the contractions of skinned cardiomyocytes were induced by the heat pulses even in free Ca{sup 2+} solution. This heat pulse-induced Ca{sup 2+}-decoupled contraction technique has the potential to stimulate heart and skeletal muscles in a manner different from the conventional electrical stimulations.

  6. Applied DC magnetic fields cause alterations in the time of cell divisions and developmental abnormalities in early sea urchin embryos

    SciTech Connect

    Levin, M.; Ernst, S.G.

    1997-05-01

    Most work on magnetic field effects focuses on AC fields. The present study demonstrates that exposure to medium-strength (10 mT--0.1 T) static magnetic fields can alter the early embryonic development of two species of sea urchin embryos. Batches of fertilized eggs from two species of urchin were exposed to fields produced by permanent magnets. Samples of the continuous cultures were scored for the timing of the first two cell divisions, time of hatching, and incidence of exogastrulation. It was found that static fields delay the onset of mitosis in both species by an amount dependent on the exposure timing relative to fertilization. The exposure time that caused the maximum effect differed between the two species. Thirty millitesla fields, but not 15 mT fields, caused an eightfold increase in the incidence of exogastrulation in Lytechinus pictus, whereas neither of these fields produced exogastrulation in Strongylocentrotus purpuratus.

  7. Developmental relations between sympathy, moral emotion attributions, moral reasoning, and social justice values from childhood to early adolescence.

    PubMed

    Daniel, Ella; Dys, Sebastian P; Buchmann, Marlis; Malti, Tina

    2014-10-01

    This study examined the development of sympathy, moral emotion attributions (MEA), moral reasoning, and social justice values in a representative sample of Swiss children (N = 1273) at 6 years of age (Time 1), 9 years of age (Time 2), and 12 years of age (Time 3). Cross-lagged panel analyses revealed that sympathy predicted subsequent increases in MEA and moral reasoning, but not vice versa. In addition, sympathy and moral reasoning at 6 and 9 years of age were associated with social justice values at 12 years of age. The results point to increased integration of affect and cognition in children's morality from middle childhood to early adolescence, as well as to the role of moral development in the emergence of social justice values.

  8. Developmental Injury to the Cerebellar Cortex Following Hydroxyurea Treatment in Early Postnatal Life: An Immunohistochemical and Electron Microscopic Study.

    PubMed

    Martí, Joaquín; Molina, Vanesa; Santa-Cruz, M C; Hervás, José P

    2017-02-01

    Postnatal development of the cerebellar cortex was studied in rats administered with a single dose (2 mg/g) of the cytotoxic agent hydroxyurea (HU) on postnatal day (P) 9 and collected at appropriate times ranging from 6 h to 45 days. Quantification of several parameters such as the density of pyknotic, mitotic, BrdU-positive, and vimentin-stained cells revealed that HU compromises the survival of the external granular layer (EGL) cells. Moreover, vimentin immunocytochemistry revealed overexpression and thicker immunoreactive glial processes in HU-treated rats. On the other hand, we also show that HU leads to the activation of apoptotic cellular events, resulting in a substantial number of dying EGL cells, as revealed by TUNEL staining and at the electron microscope level. Additionally, we quantified several features of the cerebellar cortex of rats exposed to HU in early postnatal life and collected in adulthood. Data analysis indicated that the analyzed parameters were less pronounced in rats administered with this agent. Moreover, we observed several alterations in the cerebellar cortex cytoarchitecture of rats injected with HU. Anomalies included ectopic placement of Purkinje cells and abnormities in the dendritic arbor of these macroneurons. Ectopic granule cells were also found in the molecular layer. These findings provide a clue for investigating the mechanisms of HU-induced toxicity during the development of the central nervous system. Our results also suggest that it is essential to avoid underestimating the adverse effects of this hydroxylated analog of urea when administered during early postnatal life.

  9. The Developing, Aging Neocortex: How Genetics and Epigenetics Influence Early Developmental Patterning and Age-Related Change

    PubMed Central

    Huffman, Kelly

    2012-01-01

    A hallmark of mammalian development is the generation of functional subdivisions within the nervous system. In humans, this regionalization creates a complex system that regulates behavior, cognition, memory, and emotion. During development, specification of neocortical tissue that leads to functional sensory and motor regions results from an interplay between cortically intrinsic, molecular processes, such as gene expression, and extrinsic processes regulated by sensory input. Cortical specification in mice occurs pre- and perinatally, when gene expression is robust and various anatomical distinctions are observed alongside an emergence of physiological function. After patterning, gene expression continues to shift and axonal connections mature into an adult form. The function of adult cortical gene expression may be to maintain neocortical subdivisions that were established during early patterning. As some changes in neocortical gene expression have been observed past early development into late adulthood, gene expression may also play a role in the altered neocortical function observed in age-related cognitive decline and brain dysfunction. This review provides a discussion of how neocortical gene expression and specific patterns of neocortical sensori-motor axonal connections develop and change throughout the lifespan of the animal. We posit that a role of neocortical gene expression in neocortex is to regulate plasticity mechanisms that impact critical periods for sensory and motor plasticity in aging. We describe results from several studies in aging brain that detail changes in gene expression that may relate to microstructural changes observed in brain anatomy. We discuss the role of altered glucocorticoid signaling in age-related cognitive and functional decline, as well as how aging in the brain may result from immune system activation. We describe how caloric restriction or reduction of oxidative stress may ameliorate effects of aging on the brain. PMID

  10. Single and joint action toxicity of heavy metals on early developmental stages of Chinese rare minnow (Gobiocypris rarus).

    PubMed

    Zhu, Bin; Wu, Zong-Fan; Li, Jun; Wang, Gao-Xue

    2011-11-01

    In this work, acute toxicities of heavy metals (Cu, Zn and Cd) were evaluated singly or in mixtures on Chinese rare minnow (Gobiocypris rarus) in its early stages of development (embryos, larvae). Normal embryos not later than 3 h post-fertilization and newly hatched larvae were selected for the tests. The embryos were exposed to the metal solutions studied until developing to the stages of somite formation (15 h), tail detachment (25 h 10 min), heart-beat visible (34 h 10 min), pectoral fin bud appearance (47 h 40 min) and hatching (75 h), respectively. Exposures of the larvae were continued for 24 h. Results from the single toxicity tests revealed that the mortality of embryos increases obviously with increasing exposure duration. G. rarus appears to be more sensitive to heavy metal exposures at larval stage than at embryonic stage. The toxicity order of the tested metals was Cu>Cd>Zn for the embryos and Cu>Zn>Cd for the larvae with LC₅₀ as the toxicity criterion. These data suggest that the sensitivity of G. rarus to heavy metals (Cu, Zn and Cd) is different and it depends on the exposition duration and the stages of fish development. Among the metals tested, Cu is the one most toxic to G. rarus at its early development stages. In addition, results of the mixture experiments showed that binary combinations of Cu-Zn and Cu-Cd had strictly synergistic lethal effects on the larvae. The enhanced toxicity suggested inclusion of mixture considerations in the risk assessment of heavy metals might be recommended.

  11. New frontiers in developmental neuropharmacology: Can long-term therapeutic effects of drugs be optimized through carefully timed early intervention?

    PubMed Central

    Andersen, Susan L.; Navalta, Carryl P.

    2010-01-01

    Our aim is to present a working model that may serve as a valuable heuristic to predict enduring effects of drugs when administered during development. Our primary tenet is that a greater understanding of neurodevelopment can lead to improved treatment that intervenes early in the progression of a given disorder and prevents symptoms from manifesting. The immature brain undergoes significant changes during the transitions between childhood, adolescence, and adulthood. Such changes in innervation, neurotransmitter levels, and their respective signaling mechanisms have profound and observable changes on typical behavior, but also increase vulnerability to psychiatric disorders when the maturational process goes awry. Given the remarkable plasticity of the immature brain to adapt to its external milieu, preventive interventions may be possible. We intend for this review to initiate a discussion of how currently used psychotropic agents can influence brain development. Drug exposure during sensitive periods may have beneficial long-term effects, but harmful delayed consequences may be possible as well. Regardless of the outcome, this information needs to be used to improve or develop alternative approaches for the treatment of childhood disorders. With this framework in mind, we present what is known about the effects of stimulants, antidepressants, and antipsychotics on brain maturation (including animal studies that use more clinically-relevant dosing paradigms or relevant animal models). We endeavor to provocatively set the stage for altering treatment approaches for improving mental health in non-adult populations. PMID:21309771

  12. Structure of a shark IgNAR antibody variable domain and modeling of an early-developmental isotype

    PubMed Central

    Streltsov, Victor A.; Carmichael, Jennifer A.; Nuttall, Stewart D.

    2005-01-01

    The new antigen receptor (IgNAR) antibodies from sharks are disulphide bonded dimers of two protein chains, each containing one variable and five constant domains. Three types of IgNAR variable domains have been discovered, with Type 3 appearing early in shark development and being overtaken by the antigen-driven affinity-matured Type 1 and 2 response. Here, we have determined the first structure of a naturally occurring Type 2 IgNAR variable domain, and identified the disulphide bond that links and stabilizes the CDR1 and CDR3 loops. This disulphide bridge locks the CDR3 loop in an “upright” conformation in contrast to other shark antibody structures, where a more lateral configuration is observed. Further, we sought to model the Type 3 isotype based on the crystallographic structure reported here. This modeling indicates (1) that internal Type 3-specific residues combine to pack into a compact immunoglobulin core that supports the CDR loop regions, and (2) that despite apparent low-sequence variability, there is sufficient plasticity in the CDR3 loop to form a conformationally diverse antigen-binding surface. PMID:16199666

  13. Toxicity assessment of the antifouling compound zinc pyrithione using early developmental stages of the ascidian Ciona intestinalis.

    PubMed

    Bellas, Juan

    2005-01-01

    This study investigated the toxicity of zinc pyrithione (Zpt) on the early stages of development of the ascidian Ciona intestinalis. Larval morphological abnormalities were studied after the exposure of C. intestinalis embryos at different stages of development. The median effective concentrations (EC50) ranged from 226-590 nM. The larval settlement stage was the most sensitive to Zpt. Toxic effects of Zpt on larval settlement were detected at 9 nM (EC10). The inhibition of C. intestinalis embryonic development was also used to study the loss of toxicity in Zpt solutions exposed to direct sunlight and laboratory UV light. The results showed that the toxicity of Zpt solutions decreased but did not disappear after 4 h exposure to direct sunlight (EC50 = 484 nM) or UV light (EC50 = 453 nM), compared to control Zpt solutions prepared in dark conditions. On the basis of the present data, predicted no effect concentrations of Zpt to C. intestinalis larvae are lower than predicted environmental concentrations of Zpt in certain polluted areas and therefore, may pose a risk to C. intestinalis populations.

  14. Structure of a shark IgNAR antibody variable domain and modeling of an early-developmental isotype.

    PubMed

    Streltsov, Victor A; Carmichael, Jennifer A; Nuttall, Stewart D

    2005-11-01

    The new antigen receptor (IgNAR) antibodies from sharks are disulphide bonded dimers of two protein chains, each containing one variable and five constant domains. Three types of IgNAR variable domains have been discovered, with Type 3 appearing early in shark development and being overtaken by the antigen-driven affinity-matured Type 1 and 2 response. Here, we have determined the first structure of a naturally occurring Type 2 IgNAR variable domain, and identified the disulphide bond that links and stabilizes the CDR1 and CDR3 loops. This disulphide bridge locks the CDR3 loop in an "upright" conformation in contrast to other shark antibody structures, where a more lateral configuration is observed. Further, we sought to model the Type 3 isotype based on the crystallographic structure reported here. This modeling indicates (1) that internal Type 3-specific residues combine to pack into a compact immunoglobulin core that supports the CDR loop regions, and (2) that despite apparent low-sequence variability, there is sufficient plasticity in the CDR3 loop to form a conformationally diverse antigen-binding surface.

  15. Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes.

    PubMed

    Kim, Yoon Young; Ku, Seung-Yup; Huh, Yul; Liu, Hung-Ching; Kim, Seok Hyun; Choi, Young Min; Moon, Shin Yong

    2013-10-01

    Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current lack of alternative experimental models. hPSC-derived cardiomyocytes (CMs) bear a resemblance to human cardiac cells and thus hPSC-derived CMs are considered to be a viable alternative model to study human heart cell aging. In this study, we used hPSC-derived CMs as an in vitro aging model. We generated cardiomyocytes from hPSCs and demonstrated the process of aging in both human embryonic stem cell (hESC)- and induced pluripotent stem cell (hiPSC)-derived CMs. Aging in hESC-derived CMs correlated with reduced membrane potential in mitochondria, the accumulation of lipofuscin, a slower beating pattern, and the downregulation of human telomerase RNA (hTR) and cell cycle regulating genes. Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs. In order to delay aging, vitamin C was added to the cultured CMs. When cells were treated with 100 μM of vitamin C for 48 h, anti-aging effects, specifically on the expression of telomere-related genes and their functionality in aging cells, were observed. Taken together, these results suggest that hPSC-derived CMs can be used as a unique human cardiomyocyte aging model in vitro and that vitamin C shows anti-aging effects in this model.

  16. Allele-specific RNA interference rescues the long-QT syndrome phenotype in human-induced pluripotency stem cell cardiomyocytes

    PubMed Central

    Matsa, Elena; Dixon, James E.; Medway, Christopher; Georgiou, Orestis; Patel, Minal J.; Morgan, Kevin; Kemp, Paul J.; Staniforth, Andrew; Mellor, Ian; Denning, Chris

    2014-01-01

    Aims Long-QT syndromes (LQTS) are mostly autosomal-dominant congenital disorders associated with a 1:1000 mutation frequency, cardiac arrest, and sudden death. We sought to use cardiomyocytes derived from human-induced pluripotency stem cells (hiPSCs) as an in vitro model to develop and evaluate gene-based therapeutics for the treatment of LQTS. Methods and results We produced LQTS-type 2 (LQT2) hiPSC cardiomyocytes carrying a KCNH2 c.G1681A mutation in a IKr ion-channel pore, which caused impaired glycosylation and channel transport to cell surface. Allele-specific RNA interference (RNAi) directed towards the mutated KCNH2 mRNA caused knockdown, while leaving the wild-type mRNA unaffected. Electrophysiological analysis of patient-derived LQT2 hiPSC cardiomyocytes treated with mutation-specific siRNAs showed normalized action potential durations (APDs) and K+ currents with the concurrent rescue of spontaneous and drug-induced arrhythmias (presented as early-afterdepolarizations). Conclusions These findings provide in vitro evidence that allele-specific RNAi can rescue diseased phenotype in LQTS cardiomyocytes. This is a potentially novel route for the treatment of many autosomal-dominant-negative disorders, including those of the heart. PMID:23470493

  17. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

    PubMed

    Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

    2015-08-24

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration.

  18. Does routine child health surveillance contribute to the early detection of children with pervasive developmental disorders? – An epidemiological study in Kent, U.K.

    PubMed Central

    Tebruegge, Marc; Nandini, Vridhagiri; Ritchie, Jane

    2004-01-01

    Background Recently changed guidelines for child health surveillance in the United Kingdom (U.K.) suggest targeted checks only, instead of the previously conducted routine or universal screening at 2 years and 3.5 years. There are concerns that these changes could lead to a delay in the detection of children with autism and other pervasive developmental disorders (PDD). Recent U.K. studies have suggested that the prevalence of PDD is much higher than previously estimated. This study establishes to which extent the routine checks contributed to the early detection and assessment of cases of PDD. Simultaneously we have evaluated the process involved and estimate the prevalence of PDD in our district. Methods Retrospective study design utilising community medical files. Headteachers of schools (n = 75) within Maidstone district (Kent) were asked to report all children with an established diagnosis of autism or PDD attending year 4 (born '91 and '92 / n = 2536) in October 2000 based on educational records. Results 59 schools (78.7%) took part in the study. A total of 33 children were reported. 21 fulfilled the inclusion criteria (12 falsely reported). The prevalences were (per 10,000): PDD 82.8 (male to female ratio 6:1), childhood autism 23.7, Asperger's syndrome 11.8 and autistic spectrum disorder 47.3. Co-existing medical conditions were noted in 14.3%; 52.4% were attending mainstream schools. In 63.2% of cases concerns – mainly in the area of speech and language development (SLD) – had been documented at the 2 year check. At the 3.5 year check concerns were noted in 94.1% – the main area was again SLD (76.5%), although behavioural abnormalities were becoming more frequent (47.1%). A total of 13 children (68.4%) were referred for further assessment as a direct result of the checks. Conclusions The prevalences for different types of PDD were similar to figures published recently, but much higher than reported a few years ago. Analysis of our data suggests that

  19. DEVELOPMENTALLY REGULATED PLASMA MEMBRANE PROTEIN of Nicotiana benthamiana Contributes to Potyvirus Movement and Transports to Plasmodesmata via the Early Secretory Pathway and the Actomyosin System1[OPEN

    PubMed Central

    Geng, Chao; Cong, Qian-Qian; Li, Xiang-Dong; Mou, An-Li; Gao, Rui; Liu, Jin-Liang; Tian, Yan-Ping

    2015-01-01

    The intercellular movement of plant viruses requires both viral and host proteins. Previous studies have demonstrated that the frame-shift protein P3N-PIPO (for the protein encoded by the open reading frame [ORF] containing 5′-terminus of P3 and a +2 frame-shift ORF called Pretty Interesting Potyviridae ORF and embedded in the P3) and CYLINDRICAL INCLUSION (CI) proteins were required for potyvirus cell-to-cell movement. Here, we provide genetic evidence showing that a Tobacco vein banding mosaic virus (TVBMV; genus Potyvirus) mutant carrying a truncated PIPO domain of 58 amino acid residues could move between cells and induce systemic infection in Nicotiana benthamiana plants; mutants carrying a PIPO domain of seven, 20, or 43 amino acid residues failed to move between cells and cause systemic infection in this host plant. Interestingly, the movement-defective mutants produced progeny that eliminated the previously introduced stop codons and thus restored their systemic movement ability. We also present evidence showing that a developmentally regulated plasma membrane protein of N. benthamiana (referred to as NbDREPP) interacted with both P3N-PIPO and CI of the movement-competent TVBMV. The knockdown of NbDREPP gene expression in N. benthamiana impeded the cell-to-cell movement of TVBMV. NbDREPP was shown to colocalize with TVBMV P3N-PIPO and CI at plasmodesmata (PD) and traffic to PD via the early secretory pathway and the actomyosin motility system. We also show that myosin XI-2 is specially required for transporting NbDREPP to PD. In conclusion, NbDREPP is a key host protein within the early secretory pathway and the actomyosin motility system that interacts with two movement proteins and influences virus movement. PMID:25540331

  20. Spatiotemporal expression and transcriptional regulation of heme oxygenase and biliverdin reductase genes in zebrafish (Danio rerio) suggest novel roles during early developmental periods of heightened oxidative stress.

    PubMed

    Holowiecki, Andrew; O'Shields, Britton; Jenny, Matthew J

    2017-01-01

    Heme oxygenase 1 (HMOX1) degrades heme into biliverdin, which is subsequently converted to bilirubin by biliverdin reductase (BVRa or BVRb) in a manner analogous to the classic anti-oxidant glutathione-recycling pathway. To gain a better understanding of the potential antioxidant roles the BVR enzymes may play during development, the spatiotemporal expression and transcriptional regulation of zebrafish hmox1a, bvra and bvrb were characterized under basal conditions and in response to pro-oxidant exposure. All three genes displayed spatiotemporal expression patterns consistent with classic hematopoietic progenitors during development. Transient knockdown of Nrf2a did not attenuate the ability to detect bvra or bvrb by ISH, or alter spatial expression patterns in response to cadmium exposure. While hmox1a:mCherry fluorescence was documented within the intermediate cell mass, a transient location of primitive erythrocyte differentiation, expression was not fully attenuated in Nrf2a morphants, but real-time RT-PCR demonstrated a significant reduction in hmox1a expression. Furthermore, Gata-1 knockdown did not attenuate hmox1a:mCherry fluorescence. However, while there was a complete loss of detection of bvrb expression by ISH at 24hpf, bvra expression was greatly attenuated but still detectable in Gata-1 morphants. In contrast, 96 hpf Gata-1 morphants displayed increased bvra and bvrb expression within hematopoietic tissues. Finally, temporal expression patterns of enzymes involved in the generation and maintenance of NADPH were consistent with known changes in the cellular redox state during early zebrafish development. Together, these data suggest that Gata-1 and Nrf2a play differential roles in regulating the heme degradation enzymes during an early developmental period of heightened cellular stress.

  1. Suppression of Wnt1-induced mammary tumor growth and lower serum insulin in offspring exposed to maternal blueberry diet suggest early dietary influence on developmental programming.

    PubMed

    Rahal, Omar M; Pabona, John Mark P; Kelly, Thomas; Huang, Yan; Hennings, Leah J; Prior, Ronald L; Al-Dwairi, Ahmed; Simmen, Frank A; Simmen, Rosalia C M

    2013-02-01

    Despite the well-accepted notion that early maternal influences persist beyond fetal life and may underlie many adult diseases, the risks imposed by the maternal environment on breast cancer development and underlying biological mechanisms remain poorly understood. In this study, we investigated whether early exposure to blueberry (BB) via maternal diet alters oncogene Wnt1-induced mammary tumorigenesis in offspring. Wnt1-transgenic female mice were exposed to maternal Casein (CAS, control) or blueberry-supplemented (CAS + 3%BB) diets throughout pregnancy and lactation. Offspring were weaned to CAS and mammary tumor development was followed until age 8 months. Tumor incidence and latency were similar for both groups; however, tumor weight at killing and tumor volume within 2 weeks of initial detection were lower (by 50 and 60%, respectively) in offspring of BB- versus control-fed dams. Dietary BB exposure beginning at weaning did not alter mammary tumor parameters. Tumors from maternal BB-exposed offspring showed higher tumor suppressor (Pten and Cdh1) and lower proproliferative (Ccnd1), anti-apoptotic (Bcl2) and proangiogenic (Figf, Flt1 and Ephb4) transcript levels, and displayed attenuated microvessel density. Expression of Pten and Cdh1 genes was also higher in mammary tissues of maternal BB-exposed offspring. Mammary tissues and tumors of maternal BB-exposed offspring showed increased chromatin-modifying enzyme Dnmt1 and Ezh2 transcript levels. Body weight, serum insulin and serum leptin/adiponectin ratio were lower for maternal BB-exposed than control tumor-bearing offspring. Tumor weights and serum insulin were positively correlated. Results suggest that dietary influences on the maternal environment contribute to key developmental programs in the mammary gland to modify breast cancer outcome in adult progeny.

  2. DEVELOPMENTALLY REGULATED PLASMA MEMBRANE PROTEIN of Nicotiana benthamiana contributes to potyvirus movement and transports to plasmodesmata via the early secretory pathway and the actomyosin system.

    PubMed

    Geng, Chao; Cong, Qian-Qian; Li, Xiang-Dong; Mou, An-Li; Gao, Rui; Liu, Jin-Liang; Tian, Yan-Ping

    2015-02-01

    The intercellular movement of plant viruses requires both viral and host proteins. Previous studies have demonstrated that the frame-shift protein P3N-PIPO (for the protein encoded by the open reading frame [ORF] containing 5'-terminus of P3 and a +2 frame-shift ORF called Pretty Interesting Potyviridae ORF and embedded in the P3) and CYLINDRICAL INCLUSION (CI) proteins were required for potyvirus cell-to-cell movement. Here, we provide genetic evidence showing that a Tobacco vein banding mosaic virus (TVBMV; genus Potyvirus) mutant carrying a truncated PIPO domain of 58 amino acid residues could move between cells and induce systemic infection in Nicotiana benthamiana plants; mutants carrying a PIPO domain of seven, 20, or 43 amino acid residues failed to move between cells and cause systemic infection in this host plant. Interestingly, the movement-defective mutants produced progeny that eliminated the previously introduced stop codons and thus restored their systemic movement ability. We also present evidence showing that a developmentally regulated plasma membrane protein of N. benthamiana (referred to as NbDREPP) interacted with both P3N-PIPO and CI of the movement-competent TVBMV. The knockdown of NbDREPP gene expression in N. benthamiana impeded the cell-to-cell movement of TVBMV. NbDREPP was shown to colocalize with TVBMV P3N-PIPO and CI at plasmodesmata (PD) and traffic to PD via the early secretory pathway and the actomyosin motility system. We also show that myosin XI-2 is specially required for transporting NbDREPP to PD. In conclusion, NbDREPP is a key host protein within the early secretory pathway and the actomyosin motility system that interacts with two movement proteins and influences virus movement.

  3. Exposure time to caffeine affects heartbeat and cell damage-related gene expression of zebrafish Danio rerio embryos at early developmental stages.

    PubMed

    Abdelkader, Tamer Said; Chang, Seo-Na; Kim, Tae-Hyun; Song, Juha; Kim, Dong Su; Park, Jae-Hak

    2013-11-01

    Caffeine is white crystalline xanthine alkaloid that is naturally found in some plants and can be produced synthetically. It has various biological effects, especially during pregnancy and lactation. We studied the effect of caffeine on heartbeat, survival and the expression of cell damage related genes, including oxidative stress (HSP70), mitochondrial metabolism (Cyclin G1) and apoptosis (Bax and Bcl2), at early developmental stages of zebrafish embryos. We used 100 µm concentration based on the absence of locomotor effects. Neither significant mortality nor morphological changes were detected. We monitored hatching at 48 h post-fertilization (hpf) to 96 hpf. At 60 and 72 hpf, hatching decreased significantly (P < 0.05); however, the overall hatching rate at 96 hpf was 94% in control and 93% in caffeine treatment with no significant difference (P > 0.05). Heartbeats per minute were 110, 110 and 112 in control at 48, 72 and 96 hpf, respectively. Caffeine significantly increased heartbeat - 122 and 136 at 72 and 96 hpf, respectively. Quantitative RT-PCR showed significant up-regulation after caffeine exposure in HSP70 at 72 hpf; in Cyclin G1 at 24, 48 and 72 hpf; and in Bax at 48 and 72 hpf. Significant down-regulation was found in Bcl2 at 48 and 72 hpf. The Bax/Bcl2 ratio increased significantly at 48 and 72 hpf. We conclude that increasing exposure time to caffeine stimulates oxidative stress and may trigger apoptosis via a mitochondrial-dependent pathway. Also caffeine increases heartbeat from early phases of development without affecting the morphology and survival but delays hatching. Use of caffeine during pregnancy and lactation may harm the fetus by affecting the expression of cell-damage related genes.

  4. Gene expression changes triggered by end-of-day far-red light treatment on early developmental stages of Eustoma grandiflorum (Raf.) Shinn.

    PubMed Central

    Takemura, Yoshihiro; Kuroki, Katsuou; Katou, Masahiro; Kishimoto, Masayuki; Tsuji, Wataru; Nishihara, Eiji; Tamura, Fumio

    2015-01-01

    To better understand the molecular mechanisms related to growth promotion in the early developmental stages of Eustoma grandiflorum (Raf.) Shinn. under end-of-day far-red light (EOD-FR) treatment, we analyzed the leaf transcriptome of treated (EOD) and untreated plants (Cont) by using RNA-seq technology. EOD-FR treatment for only about 2 weeks in regions with limited sunshine during winter resulted in significantly higher internode length between the 3rd and 4th nodes on the main stem in EOD than in Cont. Among the differentially expressed genes (DEGs) related to synthesis or transport of auxin, higher levels of YUCCA (CL6581) and PIN4 (CL6181) were noted after treatment in EOD than in Cont in the leaf. In addition, high expression levels of GA20ox (Unigene11862) related to gibberellin (GA) synthesis and transcription factor bHLH 135 (CL7761) were observed in the stem of EOD, 3 h after treatment. A vertical section of the stem showed that the pith length of cells at the 4th node was longer in EOD than in Cont. Collectively, these results suggested that EOD-FR treatment increased the expression of DEGs related to GA and auxin biosynthesis, bHLH transcription factor, and internodal cell elongation along the longitudinal axis of Eustoma plants. PMID:26642764

  5. Adolescent motherhood and developmental outcomes of children in early head start: the influence of maternal parenting behaviors, well-being, and risk factors within the family setting.

    PubMed

    Rafferty, Yvonne; Griffin, Kenneth W; Lodise, Michelle

    2011-04-01

    This longitudinal study examined the influence of parenting behaviors, well-being, and risk factors of low-income adolescent mothers on the cognitive and language abilities of children from infancy to age 3. Participants consisted of 1,240 mother-child dyads enrolled in the Early Head Start Research and Evaluation Project. Data were collected using structured interviews with the mothers and from videotaped mother-child interactions during play activities when children were approximately 14 months old and again at 36 months of age. Positive parenting behaviors exhibited toward the 14-month-old children predicted gains in both cognitive and language abilities more so than did maternal well-being, risk factors within the family setting, and demographic risk factors. Gains in cognitive abilities from infancy to age 3 were predicted by supportive parenting, higher family resources, and lower family conflict when children were infants. Gains in language abilities were predicted by supportive parenting, support for language and learning in the home environment, and higher family resources when children were infants. Finally, path analyses showed that maternal age had an indirect effect on child cognitive and language abilities at age 3 through effects on parenting behaviors. Older mothers were more likely to be supportive during play at age 14 months, which in turn promoted enhanced developmental outcomes at age 3. Implications for intervention and future research are discussed.

  6. (Positive) power to the child: The role of children's willing stance toward parents in developmental cascades from toddler age to early preadolescence.

    PubMed

    Kochanska, Grazyna; Kim, Sanghag; Boldt, Lea J

    2015-11-01

    In a change from the once-dominant view of children as passive in the parent-led process of socialization, children are now seen as active agents who can considerably influence that process. However, these newer perspectives typically focus on the child's antagonistic influence, due either to a difficult temperament or aversive, resistant, negative behaviors that elicit adversarial responses from the parent and lead to future coercive cascades in the relationship. Children's capacity to act as receptive, willing, even enthusiastic, active socialization agents is largely overlooked. Informed by attachment theory and other relational perspectives, we depict children as able to adopt an active willing stance and to exert robust positive influence in the mutually cooperative socialization enterprise. A longitudinal study of 100 community families (mothers, fathers, and children) demonstrates that willing stance (a) is a latent construct, observable in diverse parent-child contexts, parallel at 38, 52, and 67 months and longitudinally stable; (b) originates within an early secure parent-child relationship at 25 months; and (c) promotes a positive future cascade toward adaptive outcomes at age 10. The outcomes include the parent's observed and child-reported positive, responsive behavior, as well as child-reported internal obligation to obey the parent and parent-reported low level of child behavior problems. The construct of willing stance has implications for basic research in typical socialization and in developmental psychopathology as well as for prevention and intervention.

  7. Deletion of exon 20 of the Familial Dysautonomia gene Ikbkap in mice causes developmental delay, cardiovascular defects, and early embryonic lethality.

    PubMed

    Dietrich, Paula; Yue, Junming; E, Shuyu; Dragatsis, Ioannis

    2011-01-01

    Familial Dysautonomia (FD) is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population, and leads to death before the age of 40. The disease is characterized by abnormal development and progressive degeneration of the sensory and autonomic nervous system. A single base pair substitution in intron 20 of the Ikbkap gene accounts for 98% of FD cases, and results in the expression of low levels of the full-length mRNA with simultaneous expression of an aberrantly spliced mRNA in which exon 20 is missing. To date, there is no animal model for the disease, and the essential cellular functions of IKAP--the protein encoded by Ikbkap--remain unknown. To better understand the normal function of IKAP and in an effort to generate a mouse model for FD, we have targeted the mouse Ikbkap gene by homologous recombination. We created two distinct alleles that result in either loss of Ikbkap expression, or expression of an mRNA lacking only exon 20. Homozygosity for either mutation leads to developmental delay, cardiovascular and brain malformations, accompanied with early embryonic lethality. Our analyses indicate that IKAP is essential for expression of specific genes involved in cardiac morphogenesis, and that cardiac failure is the likely cause of abnormal vascular development and embryonic lethality. Our results also indicate that deletion of exon 20 abolishes gene function. This implies that the truncated IKAP protein expressed in FD patients does not retain any significant biological function.

  8. (Positive) Power to the Child: The Role of Children's Willing Stance toward Parents in Developmental Cascades from Toddler Age to Early Preadolescence

    PubMed Central

    Kochanska, Grazyna; Kim, Sanghag; Boldt, Lea J.

    2015-01-01

    In contrast to once dominant views of children as passive in the parent-led process of socialization, they are now seen as active agents who can considerably influence that process. But those newer perspectives typically focus on the child's antagonistic influence, due either to a difficult temperament or aversive, resistant, negative behaviors that elicit adversarial responses from the parent and lead to future coercive cascades in the relationship. Children's capacity to act as receptive, willing, even enthusiastic, active socialization agents is largely overlooked. Informed by attachment theory and other relational perspectives, we depict children as able to adopt an active willing stance and to exert robust positive influence in the mutually cooperative socialization enterprise. A longitudinal study of 100 community families (mothers, fathers, and children) demonstrates that willing stance (a) is a latent construct, observable in diverse parent-child contexts parallel at 38, 52, and 67 months, and longitudinally stable, (b) originates within an early secure parent-child relationship at 25 months, and (c) promotes a positive future cascade toward adaptive outcomes at age 10. The outcomes include the parent's observed and child-reported positive, responsive behavior, as well as child-reported internal obligation to obey the parent and parent-reported low level of child behavior problems. The construct of willing stance has implications for basic research in typical socialization and in developmental psychopathology, and for prevention and intervention. PMID:26439058

  9. Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death

    PubMed Central

    Parra, Valentina; Moraga, Francisco; Kuzmicic, Jovan; López-Crisosto, Camila; Troncoso, Rodrigo; Torrealba, Natalia; Criollo, Alfredo; Díaz-Elizondo, Jessica; Rothermel, Beverly A.; Quest, Andrew F.G.; Lavandero, Sergio

    2014-01-01

    Ceramides are important intermediates in the biosynthesis and degradation of sphingolipids that regulatenumerous cellular processes, including cell cycle progression, cell growth, differentiation and death. In cardiomyocytes, ceramides induce apoptosis by decreasing mitochondrial membrane potential and promoting cytochrome-c release. Ca2+ overload is a common feature of all types of cell death. The aim of this study was to determine the effect of ceramides on cytoplasmic Ca2+ levels, mitochondrial function and cardiomyocyte death. Our data show that C2-ceramide induces apoptosis and necrosis in cultured cardiomyocytes by a mechanism involving increased Ca2+ influx, mitochondrial network fragmentation and loss of the mitochondrial Ca2+ buffer capacity. These biochemical events increase cytosolic Ca2+ levels and trigger cardiomyocyte death via the activation of calpains. PMID:23602992

  10. Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death.

    PubMed

    Parra, Valentina; Moraga, Francisco; Kuzmicic, Jovan; López-Crisosto, Camila; Troncoso, Rodrigo; Torrealba, Natalia; Criollo, Alfredo; Díaz-Elizondo, Jessica; Rothermel, Beverly A; Quest, Andrew F G; Lavandero, Sergio

    2013-08-01

    Ceramides are important intermediates in the biosynthesis and degradation of sphingolipids that regulate numerous cellular processes, including cell cycle progression, cell growth, differentiation and death. In cardiomyocytes, ceramides induce apoptosis by decreasing mitochondrial membrane potential and promoting cytochrome-c release. Ca(2+) overload is a common feature of all types of cell death. The aim of this study was to determine the effect of ceramides on cytoplasmic Ca(2+) levels, mitochondrial function and cardiomyocyte death. Our data show that C2-ceramide induces apoptosis and necrosis in cultured cardiomyocytes by a mechanism involving increased Ca(2+) influx, mitochondrial network fragmentation and loss of the mitochondrial Ca(2+) buffer capacity. These biochemical events increase cytosolic Ca(2+) levels and trigger cardiomyocyte death via the activation of calpains.

  11. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells.

    PubMed

    Kehat, Izhak; Khimovich, Leonid; Caspi, Oren; Gepstein, Amira; Shofti, Rona; Arbel, Gil; Huber, Irit; Satin, Jonathan; Itskovitz-Eldor, Joseph; Gepstein, Lior

    2004-10-01

    Cell therapy is emerging as a promising strategy for myocardial repair. This approach is hampered, however, by the lack of sources for human cardiac tissue and by the absence of direct evidence for functional integration of donor cells into host tissues. Here we investigate whether cells derived from human embryonic stem (hES) cells can restore myocardial electromechanical properties. Cardiomyocyte cell grafts were generated from hES cells in vitro using the embryoid body differentiating system. This tissue formed structural and electromechanical connections with cultured rat cardiomyocytes. In vivo integration was shown in a large-animal model of slow heart rate. The transplanted hES cell-derived cardiomyocytes paced the hearts of swine with complete atrioventricular block, as assessed by detailed three-dimensional electrophysiological mapping and histopathological examination. These results demonstrate the potential of hES-cell cardiomyocytes to act as a rate-responsive biological pacemaker and for future myocardial regeneration strategies.

  12. Building and re-building the heart by cardiomyocyte proliferation

    PubMed Central

    Foglia, Matthew J.; Poss, Kenneth D.

    2016-01-01

    The adult human heart does not regenerate significant amounts of lost tissue after injury. Rather than making new, functional muscle, human hearts are prone to scarring and hypertrophy, which can often lead to fatal arrhythmias and heart failure. The most-cited basis of this ineffective cardiac regeneration in mammals is the low proliferative capacity of adult cardiomyocytes. However, mammalian cardiomyocytes can avidly proliferate during fetal and neonatal development, and both adult zebrafish and neonatal mice can regenerate cardiac muscle after injury, suggesting that latent regenerative potential exists. Dissecting the cellular and molecular mechanisms that promote cardiomyocyte proliferation throughout life, deciphering why proliferative capacity normally dissipates in adult mammals, and deriving means to boost this capacity are primary goals in cardiovascular research. Here, we review our current understanding of how cardiomyocyte proliferation is regulated during heart development and regeneration. PMID:26932668

  13. Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform.

    PubMed

    Denning, Chris; Borgdorff, Viola; Crutchley, James; Firth, Karl S A; George, Vinoj; Kalra, Spandan; Kondrashov, Alexander; Hoang, Minh Duc; Mosqueira, Diogo; Patel, Asha; Prodanov, Ljupcho; Rajamohan, Divya; Skarnes, William C; Smith, James G W; Young, Lorraine E

    2016-07-01

    Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  14. Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.

    PubMed

    Kokkinopoulos, Ioannis; Ishida, Hidekazu; Saba, Rie; Ruchaya, Prashant; Cabrera, Claudia; Struebig, Monika; Barnes, Michael; Terry, Anna; Kaneko, Masahiro; Shintani, Yasunori; Coppen, Steven; Shiratori, Hidetaka; Ameen, Torath; Mein, Charles; Hamada, Hiroshi; Suzuki, Ken; Yashiro, Kenta

    2015-01-01

    In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.

  15. Developmentally sensitive diagnostic criteria for mental health disorders in early childhood: the diagnostic and statistical manual of mental disorders-IV, the research diagnostic criteria-preschool age, and the diagnostic classification of mental health and developmental disorders of infancy and early childhood-revised.

    PubMed

    Egger, Helen L; Emde, Robert N

    2011-01-01

    As the infant mental health field has turned its focus to the presentation, course, and treatment of clinically significant mental health disorders, the need for reliable and valid criteria for identifying and assessing mental health symptoms and disorders in early childhood has become urgent. In this article we offer a critical perspective on diagnostic classification of mental health disorders in young children. We place the issue of early childhood diagnosis within the context of classification of psychopathology at other ages and describe, in some detail, diagnostic classifications that have been developed specifically for young children, including the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-3R; ZERO TO THREE, 2005), a diagnostic classification for mental health symptoms and disorders in infants, toddlers, and preschoolers. We briefly outline the role of diagnostic classification in clinical assessment and treatment planning. Last, we review the limitations of current approaches to the diagnostic classification of mental health disorders in young children.

  16. Biomechanical Characterization of Cardiomyocyte Using PDMS Pillar with Microgrooves

    PubMed Central

    Oyunbaatar, Nomin-Erdene; Lee, Deok-Hyu; Patil, Swati J.; Kim, Eung-Sam; Lee, Dong-Weon

    2016-01-01

    This paper describes the surface-patterned polydimethylsiloxane (PDMS) pillar arrays for enhancing cell alignment and contraction force in cardiomyocytes. The PDMS micropillar (μpillar) arrays with microgrooves (μgrooves) were fabricated using a unique micro-mold made using SU-8 double layer processes. The spring constant of the μpillar arrays was experimentally confirmed using atomic force microscopy (AFM). After culturing cardiac cells on the two different types of μpillar arrays, with and without grooves on the top of μpillar, the characteristics of the cardiomyocytes were analyzed using a custom-made image analysis system. The alignment of the cardiomyocytes on the μgrooves of the μpillars was clearly observed using a DAPI staining process. The mechanical force generated by the contraction force of the cardiomyocytes was derived from the displacement of the μpillar arrays. The contraction force of the cardiomyocytes aligned on the μgrooves was 20% higher than that of the μpillar arrays without μgrooves. The experimental results prove that applied geometrical stimulus is an effective method for aligning and improving the contraction force of cardiomyocytes. PMID:27517924

  17. σK of Clostridium acetobutylicum is the first known sporulation-specific sigma factor with two developmentally separated roles, one early and one late in sporulation.

    PubMed

    Al-Hinai, Mohab A; Jones, Shawn W; Papoutsakis, Eleftherios T

    2014-01-01

    Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σ(H) (early), σ(F), σ(E), σ(G), and σ(K) (late). Here we show that the Clostridium acetobutylicum σ(K) acts both early, prior to Spo0A expression, and late, past σ(G) activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σ(G) proteins were not detectable by Western analysis, while σ(F) protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σ(K) is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σ(F), σ(E), and σ(G), but not sporulation, which was blocked past the σ(G) stage of development, thus demonstrating that σ(K) is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles.

  18. Early prediction of typical outcome and mild developmental delay for prioritisation of service delivery for very preterm and very low birthweight infants: a study protocol

    PubMed Central

    Caesar, Rebecca; Boyd, Roslyn N; Colditz, Paul; Cioni, Giovani; Ware, Robert S; Salthouse, Kaye; Doherty, Julie; Jackson, Maxine; Matthews, Leanne; Hurley, Tom; Morosini, Anthony; Thomas, Clare; Camadoo, Laxmi; Baer, Erica

    2016-01-01

    Introduction Over 80% of very preterm (<32 weeks) and very low birthweight (<1500 g) infants will have either typical development (TD) or mild developmental delay (MDD) in multiple domains. As differentiation between TD and MDD can be difficult, infants with MDD often miss opportunities for intervention. For many clinicians, the ongoing challenge is early detection of MDD without over servicing the population. This study aims to: (1) identify early clinical biomarkers for use in this population to predict and differentiate between TD and MDD at 24 months corrected age. (2) Determine the extent to which family and caregiver factors will contribute to neurodevelopmental and behavioural outcomes. Methods and analysis Participants will be a prospective cohort of 90 infants (<32 weeks and/or <1500 g). Between 34 weeks gestational age and 16 weeks post-term, infants will have a series of 5 neurological, neuromotor, neurobehavioural and perceptual assessments including General Movement Assessment at preterm, writhing and fidgety age. Primary caregivers will complete questionnaires to identify social risk, maternal depression and family strain. Extensive perinatal data will be collected from the medical record. At 24 months, corrected age (c.a) infants will be assessed using standardised tools including the Bayley Scales of Infant and Toddler Development—Third Edition (Bayley III). Longitudinal trajectories of early assessment findings will be examined to determine any predictive relationship with motor and cognitive outcomes at 24 months c.a. Published data of a cohort of Australian children assessed with the Bayley III at 24 months c.a will provide a reference group of term-born controls. Ethics Ethical approval has been obtained from the Queensland Children's Health Services Human Research Ethics Committee (HREC/13/QRCH/66), the University of Queensland (2013001019) and the Sunshine Coast Hospital and Health Service, SC-Research Governance (SSA/13

  19. Reverse engineering life: physical and chemical mimetics for controlled stem cell differentiation into cardiomyocytes.

    PubMed

    Skuse, Gary R; Lamkin-Kennard, Kathleen A

    2013-01-01

    Our ability to manipulate stem cells in order to induce differentiation along a desired developmental pathway has improved immeasurably in recent years. That is in part because we have a better understanding of the intracellular and extracellular signals that regulate differentiation. However, there has also been a realization that stem cell differentiation is not regulated only by chemical signals but also by the physical milieu in which a particular stem cell exists. In this regard we are challenged to mimic both chemical and physical environments. Herein we describe a method to induce stem cell differentiation into cardiomyocytes using a combination of chemical and physical cues. This method can be applied to produce differentiated cells for research and potentially for cell-based therapy of cardiomyopathies.

  20. Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation “Memories”

    PubMed Central

    Tompkins, Joshua D.; Jung, Marc; Chen, Chang-yi; Lin, Ziguang; Ye, Jingjing; Godatha, Swetha; Lizhar, Elizabeth; Wu, Xiwei; Hsu, David; Couture, Larry A.; Riggs, Arthur D.

    2016-01-01

    The directed differentiation of human cardiomyocytes (CMs) from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation “memories” persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors. PMID:26981572

  1. Developmental Evaluation.

    ERIC Educational Resources Information Center

    Patton, Michael Quinn

    1994-01-01

    Developmental evaluation is proposed as a term to describe certain long-term partnering relationships with clients who are, themselves, engaged in ongoing program development. Rather than a model, developmental evaluation is a relationship founded on a shared purpose and is a way of being useful in innovative settings. (SLD)

  2. Quantitative proteomics identify DAB2 as a cardiac developmental regulator that inhibits WNT/β-catenin signaling.

    PubMed

    Hofsteen, Peter; Robitaille, Aaron M; Chapman, Daniel Patrick; Moon, Randall T; Murry, Charles E

    2016-01-26

    To reveal the molecular mechanisms involved in cardiac lineage determination and differentiation, we quantified the proteome of human embryonic stem cells (hESCs), cardiac progenitor cells (CPCs), and cardiomyocytes during a time course of directed differentiation by label-free quantitative proteomics. This approach correctly identified known stage-specific markers of cardiomyocyte differentiation, including SRY-box2 (SOX2), GATA binding protein 4 (GATA4), and myosin heavy chain 6 (MYH6). This led us to determine whether our proteomic screen could reveal previously unidentified mediators of heart development. We identified Disabled 2 (DAB2) as one of the most dynamically expressed proteins in hESCs, CPCs, and cardiomyocytes. We used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) mutagenesis in zebrafish to assess whether DAB2 plays a functional role during cardiomyocyte differentiation. We found that deletion of Dab2 in zebrafish embryos led to a significant reduction in cardiomyocyte number and increased endogenous WNT/β-catenin signaling. Furthermore, the Dab2-deficient defects in cardiomyocyte number could be suppressed by overexpression of dickkopf 1 (DKK1), an inhibitor of WNT/β-catenin signaling. Thus, inhibition of WNT/β-catenin signaling by DAB2 is essential for establishing the correct number of cardiomyocytes in the developing heart. Our work demonstrates that quantifying the proteome of human stem cells can identify previously unknown developmental regulators.

  3. Purinergic inhibition of glucose transport in cardiomyocytes.

    PubMed

    Fischer, Y; Becker, C; Löken, C

    1999-01-08

    ATP is known to act as an extracellular signal in many organs. In the heart, extracellular ATP modulates ionic processes and contractile function. This study describes a novel, metabolic effect of exogenous ATP in isolated rat cardiomyocytes. In these quiescent (i.e. noncontracting) cells, micromolar concentrations of ATP depressed the rate of basal, catecholamine-stimulated, or insulin-stimulated glucose transport by up to 60% (IC50 for inhibition of insulin-dependent glucose transport, 4 microM). ATP decreased the amount of glucose transporters (GLUT1 and GLUT4) in the plasma membrane, with a concomitant increase in intracellular microsomal membranes. A similar glucose transport inhibition was produced by P2 purinergic agonists with the following rank of potencies: ATP approximately ATPgammaS approximately 2-methylthio-ATP (P2Y-selective) > ADP > alpha,betameATP (P2X-selective), whereas the P1 purinoceptor agonist adenosine was ineffective. The effect of ATP was suppressed by the poorly subtype-selective P2 antagonist pyridoxal-phosphate-6-azophenyl-2', 4'-disulfonic acid but, surprisingly, not by the nonselective antagonist suramin nor by the P2Y-specific Reactive Blue 2. Glucose transport inhibition by ATP was not affected by a drastic reduction of the extracellular concentrations of calcium (down to 10(-9) M) or sodium (down to 0 mM), and it was not mimicked by a potassium-induced depolarization, indicating that purinoceptors of the P2X family (which are nonselective cation channels whose activation leads to a depolarizing sodium and calcium influx) are not involved. Inhibition was specific for the transmembrane transport of glucose because ATP did not inhibit (i) the rate of glycolysis under conditions where the transport step is no longer rate-limiting nor (ii) the rate of [1-14C]pyruvate decarboxylation. In conclusion, extracellular ATP markedly inhibits glucose transport in rat cardiomyocytes by promoting a redistribution of glucose transporters from the

  4. Argon Induces Protective Effects in Cardiomyocytes during the Second Window of Preconditioning.

    PubMed

    Mayer, Britta; Soppert, Josefin; Kraemer, Sandra; Schemmel, Sabrina; Beckers, Christian; Bleilevens, Christian; Rossaint, Rolf; Coburn, Mark; Goetzenich, Andreas; Stoppe, Christian

    2016-07-19

    Increasing evidence indicates that argon has organoprotective properties. So far, the underlying mechanisms remain poorly understood. Therefore, we investigated the effect of argon preconditioning in cardiomyocytes within the first and second window of preconditioning. Primary isolated cardiomyocytes from neonatal rats were subjected to 50% argon for 1 h, and subsequently exposed to a sublethal dosage of hypoxia (<1% O₂) for 5 h either within the first (0-3 h) or second window (24-48 h) of preconditioning. Subsequently, the cell viability and proliferation was measured. The argon-induced effects were assessed by evaluation of mRNA and protein expression after preconditioning. Argon preconditioning did not show any cardioprotective effects in the early window of preconditioning, whereas it leads to a significant increase of cell viability 24 h after preconditioning compared to untreated cells (p = 0.015) independent of proliferation. Argon-preconditioning significantly increased the mRNA expression of heat shock protein (HSP) B1 (HSP27) (p = 0.048), superoxide dismutase 2 (SOD2) (p = 0.001), vascular endothelial growth factor (VEGF) (p < 0.001) and inducible nitric oxide synthase (iNOS) (p = 0.001). No difference was found with respect to activation of pro-survival kinases in the early and late window of preconditioning. The findings provide the first evidence of argon-induced effects on the survival of cardiomyocytes during the second window of preconditioning, which may be mediated through the induction of HSP27, SOD2, VEGF and iNOS.

  5. Co-parenting and feeding in early childhood: Reflections of parent dyads on how they manage the developmental stages of feeding over the first three years.

    PubMed

    Thullen, Matthew; Majee, Wilson; Davis, Alexandra N

    2016-10-01

    Family-level influences on the development of healthy eating behaviors start in infancy and toddlerhood with how families manage developmental stages of feeding. Little research on home feeding environments for young children has examined how mothers and fathers collaborate around feeding issues or contribute jointly to feeding. The purpose of this qualitative study is to examine co-parenting with regard to infant/toddler feeding practices. Twenty-four sets of co-resident, biological parents with a child between 6 months and 3 years were interviewed together about their feeding practices and how they discussed and collaborated on feeding during the main stages of feeding development in the first three years. Analyses illuminate themes related to how specific domains of co-parenting (satisfaction with labor, support, agreement, conflict) factor into infant and toddler feeding as well as how additional factors such as having older children and employment schedules shape how both food parenting practices and co-parenting are managed in relation to feeding. Mothers were the primary managers of feeding labor. Fathers participated in feeding in different ways and levels starting in infancy and increased involvement in feeding over the first few years requiring an ongoing negotiation around co-parenting related to feeding. Overall, this study develops insights into how multiple caregivers construct a family environment specifically related to early feeding - a perspective missing from current conceptualizations of home feeding environment. Attention to the concept of co-parenting within home feeding environments should help inform more effective approaches to intervene with families on issues around childhood obesity and family health.

  6. Dioxin Exposure Disrupts the Differentiation of Mouse Embryonic Stem Cells into Cardiomyocytes

    PubMed Central

    Wang, Ying; Fan, Yunxia; Puga, Alvaro

    2010-01-01

    Experimental exposure of fish, birds, and rodents to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) causes multiple Ah receptor–mediated developmental abnormalities, an observation consistent with compelling evidence in human populations that TCDD exposure is responsible for a significant incidence of birth defects. To characterize molecular mechanisms that might explain the developmental effects of dioxin, we have studied the consequences of TCDD exposure on the differentiation of mouse embryonic stem (ES) cells in culture and on the expression of genes, including those coding for homeodomain containing transcription factors, with a role in progression of tissue differentiation and embryonic identity during development. We find that TCDD treatment causes expression changes in a number of homeobox genes concomitant with Ah receptor recruitment to the promoters of many of these genes, whether under naïve or dioxin-activated conditions. TCDD exposure also derails temporal expression trajectories of developmentally regulated genes in a wide diversity of differentiation pathways, including genes with functions in neural and cardiovascular development, self-renewal, hematopoiesis and mesenchymal lineage specification, and Notch and Wnt pathways. Among these, we find that TCDD represses the expression of the cardiac development–specific Nkx2.5 homeobox transcription factor, of cardiac troponin-T and of α- and β-myosin heavy chains, inhibiting the formation of beating cardiomyocytes, a characteristic phenotype of differentiating mouse ES cells in culture. These data identify potential pathways for dioxin to act as a developmental teratogen, possibly critical to cardiovascular development and disease, and provide molecular targets that may help us understand the molecular basis of Ah receptor–mediated developmental toxicity. PMID:20130022

  7. Dioxin exposure disrupts the differentiation of mouse embryonic stem cells into cardiomyocytes.

    PubMed

    Wang, Ying; Fan, Yunxia; Puga, Alvaro

    2010-05-01

    Experimental exposure of fish, birds, and rodents to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) causes multiple Ah receptor-mediated developmental abnormalities, an observation consistent with compelling evidence in human populations that TCDD exposure is responsible for a significant incidence of birth defects. To characterize molecular mechanisms that might explain the developmental effects of dioxin, we have studied the consequences of TCDD exposure on the differentiation of mouse embryonic stem (ES) cells in culture and on the expression of genes, including those coding for homeodomain containing transcription factors, with a role in progression of tissue differentiation and embryonic identity during development. We find that TCDD treatment causes expression changes in a number of homeobox genes concomitant with Ah receptor recruitment to the promoters of many of these genes, whether under naïve or dioxin-activated conditions. TCDD exposure also derails temporal expression trajectories of developmentally regulated genes in a wide diversity of differentiation pathways, including genes with functions in neural and cardiovascular development, self-renewal, hematopoiesis and mesenchymal lineage specification, and Notch and Wnt pathways. Among these, we find that TCDD represses the expression of the cardiac development-specific Nkx2.5 homeobox transcription factor, of cardiac troponin-T and of alpha- and beta-myosin heavy chains, inhibiting the formation of beating cardiomyocytes, a characteristic phenotype of differentiating mouse ES cells in culture. These data identify potential pathways for dioxin to act as a developmental teratogen, possibly critical to cardiovascular development and disease, and provide molecular targets that may help us understand the molecular basis of Ah receptor-mediated developmental toxicity.

  8. Behavioral Sexual Dimorphism in School-Age Children and Early Developmental Exposure to Dioxins and PCBs: A Follow-Up Study of the Duisburg Cohort

    PubMed Central

    Ranft, Ulrich; Wittsiepe, Jürgen; Kasper-Sonnenberg, Monika; Fürst, Peter; Krämer, Ursula; Seitner, Gabriele; Wilhelm, Michael

    2013-01-01

    , Wittsiepe J, Kasper-Sonnenberg M, Fürst P, Krämer U, Seitner G, Wilhelm M. 2014. Behavioral sexual dimorphism in school-age children and early developmental exposure to dioxins and PCBs: a follow-up study of the Duisburg Cohort. Environ Health Perspect 122:292–298; http://dx.doi.org/10.1289/ehp.1306533 PMID:24273228

  9. Standardized bioenergetic profiling of adult mouse cardiomyocytes.

    PubMed

    Readnower, Ryan D; Brainard, Robert E; Hill, Bradford G; Jones, Steven P

    2012-12-18

    Mitochondria are at the crux of life and death and as such have become ideal targets of intervention in cardiovascular disease. Generally, current methods to measure mitochondrial dysfunction rely on working with the isolated organelle and fail to incorporate mitochondrial function in a cellular context. Extracellular flux methodology has been particularly advantageous in this respect; however, certain primary cell types, such as adult cardiac myocytes, have been difficult to standardize with this technology. Here, we describe methods for using extracellular flux (XF) analysis to measure mitochondrial bioenergetics in isolated, intact, adult mouse cardiomyocytes (ACMs). Following isolation, ACMs were seeded overnight onto laminin-coated (20 μg/ml) microplates, which resulted in high attachment efficiency. After establishing seeding density, we found that a commonly used assay medium (containing a supraphysiological concentration of pyruvate at 1 mmol/l) produced a maximal bioenergetic response. After performing a pyruvate dose-response, we determined that pyruvate titrated to 0.1 mmol/l was optimal for examining alternative substrate oxidation. Methods for measuring fatty acid oxidation were established. These methods lay the framework using XF analysis to profile metabolism of ACMs and will likely augment our ability to understand mitochondrial dysfunction in heart failure and acute myocardial ischemia. This platform could easily be extended to models of diabetes or other metabolic defects.

  10. Mesenchymal Stem Cells and Cardiomyocytes Interplay to Prevent Myocardial Hypertrophy

    PubMed Central

    Tan, Xueying; Zhang, Yong; Li, Xingda; Wang, Xinyue; Zhu, Jiuxin; Wang, Yang; Yang, Fan; Wang, Baoqiu; Liu, Yanju; Xu, Chaoqian; Pan, Zhenwei; Wang, Ning; Yang, Baofeng

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) have emerged as a promising therapeutic strategy for cardiovascular disease. However, there is no evidence so far that BMSCs can heal pathological myocardial hypertrophy. In this study, BMSCs were indirectly cocultured with neonatal rat ventricular cardiomyocytes (NRVCs) in vitro or intramyocardially transplanted into hypertrophic hearts in vivo. The results showed that isoproterenol (ISO)-induced typical hypertrophic characteristics of cardiomyocytes were prevented by BMSCs in the coculture model in vitro and after BMSC transplantation in vivo. Furthermore, activation of the Ca2+/calcineurin/nuclear factor of activated T cells cytoplasmic 3 (NFATc3) hypertrophic pathway in NRVCs was abrogated in the presence of BMSCs both in vitro and in vivo. Interestingly, inhibition of vascular endothelial growth factor (VEGF) release from BMSCs, but not basic fibroblast growth factor and insulin-like growth factor 1, abolished the protective effects of BMSCs on cardiomyocyte hypertrophy. Consistently, VEGF administration attenuated ISO-induced enlargement of cellular size; the upregulation of atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain expression; and the activation of Ca2+/calcineurin/NFATc3 hypertrophic pathways, and these pathways can be abrogated by blocking VEGFR-1 in cardiomyocytes, indicating that VEGF receptor 1 is involved in the antihypertrophic role of VEGF. We further found that the ample VEGF secretion contributing to the antihypertrophic effects of BMSCs originates from the crosstalk of BMSCs and cardiac cells but not BMSCs or cardiomyocytes alone. Interplay of mesenchymal stem cells with cardiomyocytes produced synergistic effects on VEGF release. In summary, crosstalk between mesenchymal stem cells and cardiomyocytes contributes to the inhibition of myocardial hypertrophy via inhibiting Ca2+/calcineurin/NFATc3 hypertrophic pathways in cardiac cells. These results provide the

  11. AMPK and substrate availability regulate creatine transport in cultured cardiomyocytes.

    PubMed

    Darrabie, Marcus D; Arciniegas, Antonio Jose Luis; Mishra, Rajashree; Bowles, Dawn E; Jacobs, Danny O; Santacruz, Lucia

    2011-05-01

    Profound alterations in myocellular creatine and phosphocreatine levels are observed during human heart failure. To maintain its intracellular creatine stores, cardiomyocytes depend upon a cell membrane creatine transporter whose regulation is not clearly understood. Creatine transport capacity in the intact heart is modulated by substrate availability, and it is reduced in the failing myocardium, likely adding to the energy imbalance that characterizes heart failure. AMPK, a key regulator of cellular energy homeostasis, acts by switching off energy-consuming pathways in favor of processes that generate energy. Our objective was to determine the effects of substrate availability and AMPK activation on creatine transport in cardiomyocytes. We studied creatine transport in rat neonatal cardiomyocytes and HL-1 cardiac cells expressing the human creatine transporter cultured in the presence of varying creatine concentrations and the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR). Transport was enhanced in cardiomyocytes following incubation in creatine-depleted medium or AICAR. The changes in transport were due to alterations in V(max) that correlated with changes in total and cell surface creatine transporter protein content. Our results suggest a positive role for AMPK in creatine transport modulation for cardiomyocytes in culture.

  12. Glucocorticoid Induced Leucine Zipper inhibits apoptosis of cardiomyocytes by doxorubicin

    SciTech Connect

    Aguilar, David; Strom, Joshua; Chen, Qin M.

    2014-04-01

    Doxorubicin (Dox) is an indispensable chemotherapeutic agent for the treatment of various forms of neoplasia such as lung, breast, ovarian, and bladder cancers. Cardiotoxicity is a major concern for patients receiving Dox therapy. Previous work from our laboratory indicated that glucocorticoids (GCs) alleviate Dox-induced apoptosis in cardiomyocytes. Here we have found Glucocorticoid-Induced Leucine Zipper (GILZ) to be a mediator of GC-induced cytoprotection. GILZ was found to be induced in cardiomyocytes by GC treatment. Knocking down of GILZ using siRNA resulted in cancelation of GC-induced cytoprotection against apoptosis by Dox treatment. Overexpressing GILZ by transfection was able to protect cells from apoptosis induced by Dox as measured by caspase activation, Annexin V binding and morphologic changes. Western blot analyses indicate that GILZ overexpression prevented cytochrome c release from mitochondria and cleavage of caspase-3. When bcl-2 family proteins were examined, we found that GILZ overexpression causes induction of the pro-survival protein Bcl-xL. Since siRNA against Bcl-xL reverses GC induced cytoprotection, Bcl-xL induction represents an important event in GILZ-induced cytoprotection. Our data suggest that GILZ functions as a cytoprotective gene in cardiomyocytes. - Highlights: • Corticosteroids act as a cytoprotective agent in cardiomyocytes • Corticosteroids induce GILZ expression in cardiomyocytes • Elevated GILZ results in resistance against apoptosis induced by doxorubicin • GILZ induces Bcl-xL protein without inducing Bcl-xL mRNA.

  13. Profilin modulates sarcomeric organization and mediates cardiomyocyte hypertrophy

    PubMed Central

    Kooij, Viola; Viswanathan, Meera C.; Lee, Dong I.; Rainer, Peter P.; Schmidt, William; Kronert, William A.; Harding, Sian E.; Kass, David A.; Bernstein, Sanford I.; Van Eyk, Jennifer E.; Cammarato, Anthony

    2016-01-01

    Aims Heart failure is often preceded by cardiac hypertrophy, which is characterized by increased cell size, altered protein abundance, and actin cytoskeletal reorganization. Profilin is a well-conserved, ubiquitously expressed, multifunctional actin-binding protein, and its role in cardiomyocytes is largely unknown. Given its involvement in vascular hypertrophy, we aimed to test the hypothesis that profilin-1 is a key mediator of cardiomyocyte-specific hypertrophic remodelling. Methods and results Profilin-1 was elevated in multiple mouse models of hypertrophy, and a cardiomyocyte-specific increase of profilin in Drosophila resulted in significantly larger heart tube dimensions. Moreover, adenovirus-mediated overexpression of profilin-1 in neonatal rat ventricular myocytes (NRVMs) induced a hypertrophic response, measured by increased myocyte size and gene expression. Profilin-1 silencing suppressed the response in NRVMs stimulated with phenylephrine or endothelin-1. Mechanistically, we found that profilin-1 regulates hypertrophy, in part, through activation of the ERK1/2 signalling cascade. Confocal microscopy showed that profilin localized to the Z-line of Drosophila myofibrils under normal conditions and accumulated near the M-line when overexpressed. Elevated profilin levels resulted in elongated sarcomeres, myofibrillar disorganization, and sarcomeric disarray, which correlated with impaired muscle function. Conclusion Our results identify novel roles for profilin as an important mediator of cardiomyocyte hypertrophy. We show that overexpression of profilin is sufficient to induce cardiomyocyte hypertrophy and sarcomeric remodelling, and silencing of profilin attenuates the hypertrophic response. PMID:26956799

  14. Depressed phosphatidic acid-induced contractile activity of failing cardiomyocytes.

    PubMed

    Tappia, Paramjit S; Maddaford, Thane G; Hurtado, Cecilia; Panagia, Vincenzo; Pierce, Grant N

    2003-01-10

    The effects of phosphatidic acid (PA), a known inotropic agent, on Ca(2+) transients and contractile activity of cardiomyocytes in congestive heart failure (CHF) due to myocardial infarction were examined. In control cells, PA induced a significant increase (25%) in active cell shortening and Ca(2+) transients. The phospholipase C (PLC) inhibitor, 2-nitro-4-carboxyphenyl N,N-diphenylcarbonate, blocked the positive inotropic action induced by PA, indicating that PA induces an increase in contractile activity and Ca(2+) transients through stimulation of PLC. Conversely, in failing cardiomyocytes there was a loss of PA-induced increase in active cell shortening and Ca(2+) transients. PA did not alter resting cell length. Both diastolic and systolic [Ca(2+)] were significantly elevated in the failing cardiomyocytes. In vitro assessment of the cardiac sarcolemmal (SL) PLC activity revealed that the impaired failing cardiomyocyte response to PA was associated with a diminished stimulation of SL PLC activity by PA. Our results identify an important defect in the PA-PLC signaling pathway in failing cardiomyocytes, which may have significant implications for the depressed contractile function during CHF.

  15. Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells

    PubMed Central

    Zhang, Yiqiang; Zhong, Jiang F; Qiu, Hongyu; Robb MacLellan, W.; Marbán, Eduardo; Wang, Charles

    2015-01-01

    It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. PMID:26657817

  16. Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration.

    PubMed

    Zhao, Long; Borikova, Asya L; Ben-Yair, Raz; Guner-Ataman, Burcu; MacRae, Calum A; Lee, Richard T; Burns, C Geoffrey; Burns, Caroline E

    2014-01-28

    The human heart's failure to replace ischemia-damaged myocardium with regenerated muscle contributes significantly to the worldwide morbidity and mortality associated with coronary artery disease. Remarkably, certain vertebrate species, including the zebrafish, achieve complete regeneration of amputated or injured myocardium through the proliferation of spared cardiomyocytes. Nonetheless, the genetic and cellular determinants of natural cardiac regeneration remain incompletely characterized. Here, we report that cardiac regeneration in zebrafish relies on Notch signaling. Following amputation of the zebrafish ventricular apex, Notch receptor expression becomes activated specifically in the endocardium and epicardium, but not the myocardium. Using a dominant negative approach, we discovered that suppression of Notch signaling profoundly impairs cardiac regeneration and induces scar formation at the amputation site. We ruled out defects in endocardial activation, epicardial activation, and dedifferentiation of compact myocardial cells as causative for the regenerative failure. Furthermore, coronary endothelial tubes, which we lineage traced from preexisting endothelium in wild-type hearts, formed in the wound despite the myocardial regenerative failure. Quantification of myocardial proliferation in Notch-suppressed hearts revealed a significant decrease in cycling cardiomyocytes, an observation consistent with a noncell autonomous requirement for Notch signaling in cardiomyocyte proliferation. Unexpectedly, hyperactivation of Notch signaling also suppressed cardiomyocyte proliferation and heart regeneration. Taken together, our data uncover the exquisite sensitivity of regenerative cardiomyocyte proliferation to perturbations in Notch signaling.

  17. Developmental Immunotoxicity

    EPA Science Inventory

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

  18. The intrinsic circadian clock within the cardiomyocyte directly regulates myocardial gene expression, metabolism, and contractile function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology remains unknown. We hypothesized that the circadian clock within the cardiomyocyte plays a role in regulating myo...

  19. The intrinsic circadian clock within the cardiomyocyte directly regulates myocardial gene expression, metabolism, and contractile function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology remains unknown. We hypothesized that circadian clock within the cardiomyocyte plays a role in regulating myocardia...

  20. Autonomous beating rate adaptation in human stem cell-derived cardiomyocytes

    PubMed Central

    Eng, George; Lee, Benjamin W.; Protas, Lev; Gagliardi, Mark; Brown, Kristy; Kass, Robert S.; Keller, Gordon; Robinson, Richard B.; Vunjak-Novakovic, Gordana

    2016-01-01

    The therapeutic success of human stem cell-derived cardiomyocytes critically depends on their ability to respond to and integrate with the surrounding electromechanical environment. Currently, the immaturity of human cardiomyocytes derived from stem cells limits their utility for regenerative medicine and biological research. We hypothesize that biomimetic electrical signals regulate the intrinsic beating properties of cardiomyocytes. Here we show that electrical conditioning of human stem cell-derived cardiomyocytes in three-dimensional culture promotes cardiomyocyte maturation, alters their automaticity and enhances connexin expression. Cardiomyocytes adapt their autonomous beating rate to the frequency at which they were stimulated, an effect mediated by the emergence of a rapidly depolarizing cell population, and the expression of hERG. This rate-adaptive behaviour is long lasting and transferable to the surrounding cardiomyocytes. Thus, electrical conditioning may be used to promote cardiomyocyte maturation and establish their automaticity, with implications for cell-based reduction of arrhythmia during heart regeneration. PMID:26785135