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Sample records for early developmental cardiomyocytes

  1. Evaluation of bupropion hydrochloride developmental cardiotoxic effects in chick cardiomyocyte micromass culture and stem cell derived cardiomyocyte systems.

    PubMed

    Shaikh Qureshi, W M; Latif, Muhammad Liaque; Parker, Terry L; Pratten, Margaret K

    2014-10-01

    The use of antidepressant drug bupropion hydrochloride (BPN) during pregnancy results in increased cardiovascular anomalies. In this study, BPN developmental cardiotoxic effects in in vitro system were evaluated using chick cardiomyocyte micromass (MM) culture system and mouse embryonic stem cell derived cardiomyocyte (ESDC) system. In MM system, the cardiomyocyte contractile activity significantly decreased only at BPN 200 μM, while in ESDC system BPN concentration above 75 μM resulted in decreased contractile activity. The increase in drug concentration also affected the cardiomyocyte viability and total cellular protein content in both systems, but in ESDC system the cell viability failed to attain significant difference. The drug failed to induce reactive oxygen species production in both systems, but has affected the cardiac connexin43 expression especially in MM system. We observed that BPN showed developmental cardiotoxic effects irrespective of the stage of cardiac development in both in vitro systems.

  2. Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes.

    PubMed

    Zebrowski, David C; Vergarajauregui, Silvia; Wu, Chi-Chung; Piatkowski, Tanja; Becker, Robert; Leone, Marina; Hirth, Sofia; Ricciardi, Filomena; Falk, Nathalie; Giessl, Andreas; Just, Steffen; Braun, Thomas; Weidinger, Gilbert; Engel, Felix B

    2015-01-01

    Mammalian cardiomyocytes become post-mitotic shortly after birth. Understanding how this occurs is highly relevant to cardiac regenerative therapy. Yet, how cardiomyocytes achieve and maintain a post-mitotic state is unknown. Here, we show that cardiomyocyte centrosome integrity is lost shortly after birth. This is coupled with relocalization of various centrosome proteins to the nuclear envelope. Consequently, postnatal cardiomyocytes are unable to undergo ciliogenesis and the nuclear envelope adopts the function as cellular microtubule organizing center. Loss of centrosome integrity is associated with, and can promote, cardiomyocyte G0/G1 cell cycle arrest suggesting that centrosome disassembly is developmentally utilized to achieve the post-mitotic state in mammalian cardiomyocytes. Adult cardiomyocytes of zebrafish and newt, which are able to proliferate, maintain centrosome integrity. Collectively, our data provide a novel mechanism underlying the post-mitotic state of mammalian cardiomyocytes as well as a potential explanation for why zebrafish and newts, but not mammals, can regenerate their heart. PMID:26247711

  3. Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes.

    PubMed

    Zebrowski, David C; Vergarajauregui, Silvia; Wu, Chi-Chung; Piatkowski, Tanja; Becker, Robert; Leone, Marina; Hirth, Sofia; Ricciardi, Filomena; Falk, Nathalie; Giessl, Andreas; Just, Steffen; Braun, Thomas; Weidinger, Gilbert; Engel, Felix B

    2015-08-06

    Mammalian cardiomyocytes become post-mitotic shortly after birth. Understanding how this occurs is highly relevant to cardiac regenerative therapy. Yet, how cardiomyocytes achieve and maintain a post-mitotic state is unknown. Here, we show that cardiomyocyte centrosome integrity is lost shortly after birth. This is coupled with relocalization of various centrosome proteins to the nuclear envelope. Consequently, postnatal cardiomyocytes are unable to undergo ciliogenesis and the nuclear envelope adopts the function as cellular microtubule organizing center. Loss of centrosome integrity is associated with, and can promote, cardiomyocyte G0/G1 cell cycle arrest suggesting that centrosome disassembly is developmentally utilized to achieve the post-mitotic state in mammalian cardiomyocytes. Adult cardiomyocytes of zebrafish and newt, which are able to proliferate, maintain centrosome integrity. Collectively, our data provide a novel mechanism underlying the post-mitotic state of mammalian cardiomyocytes as well as a potential explanation for why zebrafish and newts, but not mammals, can regenerate their heart.

  4. Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes

    PubMed Central

    Zebrowski, David C; Vergarajauregui, Silvia; Wu, Chi-Chung; Piatkowski, Tanja; Becker, Robert; Leone, Marina; Hirth, Sofia; Ricciardi, Filomena; Falk, Nathalie; Giessl, Andreas; Just, Steffen; Braun, Thomas; Weidinger, Gilbert; Engel, Felix B

    2015-01-01

    Mammalian cardiomyocytes become post-mitotic shortly after birth. Understanding how this occurs is highly relevant to cardiac regenerative therapy. Yet, how cardiomyocytes achieve and maintain a post-mitotic state is unknown. Here, we show that cardiomyocyte centrosome integrity is lost shortly after birth. This is coupled with relocalization of various centrosome proteins to the nuclear envelope. Consequently, postnatal cardiomyocytes are unable to undergo ciliogenesis and the nuclear envelope adopts the function as cellular microtubule organizing center. Loss of centrosome integrity is associated with, and can promote, cardiomyocyte G0/G1 cell cycle arrest suggesting that centrosome disassembly is developmentally utilized to achieve the post-mitotic state in mammalian cardiomyocytes. Adult cardiomyocytes of zebrafish and newt, which are able to proliferate, maintain centrosome integrity. Collectively, our data provide a novel mechanism underlying the post-mitotic state of mammalian cardiomyocytes as well as a potential explanation for why zebrafish and newts, but not mammals, can regenerate their heart. DOI: http://dx.doi.org/10.7554/eLife.05563.001 PMID:26247711

  5. 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 ...

  6. 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.

  7. Early administration of nifedipine protects against angiotensin II-induced cardiomyocyte hypertrophy through regulating CaMKII-SERCA2a pathway and apoptosis in rat cardiomyocytes.

    PubMed

    Luo, Ji; Zhang, Wei-dong; Du, Yi-meng

    2016-04-01

    The calcium channel blocker (CCB), nifedipine, is a more effective treatment for early- than late-stage cardiac hypertrophy. We investigated the effects of early- and late-stage nifedipine administration on calcium homeostasis, CaMKII (Ca(2+) /calmodulin-dependent protein kinase II) activity and apoptosis of cardiomyocytes under hypertrophic stimulation with angiotensin II (AngII). Primary rat cardiomyocytes were divided into five treatment groups: AK, AngII plus the CaMKII inhibitor, KN-93; AN-1 (early-stage), AngII plus nifedipine × 48 h; AN-2 (late-stage), AngII × 48 h, then AngII plus nifedipine × 48 h; C, untreated; and A, AngII × 48 h. The t1/2β [time required for intracellular Ca(2+) concentration ([Ca(2+) ]i) to decline to one half of the peak value] decreased; however, CaMKII and SERCA2a (sarcoplasmic reticulum Ca(2+) -ATPase 2a) activities increased in the AN-1 group compared with the AK group. In the AN-2 group compared with the AN-1 group, CaMKII activity, t1/2α [time required for [Ca(2+) ]i to increase from the bottom to one half of peak value], t1/2β, and apoptosis increased. These results indicate that the timing of CCB administration affects the calcium concentration and apoptosis of hypertrophic cardiomyocytes through the CaMKII-SERCA2a signalling pathway, thereby influencing the drug's protective activity against cardiomyocyte hypertrophy. PMID:26968727

  8. 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…

  9. 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…

  10. Mitochondrial pyruvate dehydrogenase phosphatase 1 regulates the early differentiation of cardiomyocytes from mouse embryonic stem cells.

    PubMed

    Heo, Hye Jin; Kim, Hyoung Kyu; Youm, Jae Boum; Cho, Sung Woo; Song, In-Sung; Lee, Sun Young; Ko, Tae Hee; Kim, Nari; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin

    2016-01-01

    Mitochondria are crucial for maintaining the properties of embryonic stem cells (ESCs) and for regulating their subsequent differentiation into diverse cell lineages, including cardiomyocytes. However, mitochondrial regulators that manage the rate of differentiation or cell fate have been rarely identified. This study aimed to determine the potential mitochondrial factor that controls the differentiation of ESCs into cardiac myocytes. We induced cardiomyocyte differentiation from mouse ESCs (mESCs) and performed microarray assays to assess messenger RNA (mRNA) expression changes at differentiation day 8 (D8) compared with undifferentiated mESCs (D0). Among the differentially expressed genes, Pdp1 expression was significantly decreased (27-fold) on D8 compared to D0, which was accompanied by suppressed mitochondrial indices, including ATP levels, membrane potential, ROS and mitochondrial Ca(2+). Notably, Pdp1 overexpression significantly enhanced the mitochondrial indices and pyruvate dehydrogenase activity and reduced the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate compared to a mock control. In confirmation of this, a knockdown of the Pdp1 gene promoted the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate. In conclusion, our results suggest that mitochondrial PDP1 is a potential regulator that controls cardiac differentiation at an early differentiation stage in ESCs. PMID:27538372

  11. Mitochondrial pyruvate dehydrogenase phosphatase 1 regulates the early differentiation of cardiomyocytes from mouse embryonic stem cells

    PubMed Central

    Heo, Hye Jin; Kim, Hyoung Kyu; Youm, Jae Boum; Cho, Sung Woo; Song, In-Sung; Lee, Sun Young; Ko, Tae Hee; Kim, Nari; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin

    2016-01-01

    Mitochondria are crucial for maintaining the properties of embryonic stem cells (ESCs) and for regulating their subsequent differentiation into diverse cell lineages, including cardiomyocytes. However, mitochondrial regulators that manage the rate of differentiation or cell fate have been rarely identified. This study aimed to determine the potential mitochondrial factor that controls the differentiation of ESCs into cardiac myocytes. We induced cardiomyocyte differentiation from mouse ESCs (mESCs) and performed microarray assays to assess messenger RNA (mRNA) expression changes at differentiation day 8 (D8) compared with undifferentiated mESCs (D0). Among the differentially expressed genes, Pdp1 expression was significantly decreased (27-fold) on D8 compared to D0, which was accompanied by suppressed mitochondrial indices, including ATP levels, membrane potential, ROS and mitochondrial Ca2+. Notably, Pdp1 overexpression significantly enhanced the mitochondrial indices and pyruvate dehydrogenase activity and reduced the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate compared to a mock control. In confirmation of this, a knockdown of the Pdp1 gene promoted the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate. In conclusion, our results suggest that mitochondrial PDP1 is a potential regulator that controls cardiac differentiation at an early differentiation stage in ESCs. PMID:27538372

  12. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

    PubMed Central

    Maurer, Maria; Ebner, Thomas; Puchner, Manuela; Mayer, Richard Bernhard; Shebl, Omar; Oppelt, Peter; Duba, Hans-Christoph

    2015-01-01

    Background Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF) technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH) with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting. PMID:26644858

  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. Relationship between Intrauterine Bacterial Infection and Early Embryonic Developmental Arrest

    PubMed Central

    Yan, Shao-Fei; Liu, Xin-Yan; Cheng, Yun-Fei; Li, Zhi-Yi; Ou, Jie; Wang, Wei; Li, Feng-Qin

    2016-01-01

    Background: Early embryonic developmental arrest is the most commonly understudied adverse outcome of pregnancy. The relevance of intrauterine infection to spontaneous embryonic death is rarely studied and remains unclear. This study aimed to investigate the relationship between intrauterine bacterial infection and early embryonic developmental arrest. Methods: Embryonic chorion tissue and uterine swabs for bacterial detection were obtained from 33 patients who underwent artificial abortion (control group) and from 45 patients who displayed early embryonic developmental arrest (trial group). Results: Intrauterine bacterial infection was discovered in both groups. The infection rate was 24.44% (11/45) in the early embryonic developmental arrest group and 9.09% (3/33) in the artificial abortion group. Classification analysis revealed that the highest detection rate for Micrococcus luteus in the early embryonic developmental arrest group was 13.33% (6/45), and none was detected in the artificial abortion group. M. luteus infection was significantly different between the groups (P < 0.05 as shown by Fisher's exact test). In addition, no correlation was found between intrauterine bacterial infection and history of early embryonic developmental arrest. Conclusions: M. luteus infection is related to early embryonic developmental arrest and might be one of its causative factors. PMID:27270541

  15. 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…

  16. 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…

  17. 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…

  18. Developmental origins of early antisocial behavior

    PubMed Central

    CALKINS, SUSAN D.; KEANE, SUSAN P.

    2009-01-01

    Early antisocial behavior has its origins in childhood behavior problems, particularly those characterized by aggressive and destructive behavior. Deficits in self-regulation across multiple domains of functioning, from the physiological to the cognitive, are associated with early behavior problems, and may place children at greater risk for the development of later antisocial behavior. Data are presented from a longitudinal study of early self-regulation and behavior problems, the RIGHT Track Research Project, demonstrating that children at greatest risk for early and persistent problem behavior display patterns of physiological and emotional regulation deficits early in life. Parenting behavior and functioning have also been examined as predictors of trajectories of early problem behavior, and some data support the interaction of parenting and self-regulation as significant predictors of patterns of problematic behavior and ongoing problems with the regulation of affect. Peer relationships also affect and are affected by early self-regulation skills, and both may play a role in academic performance and subsequent school success. These data provide evidence that the social contexts of early family and peer relationships are important moderators of the more proximal mechanism of self-regulation, and both types of processes, social and biobehavioral, are likely implicated in early antisocial tendencies. Implications of these findings on self-regulation and early behavior problems are discussed in terms of future research and treatment approaches. PMID:19825259

  19. Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages.

    PubMed

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Kodama, Itsuo

    2010-12-01

    Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal rat hearts and superior cervical ganglia, and were co-cultured, either in a random or localized way. Neurite growth from SNs toward CMs was assessed by immunohistochemistry for neurofilament M and α-actinin in response to neurotrophic factors-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and a chemical repellent, semaphorin 3A. As a result, GDNF as well as NGF and BDNF stimulated neurite growth. GDNF enhanced neurite outgrowth even under the NGF-depleted culture condition, excluding an indirect effect of GDNF via NGF. Quantification of mRNA and protein by real-time PCR and immunohistochemistry at different developmental stages revealed that GDNF is abundantly expressed in the hearts of embryos and neonates, but not in adult hearts. GDNF plays an important role in inducing cardiac sympathetic innervation at the early developmental stages. A possible role in (re)innervation of injured or transplanted or cultured and transplanted myocardium may deserve investigation.

  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. Early developmental delays: neuropsychological sequelae and subsequent diagnoses.

    PubMed

    Perna, Robert; Loughan, Ashlee

    2012-01-01

    Developmental delay is a frequent diagnosis given to young children when developmental milestones are not met in an age-expected time frame. Research on early delays in speech and motor milestones is unclear regarding possible long-term cognitive functioning. The purpose of this study was to investigate the neuropsychological profile of children who suffered early developmental delays in speech or motor function. Participants (N = 60) completed the Wechsler Intelligence Scale for Children-Fourth Edition, Wechsler Individual Achievement Test-Second Edition, Wisconsin Card-Sorting Test, Children's Memory Test (CMT), the Delis-Kaplan Executive Function System, and the Child Behavior Checklist/Youth Self-Report. The Delay group had a significantly lower Full-Scale IQ (FSIQ), and when controlling for IQ (analysis of covariance), the Delay group had significantly lower scores on measures of immediate and delayed visual memory skills (CMT). Group scores were not significantly different for any other tests. Neither group had any test scores significantly below FSIQ, a finding suggesting developmental delays may subsequently lead to weaknesses but not impairments. Results appear to support the resiliency of the young brain. Chi-square analysis showed the Delay group was more likely to subsequently be diagnosed with attention-deficit hyperactivity disorder (ADHD) but not learning disorders. Data appear to suggest that early developmental delays may place children as risk for ADHD and perhaps visual memory weaknesses, though not clear impairments. PMID:23428279

  2. The Developmental Systems Approach to Early Intervention in Canada

    ERIC Educational Resources Information Center

    Underwood, Kathryn; Frankel, Elaine B.

    2012-01-01

    This article examines current policies and early intervention services for children with disabilities and their families in Canada within the principles of the Developmental Systems Approach (M. J. Guralnick, 2005, 2011). The article considers the sociopolitical context of Canada, especially with respect to diversity and equity. Applying the…

  3. Conceptualizing Developmentally Responsive Teaching in Early Field Experiences

    ERIC Educational Resources Information Center

    Howell, Penny B.

    2012-01-01

    The purpose of this descriptive qualitative study was to examine case study as a pedagogical tool used to scaffold the conceptualization of developmentally responsive pedagogy for middle level preservice teachers in early field experiences. Child study projects (CSP) completed by middle level preservice candidates were analyzed to determine if…

  4. 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.

  5. 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…

  6. Sleep problems and early developmental delay: implications for early intervention programs.

    PubMed

    Bonuck, Karen; Grant, Roy

    2012-02-01

    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 types are difficulties initiating or maintaining sleep and sleep disordered breathing. To date, attention has been focused on sleep problems in children with specific conditions (e.g., autism, genetic syndromes, prematurity, and seizure disorder). The authors review evidence of sleep problems' broader impact across the range of children screened for early intervention. Eligibility evaluations for early intervention address the five developmental domains: adaptive, motor, cognitive, communication, and socioemotional. Disordered sleep may be symptomatic of socioemotional and adaptive problems. Assessing sleep problems within the evaluation may help establish eligibility for early intervention services and would maximize developmental potential by ensuring timely identification, referral, and treatment.

  7. Early Zebrafish Embryogenesis Is Susceptible to Developmental TDCPP Exposure

    PubMed Central

    McGee, Sean P.; Cooper, Ellen M.; Stapleton, Heather M.

    2012-01-01

    Background: Chlorinated phosphate esters (CPEs) are widely used as additive flame retardants for low-density polyurethane foams and have frequently been detected at elevated concentrations within indoor environmental media. Objectives: To begin characterizing the potential toxicity of CPEs on early vertebrate development, we examined the developmental toxicity of four CPEs used in polyurethane foam: tris(1,3-dichloro-2-propyl) phosphate (TDCPP), tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCPP), and 2,2-bis(chloromethyl)propane-1,3-diyl tetrakis(2-chlorethyl) bis(phosphate) (V6). Methods: Using zebrafish as a model for vertebrate embryogenesis, we first screened the potential teratogenic effects of TDCPP, TCEP, TCPP, and V6 using a developmental toxicity assay. Based on these results, we focused on identification of susceptible windows of developmental TDCPP exposure as well as evaluation of uptake and elimination of TDCPP and bis(1,3-dichloro-2-propyl)phosphate (BDCPP, the primary metabolite) within whole embryos. Finally, because TDCPP-specific genotoxicity assays have, for the most part, been negative in vivo and because zygotic genome remethylation is a key biological event during cleavage, we investigated whether TDCPP altered the status of zygotic genome methylation during early zebrafish embryogenesis. Results: Overall, our findings suggest that the cleavage period during zebrafish embryogenesis is susceptible to TDCPP-induced delays in remethylation of the zygotic genome, a mechanism that may be associated with enhanced developmental toxicity following initiation of TDCPP exposure at the start of cleavage. Conclusions: Our results suggest that further research is needed to better understand the effects of a widely used and detected CPE within susceptible windows of early vertebrate development. PMID:23017583

  8. Probing the role of septins in cardiomyocytes.

    PubMed

    Ahuja, Preeti; Perriard, Evelyne; Trimble, William; Perriard, Jean-Claude; Ehler, Elisabeth

    2006-05-15

    Heart growth in the embryo is achieved by division of differentiated cardiomyocytes. Around birth, cardiomyocytes stop dividing and heart growth occurs only by volume increase of the individual cells. Cardiomyocytes seem to lose their capacity for cytokinesis at this developmental stage. Septins are GTP-binding proteins that have been shown to be involved in cytokinesis from yeast to vertebrates. We wanted to determine whether septin expression patterns can be correlated to the cessation of cytokinesis during heart development. We found significant levels of expression only for SEPT2, SEPT6, SEPT7 and SEPT9 in heart, in a developmentally regulated fashion, with high levels in the embryonic heart, downregulation around birth and no detectable expression in the adult. In dividing embryonic cardiomyocytes, all septins localize to the cleavage furrow. We used drugs to probe for the functional interactions of SEPT2 in dividing embryonic cardiomyocytes. Differences in the effects on subcellular septin localization in cardiomyocytes were observed, depending whether a Rho kinase (ROCK) inhibitor was used or whether actin and myosin were targeted directly. Our data show a tight correlation of high levels of septin expression and the ability to undergo cytokinesis in cardiomyocytes. In addition, we were able to dissect the different contributions of ROCK signaling and the actomyosin cytoskeleton to septin localization to the contractile ring using cardiomyocytes as an experimental system.

  9. 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

  10. 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

  11. Developmental Trajectories of Anxiety and Depression in Early Adolescence

    PubMed Central

    McLaughlin, Katie A.; King, Kevin

    2014-01-01

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

  12. A unique chromatin signature uncovers early developmental enhancers in humans.

    PubMed

    Rada-Iglesias, Alvaro; Bajpai, Ruchi; Swigut, Tomek; Brugmann, Samantha A; Flynn, Ryan A; Wysocka, Joanna

    2011-02-10

    Cell-fate transitions involve the integration of genomic information encoded by regulatory elements, such as enhancers, with the cellular environment. However, identification of genomic sequences that control human embryonic development represents a formidable challenge. Here we show that in human embryonic stem cells (hESCs), unique chromatin signatures identify two distinct classes of genomic elements, both of which are marked by the presence of chromatin regulators p300 and BRG1, monomethylation of histone H3 at lysine 4 (H3K4me1), and low nucleosomal density. In addition, elements of the first class are distinguished by the acetylation of histone H3 at lysine 27 (H3K27ac), overlap with previously characterized hESC enhancers, and are located proximally to genes expressed in hESCs and the epiblast. In contrast, elements of the second class, which we term 'poised enhancers', are distinguished by the absence of H3K27ac, enrichment of histone H3 lysine 27 trimethylation (H3K27me3), and are linked to genes inactive in hESCs and instead are involved in orchestrating early steps in embryogenesis, such as gastrulation, mesoderm formation and neurulation. Consistent with the poised identity, during differentiation of hESCs to neuroepithelium, a neuroectoderm-specific subset of poised enhancers acquires a chromatin signature associated with active enhancers. When assayed in zebrafish embryos, poised enhancers are able to direct cell-type and stage-specific expression characteristic of their proximal developmental gene, even in the absence of sequence conservation in the fish genome. Our data demonstrate that early developmental enhancers are epigenetically pre-marked in hESCs and indicate an unappreciated role of H3K27me3 at distal regulatory elements. Moreover, the wealth of new regulatory sequences identified here provides an invaluable resource for studies and isolation of transient, rare cell populations representing early stages of human embryogenesis.

  13. 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

  14. 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.

  15. The fungicide imazalil induces developmental abnormalities and alters locomotor activity during early developmental stages in zebrafish.

    PubMed

    Jin, Yuanxiang; Zhu, Zhihong; Wang, Yueyi; Yang, Enlu; Feng, Xiayan; Fu, Zhengwei

    2016-06-01

    The fungicide imazalil (IMZ) is used extensively to protect vegetable fields, fruit plantations and post-harvest crops from rot. Likely due to its wide-spread use, IMZ is frequently detected in vegetable, fruit, soil and even surface water samples. Even though several previous studies have reported on the neurotoxicity of IMZ, its effects on the neurobehavior of zebrafish have received little attention to date. In this study, we show that the heartbeat and hatchability of zebrafish were significantly influenced by IMZ concentrations of 300 μg L(-1) or higher. Moreover, in zebrafish larvae, locomotor behaviors such as average swimming speed and swimming distance were significantly decreased after exposure to 300 μg L(-1) IMZ for 96 h, and acetylcholinesterase (AChE) expression and activity were consistently inhibited in IMZ-treated fish. Our results further suggest that IMZ could act as a neuroendocrine disruptor by decreasing the expression of neurotoxicity-related genes such as Glial fibrillary acidic protein (Gfap), Myelin basic protein (Mbp) and Sonic hedgehog a (Shha) during early developmental stages of zebrafish. In conclusion, we show that exposure to IMZ has the potential to induce developmental toxicity and locomotor behavior abnormalities during zebrafish development. PMID:27035382

  16. [Developmental origins of cardiovascular disease and early intervention windows].

    PubMed

    Mi, Jie

    2016-01-01

    Cardiovascular diseases are the major threat to human health and underlie almost half of all deaths in China. Even more serious, obesity and cardiometabolic risk factors have emerged to be prevalent in children and adolescents of some affluent regions. As scientific knowledge emerges on the role of nutritional factors and exposures to environmental risk factors in the developmental origins of health and disease, evidence suggests that it is imperative to create and implement early effective prevention strategies, including optimisation of nutrition at first 1 000 days in life course and reduction of risk factors of obesity exposures during whole childhood, to suppress the rising trend of cardiovascular disease, otherwise, the future costs of diagnosis and treatment are likely to be unaffordable.

  17. From early markers to neuro-developmental mechanisms of autism

    PubMed Central

    Gliga, T.; Jones, E.J.H.; Bedford, R.; Charman, T.; Johnson, M.H.

    2014-01-01

    A fast growing field, the study of infants at risk because of having an older sibling with autism (i.e. infant sibs) aims to identify the earliest signs of this disorder, which would allow for earlier diagnosis and intervention. More importantly, we argue, these studies offer the opportunity to validate existing neuro-developmental models of autism against experimental evidence. Although autism is mainly seen as a disorder of social interaction and communication, emerging early markers do not exclusively reflect impairments of the “social brain”. Evidence for atypical development of sensory and attentional systems highlight the need to move away from localized deficits to models suggesting brain-wide involvement in autism pathology. We discuss the implications infant sibs findings have for future work into the biology of autism and the development of interventions. PMID:25187673

  18. 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. PMID:25425187

  19. 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

  20. A patient with medulloblastoma in its early developmental stage.

    PubMed

    Shinojima, Naoki; Nakamura, Hideo; Tasaki, Masayoshi; Kameno, Kouki; Anai, Shigeo; Iyama, Ken-ichi; Ando, Yukio; Seto, Hiroshi; Kuratsu, Jun-Ichi

    2014-12-01

    Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups- WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)-since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap-that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.

  1. 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.

  2. 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…

  3. 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…

  4. 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. PMID:25101027

  5. 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.

  6. 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

  7. Early Childhood Intervention and Early Childhood Special Education in Turkey within the Scope of the Developmental System Approach

    ERIC Educational Resources Information Center

    Diken, Ibrahim H.; Bayhan, Pinar; Turan, Figen; Sipal, R. Firat; Sucuoglu, Bulbin; Ceber-Bakkaloglu, Hatice; Gunel, Mintaze Kerem; Kara, Ozgun Kaya

    2012-01-01

    The purpose of this article was to provide an overview of early childhood intervention and early childhood special education (ECI/ECSE) services and practices in Turkey by using the Developmental System Approach (M. J. Guralnick, 2001). After pointing out the history of early childhood and ECI/ECSE services and current legislations with regard to…

  8. 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…

  9. 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

  10. 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.…

  11. Beliefs about the Importance of Use of Developmentally Appropriate Practices among Early Childhood Teachers in India

    ERIC Educational Resources Information Center

    Jambunathan, Sai

    2005-01-01

    This article explores beliefs of Asian Indian teachers regarding the importance of use of developmentally appropriate practices in early childhood classrooms. A total of 178 Asian Indian early childhood teachers working in various early childhood classrooms in the southern part of India participated in the study. The teachers filled out a…

  12. Matrix Metalloproteinases in Primary Culture of Cardiomyocytes.

    PubMed

    Bildyug, N B; Voronkina, I V; Smagina, L V; Yudintseva, N M; Pinaev, G P

    2015-10-01

    The highly organized contractile apparatus of cardiomyocytes in heart tissue allows for their continuous contractility, whereas extracellular matrix components are synthesized and spatially organized by fibroblasts and endothelial cells. However, reorganization of the cardiomyocyte contractile apparatus occurs upon their 2D cultivation, which is accompanied by transient loss of their contractility and acquired capability of extracellular matrix synthesis (Bildyug, N. B., and Pinaev, G. P. (2013) Tsitologiya, 55, 713-724). In this study, matrix metalloproteinases were investigated at different times of cardiomyocyte 2D cultivation and 3D cultivation in collagen gels. It was found that cardiomyocytes in 2D culture synthesize matrix metalloproteinases MMP-2 and MMP-9, wherein their amount varies with the cultivation time. The peak MMP-9 amount is at early cultivation time, when the reorganization of cardiomyocyte contractile apparatus occurs, and the MMP-2 peak precedes the recovery of the initial organization of their contractile apparatus. Upon cardiomyocyte cultivation in 3D collagen gels, in which case their contractile apparatus does not rearrange, a steady small amount of MMP-2 and MMP-9 is observed. These data indicate that the cardiomyocyte contractile apparatus reorganization in culture is associated with synthesis and spatial organization of their own extracellular matrix.

  13. 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

  14. 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…

  15. 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…

  16. 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…

  17. The Foundations of a Developmental Early Childhood Program for Children, Ages 2 1/2-6.

    ERIC Educational Resources Information Center

    Child Day Care Association of St. Louis, MO.

    Compiled are three related sets of materials: (1) a discussion of the foundations of a developmental early childhood program for children between 2 1/2 and 6 years of age; (2) guidelines for planning activity areas and providing equipment for children in the early childhood program; and (3) an inventory with approximate prices of equipment and…

  18. 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…

  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…

  20. Developmentally Appropriate Practice in Early Childhood Programs Serving Children from Birth through Age 8. Third Edition

    ERIC Educational Resources Information Center

    Copple, Carol, Ed.; Bredekamp, Sue, Ed.

    2009-01-01

    Since the first edition in 1987, National Association for the Education of Young Children's book "Developmentally Appropriate Practice in Early Childhood Programs" has been an essential resource for the early child care field. Now fully revised and expanded, the 2009 version comes with a supplementary CD containing readings on key topics, plus…

  1. 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.

  2. 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…

  3. Assessment of developmental cardiotoxic effects of some commonly used phytochemicals in mouse embryonic D3 stem cell differentiation and chick embryonic cardiomyocyte micromass culture models.

    PubMed

    Mohammed, Omar J; McAlpine, Roseanna; Chiewhatpong, Phasawee; Latif, Muhammad Liaque; Pratten, Margaret K

    2016-09-01

    Pregnant women often use herbal medicines to alleviate symptoms of pregnancy. The active phytochemicals eugenol (from holy basil) and α-bisabolol (from chamomile) are recommended to promote calmness and reduce stress. There is evidence that both eugenol and α-bisabolol possess pro-apoptotic and anti-proliferative effects and induce reactive oxygen species. The potential effect was examined by monitoring cardiomyocyte contractile activity (differentiation), cell activity, protein content and ROS production for mouse D3 embryonic stem cell and ‎chick embryonic micromass culture. The results showed that eugenol (0.01-80μM) demonstrated effects on cell activity (both systems) and ROS production (stem cell system only), as well as decreasing the contractile activity and protein content at high concentrations in both systems. Additionally, α-bisabolol (0.01-80μM) at high concentrations decreased the contractile activity and cell activity and in the stem cell system induced ROS production and decreased protein content. The results suggest only low concentrations should be ingested in pregnancy.‎. PMID:27105832

  4. Direct Cardiomyocyte Reprogramming: A New Direction for Cardiovascular Regenerative Medicine

    PubMed Central

    Yi, B. Alexander; Mummery, Christine L.; Chien, Kenneth R.

    2013-01-01

    The past few years have seen unexpected new developments in direct cardiomyocyte reprogramming. Direct cardiomyocyte reprogramming potentially offers an entirely novel approach to cardiovascular regenerative medicine by converting cardiac fibroblasts into functional cardiomyocytes in situ. There is much to be learned, however, about the mechanisms of direct reprogramming in order that the process can be made more efficient. Early efforts have suggested that this new technology can be technically challenging. Moreover, new methods of inducing heart reprogramming will need to be developed before this approach can be translated to the bedside. Despite this, direct cardiomyocyte reprogramming may lead to new therapeutic options for sufferers of heart disease. PMID:24003244

  5. Expression and reconstitution of the bioluminescent Ca(2+) reporter aequorin in human embryonic stem cells, and exploration of the presence of functional IP3 and ryanodine receptors during the early stages of their differentiation into cardiomyocytes.

    PubMed

    Chan, Harvey Y S; Cheung, Man Chun; Gao, Yi; Miller, Andrew L; Webb, Sarah E

    2016-08-01

    In order to develop a novel method of visualizing possible Ca(2+) signaling during the early differentiation of hESCs into cardiomyocytes and avoid some of the inherent problems associated with using fluorescent reporters, we expressed the bioluminescent Ca(2+) reporter, apo-aequorin, in HES2 cells and then reconstituted active holo-aequorin by incubation with f-coelenterazine. The temporal nature of the Ca(2+) signals generated by the holo-f-aequorin-expressing HES2 cells during the earliest stages of differentiation into cardiomyocytes was then investigated. Our data show that no endogenous Ca(2+) transients (generated by release from intracellular stores) were detected in 1-12-day-old cardiospheres but transients were generated in cardiospheres following stimulation with KCl or CaCl2, indicating that holo-f-aequorin was functional in these cells. Furthermore, following the addition of exogenous ATP, an inositol trisphosphate receptor (IP3R) agonist, small Ca(2+) transients were generated from day 1 onward. That ATP was inducing Ca(2+) release from functional IP3Rs was demonstrated by treatment with 2-APB, a known IP3R antagonist. In contrast, following treatment with caffeine, a ryanodine receptor (RyR) agonist, a minimal Ca(2+) response was observed at day 8 of differentiation only. Thus, our data indicate that unlike RyRs, IP3Rs are present and continually functional at these early stages of cardiomyocyte differentiation. PMID:27430888

  6. Predictors of Developmental Outcomes of High-Risk and Developmentally Delayed Infants and Children Enrolled in a State Early Childhood Intervention Program

    ERIC Educational Resources Information Center

    Giannoni, Peggy P.; Kass, Philip H.

    2012-01-01

    A retrospective cohort study was conducted to identify child, maternal, family, and community factors associated with rate of developmental disability among children enrolled in the California Early Start Program. The cohort included 8,987 children considered at high risk for developmental disability due to medical risks and/or developmental…

  7. 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…

  8. 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)

  9. 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.

  10. 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:…

  11. Epigenomic Disruption: The Effects of Early Developmental Exposures

    PubMed Central

    Bernal, Autumn J.; Jirtle, Randy L.

    2010-01-01

    Through DNA methylation, histone modifications, and small regulatory RNAs the epigenome systematically controls gene expression during development-- both in utero and throughout life. The epigenome is also a very reactionary system; its labile nature allows it to sense and respond to environmental perturbations to ensure survival during fetal growth. This pliability can lead to aberrant epigenetic modifications that persist into later life and induce numerous disease states. Endocrine disrupting compounds (EDCs) are ubiquitous chemicals that interfere with growth and development. Several EDCs also interfere with epigenetic programming. The investigation of the epigenotoxic effects of bisphenol A (BPA), an EDC used in the production of plastics and resins, has further raised concern for the impact of EDCs on the epigenome. Using the Agouti viable yellow (Avy) mouse model, dietary BPA exposure was shown to hypomethylate both the Avy and the CabpIAP metastable epialleles. This hypomethylating effect was counteracted with dietary supplementation of methyl donors or genistein. These results are consistent with reports of BPA and other EDCs causing epigenetic effects. Epigenotoxicity could lead to numerous developmental, metabolic, and behavioral disorders in exposed populations. The heritable nature of epigenetic changes also increases the risk for transgenerational inheritance of phenotypes. Thus, epigenotoxicity must be considered when assessing these compounds for safety. PMID:20568270

  12. p90 ribosomal S6 kinases play a significant role in early gene regulation in the cardiomyocyte response to G(q)-protein-coupled receptor stimuli, endothelin-1 and α(1)-adrenergic receptor agonists.

    PubMed

    Amirak, Emre; Fuller, Stephen J; Sugden, Peter H; Clerk, Angela

    2013-03-01

    ERK1/2 (extracellular-signal-regulated kinase 1/2) and their substrates RSKs (p90 ribosomal S6 kinases) phosphorylate different transcription factors, contributing differentially to transcriptomic profiles. In cardiomyocytes ERK1/2 are required for >70% of the transcriptomic response to endothelin-1. In the present study we investigated the role of RSKs in the transcriptomic responses to the G(q)-protein-coupled receptor agonists endothelin-1, phenylephrine (a generic α(1)-adrenergic receptor agonist) and A61603 (α(1A)-adrenergic receptor selective). Phospho-ERK1/2 and phospho-RSKs appeared in cardiomyocyte nuclei within 2-3 min of stimulation (endothelin-1>A61603≈phenylephrine). All agonists increased nuclear RSK2, but only endothelin-1 increased the nuclear RSK1 content. PD184352 (inhibits ERK1/2 activation) and BI-D1870 (inhibits RSKs) were used to dissect the contribution of RSKs to the endothelin-1-responsive transcriptome. Of the 213 RNAs up-regulated after 1 h, 51% required RSKs for their up-regulation, whereas 29% required ERK1/2 but not RSKs. The transcriptomic response to phenylephrine overlapped with, but was not identical with, endothelin-1. As with endothelin-1, PD184352 inhibited the up-regulation of most phenylephrine-responsive transcripts, but the greater variation in the effects of BI-D1870 suggests that differential RSK signalling influences global gene expression. A61603 induced similar changes in RNA expression in cardiomyocytes as phenylephrine, indicating that the signal was mediated largely through α(1A)-adrenergic receptors. A61603 also increased expression of immediate early genes in perfused adult rat hearts and, as in cardiomyocytes, up-regulation of the majority of genes was inhibited by PD184352. PD184352 or BI-D1870 prevented the increased surface area induced by endothelin-1 in cardiomyocytes. Thus RSKs play a significant role in regulating cardiomyocyte gene expression and hypertrophy in response to G

  13. 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.

  14. 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…

  15. 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…

  16. Early Language Patterns of Toddlers on the Autism Spectrum Compared to Toddlers with Developmental Delay

    ERIC Educational Resources Information Center

    Ellis Weismer, Susan; Lord, Catherine; Esler, Amy

    2010-01-01

    This study characterized early language abilities in toddlers with autism spectrum disorders (n = 257) using multiple measures of language development, compared to toddlers with non-spectrum developmental delay (DD, n = 69). Findings indicated moderate to high degrees of agreement among three assessment measures (one parent report and two direct…

  17. Report to the Legislature on the Early Childhood Health and Developmental Screening Program, 1985-86.

    ERIC Educational Resources Information Center

    Minnesota State Dept. of Education, St. Paul. Div. of Development and Partnership.

    Addressed to the Minnesota State Legislature, this report on Minnesota's Early Childhood Health and Developmental Screening Program discusses issues related to program goals and program implementation, overviews the program, and reports and summarizes statewide program results for 1985-86. Issues discussed concern responsibility for the program,…

  18. 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 Behavior…

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. 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.…

  4. Vicissitudes of Children's Mathematical Knowledge: Implications of Developmental Research for Early Childhood Mathematics Education

    ERIC Educational Resources Information Center

    Sophian, Catherine

    2013-01-01

    Hachey's (2013) article celebrates a revolution that is taking place in early childhood mathematics education, fueled in part by developmental research demonstrating the mathematical capabilities of young children. At the same time, Hachey notes that the mathematics revolution she describes is not yet complete. In this commentary, the author…

  5. 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…

  6. 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,…

  7. Developmentally Appropriate Technology in Early Childhood (DATEC) in Botswana: In-Service Teachers' Perspectives

    ERIC Educational Resources Information Center

    Bose, Kabita

    2009-01-01

    Developmentally Appropriate Technology in Early Childhood (DATEC) aims to identify the most appropriate applications of Information and Communication Technology to support the development of children under eight years of age. Botswana has a unique spread of population density and deep-rooted socio-cultural values. There is a need to address the…

  8. Correlations between Developmental Kindergarten Screenings and Early Reading Indicators One Year Later

    ERIC Educational Resources Information Center

    Coughlan-Mainard, Kelly A.

    2012-01-01

    School districts in the U.S. are mandated to identify young children with disabilities. Developmental screeners are typically used to screen for such skill deficits. Academic tests are used in older students. A significant challenge is identifying children with potential learning disabilities early in their school career. This study identifies a…

  9. Caregiver Descriptions of the Developmental Skills of Infants and Toddlers Entering Early Intervention Services

    ERIC Educational Resources Information Center

    Scarborough, Anita A.; Hebbeler, Kathleen M.; Simeonsson, Rune J.; Spiker, Donna

    2007-01-01

    The present study was conducted to describe the developmental skills of a national sample of infants and toddlers at entry into early intervention services. Caregivers were asked about their child's skills during a telephone interview. Summary values were derived from descriptions of motor, communication, independence, and cognitive skills. More…

  10. 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)

  11. 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…

  12. 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…

  13. 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…

  14. The Experience of Parents as Their Children with Developmental Disabilities Transition from Early Intervention to Kindergarten

    ERIC Educational Resources Information Center

    Villeneuve, Michelle; Chatenoud, Celine; Hutchinson, Nancy L.; Minnes, Patricia; Perry, Adrienne; Dionne, Carmen; Frankel, Elaine B.; Isaacs, Barry; Loh, Alvin; Versnel, Joan; Weiss, Jonathan

    2013-01-01

    Despite recognition of the importance of parent involvement to enable meaningful inclusion of young children with developmental disabilities in education contexts, few Canadian studies have reported how parents experience this collaboration. Recent research suggests that the transition process is critical to the early school experiences of…

  15. Systematic characterization of small RNAome during zebrafish early developmental stages

    PubMed Central

    2014-01-01

    Background During early vertebrate development, various small non-coding RNAs (sRNAs) such as MicroRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) are dynamically expressed for orchestrating the maternal-to-zygotic transition (MZT). Systematic analysis of expression profiles of zebrafish small RNAome will be greatly helpful for understanding the sRNA regulation during embryonic development. Results We first determined the expression profiles of sRNAs during eight distinct stages of early zebrafish development by sRNA-seq technology. Integrative analyses with a new computational platform of CSZ (characterization of small RNAome for zebrafish) demonstrated an sRNA class transition from piRNAs to miRNAs as development proceeds. We observed that both the abundance and diversity of miRNAs are gradually increased, while the abundance is enhanced more dramatically than the diversity during development. However, although both the abundance and diversity of piRNAs are gradually decreased, the diversity was firstly increased then rapidly decreased. To evaluate the computational accuracy, the expression levels of four known miRNAs were experimentally validated. We also predicted 25 potentially novel miRNAs, whereas two candidates were verified by Northern blots. Conclusions Taken together, our analyses revealed the piRNA to miRNA transition as a conserved mechanism in zebrafish, although two different types of sRNAs exhibit distinct expression dynamics in abundance and diversity, respectively. Our study not only generated a better understanding for sRNA regulations in early zebrafish development, but also provided a useful platform for analyzing sRNA-seq data. The CSZ was implemented in Perl and freely downloadable at: http://csz.biocuckoo.org. PMID:24507755

  16. Word length effect in early reading and in developmental dyslexia.

    PubMed

    Zoccolotti, Pierluigi; De Luca, Maria; Di Pace, Enrico; Gasperini, Filippo; Judica, Anna; Spinelli, Donatella

    2005-06-01

    Vocal reaction times were measured in Italian dyslexics and in proficient readers while they read single words. Three groups of control participants (for a total of 79) were tested. All were in the first, second or third grade of elementary school. Nine third graders with a low level of reading ability when assessed by standard reading procedures were also tested. Results indicated that vocal RTs of control participants were faster and less sensitive to word length as a function of age; also, there was a particularly marked change between first and second graders. Dyslexics' vocal RTs and errors were much worse than those of peer control participants and resembled those of first grade controls. It is suggested that normal readers in an orthographically transparent language (Italian) adopt a lexical strategy quite early in their learning. On the contrary, dyslexics seem unable to learn this mode of processing and continue to use a sub-lexical reading procedure. PMID:15862860

  17. 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

  18. 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.

  19. Help or hindrance? Staff perspectives on developmental assessment in multicultural early childhood settings.

    PubMed

    Schuman, Andrea

    2002-08-01

    Staff members' views on developmental assessment in a multicultural early childhood setting are described and analysis of these views used to initiate a critique of current practice in assessment and evaluation of young children. Staff members expressed opinions and beliefs along a range from endorsement to frank rejection of the utility, validity, and ethics of developmental assessment. Those who reject the practice expressed a "theory" of growth and change that is incompatible with current developmentalist orthodoxy. Opinions of "dissenters" (who stated that they do not believe assessment gives meaningful information about children) suggest alternative practice with greater authenticity for families and children who are not from European American mainstream backgrounds. PMID:12123395

  20. Effects of early-developmental stress on growth rates, body composition and developmental plasticity of the HPG-axis.

    PubMed

    Farrell, Tara M; Morgan, Amanda; Sarquis-Adamson, Yanina; MacDougall-Shackleton, Scott A

    2015-10-01

    In altricial songbirds, food restriction in early development has adverse effects on various physiological systems. When conditions improve birds can accelerate growth, but this compensatory strategy is associated with long-term adverse consequences. One system affected by altered growth rates is the hypothalamic-pituitary-gonadal (HPG) axis. Here, we subjected European starlings, Sturnus vulgaris, to an unpredictable food manipulation from 35 to 115days of age. We assessed the effects of the treatment by measuring overall body mass and body composition during and following the treatment period (i.e., accelerated growth). In adulthood, we measured the long-term effects of the treatment on overall body mass, testis volume, and HPG axis function in both sexes by quantifying androgen levels before and after a gonadotropin-releasing hormone (GnRH) challenge. During the treatment period, treatment birds had less body fat than controls. Following the treatment period, treatment birds weighed more than controls, but these gains were attributed to changes in lean mass. In adulthood, treatment males had lower baseline androgen levels, but there was no difference in peak androgen levels compared to controls. Treatment females did not differ from controls on any of the androgen measures. However, females that accelerated growth faster following the termination of the treatment had lower integrated androgen levels. When faced with limited developmental resources, birds may alter the developmental trajectory of physiological systems as a compensatory strategy. Such a strategy may have long-term consequences on endocrine regulation that could affect courtship and reproductive behaviors.

  1. Effect of acute hypoxia on the concentrations of potassium and phosphorus in the cardiomyocyte of a pregnant animal during early organogenesis.

    PubMed

    Pogorelov, A G

    2008-05-01

    The concentrations of potassium and phosphorus in the cardiomyocyte cytoplasm of the Wistar rat were measured by means of electron probe microanalysis. Pregnancy was accompanied by a decrease in cytoplasmic phosphorus concentration and an increase in cytoplasmic potassium concentration. Acute hypoxia modified the concentrations of these elements in the cytoplasm. PMID:19145292

  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. Perturbation of copper homeostasis is instrumental in early developmental arrest of intraerythrocytic Plasmodium falciparum

    PubMed Central

    2014-01-01

    Background Malaria continues to be a devastating disease. The elucidation of factors inducing asexual growth versus arrest of Plasmodium falciparum can provide information about the development of the parasite, and may help in the search for novel malaria medication. Based on information from genome-wide transcriptome profiling of different developmental stages of P. falciparum, we investigated the critical importance of copper homeostasis in the developmental succession of P. falciparum with regard to three aspects of copper function. These were:1) inhibition of copper-binding proteins, 2) copper-ion chelation, and 3) down-regulated expression of genes encoding copper-binding proteins associated with a specific growth-promoting factor. Results Inhibition of copper-binding proteins with tetrathiomolybdate (TTM) caused cessation of growth of the parasite. TTM arrested the parasite irreversibly during the trophozoite to schizont stage progression. Target molecules for TTM may be present in P. falciparum. The involvement of copper ions in developmental arrest was also investigated by copper-ion chelating methods, which indicated a critical function of reduced copper ions (Cu1+) in the parasite during the early developmental stage. Copper ions, not only in the parasite but also in host cells, were targets of the chelators. Chelation of Cu1+caused blockage of trophozoite progression from the ring stage. Profound growth arrest was detected in parasites cultured in a chemically defined medium containing hexadecanoic acid alone as a growth-promoting factor. This developmental arrest was associated with down-regulated expression of genes encoding copper-binding proteins. Cis-9-octadecenoic acid completely prevented the down-regulation of gene expression and developmental arrest that were observed with the use of hexadecanoic acid. Conclusions The critical importance of copper homeostasis in early developmental stages of P. falciparum was confirmed. Perturbation of copper

  4. [Effect of early intervention on the interaction of developmentally delayed infants and their mothers].

    PubMed

    Chen, Y J; Chu, H H

    1995-12-01

    The purpose of this study was (1) to examine the interaction patterns of mothers and their developmentally delayed infants during free play and instructional episodes; (2) to investigate the influence of an early intervention program on the interaction patterns of mothers and their developmentally delayed infants; and (3) to investigate to what extent the maternal perceptions and expectations, perceived stress and involving motivation were associated with maternal behavior while interacting with their developmentally delayed infants. The participants of this study were twenty-one developmentally delayed infants and their mothers. Each mother-child dyad was videotaped in a laboratory playroom for 10-minutes of free play and a 5-minute instructional session. Mental and psychomotor development of the child were measured by Bayley scale. The perception of child development, expectation, and the stress of mothers were measured by a self-report questionnaire which was designed by a researcher in this study. The mothers' motivation of involvement was evaluated by teachers. On year after early intervention, it was found that (1) developmentally delayed infants increased locomotion, (2) mothers demonstrated more positive emotional expression during mother-child interaction, and (3) the score of HOME, mother's involvement, and the quality of mother-child interaction which was evaluated by teachers were significantly increased. Furthermore, the differences between situations indicated that the developmentally delayed infants were more toy-oriented during play than instruction. The mothers tended to be more helpful in attitude while they instructed their children. The mother's perception of child development and stress were found to be the critical factors affecting maternal teaching, controlling, and caring behavior. PMID:8551531

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

    PubMed

    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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26144553

  7. 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

  8. 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

  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. 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…

  11. Endocrine and other physiologic modulators of perinatal cardiomyocyte endowment.

    PubMed

    Jonker, S S; Louey, S

    2016-01-01

    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

  12. Disruption of blastomeric F-actin: a potential early biomarker of developmental toxicity in zebrafish.

    PubMed

    Kanungo, Jyotshnabala; Paule, Merle G

    2011-07-01

    The expression of at least some biomarkers of toxicity is generally thought to precede the appearance of frank pathology. In the context of developmental toxicity, certain early indicators may be predictive of later drastic outcome. The search for predictive biomarkers of toxicity in the cells (blastomeres) of an early embryo can benefit from the fact that for normal development to proceed, the maintenance of blastomere cellular integrity during the process of transition from an embryo to a fully functional organism is paramount. Actin microfilaments are integral parts of blastomeres in the developing zebrafish embryo and contribute toward the proper progression of early development (cleavage and epiboly). In early embryos, the filamentous actin (F-actin) is present and helps to define the boundary of each blastomere as they remain adhered to each other. In our studies, we observed that when blastomeric F-actin is depolymerized by agents like gelsolin, the blastomeres lose cellular integrity, which results in abnormal larvae later in development. There are a variety of toxicants that depolymerize F-actin in early mammalian embryos, the later consequences of which are, at present, not known. We propose that very early zebrafish embryos (~5-h old) exposed to such toxicants will also respond in a like manner. In this review, we discuss the potential use of F-actin disruption as a predictive biomarker of developmental toxicity in zebrafish. PMID:21461911

  13. Impact of di-ethylhexylphthalate exposure on metabolic programming in P19 ECC-derived cardiomyocytes.

    PubMed

    Schaedlich, Kristina; Schmidt, Juliane-Susanne; Kwong, Wing Yee; Sinclair, Kevin D; Kurz, Randy; Jahnke, Heinz-Georg; Fischer, Bernd

    2015-07-01

    Di(2-ethylhexyl)phthalate (DEHP) is the most common plasticizer in plastic devices of everyday use. It is a ubiquitous environmental contaminant and primarily known to impair male gonadal development and fertility. Studies concerning the long-term effects of prenatal DEHP exposure on certain diseases [The Developmental Origins of Health and Disease paradigm (DOHaD) hypothesis] are scarce although it is proven that DEHP crosses the placenta. Rising environmental pollution during the last centuries coincides with an increasing prevalence of cardiovascular and metabolic diseases. We have investigated the effects of an early embryonic DEHP exposure at different developmental stages on cardiomyogenesis. We used an in-vitro model, the murine P19 embryonic carcinoma cell line (P19 ECC), mimicking early embryonic stages up to differentiated beating cardiomyocytes. P19 ECC were exposed to DEHP (5, 50, 100 µg ml(-1)) at the undifferentiated stage for 5 days and subsequently differentiated to beating cardiomyocytes. We analyzed the expression of metabolic (Pparg1, Fabp4 and Glut4), cardiac (Myh6, Gja1) and methylation (Dnmt1, Dnmt3a) marker genes by quantitative real-time PCR (qRT-PCR), beating rate and the differentiation velocity of the cells. The methylation status of Pparg1, Ppara and Glut4 was investigated by pyrosequencing. DEHP significantly altered the expression of all investigated genes. The beating rate and differentiation velocity were accelerated. Exposure to DEHP led to small but statistically significant increases in methylation of specific CpGs within Ppara and Pparg1, which otherwise were generally hypomethylated, but methylation of Glut4 was unaltered. Early DEHP exposure of P19 ECC alters the expression of genes associated with cellular metabolism and the functional features of cardiomyocytes.

  14. Global perspective on early diagnosis and intervention for children with developmental delays and disabilities

    PubMed Central

    SCHERZER, ALFRED L; CHHAGAN, MEERA; KAUCHALI, SHUAIB; SUSSER, EZRA

    2013-01-01

    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, there is an urgent need to recognize that improving the quality of life of the survivors must complement mortality reduction in healthcare practice and programs. The incorporation of early evaluation and intervention programs into routine pediatric care is likely to have the most impact on the quality of life of these children. We therefore call for leadership from practitioners, governments, and international organizations to prioritize regular childhood developmental surveillance for possible delays and disabilities, and to pursue early referral for intervention. PMID:22803576

  15. Global perspective on early diagnosis and intervention for children with developmental delays and disabilities.

    PubMed

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

    2012-12-01

    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, there is an urgent need to recognize that improving the quality of life of the survivors must complement mortality reduction in healthcare practice and programs. The incorporation of early evaluation and intervention programs into routine pediatric care is likely to have the most impact on the quality of life of these children. We therefore call for leadership from practitioners, governments, and international organizations to prioritize regular childhood developmental surveillance for possible delays and disabilities, and to pursue early referral for intervention. PMID:22803576

  16. 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

  17. New features of triacylglycerol biosynthetic pathways of peanut seeds in early developmental stages.

    PubMed

    Yu, Mingli; Liu, Fengzhen; Zhu, Weiwei; Sun, Meihong; Liu, Jiang; Li, Xinzheng

    2015-11-01

    The peanut (Arachis hypogaea L.) is one of the three most important oil crops in the world due to its high average oil content (50 %). To reveal the biosynthetic pathways of seed oil in the early developmental stages of peanut pods with the goal of improving the oil quality, we presented a method combining deep sequencing analysis of the peanut pod transcriptome and quantitative real-time PCR (RT-PCR) verification of seed oil-related genes. From the sequencing data, approximately 1500 lipid metabolism-associated Unigenes were identified. The RT-PCR results quantified the different expression patterns of these triacylglycerol (TAG) synthesis-related genes in the early developmental stages of peanut pods. Based on these results and analysis, we proposed a novel construct of the metabolic pathways involved in the biosynthesis of TAG, including the Kennedy pathway, acyl-CoA-independent pathway and proposed monoacylglycerol pathway. It showed that the biosynthetic pathways of TAG in the early developmental stages of peanut pods were much more complicated than a simple, unidirectional, linear pathway.

  18. 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

  19. 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…

  20. Early developmental processes and the continuity of risk for underage drinking and problem drinking.

    PubMed

    Zucker, Robert A; Donovan, John E; Masten, Ann S; Mattson, Margaret E; Moss, Howard B

    2008-04-01

    Developmental pathways to underage drinking emerge before the second decade of life. Many scientists, however, as well as the general public, continue to focus on proximal influences surrounding the initiation of drinking in adolescence, such as social, behavioral, and genetic variables related to availability and ease of acquisition of the drug, social reinforcement for its use, and individual differences in drug responses. In the past 20 years, a considerable body of evidence has accumulated on the early (often much earlier than the time of the first drink) predictors and pathways of youthful alcohol use and abuse. These early developmental influences involve numerous risk, vulnerability, promotive, and protective processes. Some of these factors are not related directly to alcohol use, whereas 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 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 and the 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. 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

  2. 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…

  3. 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. PMID:25109299

  4. 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. PMID:27425563

  5. 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.

  6. Isolation of contractile cardiomyocytes from human pluripotent stem-cell-derived cardiomyogenic cultures using a human NCX1-EGFP reporter.

    PubMed

    Ovchinnikov, Dmitry A; Hidalgo, Alejandro; Yang, Seung-Kwon; Zhang, Xinli; Hudson, James; Mazzone, Stuart B; Chen, Chen; Cooper-White, Justin J; Wolvetang, Ernst J

    2015-01-01

    The prospective isolation of defined contractile human pluripotent stem cell (hPSC)-derived cardiomyocytes is advantageous for regenerative medicine and drug screening applications. Currently, enrichment of cardiomyocyte populations from such cultures can be achieved by combinations of cell surface markers or the labor-intensive genetic modification of cardiac developmental genes, such as NKX2.5 or MYH6, with fluorescent reporters. To create a facile, portable method for the isolation of contractile cardiomyocytes from cardiomyogenic hPSC cultures, we employed a highly conserved cardiac enhancer sequence in the SLC8A1 (NCX1) gene to generate a lentivirally deliverable, antibiotic-selectable NCX1cp-EGFP reporter. We show that human embryonic stem cells (and induced pluripotent stem cells) transduced with the NCX1cp-EGFP reporter cassette exhibit enhanced green fluorescent protein (EGFP) expression in cardiac progenitors from 5 days into the directed cardiac hPSC differentiation protocol, with all reporter-positive cells transitioning to spontaneously contracting foci 3 days later. In subsequent stages of cardiomyocyte maturation, NCX1cp-EGFP expression was exclusively limited to contractile cells expressing high levels of cardiac troponin T (CTNT), MLC2a/v, and α-actinin proteins, and was not present in CD90/THY1(+) cardiac stromal cells or CD31/PECAM(+) endothelial cells. Flow-assisted cytometrically sorted EGFP(+) fractions of differentiated cultures were highly enriched in both early (NKX2.5 and TBX5) and late (CTNT/TNNI2, MYH6, MYH7, NPPA, and MYL2) cardiomyocyte markers, with a significant proportion of cells displaying a ventricular-like action potential pattern in patch-clamp recordings. We conclude that the use of the cardiac-specific promoter of the human SLC8A1(NCX1) gene is an effective strategy to isolate contractile cardiac cells and their progenitors from hPSC-derived cardiomyogenic cultures. PMID:25075536

  7. 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

  8. 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

  9. 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

  10. 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.

  11. Persistence of early emerging aberrant behavior in children with developmental disabilities.

    PubMed

    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 Behavior Checklist: Manual. East Aurora, NY: Slosson Educational Publications; (1994). Aberrant Behavior Checklist--Community. East Aurora, NY: Slosson Educational Publications]. Problem behaviors were present in all children at the beginning of the study. Nine of the 13 children entered the study with relatively high levels of aberrant behaviors that showed little change over the 3 years. These data suggest that aberrant behaviors often emerge early and can be highly persistent during the preschool years. Prevention would, therefore, seem to require home-based interventions that begin before 4 years of age.

  12. Early developmental delay in children with autism: A study from a developing country.

    PubMed

    Arabameri, Elahe; Sotoodeh, Mohammad Saber

    2015-05-01

    Early diagnosis is appropriate and important for developmental disorders such as autism spectrum disorder. In many less developed countries, unfortunately, diagnosis of this disorder is delayed. The aim of the present study is to determine whether this disorder can be screened using simple strategies such as comparison of the age of acquisition of motor skills. For this purpose, 124 children with autism were chosen to enter the study, and their parents were asked to retrospectively specify the age of achieving milestones of sitting without support, standing alone and walking alone. Information obtained from the parents was compared with World Health Organization standards. Results indicate that participants (male and female) have significantly delayed age of acquisition of all three skills. Based on this result, it can be suggested that existing standards, as a simple means with low cost and easy availability, can be used for early screening of the disease at a younger age so that treatment can be provided more quickly.

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

    PubMed

    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

  14. 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

  15. A study looking at the effectiveness of developmental screening in identifying learning disabilities in early childhood.

    PubMed

    Flanagan, O; Nualláin, S O

    2001-05-01

    This is a retrospective study of children under six years of age referred to the Brothers of Charity Early Intervention Services in County Galway, a service that caters for children under 6 years with learning disabilities. The aim in doing this study was to assess the value of routine developmental screening in identifying children with learning difficulties. This study also investigates the patterns and sources of referral to the remedial services provided by the Brothers of Charity and highlights possible avoidable delays in referral. The results showed that many children were referred for remedial services late. The reasons for late referral included late identification of some children with problems, insufficient co-ordination of community-based services and a lack of awareness of the importance of early intervention in some cases. As some communication disorders such as autism, autistic spectrum disorders and specific language delay may not express themselves until the later part of the second year of life, the 18-24 month developmental assessment is of vital importance. However identification of these disorders can present difficulties and may call for additional training for professionals involved in the developmental screening of children in that age group. The interval between initial identification and referral for remedial care in many cases was more than twelve months. We propose that, in order to minimize this time, children requiring a more in-depth assessment should be assessed by a community-based multidisciplinary team, enabling integrated assessment by the different disciplines and thus speedier referral to remedial services. PMID:11474856

  16. 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.

  17. 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

  18. 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.

  19. Developmental trajectories of the fronto-temporal lobes from infancy to early adulthood in healthy individuals.

    PubMed

    Tanaka, Chiaki; Matsui, Mie; Uematsu, Akiko; Noguchi, Kyo; Miyawaki, Toshio

    2012-01-01

    Brain development during early life in healthy individuals is rapid and dynamic, indicating that this period plays a very important role in neural and functional development. The frontal and temporal lobes are known to play a particularly important role in cognition. The study of healthy frontal and temporal lobe development in children is therefore of considerable importance. A better understanding of how these brain regions develop could also aid in the diagnosis and treatment of neurodevelopmental disorders. Some developmental studies have used magnetic resonance imaging (MRI) to examine infant brains, but it remains the case that relatively little is known about cortical brain development in the first few years of life. In the present study we examined whole brain, temporal lobe and frontal lobe developmental trajectories from infancy to early adulthood in healthy individuals, considering gender and brain hemisphere differences. We performed a cross-sectional, longitudinal morphometric MRI study of 114 healthy individuals (54 females and 60 males) aged 1 month to 25 years old (mean age ± SD 8.8 ± 6.9). We measured whole brain, temporal and frontal lobe gray matter (GM)/white matter (WM) volumes, following previously used protocols. There were significant non-linear age-related volume changes in all regions. Peak ages of whole brain, temporal lobe and frontal lobe development occurred around pre-adolescence (9-12 years old). GM volumes for all regions increased significantly as a function of age. Peak age was nevertheless lobe specific, with a pattern of earlier peak ages for females in both temporal and frontal lobes. Growth change in whole brain GM volume was larger in males than in females. However, GM volume growth changes for the temporal and frontal lobes showed a somewhat different pattern. GM volume for both temporal and frontal lobes showed a greater increase in females until around 5-6 years old, at which point this tendency reversed (GM volume

  20. Developmental Predictors of Inattention-Hyperactivity from Pregnancy to Early Childhood

    PubMed Central

    Foulon, Stéphanie; Pingault, Jean-Baptiste; Melchior, Maria; Falissard, Bruno; Côté, Sylvana M.

    2015-01-01

    Objective The objective of the study was to characterize the developmental sequence of pre- and postnatal risk factors for inattention-hyperactivity symptoms in preschoolers. Materials and Methods Longitudinal data came from a French population based birth cohort study (EDEN; N = 1311 mother-child pairs followed from the pregnancy onwards). Inattention-hyperactivity symptoms were assessed with the Strengths and Difficulties Questionnaire when participating children were 3 years of age. Potential risk factors were classified in four domains (fetal exposures and child somatic characteristics, child temperament, child neurodevelopmental status, psychosocial environment) and four periods (before pregnancy, prenatal/birth, infancy, toddlerhood). Their role as potential moderator or mediator was tested with path analysis to determine the developmental sequence. Results A low family socioeconomic status before pregnancy was the main environmental risk factor for inattention-hyperactivity symptoms at 3 years, and its effect occurred via two pathways. The first was a risk pathway, where lower SES was associated with higher maternal depression and anxiety during pregnancy; then to higher maternal and child distress and dysregulation in infancy; and in turn to higher levels of inattention-hyperactivity at 3 years. The second was a protective pathway, where higher SES was associated with longer duration of breastfeeding during infancy; then to better child neurodevelopmental status in toddlerhood; and in turn to lower levels of inattention-hyperactivity at 3 years. Discussion This study identified psychosocial factors at several developmental periods that represent potential targets for preventing the emergence of inattention-hyperactivity symptoms in early childhood. PMID:25938453

  1. Stressful Events in Early Childhood and Developmental Trajectories of Bedwetting at School Age

    PubMed Central

    Sullivan, Sarah; von Gontard, Alexander; Heron, Jon

    2016-01-01

    Objective To examine whether early stressful events are associated with developmental trajectories of bedwetting. Methods This is a prospective cohort study comprising 8,761 participants from the Avon Longitudinal Study of Parents and Children. Stressful events were measured using a maternal questionnaire completed at 3 time points before their child was 4 years old. The association between stressful events and trajectories of bedwetting from 4 to 9 years was examined using multinomial regression. Results The association with stressful events was strongest for the frequent persistent bedwetting trajectory (wetting at least twice a week up to age 9). A 1 standard deviation increase in the stressful events score was associated with a 29% (13–47%) increase in the odds of experiencing frequent persistent bedwetting compared with normal attainment of nighttime bladder control. Conclusions Clinicians and parents should be aware that continence is a developmental outcome that is associated with high levels of stress in the family. PMID:27072719

  2. 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.

  3. 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. PMID:27570937

  4. Early life developmental effects of marine persistent organic pollutants on the sea urchin Psammechinus miliaris.

    PubMed

    Anselmo, Henrique M R; Koerting, Lina; Devito, Sarah; van den Berg, Johannes H J; Dubbeldam, Marco; Kwadijk, Christiaan; Murk, Albertinka J

    2011-11-01

    A new 16-day echinoid early life stage (ELS) bioassay was developed to allow for prolonged observation of possible adverse effects during embryogenesis and larval development of the sea urchin Psammechinus miliaris. Subsequently, the newly developed bioassay was applied to study the effects of key marine persistent organic pollutants (POPs). Mortality, morphological abnormalities and larval development stages were quantified at specific time points during the 16-day experimental period. In contrast to amphibians and fish, P. miliaris early life development was not sensitive to dioxin-like toxicity in the prolonged early life stage test. Triclosan (TCS) levels higher than 500 nM were acutely toxic during embryo development. Morphological abnormalities were induced at concentrations higher than 50 nM hexabromocyclododecane (HBCD) and 1000 nM tetrabromobisphenol A (TBBPA). Larval development was delayed above 25 nM HBCD and 500 nM TBBPA. Heptadecafluorooctane sulfonic acid (PFOS) exposure slightly accelerated larval development at 9 days post-fertilization (dpf). However, the accelerated development was no longer observed at the end of the test period (16 dpf). The newly developed 16-day echinoid ELS bioassay proved to be sensitive to toxic effects of POPs that can be monitored for individual echinoid larvae. The most sensitive and dose related endpoint was the number of developmental penalty points. By manipulation of the housing conditions, the reproductive season could be extended from 3 to 9 months per year and the ELS experiments could be performed in artificial sea water as well.

  5. 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

  6. 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

  7. The typical developmental trajectory of social and executive functions in late adolescence and early adulthood.

    PubMed

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

    2013-07-01

    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 (Barker, Andrade, Morton, Romanowski, & Bowles, 2010; Lebel, Walker, Leemans, Phillips, & Beaulieu, 2008), although social cognition functions are also associated with widely distributed networks. Previously, nonlinear development has been reported around puberty on an emotion match-to-sample task (McGivern, Andersen, Byrd, Mutter, & Reilly, 2002) and for IQ in midadolescence (Ramsden et al., 2011). However, there are currently little data on the typical development of social and executive functions in late adolescence and early adulthood. In a cross-sectional design, 98 participants completed tests of social cognition and executive function, Wechsler Abbreviated Scale of Intelligence (Wechsler, 1999), Positive and Negative Affect Schedule (Watson, Clark, & Tellegen, 1988), Hospital Anxiety and Depression Scale (Zigmond & Snaith, 1983), and measures of pubertal development and demographics at ages 17, 18, and 19. Nonlinear age differences for letter fluency and concept formation executive functions were found, with a trough in functional ability in 18-year-olds compared with other groups. There were no age group differences on social cognition measures. Gender accounted for differences on 1 scale of concept formation, 1 dynamic social interaction scale, and 2 empathy scales. The clinical, developmental, and educational implications of these findings are discussed. PMID:22946438

  8. The developmental pathway from pubertal timing to delinquency and sexual activity from early to late adolescence.

    PubMed

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

    2011-10-01

    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

  9. Early language patterns of toddlers on the autism spectrum compared to toddlers with developmental delay.

    PubMed

    Ellis Weismer, Susan; Lord, Catherine; Esler, Amy

    2010-10-01

    This study characterized early language abilities in toddlers with autism spectrum disorders (n = 257) using multiple measures of language development, compared to toddlers with non-spectrum developmental delay (DD, n = 69). Findings indicated moderate to high degrees of agreement among three assessment measures (one parent report and two direct assessment measures). Performance on two of the three measures revealed a significant difference in the profile of receptive-expressive language abilities for toddlers with autism compared to the DD group, such that toddlers with autism had relatively more severe receptive than expressive language delays. Regression analyses examining concurrent predictors of language abilities revealed both similarities in significant predictors (nonverbal cognition) and differences (frequency of vocalization, imitation) across the diagnostic groups.

  10. Translation Repressors, an RNA Helicase, and Developmental Cues Control RNP Phase Transitions during Early Development

    PubMed Central

    Hubstenberger, Arnaud; Noble, Scott L.; Cameron, Cristiana; Evans, Thomas C.

    2013-01-01

    SUMMARY Like membranous organelles, large-scale coassembly of macromolecules can organize functions in cells. Ribonucleoproteins (RNPs) can form liquid or solid aggregates, but control and consequences of these RNP states in living, developing tissue are poorly understood. Here, we show that regulated RNP factor interactions drive transitions among diffuse, semiliquid, or solid states to modulate RNP sorting and exchange in the Caenorhabditis elegans oocyte cytoplasm. Translation repressors induce an intrinsic capacity of RNP components to coassemble into either large semiliquids or solid lattices, whereas a conserved RNA helicase prevents polymerization into nondynamic solids. Developmental cues dramatically alter both fluidity and sorting within large RNP assemblies, inducing a transition from RNP segregation in quiescent oocytes to dynamic exchange in the early embryo. Therefore, large-scale organization of gene expression extends to the cytoplasm, where regulation of supramolecular states imparts specific patterns of RNP dynamics. PMID:24176641

  11. 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.

  12. 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

    2015-09-01

    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.

  13. 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. PMID:15039986

  14. 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

  15. 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…

  16. Relationships of Preservice Early Childhood Teachers' Cultural Values, Ethical and Cognitive Developmental Levels, and Views of Nature of Science

    ERIC Educational Resources Information Center

    Akerson, Valarie L.; Buzzelli, Cary A.

    2007-01-01

    This study explored relationships between preservice early childhood teachers' views of nature of science (NOS), cognitive developmental levels, and their cultural values. Using the Views of Nature of Science Questionnaire (VNOS-B) and interviews, we assessed views of NOS. The Learning Context Questionnaire (LCQ) was used to determine the…

  17. 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…

  18. A Qualitative Metasynthesis of How Early Educators in International Contexts Address Cultural Matters That Contrast with Developmentally Appropriate Practices

    ERIC Educational Resources Information Center

    Brown, Christopher P.; Lan, Yi-Chin

    2015-01-01

    Research Findings: The National Association for the Education of Young Children's guidelines for developmentally appropriate practices (DAP) have been imported and researched by others across the globe. A central issue that has arisen for these international early childhood educators is whether these best practices are sensitive to the…

  19. Effects of a Developmentally Based Intervention with Teachers on Native American and White Early Adolescents' Schooling Adjustment in Rural Settings

    ERIC Educational Resources Information Center

    Hamm, Jill V.; Farmer, Thomas W.; Robertson, Dylan; Dadisman, Kimberly A.; Murray, Allen; Meece, Judith L.; Song, Samuel Y.

    2010-01-01

    This study reports the effectiveness of a developmentally based, teacher professional development intervention aimed at improving early adolescent school adjustment. Teachers in rural schools in a Northern Plains state took part in professional development activities across a year. Following a randomized control trial design, Native American and…

  20. Family Dynamics and Child Outcomes in Early Intervention: The Role of Developmental Theory in the Specification of Effects

    ERIC Educational Resources Information Center

    Blair, Clancy; Peters, Rachel; Lawrence, Frank

    2003-01-01

    Evaluations of early intervention for children facing biological and/or socioeconomic risk have tended to focus most directly on change in the child, treating family variables primarily as mediators of change. In contrast, the current study used developmental theory to articulate hypotheses that address one way in which a focus on the relationship…

  1. Normative Developmental Trajectories of Aggressive Behaviors in African American, American Indian, Asian American, Caucasian, and Hispanic Children and Early Adolescents

    ERIC Educational Resources Information Center

    Vazsonyi, Alexander T.; Keiley, Margaret K.

    2007-01-01

    The current 5-year accelerated longitudinal investigation modeled the developmental trajectories of aggressive behaviors in 10,107 predominantly minority (greater than 70%; African American, American Indian, Asian American, and Hispanic) children and early adolescents (Kindergarten through 8th grade, 49% female youth) from lower to lower-middle…

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

    ERIC Educational Resources Information Center

    Rentzou, Konstantina; Sakellariou, Maria

    2011-01-01

    The continuum of beliefs reported by Greek pre-service kindergarten teachers and how those beliefs relate to classroom practices are explored in this article. Considering the potentially important influence of teachers' beliefs on their practices, the level of early childhood teachers' beliefs about developmentally appropriate practices (DAPs) and…

  3. 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…

  4. 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. PMID:16712833

  5. Early acetabular cartilage degeneration in a rabbit model of developmental dysplasia of the hip

    PubMed Central

    Zhang, Xiangxin; Meng, Qingxia; Ma, Ruixue; Chen, Guangxiang; Cheng, Liang; Shen, Jun

    2015-01-01

    Background: Mild developmental dysplasia of hip (DDH) causes high morbidity of osteoarthritis (OA) on adult. It is thought that change of collagen and proteoglycans in cartilage may be the direct reasons for osteoarthritis. Objective: To detect the changes of the expressions of type II collagen of acetabular cartilage in early DDH and to investigate the relevance between type II collagen and the degeneration mechanism of the acetabular cartilage. Methods: The rabbit model of DDH was successfully established by applying the method of knee extending and fixing with cylinder cast in which left lower extremity as experimental group and right one as control group, checking with X-ray after 5 weeks. The stains of H&E and toluidine blue were applied on the samples of acetabular cartilage to observe the morphological changes of chondrocytes and extracellular matrix (ECM). The immunohistochemical staining and Western-blot were employed to respectively qualify and quantitate the expression of type II collagen. Results: Pathohistology observing indicated the signs of retrogressive changes of acetabular cartilage in experimental group. Also, the positive stained cells in type II collagen in experimental group was higher based on immunohistochemiscal staining. The quantitative amounts of type II collagen by Western-blot in experimental group was higher significant difference existed between two groups (t = 2.18, P < 0.05). Conclusions: The expression of type II collagen is correlated to a degeneration of acetabular cartilage and increase obviously in early DDH. PMID:26550441

  6. 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.

  7. 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…

  8. Early clinical characteristics according to developmental stage in children with definite moyamoya disease.

    PubMed

    Kim, Young Ok; Joo, Sung-Pil; Seo, Bo-Ra; Rho, Young Il; Yoon, Woong; Woo, Young Jong

    2013-06-01

    The objective is to clarify the early clinical characteristics in childhood moyamoya disease (MD). Epidemiologic characteristics, symptoms and diagnostic rates were assessed in 64 children (0-18 years) with definite MD according to developmental stage: infancy (5; 0-1 years); toddlerhood/preschool age (22; 2-5 years); school age (29; 6-10 years); and adolescence (8; 11-18 years). The median ages at onset was 6.25 years and the female to male ratio was 1.9 (~2.5 in toddlerhood/preschool age and in adolescence, P=0.71). Previous headache was observed in 23% (14/64): frequently in school age (38%, P=0.02) and within 6 months before main symptoms (6/11). As an initial symptom, weakness was observed in 78% (50/64) mainly as transient ischemic attack (TIA, 61%) in limbs (90%) and unilaterally (82%). TIA was less frequent in infancy (40%, P=0.04). Seizure was observed in 27% (17/64): frequently in infancy (100%, P<0.01), as the focal type (71%), and in the right extremity (3:1). Isolated seizures without other symptoms was frequent in children ~5 years (P<0.01). Severe headache associated with MD was observed in 14% (9/64). Provoking events were positive in 42% (27/64): in school age, frequently during eating (28%); and in toddlerhood/preschool age, during crying (27%). The diagnostic rates at 3 and 12 months from symptom-onset were 39% (80% during infancy vs. 28% in school age, P=0.14) and 67%, respectively. Symptomatic progression at diagnosis was observed in 38% (24/64). Initial clinical characteristics in childhood definite MD differed according to developmental stage and from at diagnosis.

  9. 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

  10. 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.

  11. The International Society for Developmental Psychobiology Annual Meeting Symposium: Impact of Early Life Experiences on Brain and Behavioral Development

    PubMed Central

    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

    2007-01-01

    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, ajuvenile 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. PMID:17016842

  12. 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

  13. 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

  14. 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. PMID:24100467

  15. S-(-)equol production is developmentally regulated and related to early diet composition.

    PubMed

    Brown, Nadine M; Galandi, Stephanie L; Summer, Suzanne S; Zhao, Xueheng; Heubi, James E; King, Eileen C; Setchell, Kenneth D R

    2014-05-01

    S-(-)7-hydroxy-3-(4'-hydroxyphenyl)-chroman, or S-(-)equol, a biologically active intestinally derived bacterial metabolite of the soy isoflavones daidzin/daidzein, is not produced in neonatal life. Because its synthesis is dependent on equol-producing bacteria, we hypothesized that early nutrition may influence equol production. This prospective 2.5-year study determined the frequency of S-(-)equol production in healthy infants (n = 90) fed breast milk, soy infant formula, or cow's milk formula in their first year. Urinary S-(-)equol and daidzein were quantified by mass spectrometry after a standardized 3.5-day soy isoflavone challenge. Infants were tested at 6, 9, 12, 18, 24, and 36 months of age, and 3-day diet records were obtained at each visit to explore the effect of early and postweaning (>12 months) macronutrient and micronutrient dietary composition and S-(-)equol production. Use of antibiotics was also recorded. At age 6 months, none of the breast-fed infants produced S-(-)equol, whereas 3.8% and 6.0%, respectively, of soy and cow's milk formula-fed infants were equol producers. By age 3 years, 50% of the formula-fed infants were equol producers, compared with 25% of breast-fed infants. Use of antibiotics was prevalent among infants and may have impacted the stability of S-(-)equol production. No significant differences among the groups were observed in postweaning dietary intakes of total energy, carbohydrate, fiber, protein, fat, saturated fatty acids, or polyunsaturated fatty acids and the propensity to make S-(-)equol. In conclusion, S-(-)equol production is developmentally regulated and initially related to diet composition with the proportion of equol producers increasing over the first 3 years of life, with a trend for formula feeding favoring S-(-)equol production.

  16. 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.

  17. S-(–)equol production is developmentally regulated and related to early diet composition

    PubMed Central

    Brown, Nadine M.; Galandi, Stephanie L.; Summer, Suzanne S.; Zhao, Xueheng; Heubi, James E.; King, Eileen C.; Setchell, Kenneth D.R.

    2016-01-01

    S-(−)7-hydroxy-3-(4′-hydroxyphenyl)-chroman, or S-(−)equol, a biologically active intestinally derived bacterial metabolite of the soy isoflavones daidzin/daidzein, is not produced in neonatal life. Because its synthesis is dependent on equol-producing bacteria, we hypothesized that early nutrition may influence equol production. This prospective 2.5-year study determined the frequency of S-(−)equol production in healthy infants (n = 90) fed breast milk, soy infant formula, or cow’s milk formula in their first year. Urinary S-(−)equol and daidzein were quantified by mass spectrometry after a standardized 3.5-day soy isoflavone challenge. Infants were tested at 6, 9, 12, 18, 24, and 36 months of age, and 3-day diet records were obtained at each visit to explore the effect of early and postweaning (>12 months) macronutrient and micronutrient dietary composition and S-(−)equol production. Use of antibiotics was also recorded. At age 6 months, none of the breast-fed infants produced S-(−)equol, whereas 3.8% and 6.0%, respectively, of soy and cow’s milk formula–fed infants were equol producers. By age 3 years, 50% of the formula-fed infants were equol producers, compared with 25% of breast-fed infants. Use of antibiotics was prevalent among infants and may have impacted the stability of S-(−)equol production. No significant differences among the groups were observed in postweaning dietary intakes of total energy, carbohydrate, fiber, protein, fat, saturated fatty acids, or polyunsaturated fatty acids and the propensity to make S-(−)equol. In conclusion, S-(−)equol production is developmentally regulated and initially related to diet composition with the proportion of equol producers increasing over the first 3 years of life, with a trend for formula feeding favoring S-(−)equol production. PMID:24916553

  18. Early maternal deprivation in rats: a proposed animal model for the study of developmental neuroimmunoendocrine interactions.

    PubMed

    De la Fuente, M; Llorente, R; Baeza, I; De Castro, N M; Arranz, L; Cruces, J; Viveros, M P

    2009-02-01

    Adult animals that had been subjected to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal day (PND) 9-10] show long-term behavioral alterations that resemble specific symptoms of schizophrenia. Moreover, at adolescence MD rats showed depressive-like behavior and altered motor responses. According to the neurodevelopmental hypothesis, certain behavioral abnormalities observed in MD animals may be related to altered neurodevelopmental processes triggered by MD-induced elevated glucocorticoids in relevant specific brain regions. We review here these neuroendocrine effects and show new data indicating that the MD procedure induces diverse detrimental effects on the immune system that are already revealed in the short term (PND 13) and persist into adulthood. These long-lasting effects might be related to altered hypothalamus-pituitary-adrenal axis activity and to social as well as nutrition-related factors. In fact, MD induces long-lasting decreases in body weight. In view of our findings we propose the present MD procedure as a potentially useful model to analyze developmental interactions between early psychophysiological stress and immunodeficient states.

  19. Developmental changes in brain activation and functional connectivity during response inhibition in the early childhood brain.

    PubMed

    Mehnert, Jan; Akhrif, Atae; Telkemeyer, Silke; Rossi, Sonja; Schmitz, Christoph H; Steinbrink, Jens; Wartenburger, Isabell; Obrig, Hellmuth; Neufang, Susanne

    2013-11-01

    Response inhibition is an attention function which develops relatively early during childhood. Behavioral data suggest that by the age of 3, children master the basic task requirements for the assessment of response inhibition but performance improves substantially until the age of 7. The neuronal mechanisms underlying these developmental processes, however, are not well understood. In this study, we examined brain activation patterns and behavioral performance of children aged between 4 and 6 years compared to adults by applying a go/no-go paradigm during near-infrared spectroscopy (NIRS) brain imaging. We furthermore applied task-independent functional connectivity measures to the imaging data to identify maturation of intrinsic neural functional networks. We found a significant group×condition related interaction in terms of inhibition-related reduced right fronto-parietal activation in children compared to adults. In contrast, motor-related activation did not differ between age groups. Functional connectivity analysis revealed that in the children's group, short-range coherence within frontal areas was stronger, and long-range coherence between frontal and parietal areas was weaker, compared to adults. Our findings show that in children aged from 4 to 6 years fronto-parietal brain maturation plays a crucial part in the cognitive development of response inhibition. PMID:23265620

  20. 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.

  1. 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.

  2. Differential Expression Levels of Integrin α6 Enable the Selective Identification and Isolation of Atrial and Ventricular Cardiomyocytes

    PubMed Central

    Wiencierz, Anne Maria; Kernbach, Manuel; Ecklebe, Josephine; Monnerat, Gustavo; Tomiuk, Stefan; Raulf, Alexandra; Christalla, Peter; Malan, Daniela; Hesse, Michael; Bosio, Andreas; Fleischmann, Bernd K.; Eckardt, Dominik

    2015-01-01

    Rationale Central questions such as cardiomyocyte subtype emergence during cardiogenesis or the availability of cardiomyocyte subtypes for cell replacement therapy require selective identification and purification of atrial and ventricular cardiomyocytes. However, current methodologies do not allow for a transgene-free selective isolation of atrial or ventricular cardiomyocytes due to the lack of subtype specific cell surface markers. Methods and Results In order to develop cell surface marker-based isolation procedures for cardiomyocyte subtypes, we performed an antibody-based screening on embryonic mouse hearts. Our data indicate that atrial and ventricular cardiomyocytes are characterized by differential expression of integrin α6 (ITGA6) throughout development and in the adult heart. We discovered that the expression level of this surface marker correlates with the intracellular subtype-specific expression of MLC-2a and MLC-2v on the single cell level and thereby enables the discrimination of cardiomyocyte subtypes by flow cytometry. Based on the differential expression of ITGA6 in atria and ventricles during cardiogenesis, we developed purification protocols for atrial and ventricular cardiomyocytes from mouse hearts. Atrial and ventricular identities of sorted cells were confirmed by expression profiling and patch clamp analysis. Conclusion Here, we introduce a non-genetic, antibody-based approach to specifically isolate highly pure and viable atrial and ventricular cardiomyocytes from mouse hearts of various developmental stages. This will facilitate in-depth characterization of the individual cellular subsets and support translational research applications. PMID:26618511

  3. 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…

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

    PubMed

    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.

  5. 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.

  6. 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

  7. Early predictors of acetabular growth after closed reduction in late detected developmental dysplasia of the hip.

    PubMed

    Li, YiQiang; Xu, HongWen; Li, JingChun; Yu, LingJia; Liu, YuanZhong; Southern, Edward; Liu, HongSheng

    2015-01-01

    This study evaluates improvement of the acetabular index (AI) in patients with developmental dysplasia of the hip at 4 years after closed reduction, and determines the association between the final AI and a set of factors. Sixty-two patients (74 hips) treated with closed reduction were categorized into three groups according to age: group A (0-12 months, 18 hips), group B (13-18 months, 24 hips), and group C (>18 months, 32 hips). There was no difference in AI among the three groups before reduction (P=0.293). In groups A and C, the AI decreased significantly over time until 3 years after reduction and no differences were observed between the time points of 3 and 4 years. At 4 years after reduction, the AI of group C was significantly higher than that of groups A (P<0.001) and B (P=0.012). The overall AI improvement rate was 28.63%. The AI improvement rate of group A was significantly higher than that of group C (P=0.005). Pearson correlation analysis indicated no correlation between center-head distance discrepancy and the final AI (P=0.811). Linear regression suggested that age and initial AI correlated significantly with the final AI (R=0.617, F=15.031, P<0.001). Other factors, such as sex, center-edge angle of Wiberg, bilaterally involved, and avascular necrosis of the femoral head, showed no correlations with the final AI (P>0.05). According to the coefficients, initial AI (β1=0.432, P<0.001) had greater effect than age (β2=0.197, P=0.023) on the final AI. In conclusion, the AI decreases in all patients after reduction and stabilizes at 3 years after reduction. The AI improvement rate is correlated negatively with age. Age and initial AI are early predictors of the progress of AI after closed reduction in developmental dysplasia of the hip patients. PMID:25305044

  8. 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

    2015-01-01

    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. PMID:25944445

  9. 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

    2015-01-01

    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.

  10. 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

  11. 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

  12. Bone morphogenetic protein-10 induces cardiomyocyte proliferation and improves cardiac function after myocardial infarction.

    PubMed

    Sun, Lijun; Yu, Jing; Qi, Shun; Hao, Yuewen; Liu, Ying; Li, Zhenwu

    2014-11-01

    Heart disease is among the leading causes of death worldwide, and the limited proliferation of mammalian cardiomyocytes prevents heart regeneration in response to injury. Bone morphogenetic protein-10 (BMP10) exerts multiple roles in various developmental events; however, the effect of BMP10 and the underlying mechanism involved in cardiac repair remains unclear. After stimulation with the recombinant BMP10, an obvious dose-dependent cardiomyocyte proliferation and reentry of differentiated mammalian cardiomyocytes into the cell cycle was observed. Furthermore, BMP10 stimulation strikingly enhanced Tbx20 expression. Further analysis demonstrated that T-box 20 (Tbx20) was involved in BMP10-induced proliferation of differentiated cardiomyocytes as preconditioning with Tbx20 siRNA significantly attenuated BMP10-induced DNA synthesis. In vivo, BMP10 induced rat cardiomyocyte DNA synthesis and cytokinesis. After myocardial infarction (MI), BMP10 stimulated cardiomyocyte cell-cycle reentry and mitosis, resulting in the decrease of infarct size and improvement of cardiac repair. Taken together, these data indicated that BMP10 stimulated cardiomyocyte proliferation and repaired cardiac function after heart injury. Consequently, BMP10 may be a potential target for innovative strategies against heart failure.

  13. The Potential of Developmental Work Research as a Professional Learning Methodology in Early Childhood Education

    ERIC Educational Resources Information Center

    Nuttall, Joce

    2013-01-01

    Developmental Work Research (DWR) is a methodology for simultaneous research and innovation in workplace settings, developed by Finnish researcher Yryo Engestrom. This interventionist approach builds on the principles of cultural-historical activity theory, articulated by developmental psychologists L.S. Vygotsky and A.N. Le'ontev. The…

  14. 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…

  15. 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…

  16. 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

  17. Longitudinal analyses of geographic differences in utilization rates of children with developmental delays who participation in early intervention services.

    PubMed

    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 governmental reported early intervention services from year 2003 to 2009 in Taiwan. Results show that, the utilization rate of early intervention services was 9.18‰ (range=6.96-12.09‰) of children in 0-5 years during the past 7 years. Mean utilization rate in age group of 0-2 years was 8.32‰ (range=5.73-10.93‰), and age group of 3-5 years was 9.92‰ (range=7.78-13.78‰). We found that the utilization rate in all children aged 0-5 years (R(2)=0.93; p<0.001), boy group (R(2)=0.93; p<0.001) and girl group (R(2)=0.92; p=0.001) were significant increased gradually. The higher utilization rate of early intervention services (aged 0-5 years) were more likely to locate in the north cities (Keelung City=14.65‰; Taipei City=13.49‰), east areas--Hualien County (14.03‰), Taitung County (11.76‰) and central or south counties such as, Chiayi City (14.05‰), Tainan City (12.47‰), and Miaoli County (12.38‰). Hsinchu County (5.97‰), Kaohsiung City (6.21‰), Taichung County (6.74‰), Taipei County (6.95‰) have lower utilization rates of early intervention in Taiwan. The study highlights that the health care system should close the gaps in geographic disparities of early intervention services for children with developmental delays, and respond timely to the needs of these vulnerable children and their families.

  18. Characterization of developmental arrest in early bovine embryos cultured in vitro.

    PubMed

    Eyestone, W H; First, N L

    1991-03-01

    The susceptibility of early bovine embryos to developmental arrest ("blocking") in vitro was examined. Embryos, obtained from superovulated donors, were cultured in vitro in Ham's F10 culture medium or in vivo in sheep oviducts. Treatments were terminated on Day 7 post-donor estrus (estrus = day 0), and the embryos were evaluated for development. Experiment 1 tested whether the 8- to 16-cell block was reversible. One- to two-cell embryos were cultured in vitro to the 8-cell stage (2 d), then in vivo for 3 d; controls were cultured in vitro or in vivo for 5 d. Forty-two percent (19/45) of in vivo controls developed normally; none (0/55; 0%) of the in vitro controls cleaved past the 9- to 16-cell stage. Only 4% (2/48) of the embryos cultured to eight cells in vitro developed normally after culture in sheep oviducts, indicating that the block was irreversible. Irreversibility was not caused by overt cell death, since 33/33 (100%) of blocked embryos responded positively to fluorescein diacetate vital staining. Experiment 2 tested the effect of in vitro exposure at specific cell stages on subsequent in vivo development. Embryos at the 1- to 2-, 3- to 4-, 5- to 8- and 9- to 16-cell stages were assigned randomly to one of the following treatments: in vivo culture; in vitro culture; or 24 h in vitro culture, followed by in vivo culture. Subsequent in vivo development was affected by 24 h of in vitro culture (P<0.05) only in 3- to 4-cell embryos (11/41, 27% vs 22/41, 54% for in vivo controls). We conclude that 1) the block is a manifestation of in vitro exposure during the four- to eight-cell stage, and 2) the block, while irreversible, is not the result of overt embryonic death. PMID:16726930

  19. Characterization of developmental arrest in early bovine embryos cultured in vitro.

    PubMed

    Eyestone, W H; First, N L

    1991-03-01

    The susceptibility of early bovine embryos to developmental arrest ("blocking") in vitro was examined. Embryos, obtained from superovulated donors, were cultured in vitro in Ham's F10 culture medium or in vivo in sheep oviducts. Treatments were terminated on Day 7 post-donor estrus (estrus = day 0), and the embryos were evaluated for development. Experiment 1 tested whether the 8- to 16-cell block was reversible. One- to two-cell embryos were cultured in vitro to the 8-cell stage (2 d), then in vivo for 3 d; controls were cultured in vitro or in vivo for 5 d. Forty-two percent (19/45) of in vivo controls developed normally; none (0/55; 0%) of the in vitro controls cleaved past the 9- to 16-cell stage. Only 4% (2/48) of the embryos cultured to eight cells in vitro developed normally after culture in sheep oviducts, indicating that the block was irreversible. Irreversibility was not caused by overt cell death, since 33/33 (100%) of blocked embryos responded positively to fluorescein diacetate vital staining. Experiment 2 tested the effect of in vitro exposure at specific cell stages on subsequent in vivo development. Embryos at the 1- to 2-, 3- to 4-, 5- to 8- and 9- to 16-cell stages were assigned randomly to one of the following treatments: in vivo culture; in vitro culture; or 24 h in vitro culture, followed by in vivo culture. Subsequent in vivo development was affected by 24 h of in vitro culture (P<0.05) only in 3- to 4-cell embryos (11/41, 27% vs 22/41, 54% for in vivo controls). We conclude that 1) the block is a manifestation of in vitro exposure during the four- to eight-cell stage, and 2) the block, while irreversible, is not the result of overt embryonic death.

  20. Effect of Maternal Age on the Ratio of Cleavage and Mitochondrial DNA Copy Number in Early Developmental Stage Bovine Embryos

    PubMed Central

    TAKEO, Shun; GOTO, Hiroya; KUWAYAMA, Takehito; MONJI, Yasunori; IWATA, Hisataka

    2012-01-01

    Abstract Age-associated deterioration in both the quality and quantity of mitochondria occurs in older women. The main aim of this study was to examine the effect of age on mitochondrial DNA copy number (mtDNA number) in early developmental stage bovine embryos as well as the dynamics of mtDNA number during early embryo development. Real-time PCR was used to determine mtDNA number. In vitro-produced embryos 48 h after insemination derived from Japanese black cows, ranging in age from 25 to 209 months were categorized based on their cleavage status. There was an overall negative relationship between the age of the cow and cleavage status, to the extent that the ratio of embryos cleaved over the 4-cell stage was greater in younger cows. The mtDNA number did not differ among the cleaved status of embryos. In the next experiment, oocytes collected from each donor cow were divided into 2 groups containing 10 oocytes each, in order to compare the mtDNA number of mature oocytes and early developmental stage embryos within individuals. Upon comparing the mtDNA number between oocytes at the M2 stage and early developmental stage 48 h post insemination, mtDNA number was found to decrease in most cows, but was found to increase in some cows. In conclusion, age affects the cleaving ability of oocytes, and very old cows (> 180 months) tend to have lower mtDNA numbers in their oocytes. The change in mtDNA number during early development varied among individual cows, although overall, it showed a tendency to decrease. PMID:23269452

  1. Developmental regression as an early manifestation of vitamin B12 deficiency.

    PubMed

    Sadowitz, P D; Livingston, A; Cavanaugh, R M

    1986-07-01

    Loss of previously attained developmental milestones in an infant is often associated with central nervous system tumor, neuromuscular disease, or an inborn metabolic error. An infant with developmental regression and involuntary movements who was found to be vitamin B12 deficient on the basis of unrecognized maternal vitamin B12 deficiency is described. The infant had a dramatic neurologic recovery after receiving vitamin B12. The case and a review of similar cases is presented.

  2. 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.

  3. 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. PMID:26219261

  4. 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. PMID:22201148

  5. 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.

  6. 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. PMID:27574772

  7. Developmental programming of the HPA and HPG axes by early-life stress in male and female song sparrows.

    PubMed

    Schmidt, Kim L; Macdougall-Shackleton, Elizabeth A; Soma, Kiran K; Macdougall-Shackleton, Scott A

    2014-01-15

    Variation in early environmental conditions can have long-term effects on physiology and behavior, a process referred to as developmental programming. In particular, exposure to early-life stressors can have long-term effects on regulation of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. Although these effects have been well documented in mammals, less is known about how early-life stress affects regulation of these endocrine systems in non-mammalian species. In the current study, we determined the long-term effects of early-life food restriction or corticosterone (CORT) treatment on the HPA axis of song sparrows (Melospiza melodia), including the responses to restraint stress, dexamethasone challenge, and ACTH challenge. In addition, we assessed long-term effects on the HPG axis by measuring sex steroid levels (testosterone in males and 17β-estradiol in females) before and after a gonadotropin-releasing hormone (GnRH) challenge. Subjects treated with CORT during development had larger increases in CORT in response to ACTH challenge than food-restricted or control subjects. Neither treatment affected the responses of CORT to restraint or dexamethasone. CORT-treated males also had higher initial testosterone levels, but neither treatment affected testosterone levels post-GnRH. Lastly, although GnRH challenge failed to increase circulating estradiol levels in females, females exposed to food restriction or CORT treatment had lower estradiol levels than control females. These results show that exposure to stress can developmentally program the endocrine system of songbirds and illustrate the importance of considering developmental conditions when determining the factors responsible for inter-individual variation in endocrine regulation.

  8. Developmental Dynamics of Intergroup Contact and Intergroup Attitudes: Long-Term Effects in Adolescence and Early Adulthood.

    PubMed

    Wölfer, Ralf; Schmid, Katharina; Hewstone, Miles; van Zalk, Maarten

    2016-09-01

    Intergroup contact represents a powerful way to improve intergroup attitudes and to overcome prejudice and discrimination. However, long-term effects of intergroup contact that consider social network dynamics have rarely been studied at a young age. Study 1 validated an optimized social network approach to investigate intergroup contact (N = 6,457; Mage  = 14.91 years). Study 2 explored the developmental trajectories of intergroup contact by applying this validated network approach in a cross-sequential design (four-cohort-four-wave; N = 3,815; 13-26 years). Accelerated growth curve models showed that contact predicts the development of attitudes in adolescence, whereas acquired attitudes buffer against decreasing contact in adulthood. Findings highlight the potential of social network analysis and the developmental importance of early intergroup contact experiences. PMID:27684399

  9. Origin of Cardiomyocytes in the Adult Heart

    PubMed Central

    Leri, Annarosa; Rota, Marcello; Pasqualini, Francesco S.; Goichberg, Polina; Anversa, Piero

    2014-01-01

    This review article discusses the mechanisms of cardiomyogenesis in the adult heart. They include the reentry of cardiomyocytes into the cell cycle; dedifferentiation of preexisting cardiomyocytes which assume an immature replicating cell phenotype; transdifferentiation of hematopoietic stem cells into cardiomyocytes; and cardiomyocytes derived from activation and lineage specification of resident cardiac stem cells. The recognition of the origin of cardiomyocytes is of critical importance for the development of strategies capable of enhancing the growth response of the myocardium; in fact, cell therapy for the decompensated heart has to be based on the acquisition of this fundamental biological knowledge. PMID:25552694

  10. Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis

    PubMed Central

    Li, Haisen; Yue, Rui; Wei, Bin; Gao, Ge; Du, Jiulin; Pei, Gang

    2014-01-01

    Primitive hematopoiesis occurs in the yolk sac blood islands during vertebrate embryogenesis, where abundant phosphatidylcholines (PC) are available as important nutrients for the developing embryo. However, whether these phospholipids also generate developmental cues to promote hematopoiesis is largely unknown. Here, we show that lysophosphatidic acid (LPA), a signaling molecule derived from PC, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 (LPAR1) or autotoxin (ATX), a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. Mechanistic experiments revealed that the regulatory effect of ATX-LPA signaling was mediated by PI3K/Akt-Smad pathway. Furthermore, during in vivo embryogenesis in zebrafish, LPA functioned as a developmental cue for hemangioblast formation and primitive hematopoiesis. Taken together, we identified LPA as an important nutrient-derived developmental cue for primitive hematopoiesis as well as a novel mechanism of hemangioblast regulation. PMID:24829209

  11. Atypical perinatal sensory stimulation and early perceptual development: insights from developmental psychobiology.

    PubMed

    Lickliter, R

    2000-12-01

    Comparative studies utilizing avian and mammalian embryos and neonates have proven particularly useful in exploring how alterations in sensory experience during the perinatal period can affect subsequent development. This article reviews research drawn from comparative developmental psychobiology and concludes that the effects of modified sensory stimulation on perceptual and behavioral development depend on several related factors, including the timing of stimulation relative to the developmental stage of the young organism, the overall amount of sensory stimulation provided or denied, and the type of sensory stimulation presented. Directions for future research on the care of the high-risk infant are discussed.

  12. 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.

  13. 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

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

    PubMed

    Champhekar, Ameya; Damle, Sagar S; Freedman, George; Carotta, Sebastian; Nutt, Stephen L; Rothenberg, Ellen V

    2015-04-15

    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.

  15. 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

  16. 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…

  17. 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…

  18. BRIGANCE(TM) Diagnostic Inventory of Early Development Including Developmental Record Book.

    ERIC Educational Resources Information Center

    Brigance, Albert H.

    Designed for use with infants and children below the developmental level of seven years, the guide contains diagnostic and instructional information on skills in the following 11 areas (sample skills in parentheses): pre-ambulatory motor skills and behaviors, gross motor skills and behaviors (hopping, kicking, rhythm), fine motor skills and…

  19. Using "Constraints" to Design Developmentally Appropriate Movement Activities for Early Childhood Education

    ERIC Educational Resources Information Center

    Gagen, Linda M.; Getchell, Nancy

    2006-01-01

    Teachers of young children know the importance of designing developmentally appropriate activities to encourage motor development but are not always prepared with the information they need to accomplish this design. When teachers choose movement activities, motor development theory must be understood and utilized in the planning of activities to…

  20. 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…

  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. Multiage Programming Effects on Cognitive Developmental Level and Reading Achievement in Early Elementary School Children

    ERIC Educational Resources Information Center

    Fosco, Andrea M.; Schleser, Robert; Andal, Jolynne

    2004-01-01

    Differences in cognitive developmental level and reading achievement of elementary school children in multiage programming and traditional classrooms were explored. There is controversy regarding the benefit of multiage classrooms for learning academic subjects. According to previous research (e.g., Almy, Chittenden, & Miller, 1967; Brekke,…

  3. 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…

  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. 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…

  6. Thinking about Feelings: Emotion Focus in the Parenting of Children with Early Developmental Risk

    ERIC Educational Resources Information Center

    Baker, J. K.; Crnic, K. A.

    2009-01-01

    Background: Children with developmental delays exhibit more difficulty with certain emotional processes than their typically developing peers, which seems to partially account for the increased risk for the development of social problems in this population. Despite considerable study with typically developing populations, research on parental…

  7. Identification and Characterization of Genes Required for Early Myxococcus xanthus Developmental Gene Expression

    PubMed Central

    Guo, Dongchuan; Wu, Yun; Kaplan, Heidi B.

    2000-01-01

    Starvation and cell density regulate the developmental expression of Myxococcus xanthus gene 4521. Three classes of mutants allow expression of this developmental gene during growth on nutrient agar, such that colonies of strains containing a Tn5 lac Ω4521 fusion are Lac+. One class of these mutants inactivates SasN, a negative regulator of 4521 expression; another class activates SasS, a sensor kinase-positive regulator of 4521 expression; and a third class blocks lipopolysaccharide (LPS) O-antigen biosynthesis. To identify additional positive regulators of 4521 expression, 11 Lac− TnV.AS transposon insertion mutants were isolated from a screen of 18,000 Lac+ LPS O-antigen mutants containing Tn5 lac Ω4521 (Tcr). Ten mutations identified genes that could encode positive regulators of 4521 developmental expression based on their ability to abolish 4521 expression during development in the absence of LPS O antigen and in an otherwise wild-type background. Eight of these mutations mapped to the sasB locus, which encodes the known 4521 regulators SasS and SasN. One mapped to sasS, whereas seven identified new genes. Three mutations mapped to a gene encoding an NtrC-like response regulator homologue, designated sasR, and four others mapped to a gene designated sasP. One mutation, designated ssp10, specifically suppressed the LPS O-antigen defect; the ssp10 mutation had no effect on 4521 expression in an otherwise wild-type background but reduced 4521 developmental expression in the absence of LPS O antigen to a level close to that of the parent strain. All of the mutations except those in sasP conferred defects during growth and development. These data indicate that a number of elements are required for 4521 developmental expression and that most of these are necessary for normal growth and fruiting body development. PMID:10913090

  8. 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

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

    PubMed

    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.

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

    PubMed

    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

  11. Developmental progression to early adult binge drinking and marijuana use from worsening versus stable trajectories of adolescent ADHD and delinquency

    PubMed Central

    Howard, Andrea L.; Molina, Brooke S. G.; Swanson, James M.; Hinshaw, Stephen P.; Belendiuk, Katherine A.; Harty, Seth C.; Arnold, L. Eugene; Abikoff, Howard B.; Hechtman, Lily; Stehli, Annamarie; Greenhill, Laurence L.; Newcorn, Jeffrey H.; Wigal, Timothy

    2015-01-01

    Aims To examine the association between developmental trajectories of inattention, hyperactivity-impulsivity, and delinquency through childhood and adolescence (ages 8-16) and subsequent binge drinking and marijuana use in early adulthood (age 21). Design Prospective naturalistic follow-up of children with attention-deficit/hyperactivity disorder (ADHD) previously enrolled in a randomized controlled trial (RCT). Treatment-phase assessments occurred at 3, 9, and 14 months after randomization; follow-up assessments occurred at 24 months, 36 months, and 6, 8, and 12 years after randomization. Setting Secondary analysis of data from the Multimodal Treatment Study of ADHD (MTA), a multi-site RCT comparing the effects of careful medication management, intensive behavior therapy, their combination, and referral to usual community care. Participants 579 children with DSM-IV ADHD combined type, aged 7.0 and 9.9 years old at baseline (M=8.5, SD=.80). Measurements Ratings of inattention, hyperactivity-impulsivity, and delinquency were collected from multiple informants at baseline and through the 8-year follow-up. Self-reports of binge drinking and marijuana use were collected at the 12-year follow-up (M age 21). Findings Trajectories of worsening inattention symptoms and delinquency (and less apparent improvement in hyperactivity-impulsivity) were associated with higher rates of early adult binge drinking and marijuana use, compared with trajectories of stable or improving symptoms and delinquency (of 24 comparisons, 22 p-values <.05), even when symptom levels in stable trajectories were high. Conclusions Worsening inattention symptoms and delinquency during adolescence are associated with increased-levels of early adult substance use; this pattern may reflect a developmental course of vulnerability to elevated substance use in early adulthood. PMID:25664657

  12. 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.

  13. 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

  14. 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. PMID:11523842

  15. 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 education"…

  16. The Developmental Relationship between Language and Low Early Numeracy Skills throughout Kindergarten

    ERIC Educational Resources Information Center

    Toll, Sylke W. M.; Van Luit, Johannes E. H.

    2014-01-01

    The relationship between basic oral language and early numeracy has been studied extensively, but results hardly include kindergartners' math language, which might mediate this relationship. The aim of this study was to investigate the development of basic language skills--specifically, math language and low early numeracy. Dutch children…

  17. Predicting the Early Developmental Course of Symptoms of Attention Deficit Hyperactivity Disorder

    ERIC Educational Resources Information Center

    von Stauffenberg, Camilla; Campbell, Susan B.

    2007-01-01

    Data from the National Institute of Child Health and Human Development Study of Early Child Care were examined to test whether: attention deficit/hyperactivity disorder (ADHD) symptoms remain stable from 54 months through early elementary school; behavioral inhibition and attention deficits assessed at 54 months predict ADHD symptoms in elementary…

  18. 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…

  19. Early predictors of helpless thoughts and behaviors in children: developmental precursors to depressive cognitions.

    PubMed

    Cole, David A; Warren, Dana E; Dallaire, Danielle H; Lagrange, Beth; Travis, Rebekah; Ciesla, Jeffrey A

    2007-04-01

    Learned helplessness behavior and cognitions were assessed in 95 kindergarten-age children during a series of impossible puzzle trials followed by a solvable puzzle trial. Latent growth curve analysis revealed reliable individual differences in the trajectories of children's affect, motivation, and self-cognitions over time. Parents' reports of negative life events, harsh/negative parenting, and warm/positive parenting were associated with their children's learned helplessness behavioral trajectories and outcomes over the course of the puzzle trials. Results support speculations about the developmental origins of depressive explanatory or attributional style in children. PMID:17533942

  20. 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. PMID:2328914

  1. 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.

  2. 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.

  3. Early Influences and Later Outcomes Associated With Developmental Trajectories of Eriksonian Fidelity

    PubMed Central

    Brittian, Aerika S.; Lerner, Richard M.

    2014-01-01

    Although Eriksonian theory suggests that adolescents’ sense of fidelity is a key component of healthy development, research on this psychosocial construct has been limited. The current study developed an index of youth fidelity, examined the developmental course of this construct, explored the influence of contextual factors on different fidelity trajectories, and tested if trajectories were associated with later indicators of adolescents’ positive development. Participants included 1,941 ethnically diverse youth (61% female) participants in the 4-H Study of Positive Youth Development who were recruited from schools and youth development programs across the United States. Results suggested that three types of developmental trajectories existed among youth: high and increasing, moderate and increasing, and low and decreasing. Fidelity group membership varied in relation to social relationships and psychosocial and behavioral characteristics (i.e., contribution, substance use, and delinquency). Girls were more likely than boys to be in the highest fidelity trajectories. Directions for future research and implications for enhancing the thriving of adolescents are discussed. PMID:22545838

  4. 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.

  5. 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

  6. Developmental toxicity and endocrine disruption of naphthenic acids on the early life stage of zebrafish (Danio rerio).

    PubMed

    Wang, Jie; Cao, Xiaofeng; Huang, Yi; Tang, Xiaoyan

    2015-12-01

    Oil sands process-affected water (OSPW) has been reported to exhibit adverse effects on the environment and wildlife. Although the compounds responsible are unknown, naphthenic acids (NAs) have been considered to be implicated. The current study was designed to investigate whether NAs might cause developmental toxicity and endocrine disruption on the early life stage of zebrafish (Danio rerio). The success of embryo hatch was inhibited by 2.5 mg l(-1) oil sands NAs (OS-NAs) exposure, and both OSPW NAs and commercial NAs (C-NAs) exposure resulted in a variety of developmental lesions in the fish larvae, such as yolk sac edema, pericardial edema and spinal malformation. The transcription of genes involved cytochrome P450 aromatase (CYP19a and CYP19b), estrogen receptors (ERα, ERβ1 and ERβ2), and vitellogenin (VTG) was analyzed to evaluate the endocrine disrupting effects of NAs. Significant up-regulated gene expressions of CYP19b, ERα and VTG were observed in both OS-NAs and C-NAs groups, which indicated the deleteriously estrogenic potential of NAs. These results confirmed that NAs derived from crude petroleum could negatively impact the development and endocrine function of zebrafish, and be primarily responsible for the toxicity of OSPW.

  7. Developmental toxicity and endocrine disruption of naphthenic acids on the early life stage of zebrafish (Danio rerio).

    PubMed

    Wang, Jie; Cao, Xiaofeng; Huang, Yi; Tang, Xiaoyan

    2015-12-01

    Oil sands process-affected water (OSPW) has been reported to exhibit adverse effects on the environment and wildlife. Although the compounds responsible are unknown, naphthenic acids (NAs) have been considered to be implicated. The current study was designed to investigate whether NAs might cause developmental toxicity and endocrine disruption on the early life stage of zebrafish (Danio rerio). The success of embryo hatch was inhibited by 2.5 mg l(-1) oil sands NAs (OS-NAs) exposure, and both OSPW NAs and commercial NAs (C-NAs) exposure resulted in a variety of developmental lesions in the fish larvae, such as yolk sac edema, pericardial edema and spinal malformation. The transcription of genes involved cytochrome P450 aromatase (CYP19a and CYP19b), estrogen receptors (ERα, ERβ1 and ERβ2), and vitellogenin (VTG) was analyzed to evaluate the endocrine disrupting effects of NAs. Significant up-regulated gene expressions of CYP19b, ERα and VTG were observed in both OS-NAs and C-NAs groups, which indicated the deleteriously estrogenic potential of NAs. These results confirmed that NAs derived from crude petroleum could negatively impact the development and endocrine function of zebrafish, and be primarily responsible for the toxicity of OSPW. PMID:25995127

  8. Developmental differences in early adolescent aggression: a gene × environment × intervention analysis.

    PubMed

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

    2015-03-01

    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.

  9. Early biases and developmental changes in self-generated object views.

    PubMed

    Pereira, Alfredo F; James, Karin H; Jones, Susan S; Smith, Linda B

    2010-01-01

    Object recognition depends on the seen views of objects. These views depend in part on the perceivers' own actions as they select and show object views to themselves. The self-selection of object views from manual exploration of objects during infancy and childhood may be particularly informative about the human object recognition system and its development. Here, we report for the first time on the structure of object views generated by 12 to 36 month old children (N = 54) and for comparison adults (N = 17) during manual and visual exploration of objects. Object views were recorded via a tiny video camera placed low on the participant's forehead. The findings indicate two viewing biases that grow rapidly in the first three years: a bias for planar views and for views of objects in an upright position. These biases also strongly characterize adult viewing. We discuss the implications of these findings for a developmentally complete theory of object recognition. PMID:20884517

  10. Motion perception: a review of developmental changes and the role of early visual experience

    PubMed Central

    Hadad, Batsheva; Schwartz, Sivan; Maurer, Daphne; Lewis, Terri L.

    2015-01-01

    Significant controversies have arisen over the developmental trajectory for the perception of global motion. Studies diverge on the age at which it becomes adult-like, with estimates ranging from as young as 3 years to as old as 16. In this article, we review these apparently conflicting results and suggest a potentially unifying hypothesis that may also account for the contradictory literature in neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD). We also discuss the extent to which patterned visual input during this period is necessary for the later development of motion perception. We conclude by addressing recent studies directly comparing different types of motion integration, both in typical and atypical development, and suggest areas ripe for future research. PMID:26441564

  11. Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells

    PubMed Central

    Ikawa, Tomokatsu; Masuda, Kyoko; Huijskens, Mirelle J.A.J.; Satoh, Rumi; Kakugawa, Kiyokazu; Agata, Yasutoshi; Miyai, Tomohiro; Germeraad, Wilfred T.V.; Katsura, Yoshimoto; Kawamoto, Hiroshi

    2015-01-01

    Summary Self-renewal potential and multipotency are hallmarks of a stem cell. It is generally accepted that acquisition of such stemness requires rejuvenation of somatic cells through reprogramming of their genetic and epigenetic status. We show here that a simple block of cell differentiation is sufficient to induce and maintain stem cells. By overexpression of the transcriptional inhibitor ID3 in murine hematopoietic progenitor cells and cultivation under B cell induction conditions, the cells undergo developmental arrest and enter a self-renewal cycle. These cells can be maintained in vitro almost indefinitely, and the long-term cultured cells exhibit robust multi-lineage reconstitution when transferred into irradiated mice. These cells can be cloned and re-expanded with 50% plating efficiency, indicating that virtually all cells are self-renewing. Equivalent progenitors were produced from human cord blood stem cells, and these will ultimately be useful as a source of cells for immune cell therapy. PMID:26607950

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

    PubMed Central

    Schwebs, David J.; Hadwiger, Jeffrey A.

    2014-01-01

    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. PMID:25451080

  13. 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

  14. 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.

  15. Trait canalization analysis of water quality, temperature, and developmental associations with early life stages of two fish species.

    PubMed

    Simon, Thomas P

    2015-06-01

    Evaluation of trait robustness based on environmental fluctuation in ontogenetic life stages are needed to evaluate stability and trait response during critical developmental events. Hardness, alkalinity, acidity, light intensity, and thermal differences were studied for trait canalization variation in morphometric, meristic, ontogenetic processes, and pigment characteristics. Trait canalization was observed with no statistical differences (p > 0.05) in mixed random two-way ANOVA comparisons between various block and treatment effects for hardness, alkalinity or acidity. Thermal block variation differences in six measures, including mandible length, yolk sac length, midpostanal depth, and head width, incubation, and hatching length, varied significantly (p ≤ 0.05) with declining temperatures. Water quality and thermal attributes exhibited trait canalization and did not increase character state variation in the early life stage morphological expression, which result in stable phenotypic inheritance rather than variable environmental conditions during embryonic and larval development.

  16. 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

  17. 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

  18. 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.

  19. Functional Differences in Engineered Myocardium from Embryonic Stem Cell-Derived versus Neonatal Cardiomyocytes

    PubMed Central

    Feinberg, Adam W.; Ripplinger, Crystal M.; van der Meer, Peter; Sheehy, Sean P.; Domian, Ibrahim; Chien, Kenneth R.; Parker, Kevin Kit

    2013-01-01

    Summary Stem cell-derived cardiomyocytes represent unique tools for cell- and tissue-based regenerative therapies, drug discovery and safety, and studies of fundamental heart-failure mechanisms. However, the degree to which stem cell-derived cardiomyocytes compare to mature cardiomyocytes is often debated. We reasoned that physiological metrics of engineered cardiac tissues offer a means of comparison. We built laminar myocardium engineered from cardiomyocytes that were differentiated from mouse embryonic stem cell-derived cardiac progenitors or harvested directly from neonatal mouse ventricles, and compared their anatomy and physiology in vitro. Tissues assembled from progenitor-derived myocytes and neonate myocytes demonstrated similar cytoskeletal architectures but different gap junction organization and electromechanical properties. Progenitor-derived myocardium had significantly less contractile stress and slower longitudinal conduction velocity than neonate-derived myocardium, indicating that the developmental state of the cardiomyocytes affects the electromechanical function of the resultant engineered tissue. These data suggest a need to establish performance metrics for future stem cell applications. PMID:24286027

  20. Cardiomyocytes display low mitochondrial priming and are highly resistant toward cytotoxic T‐cell killing

    PubMed Central

    Zheng, Xiang; Halle, Stephan; Yu, Kai; Mishra, Pooja; Scherr, Michaela; Pietzsch, Stefan; Willenzon, Stefanie; Janssen, Anika; Boelter, Jasmin; Hilfiker‐Kleiner, Denise; Eder, Matthias

    2016-01-01

    Following heart transplantation, alloimmune responses can cause graft rejection by damaging donor vascular and parenchymal cells. However, it remains unclear whether cardiomyocytes are also directly killed by immune cells. Here, we used two‐photon microscopy to investigate how graft‐specific effector CD8+ T cells interact with cardiomyocytes in a mouse heart transplantation model. Surprisingly, we observed that CD8+ T cells are completely impaired in killing cardiomyocytes. Even after virus‐mediated preactivation, antigen‐specific CD8+ T cells largely fail to lyse these cells although both cell types engage in dynamic interactions. Furthermore, we established a two‐photon microscopy‐based assay using intact myocardium to determine the susceptibility of cardiomyocytes to undergo apoptosis. This feature, also known as mitochondrial priming reveals an unexpected weak predisposition of cardiomyocytes to undergo apoptosis in situ. These observations together with the early exhaustion phenotype of graft‐infiltrating specific T cells provide an explanation why cardiomyocytes are largely protected from direct CD8+ T‐cell‐mediated killing. PMID:26970349

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. The Fate of Early Experience Following Developmental Change: Longitudinal Approaches to Individual Adaptation in Childhood.

    ERIC Educational Resources Information Center

    Sroufe, L. Alan; And Others

    1990-01-01

    Examined Bowlby's proposition that early experiences and the adaptations to which they give rise influence later development, even beyond the influence of current circumstances or very recent adaptation. Groups whose adaptation were similar during preschool years but consistently different earlier were defined and compared. Results supported…

  12. The Effect of Early Stimulation: The Problem of Focus in Developmental Stimulation.

    ERIC Educational Resources Information Center

    Fowler, William

    Studies of the effect of environmental stimulation on an individual's development in either general or specific ability conclude that some specific stimulation should be introduced at an early age while a child is still malleable. An intense, persistent, and regular tutorial approach within the family encourages the development of a special talent…

  13. 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 inadequate…

  14. 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

  15. 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.

  16. 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

    2009-04-01

    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.

  17. 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

    2009-04-01

    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. PMID:19342590

  18. Epigenetic changes caused by intrauterine malnutrition as potential disease mediator and early prevention in developmental stages.

    PubMed

    Fukuoka, Hideoki

    2014-01-01

    Presently, the incidences of noncommunicable diseases (NCD) have been increasing in both low- and middle-income countries worldwidely. Effective long-term and multigeneration interventions to decrease the risk of NCD should be developed and introduced. The environment in utero alters phenotypes mainly through epigenetic mechanisms. The epigenetic changes induced in an unfavorable developmental environment have lifelong effects on cardiovascular and metabolic functions, susceptibility to cardiovascular disease, obesity, and other NCD. Although compared with animals, epigenetic analysis of human specimens is restricted except for peripheral blood, placental, or umbilical specimens, recently, important human studies have been reported concerning the epigenetic analysis of Line 1 gene from the umbilical blood, umbilical RXRα, or the peripheral nuclear cell IGF-2. The birth weight is an indirect marker of in-the-womb nutritional status. The incidence of low-birth-weight infants, weighing less than 2,500 g, has been increasing in Japan. Presently, it is higher than that in the latter half of the 20 s of the Showa era, and is the highest among the OECD countries. This trend suggests that in Japan the intrauterine nutritional status has been deteriorating. We have to change this trend and put much attention on the prepregnancy and pregnancy nutrition for the present and future generations. PMID:24858500

  19. Glutathione transferase isoenzymes from Bufo bufo embryos at an early developmental stage.

    PubMed Central

    Di Ilio, C; Aceto, A; Bucciarelli, T; Dragani, B; Angelucci, S; Miranda, M; Poma, A; Amicarelli, F; Barra, D; Federici, G

    1992-01-01

    Six forms of glutathione transferase (GST) were resolved from the cytosolic fraction of Bufo bufo embryos at developmental stage 4 by GSH-Sepharose affinity chromatography followed by f.p.l.c. chromatofocusing in the 9-6 pH range. They have apparent isoelectric points at pH 8.37 (GST I), 8.22 (GST II), 8.10 (GST III), 7.84 (GST IV), 7.37 (GST V) and 7.12 (GST VI), and each displayed an apparent subunit molecular mass of 23 kDa by SDS/PAGE. The Bufo bufo embryo enzymes showed very similar structural, catalytic and immunological properties, as indicated by their substrate-specificities, inhibition characteristics, c.d. spectra, h.p.l.c. elution profiles and immunological reactivities, as well as by their N-terminal amino acid sequences. Although Bufo bufo embryo GSTs do not correspond to any other known GSTs, the results of our experiments indicate that amphibian GSTs could be included in the Pi family of GSTs. This conclusion is supported by the analysis of c.d. spectra, and by the fact that mammalian Pi class GSTs and amphibian GSTs showed about 80% identity in their N-terminal amino acid sequences. Furthermore, antisera prepared against Bufo bufo GST III cross-reacted in immunoblotting analysis with Pi class GSTs, and vice versa. Images Fig. 2. Fig. 3. PMID:1567369

  20. 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.

  1. Developmental Patterns of Social Trust between Early and Late Adolescence: Age and School Climate Effects

    PubMed Central

    Flanagan, Constance A.; Stout, Michael

    2010-01-01

    Social trust (i.e., beliefs that people are generally fair and trustworthy) is important to the functioning of democracies and trend studies show it has declined. We test hypotheses concerning the development of these beliefs in adolescence. Based on surveys of 1535 adolescents collected over two years, we find that middle and late adolescents had significantly lower levels of trust than early adolescents and that these beliefs became more stable and less related to interpersonal trust between early and late adolescence. Results of multiple group SEMs revealed that, regardless of age, adolescents’ reports that a strong sense of student solidarity characterized their school significantly increased ST at T2, controlling for levels at T1, and opportunities to exchange perspectives with fellow students increased ST at T2 indirectly, through feelings of student solidarity. The study points to the role of schools in nurturing the democratic dispositions of younger generations. PMID:20936077

  2. A developmental characterization of mesolimbocortical serotonergic gene expression changes following early immune challenge.

    PubMed

    Sidor, M M; Amath, A; MacQueen, G; Foster, J A

    2010-12-15

    An immunogenic challenge during early postnatal development leads to long-term changes in behavioural and physiological measures reflecting enhanced emotionality and anxiety. Altered CNS serotonin (5-HT) signalling during the third postnatal week is thought to modify the developing neurocircuitry governing anxiety-like behaviour. Changes in 5-HT signalling during this time window may underlie increased emotionality reported in early immune challenge rodents. Here we examine both the spatial and temporal profile of 5-HT related gene expression, including 5HT1A, 2A, 2C receptors, the 5-HT transporter (5HTT), and tryptophan hydroxylase 2 (TPH2) during early development (postnatal day [P]14, P17, P21, P28) in mice challenged with lipopolysaccharide (LPS) during the first postnatal week. Expression levels were measured using in situ hybridization in regions associated with mediating emotive behaviours: the dorsal raphe (DR), hippocampus, amygdala, and prefrontal cortex (PFC). Increased TPH2 and 5HTT expression in the ventrolateral region of the DR of LPS-mice accompanied decreased expression of ventral DR 5HT1A and dorsal DR 5HTT. In the forebrain, 5HT1A and 2A receptors were increased, whereas 5HT2C receptors were decreased in the hippocampus. Decreased mRNA expression of 5HT2C was detected in the amygdala and PFC of LPS-treated pups; 5HT1A was increased in the PFC. The majority of these changes were restricted to P14-21. These transient changes in 5-HT expression coincide with the critical time window in which 5-HT disturbance leads to permanent modification of anxiety-related behaviours. This suggests that alterations in CNS 5-HT during development may underlie the enhanced emotionality associated with an early immune challenge. PMID:20816924

  3. Developmental tumours, early differentiation and the transforming growth factor beta superfamily.

    PubMed

    Mummery, C L; van den Eijnden-van Raaij, A J

    1999-01-01

    Embryonal carcinoma and embryonic stem cells have been very useful models for identifying some of the factors that regulate differentiation in early mammalian development. Here, we present a brief history of their original isolation and characterization and of their later introduction into the Hubrecht Laboratory. We illustrate in a review their contribution to our current understanding of the function of transforming growth factor beta and ligands binding to the receptors of a related factor, activin, in development with some of our own work.

  4. Maternal separation with early weaning: a rodent model providing novel insights into neglect associated developmental deficits.

    PubMed

    Carlyle, Becky C; Duque, Alvaro; Kitchen, Robert R; Bordner, Kelly A; Coman, Daniel; Doolittle, Eliza; Papademetris, Xenophonios; Hyder, Fahmeed; Taylor, Jane R; Simen, Arthur A

    2012-11-01

    Child neglect is the most prevalent form of child maltreatment in the United States, and poses a serious public health concern. Children who survive such episodes go on to experience long-lasting psychological and behavioral problems, including higher rates of post-traumatic stress disorder symptoms, depression, alcohol and drug abuse, attention-deficit/hyperactivity disorder, and cognitive deficits. To date, most research into the causes of these life-long problems has focused on well-established targets such as stress responsive systems, including the hypothalamus-pituitary-adrenal axis. Using the maternal separation and early weaning model, we have attempted to provide comprehensive molecular profiling of a model of early-life neglect in an organism amenable to genomic manipulation: the mouse. In this article, we report new findings generated with this model using chromatin immunoprecipitation sequencing, diffuse tensor magnetic resonance imaging, and behavioral analyses. We also review the validity of the maternal separation and early weaning model, which reflects behavioral deficits observed in neglected humans including hyperactivity, anxiety, and attentional deficits. Finally, we summarize the molecular characterization of these animals, including RNA profiling and label-free proteomics, which highlight protein translation and myelination as novel pathways of interest. PMID:23062306

  5. Maternal separation with early weaning: A rodent model providing novel insights into neglect associated developmental deficits

    PubMed Central

    CARLYLE, BECKY C.; DUQUE, ALVARO; KITCHEN, ROBERT R.; BORDNER, KELLY A.; COMAN, DANIEL; DOOLITTLE, ELIZA; PAPADEMETRIS, XENOPHONIOS; HYDER, FAHMEED; TAYLOR, JANE R.; SIMEN, ARTHUR A.

    2013-01-01

    Child neglect is the most prevalent form of child maltreatment in the United States, and poses a serious public health concern. Children who survive such episodes go on to experience long-lasting psychological and behavioral problems, including higher rates of post-traumatic stress disorder symptoms, depression, alcohol and drug abuse, attention-deficit/hyperactivity disorder, and cognitive deficits. To date, most research into the causes of these life-long problems has focused on well-established targets such as stress responsive systems, including the hypothalamus–pituitary–adrenal axis. Using the maternal separation and early weaning model, we have attempted to provide comprehensive molecular profiling of a model of early-life neglect in an organism amenable to genomic manipulation: the mouse. In this article, we report new findings generated with this model using chromatin immunoprecipitation sequencing, diffuse tensor magnetic resonance imaging, and behavioral analyses. We also review the validity of the maternal separation and early weaning model, which reflects behavioral deficits observed in neglected humans including hyperactivity, anxiety, and attentional deficits. Finally, we summarize the molecular characterization of these animals, including RNA profiling and label-free proteomics, which highlight protein translation and myelination as novel pathways of interest. PMID:23062306

  6. 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,…

  7. 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…

  8. 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…

  9. 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,…

  10. 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,…

  11. Developmental Links of Very Early Phonological and Language Skills to Second Grade Reading Outcomes: Strong to Accuracy but Only Minor to Fluency

    ERIC Educational Resources Information Center

    Puolakanaho, Anne; Ahonen, Timo; Aro, Mikko; Eklund, Kenneth; Leppanen, Paavo H. T.; Poikkeus, Anna-Maija; Tolvanen, Asko; Torppa, Minna; Lyytinen, Heikki

    2008-01-01

    The authors examined second grade reading accuracy and fluency and their associations via letter knowledge to phonological and language predictors assessed at 3.5, 4.5, and 5.5 years in children in the Jyvaskyla Longitudinal Study of Dyslexia. Structural equation modeling showed that a developmentally highly stable factor (early phonological and…

  12. Risk Factors of Children Who Exited from an Early Intervention Program without an Identified Disability and Returned with a Developmental Disability

    ERIC Educational Resources Information Center

    Giannoni, Peggy P.; Kass, Philip H.

    2010-01-01

    A retrospective cohort study was undertaken to identify risk factors for children at greatest risk of delayed diagnosis of developmental disability. Two thousand four hundred and thirty-nine children were selected for this study due to their participation in the California Early Start (ES) Program in 1998. Comparisons were made among children that…

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  19. BMPER regulates cardiomyocyte size and vessel density in vivo

    PubMed Central

    Willis, Monte S.; Dyer, Laura A.; Ren, Rongqin; Lockyer, Pamela; Moreno-Miralles, Isabel; Schisler, Jonathan C.; Patterson, Cam

    2016-01-01

    Background BMPER, an orthologue of Drosophila melanogaster Crossveinless-2, is a secreted factor that regulates bone morphogenetic protein activity in endothelial cell precursors and during early cardiomyocyte differentiation. Although previously described in the heart, the role of BMPER in cardiac development and function remain unknown. Methods BMPER-deficient hearts were phenotyped histologically and functionally using echocardiography and Doppler analysis. Since BMPER −/− mice die perinatally, adult BMPER +/− mice were challenged to pressure-overload-induced cardiac hypertrophy and hindlimb ischemia to determine changes in angiogenesis and regulation of cardiomyocyte size. Results We identify for the first time the cardiac phenotype associated with BMPER haploinsufficiency. BMPER messenger RNA and protein are present in the heart during cardiac development through at least E14.5 but is lost by E18.5. BMPER +/− ventricles are thinner and less compact than sibling wild-type hearts. In the adult, BMPER +/− hearts present with decreased anterior and posterior wall thickness, decreased cardiomyocyte size and an increase in cardiac vessel density. Despite these changes, BMPER +/− mice respond to pressure-overload-induced cardiac hypertrophy challenge largely to the same extent as wild-type mice. Conclusion BMPER appears to play a role in regulating both vessel density and cardiac development in vivo; however, BMPER haploinsufficiency does not result in marked effects on cardiac function or adaptation to pressure overload hypertrophy. PMID:23200275

  20. Examining cardiomyocyte development with spectral domain phase microscopy

    NASA Astrophysics Data System (ADS)

    Ellerbee, Audrey K.; Creazzo, Tony L.; Izatt, Joseph A.

    2007-02-01

    Phase-sensitive detection has long been recognized as a mechanism for increasing imaging contrast. The proliferation of quantitative phase contrast techniques and the breadth of emerging applications reflects the potential for achieving subdiffraction- limited resolution of cellular structure and dynamic phenomena with phase. Our laboratory developed spectral domain phase microscopy (SDPM) as a simple, phase-stable tool for studying cell dynamics and structure. As a functional extension of optical coherence tomography (OCT), SDPM inherited the high-resolution depth-sectioning capabilities for which OCT is well known, but adds to this an ability to discriminate sub-coherence length changes in optical pathlength within target samples at discrete axial positions. Early demonstrations of SDPM showed it to be extremely sensitive to thickness changes in biological and non-biological samples; the results of our previous studies investigating cell surface motion in cardiomyocyte contractility, cytoplasmic streaming rates in single-celled organisms, and rheological properties of the cytoskeleton suggest that SDPM can contribute insights of biological relevance. The principal aim of this work is to refine SDPM to enable imaging, interrogation, and quantification of parameters of interest in developing cardiomyocytes. In this manuscript, we report on the technology advances that enable multidimensional SDPM, and the results of new inotropic imaging studies of chick embryo cardiomyocytes.

  1. Haptic grasping configurations in early infancy reveal different developmental profiles for visual guidance of the Reach versus the Grasp.

    PubMed

    Karl, Jenni M; Whishaw, Ian Q

    2014-10-01

    The Dual Visuomotor Channel theory posits that reaching consists of two movements mediated by separate but interacting visuomotor pathways that project from occipital to parietofrontal cortex. The Reach transports and orients the hand to the target while the Grasp opens and closes the hand for target purchase. Adults rely on foveal vision to synchronize the Reach and the Grasp so that the hand orients, opens, and largely closes by the time it gets to the target. Young infants produce discrete preReach and preGrasp movements, but it is unclear how these movements become synchronized under visual control throughout development. High-speed 3-D video recordings and linear kinematics were used to analyze reaching components, hand orientation, hand aperture, and grasping strategy in infants aged 4-24 months compared with adults who reached with and without vision. Infants aged 4-8 months resembled adults reaching without vision; in that, they delayed both Reach orientation and Grasp closure until after target contact, suggesting that they relied primarily on haptic cues to guide reaching. Infants aged 9-24 months oriented the Reach prior to target contact, but continued to delay the majority of Grasp closure until after target contact, suggesting that they relied on vision for the Reach versus haptics for the Grasp. Changes in sensorimotor control were associated with sequential Reach and Grasp configurations in early infancy versus partially synchronized Reach and Grasp configurations in later infancy. The results argue that (1) haptic inputs likely contribute to the initial development of separate Reach and Grasp pathways in parietofrontal cortex; (2) the Reach and the Grasp are adaptively uncoupled during development, likely to capitalize on different sensory inputs at different developmental stages; and (3) the developmental transition from haptic to visual control is asymmetrical with visual guidance of the Reach preceding that of the Grasp.

  2. Developmental plasticity, cell fate specification and morphogenesis in the early mouse embryo

    PubMed Central

    Bedzhov, Ivan; Graham, Sarah J. L.; Leung, Chuen Yan; Zernicka-Goetz, Magdalena

    2014-01-01

    A critical point in mammalian development is when the early embryo implants into its mother's uterus. This event has historically been difficult to study due to the fact that it occurs within the maternal tissue and therefore is hidden from view. In this review, we discuss how the mouse embryo is prepared for implantation and the molecular mechanisms involved in directing and coordinating this crucial event. Prior to implantation, the cells of the embryo are specified as precursors of future embryonic and extra-embryonic lineages. These preimplantation cell fate decisions rely on a combination of factors including cell polarity, position and cell–cell signalling and are influenced by the heterogeneity between early embryo cells. At the point of implantation, signalling events between the embryo and mother, and between the embryonic and extraembryonic compartments of the embryo itself, orchestrate a total reorganization of the embryo, coupled with a burst of cell proliferation. New developments in embryo culture and imaging techniques have recently revealed the growth and morphogenesis of the embryo at the time of implantation, leading to a new model for the blastocyst to egg cylinder transition. In this model, pluripotent cells that will give rise to the fetus self-organize into a polarized three-dimensional rosette-like structure that initiates egg cylinder formation. PMID:25349447

  3. Environmental factors during early developmental period influence psychobehavioral abnormalities in adult PACAP-deficient mice.

    PubMed

    Ishihama, Toshihiro; Ago, Yukio; Shintani, Norihito; Hashimoto, Hitoshi; Baba, Akemichi; Takuma, Kazuhiro; Matsuda, Toshio

    2010-06-19

    Mice lacking the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) (PACAP(-/-)) display behavioral abnormalities, and genetic variants of the genes encoding PACAP are associated with schizophrenia. Clinical studies show that environmental factors, besides genetic factors, play a key role in etiology of many psychiatric disorders. This study examined the effects of environmental factors such as short-term social isolation and an enriched environment on behavioral abnormalities of PACAP(-/-) mice. Rearing in isolation for 2-weeks from 4-weeks old induced hyperlocomotion and aggressive behaviors in the PACAP(-/-) mice without affecting the behavioral performance of the wild-type controls. Adult PACAP(-/-) mice showed not only hyperactivity, jumping behavior, and depression-like behavior, but also decreased social interaction. These abnormal behaviors were improved by rearing for 4-weeks in an early enriched environment (from 4-weeks old), although the deficits of prepulse inhibition (PPI) were not influenced by the enriched condition. In contrast, rearing for 4-weeks in late enriched environment (from 8-weeks old) did not affect the hyperactivity and jumping behaviors in the PACAP(-/-) mice. These results suggest that abnormal behaviors except PPI deficits in PACAP(-/-) mice depend on the environmental factors during the early stages of development.

  4. Intervening early to reduce developmentally harmful substance use among youth populations.

    PubMed

    Lubman, Dan I; Hides, Leanne; Yücel, Murat; Toumbourou, John W

    2007-10-01

    Early-onset or frequent substance use during adolescence increases the risk of developing mental health problems, as well as a range of other adverse outcomes (eg, alcohol or drug dependence, educational underachievement, health problems, social difficulties) during late adolescence and early adulthood. Increases in rates of risky drinking among young people are particularly concerning, suggesting that an effective, evidence-based alcohol policy and preventive framework needs to be developed. Restricting the supply of licit and illicit substances to adolescents, delaying the age that licit substances can be legally purchased, reducing positive media portrayals of substance use, and banning targeted promotions, should be universal, public prevention priorities. Mass-media campaigns need to deliver coherent and credible evidence-based messages to young people, utilising a broad array of dissemination strategies. Clear policy and guidelines for parents regarding appropriate alcohol use for adolescents also need to be developed. Prevention programs should target children and adolescents in families with parents who use drugs, young people who have been suspended from school, or those with mental health problems. Preventive screening and targeted brief interventions can be effectively delivered in a variety of settings by a range of health professionals.

  5. 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

  6. Early articular cartilage degeneration in a developmental dislocation of the hip model results from activation of β-catenin.

    PubMed

    Ning, Bo; Sun, Jun; Yuan, Yi; Yao, Jie; Wang, Peng; Ma, Ruixue

    2014-01-01

    Developmental dislocation or dysplasia of the hip (DDH) is one of the most common deformities in children. Osteoarthritis (OA) is the most frequent long-term complication. The molecular mechanism of early articular cartilage degeneration in DDH is still unclear. It is well known that β-catenin plays a crucial role in articular cartilage degeneration. The objective of this study was to verify the relationship between β-catenin and DDH cartilage degeneration. We used a DDH model that was established by modification of swaddling position in newborn Wistar rats. The hips were isolated from the DDH model rats and untreated control group at the age of 2, 4, 6 and 8 weeks. β-Catenin gene and protein were investigated by quantitative (q)RT-PCR and immunohistochemistry. Collagen X and matrix metalloproteinase (MMP)-13, markers of early cartilage degeneration, were assessed by qRT-PCR. Primary chondrocytes were cultured from cartilage of two groups at the age of 8 weeks. Expression of β-catenin, collagen X and MMP-13 was detected. Continued high expression of β-catenin was observed in cartilage from DDH model rats. mRNA and protein expression of β-catenin was significantly increased in primary chondrocytes of the DDH model compared with the control group. Collagen X and MMP-13 expression was higher in the cartilage and chondrocytes from DDH model rats than the control group. Our findings suggest that early cartilage degeneration in DDH may result from activation of β-catenin signaling. PMID:24817933

  7. 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.

  8. Clusterin: a protective mediator for ischemic cardiomyocytes?

    PubMed

    Krijnen, P A J; Cillessen, S A G M; Manoe, R; Muller, A; Visser, C A; Meijer, C J L M; Musters, R J P; Hack, C E; Aarden, L A; Niessen, H W M

    2005-11-01

    We examined the relationship between clusterin and activated complement in human heart infarction and evaluated the effect of this protein on ischemic rat neonatal cardiomyoblasts (H9c2) and isolated adult ventricular rat cardiomyocytes as in vitro models of acute myocardial infarction. Clusterin protects cells by inhibiting complement and colocalizes with complement on jeopardized human cardiomyocytes after infarction. The distribution of clusterin and complement factor C3d was evaluated in the infarcted human heart. We also analyzed the protein expression of clusterin in ischemic H9c2 cells. The binding of endogenous and purified human clusterin on H9c2 cells was analyzed by flow cytometry. Furthermore, the effect of clusterin on the viability of ischemically challenged H9c2 cells and isolated adult ventricular rat cardiomyocytes was analyzed. In human myocardial infarcts, clusterin was found on scattered, morphologically viable cardiomyocytes within the infarcted area that were negative for complement. In H9c2 cells, clusterin was rapidly expressed after ischemia. Its expression was reduced after reperfusion. Clusterin bound to single annexin V-positive or annexin V and propidium iodide-positive H9c2 cells. Clusterin inhibited ischemia-induced death in H9c2 cells as well as in isolated adult ventricular rat cardiomyocytes in the absence of complement. We conclude that ischemia induces the upregulation of clusterin in ischemically challenged, but viable, cardiomyocytes. Our data suggest that clusterin protects cardiomyocytes against ischemic cell death via a complement-independent pathway.

  9. Developmental Differences in Memory During Early Childhood: Insights From Event-Related Potentials

    PubMed Central

    Riggins, Tracy; Rollins, Leslie

    2014-01-01

    Age-related differences in behavioral and electrophysiological indices of memory were examined in 3-to-6-year-old children (n=76). Behaviorally, no differences were observed in children’s ability to identify old items; however, 3-year-old children were less accurate in correctly rejecting new items and 3- and 4-year-old children recalled fewer contextual details compared to 5- and 6-year-old children. Age-related differences in electrophysiological measures (800-1000ms after stimulus onset) were observed both to items recalled with contextual details, which increased between 3 and 4 years, and items recalled without contextual details, which were greatest in 5-year-old children, even after adjusting for global age-related differences. These findings, interpreted within a dual process framework, may suggest changes in both recollection and familiarity processes during early childhood. PMID:25677124

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

    PubMed Central

    Belsky, Jay; Pluess, Michael

    2015-01-01

    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 first grade—but not thereafter. Only children carrying the 7-repeat allele proved susceptible to quality-of-care effects. The behavior-problem interactions proved more consistent with diathesis-stress than differential-susceptibility thinking, whereas the reverse was true of the social-skills' results. Finally, the discerned gene-X-environment interactions did not account for previously reported parallel ones involving difficult temperament in infancy. PMID:23432522

  11. 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. PMID:26241857

  12. 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.

  13. Effects of lead exposure on D-serine metabolism in the hippocampus of mice at the early developmental stages.

    PubMed

    Yu, Haiyang; Li, Tingting; Cui, Yan; Liao, Yingjun; Wang, Gaoyang; Gao, Lanyue; Zhao, Fenghong; Jin, Yaping

    2014-11-01

    The aim of this study was to explore the mechanisms of lead neurotoxicity by focusing on the alteration of D-serine metabolism in the hippocampus of mice at the early life. Mother mice and their offspring were exposed to 0, 0.5, 1.0 and 2.0 g/L lead in lead acetate via drinking water from the first day of gestation until the postnatal day (PND) 40. Morris water maze was used to measure the spatial learning and memory ability of PND 40 mice. Expressions of serine racemase (SR), D-amino acid oxidase (DAAO), alanine-serine- cysteine transporter-1 (asc-1) and subunits of N-methyl-D-aspartate receptor (NMDAR) in the hippocampus of PND 10, 20 and 40 mice were examined by western blot and real time RT-PCR. Findings from this study disclosed that the spatial learning ability of mice tested by place trial could be significantly impaired by 0.5 g/L lead exposure, and the spatial memory ability tested by probe trail could be impaired by 1.0 g/L lead exposure. Exposure to 2.0 g/L lead in the water could significantly inhibit the protein and mRNA expression of SR; conversely enhance the expression of DAAO protein and mRNA in the hippocampus during the early developmental stages. However, the protein expressions of DAAO and asc-1 in the hippocampus were significantly enhanced by 0.5 g/L lead exposure at different developmental stages. On the other hand, the protein and mRNA expressions of both NR1 and NR2A were inhibited significantly by 1.0 g/L lead exposure since PND 10, and by 0.5 g/L lead exposure since PND 20. Noteworthy, the protein expression of NR2B was inhibited significantly by 0.5 g/L lead exposure in PND 10 mice, and by 1.0 g/L lead exposure in PND 20 mice, but there was no significant group difference in PND 40 mice. Meanwhile, expressions of asc-1 and NR2B mRNA were not affected obviously by lead exposure. In conclusion, chronic lead exposure during brain development might affect D-serine metabolism by enhancing its degradation, which might be related to the

  14. Effects of lead exposure on D-serine metabolism in the hippocampus of mice at the early developmental stages.

    PubMed

    Yu, Haiyang; Li, Tingting; Cui, Yan; Liao, Yingjun; Wang, Gaoyang; Gao, Lanyue; Zhao, Fenghong; Jin, Yaping

    2014-11-01

    The aim of this study was to explore the mechanisms of lead neurotoxicity by focusing on the alteration of D-serine metabolism in the hippocampus of mice at the early life. Mother mice and their offspring were exposed to 0, 0.5, 1.0 and 2.0 g/L lead in lead acetate via drinking water from the first day of gestation until the postnatal day (PND) 40. Morris water maze was used to measure the spatial learning and memory ability of PND 40 mice. Expressions of serine racemase (SR), D-amino acid oxidase (DAAO), alanine-serine- cysteine transporter-1 (asc-1) and subunits of N-methyl-D-aspartate receptor (NMDAR) in the hippocampus of PND 10, 20 and 40 mice were examined by western blot and real time RT-PCR. Findings from this study disclosed that the spatial learning ability of mice tested by place trial could be significantly impaired by 0.5 g/L lead exposure, and the spatial memory ability tested by probe trail could be impaired by 1.0 g/L lead exposure. Exposure to 2.0 g/L lead in the water could significantly inhibit the protein and mRNA expression of SR; conversely enhance the expression of DAAO protein and mRNA in the hippocampus during the early developmental stages. However, the protein expressions of DAAO and asc-1 in the hippocampus were significantly enhanced by 0.5 g/L lead exposure at different developmental stages. On the other hand, the protein and mRNA expressions of both NR1 and NR2A were inhibited significantly by 1.0 g/L lead exposure since PND 10, and by 0.5 g/L lead exposure since PND 20. Noteworthy, the protein expression of NR2B was inhibited significantly by 0.5 g/L lead exposure in PND 10 mice, and by 1.0 g/L lead exposure in PND 20 mice, but there was no significant group difference in PND 40 mice. Meanwhile, expressions of asc-1 and NR2B mRNA were not affected obviously by lead exposure. In conclusion, chronic lead exposure during brain development might affect D-serine metabolism by enhancing its degradation, which might be related to the

  15. Biochemical response to exposure to six textile dyes in early developmental stages of Xenopus laevis.

    PubMed

    Güngördü, Abbas; Birhanli, Ayse; Ozmen, Murat

    2013-01-01

    The present study was undertaken to determine the toxic effect of a lethal concentration of six different commercially used textile dyes on the 46th stage of Xenopus laevis tadpoles. The tadpoles were exposed to Astrazon Red FBL, Astrazon Blue FGRL, Remazol Red RR, Remazol Turquoise Blue G-A, Cibacron Red FN-3G, and Cibacron Blue FN-R for 168 h in static test conditions, and thus, 168-h median lethal concentrations (LC(50)s) of each dye were determined to be 0.35, 0.13, 112, 7, 359, and 15.8 mg/L, respectively. Also, to evaluate the sublethal effects of each dye, tadpoles were exposed to different concentrations of dyes (with respect to 168-h LC(50)s) for 24 h. The alteration of selected enzyme activities was tested. For this aim, glutathione S-transferase (GST), carboxylesterase, and lactate dehydrogenase (LDH) were assayed. After dye exposure, the GST induction or inhibition and LDH induction indicated some possible mechanisms of oxidative stress and deterioration in aerobic respiration processes induced by the tested dyes. Findings of the study suggest that selected biomarker enzymes are useful in understanding the toxic mechanisms of these dyes in X. laevis tadpoles as early warning indicators. Therefore, these selected biomarkers may evaluate the effect of environmental factors, such as textile dye effluents and other industrial pollutants, on amphibians in biomonitoring studies.

  16. RPE, a plant gene involved in early developmental steps of nematode feeding cells.

    PubMed Central

    Favery, B; Lecomte, P; Gil, N; Bechtold, N; Bouchez, D; Dalmasso, A; Abad, P

    1998-01-01

    Sedentary plant-parasitic nematodes are able to induce the redifferentiation of root cells into multinucleate nematode feeding sites (NFSs). We have isolated by promoter trapping an Arabidopsis thaliana gene that is essential for the early steps of NFS formation induced by the root-knot nematode Meloidogyne incognita. Its pattern of expression is similar to that of key regulators of the cell cycle, but it is not observed with the cyst nematode. Later in NFS development, this gene is induced by both root-knot and cyst nematodes. It encodes a protein similar to the D-ribulose-5-phosphate 3-epimerase (RPE) (EC 5.1.3.1), a key enzyme in the reductive Calvin cycle and the oxidative pentose phosphate pathway (OPPP). Quantitative RT-PCR showed the accumulation of RPE transcripts in potato, as in Arabidopsis NFS. Homozygous rpe plants have a germination mutant phenotype that can be rescued in dwarf plants on sucrose-supplemented medium. During root development, this gene is expressed in the meristems and initiation sites of lateral roots. These results suggest that the genetic control of NFSs and the first stages of meristem formation share common steps and confirms the previous cytological observations which indicate that root cells undergo metabolic reprogramming when they turn into NFSs. PMID:9843485

  17. Biochemical response to exposure to six textile dyes in early developmental stages of Xenopus laevis.

    PubMed

    Güngördü, Abbas; Birhanli, Ayse; Ozmen, Murat

    2013-01-01

    The present study was undertaken to determine the toxic effect of a lethal concentration of six different commercially used textile dyes on the 46th stage of Xenopus laevis tadpoles. The tadpoles were exposed to Astrazon Red FBL, Astrazon Blue FGRL, Remazol Red RR, Remazol Turquoise Blue G-A, Cibacron Red FN-3G, and Cibacron Blue FN-R for 168 h in static test conditions, and thus, 168-h median lethal concentrations (LC(50)s) of each dye were determined to be 0.35, 0.13, 112, 7, 359, and 15.8 mg/L, respectively. Also, to evaluate the sublethal effects of each dye, tadpoles were exposed to different concentrations of dyes (with respect to 168-h LC(50)s) for 24 h. The alteration of selected enzyme activities was tested. For this aim, glutathione S-transferase (GST), carboxylesterase, and lactate dehydrogenase (LDH) were assayed. After dye exposure, the GST induction or inhibition and LDH induction indicated some possible mechanisms of oxidative stress and deterioration in aerobic respiration processes induced by the tested dyes. Findings of the study suggest that selected biomarker enzymes are useful in understanding the toxic mechanisms of these dyes in X. laevis tadpoles as early warning indicators. Therefore, these selected biomarkers may evaluate the effect of environmental factors, such as textile dye effluents and other industrial pollutants, on amphibians in biomonitoring studies. PMID:22802115

  18. Developmental adaptation of withdrawal reflexes to early alteration of peripheral innervation in the rat.

    PubMed Central

    Holmberg, H; Schouenborg, J

    1996-01-01

    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. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 7 PMID

  19. 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. PMID:23432827

  20. 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.

  1. 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

  2. Rbm20-deficient cardiogenesis reveals early disruption of RNA processing and sarcomere remodeling establishing a developmental etiology for dilated cardiomyopathy.

    PubMed

    Beraldi, Rosanna; Li, Xing; Martinez Fernandez, Almudena; Reyes, Santiago; Secreto, Frank; Terzic, Andre; Olson, Timothy M; Nelson, Timothy J

    2014-07-15

    Dilated cardiomyopathy (DCM) due to mutations in RBM20, a gene encoding an RNA-binding protein, is associated with high familial penetrance, risk of progressive heart failure and sudden death. Although genetic investigations and physiological models have established the linkage of RBM20 with early-onset DCM, the underlying basis of cellular and molecular dysfunction is undetermined. Modeling human genetics using a high-throughput pluripotent stem cell platform was herein designed to pinpoint the initial transcriptome dysfunction and mechanistic corruption in disease pathogenesis. Tnnt2-pGreenZeo pluripotent stem cells were engineered to knockdown Rbm20 (shRbm20) to determine the cardiac-pathogenic phenotype during cardiac differentiation. Intracellular Ca(2+) transients revealed Rbm20-dependent alteration in Ca(2+) handling, coinciding with known pathological splice variants of Titin and Camk2d genes by Day 24 of cardiogenesis. Ultrastructural analysis demonstrated elongated and thinner sarcomeres in the absence of Rbm20 that is consistent with human cardiac biopsy samples. Furthermore, Rbm20-depleted transcriptional profiling at Day 12 identified Rbm20-dependent dysregulation with 76% of differentially expressed genes linked to known cardiac pathology ranging from primordial Nkx2.5 to mature cardiac Tnnt2 as the initial molecular aberrations. Notably, downstream consequences of Rbm20-depletion at Day 24 of differentiation demonstrated significant dysregulation of extracellular matrix components such as the anomalous overexpression of the Vtn gene. By using the pluripotent stem cell platform to model human cardiac disease according to a stage-specific cardiogenic roadmap, we established a new paradigm of familial DCM pathogenesis as a developmental disorder that is patterned during early cardiogenesis and propagated with cellular mechanisms of pathological cardiac remodeling.

  3. 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

  4. Developmental and behavioral consequences of early life maternal separation stress in a mouse model of fetal alcohol spectrum disorder.

    PubMed

    Alberry, Bonnie; Singh, Shiva M

    2016-07-15

    Prenatal alcohol exposure (PAE) can result in fetal alcohol spectrum disorder (FASD), characterized by developmental disability. As children with FASD are often raised in suboptimal conditions, we have investigated the combination of PAE via maternal preference consumption of 10% ethanol in water with early life stress (ELS) via daily 3h maternal separation and isolation. Our results focus on development and behavioral features, including activity, anxiety-like behavior, as well as learning and memory. PAE influenced the number of pups surviving to postnatal day 2 and 70, with fewer surviving pups associated with the severity of ethanol exposure. PAE and ELS both had effects on pup weight at postnatal day 21, with amount of ethanol exposure positively correlating with pup weight. We found females were more active than males in a novel open field environment, but not following PAE. In addition, PAE resulted in overall increased exploratory behavior in the open field. Further, PAE and ELS both resulted in overnight hypoactivity in a home cage environment, as well as learning deficits that were influenced by sex in the Barnes Maze for learning and memory. These results are attributed to environmental interactions involving PAE and ELS. PMID:27102339

  5. Examining antecedents of caregivers' access to early childhood developmental screening: implications for campaigns promoting use of services in Appalachian Ohio.

    PubMed

    Bates, Benjamin R; Graham, Dawn; Striley, Katie; Patterson, Spencer; Arora, Aarti; Hamel-Lambert, Jane

    2014-05-01

    Although developmental delays are common in the United States, only about one third of developmental delays are identified before a child enters school. As challenging as use of developmental screening is on a national basis, the Appalachian region faces extreme lack of screening, diagnosis, and treatment for developmental delay. Local health care providers attribute this lack to poor parent understanding and have called for communication interventions to educate caregivers. This investigation sought to understand the antecedents of Appalachian caregivers' intentions to access developmental screening and services for their children as formative research for a communication-based intervention. The investigation was grounded by the health belief model. Surveys completed by 366 caregivers were used to model antecedents to behavioral intention. Perceived severity, perceived benefits, and self-efficacy were found to be the strongest predictors of intention to access developmental screening. Implications for a communication-based intervention are provided.

  6. Effects of oxytocin on cardiomyocyte differentiation from mouse embryonic stem cells.

    PubMed

    Hatami, Leili; Valojerdi, Mojtaba Rezazadeh; Mowla, Seyed Javad

    2007-04-12

    This study sought to investigate the presence of oxytocin receptors and the possible biological role of oxytocin as an effective factor in the differentiation of embryonic stem cells (ESCs) into cardiomyocytes. Mouse ESCs were cultivated in hanging drops to form embryoid bodies (EBs). The EBs were then treated with and without oxytocin (experimental and control groups). Up to 30 days after plating, contraction and beating frequency were monitored and evaluated daily. The growth characteristics of the ESC-derived cardiomyocytes were assessed by cardioactive drugs, immunocytochemistry, transmission electron microscopy (TEM) and reverse transcription-polymerase chain reaction (RT-PCR). In the experimental group, the percentage of the EBs with spontaneous contraction was significantly increased from 17th day onward. The spontaneous beating frequency of each EB in both groups was also changed with cardioactive drugs such as Bay K, carbachol, isopernaline and phenylephrine. However, in the experimental group, changes with isopernaline were more pronounced at the early and intermediate stages of cardiomyocyte development. The beating cells of both groups, stained positive with anti alpha-actinin, desmin, cardiac troponin I and connexin antibodies, and revealed similar ultrastructural features. Oxytocin receptors were detected on the ESCs and derived-differentiated cells. In addition, cardiac-specific genes such as cardiac alpha- and beta-myosin heavy chain, myosin light chain-2v, and atrial natriuretic factor were also detected in the ESC-derived differentiated cells of both groups. In the experimental group, all the specific genes, with the exception of alpha-myosin heavy chain, were more pronounced at the early stage of cardiomyocyte development. In conclusion, oxytocin has receptors on undifferentiated ESCs and derived differentiated cells, and in spite of better improvement of the EBs with spontaneous contraction, it can only promote the early maturation of ESC

  7. Isolation and Physiological Analysis of Mouse Cardiomyocytes

    PubMed Central

    Roth, Gretchen M.; Bader, David M.; Pfaltzgraff, Elise R.

    2014-01-01

    Cardiomyocytes, the workhorse cell of the heart, contain exquisitely organized cytoskeletal and contractile elements that generate the contractile force used to pump blood. Individual cardiomyocytes were first isolated over 40 years ago in order to better study the physiology and structure of heart muscle. Techniques have rapidly improved to include enzymatic digestion via coronary perfusion. More recently, analyzing the contractility and calcium flux of isolated myocytes has provided a vital tool in the cellular and sub-cellular analysis of heart failure. Echocardiography and EKGs provide information about the heart at an organ level only. Cardiomyocyte cell culture systems exist, but cells lack physiologically essential structures such as organized sarcomeres and t-tubules required for myocyte function within the heart. In the protocol presented here, cardiomyocytes are isolated via Langendorff perfusion. The heart is removed from the mouse, mounted via the aorta to a cannula, perfused with digestion enzymes, and cells are introduced to increasing calcium concentrations. Edge and sarcomere detection software is used to analyze contractility, and a calcium binding fluorescent dye is used to visualize calcium transients of electrically paced cardiomyocytes; increasing understanding of the role cellular changes play in heart dysfunction. Traditionally used to test drug effects on cardiomyocytes, we employ this system to compare myocytes from WT mice and mice with a mutation that causes dilated cardiomyopathy. This protocol is unique in its comparison of live cells from mice with known heart function and known genetics. Many experimental conditions are reliably compared, including genetic or environmental manipulation, infection, drug treatment, and more. Beyond physiologic data, isolated cardiomyocytes are easily fixed and stained for cytoskeletal elements. Isolating cardiomyocytes via perfusion is an extremely versatile method, useful in studying cellular changes

  8. Opposite Effects of Early-Life Competition and Developmental Telomere Attrition on Cognitive Biases in Juvenile European Starlings.

    PubMed

    Bateson, Melissa; Emmerson, Michael; Ergün, Gökçe; Monaghan, Pat; Nettle, Daniel

    2015-01-01

    Moods are enduring affective states that we hypothesise should be affected by an individual's developmental experience and its current somatic state. We tested whether early-life adversity, induced by manipulating brood size, subsequently altered juvenile European starlings' (Sturnus vulgaris) decisions in a judgment bias task designed to provide a cognitive measure of mood. We predicted that starlings from larger broods, specifically those that had experienced more nest competitors larger than themselves would exhibit reduced expectation of reward, indicative of a 'pessimistic', depression-like mood. We used a go/no-go task, in which 30 starlings were trained to probe a grey card disc associated with a palatable mealworm hidden underneath and avoid a different shade of grey card disc associated with a noxious quinine-injected mealworm hidden underneath. Birds' response latencies to the trained stimuli and also to novel, ambiguous stimuli intermediate between these were subsequently tested. Birds that had experienced greater competition in the nest were faster to probe trained stimuli, and it was therefore necessary to control statistically for this difference in subsequent analyses of the birds' responses to the ambiguous stimuli. As predicted, birds with more, larger nest competitors showed relatively longer latencies to probe ambiguous stimuli, suggesting reduced expectation of reward and a 'pessimistic', depression-like mood. However, birds with greater developmental telomere attrition--a measure of cellular aging associated with increased morbidity and reduced life-expectancy that we argue could be used as a measure of somatic state--showed shorter latencies to probe ambiguous stimuli. This would usually be interpreted as evidence for a more positive or 'optimistic' affective state. Thus, increased competition in the nest and poor current somatic state appear to have opposite effects on cognitive biases. Our results lead us to question whether increased

  9. Opposite Effects of Early-Life Competition and Developmental Telomere Attrition on Cognitive Biases in Juvenile European Starlings

    PubMed Central

    Bateson, Melissa; Emmerson, Michael; Ergün, Gökçe; Monaghan, Pat; Nettle, Daniel

    2015-01-01

    Moods are enduring affective states that we hypothesise should be affected by an individual’s developmental experience and its current somatic state. We tested whether early-life adversity, induced by manipulating brood size, subsequently altered juvenile European starlings’ (Sturnus vulgaris) decisions in a judgment bias task designed to provide a cognitive measure of mood. We predicted that starlings from larger broods, specifically those that had experienced more nest competitors larger than themselves would exhibit reduced expectation of reward, indicative of a ‘pessimistic’, depression-like mood. We used a go/no-go task, in which 30 starlings were trained to probe a grey card disc associated with a palatable mealworm hidden underneath and avoid a different shade of grey card disc associated with a noxious quinine-injected mealworm hidden underneath. Birds’ response latencies to the trained stimuli and also to novel, ambiguous stimuli intermediate between these were subsequently tested. Birds that had experienced greater competition in the nest were faster to probe trained stimuli, and it was therefore necessary to control statistically for this difference in subsequent analyses of the birds’ responses to the ambiguous stimuli. As predicted, birds with more, larger nest competitors showed relatively longer latencies to probe ambiguous stimuli, suggesting reduced expectation of reward and a ‘pessimistic’, depression-like mood. However, birds with greater developmental telomere attrition—a measure of cellular aging associated with increased morbidity and reduced life-expectancy that we argue could be used as a measure of somatic state—showed shorter latencies to probe ambiguous stimuli. This would usually be interpreted as evidence for a more positive or ‘optimistic’ affective state. Thus, increased competition in the nest and poor current somatic state appear to have opposite effects on cognitive biases. Our results lead us to question

  10. Developmental Milestones.

    PubMed

    Scharf, Rebecca J; Scharf, Graham J; Stroustrup, Annemarie

    2016-01-01

    • On the basis of observational studies (level C), preterm birth is a leading cause of neurodevelopmental disabilities in children, and the degree of neurodevelopmental disability is inversely correlated with gestational age at birth. When comparing performance of preterm children to developmental norms, “corrected age” or age from due date rather than birth date should be used for the first 24 to 36 months. • On the basis of observational studies (level C), clinicians should pay specific attention to sensory function in children born preterm because the incidence of visual and hearing impairments is higher in preterm than term children. Due to the elevated risk of cognitive and behavioral disabilities, clinicians caring for children born preterm should be vigilant when performing developmental assessments to improve outcomes. • On the basis of observational studies (level C), early identification of developmental delays allows for referral to therapeutic services, and children referred for early intervention are more likely to make gains in developmental milestones. PMID:26729779

  11. Temporal impact of substrate mechanics on differentiation of human embryonic stem cells to cardiomyocytes.

    PubMed

    Hazeltine, Laurie B; Badur, Mehmet G; Lian, Xiaojun; Das, Amritava; Han, Wenqing; Palecek, Sean P

    2014-02-01

    A significant clinical need exists to differentiate human pluripotent stem cells (hPSCs) into cardiomyocytes, enabling tissue modeling for in vitro discovery of new drugs or cell-based therapies for heart repair in vivo. Chemical and mechanical microenvironmental factors are known to impact the efficiency of stem cell differentiation, but cardiac differentiation protocols in hPSCs are typically performed on rigid tissue culture polystyrene (TCPS) surfaces, which do not present a physiological mechanical setting. To investigate the temporal effects of mechanics on cardiac differentiation, we cultured human embryonic stem cells (hESCs) and their derivatives on polyacrylamide hydrogel substrates with a physiologically relevant range of stiffnesses. In directed differentiation and embryoid body culture systems, differentiation of hESCs to cardiac troponin T-expressing (cTnT+) cardiomyocytes peaked on hydrogels of intermediate stiffness. Brachyury expression also peaked on intermediate stiffness hydrogels at day 1 of directed differentiation, suggesting that stiffness impacted the initial differentiation trajectory of hESCs to mesendoderm. To investigate the impact of substrate mechanics during cardiac specification of mesodermal progenitors, we initiated directed cardiomyocyte differentiation on TCPS and transferred cells to hydrogels at the Nkx2.5/Isl1+ cardiac progenitor cell stage. No differences in cardiomyocyte purity with stiffness were observed on day 15. These experiments indicate that differentiation of hESCs is sensitive to substrate mechanics at early stages of mesodermal induction, and proper application of substrate mechanics can increase the propensity of hESCs to differentiate to cardiomyocytes.

  12. Hydrogen peroxide-induced necrotic cell death in cardiomyocytes is independent of matrix metalloproteinase-2.

    PubMed

    Ali, Mohammad A M; Kandasamy, Arulmozhi D; Fan, Xiaohu; Schulz, Richard

    2013-09-01

    Matrix metalloproteinase-2 (MMP-2) is well known to proteolyse both extracellular and intracellular proteins. Reactive oxygen species activate MMP-2 at both transcriptional and post-translational levels, thus MMP-2 activation is considered an early event in oxidative stress injury. Although hydrogen peroxide is widely used to trigger oxidative stress-induced cell death, the type of cell death (apoptosis vs. necrosis) in cardiomyocytes is still controversial depending on the concentration used and the exposure time. We carefully investigated the mode of cell death in neonatal rat cardiomyocytes induced by different concentrations (50-500 μM) of hydrogen peroxide at various time intervals after exposure and determined whether MMP-2 is implicated in hydrogen peroxide-induced cardiomyocyte death. Treating cardiomyocytes with hydrogen peroxide led to elevated MMP-2 level/activity with maximal effects seen at 200 μM. Hydrogen peroxide caused necrotic cell death by disrupting the plasmalemma as evidenced by the release of lactate dehydrogenase in a concentration- and time-dependent manner as well as the necrotic cleavage of PARP-1. The absence of both caspase-3 cleavage/activation and apoptotic cleavage of PARP-1 illustrated the weak contribution of apoptosis. Pre-treatment with selective MMP inhibitors did not protect against hydrogen peroxide-induced necrosis. In conclusion hydrogen peroxide increases MMP-2 level/activity in cardiomyocytes and induces necrotic cell death, however, the later effect is MMP-2 independent.

  13. 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…

  14. 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…

  15. 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…

  16. 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

    PubMed Central

    Schendel, Diana; DiGuiseppi, Carolyn; Croen, Lisa; Fallin, M Danielle; Reed, Philip L.; Schieve, Laura; Wiggins, Lisa; Daniels, Julie; Grether, Judith; Levy, Susan; Miller, Lisa; Newschaffer, Craig; Pinto-Martin, Jennifer; Robinson, Cordelia; Windham, Gayle; Alexander, Aimee; Aylsworth, Arthur; Bernal, Pilar; Bonner, Joseph D.; Blaskey, Lisa; Bradley, Chyrise; Collins, Jack; Ferretti, Casara; 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, Steve; Rusyniak, Julie; Shapira, Stuart K.; Smith, Karen; Souders, Margaret; AaronThompson, Patrick; Young, Lisa; Yeargin-Allsopp, Marshalyn

    2015-01-01

    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, gastrointestinal, and sociodemographic characteristics. SEED uses a case–control design with population-based ascertainment of children aged 2–5 years with an autism spectrum disorder (ASD) and children in two control groups—one from the general population and one with non-ASD developmental problems. Data from parent-completed questionnaires, interviews, clinical evaluations, biospecimen sampling, and medical record abstraction focus on the prenatal and early postnatal periods. SEED is a valuable resource for testing hypotheses regarding ASD characteristics and causes. PMID:22350336

  17. Causative novel PNKP mutations and concomitant PCDH15 mutations in a patient with microcephaly with early-onset seizures and developmental delay syndrome and hearing loss.

    PubMed

    Nakashima, Mitsuko; Takano, Kyoko; Osaka, Hitoshi; Aida, Noriko; Tsurusaki, Yoshinori; Miyake, Noriko; Saitsu, Hirotomo; Matsumoto, Naomichi

    2014-08-01

    We report on a 1-year-old boy with microcephaly with a simplified gyral pattern, early-onset seizures, congenital hearing loss and a severe developmental delay. Trio-based whole-exome sequencing identified candidate compound heterozygous mutations in two genes: c.163G>T (p.Ala55Ser) and c.874G>A (p.Gly292Arg) in polynucleotide kinase 3'-phosphatase gene (PNKP), and c.195G>A (p.Met65Ile) and c.1210A>C (p.Ser404Arg) in PCDH15. PNKP and PCDH15 mutations have been reported in autosomal recessive microcephaly with early-onset seizures and developmental delay syndrome, and Usher syndrome type 1F, respectively. Our patient showed neurological features similar to reported cases of both syndromes that could be explained by the observed mutations in both PNKP and PCDH15, which therefore appear to be pathogenic in this case.

  18. Cardiomyocyte marker expression in a human lymphocyte cell line using mouse cardiomyocyte extract.

    PubMed

    Vojdani, Zahra; Tavakolinejad, Sima; Talaei-Khozani, Tahereh; Esmaeilpour, Tahereh; Rasooli, Manuchehr

    2011-03-01

    Cell transplantation shows potential for the treatment of cardiac diseases. Embryonic stem cells, cord blood and mesenchymal stem cells have been suggested as sources for transplantation therapy. Because of some technical limitations with the use of stem cells, transdifferentiation of fully differentiated cells is a potentially useful alternative. We investigated whether human peripheral blood cells could transdifferentiate into cardiomyocyte. Transdifferentiation was induced in a human B lymphocyte cell line (Raji). Cardiomyocyte extract was prepared from adult mouse cardiomyocytes. The cells were treated with 5-aza-2-deoxycytidine and trichostatin A, permeabilized with streptolysin O, and exposed to the mouse cardiomyocyte extract. They were cultured for 10 days, 3 weeks and 4 weeks. Cardiomyocyte markers were detected with immunohistochemistry and flow cytometry. Immunocytochemistry revealed that some cells expressed myosin heavy chain, α-actinin and cardiac troponin T after 3 and 4 weeks. Flow cytometry confirmed these data. In cells exposed to trichostatin A and 5-aza-2-deoxycytidine and permeabilized in the presence of the cardiomyocyte extract, troponin T expression was seen in 3.53% of the cells and 3.11% of them expressed α-actinin. After exposure to the cardiomyocyte extract, some permeabilized cells adhered to the plate loosely; however, the morphology did not change significantly, and they continued to show a rounded shape after 4 weeks. Our treated lymphocytes expressed cardiomyocyte markers. Our results suggest that lymphocytes may be useful in future research as a source of cells for reprogramming procedures.

  19. 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 Central

    Kim, Sanghag; Kochanska, Grazyna; Boldt, Lea J.; Nordling, Jamie Koenig; O’Bleness, Jessica J.

    2014-01-01

    Parent-child relationships are critical in development, but much remains to be learned about mechanisms of their impact. We examined 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 Family Study (102 community mothers, fathers, and infants, followed through age 8) and Play Study (186 low-income, diverse mothers and toddlers, followed for 10 months). The relationship quality was indexed by attachment security in Family Study and maternal responsiveness in Play Study. Responses to transgressions (tense discomfort and reparation) were observed in laboratory mishaps that led children to believe they had damaged a valued object. Antisocial outcomes were rated by parents. In both studies, early relationship moderated the future developmental trajectory: Children’s attenuated 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 Family Study indicated that the links between low tense discomfort and future antisocial behavior in insecure parent-child dyads were mediated by parental stronger discipline pressure. By influencing indirectly future developmental sequelae, early relationship may increase or decrease the probability that the parent-child dyad will embark on a path toward antisocial outcomes. PMID:24280347

  20. 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.

  1. 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

  2. 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.

  3. The electrophysiological development of cardiomyocytes.

    PubMed

    Liu, Jie; Laksman, Zachary; Backx, Peter H

    2016-01-15

    The generation of human cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs) has become an important resource for modeling human cardiac disease and for drug screening, and also holds significant potential for cardiac regeneration. Many challenges remain to be overcome however, before innovation in this field can translate into a change in the morbidity and mortality associated with heart disease. Of particular importance for the future application of this technology is an improved understanding of the electrophysiologic characteristics of CMs, so that better protocols can be developed and optimized for generating hPSC-CMs. Many different cell culture protocols are currently utilized to generate CMs from hPSCs and all appear to yield relatively “developmentally” immature CMs with highly heterogeneous electrical properties. These hPSC-CMs are characterized by spontaneous beating at highly variable rates with a broad range of depolarization-repolarization patterns, suggestive of mixed populations containing atrial, ventricular and nodal cells. Many recent studies have attempted to introduce approaches to promote maturation and to create cells with specific functional properties. In this review, we summarize the studies in which the electrical properties of CMs derived from stem cells have been examined. In order to place this information in a useful context, we also review the electrical properties of CMs as they transition from the developing embryo to the adult human heart. The signal pathways involved in the regulation of ion channel expression during development are also briefly considered. PMID:26788696

  4. The electrophysiological development of cardiomyocytes.

    PubMed

    Liu, Jie; Laksman, Zachary; Backx, Peter H

    2016-01-15

    The generation of human cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs) has become an important resource for modeling human cardiac disease and for drug screening, and also holds significant potential for cardiac regeneration. Many challenges remain to be overcome however, before innovation in this field can translate into a change in the morbidity and mortality associated with heart disease. Of particular importance for the future application of this technology is an improved understanding of the electrophysiologic characteristics of CMs, so that better protocols can be developed and optimized for generating hPSC-CMs. Many different cell culture protocols are currently utilized to generate CMs from hPSCs and all appear to yield relatively “developmentally” immature CMs with highly heterogeneous electrical properties. These hPSC-CMs are characterized by spontaneous beating at highly variable rates with a broad range of depolarization-repolarization patterns, suggestive of mixed populations containing atrial, ventricular and nodal cells. Many recent studies have attempted to introduce approaches to promote maturation and to create cells with specific functional properties. In this review, we summarize the studies in which the electrical properties of CMs derived from stem cells have been examined. In order to place this information in a useful context, we also review the electrical properties of CMs as they transition from the developing embryo to the adult human heart. The signal pathways involved in the regulation of ion channel expression during development are also briefly considered.

  5. Simultaneous Assessment of Cardiomyocyte DNA Synthesis and Ploidy: A Method to Assist Quantification of Cardiomyocyte Regeneration and Turnover.

    PubMed

    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

  6. 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

  7. Extracellular signal-regulated kinase and phosphoinositol-3 kinase mediate IGF-1 induced proliferation of fetal sheep cardiomyocytes.

    PubMed

    Sundgren, Nathan C; Giraud, George D; Schultz, Jess M; Lasarev, Michael R; Stork, Philip J S; Thornburg, Kent L

    2003-12-01

    Growth of the fetal heart involves cardiomyocyte enlargement, division, and maturation. Insulin-like growth factor-1 (IGF-1) is implicated in many aspects of growth and is likely to be important in developmental heart growth. IGF-1 stimulates the IGF-1 receptor (IGF1R) and downstream signaling pathways, including extracellular signal-regulated kinase (ERK) and phosphoinositol-3 kinase (PI3K). We hypothesized that IGF-1 stimulates cardiomyocyte proliferation and enlargement through stimulation of the ERK cascade and stimulates cardiomyocyte differentiation through the PI3K cascade. In vivo administration of Long R3 IGF-1 (LR3 IGF-1) did not stimulate cardiomyocyte hypertrophy but led to a decreased percentage of cells that were binucleated in vivo. In culture, LR3 IGF-1 increased myocyte bromodeoxyuridine (BrdU) uptake by three- to five-fold. The blockade of either ERK or PI3K signaling (by UO-126 or LY-294002, respectively) completely abolished BrdU uptake stimulated by LR3 IGF-1. LR3 IGF-1 did not increase footprint area, but as expected, phenylephrine stimulated an increase in binucleated cardiomyocyte size. We conclude that 1) IGF-1 through IGF1R stimulates cardiomyocyte division in vivo; hyperplastic growth is the most likely explanation of IGF-1 stimulated heart growth in vivo; 2) IGF-1 through IGF1R does not stimulate binucleation in vitro or in vivo; 3) IGF-1 through IGF1R does not stimulate hypertrophy either in vivo or in vitro; and 4) IGF-1 through IGF1R requires both ERK and PI3K signaling for proliferation of near-term fetal sheep cardiomyocytes in vitro. PMID:12947030

  8. 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...

  9. 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

  10. 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

  11. 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

  12. 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. PMID:27556740

  13. 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.

  14. Notch1 signaling stimulates proliferation of immature cardiomyocytes.

    PubMed

    Collesi, Chiara; Zentilin, Lorena; Sinagra, Gianfranco; Giacca, Mauro

    2008-10-01

    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

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. Technology and Pedagogy in Early Childhood Education: Guidance from Cultural-Historical-Activity Theory and Developmentally Appropriate Instruction

    ERIC Educational Resources Information Center

    Rivera, Hector; Galarza, Sheri Lyn; Entz, Susan; Tharp, Roland G.

    2002-01-01

    Technology can facilitate a pedagogy-based on neo-Vygotskian sociocultural theory, and on developmentally appropriate instruction. This article reviews the basic principles of such a pedagogy, and then presents a detailed case study of one day's instruction in a preschool classroom, that is richly infused with a system employing digital…

  20. 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…

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. Cardiomyocyte-specific conditional knockout of the histone chaperone HIRA in mice results in hypertrophy, sarcolemmal damage and focal replacement fibrosis

    PubMed Central

    Valenzuela, Nicolas; Fan, Qiying; Fa'ak, Faisal; Soibam, Benjamin; Nagandla, Harika; Liu, Yu; Schwartz, Robert J.; McConnell, Bradley K.; Stewart, M. David

    2016-01-01

    ABSTRACT HIRA is the histone chaperone responsible for replication-independent incorporation of histone variant H3.3 within gene bodies and regulatory regions of actively transcribed genes, and within the bivalent promoter regions of developmentally regulated genes. The HIRA gene lies within the 22q11.2 deletion syndrome critical region; individuals with this syndrome have multiple congenital heart defects. Because terminally differentiated cardiomyocytes have exited the cell cycle, histone variants should be utilized for the bulk of chromatin remodeling. Thus, HIRA is likely to play an important role in epigenetically defining the cardiac gene expression program. In this study, we determined the consequence of HIRA deficiency in cardiomyocytes in vivo by studying the phenotype of cardiomyocyte-specific Hira conditional-knockout mice. Loss of HIRA did not perturb heart development, but instead resulted in cardiomyocyte hypertrophy and susceptibility to sarcolemmal damage. Cardiomyocyte degeneration gave way to focal replacement fibrosis and impaired cardiac function. Gene expression was widely altered in Hira conditional-knockout hearts. Significantly affected pathways included responses to cellular stress, DNA repair and transcription. Consistent with heart failure, fetal cardiac genes were re-expressed in the Hira conditional knockout. Our results suggest that transcriptional regulation by HIRA is crucial for cardiomyocyte homeostasis. PMID:26935106

  6. 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

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

    PubMed

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

    2014-12-01

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

  8. 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…

  9. Endurance Exercise Mobilizes Developmentally Early Stem Cells into Peripheral Blood and Increases Their Number in Bone Marrow: Implications for Tissue Regeneration.

    PubMed

    Marycz, Krzysztof; Mierzejewska, Katarzyna; Śmieszek, Agnieszka; Suszynska, Ewa; Malicka, Iwona; Kucia, Magda; Ratajczak, Mariusz Z

    2016-01-01

    Endurance exercise has been reported to increase the number of circulating hematopoietic stem/progenitor cells (HSPCs) in peripheral blood (PB) as well as in bone marrow (BM). We therefore became interested in whether endurance exercise has the same effect on very small embryonic-like stem cells (VSELs), which have been described as a population of developmentally early stem cells residing in BM. Mice were run daily for 1 hour on a treadmill for periods of 5 days or 5 weeks. Human volunteers had trained in long-distance running for one year, six times per week. FACS-based analyses and RT-PCR of murine and human VSELs and HSPCs from collected bone marrow and peripheral blood were performed. We observed that endurance exercise increased the number of VSELs circulating in PB and residing in BM. In parallel, we observed an increase in the number of HSPCs. These observations were subsequently confirmed in young athletes, who showed an increase in circulating VSELs and HSPCs after intensive running exercise. We provide for the first time evidence that endurance exercise may have beneficial effects on the expansion of developmentally early stem cells. We hypothesize that these circulating stem cells are involved in repairing minor exercise-related tissue and organ injuries.

  10. Altered developmental timing in early life stages of Antarctic krill (Euphausia superba) exposed to p,p'-DDE.

    PubMed

    Poulsen, Anita H; Kawaguchi, So; Leppänen, Matti T; Kukkonen, Jussi V K; Bengtson Nash, Susan M

    2011-11-15

    Persistent organic pollutants (POPs) are persistent, toxic and bioaccumulative anthropogenic organic chemicals, capable of undergoing long range environmental transport to remote areas including the Antarctic. p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE) has been identified as a dominant POP accumulating in Antarctic krill (Euphausia superba), which is a key Southern Ocean species. This study examined the developmental toxicity of p,p'-DDE via aqueous exposure to Antarctic krill larvae. p,p'-DDE exposure was found to stimulate developmental timing in the first three larval stages of Antarctic krill, while extended monitoring of larvae after a five day exposure period had ended, revealed delayed inhibitory responses during development to the fourth larval stage. Stimulatory responses were observed from the lowest p,p'-DDE body residue tested of 10.1±3.0 μmol/kg (3.2±0.95 mg/kg) preserved wet weight, which is comparable to findings for temperate species and an order of magnitude lower than the exposure level found to cause sublethal behavioural effects in Antarctic krill. The delayed responses included increased mortality, which had doubled in the highest p,p'-DDE treatment (95±8.9% mortality at 20 μg/L p,p'-DDE) compared to the solvent control (44±11% mortality) 2 weeks after end of exposure. Development of surviving metanauplius larvae to calyptopis 1 larvae was delayed by 2 days in p,p'-DDE exposed larvae compared with untreated larvae. Finally, the developmental success of surviving p,p'-DDE exposed larvae was reduced by 50 to 75% compared to the solvent control (100% developmental success). The lowest observed effect concentration for all delayed effects was 1 μg/L, the lowest exposure concentration tested. These findings demonstrate the importance of delayed and indirect effects of toxicant exposure. Further, the findings of this study are important for environmental risk assessment of POPs in the Southern Ocean ecosystem and strongly highlight the

  11. 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...

  12. Targeted Deletion of Tsc1 Causes Fatal Cardiomyocyte Hyperplasia Independently of Afterload

    PubMed Central

    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.

    2014-01-01

    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, 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-ERT2+/−). The Tsc1c/cSMAcre-ERT2+/− 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. PMID:25434723

  13. Developmental links of very early phonological and language skills to second grade reading outcomes: strong to accuracy but only minor to fluency.

    PubMed

    Puolakanaho, Anne; Ahonen, Timo; Aro, Mikko; Eklund, Kenneth; Leppänen, Paavo H T; Poikkeus, Anna-Maija; Tolvanen, Asko; Torppa, Minna; Lyytinen, Heikki

    2008-01-01

    The authors examined second grade reading accuracy and fluency and their associations via letter knowledge to phonological and language predictors assessed at 3.5, 4.5, and 5.5 years in children in the Jyväskylä Longitudinal Study of Dyslexia. Structural equation modeling showed that a developmentally highly stable factor (early phonological and language processing [EPLP]) behind key dyslexia predictors (i.e., phonological awareness, short-term memory, rapid naming, vocabulary, and pseudoword repetition) could already be identified at 3.5 years. EPLP was significantly associated with reading and spelling accuracy and by age with letter knowledge. However, EPLP had only a minor link with reading fluency, which was additionally explained by early letter knowledge. The results show that reading accuracy is well predicted by early phonological and language skills. Variation in fluent reading skills is not well explained by early skills, suggesting factors other than phonological core skills. Future research is suggested to explore the factors behind the development of fast and accurate decoding skills. PMID:18560022

  14. Early childhood growth failure and the developmental origins of adult disease: do enteric infections and malnutrition increase risk for the metabolic syndrome?

    PubMed

    DeBoer, Mark D; Lima, Aldo A M; Oría, Reinaldo B; Scharf, Rebecca J; Moore, Sean R; Luna, Max A; Guerrant, Richard L

    2012-11-01

    Hypotheses regarding the developmental origins of health and disease postulate that developing fetuses - and potentially young children - undergo adaptive epigenetic changes that have longstanding effects on metabolism and other processes. Ongoing research explores whether these adaptations occur during early life following early childhood malnutrition. In the developing world, there remains a high degree of nutritional stunting, defined as linear growth failure caused by inadequate caloric intake, which may be exacerbated by inflammation from ongoing infections. In areas with poor sanitation, children experience vicious cycles of enteric infections and malnutrition, resulting in poor nutrient absorption as a result of changes in the intestinal mucosa, now termed "environmental enteropathy." Emerging evidence links early childhood diarrhea and/or growth failure with an increased occurrence of risk factors for cardiovascular disease in later life, including dyslipidemia, hypertension, and glucose intolerance. The mechanisms for these associations remain poorly understood and may relate to epigenetic responses to poor nutrition, increased inflammation, or both. Given the increased incidence of cardiovascular disease in developing areas of the world, associations between childhood malnutrition, early-life infections, and the increased occurrence of risk factors for cardiovascular disease underscore further reasons to improve nutrition and infection-related outcomes for young children worldwide.

  15. 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.…

  16. Directed Differentiation of Zebrafish Pluripotent Embryonic Cells to Functional Cardiomyocytes.

    PubMed

    Xiao, Yao; Gao, Maomao; Gao, Luna; Zhao, Yu; Hong, Qiang; Li, Zhigang; Yao, Jing; Cheng, Hanhua; Zhou, Rongjia

    2016-09-13

    A cardiomyocyte differentiation in vitro system from zebrafish embryos remains to be established. Here, we have determined pluripotency window of zebrafish embryos by analyzing their gene-expression patterns of pluripotency factors together with markers of three germ layers, and have found that zebrafish undergoes a very narrow period of pluripotency maintenance from zygotic genome activation to a brief moment after oblong stage. Based on the pluripotency and a combination of appropriate conditions, we established a rapid and efficient method for cardiomyocyte generation in vitro from primary embryonic cells. The induced cardiomyocytes differentiated into functional and specific cardiomyocyte subtypes. Notably, these in vitro generated cardiomyocytes exhibited typical contractile kinetics and electrophysiological features. The system provides a new paradigm of cardiomyocyte differentiation from primary embryonic cells in zebrafish. The technology provides a new platform for the study of heart development and regeneration, in addition to drug discovery, disease modeling, and assessment of cardiotoxic agents. PMID:27569061

  17. 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.

  18. 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. PMID:27352146

  19. Characterizing functional stem cell–cardiomyocyte interactions

    PubMed Central

    Bursac, Nenad; Kirkton, Robert D; McSpadden, Luke C; Liau, Brian

    2010-01-01

    Despite the progress in traditional pharmacological and organ transplantation therapies, heart failure still afflicts 5.3 million Americans. Since June 2000, stem cell-based approaches for the prevention and treatment of heart failure have been pursued in clinics with great excitement; however, the exact mechanisms of how transplanted cells improve heart function remain elusive. One of the main difficulties in answering these questions is the limited ability to directly access and study interactions between implanted cells and host cardiomyocytes in situ. With the growing number of candidate cell types for potential clinical use, it is becoming increasingly more important to establish standardized, well-controlled in vitro and in situ assays to compare the efficacy and safety of different stem cells in cardiac repair. This article describes recent innovative methodologies to characterize direct functional interactions between stem cells and cardiomyocytes, aimed to facilitate the rational design of future cell-based therapies for heart disease. PMID:20017697

  20. Brief report: Assessing youth well-being in global emergency settings: Early results from the Emergency Developmental Assets Profile.

    PubMed

    Scales, Peter C; Roehlkepartain, Eugene C; Wallace, Teresa; Inselman, Ashley; Stephenson, Paul; Rodriguez, Michael

    2015-12-01

    The 13-item Emergency Developmental Assets Profile measures the well-being of children and youth in emergency settings such as refugee camps and armed conflict zones, assessing whether young people are experiencing adequate positive relationships and opportunities, and developing positive values, skills, and self-perceptions, despite being in crisis circumstances. The instrument was found to have acceptable and nearly identical internal consistency reliability in 22 administrations in non-emergency samples in 15 countries (.75), and in 4 samples of youth ages 10-18 (n = 1550) in the emergency settings (war refugees and typhoon victims, .74) that are the measure's focus, and evidence of convergent validity. Confirmatory Factor Analysis showed acceptable model fit among those youth in emergency settings. Measures of model fit showed that the Em-DAP has configural and metric invariance across all emergency contexts and scalar invariance across some. The Em-DAP is a promising brief cross-cultural tool for assessing the developmental quality of life as reported by samples of youth in a current humanitarian crisis situation. The results can help to inform international relief program decisions about services and activities to be provided for children, youth, and families in emergency settings. PMID:26426457

  1. 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

  2. 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.

  3. Brief report: Assessing youth well-being in global emergency settings: Early results from the Emergency Developmental Assets Profile.

    PubMed

    Scales, Peter C; Roehlkepartain, Eugene C; Wallace, Teresa; Inselman, Ashley; Stephenson, Paul; Rodriguez, Michael

    2015-12-01

    The 13-item Emergency Developmental Assets Profile measures the well-being of children and youth in emergency settings such as refugee camps and armed conflict zones, assessing whether young people are experiencing adequate positive relationships and opportunities, and developing positive values, skills, and self-perceptions, despite being in crisis circumstances. The instrument was found to have acceptable and nearly identical internal consistency reliability in 22 administrations in non-emergency samples in 15 countries (.75), and in 4 samples of youth ages 10-18 (n = 1550) in the emergency settings (war refugees and typhoon victims, .74) that are the measure's focus, and evidence of convergent validity. Confirmatory Factor Analysis showed acceptable model fit among those youth in emergency settings. Measures of model fit showed that the Em-DAP has configural and metric invariance across all emergency contexts and scalar invariance across some. The Em-DAP is a promising brief cross-cultural tool for assessing the developmental quality of life as reported by samples of youth in a current humanitarian crisis situation. The results can help to inform international relief program decisions about services and activities to be provided for children, youth, and families in emergency settings.

  4. Cardiomyocyte Death: Insights from Molecular and Microstructural Magnetic Resonance Imaging

    PubMed Central

    Berry, Natalia C.

    2011-01-01

    Cardiomyocytes can die via necrosis, apoptosis, and autophagy. Although the molecular signals and pathways underlying these processes have been well elucidated, the pathophysiology of cardiomyocyte death remains incompletely understood. This review describes the development and application of novel imaging techniques to detect and characterize cardiomyocyte death noninvasively in vivo. It focuses on molecular and microstructural magnetic resonance images (MRIs) and their respective abilities to image cellular events such as apoptosis, inflammation, and myofiber architecture. These in vivo imaging techniques have the potential to provide novel insights into the mechanisms of cardiomyocyte death and to help guide the development of novel cardioprotective therapies. PMID:21298427

  5. BRG1 and BRM SWI/SNF ATPases redundantly maintain cardiomyocyte homeostasis by regulating cardiomyocyte mitophagy and mitochondrial dynamics in vivo.

    PubMed

    Bultman, Scott J; Holley, Darcy Wood; G de Ridder, Gustaaf; Pizzo, Salvatore V; Sidorova, Tatiana N; Murray, Katherine T; Jensen, Brian C; Wang, Zhongjing; Bevilacqua, Ariana; Chen, Xin; Quintana, Megan T; Tannu, Manasi; Rosson, Gary B; Pandya, Kumar; Willis, Monte S

    2016-01-01

    There has been an increasing recognition that mitochondrial perturbations play a central role in human heart failure. Mitochondrial networks, whose function is to maintain the regulation of mitochondrial biogenesis, autophagy ('mitophagy') and mitochondrial fusion/fission, are new potential therapeutic targets. Yet our understanding of the molecular underpinning of these processes is just emerging. We recently identified a role of the SWI/SNF ATP-dependent chromatin remodeling complexes in the metabolic homeostasis of the adult cardiomyocyte using cardiomyocyte-specific and inducible deletion of the SWI/SNF ATPases BRG1 and BRM in adult mice (Brg1/Brm double mutant mice). To build upon these observations in early altered metabolism, the present study looks at the subsequent alterations in mitochondrial quality control mechanisms in the impaired adult cardiomyocyte. We identified that Brg1/Brm double-mutant mice exhibited increased mitochondrial biogenesis, increases in 'mitophagy', and alterations in mitochondrial fission and fusion that led to small, fragmented mitochondria. Mechanistically, increases in the autophagy and mitophagy-regulated proteins Beclin1 and Bnip3 were identified, paralleling changes seen in human heart failure. Evidence for perturbed cardiac mitochondrial dynamics included decreased mitochondria size, reduced numbers of mitochondria, and an altered expression of genes regulating fusion (Mfn1, Opa1) and fission (Drp1). We also identified cardiac protein amyloid accumulation (aggregated fibrils) during disease progression along with an increase in pre-amyloid oligomers and an upregulated unfolded protein response including increased GRP78, CHOP, and IRE-1 signaling. Together, these findings described a role for BRG1 and BRM in mitochondrial quality control, by regulating mitochondrial number, mitophagy, and mitochondrial dynamics not previously recognized in the adult cardiomyocyte. As critical to the pathogenesis of heart failure, epigenetic

  6. Unique metabolic features of stem cells, cardiomyocytes, and their progenitors.

    PubMed

    Gaspar, John Antonydas; Doss, Michael Xavier; Hengstler, Jan Georg; Cadenas, Cristina; Hescheler, Jürgen; Sachinidis, Agapios

    2014-04-11

    Recently, growing attention has been directed toward stem cell metabolism, with the key observation that the plasticity of stem cells also reflects the plasticity of their energy substrate metabolism. There seems to be a clear link between the self-renewal state of stem cells, in which cells proliferate without differentiation, and the activity of specific metabolic pathways. Differentiation is accompanied by a shift from anaerobic glycolysis to mitochondrial respiration. This metabolic switch of differentiating stem cells is required to cover the energy demands of the different organ-specific cell types. Among other metabolic signatures, amino acid and carbohydrate metabolism is most prominent in undifferentiated embryonic stem cells, whereas the fatty acid metabolic signature is unique in cardiomyocytes derived from embryonic stem cells. Identifying the specific metabolic pathways involved in pluripotency and differentiation is critical for further progress in the field of developmental biology and regenerative medicine. The recently generated knowledge on metabolic key processes may help to generate mature stem cell-derived somatic cells for therapeutic applications without the requirement of genetic manipulation. In the present review, the literature about metabolic features of stem cells and their cardiovascular cell derivatives as well as the specific metabolic gene signatures differentiating between stem and differentiated cells are summarized and discussed.

  7. 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

  8. 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

  9. Developmental consequences of early parenting experiences: self-recognition and self-regulation in three cultural communities.

    PubMed

    Keller, Heidi; Yovsi, Relindis; Borke, Joern; Kärtner, Joscha; Jensen, Henning; Papaligoura, Zaira

    2004-01-01

    This study relates parenting of 3-month-old children to children's self-recognition and self-regulation at 18 to 20 months. As hypothesized, observational data revealed differences in the sociocultural orientations of the 3 cultural samples' parenting styles and in toddlers' development of self-recognition and self-regulation. Children of Cameroonian Nso farmers who experience a proximal parenting style develop self-regulation earlier, children of Greek urban middle-class families who experience a distal parenting style develop self-recognition earlier, and children of Costa Rican middle-class families who experience aspects of both distal and proximal parenting styles fall between the other 2 groups on both self-regulation and self-recognition. Results are discussed with respect to their implications for culturally informed developmental pathways.

  10. Nonmentalizing states in early-childhood survivors of the Holocaust: developmental considerations regarding treatment of child survivors of genocidal atrocities.

    PubMed

    Sossin, K Mark

    2007-03-01

    This paper attempts to coalesce considerations of attachment processes, trauma, mentalization, and nonverbal behavior to underscore some of the developmental and therapeutic challenges demonstrated by older-adult child survivors of the Holocaust, and by implication, other child victims of similar genocidal and traumatic events. Young child survivors experienced not only their own traumatic exposure to violence, harm, and loss, but also the stress-transmission of the adult caregivers who raised them in the years that followed. For some, the horrendous losses, combined with impediments to organizing relationships, and to experiences of predictable and trusted continuities, negatively impact the development of the reflective function, and of interpretive skills basic to successful implicit relatedness and explicit exchanges. "Neutral flow" of bodily tension and shape often signals the freezing accompanying nonmentalizing states. Misalignments in individual personality structure and discordances in interpersonal exchange underscore the need to address fundamental building blocks of relatedness and mentalization in the therapeutic process. PMID:17510620

  11. Identity statuses as developmental trajectories: a five-wave longitudinal study in early-to-middle and middle-to-late adolescents.

    PubMed

    Meeus, Wim; van de Schoot, Rens; Keijsers, Loes; Branje, Susan

    2012-08-01

    This study tested whether Marcia's original identity statuses of achievement, moratorium, early closure (a new label for foreclosure), and diffusion, can be considered identity status trajectories. That is, we examined whether these statuses are distinct and relatively stable, over-time configurations of commitment strength, levels of in-depth exploration of present commitments, and consideration of alternative commitments. The study examined identity development in a five-wave study of 923 early-to-middle (49.3% female) and 390 middle-to-late adolescents (56.7% female), covering the ages of 12-20. Using Latent class growth analysis (LCGA), the authors found that Marcia's (1966) statuses are indeed identity status trajectories. Two kinds of moratorium were also found: the classical moratorium and searching moratorium. Support was found for Waterman's developmental hypothesis of the identity status model: the number of achievers was significantly higher, and the number of diffusions lower, in middle-to-late adolescence than in early-to-middle adolescence. Females were more often in the advanced identity status trajectories, and stable differences were found between the trajectories in psychosocial adjustment. Study findings highlight that identity formation should be conceptualized as an over-time process.

  12. Early childhood growth failure and the developmental origins of adult disease: Do enteric infections and malnutrition increase risk for the metabolic syndrome?

    PubMed Central

    DeBoer, Mark D.; Lima, Aldo A. M.; Oría, Reinaldo B.; Scharf, Rebecca J.; Moore, Sean R.; Luna, Max A.; Guerrant, Richard L.

    2012-01-01

    Hypotheses regarding the developmental origins of health and disease postulate that developing fetuses–and potentially young children—undergo adaptive epigenetic changes with longstanding effects on metabolism and other processes. Ongoing research explores whether these adaptations occur during early life following malnutrition. In the developing world there remains a high degree of nutritional stunting—linear growth failure due to inadequate calories that may be exacerbated by inflammation from ongoing infections. In areas with poor sanitation children experience vicious cycles of enteric infections and malnutrition, resulting in poor nutrient absorption from intestinal mucosa changes now termed “environmental enteropathy.” Emerging evidence links early childhood diarrhea and/or growth failure with increased CVD risk factors in later life, including dyslipidemia, hypertension and glucose intolerance. The mechanisms for these associations remain poorly understood and may relate to epigenetic responses to poor nutrition, increased inflammation or both. Given increases in CVD in developing areas of the world, associations between childhood malnutrition, early life infections and increased CVD risk factors underscore further reasons to improve nutrition and infection-related outcomes for young children worldwide. PMID:23110643

  13. Developmental Trajectories of Auditory Cortex Synaptic Structures and Gap-Prepulse Inhibition of Acoustic Startle Between Early Adolescence and Young Adulthood in Mice.

    PubMed

    Moyer, Caitlin E; Erickson, Susan L; Fish, Kenneth N; Thiels, Edda; Penzes, Peter; Sweet, Robert A

    2016-05-01

    Cortical excitatory and inhibitory synapses are disrupted in schizophrenia, the symptoms of which often emerge during adolescence, when cortical excitatory synapses undergo pruning. In auditory cortex, a brain region implicated in schizophrenia, little is known about the development of excitatory and inhibitory synapses between early adolescence and young adulthood, and how these changes impact auditory cortex function. We used immunohistochemistry and quantitative fluorescence microscopy to quantify dendritic spines and GAD65-expressing inhibitory boutons in auditory cortex of early adolescent, late adolescent, and young adult mice. Numbers of spines decreased between early adolescence and young adulthood, during which time responses increased in an auditory cortex-dependent sensory task, silent gap-prepulse inhibition of the acoustic startle reflex (gap-PPI). Within-bouton GAD65 protein and GAD65-expressing bouton numbers decreased between late adolescence and young adulthood, a delay in onset relative to spine and gap-PPI changes. In mice lacking the spine protein kalirin, there were no significant changes in spine number, within-bouton GAD65 protein, or gap-PPI between adolescence and young adulthood. These results illustrate developmental changes in auditory cortex spines, inhibitory boutons, and auditory cortex function between adolescence and young adulthood, and provide insights into how disrupted adolescent neurodevelopment could contribute to auditory cortex synapse pathology and auditory impairments.

  14. Early onset Charcot-Marie-Tooth neuropathy type 2A and severe developmental delay: expanding the clinical phenotype of MFN2-related neuropathy.

    PubMed

    Tufano, Maria; Cappuccio, Gerarda; Terrone, Gaetano; Manganelli, Fiore; Pisciotta, Chiara; Geroldi, Alessandro; Capponi, Simona; Del Giudice, Ennio

    2015-12-01

    Charcot-Marie-Tooth (CMT) syndromes are a group of clinically heterogeneous disorders of the peripheral nervous system. Mutations of mitofusin 2 (MFN2) have been recognized to be associated with CMT type 2A (CMT2A). CMT2A is primarily an axonal disorder resulting in motor and sensory neuropathy. We report a male child with psychomotor delay, dysmorphic features, and weakness of lower limbs associated with electrophysiological features of severe, sensory-motor, axonal neuropathy. The patient was diagnosed with early onset CMT2A and severe psychomotor retardation associated with c.310C>T mutation (p.R104W) in MFN2 gene. CMT2A should be considered in patients with both axonal sensory-motor neuropathy and developmental delay.

  15. Risk factors of children who exited from an early intervention program without an identified disability and returned with a developmental disability.

    PubMed

    Giannoni, Peggy P; Kass, Philip H

    2010-01-01

    A retrospective cohort study was undertaken to identify risk factors for children at greatest risk of delayed diagnosis of developmental disability. Two thousand four hundred and thirty-nine children were selected for this study due to their participation in the California Early Start (ES) Program in 1998. Comparisons were made among children that had no break in services offered through the ES Program versus children that returned with a disability after exiting the ES Program. Factors examined include child's condition and qualifying risk factors, mother's demographic characteristics, family's risk factors, and risk scores developed for each county in which the family resided. Children with a delay in diagnosis of a disability have characteristics that fall outside the norm for the identification of a disability. It is not clear if this is related to age-specific manifestation to the appearance of a disability or to conditions difficult to diagnose.

  16. 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

  17. Developmental Pathways from Childhood Aggression-Disruptiveness, Chronic Peer Rejection and Deviant Friendships to Early-Adolescent Rule Breaking

    PubMed Central

    Ettekal, Idean; Ladd, Gary W.

    2015-01-01

    Childhood aggression-disruptiveness, 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 aggression-disruptiveness 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. PMID:25403544

  18. 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.

  19. [Hypoxic preconditioning is a phenomenon increasing tolerance of cardiomyocytes to hypoxia-reoxygenation].

    PubMed

    Maslov, L N; Lishmanov, Iu B; Kolar, F; Portnichenko, A G; Podoksenov, Iu K; Khaliulin, I G; Wang, H; Pei, J M

    2010-12-01

    The work covers the problem of hypoxic preconditioning (HP) carried out in isolated cardiomyocytes. Papers on delayed HP in vivo are comparatively few, and only some single works are devoted to early preconditioning in vivo. It has been established that the HP limits necrosis and apoptosis of cardiomyocytes and improves contractility of the isolated heart after ischemia (hypoxia) and reperfusion (reoxygenation). It was found that adenosine was a trigger of iP in vitro. It was proved that NO* was a trigger of HP both in vitro and in vivo. It was shown that reactive oxygen species also were triggers of hypoxic preconditioning. It was shown that ERK1/2 and p38 kinase played important role in delayed HP in vitro. PMID:21473105

  20. 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

  1. 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…

  2. "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…

  3. 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.…

  4. Envisioning an Adult Learning Graduate Program for the Early 21st Century: A Developmental Action Inquiry Study

    ERIC Educational Resources Information Center

    Dzubinski, Leanne; Hentz, Brian; Davis, Katherine L.; Nicolaides, Aliki

    2012-01-01

    The rapid pace of social and technological change in the early 21st century leaves many adults scrambling to meet the complexities that characterize their daily lives. Adult learners are faced with multiple, often competing, demands from work, education, family, and leisure, which requires adult education graduate programs to carefully consider…

  5. 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…

  6. 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...

  7. 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…

  8. Downregulation of Early Ionotrophic Glutamate Receptor Subunit Developmental Expression as a Mechanism for Observed Plasticity Deficits Following Gestational Exposure to Benzo(a)pyrene

    PubMed Central

    Brown, La’Nissa A.; Khoshbouei, Habibeh; Goodwin, J. Shawn; Irvin-Wilson, Charletha V.; Ramesh, Aramandla; Sheng, Liu; McCallister, Monique M.; Jiang, George C. T.; Aschner, Michael; Hood, Darryl B.

    2007-01-01

    The focus of this study was to characterize the impact of gestational exposure to benzo(a)pyrene, [B(a)P] on modulation of glutamate receptor subunit expression that is critical for the maintenance of synaptic plasticity mechanisms during hippocampal or cortical development in offspring. Previous studies have demonstrated that hippocampal and/or cortical synaptic plasticity (as measured by long-term potentiation and S1-cortex spontaneous/evoked neuronal activity) and learning behavior (as measured by fixed-ratio performance operant testing) is significantly impaired in polycyclic aromatic or halogenated aromatic hydrocarbon-exposed offspring as compared to controls. These previous studies have also revealed that brain to body weight ratios are greater in exposed offspring relative to controls indicative of intrauterine growth retardation which has been shown to manifest as low birth weight in offspring. Recent epidemiological studies have identified an effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 Years of life among inner-city children (Perera et al., 2006). The present study utilizes a well-characterized animal model to test the hypothesis that gestational exposure to B(a)P causes dysregulation of developmental ionotropic glutamate receptor subunit expression, namely the N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptor (AMPAR) both critical to the expression of synaptic plasticity mechanisms. To mechanistically ascertain the basis of B(a)P-induced plasticity perturbations, timed pregnant Long-Evans rats were exposed in an oral subacute exposure regimen to 0, 25 and 150µg/kg BW B(a)P on gestation days 14–17. The first sub-hypothesis tested whether gestational exposure to B(a)P would result in significant disposition in offspring. The second sub-hypothesis tested whether gestational exposure to B(a)P would result in downregulation of early

  9. Mammalian heart renewal by pre-existing cardiomyocytes.

    PubMed

    Senyo, Samuel E; Steinhauser, Matthew L; Pizzimenti, Christie L; Yang, Vicky K; Cai, Lei; Wang, Mei; Wu, Ting-Di; Guerquin-Kern, Jean-Luc; Lechene, Claude P; Lee, Richard T

    2013-01-17

    Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes. Other studies suggest that new cardiomyocytes are born at a very low rate, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches--genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry--that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinucleation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.

  10. Calcium signaling in diabetic cardiomyocytes.

    PubMed

    Pereira, Laetitia; Ruiz-Hurtado, Gema; Rueda, Angélica; Mercadier, Jean-Jacques; Benitah, Jean-Pierre; Gómez, Ana María

    2014-11-01

    Diabetes mellitus is one of the most common medical conditions. It is associated to medical complications in numerous organs and tissues, of which the heart is one of the most important and most prevalent organs affected by this disease. In fact, cardiovascular complications are the most common cause of death among diabetic patients. At the end of the 19th century, the weakness of the heart in diabetes was noted as part of the general muscular weakness that exists in that disease. However, it was only in the eighties that diabetic cardiomyopathy was recognized, which comprises structural and functional abnormalities in the myocardium in diabetic patients even in the absence of coronary artery disease or hypertension. This disorder has been associated with both type 1 and type 2 diabetes, and is characterized by early-onset diastolic dysfunction and late-onset systolic dysfunction, in which alteration in Ca(2+) signaling is of major importance, since it controls not only contraction, but also excitability (and therefore is involved in rhythmic disorder), enzymatic activity, and gene transcription. Here we attempt to give a brief overview of Ca(2+) fluxes alteration reported on diabetes, and provide some new data on differential modulation of Ca(2+) handling alteration in males and females type 2 diabetic mice to promote further research. Due to space limitations, we apologize for those authors whose important work is not cited.

  11. Behavior of carbonate and magnesium ions in the initial crystallites at the early developmental stages of the rat calvaria.

    PubMed

    Kakei, M; Nakahara, H; Tamura, N; Itoh, H; Kumegawa, M

    1997-08-01

    Analysis of the contents of calcium (Ca), magnesium (Mg), phosphate, and carbonate ions in the mineral phase of rat calvaria specimens obtained at different developmental stages indicated that the mineral at the newborn stage contained a negligible amount of carbonate, but a high content of Mg. There was no significant difference in Ca and phosphate (as PO4) contents between the newborn material and that from later stages. A relatively large amount of carbonate was detected in the calvaria from 6-day-old rats, in which only immature crystals were observed, thus indicating the beginning of apatite formation. Furthermore, using laser Raman microprobe analysis we confirmed that the Raman peak at 1120 cm-1 band, indicative of a Mg-CO3 compound, appeared at the 6-day stage. We also observed that the Raman peak at 988 cm-1 found in the samples from the newborn seemed to have shifted to 963-962 cm-1 in the case of those obtained from 6-day-old rats, a shift which suggests the conversion from the non-apatitic to the apatitic form. These results indicate that carbonate ions might facilitate the initiation of crystal development by converting the inhibitory Mg ion into its inactive form (Mg-carbonate compound).

  12. 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.

  13. 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

    2014-01-01

    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

  14. 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.

  15. 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

  16. Lack of long-term behavioral alterations after early postnatal treatment with tropisetron: implications for developmental psychobiology.

    PubMed

    Inta, Dragos; Vogt, Miriam A; Lima-Ojeda, Juan M; Pfeiffer, Natascha; Schneider, Miriam; Gass, Peter

    2011-07-01

    The early postnatal period represents a critical time window for brain development. Transient Cajal-Retzius cells in layer I of the cortex play an important role in cortical lamination by modulating neuronal migration and maturation. Recent data have demonstrated that the 5-HT(3) receptor antagonist and alpha7 nicotinic receptor partial agonist tropisetron, acting via 5-HT(3) receptors expressed on Cajal-Retzius cells, can disturb the formation of cortical columns at perinatal stages. This process is thought to be involved in several neuropsychiatric disorders. Here we investigated the possible long-term behavioral effects of exposure to tropisetron at early postnatal stages in mice. We found that the administration of 1mg/kg, intraperitoneal (i.p.) tropisetron from postnatal days 2-12 (P2-P12) did not induce significant cognitive, schizophrenia-like or emotional alterations in tropisetron-treated animals as compared to controls, when tested in multiple behavioral assays. These results may be of relevance regarding the possible protracted deleterious neuropsychiatric effects of tropisetron during early life.

  17. A role for Gcn5 in cardiomyocyte differentiation of rat mesenchymal stem cells.

    PubMed

    Li, Li; Zhu, Jing; Tian, Jie; Liu, Xiaoyan; Feng, Chuan

    2010-12-01

    MSCs possess the capacity of self-renewal and potential of differentiation into various kinds of specialized tissue cells including myocardiocytes. From self-renewing to oriented differentiation, chromatin is remodeled into heritable states that allow activation or maintain the repression of regulatory genes, which means specific genes in self-renewing switched off and specific genes in oriented differentiation activated (Bernstein et al. Cell 125:315-326, 2006). These epigenetic states are established and controlled largely by specific patterns of histone posttranslational modifications, in particular, histone acetylation (Li Nat Rev Genet 3:662-673, 2002). In cardiomyocyte differentiation of rat MSCs, we focused on Gcn5, which linked a known transcriptional coactivator with catalytic histone acetyltransferase activity (Brownell et al. Cell 84:843-851, 1996). To clarify participatory in vivo role of Gcn5, using an RNA interference (RNAi) strategy employing shRNA to specifically knockdown Gcn5 expression in MSCs, we found that HAT activity altered dynamically depended on the inhibition of Gcn5 during MSCs differentiation. Chromatin immunoprecipitation (ChIP) assay showed the increased binding of acetyl histone H3 to the early cardiomyocyte-specific genes GATA4 and NKx2.5 promoters in cardiomyocyte differentiation of MSCs by 5-azacytidine inducing, whereas the decreased binding with lower Gcn5 expression. Cell ultrastructure analysis revealed that MSCs induced by 5-azacytidine possess morphological characteristics of cardiomyocyte cells. The shape of MSCs transfected by Gcn5 RNAi was similar to normal MSCs, but the chromatin showed heavy electron-density and a hard-packed structure. This intermediate state of chromatin may be an inactive part of MSCs differentiation. These results demonstrate that Gcn5, possessing acetyltransferase activity, is involved in regulating chromatin configuration around GATA4 and NKx2.5 in cardiomyocyte differentiation of rat MSCs by

  18. 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…

  19. 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. PMID:25179105

  20. 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.

  1. Effects of ultraviolet A on the activity of two metabolic enzymes, DNA damage and lipid peroxidation during early developmental stages of the African catfish, Clarias gariepinus (Burchell, 1822)

    PubMed Central

    Mekkawy, Imam A. A.; Mahmoud, Usama M.; Osman, Alaa G.

    2009-01-01

    Many ultraviolet-A (UVA)-induced biochemical and physiological changes are valid as biomarkers using aquatic species for detection of the degree of stress. Changes in the concentration and activities of enzymes, such as glucose-6-phosphate dehyderogenase (G6PDH), lactate dehyderogenase (LDH), DNA damage and lipid peroxidation (LPO), can be used as biomarkers to identify possible environmental contamination in fish. This study aimed to investigate the impact of UVA on the activity of the selected enzymes, DNA damage and LPO during early developmental stages of the African catfish Clarias gariepinus. Embryo hemogenates were used for measurements of G6PDH, LDH, DNA damage and LPO concentrations and activities spectrophotometrically at 37°C. The normal ontogenetic variations in enzyme activities, DNA damage and LPO of the early developmental stages (24–168 h-PFS; hours-post fertilization stage) were studied. There was a significant decrease in the activity of G6PDH till 120 h-PFS. Then after 120 h-PFS, the activity of such enzymes insignificantly increased toward higher stages. The LDH activity was recorded with a pattern of decrease till 96 h-PFS, followed by a significant increase toward 168 h-PFS. The polynomial pattern of variations in DNA damage and LPO was also evident. The patterns of the enzyme activities, corresponding DNA damage and LPO of the early ontogenetic stages under the influence of three different UVA doses (15, 30 and 60 min), were recorded. The pattern of variations in G6PDH activity in UVA-induced groups was similar to that of the control group with variation in the magnitude of such activity. In all treated groups, LDH activity decreased till 96 h-PFS, then increased till 168 h-PFS. Within each of the embryonic stages, the increase in UVA led to a significant increase in DNA damage. A significant increase in lipid peroxidation under UVA doses was recorded. The variability in number and molecular weight of proteins under exposure to UVA

  2. 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...

  3. 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, ...

  4. Developmental Education.

    ERIC Educational Resources Information Center

    Bibb, T. Clifford

    1998-01-01

    Outlines steps developmental educators need to take to win the cooperation of more students. Argues also that developmental educators must include computer literacy in their understanding of literacy. (SR)

  5. The Developmental Progression of Age 14 Behavioral Disinhibition, Early Age of Sexual Initiation, and Subsequent Sexual Risk-Taking Behavior

    PubMed Central

    Samek, Diana R.; Iacono, William G.; Keyes, Margaret A.; Epstein, Marina; Bornovalova, Marina A.; McGue, Matt

    2013-01-01

    Background Research has demonstrated a consistent relationship between early sexual experience and subsequent sexual risk-taking behaviors. We hypothesized that this relationship is due to a general predisposition towards behavioral disinhibition (BD), and that relationships among BD, early sex, and subsequent risky sexual behavior may be influenced by common genetic influences for males and common environmental influences for females. Methods A prospective sample of 1,512 same-sex adolescent twins (50.2% female) was used. Adolescent BD was measured by clinical symptom counts of conduct disorder, oppositional defiant disorder, and self-reported delinquent behavior (age 14). Age of sexual initiation was defined as first age of consensual oral or penetrative sex (mean age ~17). Adult risky sexual behavior was defined by sexual behaviors under the influence of drugs and alcohol and number of casual sexual partners in the past year (age 24). Results Multivariate analyses showed evidence for substantial common genetic variance among age 14 BD, age at sexual initiation, and adult risky sexual behavior for males, but not females. There was no significant difference in the degree of common environmental influence on these variables for females compared to males. Notably, age of sexual initiation was not significantly correlated with age 24 risky sexual behavior for females. Conclusion The relationship between early sex and later risky sex can be better understood through a general liability towards BD, which is influenced primarily by genetic factors for males. The association between age 14 BD and age of sexual initiation was influenced through a combination of genetic and environmental factors for females; however, age of sexual initiation does not appear to be a salient predictor of adult women’s sexual risk-taking behavior. Findings suggest that prevention programs aimed at reducing sexual risk behavior might target youth exhibiting BD by age 14, particularly males

  6. 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. PMID:23316767

  7. Early developmental changes in the timing of turn-taking: a longitudinal study of mother–infant interaction

    PubMed Central

    Hilbrink, Elma E.; Gattis, Merideth; Levinson, Stephen C.

    2015-01-01

    To accomplish a smooth transition in conversation from one speaker to the next, a tight coordination of interaction between speakers is required. Recent studies of adult conversation suggest that this close timing of interaction may well be a universal feature of conversation. In the present paper, we set out to assess the development of this close timing of turns in infancy in vocal exchanges between mothers and infants. Previous research has demonstrated an early sensitivity to timing in interactions (e.g., Murray and Trevarthen, 1985). In contrast, less is known about infants’ abilities to produce turns in a timely manner and existing findings are rather patchy. We conducted a longitudinal study of 12 mother–infant dyads in free-play interactions at the ages of 3, 4, 5, 9, 12, and 18 months. Based on existing work and the predictions made by the Interaction Engine Hypothesis (Levinson, 2006), we expected that infants would begin to develop the temporal properties of turn-taking early in infancy but that their timing of turns would slow down at 12 months, which is around the time when infants start to produce their first words. Findings were consistent with our predictions: infants were relatively fast at timing their turn early in infancy but slowed down toward the end of the first year. Furthermore, the changes observed in infants’ turn-timing skills were not caused by changes in maternal timing, which remained stable across the 3–18 months period. However, the slowing down of turn-timing started somewhat earlier than predicted: at 9 months. PMID:26483741

  8. Developmental emergence of alcohol use disorder symptoms and their potential as early indicators for progression to alcohol dependence in a high risk sample: a longitudinal study from childhood to early adulthood.

    PubMed

    Buu, Anne; Wang, Wei; Schroder, Stephanie A; Kalaida, Natalia L; Puttler, Leon I; Zucker, Robert A

    2012-11-01

    This study characterized developmental emergence of individual alcohol use disorder (AUD) symptoms, and evaluated their ability as early indicators of progression into alcohol dependence (AD), conditional upon gender, parental alcohol dependence, early onset of drinking, and level of delinquent behavior at onset. The two parameters of interest were (a) likelihood of specific AUD symptom appearance once drinking has begun, and (b) primacy of symptom appearance as an indicator of likelihood for eventual move into diagnosis. We analyzed prospective data from a community sample of high risk youth from childhood to early adulthood. Symptoms that were at higher probability of being experienced at drinking onset and that could serve as good indicators for the early stage of disease progression were: persistent desire or unsuccessful efforts to control alcohol use (AD4), and continued use despite having persistent or recurrent interpersonal problems (AA4). Tolerance (AD1) may serve as an indicator for the intermediate stage of progression. Young people tended to be at an elevated risk for developing AD6 (activities given up), AD7 (physical/psychological problems), and AA3 (legal problems) in later years so these symptoms may be good indicators for later stages of progression. In addition to being male, an early onset drinker, or high in delinquent behavior, drinkers who experienced AA4 or AD1 as first symptoms were at higher risk for progression to AD. We also identified two high risk clusters: late onset drinkers with AA4 as first symptom, and children of alcoholics with AD1 as first symptom. PMID:21842966

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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. PMID:25199452

  14. 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. PMID:27572699

  15. 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.

  16. 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.

  17. High concentrations of H2O2 trigger hypertrophic cascade and phosphatase and tensin homologue (PTEN) glutathionylation in H9c2 cardiomyocytes.

    PubMed

    Panera, Nadia; Gnani, Daniela; Piermarini, Emanuela; Petrini, Stefania; Bertini, Enrico; Nobili, Valerio; Pastore, Anna; Piemonte, Fiorella; Alisi, Anna

    2016-02-01

    Cardiac hypertrophy occurs in response to different stimuli and is mainly characterized by an enlargement of cardiomyocyte size. During hypertrophy, cardiomyocytes undergo not only radical changes of the cellular architecture but also activation of signaling cascades that counteract the atrophy genes. Experimental studies highlighted that chronic low concentrations of H2O2, induce a hypertrophic phenotype, while higher levels of H2O2 promote apoptosis. In this study, we explored the early and long-term hypertrophic effects of high concentrations of H2O2 on H9c2 rat cardiomyocytes. We found that 2-h stimulation with 200μM H2O2 caused an early dramatic reduction of cell viability, accompanied, 5-days later, by increased cell size and up-regulation of atrial natriuretic peptide transcription. This hypertrophic phenotype is associated to increased Akt phosphorylation and a consequent reduction of the FOXO3a and atrogin-1 gene expression. Moreover, we observed that H2O2 caused the overexpression of miR-212/miR-132 cluster concomitantly to a down-regulation of PTEN transcript without changes in its protein expression. Noteworthy, we found that the treatment of cardiomyocytes with H2O2 further led to an increase of oxidized glutathione and glutathionylation of proteins, including PTEN. In conclusion, our results permit to reconstruct the molecular cascade triggering the cardiomyocyte hypertrophy upon high concentrations of H2O2.

  18. High concentrations of H2O2 trigger hypertrophic cascade and phosphatase and tensin homologue (PTEN) glutathionylation in H9c2 cardiomyocytes.

    PubMed

    Panera, Nadia; Gnani, Daniela; Piermarini, Emanuela; Petrini, Stefania; Bertini, Enrico; Nobili, Valerio; Pastore, Anna; Piemonte, Fiorella; Alisi, Anna

    2016-02-01

    Cardiac hypertrophy occurs in response to different stimuli and is mainly characterized by an enlargement of cardiomyocyte size. During hypertrophy, cardiomyocytes undergo not only radical changes of the cellular architecture but also activation of signaling cascades that counteract the atrophy genes. Experimental studies highlighted that chronic low concentrations of H2O2, induce a hypertrophic phenotype, while higher levels of H2O2 promote apoptosis. In this study, we explored the early and long-term hypertrophic effects of high concentrations of H2O2 on H9c2 rat cardiomyocytes. We found that 2-h stimulation with 200μM H2O2 caused an early dramatic reduction of cell viability, accompanied, 5-days later, by increased cell size and up-regulation of atrial natriuretic peptide transcription. This hypertrophic phenotype is associated to increased Akt phosphorylation and a consequent reduction of the FOXO3a and atrogin-1 gene expression. Moreover, we observed that H2O2 caused the overexpression of miR-212/miR-132 cluster concomitantly to a down-regulation of PTEN transcript without changes in its protein expression. Noteworthy, we found that the treatment of cardiomyocytes with H2O2 further led to an increase of oxidized glutathione and glutathionylation of proteins, including PTEN. In conclusion, our results permit to reconstruct the molecular cascade triggering the cardiomyocyte hypertrophy upon high concentrations of H2O2. PMID:26772165

  19. CYP1A Induction and Blue SAC Disease in Early Developmental Stages of Rainbow Trout (Oncorhynchus Mykiss) Exposed to Retene.

    PubMed

    Brinkworth, Lyndon; Hodson, Peter; Tabash, Samir; Lee, Patricia

    2003-01-01

    Early life stages of rainbow trout were exposed to different regimes of water-borne retene (7-isopropyl-1-methylphenanthrene) to determine if there is an ontogenic stage particularly sensitive to retene toxicity, and if cytochrome P-4501A (CYP1A) induction is a forerunner to blue sac disease (BSD), the syndrome of toxicity. CYP1A protein concentrations, measured by immunohistochemistry, were first detected during organogenesis, when organ and enzyme systems are first being developed, and steadily increased until swim-up. The prevalence of signs of BSD rose 1 wk following a marked increase in CYP1A activity after hatch, suggesting that CYP1A induction is related to BSD. The larval stage was the most sensitive to retene toxicity, based on CYP1A induction and a high prevalence of BSD. The most common signs of BSD were hemorrhaging, yolk-sac edema, and mortality, but hemorrhaging was the first and most frequently observed response. Tissue concentrations of retene were elevated just after fertilization, but decreased steadily as fish developed to the swim-up stage, most likely due to the establishment of more efficient metabolic and excretory systems in later stages of development. PMID:12746134

  20. CYP1A induction and blue sac disease in early developmental stages of rainbow trout (Oncorhynchus Mykiss) exposed to retene.

    PubMed

    Brinkworth, Lyndon C; Hodson, Peter V; Tabash, Samir; Lee, Patricia

    2003-04-11

    Early life stages of rainbow trout were exposed to different regimes of water-borne retene (7-isopropyl-1-methylphenanthrene) to determine if there is an ontogenic stage particularly sensitive to retene toxicity, and if cytochrome P-4501A (CYP1A) induction is a forerunner to blue sac disease (BSD), the syndrome of toxicity. CYP1A protein concentrations, measured by immunohistochemistry, were first detected during organogenesis, when organ and enzyme systems are first being developed, and steadily increased until swim-up. The prevalence of signs of BSD rose 1 wk following a marked increase in CYP1A activity after hatch, suggesting that CYP1A induction is related to BSD. The larval stage was the most sensitive to retene toxicity, based on CYP1A induction and a high prevalence of BSD. The most common signs of BSD were hemorrhaging, yolk-sac edema, and mortality, but hemorrhaging was the first and most frequently observed response. Tissue concentrations of retene were elevated just after fertilization, but decreased steadily as fish developed to the swim-up stage, most likely due to the establishment of more efficient metabolic and excretory systems in later stages of development. PMID:12751390

  1. 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. PMID:16522542

  2. Ischemia/Reperfusion Injury of Primary Porcine Cardiomyocytes in a Low-Shear Microfluidic Culture and Analysis Device

    PubMed Central

    Khanal, Grishma; Chung, Kiyong; Solis-Wever, Ximena; Johnson, Bradley; Pappas, Dimitri

    2011-01-01

    Ischemia/reperfusion (I/R) injury was induced in primary porcine cardiomyocytes in a low-shear microfluidic culture chip. The chip was capable of sustaining cardiomyocyte culture and inducing I/R injury by subjecting the cells to periods of hypoxia lasting 3-4 hours followed by normoxia. Mitochondrial membrane potential was assayed using MitoTracker Red to follow mitochondrial depolarization, the earliest stage of apoptosis. Cell adhesion and morphology were also determined simultaneously with fluorescence measurements. Changes in membrane potential were observed earlier than previously reported, with mitochondria becoming depolarized as early as 2 hours into the ischemia period. The cells with depolarized mitochondria were deemed apoptotic. Out of 38-61 cells per time frame, the fraction of apoptotic cells was found to be similar to control samples (3%) at two hours of ischemia, which increased up to 22% at the end of ischemia period as compared to 0% in the control samples. Morphological analysis of cells showed that 4 hours of ischemia followed by reperfusion produced blebbing cells within 2 hours of restoring oxygen to the chip. This approach is a versatile method for cardiomyocyte stress, and in future work additional analytical probes can be incorporated for a multi-analyte assays of cardiomyocyte apoptosis. PMID:21271001

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. (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.

  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. Gene expression changes triggered by end-of-day far-red light treatment on early developmental stages of Eustoma grandiflorum (Raf.) Shinn.

    PubMed

    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

  10. Morphological Properties in Dopaminergic Neurons of the Rat Midbrain during Early Developmental Stages and One Numerical Approach to Passive-Membrane Modeling

    NASA Astrophysics Data System (ADS)

    Tateno, Takashi

    In this study, I aim to understand morphological changes in dopaminergic neurons of the rat midbrain during early developmental stages and their computational properties in the dendrites. To this end, firstly, I measured morphological details of dopaminergic neurons using an immunochemical double-staining technique. In the viewpoint of the Rall's equivalent-cylinder model, secondly, I tested if the data satisfied one of conditions (3/2 power law) of the Rall's model. On the basis of the experimental data, I next investigated if some branches in the individual dendrites had special selectivity in efficient passive propagation of membrane potentials between the branches of individual cells and different cells. The results show that the Rall's 3/2 power law was not satisfied in many branch points and that among branches of each dendrite, specific selectivity in efficient propagation was not found. In addition, I note an implementation method in which the finite element method is applied to one-dimensional cable model of dendrites and give some numerical examples.

  11. (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. PMID:26439058

  12. Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo

    PubMed Central

    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. PMID:26469858

  13. 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.

  14. Embryonic Cardiac Chamber Maturation: Trabeculation, Conduction and Cardiomyocyte Proliferation

    PubMed Central

    Samsa, Leigh Ann; Yang, Betsy; Liu, Jiandong

    2013-01-01

    Congenital heart diseases are one of the most common human birth defects. Though some congenital heart defects can be surgically corrected, treatment options for other congenital heart diseases are very limited. In many congenital heart diseases, genetic defects lead to impaired embryonic heart development or growth. One of the key development processes in cardiac development is chamber maturation, and alterations in this maturation process can manifest as a variety of congenital defects including noncompaction, systolic dysfunction, diastolic dysfunction, and arrhythmia. During development, to meet the increasing metabolic demands of the developing embryo, the myocardial wall undergoes extensive remodeling characterized by the formation of muscular luminal protrusions called cardiac trabeculae, increased cardiomyocyte mass, and development of the ventricular conduction system. Though the basic morphological and cytological changes involved in early heart development are clear, much remains unknown about the complex biomolecular mechanisms governing chamber maturation. In this review, we highlight evidence suggesting that a wide variety of basic signaling pathways and biomechanical forces are involved in cardiac wall maturation. PMID:23720419

  15. Developmental dyscalculia.

    PubMed

    Shalev, R S; Gross-Tsur, V

    2001-05-01

    Developmental dyscalculia is a specific learning disability affecting the acquisition of arithmetic skills in an otherwise-normal child. Although poor teaching, environmental deprivation, and low intelligence have been implicated in the etiology of developmental dyscalculia, current data indicate that this learning disability is a brain-based disorder with a familial-genetic predisposition. The neurologic substrate of developmental dyscalculia is thought to involve both hemispheres, particularly the left parietotemporal areas. Developmental dyscalculia is a common cognitive handicap; its prevalence in the school population is about 5-6%, a frequency similar to those of developmental dyslexia and attention-deficit-hyperactivity disorder. Unlike these, however, it is as common in females as in males. Developmental dyscalculia frequently is encountered in neurologic disorders, examples of which include attention-deficit-hyperactivity disorder, developmental language disorder, epilepsy, and fragile X syndrome. The long-term prognosis of developmental dyscalculia is unknown; it appears, however, to persist, at least for the short-term, in about half of affected preteen children. The consequences of developmental dyscalculia and its impact on education, employment, and psychologic well-being of affected individuals are unknown. PMID:11516606

  16. 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.

  17. 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

  18. Building and re-building the heart by cardiomyocyte proliferation.

    PubMed

    Foglia, Matthew J; Poss, Kenneth D

    2016-03-01

    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.

  19. 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. PMID:23602992

  20. 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.

  1. Developmental Concept of Idiocy

    ERIC Educational Resources Information Center

    Simpson, Murray

    2007-01-01

    In dominant definitions of mental retardation, researchers have insisted on the diagnosis being restricted to conditions manifested during the developmental period. However, even in the 19th century, this was only one of several conceptual options, some of which did not exclude adult brain injury or dementia. Events in the 19th and early 20th…

  2. 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.

  3. 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

  4. Calcium-sensing receptor induces rat neonatal ventricular cardiomyocyte apoptosis

    SciTech Connect

    Sun Yihua; Liu Meina; Li Hong; Shi Sa; Zhao Yajun; Wang Rui; Xu Changqing . E-mail: syh200415@yahoo.com.cn

    2006-12-01

    The calcium-sensing receptor (CaSR) exists in many tissues, and its expression has been identified in rat cardiac tissue. However, Physiological importance and pathophysiological involvement of CaSR in homeostatic regulation of cardiac function are unclear. To investigate the relation of CaSR and apoptosis in cardiomyocytes, we examined the role of the CaSR activator gadolinium chloride (GdCl{sub 3}) in rat neonatal ventricular cardiomyocytes. Expression of the CaSR protein was observed by Western blot. The apoptotic ratio of rat neonatal ventricular cardiomyocytes was measured with flow cytometry and immunofluorescence techniques. A laser scan confocal microscope was used to detect the intracellular concentration of calcium ([Ca{sup 2+}]{sub i}) in rat neonatal ventricular cardiomyocytes using the acetoxymethyl ester of fluo-3 (fluo-3/(AM)) as a fluorescent dye. The results showed that GdCl{sub 3} increased the phosphorylation of extracellular signal-regulated protein kinase (ERK), c-Jun NH{sub 2}-terminal protein kinases (JNK), and p38. GdCl{sub 3} also activated caspase 9 and increased apoptosis in myocyte by increasing [Ca{sup 2+}]{sub i}. In conclusion, these results suggest that CaSR promotes cardiomyocyte apoptosis in rat neonatal ventricular cardiomyocytes through activation of mitogen-activated protein kinases and caspase 9 signaling pathways.

  5. 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

  6. Biomechanical Characterization of Cardiomyocyte Using PDMS Pillar with Microgrooves.

    PubMed

    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

  7. 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.

  8. Non-invasive Chamber-Specific Identification of Cardiomyocytes in Differentiating Pluripotent Stem Cells

    PubMed Central

    Brauchle, Eva; Knopf, Anne; Bauer, Hannah; Shen, Nian; Linder, Sandra; Monaghan, Michael G.; Ellwanger, Kornelia; Layland, Shannon L.; Brucker, Sara Y.; Nsair, Ali; Schenke-Layland, Katja

    2016-01-01

    Summary One major obstacle to the application of stem cell-derived cardiomyocytes (CMs) for disease modeling and clinical therapies is the inability to identify the developmental stage of these cells without the need for genetic manipulation or utilization of exogenous markers. In this study, we demonstrate that Raman microspectroscopy can non-invasively identify embryonic stem cell (ESC)-derived chamber-specific CMs and monitor cell maturation. Using this marker-free approach, Raman peaks were identified for atrial and ventricular CMs, ESCs were successfully discriminated from their cardiac derivatives, a distinct phenotypic spectrum for ESC-derived CMs was confirmed, and unique spectral differences between fetal versus adult CMs were detected. The real-time identification and characterization of CMs, their progenitors, and subpopulations by Raman microspectroscopy strongly correlated to the phenotypical features of these cells. Due to its high molecular resolution, Raman microspectroscopy offers distinct analytical characterization for differentiating cardiovascular cell populations. PMID:26777059

  9. 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

  10. Argon Induces Protective Effects in Cardiomyocytes during the Second Window of Preconditioning

    PubMed Central

    Mayer, Britta; Soppert, Josefin; Kraemer, Sandra; Schemmel, Sabrina; Beckers, Christian; Bleilevens, Christian; Rossaint, Rolf; Coburn, Mark; Goetzenich, Andreas; Stoppe, Christian

    2016-01-01

    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. PMID:27447611

  11. 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

    2016-01-01

    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. PMID:27447611

  12. 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.

  13. 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. PMID:27288148

  14. 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

  15. 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

  16. Cardiomyocyte cytoskeleton and myofibrillogenesis in healthy and diseased heart.

    PubMed

    Ehler, E; Perriard, J C

    2000-10-01

    The unique cytoarchitecture of cardiomyocytes arises by complex interactions of different filamentous structures of the cytoskeleton. Intermediate filaments of the non-sarcomeric cytoskeleton are not essential for development but important for maintenance of myofibrils. Myofibrils consist of contractile proteins involved in force generation and the muscle cytoskeleton framework. The latter is essential for proper assembly and maintenance as well as for interaction with other cardiomyocytes or the extracellular matrix, thus being involved in force transmission. The information for sarcomere assembly is encoded in the proteins and some domains essential for faithful incorporation have been identified by epitope tagging experiments. Many KO mutations result in embryonic lethal phenotypes and new techniques e.g. using cardiomyocytes derived from ES cell-lines will have to be developed that allow to study such mutations in cardiomyocytes rather than whole organisms. Alterations in the expression levels of several proteins of the muscle cytoskeleton or impairment of their function by point mutations can result in increased mechanical stress in the cardiomyocytes which finally leads to cellular responses such as the development of dilated cardiomyopathy (DCM). MLP (muscle-LIM-protein) deficient mice develop DCM and changes in the mechanical coupling of cardiomyocytes result in alterations at the intercalated disks and enhanced accumulation of adherens junction proteins. Therefore, controlled interactions between proteins of the muscle cytoskeleton and contractile proteins are essential to ensure proper cardiac function and a more detailed insight in these processes might provide new tools to improve the contractile efficiency of the cardiomyocytes and thus working output in cardiomyopathies.

  17. Dopamine and lipophilic derivates protect cardiomyocytes against cold preservation injury.

    PubMed

    Vettel, Christiane; Hottenrott, Maximilia C; Spindler, Rahel; Benck, Urs; Schnuelle, Peter; Tsagogiorgas, Charalambos; Krämer, Bernhard K; Hoeger, Simone; El-Armouche, Ali; Wieland, Thomas; Yard, Benito A

    2014-01-01

    Donor heart allografts are extremely susceptible to prolonged static cold storage. Because donor treatment with low-dose dopamine improves clinical outcome after heart transplantation, we tested the hypothesis that dopamine and its lipophilic derivate, N-octanoyl dopamine (NOD), protect cardiomyocytes from cold storage injury. Neonatal rat cardiomyocytes were treated with dopamine or NOD or left untreated and subsequently subjected to static cold storage (8-12 hours). Dopamine- and NOD-treated cardiomyocytes displayed a better viability compared with untreated cells after hypothermia. In untreated cardiomyocytes, cell damage was reflected by lactate dehydrogenase (LDH) release and a decrease in intracellular ATP. NOD was approximately 20-fold more potent than dopamine. Similarly to cardiomyocytes in vitro, rat hearts perfused with NOD before explantation showed significantly lower LDH release after static cold storage. ATP regeneration and spontaneous contractions after cold storage and rewarming only occurred in treated cardiomyocytes. Hypothermia severely attenuated isoprenaline-induced cAMP formation in control but not in dopamine- or NOD-treated cells. Esterified derivates of NOD with redox potential and lipophilic side chains reduced cell damage during cold storage similarly to NOD. In contrast to dopamine, neither NOD nor its derivates induced a significant β-adrenoceptor-mediated elevation of cellular cAMP levels. The β1-adrenoceptor antagonist atenolol and D1/D2 receptor antagonist fluphenazine had no impact on the protective effect of NOD or dopamine. We conclude that dopamine as well as NOD treatment mitigates cold preservation injury to cardiomyocytes. The beneficial effects are independent of β-adrenoceptor or dopaminergic receptor stimulation but correlate with redox potential and lipophilic properties.

  18. Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy

    PubMed Central

    Alvarez, Bernardo V; Johnson, Danielle E; Sowah, Daniel; Soliman, Daniel; Light, Peter E; Xia, Ying; Karmazyn, Morris; Casey, Joseph R

    2007-01-01

    Hypertrophic cardiomyocyte growth contributes substantially to the progression of heart failure. Activation of the plasma membrane Na+–H+ exchanger (NHE1) and Cl−–HCO3− exchanger (AE3) has emerged as a central point in the hypertrophic cascade. Both NHE1 and AE3 bind carbonic anhydrase (CA), which activates their transport flux, by providing H+ and HCO3−, their respective transport substrates. We examined the contribution of CA activity to the hypertrophic response of cultured neonatal and adult rodent cardiomyocytes. Phenylephrine (PE) increased cell size by 37 ± 2% and increased expression of the hypertrophic marker, atrial natriuretic factor mRNA, twofold in cultured neonatal rat cardiomyocytes. Cell size was also increased in adult cardiomyocytes subjected to angiotensin II or PE treatment. These effects were associated with increased expression of cytosolic CAII protein and the membrane-anchored isoform, CAIV. The membrane-permeant CA inhibitor, 6-ethoxyzolamide (ETZ), both prevented and reversed PE-induced hypertrophy in a concentration-dependent manner in neonate cardiomyocytes (IC50 = 18 μm). ETZ and the related CA inhibitor methazolamide prevented hypertrophy in adult cardiomyocytes. In addition, ETZ inhibited transport activity of NHE1 and the AE isoform, AE3, with respective EC50 values of 1.2 ± 0.3 μm and 2.7 ± 0.3 μm. PE significantly increased neonatal cardiomyocyte Ca2+ transient frequency from 0.33 ± 0.4 Hz to 0.77 ± 0.04 Hz following 24 h treatment; these Ca2+-handling abnormalities were completely prevented by ETZ (0.28 ± 0.07 Hz). Our study demonstrates a novel role for CA in mediating the hypertrophic response of cardiac myocytes to PE and suggests that CA inhibition represents an effective therapeutic approach towards mitigation of the hypertrophic phenotype. PMID:17124262

  19. Developmental Disabilities

    MedlinePlus

    ... many causes of developmental disabilities, including Genetic or chromosome abnormalities. These cause conditions such as Down syndrome and Rett syndrome. Prenatal exposure to substances. Drinking alcohol when ... also help. NIH: National Institute of Child Health and Human Development

  20. 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...

  1. Developmental Trends.

    ERIC Educational Resources Information Center

    Howe, Frederick C.

    1993-01-01

    Explores developmental patterns in children from kindergarten through grade six. Highlights physical development, including height, activity level, motor skills, and health; mental development, including abstract thought, academic focus, learning difficulties, subject preferences, and creativity; psychosocial development, including interpersonal…

  2. Comparison of osteoblast and cardiomyocyte differentiation in the embryonic stem cell test for predicting embryotoxicity in vivo.

    PubMed

    de Jong, Esther; van Beek, Lianne; Piersma, Aldert H

    2014-09-01

    One of the most studied alternative embryotoxicity assays is the embryonic stem cell test, in which the effect of compounds on cardiomyocyte differentiation is evaluated (subsequently termed the ESTc). This single differentiation endpoint may limit the predictive value of the assay. We recently published a novel embryonic stem cell based osteoblast differentiation assay (subsequently termed the ESTo), in which we studied the effect of six embryotoxic compounds. Differentiation is monitored via the differential expression of three genes related to osteogenesis (Runx2, SPARC and collagen type I). In the current study, we evaluated the effect of 14 additional compounds in the ESTo, to assess its added value as compared to the ESTc. To this end, we compared the effects of the compounds in the ESTo to their effects in the ESTc and to their published in vivo developmental toxicity profiles. The results show that there is a high overall correlation between compound potencies as regards inhibition of osteoblast and cardiomyocyte differentiation. Moreover, the results in both the ESTo and ESTc showed a significant correlation to in vivo developmental toxicity potency ranking of compounds tested. Interestingly, the embryotoxic effect of TCDD could only be detected using the ESTo, which can be explained based on its mechanism of action and its known inhibitory effect on osteogenesis. The results of TCDD suggest that incorporating the ESTo into a testing battery together with the ESTc could improve the overall predictive value of the battery.

  3. Disruption of the circadian clock within the cardiomyocyte influences mycardial contractile function, metabolism, and gene expression

    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 is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variatio...

  4. 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...

  5. Autonomous beating rate adaptation in human stem cell-derived cardiomyocytes.

    PubMed

    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

  6. 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

  7. 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.

  8. Glucocorticoid signaling in the heart: A cardiomyocyte perspective.

    PubMed

    Oakley, Robert H; Cidlowski, John A

    2015-09-01

    Heart failure is one of the leading causes of death in the Western world. Glucocorticoids are primary stress hormones that regulate a vast array of biological processes, and synthetic derivatives of these steroids have been mainstays in the clinic for the last half century. Abnormal levels of glucocorticoids are known to negatively impact the cardiovascular system; however, surprisingly little is known about the direct role of glucocorticoid signaling in the heart. The actions of glucocorticoids are mediated classically by the glucocorticoid receptor (GR). In certain cells, such as cardiomyocytes, glucocorticoid occupancy and activation of the mineralocorticoid receptor (MR) may also contribute to the observed response. Recently, there has been a surge of reports investigating the in vivo function of glucocorticoid signaling in the heart using transgenic mice that specifically target GR or MR in cardiomyocytes. Results from these studies suggest that GR signaling in cardiomyocytes is critical for the normal development and function of the heart. In contrast, MR signaling in cardiomyocytes participates in the development and progression of cardiac disease. In the following review, we discuss these genetic mouse models and the new insights they are providing into the direct role cardiomyocyte glucocorticoid signaling plays in heart physiology and pathophysiology. This article is part of a Special Issue entitled 'Steroid Perspectives'.

  9. On the presence of serotonin in mammalian cardiomyocytes.

    PubMed

    Pönicke, Klaus; Gergs, Ulrich; Buchwalow, Igor B; Hauptmann, Steffen; Neumann, Joachim

    2012-06-01

    Pleiotropic effects of serotonin (5-HT) in the cardiovascular system are well documented. However, it remains to be elucidated, whether 5-HT is present in adult mammalian cardiomyocytes. To address this issue, we investigated the levels of 5-HT in blood, plasma, platelets, cardiac tissue, and cardiomyocytes from adult mice and for comparison in human right atrial tissue. Immunohistochemically, 5-HT was hardly found in mouse cardiac tissue, but small amounts could be detected in renal preparations, whereas adrenal preparations revealed a strong positive immunoreaction for 5-HT. Using a sensitive HPLC detection system, 5-HT was also detectable in the mouse heart and human atrium. Furthermore, we could identify 5-HT in isolated cardiomyocytes from adult mice. These findings were supported by detection of the activity of 5-HT-forming enzymes-tryptophan hydroxylase and aromatic L-amino acid decarboxylase-in isolated cardiomyocytes from adult mice and by inhibition of these enzymes with p-chlorophenylalanine and 3-hydroxybenzyl hydrazine. Addition of the first intermediate of 5-HT generation, that is 5-hydroxytryptophan, enhanced the 5-HT level and inhibition of monoamine oxidase by tranylcypromine further increased the level of 5-HT. Our findings reveal the presence and synthesis of 5-HT in cardiomyocytes of the mammalian heart implying that 5-HT may play an autocrine and/or paracrine role in the heart. PMID:22367115

  10. 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.

  11. 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

  12. Developmental Triclosan Exposure Decreases Maternal, Fetal, and Early Neonatal Thyroxine: Dynamic and Kinetic Evaluation of a Putative Mode-of-Action

    PubMed Central

    Paul, Katie B.; Hedge, Joan M.; Bansal, Ruby; Zoeller, R. Thomas; Peter, Robert; DeVito, Michael J.; Crofton, Kevin M.

    2012-01-01

    This work tests the mode-of-action (MOA) hypothesis that maternal and developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via up-regulation of hepatic catabolism and elimination of T4. Time-pregnant Long-Evans rats received TCS po (0–300 mg/kg/day) from gestational day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, triiodothyronine (T3), and thyroid stimulating hormone (TSH) concentrations were measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. Custom Taqman® qPCR arrays were employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid-hormone responsive genes. TCS was quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and PND22 dams (300 mg/kg/day). Hepatic PROD activity increased 2- to 3-fold in PND4 pups and PND22 dams, and UGT activity was 1.5-fold higher in PND22 dams only (300 mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was consistent with hypothesized activation of the constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute to TCS–induced hypothyroxinemia during development. Serum and liver TCS concentrations demonstrated greater fetal than postnatal internal exposure, consistent with the lack of T4 changes in PND14 and PND21 offspring. These data support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via increased hepatic catabolism; however, the minor effects on thyroid hormone metabolism may

  13. Developmental triclosan exposure decreases maternal, fetal, and early neonatal thyroxine: a dynamic and kinetic evaluation of a putative mode-of-action.

    PubMed

    Paul, Katie B; Hedge, Joan M; Bansal, Ruby; Zoeller, R Thomas; Peter, Robert; DeVito, Michael J; Crofton, Kevin M

    2012-10-01

    This work tests the mode-of-action (MOA) hypothesis that maternal and developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via up-regulation of hepatic catabolism and elimination of T4. Time-pregnant Long-Evans rats received TCS po (0-300mg/kg/day) from gestational day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations were measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. Custom Taqman(®) qPCR arrays were employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid hormone-responsive genes. TCS was quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and PND22 dams (300mg/kg/day). Hepatic PROD activity increased 2-3 fold in PND4 pups and PND22 dams, and UGT activity was 1.5 fold higher in PND22 dams only (300mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was consistent with hypothesized activation of the constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute to TCS-induced hypothyroxinemia during development. Serum and liver TCS concentrations demonstrated greater fetal than postnatal internal exposure, consistent with the lack of T4 changes in PND14 and PND21 offspring. These data support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via increased hepatic catabolism; however, the minor effects on thyroid hormone metabolism may reflect the

  14. Risk factors for early redislocation after primary treatment of developmental dysplasia of the hip: Is there a protective influence of the ossific nucleus?

    PubMed Central

    Bhaskar, Atul; Desai, Hardik; Jain, Gaurav

    2016-01-01

    Background: Re-dislocation after primary treatment of developmental dysplasia of the hip is a serious complication. We analyzed the various risk factors that contribute to re-dislocation, and whether the bony ossific nucleus (ON) confers increased stability against re-dislocation. Materials and Methods: Fifty-five children (60 hips) were classified into three treatment groups: Closed reduction (CR) in 15 children (17 hips), open reduction (OR) in 26 children (28 hips), and OR with bony surgery (ORB) in 14 children (15 hips). The mean age at initial treatment was 16 months (range 6–36 months). Fifty-one hips and 9 hips were Tonnis Grade 4 and 3, respectively. The mean preoperative acetabular index (AI) was 44.82° (range 32°–56°) for the study group. At initial treatment, bony ON was absent in 8 hips and present in 52 hips. Results: No hip developed stiffness and pain after primary treatment. Although the AI index, Tonnis grade, and absence of ossific nucleus were higher in the re-dislocated groups, this was not statistically significant. Excluding the re-dislocations, four children had a fair outcome, 11 had good outcome, and 36 had excellent outcome as per McKay's criteria. In the CR group (17 hips), two children (2 hips) with absent ON had re-dislocation. In the OR group (28 hips), three re-dislocations were seen (three children) at 3, 5, and 7 months, respectively. Two of these had an absent bony ON. In the ORB group (15 hips), one late sub-luxation occurred in a child with absent ON. The mean preoperative AI for the re-dislocated and located group was 44.66° (range 42°–48°) and 44.53° (range 39°–56°), respectively. The postoperative AI was 34.53. Conclusion: The experience of the treating surgeon and technical factors play an overwhelming role in preventing early dislocation. The absence of ON should perhaps alert the surgeon for enhanced spica care, postoperative splinting, and meticulous intra-operative management. PMID:27746489

  15. Endothelial cell-cardiomyocyte crosstalk in diabetic cardiomyopathy.

    PubMed

    Wan, Andrea; Rodrigues, Brian

    2016-08-01

    The incidence of diabetes is increasing globally, with cardiovascular disease accounting for a substantial number of diabetes-related deaths. Although atherosclerotic vascular disease is a primary reason for this cardiovascular dysfunction, heart failure in patients with diabetes might also be an outcome of an intrinsic heart muscle malfunction, labelled diabetic cardiomyopathy. Changes in cardiomyocyte metabolism, which encompasses a shift to exclusive fatty acid utilization, are considered a leading stimulus for this cardiomyopathy. In addition to cardiomyocytes, endothelial cells (ECs) make up a significant proportion of the heart, with the majority of ATP generation in these cells provided by glucose. In this review, we will discuss the metabolic machinery that drives energy metabolism in the cardiomyocyte and EC, its breakdown following diabetes, and the research direction necessary to assist in devising novel therapeutic strategies to prevent or delay diabetic heart disease. PMID:27288009

  16. Dietary levels of acrylamide affect rat cardiomyocyte properties.

    PubMed

    Walters, Brandan; Hariharan, Venkatesh; Huang, Hayden

    2014-09-01

    The toxic effects of acrylamide on cytoskeletal integrity and ion channel balance is well-established in many cell types, but there has been little examination regarding the effects of acrylamide on primary cardiomyocytes, despite the importance of such components in their function. Furthermore, acrylamide toxicity is generally examined using concentrations higher than those found in vivo under starch-rich diets. Accordingly, we sought to characterize the dose-dependent effects of acrylamide on various properties, including cell morphology, contraction patterns, and junctional connexin 43 staining, in primary cardiomyocytes. We show that several days exposure to 1-100 μM acrylamide resulted in altered morphology, irregular contraction patterns, and an increase in the amount of immunoreactive signal for connexin 43 at cell junctions. We conclude that dietary levels of acrylamide may alter cellular function with prolonged exposure, in primary cardiomyocytes.

  17. Redox mechanisms of cardiomyocyte mitochondrial protection

    PubMed Central

    Bartz, Raquel R.; Suliman, Hagir B.; Piantadosi, Claude A.

    2015-01-01

    Oxidative and nitrosative stress are primary contributors to the loss of myocardial tissue in insults ranging from ischemia/reperfusion injury from coronary artery disease and heart transplantation to sepsis-induced myocardial dysfunction and drug-induced myocardial damage. This cell damage caused by oxidative and nitrosative stress leads to mitochondrial protein, DNA, and lipid modifications, which inhibits energy production and contractile function, potentially leading to cell necrosis and/or apoptosis. However, cardiomyocytes have evolved an elegant set of redox-sensitive mechanisms that respond to and contain oxidative and nitrosative damage. These responses include the rapid induction of antioxidant enzymes, mitochondrial DNA repair mechanisms, selective mitochondrial autophagy (mitophagy), and mitochondrial biogenesis. Coordinated cytoplasmic to nuclear cell-signaling and mitochondrial transcriptional responses to the presence of elevated cytoplasmic oxidant production, e.g., H2O2, allows nuclear translocation of the Nfe2l2 transcription factor and up-regulation of downstream cytoprotective genes such as heme oxygenase-1 which generates physiologic signals, such as CO that up-regulates Nfe212 gene transcription. Simultaneously, a number of other DNA binding transcription factors are expressed and/or activated under redox control, such as Nuclear Respiratory Factor-1 (NRF-1), and lead to the induction of genes involved in both intracellular and mitochondria-specific repair mechanisms. The same insults, particularly those related to vascular stress and inflammation also produce elevated levels of nitric oxide, which also has mitochondrial protein thiol-protective functions and induces mitochondrial biogenesis through cyclic GMP-dependent and perhaps other pathways. This brief review provides an overview of these pathways and interconnected cardiac repair mechanisms. PMID:26578967

  18. Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity.

    PubMed

    Dutta, Debapriya; Xu, Jinze; Kim, Jae-Sung; Dunn, William A; Leeuwenburgh, Christiaan

    2013-03-01

    Autophagy is a cellular self-digestion process that mediates protein quality control and serves to protect against neurodegenerative disorders, infections, inflammatory diseases and cancer. Current evidence suggests that autophagy can selectively remove damaged organelles such as the mitochondria. Mitochondria-induced oxidative stress has been shown to play a major role in a wide range of pathologies in several organs, including the heart. Few studies have investigated whether enhanced autophagy can offer protection against mitochondrially-generated oxidative stress. We induced mitochondrial stress in cardiomyocytes using antimycin A (AMA), which increased mitochondrial superoxide generation, decreased mitochondrial membrane potential and depressed cellular respiration. In addition, AMA augmented nuclear DNA oxidation and cell death in cardiomyocytes. Interestingly, although oxidative stress has been proposed to induce autophagy, treatment with AMA did not result in stimulation of autophagy or mitophagy in cardiomyocytes. Our results showed that the MTOR inhibitor rapamycin induced autophagy, promoted mitochondrial clearance and protected cardiomyocytes from the cytotoxic effects of AMA, as assessed by apoptotic marker activation and viability assays in both mouse atrial HL-1 cardiomyocytes and human ventricular AC16 cells. Importantly, rapamycin improved mitochondrial function, as determined by cellular respiration, mitochondrial membrane potential and morphology analysis. Furthermore, autophagy induction by rapamycin suppressed the accumulation of ubiquitinylated proteins induced by AMA. Inhibition of rapamycin-induced autophagy by pharmacological or genetic interventions attenuated the cytoprotective effects of rapamycin against AMA. We propose that rapamycin offers cytoprotection against oxidative stress by a combined approach of removing dysfunctional mitochondria as well as by degrading damaged, ubiquitinated proteins. We conclude that autophagy induction by

  19. Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity

    PubMed Central

    Dutta, Debapriya; Xu, Jinze; Kim, Jae-Sung; Dunn, Jr., William A.; Leeuwenburgh, Christiaan

    2013-01-01

    Autophagy is a cellular self-digestion process that mediates protein quality control and serves to protect against neurodegenerative disorders, infections, inflammatory diseases and cancer. Current evidence suggests that autophagy can selectively remove damaged organelles such as the mitochondria. Mitochondria-induced oxidative stress has been shown to play a major role in a wide range of pathologies in several organs, including the heart. Few studies have investigated whether enhanced autophagy can offer protection against mitochondrially-generated oxidative stress. We induced mitochondrial stress in cardiomyocytes using antimycin A (AMA), which increased mitochondrial superoxide generation, decreased mitochondrial membrane potential and depressed cellular respiration. In addition, AMA augmented nuclear DNA oxidation and cell death in cardiomyocytes. Interestingly, although oxidative stress has been proposed to induce autophagy, treatment with AMA did not result in stimulation of autophagy or mitophagy in cardiomyocytes. Our results showed that the MTOR inhibitor rapamycin induced autophagy, promoted mitochondrial clearance and protected cardiomyocytes from the cytotoxic effects of AMA, as assessed by apoptotic marker activation and viability assays in both mouse atrial HL-1 cardiomyocytes and human ventricular AC16 cells. Importantly, rapamycin improved mitochondrial function, as determined by cellular respiration, mitochondrial membrane potential and morphology analysis. Furthermore, autophagy induction by rapamycin suppressed the accumulation of ubiquitinylated proteins induced by AMA. Inhibition of rapamycin-induced autophagy by pharmacological or genetic interventions attenuated the cytoprotective effects of rapamycin against AMA. We propose that rapamycin offers cytoprotection against oxidative stress by a combined approach of removing dysfunctional mitochondria as well as by degrading damaged, ubiquitinated proteins. We conclude that autophagy induction by

  20. Lumican deficiency results in cardiomyocyte hypertrophy with altered collagen assembly.

    PubMed

    Dupuis, Loren E; Berger, Matthew G; Feldman, Samuel; Doucette, Lorna; Fowlkes, Vennece; Chakravarti, Shukti; Thibaudeau, Sarah; Alcala, Nicolas E; Bradshaw, Amy D; Kern, Christine B

    2015-07-01

    The ability of the heart to adapt to increased stress is dependent on the modification of its extracellular matrix (ECM) architecture that is established during postnatal development as cardiomyocytes differentiate, a process that is poorly understood. We hypothesized that the small leucine-rich proteoglycan (SLRP) lumican (LUM), which binds collagen and facilitates collagen assembly in other tissues, may play a critical role in establishing the postnatal murine myocardial ECM. Although previous studies suggest that LUM deficient mice (lum(-/-)) exhibit skin anomalies consistent with Ehlers-Danlos syndrome, lum(-/-) hearts have not been evaluated. These studies show that LUM was immunolocalized to non-cardiomyocytes of the cardiac ventricles and its expression increased throughout development. Lumican deficiency resulted in significant (50%) perinatal death and further examination of the lum(-/-) neonatal hearts revealed an increase in myocardial tissue without a significant increase in cell proliferation. However cardiomyocytes from surviving postnatal day 0 (P0), 1 month (1 mo) and adult (4 mo) lum(-/-) hearts were significantly larger than their wild type (WT) littermates. Immunohistochemistry revealed that the increased cardiomyocyte size in the lum(-/-) hearts correlated with alteration of the cardiomyocyte pericellular ECM components collagenα1(I) and the class I SLRP decorin (DCN). Western blot analysis demonstrated that the ratio of glycosaminoglycan (GAG) decorated DCN to core DCN was reduced in P0 and 1 mo lum(-/-) hearts. There was also a reduction in the β and γ forms of collagenα1(I) in lum(-/-) hearts. While the total insoluble collagen content was significantly reduced, the fibril size was increased in lum(-/-) hearts, indicating that LUM may play a role in collagen fiber stability and lateral fibril assembly. These results suggest that LUM controls cardiomyocyte growth by regulating the pericellular ECM and also indicates that LUM may coordinate