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Sample records for early developmental defects

  1. Biochemical defects of mutant nudel alleles causing early developmental arrest or dorsalization of the Drosophila embryo.

    PubMed Central

    LeMosy, E K; Leclerc, C L; Hashimoto, C

    2000-01-01

    The nudel gene of Drosophila is maternally required both for structural integrity of the egg and for dorsoventral patterning of the embryo. It encodes a structurally modular protein that is secreted by ovarian follicle cells. Genetic and molecular studies have suggested that the Nudel protein is also functionally modular, with a serine protease domain that is specifically required for ventral development. Here we describe biochemical and immunolocalization studies that provide insight into the molecular basis for the distinct phenotypes produced by nudel mutations and for the interactions between these alleles. Mutations causing loss of embryonic dorsoventral polarity result in a failure to activate the protease domain of Nudel. Our analyses support previous findings that catalytic activity of the protease domain is required for dorsoventral patterning and that the Nudel protease is auto-activated and reveal an important role for a region adjacent to the protease domain in Nudel protease function. Mutations causing egg fragility and early embryonic arrest result in a significant decrease in extracellular Nudel protein, due to defects in post-translational processing, stability, or secretion. On the basis of these and other studies of serine proteases, we suggest potential mechanisms for the complementary and antagonistic interactions between the nudel alleles. PMID:10628985

  2. Near-infrared imaging of developmental defects in dental enamel.

    PubMed

    Hirasuna, Krista; Fried, Daniel; Darling, Cynthia L

    2008-01-01

    Polarization-sensitive optical coherence tomography (PS-OCT) and near-infrared (NIR) imaging are promising new technologies under development for monitoring early carious lesions. Fluorosis is a growing problem in the United States, and the more prevalent mild fluorosis can be visually mistaken for early enamel demineralization. Unfortunately, there is little quantitative information available regarding the differences in optical properties of sound enamel, enamel developmental defects, and caries. Thirty extracted human teeth with various degrees of suspected fluorosis were imaged using PS-OCT and NIR. An InGaAs camera and a NIR diode laser were used to measure the optical attenuation through transverse tooth sections (approximately 200 microm). A digital microradiography system was used to quantify the enamel defect severity by measurement of the relative mineral loss for comparison with optical scattering measurements. Developmental defects were clearly visible in the polarization-resolved OCT images, demonstrating that PS-OCT can be used to nondestructively measure the depth and possible severity of the defects. Enamel defects on whole teeth that could be imaged with high contrast with visible light were transparent in the NIR. This study suggests that PS-OCT and NIR methods may potentially be used as tools to assess the severity and extent of enamel defects.

  3. Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage.

    PubMed

    Tulpule, Asmin; Lensch, M William; Miller, Justine D; Austin, Karyn; D'Andrea, Alan; Schlaeger, Thorsten M; Shimamura, Akiko; Daley, George Q

    2010-04-29

    Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.

  4. 38 CFR 4.9 - Congenital or developmental defects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Congenital or... SCHEDULE FOR RATING DISABILITIES General Policy in Rating § 4.9 Congenital or developmental defects. Mere congenital or developmental defects, absent, displaced or supernumerary parts, refractive error of the eye...

  5. Blood flow patterns underlie developmental heart defects

    PubMed Central

    Midgett, Madeline; Thornburg, Kent

    2017-01-01

    Although cardiac malformations at birth are typically associated with genetic anomalies, blood flow dynamics also play a crucial role in heart formation. However, the relationship between blood flow patterns in the early embryo and later cardiovascular malformation has not been determined. We used the chicken embryo model to quantify the extent to which anomalous blood flow patterns predict cardiac defects that resemble those in humans and found that restricting either the inflow to the heart or the outflow led to reproducible abnormalities with a dose-response type relationship between blood flow stimuli and the expression of cardiac phenotypes. Constricting the outflow tract by 10–35% led predominantly to ventricular septal defects, whereas constricting by 35–60% most often led to double outlet right ventricle. Ligation of the vitelline vein caused mostly pharyngeal arch artery malformations. We show that both cardiac inflow reduction and graded outflow constriction strongly influence the development of specific and persistent abnormal cardiac structure and function. Moreover, the hemodynamic-associated cardiac defects recapitulate those caused by genetic disorders. Thus our data demonstrate the importance of investigating embryonic blood flow conditions to understand the root causes of congenital heart disease as a prerequisite to future prevention and treatment. NEW & NOTEWORTHY Congenital heart defects result from genetic anomalies, teratogen exposure, and altered blood flow during embryonic development. We show here a novel “dose-response” type relationship between the level of blood flow alteration and manifestation of specific cardiac phenotypes. We speculate that abnormal blood flow may frequently underlie congenital heart defects. PMID:28062416

  6. Developmental Defects of Enamel in Children with Intellectual Disability.

    PubMed

    Erika, Vesna; Modrić; Verzak, Željko; Karlović, Zoran

    2016-03-01

    To investigate the frequency of developmental defects of enamel (DDE) in children with intellectual disability. Children aged 5-18 years (72 children with intellectual disabilities and 72 controls) were included in the study. All the teeth were screened for developmental defects of enamel using the modified Developmental defects of enamel (mDDE) index. Out of the 72 children with intellectual disabilities in this study, 20 (27.78%) presented dental defects of enamel, compared with 8 (11.11%) of those in the control group, which was considered statistically significant (p = 0.021). The majority of children in both groups had white demarcated opacities. Children in both groups were more likely to have maxillary teeth affected than the mandibular teeth and the asymmetrical demarcated enamel defects were more common than the symmetric ones. Majority of opacities in children in both groups were on the maxillary incisors. Children with intellectual disabilities have more developmental defects of enamel than children in the control group. Enamel defects increase caries risk and cause reduction in enamel mechanical properties leading to restoration failures.

  7. Color masking of developmental enamel defects: a case series.

    PubMed

    Torres, C R G; Borges, A B

    2015-01-01

    Developmental defects involving color alteration of enamel frequently compromise the esthetic appearance of the tooth. The resin infiltration technique represents an alternative treatment for color masking of these lesions and uniformization of tooth color. This technique is considered relatively simple and microinvasive, since only a minimal portion of enamel is removed. This article illustrates the color-masking effect with resin infiltration of fluorosis and traumatic hypomineralization lesions with a case series. The final esthetic outcomes demonstrated the ability of the resin infiltrant to mask the color of white developmental defect lesions, resulting in satisfactory clinical esthetic improvements. However, in more severe cases, the color-masking effect was not complete.

  8. Developmental defects in zebrafish for classification of EGF pathway inhibitors

    SciT

    Pruvot, Benoist; Curé, Yoann; Djiotsa, Joachim

    2014-01-15

    One of the major challenges when testing drug candidates targeted at a specific pathway in whole animals is the discrimination between specific effects and unwanted, off-target effects. Here we used the zebrafish to define several developmental defects caused by impairment of Egf signaling, a major pathway of interest in tumor biology. We inactivated Egf signaling by genetically blocking Egf expression or using specific inhibitors of the Egf receptor function. We show that the combined occurrence of defects in cartilage formation, disturbance of blood flow in the trunk and a decrease of myelin basic protein expression represent good indicators for impairmentmore » of Egf signaling. Finally, we present a classification of known tyrosine kinase inhibitors according to their specificity for the Egf pathway. In conclusion, we show that developmental indicators can help to discriminate between specific effects on the target pathway from off-target effects in molecularly targeted drug screening experiments in whole animal systems. - Highlights: • We analyze the functions of Egf signaling on zebrafish development. • Genetic blocking of Egf expression causes cartilage, myelin and circulatory defects. • Chemical inhibition of Egf receptor function causes similar defects. • Developmental defects can reveal the specificity of Egf pathway inhibitors.« less

  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. 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…

  11. Live dynamic imaging and analysis of developmental cardiac defects in mouse models with optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Lopez, Andrew L.; Wang, Shang; Garcia, Monica; Valladolid, Christian; Larin, Kirill V.; Larina, Irina V.

    2015-03-01

    Understanding mouse embryonic development is an invaluable resource for our interpretation of normal human embryology and congenital defects. Our research focuses on developing methods for live imaging and dynamic characterization of early embryonic development in mouse models of human diseases. Using multidisciplinary methods: optical coherence tomography (OCT), live mouse embryo manipulations and static embryo culture, molecular biology, advanced image processing and computational modeling we aim to understand developmental processes. We have developed an OCT based approach to image live early mouse embryos (E8.5 - E9.5) cultured on an imaging stage and visualize developmental events with a spatial resolution of a few micrometers (less than the size of an individual cell) and a frame rate of up to hundreds of frames per second and reconstruct cardiodynamics in 4D (3D+time). We are now using these methods to study how specific embryonic lethal mutations affect cardiac morphology and function during early development.

  12. Early developmental trajectories of preterm infants.

    PubMed

    Yaari, Maya; Mankuta, David; Harel-Gadassi, Ayelet; Friedlander, Edwa; Bar-Oz, Benjamin; Eventov-Friedman, Smadar; Maniv, Nimrod; Zucker, David; Yirmiya, Nurit

    2017-11-04

    Preterm infants are at risk for neuro-developmental impairments and atypical developmental trajectories. The aims of this study were to delineate early developmental trajectories of preterm and full-term infants. The cognitive, language, and motor development of 149 infants - 19 extremely preterm (EPT), 34 very preterm (VPT), 57 moderately preterm (MPT), and 39 full-term (FT) - was evaluated using Mullen Scales at 1, 4, 8, 12, and 18 months. Mixed models were applied to examine group differences. Gender, maternal education, and neurobehavior were included as predictors of developmental trajectories. The EPT and VPT infants achieved significantly lower scores than the FT infants in all domains, with a significantly increasing gap over time. The MPT infants' trajectories were more favorable than those of the EPT and VPT infants yet lower than the FT infants on the Visual Reception, Gross, and Fine Motor subscales. Male gender and lower maternal education were associated with lower scores that declined over time. Abnormal neonatal neurobehavior was associated lower Mullen scores and with less stability in scores over time. The EPT and VPT infants were found to have disadvantages across all domains. The MPT infants revealed more favorable developmental trajectories yet displayed vulnerability compared to the FT infants. Gender, maternal education, and neonatal neurobehavior are important in predicting the developmental outcomes of preterm infants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Developmental outcomes after early prefrontal cortex damage.

    PubMed

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

    2004-06-01

    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 profiles and real life developmental outcomes. Based on these cases, there is preliminary evidence to support distinctive developmental differences after: (1) dorsolateral, (2) mesial, and (3) orbital-polar prefrontal lesions, for more profound impairments after bilateral damage, and possibly for recovery differences after very early vs. later childhood lesion onset. Further case and group studies are needed to confirm reliable effects of specific lesion locations, the influence of age of lesion onset, and related experiential and treatment variables in determining adult outcomes. Rather than a single underlying deficit associated with early prefrontal cortex damage, we interpret the findings to suggest that it is the altered integration and interplay of cognitive, emotional, self-regulatory, and executive/metacognitive deficits that contribute to diverse developmental frontal lobe syndromes. The findings support the fundamental importance of prefrontal cortex maturation in protracted cognitive, social-emotional, and moral development.

  14. High Fat Diet Induced Developmental Defects in the Mouse: Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects

    PubMed Central

    Purcell, Scott H.; Chi, Maggie; Jimenez, Patricia T.; Grindler, Natalia; Schedl, Tim; Moley, Kelle H.

    2012-01-01

    Background Maternal obesity is associated with poor outcomes across the reproductive spectrum including infertility, increased time to pregnancy, early pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions. Furthermore, the proportion of reproductive-aged woman that are obese in the population is increasing sharply. From current studies it is not clear if the origin of the reproductive complications is attributable to problems that arise in the oocyte or the uterine environment. Methodology/Principal Findings We examined the developmental basis of the reproductive phenotypes in obese animals by employing a high fat diet mouse model of obesity. We analyzed very early embryonic and fetal phenotypes, which can be parsed into three abnormal developmental processes that occur in obese mothers. The first is oocyte meiotic aneuploidy that then leads to early embryonic loss. The second is an abnormal process distinct from meiotic aneuploidy that also leads to early embryonic loss. The third is fetal growth retardation and brain developmental abnormalities, which based on embryo transfer experiments are not due to the obese uterine environment but instead must be from a defect that arises prior to the blastocyst stage. Conclusions/Significance Our results suggest that reproductive complications in obese females are, at least in part, from oocyte maternal effects. This conclusion is consistent with IVF studies where the increased pregnancy failure rate in obese women returns to the normal rate if donor oocytes are used instead of autologous oocytes. We postulate that preconceptional weight gain adversely affects pregnancy outcomes and fetal development. In light of our findings, preconceptional counseling may be indicated as the preferable, earlier target for intervention in obese women desiring pregnancy and healthy outcomes. PMID:23152876

  15. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest.

    PubMed

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

    2015-01-01

    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. 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. 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. 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.

  16. 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

  17. Current Evidence for Developmental, Structural, and Functional Brain Defects following Prenatal Radiation Exposure

    PubMed Central

    Verreet, Tine; Quintens, Roel; Baatout, Sarah; Benotmane, Mohammed A.

    2016-01-01

    Ionizing radiation is omnipresent. We are continuously exposed to natural (e.g., radon and cosmic) and man-made radiation sources, including those from industry but especially from the medical sector. The increasing use of medical radiation modalities, in particular those employing low-dose radiation such as CT scans, raises concerns regarding the effects of cumulative exposure doses and the inappropriate utilization of these imaging techniques. One of the major goals in the radioprotection field is to better understand the potential health risk posed to the unborn child after radiation exposure to the pregnant mother, of which the first convincing evidence came from epidemiological studies on in utero exposed atomic bomb survivors. In the following years, animal models have proven to be an essential tool to further characterize brain developmental defects and consequent functional deficits. However, the identification of a possible dose threshold is far from complete and a sound link between early defects and persistent anomalies has not yet been established. This review provides an overview of the current knowledge on brain developmental and persistent defects resulting from in utero radiation exposure and addresses the many questions that still remain to be answered. PMID:27382490

  18. Developmentally induced Mll1 loss reveals defects in postnatal haematopoiesis.

    PubMed

    Gan, T; Jude, C D; Zaffuto, K; Ernst, P

    2010-10-01

    The mixed lineage leukemia (MLL) gene is disrupted by chromosomal translocations in acute leukemia, producing a fusion oncogene with altered properties relative to the wild-type gene. Murine loss-of-function studies have shown an essential role for Mll in developing the haematopoietic system, yet studies using different conditional knockout models have yielded conflicting results regarding the requirement for Mll during adult steady-state haematopoiesis. In this study, we used a loxP-flanked Mll allele (Mll(F)) and a developmentally regulated, haematopoietic-specific VavCre transgene to reassess the consequences of Mll loss in the haematopoietic lineage, without the need for inducers of Cre recombinase. We show that VavCre;Mll mutants exhibit phenotypically normal fetal haematopoiesis, but rarely survive past 3 weeks of age. Surviving animals are anemic, thrombocytopenic and exhibit a significant reduction in bone marrow haematopoietic stem/progenitor populations, consistent with our previous findings using the inducible Mx1Cre transgene. Furthermore, the analysis of VavCre mutants revealed additional defects in B-lymphopoiesis that could not be assessed using Mx1Cre-mediated Mll deletion. Collectively, these data support the conclusion that Mll has an essential role in sustaining postnatal haematopoiesis.

  19. Mechanical analysis of a heat-shock induced developmental defect

    NASA Astrophysics Data System (ADS)

    Crews, Sarah M.; McCleery, W. Tyler; Hutson, M. Shane

    2014-03-01

    Embryonic development in Drosophila is a complex process involving coordinated movements of mechanically interacting tissues. Perturbing this system with a transient heat shock can result in a number of developmental defects. In particular, a heat shock applied during the earliest morphogenetic movements of gastrulation can lead to apparent recovery, but then subsequent morphogenetic failure 5-6 hours later during germ band retraction. The process of germ band retraction requires an intact amnioserosa - a single layered extra-embryonic epithelial tissue - and heat shock at gastrulation can induce the later opening of holes in the amnioserosa. These holes are highly correlated with failures of germ band retraction. These holes could be caused by a combination of mechanical weakness in the amnioserosa or local increases in mechanical stress. Here, we assess the role of mechanical stress using confocal imaging to compare cell and tissue morphology in the amnioserosa of normal and heat-shocked embryos and laser hole drilling to map the stress field around the times and locations at which heat-shock induced holes open.

  20. Early closure of postinfarction ventricular septal defects.

    PubMed

    Martinelli, Luigi; Dottori, Vincenzo; Caputo, Enrico; Graffigna, Angelo; Pederzolli, Carlo

    2003-05-01

    According to the guidelines of the American College of Cardiology/American Heart Association early closure of postinfarction septal defects is now a class I indication although it still carries a relevant morbidity and mortality. The operative risk is related both to the critical hemodynamic conditions of the patient and to the technical difficulties posed by the friable tissue of the infarcted area. The most recent techniques involving the use of pericardial patches reinforced by acrylic glue have significantly reduced the hospital mortality. The aim of this study was to discuss the reliability of an aggressive, tissue-sparing surgical approach to this complication. We present a consecutive series of 12 patients operated upon between January 1998 and October 2001 within 12 hours of the onset of clinical evidence of postinfarction septal rupture. Repair was achieved with minimal septal debridement and the use of a large pericardial patch reinforced by a biological glue. Three cases of dehiscence required early reoperation with no hospital mortality. This procedure is technically feasible and allows early aggressive treatment of postinfarction septal rupture with satisfactory results.

  1. 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…

  2. A developmental perspective on early-life exposure to neurotoxicants.

    PubMed

    Bellinger, David C; Matthews-Bellinger, Julia A; Kordas, Katarzyna

    2016-09-01

    Studies of early-life neurotoxicant exposure have not been designed, analyzed, or interpreted in the context of a fully developmental perspective. The goal of this paper is to describe the key principles of a developmental perspective and to use examples from the literature to illustrate the relevance of these principles to early-life neurotoxicant exposures. Four principles are discussed: 1) the effects of early-life neurotoxicant exposure depend on a child's developmental context; 2) deficits caused by early-life exposure initiate developmental cascades that can lead to pathologies that differ from those observed initially; 3) early-life neurotoxicant exposure has intra-familial and intergenerational impacts; 4) the impacts of early-life neurotoxicant exposure influence a child's ability to respond to future insults. The first principle is supported by considerable evidence, but the other three have received much less attention. Incorporating a developmental perspective in studies of early-life neurotoxicant exposures requires prospective collection of data on a larger array of covariates than usually considered, using analytical approaches that acknowledge the transactional processes between a child and the environment and the phenomenon of developmental cascades. Consideration of early-life neurotoxicant exposure within a developmental perspective reveals that many issues remain to be explicated if we are to achieve a deep understanding of the societal health burden associated with early-life neurotoxicant exposures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Plant alkaloids that cause developmental defects through the disruption of cholinergic neurotransmission

    The exposure of a developing embryo or fetus to alkaloids from plants, plant products, or plant extracts has the potential to cause developmental defects in humans and animals. These defects may have multiple causes but those induced by piperidine and quinolizidine alkaloids arise from the inhibiti...

  4. Near-infrared imaging of enamel hypomineralization due to developmental defects

    NASA Astrophysics Data System (ADS)

    Lee, Robert C.; Jang, Andrew; Fried, Daniel

    2017-02-01

    The increasing prevalence of mild hypomineralization due to developmental defects on tooth surfaces poses a challenge for caries detection and caries risk assessment and reliable methods need to be developed to discriminate such lesions from active caries lesions that need intervention. Previous studies have demonstrated that areas of hypomineralization are typically covered with a relatively thick surface layer of highly mineralized and transparent enamel similar to arrested lesions. Seventy-six extracted human teeth with mild to moderate degrees of suspicious fluorosis were imaged using near-infrared reflectance and transillumination. Enamel hypomineralization was clearly visible in both modalities. However, it was difficult to distinguish hypomineralization due to developmental defects from caries lesions with contrast measurements alone. The location of the lesion on tooth coronal surface (i.e. generalized vs. localized) seems to be the most important indicator for the presence of enamel hypomineralization due to developmental defects.

  5. Near-infrared imaging of enamel hypomineralization due to developmental defects.

    PubMed

    Lee, Robert C; Jang, Andrew; Fried, Daniel

    2017-01-28

    The increasing prevalence of mild hypomineralization due to developmental defects on tooth surfaces poses a challenge for caries detection and caries risk assessment and reliable methods need to be developed to discriminate such lesions from active caries lesions that need intervention. Previous studies have demonstrated that areas of hypomineralization are typically covered with a relatively thick surface layer of highly mineralized and transparent enamel similar to arrested lesions. Seventy-six extracted human teeth with mild to moderate degrees of suspicious fluorosis were imaged using near-infrared reflectance and transillumination. Enamel hypomineralization was clearly visible in both modalities. However, it was difficult to distinguish hypomineralization due to developmental defects from caries lesions with contrast measurements alone. The location of the lesion on tooth coronal surface (i.e. generalized vs. localized) seems to be the most important indicator for the presence of enamel hypomineralization due to developmental defects.

  6. 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…

  7. 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…

  8. Does early paternal involvement predict offspring developmental diagnoses?

    PubMed

    Jackson, Dylan B; Newsome, Jamie; Beaver, Kevin M

    2016-12-01

    A long line of research has illustrated that fathers play an important role in the development of their children. Few studies, however, have examined the impact of paternal involvement at the earliest stages of life on developmental diagnoses in childhood. The present study extends this line of research by exploring the possibility that paternal involvement prenatally, postnatally, and at the time of birth may influence offspring risk for various diagnoses in childhood. A quasi-experimental, propensity score matching design was used to create treatment and control groups to assess the relationship between paternal involvement at each stage of development and developmental diagnoses. Approximately 6000 children, and a subsample of fathers, who participated in the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B). Activity, attention and learning, speech or language, and other diagnoses in early childhood, and overall number of diagnoses at 4years of age. We find no consistent evidence that low paternal involvement prenatally or postnatally increases the risk of various developmental diagnoses by age 4. However, children whose fathers were absent at the time of their birth were at significantly greater risk of incurring various developmental diagnoses, as well as a significantly greater number of developmental diagnoses. The findings expand our understanding of exactly how early paternal influence begins and the specific dimensions of early father behaviors that are related to the risk of various developmental diagnoses. Ultimately, these results have important implications concerning father involvement during the earliest stages of the life course. Copyright © 2016. Published by Elsevier Ireland Ltd.

  9. 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…

  10. Scalp defects, polythelia, microcephaly, and developmental delay: a new syndrome with apparent autosomal dominant inheritance.

    PubMed

    Marble, Michael; Pridjian, Gabriella

    2002-04-01

    We report a family with apparent autosomal dominant inheritance of scalp defects, polythelia, microcephaly, and developmental delay. A review of the literature revealed no previous report of this combination of anomalies. We conclude that these patients have a new autosomal dominant syndrome. Copyright 2002 Wiley-Liss, Inc.

  11. Early Adolescent Sexual Activity: A Developmental Study.

    ERIC Educational Resources Information Center

    Whitbeck, Les B.; Yoder, Kevin A.; Hoyt, Dan R.; Conger, Rand D.

    1999-01-01

    Examines predictors of early sexual intercourse for a sample of 457 adolescents in grades 8 through 10, from two-parent and single-mother families. Significant decreases were noted in the effect of mother monitoring by 10th grade. The primary predictors of early intercourse were age, opportunity (steady relationship), sexually permissive attitude,…

  12. Orangutans, enamel defects, and developmental health: A comparison of Borneo and Sumatra.

    PubMed

    Skinner, Mark F; Skinner, Matthew M

    2017-08-01

    Orangutans (Pongo sp.) show among the highest occurrence of three types of developmental enamel defect. Two are attributed to nutritional factors that reduce bone growth in the infant's face early in development. Their timing and prevalence indicate that Sumatra provides a better habitat than does Borneo. The third type, repetitive linear enamel hypoplasia (rLEH) is very common but its etiology is not understood. Our objective is to draw attention to this enigmatic, episodic stressor in the lives of orangutans. We are concerned that neglect of this possible marker of ill health may be contributing, through inaction, to their alarming decline in numbers. Width and depth of an LEH are considered proxies for duration and intensity of stress. The hypothesis that Bornean orangutans would exhibit relatively wider and deeper LEH was tested on 163 independent episodes of LEH from 9 Sumatran and 26 Bornean orangutans measured with a NanoFocus AG "µsurf Mobile Plus" scanner. Non-normally distributed data (depths) were converted to natural logs. No difference was found in width of LEH among the two island taxa; nor are their differences in width or depth between the sexes. After controlling for significant differences in LEH depths between incisors and canines, defects are, contrary to prediction, significantly deeper in Sumatran than Bornean animals (median = 28, 18 µm, respectively). It is concluded that repetitive LEH records an unknown but significant stressor present in both Sumatra and Borneo, with an average periodicity of 6 months (or multiples thereof) that lasts about 6-8 weeks. It is worse in Sumatra. Given this patterning, shared with apes from a wide range of ecological and temporal sources, rLEH is more likely attributable to disease than to malnutrition. © 2017 Wiley Periodicals, Inc.

  13. Diversity & Developmentally Appropriate Practices: Challenges for Early Childhood Education.

    ERIC Educational Resources Information Center

    Mallory, Bruce L., Ed.; New, Rebecca S., Ed.

    The current conceptualization of what is appropriate in early childhood education is overly narrow in its interpretation of the role of the teacher, and with respect to variations in cultural and developmental diversity. Based on this observation, this book discusses various issues surrounding diversity, inclusion, and appropriate early…

  14. Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects.

    PubMed

    Slavotinek, A M; Garcia, S T; Chandratillake, G; Bardakjian, T; Ullah, E; Wu, D; Umeda, K; Lao, R; Tang, P L-F; Wan, E; Madireddy, L; Lyalina, S; Mendelsohn, B A; Dugan, S; Tirch, J; Tischler, R; Harris, J; Clark, M J; Chervitz, S; Patwardhan, A; West, J M; Ursell, P; de Alba Campomanes, A; Schneider, A; Kwok, P-Y; Baranzini, S; Chen, R O

    2015-11-01

    Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing with the ACE Exome(TM) (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 cases) to sequence 28 patients with A/M and four patients with varied developmental eye defects. In the 28 patients with A/M, we identified de novo mutations in three patients (OTX2, p.(Gln91His), RARB, p.Arg387Cys and GDF6, p.Ala249Glu) and inherited mutations in STRA6 in two patients. In patients with developmental eye defects, a female with cataracts and cardiomyopathy had a de novo COL4A1 mutation, p.(Gly773Arg), expanding the phenotype associated with COL4A1 to include cardiomyopathy. A male with a chorioretinal defect, microcephaly, seizures and sensorineural deafness had two PNPT1 mutations, p.(Ala507Ser) and c.401-1G>A, and we describe eye defects associated with this gene for the first time. Exome sequencing was efficient for identifying mutations in pathogenic genes for which there is no clinical testing available and for identifying cases that expand phenotypic spectra, such as the PNPT1 and COL4A1-associated disorders described here. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Exome Sequencing in 32 Patients with Anophthalmia/Microphthalmia and Developmental Eye Defects

    PubMed Central

    Slavotinek, Anne M.; Garcia, Sarah T.; Chandratillake, Gemma; Bardakjian, Tanya; Ullah, Ehsan; Wu, Di; Umeda, Kyle; Lao, Richard; Tang, Paul Ling-Fung; Wan, Eunice; Madireddy, Lohith; Lyalina, Svetlana; Mendelsohn, Bryce A.; Dugan, Sarah; Tirch, Jean; Tischler, Reana; Harris, Jason; Clark, Michael J.; Chervitz, Stephen; Patwardhan, Anil; West, John M.; Ursell, Phillip; de Alba Campomanes, Alejandra; Schneider, Adele; Kwok, Pui-yan; Baranzini, Sergio; Chen, Richard O.

    2014-01-01

    Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing with the ACE Exome™ (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 cases) to sequence 28 patients with A/M and four patients with varied developmental eye defects. In the 28 patients with A/M, we identified de novo mutations in three patients (OTX2, p.(Gln91His), RARB, p.Arg387Cys and GDF6, p.Ala249Glu) and inherited mutations in STRA6 in two patients. In patients with developmental eye defects, a female with cataracts and cardiomyopathy had a de novo COL4A1 mutation, p.(Gly773Arg), expanding the phenotype associated with COL4A1 to include cardiomyopathy. A male with a chorioretinal defect, microcephaly, seizures and sensorineural deafness had two PNPT1 mutations, p.(Ala507Ser) and c.401-1G>A, and we describe eye defects associated with this gene for the first time. Exome sequencing was efficient for identifying mutations in pathogenic genes for which there is no clinical testing available and for identifying cases that expand phenotypic spectra, such as the PNPT1 and COL4A1-associated disorders described here. PMID:25457163

  16. Mechanical design in embryos: mechanical signalling, robustness and developmental defects.

    PubMed

    Davidson, Lance A

    2017-05-19

    Embryos are shaped by the precise application of force against the resistant structures of multicellular tissues. Forces may be generated, guided and resisted by cells, extracellular matrix, interstitial fluids, and how they are organized and bound within the tissue's architecture. In this review, we summarize our current thoughts on the multiple roles of mechanics in direct shaping, mechanical signalling and robustness of development. Genetic programmes of development interact with environmental cues to direct the composition of the early embryo and endow cells with active force production. Biophysical advances now provide experimental tools to measure mechanical resistance and collective forces during morphogenesis and are allowing integration of this field with studies of signalling and patterning during development. We focus this review on concepts that highlight this integration, and how the unique contributions of mechanical cues and gradients might be tested side by side with conventional signalling systems. We conclude with speculation on the integration of large-scale programmes of development, and how mechanical responses may ensure robust development and serve as constraints on programmes of tissue self-assembly.This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'. © 2017 The Author(s).

  17. 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…

  18. The quantum defect: Early history and recent developments

    SciT

    Rau, A.R.; Inokuti, M.

    1997-03-01

    The notion of the quantum defect is important in atomic and molecular spectroscopy and also in unifying spectroscopy with collision theory. In the latter context, the quantum defect may be viewed as an ancestor of the phase shift. However, the origin of the term {open_quotes}quantum defect{close_quotes} does not seem to be explained in standard textbooks. It occurred in a 1921 paper by Schr{umlt o}dinger, preceding quantum mechanics, yet giving the correct meaning as an index of the short-range interactions with the core of an atom. We present the early history of the quantum-defect idea, and sketch its recent developments. {copyright}more » {ital 1997 American Association of Physics Teachers.}« less

  19. Loss of FTO antagonises Wnt signaling and leads to developmental defects associated with ciliopathies.

    PubMed

    Osborn, Daniel P S; Roccasecca, Rosa Maria; McMurray, Fiona; Hernandez-Hernandez, Victor; Mukherjee, Sriparna; Barroso, Inês; Stemple, Derek; Cox, Roger; Beales, Philip L; Christou-Savina, Sonia

    2014-01-01

    Common intronic variants in the Human fat mass and obesity-associated gene (FTO) are found to be associated with an increased risk of obesity. Overexpression of FTO correlates with increased food intake and obesity, whilst loss-of-function results in lethality and severe developmental defects. Despite intense scientific discussions around the role of FTO in energy metabolism, the function of FTO during development remains undefined. Here, we show that loss of Fto leads to developmental defects such as growth retardation, craniofacial dysmorphism and aberrant neural crest cells migration in Zebrafish. We find that the important developmental pathway, Wnt, is compromised in the absence of FTO, both in vivo (zebrafish) and in vitro (Fto(-/-) MEFs and HEK293T). Canonical Wnt signalling is down regulated by abrogated β-Catenin translocation to the nucleus whilst non-canonical Wnt/Ca(2+) pathway is activated via its key signal mediators CaMKII and PKCδ. Moreover, we demonstrate that loss of Fto results in short, absent or disorganised cilia leading to situs inversus, renal cystogenesis, neural crest cell defects and microcephaly in Zebrafish. Congruently, Fto knockout mice display aberrant tissue specific cilia. These data identify FTO as a protein-regulator of the balanced activation between canonical and non-canonical branches of the Wnt pathway. Furthermore, we present the first evidence that FTO plays a role in development and cilia formation/function.

  20. Rapamycin treatment causes developmental delay, pigmentation defects, and gastrointestinal malformation on Xenopus embryogenesis.

    PubMed

    Moriyama, Yuki; Ohata, Yoshihisa; Mori, Shoko; Matsukawa, Shinya; Michiue, Tatsuo; Asashima, Makoto; Kuroda, Hiroki

    2011-01-28

    Rapamycin is a drug working as an inhibitor of the TOR (target of rapamycin) signaling pathway and influences various life phenomena such as cell growth, proliferation, and life span extension in eukaryote. However, the extent to which rapamycin controls early developmental events of amphibians remains to be understood. Here we report an examination of rapamycin effects during Xenopus early development, followed by a confirmation of suppression of TOR downstream kinase S6K by rapamycin treatment. First, we found that developmental speed was declined in dose-dependent manner of rapamycin. Second, black pigment spots located at dorsal and lateral skin in tadpoles were reduced by rapamycin treatment. Moreover, in tadpole stages severe gastrointestinal malformations were observed in rapamycin-treated embryos. Taken together with these results, we conclude that treatment of the drug rapamycin causes enormous influences on early developmental period. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Effects of gamma radiation on the early developmental stages of Zebrafish (Danio rerio).

    PubMed

    Praveen Kumar, M K; Shyama, S K; Kashif, Shamim; Dubey, S K; Avelyno, D'costa; Sonaye, B H; Kadam Samit, B; Chaubey, R C

    2017-08-01

    The zebrafish is gaining importance as a popular vertebrate model organism and is widely employed in ecotoxicological studies, especially for the biomonitoring of pollution in water bodies. There is limited data on the genetic mechanisms governing the adverse health effects in regards to an early developmental exposure to gamma radiation. In the present study zebrafish (Danio rerio) embryos were exposed to 1, 2.5, 5, 7.5 and 10Gy of gamma radiation at 3h post fertilization (hpf). Different developmental toxicity endpoints were investigated. Further, expression of genes associated with the development and DNA damage i.e. (sox2 sox19a and p53) were evaluated using Quantitative PCR (qPCR). The significant changes in the expression of sox2 sox19a and p53 genes were observed. This data was supported the developmental defects observed in the zebrafish embryo exposed to gamma radiation such as i.e. increased DNA damage, decreased hatching rate, increase in median hatching time, decreased body length, increased mortality rate, increased morphological deformities. Further, study shows that the potential ecotoxicological threat of gamma radiation on the early developmental stages of zebrafish. Further, it revealed that the above parameters can be used as predictive biomarkers of gamma radiation exposure. Copyright © 2017. Published by Elsevier Inc.

  2. Pollen developmental defects in ZD-CMS rice line explored by cytological, molecular and proteomic approaches.

    PubMed

    Yan, Junjie; Tian, Han; Wang, Shuzhen; Shao, Jinzhen; Zheng, Yinzhen; Zhang, Hongyuan; Guo, Lin; Ding, Yi

    2014-08-28

    Cytoplasmic male sterility (CMS) is a widely observed phenomenon, which is especially useful in hybrid seed production. Meixiang A (MxA) is a new rice CMS line derived from a pollen-free sterile line named Yunnan ZidaoA (ZD-CMS). In this study, a homologous WA352 gene with variation in two nucleotides was identified in MxA. Cytological analysis revealed that MxA was aborted in the early uninucleate stage. The protein expression profiles of MxA and its maintainer line MeixiangB (MxB) were systematically compared using iTRAQ-based quantitative proteomics technology using young florets at the early uninucleate stage. A total of 688 proteins were quantified in both rice lines, and 45 of these proteins were found to be differentially expressed. Bioinformatics analysis indicated a large number of the proteins involved in carbohydrate metabolism or the stress response were downregulated in MxA, suggesting that these metabolic processes had been hindered during pollen development in MxA. The ROS (reactive oxygen species) level was increased in the mitochondrion of MxA, and further ultrastructural analysis showed the mitochondria with disrupted cristae in the rice CMS line MxA. These findings substantially contribute to our knowledge of pollen developmental defects in ZD-CMS rice line. MeixiangA (MxA) is a new type of rice CMS line, which is derived from pollen-free sterile line Yunnan ZidaoA. In this study, the cytological, molecular and proteomic approaches were used to study the characteristics of this new CMS line. Cytological study indicates the CMS line is aborted at the early uninucleate stage. A potential sterile gene ZD352 is identified in MxA, the protein product of which is mainly accumulated at the MMC/Meiotic stage. iTRAQ based proteomic analysis is performed to study the relevant proteins involved in the CMS occurance, 45 proteins are found to be significant differentially expressed and these proteins are involved in many cellular processes such as

  3. Association between developmental defects of enamel and dental caries: A systematic review and meta-analysis.

    PubMed

    Vargas-Ferreira, F; Salas, M M S; Nascimento, G G; Tarquinio, S B C; Faggion, C M; Peres, M A; Thomson, W M; Demarco, F F

    2015-06-01

    Dental caries is the main problem oral health and it is not well established in the literature if the enamel defects are a risk factor for its development. Studies have reported a potential association between developmental defects enamel (DDE) and dental caries occurrence. We investigated the association between DDE and caries in permanent dentition of children and teenagers. A systematic review was carried out using four databases (Pubmed, Web of Science, Embase, and Science Direct), which were searched from their earliest records until December 31, 2014. Population-based studies assessing differences in dental caries experience according to the presence of enamel defects (and their types) were included. PRISMA guidelines for reporting systematic reviews were followed. Meta-analysis was performed to assess the pooled effect, and meta-regression was carried out to identify heterogeneity sources. From the 2558 initially identified papers, nine studies fulfilled all inclusion criteria after checking the titles, abstracts, references, and complete reading. Seven of them were included in the meta-analysis with random model. A positive association between enamel defects and dental caries was identified; meta-analysis showed that individuals with DDE had higher pooled odds of having dental caries experience [OR 2.21 (95% CI 1.3; 3.54)]. Meta-regression analysis demonstrated that adjustment for sociodemographic factors, countries' socioeconomic status, and bias (quality of studies) explained the high heterogeneity observed. A higher chance of dental caries should be expected among individuals with enamel defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Neuropsychological dysfunction and developmental defects associated with genetic changes in infants with neonatal diabetes mellitus: a prospective cohort study [corrected].

    PubMed

    Busiah, Kanetee; Drunat, Séverine; Vaivre-Douret, Laurence; Bonnefond, Amélie; Simon, Albane; Flechtner, Isabelle; Gérard, Bénédicte; Pouvreau, Nathalie; Elie, Caroline; Nimri, Revital; De Vries, Liat; Tubiana-Rufi, Nadia; Metz, Chantal; Bertrand, Anne-Marie; Nivot-Adamiak, Sylvie; de Kerdanet, Marc; Stuckens, Chantal; Jennane, Farida; Souchon, Pierre-François; Le Tallec, Claire; Désirée, Christelle; Pereira, Sabrina; Dechaume, Aurélie; Robert, Jean-Jacques; Phillip, Moshe; Scharfmann, Raphaël; Czernichow, Paul; Froguel, Philippe; Vaxillaire, Martine; Polak, Michel; Cavé, Hélène

    2013-11-01

    early diagnosis (median age 5·0 days, IQR 1·0-14·5 vs 45·5 days, IQR 27·2-95·0; p<0·0001). Remission of neonatal diabetes mellitus occurred in 89 (51%) index patients at a median age of 17 weeks (IQR 9·5-39·0; median follow-up 4·7 years, IQR 1·5-12·8). Recurrence was common, with no difference between the groups who had 6q24 abnormalities versus mutations in KATP channel subunit genes (82% vs 86%; p=0·36). Neonatal diabetes mellitus is often associated with neuropsychological dysfunction and developmental defects that are specific to the underlying genetic abnormality. A multidisciplinary assessment is therefore essential when patients are diagnosed. Features of neuropsychological dysfunction and developmental defects should be tested for in adults with a history of neonatal diabetes mellitus. Agence Nationale de la Recherche-Maladies Rares Research Program Grant, the Transnational European Research Grant on Rare Diseases, the Société Francophone du Diabète-Association Française du Diabète, the Association Française du Diabète, Aide aux Jeunes Diabétiques, a CIFRE grant from the French Government, HRA-Pharma, the French Ministry of Education and Research, and the Société Française de Pédiatrie. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Rapamycin treatment causes developmental delay, pigmentation defects, and gastrointestinal malformation on Xenopus embryogenesis

    SciT

    Moriyama, Yuki; Ohata, Yoshihisa; Mori, Shoko

    Research highlights: {yields} Does famous anti-aging drug rapamycin work from the beginning of life? The answer is yes. {yields} This study shows that developmental speed of frog embryo was dose-dependently decreased by rapamycin treatment. {yields} In additions, morphogenetic effects such as less pigmentations and gut malformation are occurred by rapamycin. -- Abstract: Rapamycin is a drug working as an inhibitor of the TOR (target of rapamycin) signaling pathway and influences various life phenomena such as cell growth, proliferation, and life span extension in eukaryote. However, the extent to which rapamycin controls early developmental events of amphibians remains to be understood.more » Here we report an examination of rapamycin effects during Xenopus early development, followed by a confirmation of suppression of TOR downstream kinase S6K by rapamycin treatment. First, we found that developmental speed was declined in dose-dependent manner of rapamycin. Second, black pigment spots located at dorsal and lateral skin in tadpoles were reduced by rapamycin treatment. Moreover, in tadpole stages severe gastrointestinal malformations were observed in rapamycin-treated embryos. Taken together with these results, we conclude that treatment of the drug rapamycin causes enormous influences on early developmental period.« less

  6. [Developmental amnesia and early brain damage: neuropsychology and neuroimaging].

    PubMed

    Crespo-Eguilaz, N; Dominguez, P D; Vaquero, M; Narbona, J

    2018-03-01

    To contribute to neuropsychological profiling of developmental amnesia subsequent to bilateral damage to both hippocampi in early age. The total sample of 24 schoolchildren from both sexes is distributed in three groups: perinatal hypoxic-ischaemic encephalopathy and everyday complaints of memory in school age (n = 8); perinatal hypoxic-ischaemic encephalopathy without memory complaints (n = 7); and a group of typically developing (n = 9). All participants in every groups did have normal general intelligence and attention. Both clinical groups had, as another clinical consequence, spastic cerebral palsy (diplegia). Neuropsychological exam consisted on tests of general intelligence, attentional abilities, declarative memory and semantic knowledge. All participants had a brain magnetic resonance image and spectroscopy of hippocampi. Scheltens criteria were used for visual estimation of hippocampal atrophy. Parametric and non-parametric statistical contrasts were made. Despite preservation of semantic and procedural learning, declarative-episodic memory is impaired in the first group versus the other two groups. A significant proportion of bilateral hippocampal atrophy is only present in the first group versus the other two non-amnesic groups using Scheltens estimation on MRI. Two cases without evident atrophy did have diminished NAA/(Cho + Cr) index in both hippocampi. Taken together, these results contribute to delineate developmental amnesia as an specific impairment due to early partial bihippocampal damage, in agreement with previous studies. After diagnosis of developmental amnesia, a specific psychoeducational intervention must be made; also this impairment could be candidate for pharmacological trials in the future.

  7. Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism

    SciT

    Shao, Xue; Hu, Zhengtao; Hu, Chunyan

    Investigations have characterized addictive drug-induced developmental cardiovascular malformation in human, non-human primate and rodent. However, the underlying mechanism of malformation caused by drugs during pregnancy is still largely unknown, and preventive and therapeutic measures have been lacking. Using {sup 1}H NMR spectroscopy, we profiled the metabolites from human embryo endothelial cells exposed to methamphetamine (METH) and quantified a total of 226 peaks. We identified 11 metabolites modified robustly and found that taurine markedly increased. We then validated the hypothesis that this dramatic increase in taurine could attribute to its effect in inhibiting METH-induced developmental angiogenesis defect. Taurine supplement showed amore » more significant potential than other metabolites in protecting against METH-induced injury in endothelial cells. Taurine strongly attenuated METH-induced inhibition of proliferation and migration in endothelial cells. Furthermore, death rate and vessel abnormality of zebrafish embryos treated with METH were greatly reversed by taurine. In addition, taurine supplement caused a rapid decrease in reactive oxygen species generation and strongly attenuated the excitable arise of antioxidase activities in the beginning of METH exposure prophase. Dysregulations of NF-κB, p-ERK as well as Bax, which reflect apoptosis, cell cycle arrest and oxidative stress in vascular endothelium, were blocked by taurine. Our results provide the first evidence that taurine prevents METH-caused developmental angiogenesis defect through antioxidant mechanism. Taurine could serve as a potential therapeutic or preventive intervention of developmental vascular malformation for the pregnant women with drug use. Highlights: ► Metabonomics findings. ► Abnormal development. ► Dysregulations of key proteins.« less

  8. Developmental patterns of spatial ability: an early sex difference.

    PubMed

    Johnson, E S; Meade, A C

    1987-06-01

    Over 1,800 public school students (grades K-12, ages 6-18) took a battery of 7 spatial tests tailored to their respective developmental levels. Analyses of resulting data indicate that it is feasible to measure spatial ability throughout this developmental range with modified versions of adult paper-and-pencil tests, that a male advantage in spatial performance appears reliably by age 10, and that the magnitude of the advantage remains constant through age 18. Analysis of covariance suggests that an early female precocity in language skills may mask a male advantage in spatial ability during the primary school years. There is no indication of a sex difference in kindergarten children.

  9. Esthetic perception and psychosocial impact of developmental enamel defects among Malaysian adolescents.

    PubMed

    Sujak, Sharol Lail; Abdul Kadir, Rahimah; Dom, Tuti Ningseh Mohd

    2004-12-01

    The aim of this study was to investigate the prevalence and psychosocial impact of enamel defects among 16-year-old school children on the island of Penang. The data were collected through a self-administered questionnaire survey and an oral examination, using the Modified Developmental Defects of Enamel Index (FDI, 1992). In all, 1024 subjects were selected using a multistage random sampling technique. About two-thirds of the sample (67.1%) had at least one tooth affected by enamel defects. Enamel opacities accounted for 85.6% of the total condition. Diffuse-type opacity predominated (63.5%). Among subjects who expressed dissatisfaction, 18.8% reported covering their mouths when smiling, 8.7% avoided going out with friends and 39.1% had consulted their dentists. About 17% of the subjects reported that their parents had complained about the color of their front teeth but only 5.7% had experienced being teased by their friends about the problem. Two-thirds of the subjects were affected by enamel defects involving at least one tooth; however, the esthetic perception and psychosocial impact of those affected were minor.

  10. Maternal Obesity: Risks for Developmental Delays in Early Childhood.

    PubMed

    Duffany, Kathleen O'Connor; McVeigh, Katharine H; Kershaw, Trace S; Lipkind, Heather S; Ickovics, Jeannette R

    2016-02-01

    To assess the risk for neurodevelopmental delays for children of mothers who were obese (≥200 pounds) prior to pregnancy, and to characterize delays associated with maternal obesity among children referred to and found eligible to receive Early Intervention Program services. We conducted a retrospective cohort study (N = 541,816) using a population-based New York City data warehouse with linked birth and Early Intervention data. Risks for children suspected of a delay and 'significantly delayed', with two moderate or one severe delay, were calculated. Among the group of children eligible by delay for Early Intervention, analyses assessed risk for being identified with a moderate-to-severe delay across each of five functional domains as well as risks for multiple delays. Children of mothers who were obese were more likely to be suspected of a delay (adjusted RR 1.19 [CI 1.15-1.22]) and borderline association for 'significantly delayed' (adjusted RR 1.01 [CI 1.00-1.02). Among children eligible by delay, children of mothers who were obese evidenced an increased risk for moderate-to-severe cognitive (adjusted RR 1.04 [CI 1.02-1.07]) and physical (adjusted RR 1.04 [CI 1.01-1.08]) delays and for global developmental delay (adjusted RR 1.05 [CI 1.01-1.08]). Maternal obesity is associated with increased risk of developmental delay in offspring. Among children with moderate or severe delays, maternal obesity is associated with increased risk of cognitive and physical delays as well as with increased risk for global developmental delay. While causation remains uncertain, this adds to the growing body of research reporting an association between maternal obesity and neurodevelopmental delays in offspring.

  11. Antihistamine Use in Early Pregnancy and Risk of Birth Defects

    PubMed Central

    Li, Qian; Mitchell, Allen A.; Werler, Martha M.; Yau, Wai-Ping; Hernández-Díaz, Sonia

    2014-01-01

    Background Several studies have reported an association between use of specific antihistamines in early pregnancy and certain specific birth defects. Objective To test 16 previously-hypothesized associations between specific antihistamines and specific birth defects, and identify possible new associations. Methods We used 1998-2010 data from the Slone Epidemiology Center Birth Defects Study, a multicenter case-control surveillance program of birth defects in North America. Mothers were interviewed within six months of delivery about demographic, reproductive, medical, and behavioral factors, and details on use of prescription and non-prescription medications. We compared 1st trimester exposure to specific antihistamines between 13,213 infants with specific malformations and 6,982 non-malformed controls, using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders, including indication for use. Results Overall, 13.7% of controls were exposed to antihistamines during the 1st trimester. The most commonly-used medications were diphenhydramine (4.2%), loratadine (3.1%), doxylamine (1.9%), and chlorpheniramine (1.7%). Where estimates were stable, none supported the previously-hypothesized associations. Among over 100 exploratory comparisons of other specific antihistamine/defect pairs, 14 had ORs ≥1.5 of which 6 had 95% CI bounds excluding 1.0 before but not after adjustment for multiple comparisons. Conclusion Our findings do not provide meaningful support for previously-posited associations between antihistamines and major congenital anomalies; at the same time, we identified associations that had not been previously suggested. We suspect that previous associations may be chance findings in the context of multiple comparisons, a situation which may also apply to our new findings. PMID:24565715

  12. 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

  13. Trajectories of physical discipline: early childhood antecedents and developmental outcomes.

    PubMed

    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 ages 5 to 16 and from 258 children in an independent sample followed from ages 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.

  14. 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

  15. Defining the developmental parameters of temper loss in early childhood: implications for developmental psychopathology

    PubMed Central

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

    2013-01-01

    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 Parent-reported patterns of temper loss were delineated in a diverse community sample of preschoolers (n = 1,490). A developmentally sensitive questionnaire, the Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB), was used to assess temper loss in terms of tantrum features and anger regulation. Specific aims were: (a) document the normative distribution of temper loss in preschoolers from normative misbehaviors to clinically concerning temper loss behaviors, and test for sociodemographic differences; (b) use Item Response Theory (IRT) to model a Temper Loss dimension; and (c) examine associations of temper loss and concurrent emotional and behavioral problems. Results Across sociodemographic subgroups, a unidimensional Temper Loss model fit the data well. Nearly all (83.7%) preschoolers had tantrums sometimes but only 8.6% had daily tantrums. Normative misbehaviors occurred more frequently than clinically concerning temper loss behaviors. Milder behaviors tended to reflect frustration in expectable contexts, whereas clinically concerning problem indicators were unpredictable, prolonged, and/or destructive. In multivariate models, Temper Loss was associated with emotional and behavioral problems. Conclusions Parent reports on a developmentally informed questionnaire, administered to a large and diverse sample, distinguished normative and problematic manifestations of preschool temper loss. A developmental, dimensional approach shows promise for elucidating the boundaries between normative early childhood temper loss and emergent psychopathology. PMID:22928674

  16. Contribution of olivofloccular circuitry developmental defects to atypical gaze in autism

    PubMed Central

    Wegiel, Jerzy; Kuchna, Izabela; Nowicki, Krzysztof; Imaki, Humi; Wegiel, Jarek; Ma, Shuang Yong; Azmitia, Efrain C.; Banerjee, Probal; Flory, Michael; Cohen, Ira L.; London, Eric; Brown, W. Ted; Hare, Carolyn Komich; Wisniewski, Thomas

    2014-01-01

    Individuals with autism demonstrate atypical gaze, impairments in smooth pursuit, altered movement perception and deficits in facial perception. The olivofloccular neuronal circuit is a major contributor to eye movement control. This study of the cerebellum in 12 autistic and 10 control subjects revealed dysplastic changes in the flocculus of eight autistic (67%) and two control (20%) subjects. Defects of the oculomotor system, including avoidance of eye contact and poor or no eye contact, were reported in 88% of autistic subjects with postmortem-detected floccular dysplasia. Focal disorganization of the flocculus cytoarchitecture with deficit, altered morphology, and spatial disorientation of Purkinje cells (PCs); deficit and abnormalities of granule, basket, stellate and unipolar brush cells; and structural defects and abnormal orientation of Bergmann glia are indicators of profound disruption of flocculus circuitry in a dysplastic area. The average volume of PCs was 26% less in the dysplastic region than in the unaffected region of the flocculus (p<0.01) in autistic subjects. Moreover, the average volume of PCs in the entire cerebellum was 25% less in the autistic subjects than in the control subjects (p<0.001). Findings from this study and a parallel study of the inferior olive (IO) suggest that focal floccular dysplasia combined with IO neurons and PC developmental defects may contribute to oculomotor system dysfunction and atypical gaze in autistic subjects. PMID:23558308

  17. Toxicity and developmental defects of different sizes and shape nickel nanoparticles in zebrafish

    PubMed Central

    Ispas, Cristina; Andreescu, Daniel; Patel, Avni; Goia, Dan V.; Andreescu, Silvana; Wallace, Kenneth N.

    2009-01-01

    Metallic nanoparticles such as nickel are used in catalytic, sensing and electronic applications, but health and environmental affects have not been fully investigated. While some metal nanoparticles result in toxicity, it is also important to determine whether nanoparticles of the same metal but of different size and shape changes toxicity. Three different size nickel nanoparticle (Ni NPs) of 30, 60, and 100 nm and larger particle clusters of aggregated 60 nm entities with a dendritic structure were synthesized and exposed to zebrafish embryos assessing mortality and developmental defects. Ni NPs exposure was compared to soluble nickel salts. All three 30, 60, and 100 nm Ni NPs are equal to or less toxic than soluble nickel while dendritic clusters were more toxic. With each Ni NP exposure, thinning of the intestinal epithelium first occurs around the LD10 continuing into the LD50. LD50 exposure also results in skeletal muscle fiber separation. Exposure to soluble nickel does not cause intestinal defects while skeletal muscle separation occurs at concentrations well over LD50. These results suggest that configuration of nanoparticles may affect toxicity more than size and defects from Ni NPs exposure occur by different biological mechanisms than soluble nickel. PMID:19746736

  18. [The Battelle developmental inventory screening test for early detection of developmental disorders in cerebral palsy].

    PubMed

    Moraleda-Barreno, E; Romero-López, M; Cayetano-Menéndez, M J

    2011-12-01

    Cerebral palsy is usually associated with motor, cognitive, and language deficits, and with other disorders that cause disability in daily living skills, personal independence, social interaction and academic activities. Early detection of these deficits in the clinical setting is essential to anticipate and provide the child with the necessary support for adapting to the environment in all possible areas. The main objective of this study is to demonstrate that these deficits can be detected at an early age and comprehensively through the use of a brief development scale. We studied 100 children between 4 and 70 months old, half of them with cerebral palsy and the other half without any disorder. All subjects were evaluated using the Battelle Developmental Inventory screening test. We compared the developmental quotients in both groups and between the subjects with different motor impairments, using a simple prospective ex post facto design. The test detected statistically significant differences between the clinical group and the control group at all age levels. Statistically significant differences were also found between tetraplegia and other motor disorders. There were no differences by gender. The deficit in development associated with cerebral palsy can be quantified at early ages through the use of a brief development scale, thus we propose that the systematic implementation of protocols with this screening tool would be helpful for treatment and early intervention. This would also help in anticipating and establishing the means for the multidisciplinary actions required, and could provide guidance to other health professionals, to provide adequate school, social, and family support,. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  19. Developmental defects of enamel and dental caries in the primary dentition: A systematic review and meta-analysis.

    PubMed

    Costa, Francine S; Silveira, Ethieli R; Pinto, Gabriela S; Nascimento, Gustavo G; Thomson, William Murray; Demarco, Flávio F

    2017-05-01

    This systematic review and meta-analysis evaluated the association between developmental defects of enamel and dental caries in the primary dentition. Electronic searches were performed in PubMed, Web of Knowledge, Scopus and Scielo for the identification of relevant studies. Observational studies that examined the association between developmental defects of enamel and dental caries in the deciduous dentition were included. Additionally, meta-analysis, funnel plots and sensitivity analysis were employed to synthesize the available evidence. Multivariable meta-regression analysis was performed to explore heterogeneity among studies. A total of 318 articles were identified in the electronic searches. Of those, 16 studies were included in the meta-analysis. Pooled estimates revealed that children with developmental defects of enamel had higher odds of having dental caries (OR 3.32; 95%CI 2.41-4.57), with high heterogeneity between studies (I 2 80%). Methodological characteristic of the studies, such as where it was conducted, the examined teeth and the quality of the study explained about 30% of the variability. Concerning type of defect, children with hypoplasia and diffuse opacities had higher odds of having dental caries (OR 4.28; 95%CI 2.24-8.15; OR1.42; 95%CI 1.15-1.76, respectively). This systematic review and meta-analysis demonstrates a clear association between developmental defects of enamel and dental caries in the primary dentition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. 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

  1. Dental enamel defects in German medieval and early-modern-age populations.

    PubMed

    Lang, J; Birkenbeil, S; Bock, S; Heinrich-Weltzien, R; Kromeyer-Hauschild, K

    2016-11-01

    Aim of this study was to investigate the frequency and type of developmental defects of enamel (DDE) in a medieval and an early-modern-age population from Thuringia, Germany. Sixty-six skeletons subdivided into 31 single burials (12 th /13 th c.) and 35 individuals buried in groups (15 th /16 th c.) were examined. DDE were classified on 1,246 teeth according to the DDE index. Molar-incisor-hypomineralisation (MIH), a special type of DDE, was recorded according to the European Academy of Paediatric Dentistry (EAPD) criteria. DDE was found in 89.4% of the individuals (single burials 90.3% and group burials 88.6%). Hypoplastic pits were the most frequent defect in primary teeth and linear enamel hypoplasia (LEH) in permanent teeth. 13 individuals (24.1%) showed at least one hypomineralised permanent tooth, 12.2% had MIH on at least one first permanent molar and 10.0% in permanent incisors. Second primary molars were affected in 8.0% of the children and juveniles. No individual suffered from affected molars and incisors in combination. Endogenous factors like nutritional deficiencies and health problems in early childhood could have been aetiological reasons of DDE and MIH. The frequency of DDE and MIH might have been masked by extended carious lesions, dental wear and ante-mortem tooth loss.

  2. 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

  3. 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.

  4. 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…

  5. 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…

  6. Developmental Changes in Ultradian Sleep Cycles across Early Childhood.

    PubMed

    Lopp, Sean; Navidi, William; Achermann, Peter; LeBourgeois, Monique; Diniz Behn, Cecilia

    2017-02-01

    Nocturnal human sleep is composed of cycles between rapid eye movement (REM) sleep and non-REM (NREM) sleep. In adults, the structure of ultradian cycles between NREM and REM sleep is well characterized; however, less is known about the developmental trajectories of ultradian sleep cycles across early childhood. Cross-sectional studies indicate that the rapid ultradian cycling of active-quiet sleep in infancy shifts to a more adult-like pattern of NREM-REM sleep cycling by the school-age years, yet longitudinal studies elucidating the details of this transition are scarce. To address this gap, we examined ultradian cycling during nocturnal sleep following 13 h of prior wakefulness in 8 healthy children at 3 longitudinal points: 2Y (2.5-3.0 years of age), 3Y (3.5-4.0 years of age), and 5Y (5.5-6.0 years of age). We found that the length of ultradian cycles increased with age as a result of increased NREM sleep episode duration. In addition, we observed a significant decrease in the number of NREM sleep episodes as well as a nonsignificant trend for a decrease in the number of cycles with increasing age. Together, these findings suggest a concurrent change in which cycle duration increases and the number of cycles decreases across development. We also found that, consistent with data from adolescents and adults, the duration of NREM sleep episodes decreased with time since lights-off whereas the duration of REM sleep episodes increased over this time period. These results indicate the presence of circadian modulation of nocturnal sleep in preschool children. In addition to characterizing changes in ultradian cycling in healthy children ages 2 to 5 years, this work describes a developmental model that may provide insights into the emergence of normal adult REM sleep regulatory circuitry as well as potential trajectories of dysregulated ultradian cycles such as those associated with affective disorders.

  7. Developmental amnesia associated with early hypoxic-ischaemic injury.

    PubMed

    Gadian, D G; Aicardi, J; Watkins, K E; Porter, D A; Mishkin, M; Vargha-Khadem, F

    2000-03-01

    We recently reported on three young patients with severe impairments of episodic memory resulting from brain injury sustained early in life. These findings have led us to hypothesize that such impairments might be a previously unrecognized consequence of perinatal hypoxic-ischaemic injury. Neuropsychological and quantitative magnetic resonance investigations were carried out on five young patients, all of whom had suffered hypoxic-ischaemic episodes at or shortly after birth. All five patients showed severe impairments of episodic memory (memory for events), with relative preservation of semantic memory (memory for facts). However, none had any of the major neurological deficits that are typically associated with hypoxic-ischaemic injury, and all attended mainstream schools. Quantitative magnetic resonance investigations revealed severe bilateral hippocampal atrophy in all cases. As a group, the patients also showed bilateral reductions in grey matter in the regions of the putamen and the ventral part of the thalamus. On the basis of their clinical histories and the pattern of magnetic resonance findings, we attribute the patients' pathology and associated memory impairments primarily to hypoxic-ischaemic episodes sustained very early in life. We suggest that the degree of hypoxia-ischaemia was sufficient to produce selective damage to particularly vulnerable regions of the brain, notably the hippocampi, but was not sufficient to result in the more severe neurological and cognitive deficits that can follow hypoxic-ischaemic injury. The impairments in episodic memory may be difficult to recognize, particularly in early childhood, but this developmental amnesia can have debilitating consequences, both at home and at school, and may preclude independent life in adulthood.

  8. Excessive apoptosis and defective autophagy contribute to developmental testicular toxicity induced by fluoride.

    PubMed

    Zhang, Shun; Niu, Qiang; Gao, Hui; Ma, Rulin; Lei, Rongrong; Zhang, Cheng; Xia, Tao; Li, Pei; Xu, Chunyan; Wang, Chao; Chen, Jingwen; Dong, Lixing; Zhao, Qian; Wang, Aiguo

    2016-05-01

    Fluoride, a ubiquitous environmental contaminant, is known to impair testicular functions and fertility; however the underlying mechanisms remain obscure. In this study, we used a rat model to mimic human exposure and sought to investigate the roles of apoptosis and autophagy in testicular toxicity of fluoride. Sprague-Dawley rats were developmentally exposed to 25, 50, or 100 mg/L sodium fluoride (NaF) via drinking water from pre-pregnancy to post-puberty, and then the testes of offspring were excised on postnatal day 56. Our results demonstrated that developmental NaF exposure induced an enhanced testicular apoptosis, as manifested by a series of hallmarks such as caspase-3 activation, chromatin condensation and DNA fragmentation. Further study revealed that fluoride exposure elicited significant elevations in the levels of cell surface death receptor Fas with a parallel increase in cytoplasmic cytochrome c, indicating the involvement of both extrinsic and intrinsic apoptotic pathways. Intriguingly, fluoride treatment also simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II but not Beclin1. Unexpectedly, the expression of p62, a substrate that is degraded by autophagy, was also significantly elevated, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation rather than increased formation. Importantly, these were associated with marked histopathological lesions including spermatogenic failure and germ cell loss, along with severe ultrastructural abnormalities in testes. Taken together, our findings provide deeper insights into roles of excessive apoptosis and defective autophagy in the aggravation of testicular damage, which could contribute to a better understanding of fluoride-induced male reproductive toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Association between developmental enamel defects in the primary and permanent dentitions.

    PubMed

    Casanova-Rosado, A J; Medina-Solís, C E; Casanova-Rosado, J F; Vallejos-Sánchez, A A; Martinez-Mier, E A; Loyola-Rodríguez, J P; Islas-Márquez, A J; Maupomé, G

    2011-09-01

    To determine if the presence of developmental enamel defects (DED) in the primary dentition is a risk indicator for the presence of DED in the permanent dentition in children with mixed dentition, as well as others factors. A cross-sectional study was undertaken in 1296 school children ages six to 72 years. The DED [FDI; 1982] in both dentitions were identified by means of an oral exam scoring enamel opacities [classified as demarcated or diffused], and enamel hypoplasia. Sociodemographic and socioeconomic variables were collected through a questionnaire. Socioeconomic status (SES) was determined based on the occupation and maximum level of education of parents. Statistical analysis included logistic regression. Mean age of participants was 8.40 +/- 1.68; 51.6% were boys. DED prevalence was 7.5% in the permanent dentition and 10.0% in the primary dentition. The logistic regression model, adjusting for sociodemographic and socioeconomic variables, showed that for each primary tooth with DED, the odds of observing DED in the permanent dentition increased 7.38 times [95% CI = 1.17-1.64; p < 0.001]. An association between DED presence in both permanent and primary dentitions was observed. Further studies are necessary to fully characterise such relationship.

  10. 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

  11. 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.

  12. Increased body mass in infancy and early toddlerhood in Angelman syndrome patients with uniparental disomy and imprinting center defects.

    PubMed

    Brennan, Marie-Luise; Adam, Margaret P; Seaver, Laurie H; Myers, Angela; Schelley, Susan; Zadeh, Neda; Hudgins, Louanne; Bernstein, Jonathan A

    2015-01-01

    The diagnosis of Angelman syndrome (AS) is based on clinical features and genetic testing. Developmental delay, severe speech impairment, ataxia, atypical behavior and microcephaly by two years of age are typical. Feeding difficulties in young infants and obesity in late childhood can also be seen. The NIH Angelman-Rett-Prader-Willi Consortium and others have documented genotype-phenotype associations including an increased body mass index in children with uniparental disomy (UPD) or imprinting center (IC) defects. We recently encountered four cases of infantile obesity in non-deletion AS cases, and therefore examined body mass measures in a cohort of non-deletion AS cases. We report on 16 infants and toddlers (ages 6 to 44 months; 6 female, and 10 male) with severe developmental delay. Birth weights were appropriate for gestational age in most cases, >97th% in one case and not available in four cases. The molecular subclass case distribution consisted of: UPD (n = 2), IC defect (n = 3), UPD or IC defect (n = 3), and UBE3A mutation (n = 8). Almost all (7 out of 8) UPD, IC and UPD/IC cases went on to exhibit >90th% age- and gender-appropriate weight for height or BMI within the first 44 months. In contrast, no UBE3A mutation cases exhibited obesity or pre-obesity measures (percentiles ranged from <3% to 55%). These findings demonstrate that increased body mass may be evident as early as the first year of life and highlight the utility of considering the diagnosis of AS in the obese infant or toddler with developmental delay, especially when severe. Although a mechanism explaining the association of UPD, and IC defects with obesity has not been identified, recognition of this correlation may inform investigation of imprinting at the PWS/AS locus and obesity. © 2014 Wiley Periodicals, Inc.

  13. Another View on "Reinforcement in Developmentally Appropriate Early Childhood Classrooms."

    ERIC Educational Resources Information Center

    Wolfgang, Charles H.

    2001-01-01

    Contrasts the use of behavioral and developmental theories to address a child's aggression. Presents concerns about the use of social reinforcers, activity reinforcers, and tangible reinforcers. Asserts that behavioral techniques that shape children's surface behaviors without placing the behaviors within a developmental context may interfere with…

  14. Associations of Early Developmental Milestones with Adult Intelligence

    ERIC Educational Resources Information Center

    Flensborg-Madsen, Trine; Mortensen, Erik L.

    2018-01-01

    The study investigated whether age at attainment of 20 developmental milestones within the areas of language, walking, eating, dressing, social interaction, and toilet training was associated with adult intelligence. Mothers of 821 children of the Copenhagen Perinatal Cohort recorded 20 developmental milestones at a 3-year examination, and all…

  15. 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…

  16. Topological Defects and Structures in the Early Universe

    NASA Astrophysics Data System (ADS)

    Zhu, Yong

    1997-08-01

    This thesis discusses the topological defects generated in the early universe and their contributions to cosmic structure formation. First, we investigate non-Gaussian isocurvature perturbations generated by the evolution of Goldstone modes during inflation. If a global symmetry is broken before inflation, the resulting Goldstone modes are disordered during inflation in a precise and predictable way. After inflation these Goldstone modes order themselves in a self-similar way, much as Goldstone modes in field ordering scenarios based on the Kibble mechanism. For (Hi2/Mpl2)~10- 6, through their gravitational interaction these Goldstone modes generate density perturbations of approximately the right magnitude to explain the cosmic microwave background (CMB) anisotropy and seed the structure seen in the universe today. In such a model non-Gaussian perturbations result because to lowest order density perturbations are sourced by products of Gaussian fields. We explore the issue of phase dispersion and conclude that this non-Gaussian model predicts Doppler peaks in the CMB anisotropy. Topological defects generated from quantum fluctuations during inflation are studied in chapter four. We present a calculation of the power spectrum generated in a classically symmetry-breaking O(N) scalar field through inflationary quantum fluctuations, using the large-N limit. The effective potential of the theory in de Sitter space is obtained from a gap equation which is exact at large N. Quantum fluctuations restore the O(N) symmetry in de Sitter space, but for the finite values of N of interest, there is symmetry breaking and phase ordering after inflation, described by the classical nonlinear sigma model. The scalar field power spectrum is obtained as a function of the scalar field self-coupling. In the second part of the thesis, we investigate non-Abelian topological worm-holes, obtained when winding number one texture field is coupled to Einstein gravity with a conserved global

  17. Pluripotent cell models of fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors.

    PubMed

    Suzuki, Naoya M; Niwa, Akira; Yabe, Miharu; Hira, Asuka; Okada, Chihiro; Amano, Naoki; Watanabe, Akira; Watanabe, Ken-Ichiro; Heike, Toshio; Takata, Minoru; Nakahata, Tatsutoshi; Saito, Megumu K

    2015-04-01

    Fanconi anemia (FA) is a disorder of genomic instability characterized by progressive bone marrow failure (BMF), developmental abnormalities, and an increased susceptibility to cancer. Although various consequences in hematopoietic stem/progenitor cells have been attributed to FA-BMF, the quest to identify the initial pathological event is still ongoing. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts of six patients with FA and FANCA mutations. An improved reprogramming method yielded iPSC-like colonies from all patients, and iPSC clones were propagated from two patients. Quantitative evaluation of the differentiation ability demonstrated that the differentiation propensity toward the hematopoietic and endothelial lineages is already defective in early hemoangiogenic progenitors. The expression levels of critical transcription factors were significantly downregulated in these progenitors. These data indicate that the hematopoietic consequences in FA patients originate from the early hematopoietic stage and highlight the potential usefulness of iPSC technology for elucidating the pathogenesis of FA-BMF. ©AlphaMed Press.

  18. 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.…

  19. Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1.

    PubMed

    Kim, Edward; Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S; Anthony, Todd E; Wang, Chenran; Li, Yi E; Guan, Jun-Lin; Murphy, Geoffrey G; Zhu, Yuan

    2014-12-23

    Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities.

  20. Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1

    PubMed Central

    Kim, Edward; Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S; Anthony, Todd E; Wang, Chenran; Li, Yi E; Guan, Jun-Lin; Murphy, Geoffrey G; Zhu, Yuan

    2014-01-01

    Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities. DOI: http://dx.doi.org/10.7554/eLife.05151.001 PMID:25535838

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

    ERIC Educational Resources Information Center

    Sackes, Mesut

    2013-01-01

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

  2. 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

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

    PubMed

    Font, Sarah A; Berger, Lawrence M

    2015-01-01

    Associations between experiencing child maltreatment and adverse developmental outcomes are widely studied, yet conclusions regarding the extent to which effects are bidirectional, and whether they are likely causal, remain elusive. This study uses the Fragile Families and Child Wellbeing Study, a birth cohort of 4,898 children followed from birth through age 9. Hierarchical linear modeling and structural equation modeling are employed to estimate associations of maltreatment with cognitive and social-emotional well-being. Results suggest that effects of early childhood maltreatment emerge immediately, though developmental outcomes are also affected by newly occurring maltreatment over time. Additionally, findings indicate that children's early developmental scores predict their subsequent probability of experiencing maltreatment, though to a lesser extent than early maltreatment predicts subsequent developmental outcomes. © 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.

  4. Multidisciplinary Developmental Evaluation Improves Early Diagnosis of Infantile Autism.

    ERIC Educational Resources Information Center

    Siegel, B.; And Others

    A life-course perspective of the diagnostic histories of 75 autistic individuals (ages 4-25) was obtained through the use of parent surveys and a review of their charts. The study was made to understand better how children who presented with uneven or unusual behavioral development are identified as developmentally multihandicapped. Areas examined…

  5. 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…

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

    ERIC Educational Resources Information Center

    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 ages 5 to 16 and from 258 children in an independent sample followed from ages 5 to 15. Analyses indicated…

  7. A Novel Apoptosis Pathway that is Defective in Early Breast Cancer

    DTIC Science & Technology

    2005-04-01

    AD Award Number: DAMD17-02-1-0612 TITLE: A Novel Apoptosis Pathway that is Defective in Early Breast Cancer PRINCIPAL INVESTIGATOR: Scott Cramer...Defective in Early DAMD17-02-1-0612 Breast Cancer 6. AUTHOR(S) Scott Cramer, Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING...These experiments were intended to determine why breast cancer cells are resistant to this apoptosis pathway BODY. As outlined in the previous

  8. Evolutionary developmental pathology and anthropology: A new field linking development, comparative anatomy, human evolution, morphological variations and defects, and medicine.

    PubMed

    Diogo, Rui; Smith, Christopher M; Ziermann, Janine M

    2015-11-01

    We introduce a new subfield of the recently created field of Evolutionary-Developmental-Anthropology (Evo-Devo-Anth): Evolutionary-Developmental-Pathology-and-Anthropology (Evo-Devo-P'Anth). This subfield combines experimental and developmental studies of nonhuman model organisms, biological anthropology, chordate comparative anatomy and evolution, and the study of normal and pathological human development. Instead of focusing on other organisms to try to better understand human development, evolution, anatomy, and pathology, it places humans as the central case study, i.e., as truly model organism themselves. We summarize the results of our recent Evo-Devo-P'Anth studies and discuss long-standing questions in each of the broader biological fields combined in this subfield, paying special attention to the links between: (1) Human anomalies and variations, nonpentadactyly, homeotic transformations, and "nearest neighbor" vs. "find and seek" muscle-skeleton associations in limb+facial muscles vs. other head muscles; (2) Developmental constraints, the notion of "phylotypic stage," internalism vs. externalism, and the "logic of monsters" vs. "lack of homeostasis" views about human birth defects; (3) Human evolution, reversions, atavisms, paedomorphosis, and peromorphosis; (4) Scala naturae, Haeckelian recapitulation, von Baer's laws, and parallelism between phylogeny and development, here formally defined as "Phylo-Devo parallelism"; and (5) Patau, Edwards, and Down syndrome (trisomies 13, 18, 21), atavisms, apoptosis, heart malformations, and medical implications. © 2015 Wiley Periodicals, Inc.

  9. Early Identification of Developmental Delays through Surveillance, Screening, and Diagnostic Evaluation

    ERIC Educational Resources Information Center

    Pizur-Barnekow, Kris; Erickson, Stephanie; Johnston, Mark; Bass, Tamicah; Lucinski, Loraine; Bleuel, Dan

    2010-01-01

    Developmental and behavioral problems in young children are prevalent in the United States. While young children experience an increased prevalence of such problems, a lack of early identification services continues to exist. Not only are early identification services required under American law, such as the Individual with Disabilities Education…

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

    ERIC Educational Resources Information Center

    Colgan, Siobhan Eileen

    2012-01-01

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

  11. Autism in Early Childhood: An Unusual Developmental Course—Three Case Reports

    PubMed Central

    Cohen-Ophir, Michal; Castel-Deutsh, Tsophia; Tirosh, Emanuel

    2012-01-01

    Autistic spectrum disorder (ASD) is typically characterized by either an emerging and gradual course or developmental regression in early childhood. The versatile clinical course is progressively acknowledged in recent years. Children with developmental disorders in general are referred to the Child Development Center for a multidisciplinary assessment, investigation, treatment and followup. We report three infants with an initial diagnosis of developmental delays, recovery of normal development following intervention in a multidisciplinary center, and subsequent regression into classic autism following their discharge from the program. An extensive medical workup was noncontributory. This unusual presentation, to our knowledge not reported previously, should be recognized by professionals involved in child development and psychiatry. PMID:22937419

  12. 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. © 2014 The Authors Development, Growth & Differentiation © 2014 Japanese Society of Developmental Biologists.

  13. The developmental neurotoxicity of arsenic: cognitive and behavioral consequences of early life exposure.

    PubMed

    Tolins, Molly; Ruchirawat, Mathuros; Landrigan, Philip

    2014-01-01

    More than 200 million people worldwide are chronically exposed to arsenic. Arsenic is a known human carcinogen, and its carcinogenic and systemic toxicity have been extensively studied. By contrast, the developmental neurotoxicity of arsenic has been less well described. The aim of this review was to provide a comprehensive review of the developmental neurotoxicity of arsenic. We reviewed the published epidemiological and toxicological literature on the developmental neurotoxicity of arsenic. Arsenic is able to gain access to the developing brain and cause neurotoxic effects. Animal models link prenatal and early postnatal exposure to reduction in brain weight, reductions in numbers of glia and neurons, and alterations in neurotransmitter systems. Animal and in vitro studies both suggest that oxidative stress may be a mechanism of arsenic neurotoxicity. Fifteen epidemiological studies indicate that early life exposure is associated with deficits in intelligence and memory. These effects may occur at levels of exposure below current safety guidelines, and some neurocognitive consequences may become manifest only later in life. Sex, concomitant exposures, and timing of exposure appear to modify the developmental neurotoxicity of arsenic. Four epidemiological studies failed to show behavioral outcomes of arsenic exposure. The published literature indicates that arsenic is a human developmental neurotoxicant. Ongoing and future prospective birth cohort studies will allow more precise definition of the developmental consequences of arsenic exposure in early life. Copyright © 2014. Published by Elsevier Inc.

  14. 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…

  15. 78 FR 78321 - Early Warning Reporting, Foreign Defect Reporting, and Motor Vehicle and Equipment Recall...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-26

    ... DEPARTMENT OF TRANSPORTATION National Highway Traffic Safety Administration 49 CFR Parts 573, 577, and 579 [Docket No. NHTSA--2012-0068; Notice 3] RIN 2127-AK72 Early Warning Reporting, Foreign Defect... final rule. Id. Manufacturers with early warning reporting (EWR) accounts may obtain a copy of the VIN...

  16. 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…

  17. Cats, frogs, and snakes: early concepts of neural tube defects.

    PubMed

    Obladen, Michael

    2011-11-01

    Disturbed neurulation fascinated scientists of all times. In Egypt, anencephalic infants were venerated as animal-headed gods. Roman law required them to be killed. The medieval world held the mother responsible, either because of assumed imagination or "miswatching," or because of suspected intercourse with animals or devils. Modern embryology and teratology began with the use of the microscope by Malpighi in 1672. Details of neural tube closure were described by Koelliker in 1861 and by His in 1874. From 1822, genetic disease and familial recurrence due to insufficient nutrition were discerned and lower social class identified as a risk factor. It took a century to define the malnutrition as insufficient folate intake. The mandatory supplementation of folate in staple foods successfully reduced the incidence of neural tube defects in the United States, Australia, Canada, and Chile, but it was not adopted by most European countries.

  18. Suppressed production of methyl farnesoid hormones yields developmental defects and lethality in Drosophila larvae

    A long-unresolved question in the developmental biology of Drosophila melanogaster has been whether methyl farnesoid hormones secreted by the ring gland are necessary for larval maturation and metamorphosis. In this study, we have used RNAi techniques to inhibit 3-Hydroxy-3-Methylglutaryl CoA Reduct...

  19. Mechanistic modeling of developmental defects through computational embryology (WC10th)

    EPA Science Inventory

    Abstract: An important consideration for 3Rs is to identify developmental hazards utilizing mechanism-based in vitro assays (e.g., ToxCast) and in silico predictive models. Steady progress has been made with agent-based models that recapitulate morphogenetic drivers for angiogen...

  20. Usherin defects lead to early-onset retinal dysfunction in zebrafish.

    PubMed

    Dona, Margo; Slijkerman, Ralph; Lerner, Kimberly; Broekman, Sanne; Wegner, Jeremy; Howat, Taylor; Peters, Theo; Hetterschijt, Lisette; Boon, Nanda; de Vrieze, Erik; Sorusch, Nasrin; Wolfrum, Uwe; Kremer, Hannie; Neuhauss, Stephan; Zang, Jingjing; Kamermans, Maarten; Westerfield, Monte; Phillips, Jennifer; van Wijk, Erwin

    2018-05-16

    Mutations in USH2A are the most frequent cause of Usher syndrome and autosomal recessive nonsyndromic retinitis pigmentosa. To unravel the pathogenic mechanisms underlying USH2A-associated retinal degeneration and to evaluate future therapeutic strategies that could potentially halt the progression of this devastating disorder, an animal model is needed. The available Ush2a knock-out mouse model does not mimic the human phenotype, because it presents with only a mild and late-onset retinal degeneration. Using CRISPR/Cas9-technology, we introduced protein-truncating germline lesions into the zebrafish ush2a gene (ush2a rmc1 : c.2337_2342delinsAC; p.Cys780GlnfsTer32 and ush2a b1245 : c.15520_15523delinsTG; p.Ala5174fsTer). Homozygous mutants were viable and displayed no obvious morphological or developmental defects. Immunohistochemical analyses with antibodies recognizing the N- or C-terminal region of the ush2a-encoded protein, usherin, demonstrated complete absence of usherin in photoreceptors of ush2a rmc1 , but presence of the ectodomain of usherin at the periciliary membrane of ush2a b1245 -derived photoreceptors. Furthermore, defects of usherin led to a reduction in localization of USH2 complex members, whirlin and Adgrv1, at the photoreceptor periciliary membrane of both mutants. Significantly elevated levels of apoptotic photoreceptors could be observed in both mutants when kept under constant bright illumination for three days. Electroretinogram (ERG) recordings revealed a significant and similar decrease in both a- and b-wave amplitudes in ush2a rmc1 as well as ush2a b1245 larvae as compared to strain- and age-matched wild-type larvae. In conclusion, this study shows that mutant ush2a zebrafish models present with early-onset retinal dysfunction that is exacerbated by light exposure. These models provide a better understanding of the pathophysiology underlying USH2A-associated RP and a unique opportunity to evaluate future therapeutic strategies. Copyright

  1. Mother-Child Interaction and Resilience in Children with Early Developmental Risk

    PubMed Central

    Fenning, Rachel M.; Baker, Jason K.

    2014-01-01

    Although prenatal and genetic factors make strong contributions to the emergence of intellectual disability (ID), children's early environment may have the potential to alter developmental trajectories and to foster resilience in children with early risk. The present study examined mother-child interaction and the promotion of competence in 50 children with early developmental delays. Three related but distinct aspects of mother-child interaction were considered: maternal technical scaffolding, maternal positive-sensitivity, and mother-child dyadic pleasure. Children were classified as exhibiting undifferentiated delays at age three based upon performance on developmental assessments and the absence of known genetic syndromes. Mother-child interaction was assessed at age four through observational ratings of structured laboratory tasks and through naturalistic home observations. ID was identified at age five using the dual criteria of clinically significant delays in cognitive functioning and adaptive behavior. Maternal technical scaffolding and dyadic pleasure each uniquely predicted reduced likelihood of later ID, beyond the contributions of children's early developmental level and behavioral functioning. Follow-up analyses suggested that mother-child interaction was primarily important to resilience in the area of adaptive behavior, with scaffolding and dyadic pleasure differentially associated with particular sub-domains. Implications for theories of intellectual disability and for family-based early intervention and prevention efforts are discussed. PMID:22662771

  2. 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:…

  3. 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…

  4. 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)

  5. Developmental Needs and Early Childhood Education: Evolutionary, My Dear Watson

    ERIC Educational Resources Information Center

    Henry, Margaret

    2004-01-01

    Examining the processes of natural selection, described by Darwin in "The Origin of Species", casts light on our own species' fundamental needs and on the far greater role that early childhood educators can play in their fulfillment. The second section of this paper analyzes how our fundamental needs emerge in a sequence underpinned by the…

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

    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.

  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. A Mobile Early Stimulation Program to Support Children with Developmental Delays in Brazil.

    PubMed

    Dias, Raquel da Luz; Silva, Kátia Cristina Correa Guimarães; Lima, Marcela Raquel de Oliveira; Alves, João Guilherme Bezerra; Abidi, Syed Sibte Raza

    2018-01-01

    Developmental delay is a deviation development from the normative milestones during the childhood and it may be caused by neurological disorders. Early stimulation is a standardized and simple technique to treat developmental delays in children (aged 0-3 years), allowing them to reach the best development possible and to mitigate neuropsychomotor sequelae. However, the outcomes of the treatment depending on the involvement of the family, to continue the activities at home on a daily basis. To empower and educate parents of children with neurodevelopmental delays to administer standardized early stimulation programs at home, we developed a mobile early stimulation program that provides timely and evidence-based clinical decision support to health professionals and a personalized guidance to parents about how to administer early stimulation to their child at home.

  9. 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…

  10. 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…

  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. 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…

  13. 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…

  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. 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…

  16. 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…

  17. 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…

  18. 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…

  19. 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…

  20. 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.…

  1. 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…

  2. 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,…

  3. Early Developmental Regression in Autism Spectrum Disorder: Evidence from an International Multiplex Sample

    ERIC Educational Resources Information Center

    Parr, Jeremy R.; Le Couteur, Ann; Baird, Gillian; Rutter, Michael; Pickles, Andrew; Fombonne, Eric; Bailey, Anthony J.

    2011-01-01

    The characteristics of early developmental regression (EDR) were investigated in individuals with ASD from affected relative pairs recruited to the International Molecular Genetic Study of Autism Consortium (IMGSAC). Four hundred and fifty-eight individuals with ASD were recruited from 226 IMGSAC families. Regression before age 36 months occurred…

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  5. 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…

  6. Small Steps: An Early Intervention Program for Children with Developmental Delays.

    ERIC Educational Resources Information Center

    Pieterse, Moira; And Others

    This boxed set includes eight booklets of home activities for early intervention for young children with developmental delays. The first book provides an introduction to the program and its implementation, lists 23 resources, describes a videotape which supplements the booklets, and includes a glossary. Book 2 covers how to select goals for the…

  7. Rituximab does not reset defective early B cell tolerance checkpoints

    PubMed Central

    Chamberlain, Nicolas; Massad, Christopher; Oe, Tyler; Cantaert, Tineke; Herold, Kevan C.; Meffre, Eric

    2015-01-01

    Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve β cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti–B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti–B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti–B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti–B cell therapy. PMID:26642366

  8. Early-life stress and reproductive cost: A two-hit developmental model of accelerated aging?

    PubMed

    Shalev, Idan; Belsky, Jay

    2016-05-01

    Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Juxtaposition of chemical and mutation-induced developmental defects in zebrafish reveal a copper-chelating activity for kalihinol F.

    PubMed

    Sandoval, Imelda T; Manos, Elizabeth J; Van Wagoner, Ryan M; Delacruz, Richard Glenn C; Edes, Kornelia; Winge, Dennis R; Ireland, Chris M; Jones, David A

    2013-06-20

    A major hurdle in using complex systems for drug screening is the difficulty of defining the mechanistic targets of small molecules. The zebrafish provides an excellent model system for juxtaposing developmental phenotypes with mechanism discovery using organism genetics. We carried out a phenotype-based screen of uncharacterized small molecules in zebrafish that produced a variety of chemically induced phenotypes with potential genetic parallels. Specifically, kalihinol F caused an undulated notochord, defects in pigment formation, hematopoiesis, and neural development. These phenotypes were strikingly similar to the zebrafish mutant, calamity, an established model of copper deficiency. Further studies into the mechanism of action of kalihinol F revealed a copper-chelating activity. Our data support this mechanism of action for kalihinol F and the utility of zebrafish as an effective system for identifying therapeutic and target pathways. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Mouse Models for Investigating the Developmental Bases of Human Birth Defects

    PubMed Central

    MOON, ANNE M.

    2006-01-01

    Clinicians and basic scientists share an interest in discovering how genetic or environmental factors interact to perturb normal development and cause birth defects and human disease. Given the complexity of such interactions, it is not surprising that 4% of human infants are born with a congenital malformation, and cardiovascular defects occur in nearly 1%. Our research is based on the fundamental hypothesis that an understanding of normal and abnormal development will permit us to generate effective strategies for both prevention and treatment of human birth defects. Animal models are invaluable in these efforts because they allow one to interrogate the genetic, molecular and cellular events that distinguish normal from abnormal development. Several features of the mouse make it a particularly powerful experimental model: it is a mammalian system with similar embryology, anatomy and physiology to humans; genes, proteins and regulatory programs are largely conserved between human and mouse; and finally, gene targeting in murine embryonic stem cells has made the mouse genome amenable to sophisticated genetic manipulation currently unavailable in any other model organism. PMID:16641221

  11. Trajectories of Early Childhood Developmental Skills and Early Adolescent Psychotic Experiences: Findings from the ALSPAC UK Birth Cohort.

    PubMed

    Hameed, Mohajer A; Lingam, Raghu; Zammit, Stanley; Salvi, Giovanni; Sullivan, Sarah; Lewis, Andrew J

    2017-01-01

    Objective: The aim of this study was to use prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine association between trajectories of early childhood developmental skills and psychotic experiences (PEs) in early adolescence. Method: This study examined data from n = 6790 children from the ALSPAC cohort who participated in a semi-structured interview to assess PEs at age 12. Child development was measured using parental report at 6, 18, 30, and 42 months of age using a questionnaire of items adapted from the Denver Developmental Screening Test - II. Latent class growth analysis was used to generate trajectories over time for measures of fine and gross motor development, social, and communication skills. Logistic regression was used to investigate associations between developmental trajectories in each of these early developmental domains and PEs at age 12. Results: The results provided evidence that decline rather than enduringly poor social (adjusted OR = 1.28, 95% CI = 1.10-1.92, p = 0.044) and communication skills (adjusted OR 1.12, 95% CI = 1.03-1.22, p = 0.010) is predictive of suspected or definite PEs in early adolescence, than those with stable and/or improving skills. Motor skills did not display the same pattern of association; although gender specific effects provided evidence that only declining pattern of fine motor skills was associated with suspected and definite PEs in males compared to females (interaction OR = 1.47, 95% CI = 1.09-1.97, p = 0.012). Conclusion: Findings suggest that decline rather than persistent impairment in social and communication skills were most predictive of PEs in early adolescence. Findings are discussed in terms of study's strengths, limitations, and clinical implications.

  12. Trajectories of Early Childhood Developmental Skills and Early Adolescent Psychotic Experiences: Findings from the ALSPAC UK Birth Cohort

    PubMed Central

    Hameed, Mohajer A.; Lingam, Raghu; Zammit, Stanley; Salvi, Giovanni; Sullivan, Sarah; Lewis, Andrew J.

    2018-01-01

    Objective: The aim of this study was to use prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine association between trajectories of early childhood developmental skills and psychotic experiences (PEs) in early adolescence. Method: This study examined data from n = 6790 children from the ALSPAC cohort who participated in a semi-structured interview to assess PEs at age 12. Child development was measured using parental report at 6, 18, 30, and 42 months of age using a questionnaire of items adapted from the Denver Developmental Screening Test – II. Latent class growth analysis was used to generate trajectories over time for measures of fine and gross motor development, social, and communication skills. Logistic regression was used to investigate associations between developmental trajectories in each of these early developmental domains and PEs at age 12. Results: The results provided evidence that decline rather than enduringly poor social (adjusted OR = 1.28, 95% CI = 1.10–1.92, p = 0.044) and communication skills (adjusted OR 1.12, 95% CI = 1.03–1.22, p = 0.010) is predictive of suspected or definite PEs in early adolescence, than those with stable and/or improving skills. Motor skills did not display the same pattern of association; although gender specific effects provided evidence that only declining pattern of fine motor skills was associated with suspected and definite PEs in males compared to females (interaction OR = 1.47, 95% CI = 1.09–1.97, p = 0.012). Conclusion: Findings suggest that decline rather than persistent impairment in social and communication skills were most predictive of PEs in early adolescence. Findings are discussed in terms of study’s strengths, limitations, and clinical implications. PMID:29375433

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

    PubMed

    Tyler, Frances; Rodríguez-Muñoz, Rolando; Tregenza, Tom

    2013-02-15

    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. 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. 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 number of eggs that fail to develop

  14. Turmeric Extract Rescues Ethanol-Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD).

    PubMed

    Muralidharan, Pooja; Connors, Craig T; Mohammed, Arooj S; Sarmah, Swapnalee; Marrs, Kathleen; Marrs, James A; Chism, Grady W

    2017-09-01

    Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol-induced developmental defect using zebrafish as a model was determined. Ethanol-induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol-induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol-treated embryos. The mechanism underlying the rescue remains to be determined. © 2017 Institute of Food Technologists®.

  15. Next generation sequencing identifies mutations in Atonal homolog 7 (ATOH7) in families with global eye developmental defects

    PubMed Central

    Khan, Kamron; Logan, Clare V.; McKibbin, Martin; Sheridan, Eamonn; Elçioglu, Nursel H.; Yenice, Ozlem; Parry, David A.; Fernandez-Fuentes, Narcis; Abdelhamed, Zakia I.A.; Al-Maskari, Ahmed; Poulter, James A.; Mohamed, Moin D.; Carr, Ian M.; Morgan, Joanne E.; Jafri, Hussain; Raashid, Yasmin; Taylor, Graham R.; Johnson, Colin A.; Inglehearn, Chris F.; Toomes, Carmel; Ali, Manir

    2012-01-01

    The atonal homolog 7 (ATOH7) gene encodes a transcription factor involved in determining the fate of retinal progenitor cells and is particularly required for optic nerve and ganglion cell development. Using a combination of autozygosity mapping and next generation sequencing, we have identified homozygous mutations in this gene, p.E49V and p.P18RfsX69, in two consanguineous families diagnosed with multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus. Most of these clinical features overlap with defects in the Norrin/β-catenin signalling pathway that is characterized by dysgenesis of the retinal and hyaloid vasculature. Our findings document Mendelian mutations within ATOH7 and imply a role for this molecule in the development of structures at the front as well as the back of the eye. This work also provides further insights into the function of ATOH7, especially its importance in retinal vascular development and hyaloid regression. PMID:22068589

  16. Early developmental characteristics and features of major depressive disorder among child psychiatric patients in Hungary.

    PubMed

    Kapornai, Krisztina; Gentzler, Amy L; Tepper, Ping; Kiss, Eniko; Mayer, László; Tamás, Zsuzsanna; Kovacs, Maria; Vetró, Agnes

    2007-06-01

    We investigate the relations of early atypical characteristics (perinatal problems, developmental delay, and difficult temperament) and onset-age (as well as severity of) first major depressive disorder (MDD) and first internalizing disorder in a clinical sample of depressed children in Hungary. Participants were 371 children (ages 7-14) with MDD, and their biological mothers, recruited through multiple clinical sites. Diagnoses (via DSM-IV criteria) and onset dates of disorders were finalized "best estimate" psychiatrists, and based on multiple information sources. Mothers provided developmental data in a structured interview. Difficult temperament predicted earlier onset of MDD and first internalizing disorder, but its effect was ameliorated if the family was intact during early childhood. Further, the importance of difficult temperament decreased as a function of time. Perinatal problems and developmental delay did not impact onset ages of disorders, and none of the early childhood characteristics associated with MDD episode severity. Children with MDD may have added disadvantage of earlier onset if they had a difficult temperament in infancy. Because early temperament mirrors physiological reactivity and regulatory capacity, it can affect various areas of functioning related to psychopathology. Early caregiver stability may attenuate some adverse effects of difficult infant temperament.

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

    PubMed Central

    Tain, You-Lin; Hsu, Chien-Ning

    2017-01-01

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

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

    PubMed

    Myers, Sonya S; Pianta, Robert C

    2008-07-01

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

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

    PubMed

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

    2016-04-01

    Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. History Of Self-Disclosure In Females And Early Defection From Psychotherapy

    ERIC Educational Resources Information Center

    Heilbrun, Alfred B., Jr.

    1973-01-01

    Late adolescent girls who would more likely defect from psychotherapy early had a self-rated history of greater self-disclosure than did girls who would more likely continue. This difference was especially clear with male targets. The second experimental study revealed a similar finding; terminators are higher self-disclosers to males whereas…

  1. Risk of Congenital Heart Defects after Ambient Heat Exposure Early in Pregnancy.

    PubMed

    Auger, Nathalie; Fraser, William D; Sauve, Reg; Bilodeau-Bertrand, Marianne; Kosatsky, Tom

    2017-01-01

    Congenital heart defects may be environmentally related, but the association with elevated ambient temperature has received little attention. We studied the relationship between outdoor heat during the first trimester of pregnancy and risk of congenital heart defects. We carried out a retrospective cohort study of 704,209 fetuses between 2 and 8 weeks postconception from April to September in Quebec, Canada, 1988-2012. We calculated the prevalence of congenital heart defects at birth according to the number of days women were exposed to maximum temperature ≥ 30°C. In log-binomial regression models, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) for the relationship of temperature with seven critical and eight noncritical heart defects, adjusted for pregnancy characteristics. Prevalence of congenital heart defects was 979.5 per 100,000 for 10 days or more of temperature ≥ 30°C compared with 878.9 per 100,000 for 0 days of exposure. Temperature was more precisely associated with noncritical than critical defects, which had lower prevalence. Fetuses exposed to 15 days of temperature ≥ 30°C between 2 and 8 weeks postconception had 1.06 times the risk of critical defects (95% CI: 0.67, 1.67) and 1.12 times the risk of noncritical defects (95% CI: 0.98, 1.29) relative to 0 days. Associations were higher for atrial septal defects (PR 1.37, 95% CI: 1.10, 1.70) than for other noncritical defects. For atrial septal defects, associations with elevated temperatures began the 3rd week postconception. Extreme heat exposure during the first trimester may be associated with noncritical heart defects, especially of the atrial septum. Citation: Auger N, Fraser WD, Sauve R, Bilodeau-Bertrand M, Kosatsky T. 2017. Risk of congenital heart defects after ambient heat exposure early in pregnancy. Environ Health Perspect 125:8-14; http://dx.doi.org/10.1289/EHP171.

  2. Prenatal corticosteroid exposure alters early developmental seizures and behavior

    PubMed Central

    Velíšek, Libor

    2011-01-01

    In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hydrocortisone (2× 10 mg/kg), betamethasone (2× 0.4 mg/kg) or vehicle. On postnatal day (P)15, seizures were induced by flurothyl or kainic acid (3.5 or 5.0 mg/kg). Horizontal bar holding was determined prior to seizures and again on P17. Performance in the elevated plus maze was assessed on P20-22. Prenatal exposure to betamethasone decreased postnatal susceptibility to flurothyl-induced clonic seizures but not to kainic acid-induced seizures. Prenatal hydrocortisone decreased postnatal weight but did not affect seizure susceptibility. Hydrocortisone alone did not affect performance in behavioral tests except for improving horizontal bar holding on P17. A combination of prenatal hydrocortisone and postnatal seizures resulted in increased anxiety. Prenatal exposure to mineralocorticoid receptor blocker canrenoic acid did not attenuate, but surprisingly amplified the effects of hydrocortisone on body weight and significantly worsened horizontal bar performance. Thus, prenatal exposure to excess corticosteroids alters postnatal seizure susceptibility and behaviors. Specific effects may depend on corticosteroid species. PMID:21429712

  3. l-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome

    PubMed Central

    Xu, Baoshan; Sowa, Nenja; Cardenas, Maria E.; Gerton, Jennifer L.

    2015-01-01

    Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that RBS was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation. l-leucine stimulation of the mTOR pathway partially rescued translation in human RBS cells and development in zebrafish models of RBS. In this study, we investigate protein translation in zebrafish models of CdLS. Our results show that phosphorylation of RPS6 as well as 4E-binding protein 1 (4EBP1) was reduced in nipbla/b, rad21 and smc3-morphant embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis and rRNA production were decreased in the cohesin morphant embryo cells. l-leucine partly rescued protein synthesis and rRNA production in the cohesin morphants and partially restored phosphorylation of RPS6 and 4EBP1. Concomitantly, l-leucine treatment partially improved cohesinopathy embryo development including the formation of craniofacial cartilage. Interestingly, we observed that alpha-ketoisocaproate (α-KIC), which is a keto derivative of leucine, also partially rescued the development of rad21 and nipbla/b morphants by boosting mTOR-dependent translation. In summary, our results suggest that cohesinopathies are caused in part by defective protein synthesis, and stimulation of the mTOR pathway through l-leucine or its metabolite α-KIC can partially rescue development in zebrafish models for CdLS. PMID:25378554

  4. L-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome.

    PubMed

    Xu, Baoshan; Sowa, Nenja; Cardenas, Maria E; Gerton, Jennifer L

    2015-03-15

    Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that RBS was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation. l-leucine stimulation of the mTOR pathway partially rescued translation in human RBS cells and development in zebrafish models of RBS. In this study, we investigate protein translation in zebrafish models of CdLS. Our results show that phosphorylation of RPS6 as well as 4E-binding protein 1 (4EBP1) was reduced in nipbla/b, rad21 and smc3-morphant embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis and rRNA production were decreased in the cohesin morphant embryo cells. l-leucine partly rescued protein synthesis and rRNA production in the cohesin morphants and partially restored phosphorylation of RPS6 and 4EBP1. Concomitantly, l-leucine treatment partially improved cohesinopathy embryo development including the formation of craniofacial cartilage. Interestingly, we observed that alpha-ketoisocaproate (α-KIC), which is a keto derivative of leucine, also partially rescued the development of rad21 and nipbla/b morphants by boosting mTOR-dependent translation. In summary, our results suggest that cohesinopathies are caused in part by defective protein synthesis, and stimulation of the mTOR pathway through l-leucine or its metabolite α-KIC can partially rescue development in zebrafish models for CdLS. © The Author 2014. Published by Oxford University Press.

  5. Maternal report of fever from cold or flu during early pregnancy and the risk for noncardiac birth defects, National Birth Defects Prevention Study, 1997-2011.

    PubMed

    Waller, Dorothy Kim; Hashmi, Syed Shahrukh; Hoyt, Adrienne T; Duong, Hao T; Tinker, Sarah C; Gallaway, Michael Shayne; Olney, Richard S; Finnell, Richard H; Hecht, Jacqueline Tauber; Canfield, Mark A

    2018-03-01

    As maternal fever affects approximately 6-8% of early pregnancies, it is important to expand upon previous observations of an association between maternal fever and birth defects. We analyzed data from the National Birth Defects Prevention Study, a multistate, case-control study of major structural birth defects. Telephone interviews were completed by mothers of cases (n = 17,162) and controls (n = 10,127). Using multivariable logistic regression, we assessed the association between maternal self-report of cold or flu with fever and cold or flu without fever during early pregnancy and 30 categories of non-cardiac birth defects. Maternal report of cold or flu with fever was significantly associated with 8 birth defects (anencephaly, spina bifida, encephalocele, cleft lip with or without cleft palate, colonic atresia/stenosis, bilateral renal agenesis/hypoplasia, limb reduction defects, and gastroschisis) with elevated adjusted odds ratios ranging from 1.2 to 3.7. Maternal report of cold or flu without fever was not associated with any of the birth defects studied. This study adds to the evidence that maternal fever during early pregnancy is associated with an increased risk for selected birth defects. Elevated associations were limited to mothers who reported a fever, suggesting that it is fever that contributes to the excess risk rather than illnesses associated with it. However, fever may also serve as a marker for more severe infections. © 2017 Wiley Periodicals, Inc.

  6. 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

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

    PubMed Central

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

    2017-01-01

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

  8. Novel degenerative and developmental defects in a zebrafish model of mucolipidosis type IV

    PubMed Central

    Li, Huiqing; Pei, Wuhong; Vergarajauregui, Sivia; Zerfas, Patricia M.; Raben, Nina; Burgess, Shawn M.; Puertollano, Rosa

    2017-01-01

    Abstract Mucolipidosis type IV (MLIV) is a lysosomal storage disease characterized by neurologic and ophthalmologic abnormalities. There is currently no effective treatment. MLIV is caused by mutations in MCOLN1, a lysosomal cation channel from the transient receptor potential (TRP) family. In this study, we used genome editing to knockout the two mcoln1 genes present in Danio rerio (zebrafish). Our model successfully reproduced the retinal and neuromuscular defects observed in MLIV patients, indicating that this model is suitable for studying the disease pathogenesis. Importantly, our model revealed novel insights into the origins and progression of the MLIV pathology, including the contribution of autophagosome accumulation to muscle dystrophy and the role of mcoln1 in embryonic development, hair cell viability and cellular maintenance. The generation of a MLIV model in zebrafish is particularly relevant given the suitability of this organism for large-scale in vivo drug screening, thus providing unprecedented opportunities for therapeutic discovery. PMID:28449103

  9. Armc5 deletion causes developmental defects and compromises T-cell immune responses

    PubMed Central

    Hu, Yan; Lao, Linjiang; Mao, Jianning; Jin, Wei; Luo, Hongyu; Charpentier, Tania; Qi, Shijie; Peng, Junzheng; Hu, Bing; Marcinkiewicz, Mieczyslaw Martin; Lamarre, Alain; Wu, Jiangping

    2017-01-01

    Armadillo repeat containing 5 (ARMC5) is a cytosolic protein with no enzymatic activities. Little is known about its function and mechanisms of action, except that gene mutations are associated with risks of primary macronodular adrenal gland hyperplasia. Here we map Armc5 expression by in situ hybridization, and generate Armc5 knockout mice, which are small in body size. Armc5 knockout mice have compromised T-cell proliferation and differentiation into Th1 and Th17 cells, increased T-cell apoptosis, reduced severity of experimental autoimmune encephalitis, and defective immune responses to lymphocytic choriomeningitis virus infection. These mice also develop adrenal gland hyperplasia in old age. Yeast 2-hybrid assays identify 16 ARMC5-binding partners. Together these data indicate that ARMC5 is crucial in fetal development, T-cell function and adrenal gland growth homeostasis, and that the functions of ARMC5 probably depend on interaction with multiple signalling pathways. PMID:28169274

  10. Homozygous EEF1A2 mutation causes dilated cardiomyopathy, failure to thrive, global developmental delay, epilepsy and early death.

    PubMed

    Cao, Siqi; Smith, Laura L; Padilla-Lopez, Sergio R; Guida, Brandon S; Blume, Elizabeth; Shi, Jiahai; Morton, Sarah U; Brownstein, Catherine A; Beggs, Alan H; Kruer, Michael C; Agrawal, Pankaj B

    2017-09-15

    Eukaryotic elongation factor 1A (EEF1A), is encoded by two distinct isoforms, EEF1A1 and EEF1A2; whereas EEF1A1 is expressed almost ubiquitously, EEF1A2 expression is limited such that it is only detectable in skeletal muscle, heart, brain and spinal cord. Currently, the role of EEF1A2 in normal cardiac development and function is unclear. There have been several reports linking de novo dominant EEF1A2 mutations to neurological issues in humans. We report a pair of siblings carrying a homozygous missense mutation p.P333L in EEF1A2 who exhibited global developmental delay, failure to thrive, dilated cardiomyopathy and epilepsy, ultimately leading to death in early childhood. A third sibling also died of a similar presentation, but DNA was unavailable to confirm the mutation. Functional genomic analysis was performed in S. cerevisiae and zebrafish. In S. cerevisiae, there was no evidence for a dominant-negative effect. Previously identified putative de novo mutations failed to complement yeast strains lacking the EEF1A ortholog showing a major growth defect. In contrast, the introduction of the mutation seen in our family led to a milder growth defect. To evaluate its function in zebrafish, we knocked down eef1a2 expression using translation blocking and splice-site interfering morpholinos. EEF1A2-deficient zebrafish had skeletal muscle weakness, cardiac failure and small heads. Human EEF1A2 wild-type mRNA successfully rescued the morphant phenotype, but mutant RNA did not. Overall, EEF1A2 appears to be critical for normal heart function in humans, and its deficiency results in clinical abnormalities in neurologic function as well as in skeletal and cardiac muscle defects. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. 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

  12. 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…

  13. Defective chromatic and achromatic visual pathways in developmental dyslexia: Cues for an integrated intervention programme.

    PubMed

    Bonfiglio, Luca; Bocci, Tommaso; Minichilli, Fabrizio; Crecchi, Alessandra; Barloscio, Davide; Spina, Donata Maria; Rossi, Bruno; Sartucci, Ferdinando

    2017-01-01

    As well as obtaining confirmation of the magnocellular system involvement in developmental dyslexia (DD); the aim was primarily to search for a possible involvement of the parvocellular system; and, furthermore, to complete the assessment of the visual chromatic axis by also analysing the koniocellular system. Visual evoked potentials (VEPs) in response to achromatic stimuli with low luminance contrast and low spatial frequency, and isoluminant red/green and blue/yellow stimuli with high spatial frequency were recorded in 10 dyslexic children and 10 age- and sex-matched, healthy subjects. Dyslexic children showed delayed VEPs to both achromatic stimuli (magnocellular-dorsal stream) and isoluminant red/green and blue/yellow stimuli (parvocellular-ventral and koniocellular streams). To our knowledge, this is the first time that a dysfunction of colour vision has been brought to light in an objective way (i.e., by means of electrophysiological methods) in children with DD. These results give rise to speculation concerning the need for a putative approach for promoting both learning how to read and/or improving existing reading skills of children with or at risk of DD. The working hypothesis would be to combine two integrated interventions in a single programme aimed at fostering the function of both the magnocellular and the parvocellular streams.

  14. Sodium benzoate induced developmental defects, oxidative stress and anxiety-like behaviour in zebrafish larva.

    PubMed

    Gaur, Himanshu; Purushothaman, Srinithi; Pullaguri, Narasimha; Bhargava, Yogesh; Bhargava, Anamika

    2018-07-20

    Sodium benzoate (SB) is a common food preservative. Its FDA described safety limit is 1000 ppm. Lately, increased use of SB has prompted investigations regarding its effects on biological systems. Data regarding toxicity of SB is divergent and controversial with studies reporting both harmful and beneficial effects. Therefore, we did a systematic dose dependent toxicity study of SB using zebrafish vertebrate animal model. We also investigated oxidative stress and anxiety-like behaviour in zebrafish larva treated with SB. Our results indicate that SB induced developmental (delayed hatching), morphological (pericardial edema, yolk sac edema and tail bending), biochemical (oxidative stress) and behavioural (anxiety-like behaviour) abnormalities in developing zebrafish larva. LC 50 of SB induced toxicity was approximately 400 ppm after 48 h of SB exposure. Our study strongly supports its harmful effects on vertebrates at increasing doses. Thus, we suggest caution in the excessive use of this preservative in processed and convenience foods. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo

    PubMed Central

    Abdel-Wahab, Omar; Gao, Jie; Adli, Mazhar; Dey, Anwesha; Trimarchi, Thomas; Chung, Young Rock; Kuscu, Cem; Hricik, Todd; Ndiaye-Lobry, Delphine; LaFave, Lindsay M.; Koche, Richard; Shih, Alan H.; Guryanova, Olga A.; Kim, Eunhee; Li, Sheng; Pandey, Suveg; Shin, Joseph Y.; Telis, Leon; Liu, Jinfeng; Bhatt, Parva K.; Monette, Sebastien; Zhao, Xinyang; Mason, Christopher E.; Park, Christopher Y.; Bernstein, Bradley E.

    2013-01-01

    Somatic Addition of Sex Combs Like 1 (ASXL1) mutations occur in 10–30% of patients with myeloid malignancies, most commonly in myelodysplastic syndromes (MDSs), and are associated with adverse outcome. Germline ASXL1 mutations occur in patients with Bohring-Opitz syndrome. Here, we show that constitutive loss of Asxl1 results in developmental abnormalities, including anophthalmia, microcephaly, cleft palates, and mandibular malformations. In contrast, hematopoietic-specific deletion of Asxl1 results in progressive, multilineage cytopenias and dysplasia in the context of increased numbers of hematopoietic stem/progenitor cells, characteristic features of human MDS. Serial transplantation of Asxl1-null hematopoietic cells results in a lethal myeloid disorder at a shorter latency than primary Asxl1 knockout (KO) mice. Asxl1 deletion reduces hematopoietic stem cell self-renewal, which is restored by concomitant deletion of Tet2, a gene commonly co-mutated with ASXL1 in MDS patients. Moreover, compound Asxl1/Tet2 deletion results in an MDS phenotype with hastened death compared with single-gene KO mice. Asxl1 loss results in a global reduction of H3K27 trimethylation and dysregulated expression of known regulators of hematopoiesis. RNA-Seq/ChIP-Seq analyses of Asxl1 in hematopoietic cells identify a subset of differentially expressed genes as direct targets of Asxl1. These findings underscore the importance of Asxl1 in Polycomb group function, development, and hematopoiesis. PMID:24218140

  16. Prevention and early intervention for behaviour problems in children with developmental disabilities.

    PubMed

    Einfeld, Stewart L; Tonge, Bruce J; Clarke, Kristina S

    2013-05-01

    To review the recent evidence regarding early intervention and prevention studies for children with developmental disabilities and behaviour problems from 2011 to 2013. Recent advances in the field are discussed and important areas for future research are highlighted. Recent reviews and studies highlight the utility of antecedent interventions and skills training interventions for reducing behaviour problems. There is preliminary evidence for the effectiveness of parent training interventions when delivered in minimally sufficient formats or in clinical settings. Two recent studies have demonstrated the utility of behavioural interventions for children with genetic causes of disability. Various forms of behavioural and parent training interventions are effective at reducing the behaviour problems in children with developmental disabilities. However, research on prevention and early intervention continues to be relatively scarce. Further large-scale dissemination studies and effectiveness studies in clinical or applied settings are needed.

  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. Birth defects after use of antithyroid drugs in early pregnancy: a Swedish nationwide study.

    PubMed

    Andersen, Stine Linding; Lönn, Stefan; Vestergaard, Peter; Törring, Ove

    2017-10-01

    Antithyroid drugs (ATDs) may have teratogenic effects, but more evidence is needed on the risk and types of birth defects after the use of methimazole (MMI) and propylthiouracil (PTU). This study aimed to evaluate the association between the use of ATDs in early pregnancy and birth defects. Swedish nationwide register-based cohort study. The study included 684 340 children live-born in Sweden from 2006 to 2012. Exposure groups defined by maternal ATD use in early pregnancy were MMI ( n  = 162); PTU ( n  = 218); MMI and PTU ( n  = 66); ATD before or after, but not in pregnancy ( n  = 1551) and non-exposed (never ATD ( n  = 682 343)). Outcome was cumulative incidence of birth defects diagnosed before two years of age. The cumulative incidence of birth defects was not significantly different in children exposed to MMI (6.8%, P  = 0.6) or PTU (6.4%, P  = 0.4) vs non-exposed (8.0%). For subtypes of birth defects, MMI was associated with an increased incidence of septal heart defects ( P  = 0.02). PTU was associated with ear ( P  = 0.005) and obstructive urinary system malformations ( P  = 0.006). A case of choanal atresia was observed after exposure to both MMI and PTU. The incidence of birth defects in children born to mothers who received ATD before or after, but not in pregnancy, was 8.8% and not significantly different from non-exposed ( P  = 0.3), MMI exposed ( P  = 0.4) or PTU exposed ( P  = 0.2). MMI and PTU were associated with subtypes of birth defects previously reported, but the frequency of ATD exposure in early pregnancy was low and severe malformations described in the MMI embryopathy were rarely observed. © 2017 European Society of Endocrinology.

  19. Beyond Developmentalism? Early Childhood Teachers' Understandings of Multiage Grouping in Early Childhood Education and Care

    ERIC Educational Resources Information Center

    Edwards, Susan; Blaise, Mindy; Hammer, Marie

    2009-01-01

    Postdevelopmental perspectives in early childhood education and care increasingly reference alternative ways of understanding learning, growth and development in early learning. Drawing on these ideas, this paper examines research findings which focused on early childhood teachers' understandings of multiage grouping. The findings suggested that…

  20. Repair of Craniomaxillofacial Traumatic Soft Tissue Defects With Tissue Expansion in the Early Stage.

    PubMed

    Han, Yan; Zhao, Jianhui; Tao, Ran; Guo, Lingli; Yang, Hongyan; Zeng, Wei; Song, Baoqiang; Xia, Wensen

    2017-09-01

    Craniomaxillofacial traumatic soft tissue defects severely affect the function and appearance of the patients. The traditional skin grafting or free flap transplantation can only close the defects in the early stage of operation but cannot ensure similar color, texture, and relative aesthetic contour. In the present study, the authors have explored a novel strategy to repair craniomaxillofacial traumatic soft tissue defects by tissue expansion in the early stage and have obtained satisfactory results. Eighteen patients suffering large craniomaxillofacial traumatic soft tissue defects were treated by thorough debridement leaving the wounds unclosed or simply closed with thin split-thickness scalp grafts, adjacent expander implantation in the first stage, and expanded flap transposition in the second stage. There were 11 male patients and 7 female patients ranging in age from 3.5 to 40 years (mean, 19.4 ± 12.2 years), with average 15 months follow-up (range, 3-67 months). The average expansion time was 74.3 days (range, 53-96 days). The 18 patients with a total of 22 expanders were treated with satisfactory results. All the flaps survived and the skin color, texture, and contour well matched those of the peripheral tissue. Only 1 complication of infection happened in the 18 cases (5.56%) and the 22 expanders (4.55%), which was similar to the rate reported in the literature. No other complications related to the expanders occurred. Debridement and tissue expansion in the early stage has been proved to be a more effective strategy to repair craniomaxillofacial traumatic soft tissue defects. This strategy can not only achieve satisfactory color, unbulky and well-matched texture similar to normal, but also avoid unnecessary donor site injuries.

  1. Vision-Based Sensor for Early Detection of Periodical Defects in Web Materials

    PubMed Central

    Bulnes, Francisco G.; Usamentiaga, Rubén; García, Daniel F.; Molleda, Julio

    2012-01-01

    During the production of web materials such as plastic, textiles or metal, where there are rolls involved in the production process, periodically generated defects may occur. If one of these rolls has some kind of flaw, it can generate a defect on the material surface each time it completes a full turn. This can cause the generation of a large number of surface defects, greatly degrading the product quality. For this reason, it is necessary to have a system that can detect these situations as soon as possible. This paper presents a vision-based sensor for the early detection of this kind of defects. It can be adapted to be used in the inspection of any web material, even when the input data are very noisy. To assess its performance, the sensor system was used to detect periodical defects in hot steel strips. A total of 36 strips produced in ArcelorMittal Avilés factory were used for this purpose, 18 to determine the optimal configuration of the proposed sensor using a full-factorial experimental design and the other 18 to verify the validity of the results. Next, they were compared with those provided by a commercial system used worldwide, showing a clear improvement. PMID:23112629

  2. 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…

  3. Early risk factors and developmental pathways to chronic high inhibition and social anxiety disorder in adolescence.

    PubMed

    Essex, Marilyn J; Klein, Marjorie H; Slattery, Marcia J; Goldsmith, H Hill; Kalin, Ned H

    2010-01-01

    Evidence suggests that chronic high levels of behavioral inhibition are a precursor of social anxiety disorder. The authors sought to identify early risk factors for, and developmental pathways to, chronic high inhibition among school-age children and the association of chronic high inhibition with social anxiety disorder by adolescence. A community sample of 238 children was followed from birth to grade 9. Mothers, teachers, and children reported on the children's behavioral inhibition from grades 1 to 9. Lifetime history of psychiatric disorders was available for the subset of 60 (25%) children who participated in an intensive laboratory assessment at grade 9. Four early risk factors were assessed: female gender; exposure to maternal stress during infancy and the preschool period; and at age 4.5 years, early manifestation of behavioral inhibition and elevated afternoon salivary cortisol levels. All four risk factors predicted greater and more chronic inhibition from grades 1 to 9, and together they defined two developmental pathways. The first pathway, in girls, was partially mediated by early evidence of behavioral inhibition and elevated cortisol levels at age 4.5 years. The second pathway began with exposure to early maternal stress and was also partially mediated by childhood cortisol levels. By grade 9, chronic high inhibition was associated with a lifetime history of social anxiety disorder. Chronic high levels of behavioral inhibition are associated with social anxiety disorder by adolescence. The identification of two developmental pathways suggests the potential importance of considering both sets of risk factors in developing preventive interventions for social anxiety disorder.

  4. 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

  5. Evidence of Early Childhood Defects Due to Prenatal Over-Exposure to Vitamin A: A Case Study

    ERIC Educational Resources Information Center

    Naude, H.; Marx, J.; Pretorius, E.; Hislop-Esterhuyzen, N.

    2007-01-01

    One of the important nutrients during pregnancy is vitamin A or related compounds called retinoids. Although it is well-known that vitamin A deficiency may be detrimental to foetal development, overdosage of retinoids might cause developmental defects, particularly affecting the central nervous system development of the foetus, causing hindbrain…

  6. Analysis of the Developmental Functioning of Early Intervention and Early Childhood Special Education Populations in Oregon. Issues & Answers. REL 2009-078

    ERIC Educational Resources Information Center

    Nave, Gary; Nishioka, Vicki; Burke, Arthur

    2009-01-01

    This study reports on the developmental functioning levels of children from birth through age 2 in early intervention services and children ages 3-5 in early childhood special education services at the time of entry into services, using data from the Oregon Early Childhood Assessment System. The assessment system contains data on the assessed…

  7. The developmental disruptions of serotonin signaling may involved in autism during early brain development.

    PubMed

    Yang, C-J; Tan, H-P; Du, Y-J

    2014-05-16

    Autism is a developmental disorder defined by the presence of a triad of communication, social and stereo typical behavioral characteristics with onset before 3years of age. In spite of the fact that there are potential environmental factors for autistic behavior, the dysfunction of serotonin during early development of the brain could be playing a role in this prevalence rise. Serotonin can modulate a number of developmental events, including cell division, neuronal migration, cell differentiation and synaptogenesis. Hyperserotonemia during fetal development results in the loss of serotonin terminals through negative feedback. The increased serotonin causes a decrease of oxytocin in the paraventricular nucleus of the hypothalamus and an increase in calcitonin gene-related peptide (CGRP) in the central nucleus of the amygdale, which are associated with social interactions and vital in autism. However, hyposerotonemia may be also relevant to the development of sensory as well as motor and cognitive faculties. And the paucity of placenta-derived serotonin should have potential importance when the pathogenesis of autism is considered. This review briefly summarized the developmental disruptions of serotonin signaling involved in the pathogenesis of autism during early development of the brain. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2011-01-01

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

  9. Acquired color vision and visual field defects in patients with ocular hypertension and early glaucoma

    PubMed Central

    Papaconstantinou, Dimitris; Georgalas, Ilias; Kalantzis, George; Karmiris, Efthimios; Koutsandrea, Chrysanthi; Diagourtas, Andreas; Ladas, Ioannis; Georgopoulos, Gerasimos

    2009-01-01

    Purpose: To study acquired color vision and visual field defects in patients with ocular hypertension (OH) and early glaucoma. Methods: In a prospective study we evaluated 99 eyes of 56 patients with OH without visual field defects and no hereditary color deficiencies, followed up for 4 to 6 years (mean = 4.7 ± 0.6 years). Color vision defects were studied using a special computer program for Farnsworth–Munsell 100 hue test and visual field tests were performed with Humphrey analyzer using program 30–2. Both tests were repeated every six months. Results: In fifty-six eyes, glaucomatous defects were observed during the follow-up period. There was a statistically significant difference in total error score (TES) between eyes that eventually developed glaucoma (157.89 ± 31.79) and OH eyes (75.51 ± 31.57) at the first examination (t value 12.816, p < 0.001). At the same time visual field indices were within normal limits in both groups. In the glaucomatous eyes the earliest statistical significant change in TES was identified at the first year of follow-up and was −20.62 ± 2.75 (t value 9.08, p < 0.001) while in OH eyes was −2.11 ± 4.36 (t value 1.1, p = 0.276). Pearson’s coefficient was high in all examinations and showed a direct correlation between TES and mean deviation and corrected pattern standard deviation in both groups. Conclusion: Quantitative analysis of color vision defects provides the possibility of follow-up and can prove a useful means for detecting early glaucomatous changes in patients with normal visual fields. PMID:19668575

  10. Acquired color vision and visual field defects in patients with ocular hypertension and early glaucoma.

    PubMed

    Papaconstantinou, Dimitris; Georgalas, Ilias; Kalantzis, George; Karmiris, Efthimios; Koutsandrea, Chrysanthi; Diagourtas, Andreas; Ladas, Ioannis; Georgopoulos, Gerasimos

    2009-01-01

    To study acquired color vision and visual field defects in patients with ocular hypertension (OH) and early glaucoma. In a prospective study we evaluated 99 eyes of 56 patients with OH without visual field defects and no hereditary color deficiencies, followed up for 4 to 6 years (mean = 4.7 +/- 0.6 years). Color vision defects were studied using a special computer program for Farnsworth-Munsell 100 hue test and visual field tests were performed with Humphrey analyzer using program 30-2. Both tests were repeated every six months. In fifty-six eyes, glaucomatous defects were observed during the follow-up period. There was a statistically significant difference in total error score (TES) between eyes that eventually developed glaucoma (157.89 +/- 31.79) and OH eyes (75.51 +/- 31.57) at the first examination (t value 12.816, p < 0.001). At the same time visual field indices were within normal limits in both groups. In the glaucomatous eyes the earliest statistical significant change in TES was identified at the first year of follow-up and was -20.62 +/- 2.75 (t value 9.08, p < 0.001) while in OH eyes was -2.11 +/- 4.36 (t value 1.1, p = 0.276). Pearson's coefficient was high in all examinations and showed a direct correlation between TES and mean deviation and corrected pattern standard deviation in both groups. Quantitative analysis of color vision defects provides the possibility of follow-up and can prove a useful means for detecting early glaucomatous changes in patients with normal visual fields.

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

    PubMed

    Hammond, LaTisha M; Hofmann, Gretchen E

    2012-07-15

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

  12. Temporal variations in early developmental decisions: an engine of forebrain evolution.

    PubMed

    Bielen, H; Pal, S; Tole, S; Houart, C

    2017-02-01

    Tight control of developmental timing is pivotal to many major processes in developmental biology, such as patterning, fate specification, cell cycle dynamics, cell migration and connectivity. Temporal change in these ontogenetic sequences is known as heterochrony, a major force in the evolution of body plans and organogenesis. In the last 5 years, studies in fish and rodents indicate that heterochrony in signaling during early development generates diversity in forebrain size and complexity. Here, we summarize these findings and propose that, additionally to spatio-temporal tuning of neurogenesis, temporal and quantitative modulation of signaling events drive pivotal changes in shape, size and complexity of the forebrain across evolution, participating to the generation of diversity in animal behavior and emergence of cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. 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.

  14. Early-onset sleep defects in Drosophila models of Huntington's disease reflect alterations of PKA/CREB signaling

    PubMed Central

    Gonzales, Erin D.; Tanenhaus, Anne K.; Zhang, Jiabin; Chaffee, Ryan P.; Yin, Jerry C.P.

    2016-01-01

    Huntington's disease (HD) is a progressive neurological disorder whose non-motor symptoms include sleep disturbances. Whether sleep and activity abnormalities are primary molecular disruptions of mutant Huntingtin (mutHtt) expression or result from neurodegeneration is unclear. Here, we report Drosophila models of HD exhibit sleep and activity disruptions very early in adulthood, as soon as sleep patterns have developed. Pan-neuronal expression of full-length or N-terminally truncated mutHtt recapitulates sleep phenotypes of HD patients: impaired sleep initiation, fragmented and diminished sleep, and nighttime hyperactivity. Sleep deprivation of HD model flies results in exacerbated sleep deficits, indicating that homeostatic regulation of sleep is impaired. Elevated PKA/CREB activity in healthy flies produces patterns of sleep and activity similar to those in our HD models. We were curious whether aberrations in PKA/CREB signaling were responsible for our early-onset sleep/activity phenotypes. Decreasing signaling through the cAMP/PKA pathway suppresses mutHtt-induced developmental lethality. Genetically reducing PKA abolishes sleep/activity deficits in HD model flies, restores the homeostatic response and extends median lifespan. In vivo reporters, however, show dCREB2 activity is unchanged, or decreased when sleep/activity patterns are abnormal, suggesting dissociation of PKA and dCREB2 occurs early in pathogenesis. Collectively, our data suggest that sleep defects may reflect a primary pathological process in HD, and that measurements of sleep and cAMP/PKA could be prodromal indicators of disease, and serve as therapeutic targets for intervention. PMID:26604145

  15. The utility of early developmental assessments on understanding later nonverbal IQ in children who are deaf or hard of hearing.

    PubMed

    Meinzen-Derr, Jareen; Wiley, Susan; Phillips, Jannel; Altaye, Mekibib; Choo, Daniel I

    2017-01-01

    In children who are deaf or hard of hearing (DHH), it is helpful to have meaningful early measures of development in order to provide effective interventions and offer benchmarks that help recognize varied developmental trajectories. The main objective of this study was to compare results of an early developmental assessment prior to 3 years of age to later nonverbal IQ assessed between 3 and 6 years of age in children who are DHH. This study included children 3-6 years of age with bilateral permanent hearing who were enrolled in a prospective cohort study on developmental outcomes. As part of the study, children received the Leiter International Performance Scale-Revised, which provided a nonverbal Brief IQ, as well as standardized language assessment and behavioral checklists. Children were included in this analysis if they had received an early developmental assessment with the Gesell Developmental Schedules-Revised as part of a clinical visit with a developmental pediatrician. Correlation coefficients and multiple regression analysis were used to associate the scores on the Gesell (using a developmental quotient) with scores on the Leiter-R Brief IQ. Forty-five participants who enrolled in the observational study had available evaluation results from the Gesell and complete Brief IQ results from the Leiter-R. The adaptive domain of the Gesell had good correlation (r = 0.61, p < 0.0001) with the Brief IQ on the Leiter-R. Children who had stable developmental or intelligence classifications based on scores (<70, 70 to <85, 85 to <100, ≥100) over time were older (>24 months) at the early Gesell assessment. Degree of hearing loss or maternal education did not appear to confound the relationship between the Gesell and the Leiter-R. The adaptive domain of the Gesell Developmental Schedules - Revised administered in early childhood (under 3 years of age) has good correlation with the nonverbal Brief IQ on the Leiter International Performance Scale-R. Because

  16. Interactions of sex and early life social experiences at two developmental stages shape nonapeptide receptor profiles.

    PubMed

    Hiura, Lisa C; Ophir, Alexander G

    2018-05-31

    Early life social experiences are critical to behavioral and cognitive development, and can have a tremendous influence on developing social phenotypes. Most work has focused on outcomes of experiences at a single stage of development (e.g., perinatal, or post-weaning). Few studies have assessed the impact of social experience at multiple developmental stages and across sex. Oxytocin and vasopressin are profoundly important for modulating social behavior and these nonapeptide systems are highly sensitive to developmental social experience, particularly in brain areas important for social behavior. We investigated whether oxytocin receptor (OTR) and vasopressin receptor (V1aR) distributions of prairie voles (Microtus ochrogaster) change as a function of parental composition within the natal nest or social composition after weaning. We raised pups either in the presence or absence of their fathers. At weaning, offspring were housed either individually or with a same-sex sibling. We also examined whether changes in receptor distributions are sexually dimorphic because the impact of the developmental environment on the nonapeptide system could be sex-dependent. We found that differences in nonapeptide receptor expression were region-, sex-, and rearing condition-specific, indicating a high level of complexity in the ways that early life experiences shape the social brain. We found many more differences in V1aR density compared to OTR density, indicating that nonapeptide receptors demonstrate differential levels of neural plasticity and sensitivity to environmental and biological variables. Our data highlight that critical factors including biological sex and multiple experiences across the developmental continuum interact in complex ways to shape the social brain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. 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. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  18. Parenting and the development of effortful control from early childhood to early adolescence: A transactional developmental model.

    PubMed

    Tiberio, Stacey S; Capaldi, Deborah M; Kerr, David C R; Bertrand, Maria; Pears, Katherine C; Owen, Lee

    2016-08-01

    Poor effortful control is a key temperamental factor underlying behavioral problems. The bidirectional association of child effortful control with both positive parenting and negative discipline was examined from ages approximately 3 to 13-14 years, involving five time points, and using data from parents and children in the Oregon Youth Study-Three Generational Study (N = 318 children from 150 families). Based on a dynamic developmental systems approach, it was hypothesized that there would be concurrent associations between parenting and child effortful control and bidirectional effects across time from each aspect of parenting to effortful control and from effortful control to each aspect of parenting. It was also hypothesized that associations would be more robust in early childhood, from ages 3 to 7 years, and would diminish as indicated by significantly weaker effects at the older ages, 11-12 to 13-14 years. Longitudinal feedback or mediated effects were also tested. The findings supported (a) stability in each construct over multiple developmental periods; (b) concurrent associations, which were significantly weaker at the older ages; (c) bidirectional effects, consistent with the interpretation that at younger ages children's effortful control influenced parenting, whereas at older child ages, parenting influenced effortful control; and (d) a transactional effect, such that maternal parenting in late childhood was a mechanism explaining children's development of effortful control from middle childhood to early adolescence.

  19. Parenting and the Development of Effortful Control from Early Childhood to Early Adolescence: A Transactional Developmental Model

    PubMed Central

    Capaldi, Deborah M.; Kerr, David C. R.; Bertrand, Maria; Pears, Katherine C.; Owen, Lee

    2016-01-01

    Poor effortful control is a key temperamental factor underlying behavioral problems. The bidirectional association of child effortful control with both positive parenting and negative discipline was examined from ages approximately 3 to 13–14 years, involving 5 time points, and using data from parents and children in the Oregon Youth Study-Three Generational Study (N = 318 children from 150 families). Based on a dynamic developmental systems approach, it was hypothesized that there would be concurrent associations between parenting and child effortful control and bidirectional effects across time from each aspect of parenting to effortful control and from effortful control to each aspect of parenting. It was also hypothesized that associations would be more robust in early childhood, from ages 3 to 7 years, and would diminish as indicated by significantly weaker effects at the older ages, 11–12 to 13–14 years. Longitudinal feedback or mediated effects were also tested. Findings supported (a) stability in each construct over multiple developmental periods; (b) concurrent associations, which were significantly weaker at the older ages; (c) bidirectional effects, consistent with the interpretation that at younger ages children’s effortful control influenced parenting, whereas at older child ages, parenting influenced effortful control; and (d) a transactional effect, such that maternal parenting in late childhood was a mechanism explaining children’s development of effortful control from midchildhood to early adolescence. PMID:27427809

  20. 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

  1. Early Adversity and Developmental Outcomes: Interaction Between Genetics, Epigenetics, and Social Experiences Across the Life Span.

    PubMed

    Champagne, Frances A

    2010-09-01

    Longitudinal studies in humans demonstrate the association between prenatal and postnatal experiences of adversity and long-term changes in neurodevelopment. These studies raise the question of how experiences become incorporated at a biological level to induce persistent changes in functioning. Laboratory studies using animal models and recent analyses in human cohorts implicate epigenetic mechanisms as a possible route through which these environmental effects are achieved. In particular, there is evidence that changes in DNA methylation are associated with early life experiences with consequences for gene expression and behavior. Despite the potential stability of DNA methylation, it is apparent that this epigenetic mark can be dynamically modified through pharmacological targeting and behavioral experiences. Developmental plasticity may also be achieved through modification of the juvenile environment. Although these juvenile experiences may lead to common endpoints, there is evidence suggesting that the effects of early and later life experiences may be achieved by different molecular pathways. This review discusses evidence for the role of epigenetic mechanisms in shaping developmental trajectories in response to early life experience as well as the potential plasticity that can occur beyond the perinatal period. These studies have implications for approaches to intervention and suggest the importance of considering individual differences in genetic and epigenetic vulnerability in developing treatment strategies. © The Author(s) 2010.

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

    PubMed Central

    Fitch, R. Holly; Alexander, Michelle L.; Threlkeld, Steven W.

    2013-01-01

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

  3. Childhood developmental vulnerabilities associated with early life exposure to infectious and noninfectious diseases and maternal mental illness.

    PubMed

    Green, Melissa J; Kariuki, Maina; Dean, Kimberlie; Laurens, Kristin R; Tzoumakis, Stacy; Harris, Felicity; Carr, Vaughan J

    2017-12-26

    Fetal exposure to infectious and noninfectious diseases may influence early childhood developmental functioning, on the path to later mental illness. Here, we investigated the effects of in utero exposure to maternal infection and noninfectious diseases during pregnancy on offspring developmental vulnerabilities at age 5 years, in the context of estimated effects for early childhood exposures to infectious and noninfectious diseases and maternal mental illness. We used population data for 66,045 children from an intergenerational record linkage study (the New South Wales Child Development Study), for whom a cross-sectional assessment of five developmental competencies (physical, social, emotional, cognitive, and communication) was obtained at school entry, using the Australian Early Development Census (AEDC). Child and maternal exposures to infectious or noninfectious diseases were determined from the NSW Ministry of Health Admitted Patients Data Collection (APDC) and maternal mental illness exposure was derived from both APDC and Mental Health Ambulatory Data collections. Multinomial logistic regression analyses were used to examine unadjusted and adjusted associations between these physical and mental health exposures and child developmental vulnerabilities at age 5 years. Among the physical disease exposures, maternal infectious diseases during pregnancy and early childhood infection conferred the largest associations with developmental vulnerabilities at age 5 years; maternal noninfectious illness during pregnancy also retained small but significant associations with developmental vulnerabilities even when adjusted for other physical and mental illness exposures and covariates known to be associated with early childhood development (e.g., child's sex, socioeconomic disadvantage, young maternal age, prenatal smoking). Among all exposures examined, maternal mental illness first diagnosed prior to childbirth conferred the greatest odds of developmental

  4. Impairment of Human Immunodeficiency Virus Type-1 Integrase SUMOylation Correlates with an Early Replication Defect*

    PubMed Central

    Zamborlini, Alessia; Coiffic, Audrey; Beauclair, Guillaume; Delelis, Olivier; Paris, Joris; Koh, Yashuiro; Magne, Fabian; Giron, Marie-Lou; Tobaly-Tapiero, Joelle; Deprez, Eric; Emiliani, Stephane; Engelman, Alan; de Thé, Hugues; Saïb, Ali

    2011-01-01

    HIV-1 integrase (IN) orchestrates the integration of the reverse transcribed viral cDNA into the host cell genome and participates also in other steps of HIV-1 replication. Cellular and viral factors assist IN in performing its multiple functions, and post-translational modifications contribute to modulate its activities. Here, we show that HIV-1 IN is modified by SUMO proteins and that phylogenetically conserved SUMOylation consensus motifs represent major SUMO acceptor sites. Viruses harboring SUMOylation site IN mutants displayed a replication defect that was mapped during the early stages of infection, before integration but after reverse transcription. Because SUMOylation-defective IN mutants retained WT catalytic activity, we hypothesize that SUMOylation might regulate the affinity of IN for co-factors, contributing to efficient HIV-1 replication. PMID:21454548

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

    PubMed

    Stringaris, Argyris; Lewis, Glyn; Maughan, Barbara

    2014-07-01

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

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

    PubMed Central

    Stringaris, Argyris; Lewis, Glyn; Maughan, Barbara

    2014-01-01

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

  7. Developmental predictors of inattention-hyperactivity from pregnancy to early childhood.

    PubMed

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

    2015-01-01

    The objective of the study was to characterize the developmental sequence of pre- and postnatal risk factors for inattention-hyperactivity symptoms in preschoolers. 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. 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. This study identified psychosocial factors at several developmental periods that represent potential targets for preventing the emergence of inattention-hyperactivity symptoms in early childhood.

  8. Early postoperative healing following buccal single flap approach to access intraosseous periodontal defects.

    PubMed

    Farina, Roberto; Simonelli, Anna; Rizzi, Alessandro; Pramstraller, Mattia; Cucchi, Alessandro; Trombelli, Leonardo

    2013-07-01

    This study aims to evaluate the early postoperative healing of papillary incision wounds and its association with (1) patient/site-related factors and technical (surgical) aspects as well as with (2) 6-month clinical outcomes following buccal single flap approach (SFA) in the treatment of intraosseous periodontal defects. Forty-three intraosseous defects in 35 patients were accessed with a buccal SFA alone or in combination with a reconstructive technology (graft, enamel matrix derivative (EMD), graft + EMD, or graft + membrane). Postoperative healing was evaluated at 2 weeks using the Early Wound-Healing Index (EHI). EHI ranged from score 1 (i.e., complete flap closure and optimal healing) to score 4 (i.e., loss of primary closure and partial tissue necrosis). SFA resulted in a complete wound closure at 2 weeks in the great majority of sites. A significantly more frequent presence of interdental contact point and interdental soft tissue crater, and narrower base of the interdental papilla were observed at sites with either EHI > 1 or EHI = 4 compared to sites with EHI = 1. No association between EHI and the 6-month clinical outcomes was observed. At 2 weeks, buccal SFA may result in highly predictable complete flap closure. Site-specific characteristics may influence the early postoperative healing of the papillary incision following SFA procedure. Two-week soft tissue healing, however, was not associated with the 6-month clinical outcomes.

  9. Neural tube and other developmental anomalies in the guinea pig following maternal hyperthermia during early neural tube development.

    PubMed

    Cawdell-Smith, J; Upfold, J; Edwards, M; Smith, M

    1992-01-01

    Guinea pigs were exposed to hyperthermia for 1 hr once or twice on day 11, 12, 13, or 14 (E11-E14) of pregnancy. The mean rectal temperatures were elevated by 3.4 degrees C-4.0 degrees C. This treatment resulted in a marked elevation of rates of resorption and developmental defects in embryos examined at day E23. The defects observed were those affecting the neural tube (NTD) (exencephaly, encephaloceles, and microphthalmia), kyphosis/scoliosis, branchial arch defects, and pericardial edema. Embryos with NTD and kyphosis/scoliosis have not been found among newborn guinea pigs to date following maternal heat exposure on days E12-E14. It appears that embryos with these defects are filtered out by resorption or abortion by days E30-E35.

  10. Transient Early Embryonic Expression of Nkx2-5 Mutations Linked to Congenital Heart Defects in Human Causes Heart Defects in Xenopus laevis

    PubMed Central

    Bartlett, Heather L.; Sutherland, Lillian; Kolker, Sandra J.; Welp, Chelsea; Tajchman, Urszula; Desmarais, Vera; Weeks, Daniel L.

    2007-01-01

    Nkx2-5 is a homeobox containing transcription factor that is conserved and expressed in organisms that form hearts. Fruit flies lacking the gene (tinman) fail to form a dorsal vessel, mice that are homozygous null for Nkx2-5 form small, deformed hearts, and several human cardiac defects have been linked to dominant mutations in the Nkx2-5 gene. The Xenopus homologs (XNkx2-5) of two truncated forms of Nkx2-5 that have been identified in humans with congenital heart defects were used in the studies reported here. mRNAs encoding these mutations were injected into single cell Xenopus embryos, and heart development was monitored. Our results indicate that the introduction of truncated XNkx2-5 variants leads to three principle developmental defects. The atrial septum and the valve of the atrioventricular canal were both abnormal. In addition, video microscopic timing of heart contraction indicated that embryos injected with either mutant form of XNkx2-5 have conduction defects. PMID:17685485

  11. Mothers of children with developmental disabilities: stress in early and middle childhood.

    PubMed

    Azad, Gazi; Blacher, Jan; Marcoulides, George A

    2013-10-01

    Using a sample of 219 families of children with (n=94) and without (n=125) developmental disabilities, this study examined the longitudinal perspectives of maternal stress in early (ages 3-5) and middle childhood (ages 6-13) and its relationship to mothers' and children's characteristics. Multivariate latent curve models indicated that maternal stress remained high and stable with minimal individual variation in early childhood, but declined with significant individual variation in middle childhood. Maternal stress at the beginning of middle childhood was associated with earlier maternal stress, as well as children's behavioral problems and social skills. The trajectory of maternal stress across middle childhood was related to children's behavioral problems. Implications for interventions are discussed. Copyright © 2013. Published by Elsevier Ltd.

  12. 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

  13. Parsing the Effects Violence Exposure in Early Childhood: Modeling Developmental Pathways

    PubMed Central

    Carter, Alice S.; Ford, Julian D.

    2012-01-01

    Objective To prospectively examine pathways from early childhood violence exposure and trauma-related symptoms to school-age emotional health. Methods A longitudinal, birth cohort (N = 437) was assessed with parent reports of lifetime violence exposure and trauma-related symptoms at 3 years of age and later, internalizing and externalizing symptoms, and social competence at school age. Results Early family and neighborhood violence correlated significantly with early trauma-related symptoms and also significantly predicted school-age internalizing and externalizing symptoms and poorer competence, independent of sociodemographic risk and past-year violence exposure. Longitudinal pathways were significantly mediated by arousal and avoidance symptoms at 3 years of age, which increased risk for clinically significant emotional problems and lower competence at school age (adjusted odds ratios = 3.1–6.1, p < 0.01). Conclusions Trauma-related symptoms may mediate developmental pathways from early violence exposure to later emotional health. Interventions that prevent or reduce early trauma-related symptoms may ameliorate the long-term deleterious impact of violence exposure. PMID:21903730

  14. Similar developmental trajectories in autism and Asperger syndrome: from early childhood to adolescence.

    PubMed

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

    2009-12-01

    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). Sixty-four high-functioning children with ASD were ascertained at 4-6 years of age from several different regional diagnostic and treatment centers. At 6-8 years of age, the ADI-R and the Test of Oral Language Development were used to define an autism group (those with StrLI at 6-8 years of age) and an AS group (those without StrLI). Growth curve analysis was then used to chart the developmental trajectories of these children on measures of autistic symptoms, and adaptive skills in communication, daily living and socialization. Differentiating the ASD group in terms of the presence/absence of StrLI provided a better explanation of the variation in growth curves than not differentiating high-functioning ASD children. The two groups had similar developmental trajectories but the group without StrLI (the AS group) was functioning better and had fewer autistic symptoms than the group with StrLI (the autism group) on all measures across time. The differences in outcome could not be explained by non-verbal IQ or change in early language skills. Distinguishing between autism and Asperger syndrome based on the presence or absence of StrLI appears to be a clinically useful way of classifying ASD sub-types.

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

    PubMed Central

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

    2013-01-01

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

  16. The presence of MWCNTs reduces developmental toxicity of PFOS in early life stage of zebrafish.

    PubMed

    Wang, Shutao; Zhuang, Changlu; Du, Jia; Wu, Chuan; You, Hong

    2017-03-01

    Both carbon nanotubes (CNTs) and perfluorooctane sulfonate (PFOS) are used widely. There is considerable concern regarding their ecotoxicity. CNTs might interact with PFOS in water and result in different impacts compared with those after single exposures. To our knowledge, the developmental toxicity of PFOS in the presence of multi-walled carbon nanotubes (MWCNTs) in the early life stage of zebrafish (from 3 h post fertilization (hpf) to 96 hpf) was investigated for the first time in this study. The embryos and larvae were exposed to PFOS (0.2, 0.4, 0.8, and 1.6 mg/L), MWCNTs (50 mg/L), and a mixture of both. Compared with PFOS exposure, the adverse effects induced by PFOS on the hatching rate of zebrafish embryos and the heart rate and body length of zebrafish larvae were reduced in the presence of MWCNTs, and mortality and malformation were also alleviated. In addition, zebrafish larvae exposed to PFOS showed decreased activities of superoxide dismutase, catalase, and glutathione peroxidase, as well as decreased levels of reactive oxygen species and malondialdehyde, in the presence of MWCNTs, indicating that oxidative stress and lipid peroxidation was relieved. Thus, the presence of MWCNTs reduces the developmental toxicity of PFOS in the early life stage of zebrafish. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. A longitudinal twin study of physical aggression during early childhood: evidence for a developmentally dynamic genome.

    PubMed

    Lacourse, E; Boivin, M; Brendgen, M; Petitclerc, A; Girard, A; Vitaro, F; Paquin, S; Ouellet-Morin, I; Dionne, G; Tremblay, R E

    2014-09-01

    Physical aggression (PA) tends to have its onset in infancy and to increase rapidly in frequency. Very little is known about the genetic and environmental etiology of PA development during early childhood. We investigated the temporal pattern of genetic and environmental etiology of PA during this crucial developmental period. Participants were 667 twin pairs, including 254 monozygotic and 413 dizygotic pairs, from the ongoing longitudinal Quebec Newborn Twin Study. Maternal reports of PA were obtained from three waves of data at 20, 32 and 50 months. These reports were analysed using a biometric Cholesky decomposition and linear latent growth curve model. The best-fitting Cholesky model revealed developmentally dynamic effects, mostly genetic attenuation and innovation. The contribution of genetic factors at 20 months substantially decreased over time, while new genetic effects appeared later on. The linear latent growth curve model revealed a significant moderate increase in PA from 20 to 50 months. Two separate sets of uncorrelated genetic factors accounted for the variation in initial level and growth rate. Non-shared and shared environments had no effect on the stability, initial status and growth rate in PA. Genetic factors underlie PA frequency and stability during early childhood; they are also responsible for initial status and growth rate in PA. The contribution of shared environment is modest, and perhaps limited, as it appears only at 50 months. Future research should investigate the complex nature of these dynamic genetic factors through genetic-environment correlation (r GE) and interaction (G×E) analyses.

  18. Developmental delay and emotion dysregulation: Predicting parent-child conflict across early to middle childhood.

    PubMed

    Marquis, Willa A; Noroña, Amanda N; Baker, Bruce L

    2017-04-01

    Cumulative risk research has increased understanding of how multiple risk factors impact various socioemotional and interpersonal outcomes across the life span. However, little is known about risk factors for parent-child conflict early in development, where identifying predictors of change could be highly salient for intervention. Given their established association with parent-child conflict, child developmental delay (DD) and emotion dysregulation were examined as predictors of change in conflict across early to middle childhood (ages 3 to 7 years). Participants (n = 211) were part of a longitudinal study examining the development of psychopathology in children with or without DD. Level of parent-child conflict was derived from naturalistic home observations, whereas child dysregulation was measured using an adapted CBCL-Emotion Dysregulation Index. PROCESS was used to examine the conditional interactive effects of delay status (typically developing, DD) and dysregulation on change in conflict from child ages 3 to 5 and 5 to 7 years. Across both of these timeframes, parent-child conflict increased only for families of children with both DD and high dysregulation, providing support for an interactive risk model of parent-child conflict. Findings are considered in the context of developmental transitions, and implications for intervention are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. 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. © Georg Thieme Verlag KG Stuttgart · New York.

  20. How Competent are Adolescent Bullying Perpetrators and Victims in Mastering Normative Developmental Tasks in Early Adulthood?

    PubMed

    Kretschmer, Tina; Veenstra, René; Branje, Susan; Reijneveld, Sijmen A; Meeus, Wim H J; Deković, Maja; Koot, Hans M; Vollebergh, Wilma A M; Oldehinkel, Albertine J

    2018-01-01

    A substantive body of literature suggests that those involved in bullying as perpetrators but particularly victims are at greater risk for psychological maladjustment. In comparison, relatively little is known about associations between bullying-victimization and perpetration and mastery of early adult tasks in domains including romantic relationships, education, work, financial competence, and conduct. These links were tested using data from two Dutch cohorts (RADAR-young, n = 497, 43% girls; TRAILS, n = 2230, 51% girls) who reported on victimization and perpetration at age 11 (TRAILS) and 13 (RADAR-young) and mastery of developmental tasks in early adulthood. Unadjusted regression analyses suggested for both cohorts that perpetrators were less likely to abide the law and more likely to smoke. Victims in TRAILS were less competent in the domains of education, work, and finances, and more likely to smoke in RADAR-young. Adjusting for childhood demographics and child intelligence and including psychopathology in the prediction models substantially reduced the strength of associations between bullying involvement and later outcomes in both cohorts; although association were retained between victimization and welfare dependence and perpetration and crime involvement in TRAILS. Parental support did not buffer associations in either sample and neither were gender differences detected. Overall, findings underline that negative outcomes of bullying are not only a concern for victims but also for their perpetrators although involvement in bullying is not a stable predictor of mastery of developmental tasks when childhood demographics, child intelligence, and psychopathology are taken into account.

  1. Developmental delay and emotion dysregulation: Predicting parent-child conflict across early to middle childhood

    PubMed Central

    Marquis, Willa A.; Noroña, Amanda N.; Baker, Bruce L.

    2016-01-01

    Cumulative risk research has increased understanding of how multiple risk factors impact various socioemotional and interpersonal outcomes across the life span. However, little is known about risk factors for parent-child conflict early in development, where identifying predictors of change could be highly salient for intervention. Given their established association with parent-child conflict, child developmental delay (DD) and emotion dysregulation were examined as predictors of change in conflict across early to middle childhood (ages 3 to 7 years). Participants (n=211) were part of a longitudinal study examining the development of psychopathology in children with or without DD. Level of parent-child conflict was derived from naturalistic home observations, while child dysregulation was measured using an adapted CBCL-Emotion Dysregulation Index. PROCESS was used to examine the conditional interactive effects of delay status (typically developing, DD) and dysregulation on change in conflict from child ages 3 to 5 and 5 to 7 years. Across both of these timeframes, parent-child conflict increased only for families of children with both DD and high dysregulation, providing support for an interactive risk model of parent-child conflict. Findings are considered in the context of developmental transitions, and implications for intervention are discussed. PMID:28054804

  2. Latent class analysis of early developmental trajectory in baby siblings of children with autism.

    PubMed

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

    2012-09-01

    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. Sibs-A (N = 204) were assessed with the Mullen Scales of Early Learning from age 6 to 36 months. Mullen T scores served as dependent variables. Outcome classifications at age 36 months included: ASD (N = 52); non-ASD social/communication delay (broader autism phenotype; BAP; N = 31); and unaffected (N = 121). Child-specific patterns of performance were studied using latent class growth analysis. Latent class membership was then related to diagnostic outcome through estimation of within-class proportions of children assigned to each diagnostic classification. A 4-class model was favored. Class 1 represented accelerated development and consisted of 25.7% of the sample, primarily unaffected children. Class 2 (40.0% of the sample), was characterized by normative development with above-average nonverbal cognitive outcome. Class 3 (22.3% of the sample) was characterized by receptive language, and gross and fine motor delay. Class 4 (12.0% of the sample), was characterized by widespread delayed skill acquisition, reflected by declining trajectories. Children with an outcome diagnosis of ASD were spread across Classes 2, 3, and 4. Results support a category of ASD that involves slowing in early non-social development. Receptive language and motor development is vulnerable to early delay in sibs-A with and without ASD outcomes. Non-ASD sibs-A are largely distributed across classes depicting average or accelerated development. Developmental trajectories of motor, language, and cognition appear independent of communication and social delays in non-ASD sibs-A. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

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

    PubMed Central

    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 with the Mullen Scales of Early Learning from age 6–36 months. Mullen T scores served as dependent variables. Outcome classifications at age 36 months included: ASD (n=52); non-ASD social/communication delay (broader autism phenotype; BAP) (n=31); and unaffected (n=121). Child-specific patterns of performance were studied using latent class growth analysis. Latent class membership was then related to diagnostic outcome through estimation of within-class proportions of children assigned to each diagnostic classification. Results A 4-class model was favored. Class 1 represented accelerated development and consisted of 25.7% of the sample, primarily unaffected children. Class 2 (40.0% of the sample), was characterized by normative development with above-average nonverbal cognitive outcome. Class 3 (22.3% of the sample) was characterized by receptive language, and gross and fine motor delay. Class 4 (12.0% of the sample), was characterized by widespread delayed skill acquisition, reflected by declining trajectories. Children with an outcome diagnosis of ASD were spread across Classes 2, 3, and 4. Conclusions Results support a category of ASD that involves slowing in early non-social development. Receptive language and motor development is vulnerable to early delay in sibs-A with and without ASD outcomes. Non-ASD sibs-A are largely distributed across classes depicting average or accelerated development. Developmental trajectories of motor, language, and cognition appear independent of communication and social delays in non-ASD sibs-A. PMID:22574686

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

    PubMed

    Norona, A N; Baker, B L

    2017-02-01

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

  5. Dental caries and developmental defects of enamel in relation to fluoride levels in drinking water in an arid area of Sri Lanka.

    PubMed

    Ekanayake, L; van der Hoek, W

    2002-01-01

    The study was conducted to assess caries and developmental defects of enamel in relation to fluoride levels in drinking water and the association between caries experience and the severity of diffuse opacities in children living in Uda Walawe, an area with varying concentrations of fluoride in drinking water in Sri Lanka. A total of 518 14-year-old children who were lifelong residents in this area were examined for dental caries and developmental defects of enamel. But the present analysis is confined to 486 children from whom drinking water samples were collected. The prevalence of enamel defects and diffuse opacities ranged from 27 to 57% while the prevalence of caries ranged from 18 to 29% in the different fluoride exposure groups. The prevalence of enamel defects increased significantly with the increase in the fluoride level in drinking water. Both the caries prevalence and the mean caries experience were significantly higher in children with diffuse opacities than in those without in the group consuming water containing >0.70 mg/l of fluoride. The association between dental caries and the severity of diffuse opacities was also significant only in this group. Children with the mildest form of opacities (DDE scores 3 and 4) had the lowest DMFS (0.25 +/- 0.7), and the highest DMFS (1.1 +/- 1.7) was found in those with the most severe form of opacities (DDE score 6). In conclusion, the relationship that was observed in this study between fluoride levels in drinking water, diffuse opacities and caries suggests that the appropriate level of fluoride in drinking water for arid areas of Sri Lanka is around 0.3 mg/l. Also individuals with severe forms of enamel defects in high-fluoride areas are susceptible to dental caries. Copyright 2002 S. Karger AG, Basel

  6. Developmental and Post-Eruptive Defects in Molar Enamel of Free-Ranging Eastern Grey Kangaroos (Macropus giganteus) Exposed to High Environmental Levels of Fluoride

    PubMed Central

    Kierdorf, Uwe; Death, Clare; Hufschmid, Jasmin; Witzel, Carsten; Kierdorf, Horst

    2016-01-01

    Dental fluorosis has recently been diagnosed in wild marsupials inhabiting a high-fluoride area in Victoria, Australia. Information on the histopathology of fluorotic marsupial enamel has thus far not been available. This study analyzed the developmental and post-eruptive defects in fluorotic molar enamel of eastern grey kangaroos (Macropus giganteus) from the same high-fluoride area using light microscopy and backscattered electron imaging in the scanning electron microscope. The fluorotic enamel exhibited a brownish to blackish discolouration due to post-eruptive infiltration of stains from the oral cavity and was less resistant to wear than normally mineralized enamel of kangaroos from low-fluoride areas. Developmental defects of enamel included enamel hypoplasia and a pronounced hypomineralization of the outer (sub-surface) enamel underneath a thin rim of well-mineralized surface enamel. While the hypoplastic defects denote a disturbance of ameloblast function during the secretory stage of amelogenesis, the hypomineralization is attributed to an impairment of enamel maturation. In addition to hypoplastic defects, the fluorotic molars also exhibited numerous post-eruptive enamel defects due to the flaking-off of portions of the outer, hypomineralized enamel layer during mastication. The macroscopic and histopathological lesions in fluorotic enamel of M. giganteus match those previously described for placental mammals. It is therefore concluded that there exist no principal differences in the pathogenic mechanisms of dental fluorosis between marsupial and placental mammals. The regular occurrence of hypomineralized, opaque outer enamel in the teeth of M. giganteus and other macropodids must be considered in the differential diagnosis of dental fluorosis in these species. PMID:26895178

  7. Effects of chronic crude oil exposure on early developmental stages of the Northern krill (Meganyctiphanes norvegica).

    PubMed

    Arnberg, Maj; Moodley, Leon; Dunaevskaya, Evgenia; Ramanand, Sreerekha; Ingvarsdóttir, Anna; Nilsen, Marianne; Ravagnan, Elisa; Westerlund, Stig; Sanni, Steinar; Tarling, Geraint A; Bechmann, Renée K

    2017-01-01

    Rising oil and gas activities in northern high latitudes have led to an increased risk of petroleum pollution in these ecosystems. Further, seasonal high UV radiation at high latitudes may elevate photo-enhanced toxicity of petroleum pollution to marine organisms. Zooplanktons are a key ecological component of northern ecosystems; therefore, it is important to assess their sensitivity to potential pollutants of oil and gas activity. As ontogenetic development may be particularly sensitive, the aim of this study was to examine the impact of chronic exposure to oil water dispersion (OWD) on development and feeding of early life stages of the Northern krill, Meganyctiphanes norvegica. In a range of experiments, embryonic, nonfeeding, and feeding larval stages were exposed to concentrations of between 0.01 and 0.1 mg/L of oil or photo-modified oil for 19 and 21 d. No significant effects on egg respiration, hatching success, development, length and larval survival were observed from these treatments. Similarly, evolution of fatty acid composition patterns during ontogenetic development was unaffected. The results indicates a high degree of resilience of these early developmental stages to such types and concentrations of pollutants. However, feeding and motility in later calyptopis-stage larvae were significantly impaired at exposure of 0.1 mg/L oil. Data indicate that feeding larval stage of krill was more sensitive to OWD than early nonfeeding life stages. This might be attributed to the narcotic effects of oil pollutants, their direct ingestion, or accumulated adverse effects over early development.

  8. Laminarin improves developmental competence of porcine early stage embryos by inhibiting oxidative stress.

    PubMed

    Jiang, Hao; Liang, Shuang; Yao, Xue-Rui; Jin, Yong-Xun; Shen, Xing-Hui; Yuan, Bao; Zhang, Jia-Bao; Kim, Nam-Hyung

    2018-04-23

    Laminarin (LMA), a β-glucan mixture with good biocompatibility, improves the growth performance and immune response when used as food additives and nutraceuticals. The aim of the present research was to explore the effects of LMA on porcine early stage embryo development, as well as the underlying mechanisms. The results showed that the developmental competence of porcine early stage embryos was dramatically improved after LMA supplementation during the in vitro culture period. The presence of 20 μg/mL LMA during the in vitro culture period significantly improved cleavage rate, blastocyst formation rates, hatching rate, and total cell number in the blastocyst compared to that in the control group. Notably, LMA attenuated the intracellular reactive oxygen species generation induced by H 2 O 2 . Furthermore, LMA not only increased intracellular glutathione levels, but also ameliorated mitochondrial membrane potential. In addition, the expression of a zygotic genome activation related gene (YAP1), pluripotency-related genes (OCT4, NANOG, and SOX2), and hatching-related genes (COX2, GATA4, and ITGA5) were up-regulated following LMA supplementation during porcine early stage embryo development. These results demonstrate that LMA has beneficial effects on the development of porcine early stage embryos via regulation of oxidative stress. This evidence provides a novel method for embryo development improvement associated with exposure to LMA. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Developmental Defects of Caenorhabditis elegans Lacking Branched-chain α-Ketoacid Dehydrogenase Are Mainly Caused by Monomethyl Branched-chain Fatty Acid Deficiency.

    PubMed

    Jia, Fan; Cui, Mingxue; Than, Minh T; Han, Min

    2016-02-05

    Branched-chain α-ketoacid dehydrogenase (BCKDH) catalyzes the critical step in the branched-chain amino acid (BCAA) catabolic pathway and has been the focus of extensive studies. Mutations in the complex disrupt many fundamental metabolic pathways and cause multiple human diseases including maple syrup urine disease (MSUD), autism, and other related neurological disorders. BCKDH may also be required for the synthesis of monomethyl branched-chain fatty acids (mmBCFAs) from BCAAs. The pathology of MSUD has been attributed mainly to BCAA accumulation, but the role of mmBCFA has not been evaluated. Here we show that disrupting BCKDH in Caenorhabditis elegans causes mmBCFA deficiency, in addition to BCAA accumulation. Worms with deficiency in BCKDH function manifest larval arrest and embryonic lethal phenotypes, and mmBCFA supplementation suppressed both without correcting BCAA levels. The majority of developmental defects caused by BCKDH deficiency may thus be attributed to lacking mmBCFAs in worms. Tissue-specific analysis shows that restoration of BCKDH function in multiple tissues can rescue the defects, but is especially effective in neurons. Taken together, we conclude that mmBCFA deficiency is largely responsible for the developmental defects in the worm and conceivably might also be a critical contributor to the pathology of human MSUD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease.

    PubMed

    Beck, Susanne C; Feng, Yuxi; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Acar, Niyazi; Shan, Shenliang; Seebauer, Britta; Berger, Wolfgang; Hammes, Hans-Peter; Seeliger, Mathias W

    2017-01-01

    Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects.

  11. Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease

    PubMed Central

    Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Acar, Niyazi; Shan, Shenliang; Seebauer, Britta; Berger, Wolfgang; Hammes, Hans-Peter; Seeliger, Mathias W.

    2017-01-01

    Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects. PMID:28575130

  12. Early childhood predictors of mothers' and fathers' relationships with adolescents with developmental disabilities.

    PubMed

    Mitchell, D B; Hauser-Cram, P

    2010-06-01

    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 questions regarding these relationships. In particular, we asked: are there differences in the relationships of mothers and fathers with their adolescent with DD? Are there early childhood predictors of the parent-teen relationship and are those based on variables that are amenable to intervention? Finally, do these predictors differ for mothers and fathers? This study focused on the relationships of 72 mothers and 53 fathers with their 15-year-old teens with DD and their predictors from the early childhood years. Data were collected from parents through interviews and self-administered questionnaires, and from their children with disabilities through structured assessment when children were age 3 years and again at age 15 years. Analyses indicated that both mother-teen and father-teen relationships were predicted by earlier parenting stress. The father-teen relationship was also predicted by early behaviour problems, but this relation was mediated by parenting stress. Socio-economic status, type of disability and the child's level of functioning were not predictive of later relationships between parents and teens. Mothers and fathers did not differ significantly in their reports of perceived positive relationships with their teens. The findings from this study suggest two important points of potential intervention during the early intervention years. First, parenting assistance and support to reduce stress during the early childhood years can benefit both mothers and fathers. Second, helping families and children cope with and diminish problem behaviours is likely to yield multiple advantages for parents and children and deserves

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

    PubMed

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

    2018-01-01

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

  14. Developmental changes in automatic rule-learning mechanisms across early childhood.

    PubMed

    Mueller, Jutta L; Friederici, Angela D; Männel, Claudia

    2018-06-27

    Infants' ability to learn complex linguistic regularities from early on has been revealed by electrophysiological studies indicating that 3-month-olds, but not adults, can automatically detect non-adjacent dependencies between syllables. While different ERP responses in adults and infants suggest that both linguistic rule learning and its link to basic auditory processing undergo developmental changes, systematic investigations of the developmental trajectories are scarce. In the present study, we assessed 2- and 4-year-olds' ERP indicators of pitch discrimination and linguistic rule learning in a syllable-based oddball design. To test for the relation between auditory discrimination and rule learning, ERP responses to pitch changes were used as predictor for potential linguistic rule-learning effects. Results revealed that 2-year-olds, but not 4-year-olds, showed ERP markers of rule learning. Although, 2-year-olds' rule learning was not dependent on differences in pitch perception, 4-year-old children demonstrated a dependency, such that those children who showed more pronounced responses to pitch changes still showed an effect of rule learning. These results narrow down the developmental decline of the ability for automatic linguistic rule learning to the age between 2 and 4 years, and, moreover, point towards a strong modification of this change by auditory processes. At an age when the ability of automatic linguistic rule learning phases out, rule learning can still be observed in children with enhanced auditory responses. The observed interrelations are plausible causes for age-of-acquisition effects and inter-individual differences in language learning. © 2018 John Wiley & Sons Ltd.

  15. 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

  16. Peroxy defects in Rocks and H2O2 formation on the early Earth

    NASA Astrophysics Data System (ADS)

    Gray, A.; Balk, M.; Mason, P.; Freund, F.; Rothschild, L.

    2013-12-01

    An oxygen-rich atmosphere appears to have been a prerequisite for complex life to evolve on Earth and possibly elsewhere in the Universe. The question is still shrouded in uncertainty how free oxygen became available on the early Earth. Here we study processes of peroxy defects in silicate minerals which, upon weathering, generate mobilized electronic charge carriers resulting in oxygen formation in an initially anoxic subsurface environment. Reactive Oxygen Species (ROS) are precursors to molecular oxygen during this process. Due to their toxicity they may have strongly influenced the evolution of life. ROS are generated during hydrolysis of peroxy defects, which consist of pairs of oxygen anions. A second pathway for formation occurs during (bio) transformations of iron sulphide minerals. ROS are produced and consumed by intracellular and extracellular reactions of Fe, Mn, C, N, and S species. We propose that despite an overall reducing or neutral oxidation state of the macroenvironment and the absence of free O2 in the atmosphere, microorganisms on the early Earth had to cope with ROS in their microenvironments. They were thus under evolutionary pressure to develop enzymatic and other defenses against the potentially dangerous, even lethal effects of ROS and oxygen. We have investigated how oxygen might be released through weathering and test microorganisms in contact with rock surfaces. Our results show how early Life might have adapted to oxygen. Early microorganisms must have "trained" to detoxify ROS prior to the evolution of aerobic metabolism and oxygenic photosynthesis. A possible way out of this dilemma comes from a study of igneous and high-grade metamorphic rocks, whose minerals contain a small but significant fraction of oxygen anions in the valence state 1- , forming peroxy links of the type O3Si-OO-SiO3 [1, 2]. As water hydrolyzes the peroxy links hydrogen peroxide, H2O2, forms. Continued experimental discovery of H2O2 formation at rock

  17. [Multiplex Ligation - dependent Probe Amplification (MLPA) as a screening test in children with developmental defects and intellectual disability of unknown etiology].

    PubMed

    Laczmańska, Izabela; Jakubiak, Aleksandra; Slęzak, Ryszard; Pesz, Karolina; Stembalska, Agnieszka; Laczmański, Lukasz; Sąsiadek, Maria M; Smigiel, Robert

    2011-01-01

    Developmental delay and intellectual disability are significant medical and social problems which concern 1-3% of population. The etiology remains unknown in over half of the cases. To evaluate the efficiency of MLPA (Multiplex Ligation-dependent Probe Amplification) as a screening test in diagnosis of patients with developmental delay and/or intellectual disability. 313 MLPA tests were performed in 256 patients with developmental delay and/ or intellectual disability with unknown etiology. MLPA test was made after exclusion of genetic disorders possible to diagnose by dysmorphological examination or using specifi c genetic tests. Positive results were confirmed by FISH analysis with appropriate probes. Chromosomal microaberrations were identifi ed in 15 patients (4,8%): deletions of 1p36 in 4 cases, in one case deletion of 22q11.21, 22q13.33, SNRPN1, 4ptel, 6qtel, 7q11.23, 16ptel, 18qtel as well as one ca se of deletion 3ptel/duplication 15qtel; deletion 18qtel/duplication Xqtel, and also duplication 7q11.23. Detail clinical analysis was performed in patients with diagnosed microaberrations in MLPA test. The molecular MLPA test, screening for chromosomal microaberration syndromes, should be performed in each patient with developmental delay and/or intellectual disability of unknown etiology and normal cytogenetic analysis, even if congenital defects and positive familial history do not exist.

  18. Impact of early developmental fluoride exposure on the peripheral pain sensitivity in mice.

    PubMed

    Ma, Jing; Liu, Fei; Liu, Peng; Dong, Ying-Ying; Chu, Zheng; Hou, Tie-Zhou; Dang, Yong-Hui

    2015-12-01

    Consumption of high concentration of fluoride in the drinking water would cause the fluorosis and chronic pain. Similar pain syndrome appeared in the patients in fluoride therapy of osteoporotic. The aim of the current study was to examine whether exposing immature mice to fluoride would modify the peripheral pain sensitivity or even cause a pain syndrome. We gave developmental fluoride exposure to mice in different concentration (0mg/L, 50mg/L and 100mg/L) and evaluated their basal pain threshold. Von Frey hair test, hot plate test and formalin test were conducted to examine the mechanical, thermal nociceptive threshold and inflammatory pain, respectively. In addition, the expression of hippocampal brain-derived neurotrophic factor (BDNF) was also evaluated by Western blotting. Hyperalgesia in fluoride exposure mice was exhibited in the Von Frey hair test, hot plate test and formalin test. Meanwhile, the expression of BDNF was significantly higher than that of control group. The results suggest that early developmental fluoride exposure may lower the basal pain threshold and be associated with the increasing of BDNF expression in hippocampus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Early object labels: the case for a developmental lexical principles framework.

    PubMed

    Golinkoff, R M; Mervis, C B; Hirsh-Pasek, K

    1994-02-01

    Universally, object names make up the largest proportion of any word type found in children's early lexicons. Here we present and critically evaluate a set of six lexical principles (some previously proposed and some new) for making object label learning a manageable task. Overall, the principles have the effect of reducing the amount of information that language-learning children must consider for what a new word might mean. These principles are constructed by children in a two-tiered developmental sequence, as a function of their sensitivity to linguistic input, contextual information, and social-interactional cues. Thus, the process of lexical acquisition changes as a result of the particular principles a given child has at his or her disposal. For children who have only the principles of the first tier (reference, extendibility, and object scope), word learning has a deliberate and laborious look. The principles of the second tier (categorical scope, novel name-nameless category' or N3C, and conventionality) enable the child to acquire many new labels rapidly. The present unified account is argued to have a number of advantages over treating such principles separately and non-developmentally. Further, the explicit recognition that the acquisition and operation of these principles is influenced by the child's interpretation of both linguistic and non-linguistic input is seen as an advance.

  20. Early Developmental Disturbances of Cortical Inhibitory Neurons: Contribution to Cognitive Deficits in Schizophrenia

    PubMed Central

    Volk, David W.; Lewis, David A.

    2014-01-01

    Cognitive dysfunction is a disabling and core feature of schizophrenia. Cognitive impairments have been linked to disturbances in inhibitory (gamma-aminobutyric acid [GABA]) neurons in the prefrontal cortex. Cognitive deficits are present well before the onset of psychotic symptoms and have been detected in early childhood with developmental delays reported during the first year of life. These data suggest that the pathogenetic process that produces dysfunction of prefrontal GABA neurons in schizophrenia may be related to altered prenatal development. Interestingly, adult postmortem schizophrenia brain tissue studies have provided evidence consistent with a disease process that affects different stages of prenatal development of specific subpopulations of prefrontal GABA neurons. Prenatal ontogeny (ie, birth, proliferation, migration, and phenotypic specification) of distinct subpopulations of cortical GABA neurons is differentially regulated by a host of transcription factors, chemokine receptors, and other molecular markers. In this review article, we propose a strategy to investigate how alterations in the expression of these developmental regulators of subpopulations of cortical GABA neurons may contribute to the pathogenesis of cortical GABA neuron dysfunction and consequently cognitive impairments in schizophrenia. PMID:25053651

  1. From Cheerleader to Coach: The Developmental Progression of Bedside Teachers in Giving Feedback to Early Learners.

    PubMed

    Wenrich, Marjorie D; Jackson, Molly Blackley; Maestas, Ramoncita R; Wolfhagen, Ineke H A P; Scherpbier, Albert J J

    2015-11-01

    Medical students learn clinical skills at the bedside from teaching clinicians, who often learn to teach by teaching. Little is known about the process of becoming an effective clinical teacher. Understanding how teaching skills and approaches change with experience may help tailor faculty development for new teachers. Focusing on giving feedback to early learners, the authors asked: What is the developmental progression of clinician-teachers as they learn to give clinical skills feedback to medical students? This qualitative study included longitudinal interviews with clinician-teachers over five years in a new clinical skills teaching program for preclinical medical students. Techniques derived from grounded theory were used for initial analyses. The current study focused on one theme identified in initial analyses: giving feedback to students. Transcript passages were organized by interview year, coded, and discussed in year clusters; thematic codes were compared and emergent codes developed. Themes related to giving feedback demonstrated a dyadic structure: characteristic of less experienced teachers versus characteristic of experienced teachers. Seven dominant dyadic themes emerged, including teacher as cheerleader versus coach, concern about student fragility versus understanding resilience, and focus on creating a safe environment versus challenging students within a safe environment. With consistent teaching, clinical teachers demonstrated progress in giving feedback to students in multiple areas, including understanding students' developmental trajectory and needs, developing tools and strategies, and adopting a dynamic, challenging, inclusive team approach. Ongoing teaching opportunities with targeted faculty development may help improve clinician-teachers' feedback skills and approaches.

  2. The classification of motor neuron defects in the zebrafish embryo toxicity test (ZFET) as an animal alternative approach to assess developmental neurotoxicity.

    PubMed

    Muth-Köhne, Elke; Wichmann, Arne; Delov, Vera; Fenske, Martina

    2012-07-01

    Rodents are widely used to test the developmental neurotoxicity potential of chemical substances. The regulatory test procedures are elaborate and the requirement of numerous animals is ethically disputable. Therefore, non-animal alternatives are highly desirable, but appropriate test systems that meet regulatory demands are not yet available. Hence, we have developed a new developmental neurotoxicity assay based on specific whole-mount immunostainings of primary and secondary motor neurons (using the monoclonal antibodies znp1 and zn8) in zebrafish embryos. By classifying the motor neuron defects, we evaluated the severity of the neurotoxic damage to individual primary and secondary motor neurons caused by chemical exposure and determined the corresponding effect concentration values (EC₅₀). In a proof-of-principle study, we investigated the effects of three model compounds thiocyclam, cartap and disulfiram, which show some neurotoxicity-indicating effects in vertebrates, and the positive controls ethanol and nicotine and the negative controls 3,4-dichloroaniline (3,4-DCA) and triclosan. As a quantitative measure of the neurotoxic potential of the test compounds, we calculated the ratios of the EC₅₀ values for motor neuron defects and the cumulative malformations, as determined in a zebrafish embryo toxicity test (zFET). Based on this index, disulfiram was classified as the most potent and thiocyclam as the least potent developmental neurotoxin. The index also confirmed the control compounds as positive and negative neurotoxicants. Our findings demonstrate that this index can be used to reliably distinguish between neurotoxic and non-neurotoxic chemicals and provide a sound estimate for the neurodevelopmental hazard potential of a chemical. The demonstrated method can be a feasible approach to reduce the number of animals used in developmental neurotoxicity evaluation procedures. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Early-developmental stress, repeatability, and canalization in a suite of physiological and behavioral traits in female zebra finches.

    PubMed

    Careau, Vincent; Buttemer, William A; Buchanan, Katherine L

    2014-10-01

    Adaptive developmental plasticity allows individuals experiencing poor environmental conditions in early life to adjust their life-history strategy in order to prioritize short-term fitness benefits and maximize reproductive output in challenging environments. Much research has been conducted to test whether such adoption of a "faster" life-history strategy is accompanied by concordant changes in behavior and physiology, with mixed results. As research in this field has focused on comparison of mean-level responses of treatment groups, few studies include repeated measures of response variables and the effect that developmental stress may have on repeatability per se. We investigated how early-developmental stress affects the mean expression of (and repeatability in) a variety of behavioral and physiological traits in female zebra finches. We predicted that: (1) individuals subjected to nutritional restriction in the nestling phase would have higher feeding and activity rates, with associated increases in hematocrit and basal metabolic rates (BMRs), (2) nutritional restriction in early life would alter adults' stress-induced corticosterone level, and (3) developmental stress would, respectively, influence the amount of among-individual and within-individual variation in behavioral and physiological traits, hence affecting the repeatability of these traits. In comparison to control females, stressed females did not differ in activity rate or stress-induced corticosterone level, but they did have higher levels of feeding, hematocrit, and BMR. Among-individual variance and repeatability were generally higher in stressed females than in controls. Finally, we found that developmental dietary restriction significantly reduced the amount of within-individual variance both in activity rate in the novel environment and in stress-induced corticosterone level. Our results not only confirm previous findings on the effect of early-developmental stress on BMR, but also extend

  4. 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

  5. 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.

  6. 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.

  7. 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. © 2016 Michigan Association for Infant Mental Health.

  8. Developmental Trajectories of Anxiety Symptoms Among Boys Across Early and Middle Childhood

    PubMed Central

    Feng, Xin; Shaw, Daniel S.; Silk, Jennifer S.

    2009-01-01

    This study examined the developmental trajectory of anxiety symptoms among 290 boys and evaluated the association of trajectory groups with child and family risk factors and children’s internalizing disorders. Anxiety symptoms were measured using maternal reports from the Child Behavior Checklist (T. M. Achenbach, 1991, 1992) for boys between the ages of 2 and 10. A group-based trajectory analysis revealed 4 distinct trajectories in the development of anxiety symptoms: low, low increasing, high declining, and high-increasing trajectories. Child shy temperament tended to differentiate between initial high and low groups, whereas maternal negative control and maternal depression were associated with increasing trajectories and elevated anxiety symptoms in middle childhood. Follow-up analyses to diagnoses of preadolescent depression and/or anxiety disorders revealed different patterns on the basis of trajectory group membership. The results are discussed in terms of the mechanisms of risk factors and implications for early identification and prevention. PMID:18266484

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

    PubMed

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

    2015-12-01

    Magnesium oxide nanoparticles (MgONPs) are used in medicine, manufacturing and food industries. Because of their extensive application in our daily lives, environmental exposure to these nanoparticles is inevitable. The present study examined the effects of MgONPs on zebrafish (Danio rerio) early developmental stages. The results showed that, at different concentrations, MgONPs induced cellular apoptosis and intracellular reactive oxygen species. The hatching rate and survival of embryos decreased in a dose dependent manner. The 96-h LC50 value of MgONPs on zebrafish survival was 428 mg/l and the 48-h EC50 value of MgONPs on zebrafish embryo hatching rate was 175 mg/l. Moreover different types of malformation were observed in exposed embryos. The results demonstrate the toxic effects of MgONPs on zebrafish embryos and emphasize the need for further studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Infants’ Early Visual Attention and Social Engagement as Developmental Precursors to Joint Attention

    PubMed Central

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

    2016-01-01

    This study examined infants’ early visual attention (at 1 month of age) and social engagement (4 months) as predictors of their later joint attention (12 and 18 months). The sample (n=325), drawn from the Maternal Lifestyle Study, a longitudinal multicenter project conducted at four centers of the NICHD Neonatal Research Network, included high-risk (cocaine exposed) and matched non-cocaine exposed infants. Hierarchical regressions revealed that infants’ attention orienting at 1 month significantly predicted more frequent initiating joint attention at 12 (but not 18) months of age. Social engagement at 4 months predicted initiating joint attention at 18 months. Results provide the first empirical evidence for the role of visual attention and social engagement behaviors as developmental precursors for later joint attention outcome. PMID:27786527

  11. Homozygosity Mapping and Candidate Prioritization Identify Mutations, Missed by Whole-Exome Sequencing, in SMOC2, Causing Major Dental Developmental Defects

    PubMed Central

    Bloch-Zupan, Agnès; Jamet, Xavier; Etard, Christelle; Laugel, Virginie; Muller, Jean; Geoffroy, Véronique; Strauss, Jean-Pierre; Pelletier, Valérie; Marion, Vincent; Poch, Olivier; Strahle, Uwe; Stoetzel, Corinne; Dollfus, Hélène

    2011-01-01

    Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on a severe developmental dental defect that results in a dentin dysplasia phenotype with major microdontia, oligodontia, and shape abnormalities in a highly consanguineous family. Homozygosity mapping revealed a unique zone on 6q27-ter. The two affected children were found to carry a homozygous mutation in SMOC2. Knockdown of smoc2 in zebrafish showed pharyngeal teeth that had abnormalities reminiscent of the human phenotype. Moreover, smoc2 depletion in zebrafish affected the expression of three major odontogenesis genes: dlx2, bmp2, and pitx2. PMID:22152679

  12. Absence of post-translational aspartyl beta-hydroxylation of epidermal growth factor domains in mice leads to developmental defects and an increased incidence of intestinal neoplasia.

    PubMed

    Dinchuk, Joseph E; Focht, Richard J; Kelley, Jennifer A; Henderson, Nancy L; Zolotarjova, Nina I; Wynn, Richard; Neff, Nicola T; Link, John; Huber, Reid M; Burn, Timothy C; Rupar, Mark J; Cunningham, Mark R; Selling, Bernard H; Ma, Jianhong; Stern, Andrew A; Hollis, Gregory F; Stein, Robert B; Friedman, Paul A

    2002-04-12

    The BAH genomic locus encodes three distinct proteins: junctin, humbug, and BAH. All three proteins share common exons, but differ significantly based upon the use of alternative terminal exons. The biological roles of BAH and humbug and their functional relationship to junctin remain unclear. To evaluate the role of BAH in vivo, the catalytic domain of BAH was specifically targeted such that the coding regions of junctin and humbug remained undisturbed. BAH null mice lack measurable BAH protein in several tissues, lack aspartyl beta-hydroxylase activity in liver preparations, and exhibit no hydroxylation of the epidermal growth factor (EGF) domain of clotting Factor X. In addition to reduced fertility in females, BAH null mice display several developmental defects including syndactyly, facial dysmorphology, and a mild defect in hard palate formation. The developmental defects present in BAH null mice are similar to defects observed in knock-outs and hypomorphs of the Notch ligand Serrate-2. In this work, beta-hydroxylation of Asp residues in EGF domains is demonstrated for a soluble form of a Notch ligand, human Jagged-1. These results along with recent reports that another post-translational modification of EGF domains in Notch gene family members (glycosylation by Fringe) alters Notch pathway signaling, lends credence to the suggestion that aspartyl beta-hydroxylation may represent another post-translational modification of EGF domains that can modulate Notch pathway signaling. Previous work has demonstrated increased levels of BAH in certain tumor tissues and a role for BAH in tumorigenesis has been proposed. The role of hydroxylase in tumor formation was tested directly by crossing BAH KO mice with an intestinal tumor model, APCmin mice. Surprisingly, BAH null/APCmin mice show a statistically significant increase in both intestinal polyp size and number when compared with BAH wild-type/APCmin controls. These results suggest that, in contrast to expectations

  13. Early transcriptional responses of internalization defective Brucella abortus mutants in professional phagocytes, RAW 264.7.

    PubMed

    Cha, Seung Bin; Lee, Won Jung; Shin, Min Kyoung; Jung, Myung Hwan; Shin, Seung Won; Yoo, An Na; Kim, Jong Wan; Yoo, Han Sang

    2013-06-27

    Brucella abortus is an intracellular zoonotic pathogen which causes undulant fever, endocarditis, arthritis and osteomyelitis in human and abortion and infertility in cattle. This bacterium is able to invade and replicate in host macrophage instead of getting removed by this defense mechanism. Therefore, understanding the interaction between virulence of the bacteria and the host cell is important to control brucellosis. Previously, we generated internalization defective mutants and analyzed the envelope proteins. The present study was undertaken to evaluate the changes in early transcriptional responses between wild type and internalization defective mutants infected mouse macrophage, RAW 264.7. Both of the wild type and mutant infected macrophages showed increased expression levels in proinflammatory cytokines, chemokines, apoptosis and G-protein coupled receptors (Gpr84, Gpr109a and Adora2b) while the genes related with small GTPase which mediate intracellular trafficking was decreased. Moreover, cytohesin 1 interacting protein (Cytip) and genes related to ubiquitination (Arrdc3 and Fbxo21) were down-regulated, suggesting the survival strategy of this bacterium. However, we could not detect any significant changes in the mutant infected groups compared to the wild type infected group. In summary, it was very difficult to clarify the alterations in host cellular transcription in response to infection with internalization defective mutants. However, we found several novel gene changes related to the GPCR system, ubiquitin-proteosome system, and growth arrest and DNA damages in response to B. abortus infection. These findings may contribute to a better understanding of the molecular mechanisms underlying host-pathogen interactions and need to be studied further.

  14. Early transcriptional responses of internalization defective Brucella abortus mutants in professional phagocytes, RAW 264.7

    PubMed Central

    2013-01-01

    Background Brucella abortus is an intracellular zoonotic pathogen which causes undulant fever, endocarditis, arthritis and osteomyelitis in human and abortion and infertility in cattle. This bacterium is able to invade and replicate in host macrophage instead of getting removed by this defense mechanism. Therefore, understanding the interaction between virulence of the bacteria and the host cell is important to control brucellosis. Previously, we generated internalization defective mutants and analyzed the envelope proteins. The present study was undertaken to evaluate the changes in early transcriptional responses between wild type and internalization defective mutants infected mouse macrophage, RAW 264.7. Results Both of the wild type and mutant infected macrophages showed increased expression levels in proinflammatory cytokines, chemokines, apoptosis and G-protein coupled receptors (Gpr84, Gpr109a and Adora2b) while the genes related with small GTPase which mediate intracellular trafficking was decreased. Moreover, cytohesin 1 interacting protein (Cytip) and genes related to ubiquitination (Arrdc3 and Fbxo21) were down-regulated, suggesting the survival strategy of this bacterium. However, we could not detect any significant changes in the mutant infected groups compared to the wild type infected group. Conclusions In summary, it was very difficult to clarify the alterations in host cellular transcription in response to infection with internalization defective mutants. However, we found several novel gene changes related to the GPCR system, ubiquitin-proteosome system, and growth arrest and DNA damages in response to B. abortus infection. These findings may contribute to a better understanding of the molecular mechanisms underlying host-pathogen interactions and need to be studied further. PMID:23802650

  15. Mutation update of transcription factor genes FOXE3, HSF4, MAF, and PITX3 causing cataracts and other developmental ocular defects.

    PubMed

    Anand, Deepti; Agrawal, Smriti A; Slavotinek, Anne; Lachke, Salil A

    2018-04-01

    Mutations in the transcription factor genes FOXE3, HSF4, MAF, and PITX3 cause congenital lens defects including cataracts that may be accompanied by defects in other components of the eye or in nonocular tissues. We comprehensively describe here all the variants in FOXE3, HSF4, MAF, and PITX3 genes linked to human developmental defects. A total of 52 variants for FOXE3, 18 variants for HSF4, 20 variants for MAF, and 19 variants for PITX3 identified so far in isolated cases or within families are documented. This effort reveals FOXE3, HSF4, MAF, and PITX3 to have 33, 16, 18, and 7 unique causal mutations, respectively. Loss-of-function mutant animals for these genes have served to model the pathobiology of the associated human defects, and we discuss the currently known molecular function of these genes, particularly with emphasis on their role in ocular development. Finally, we make the detailed FOXE3, HSF4, MAF, and PITX3 variant information available in the Leiden Online Variation Database (LOVD) platform at https://www.LOVD.nl/FOXE3, https://www.LOVD.nl/HSF4, https://www.LOVD.nl/MAF, and https://www.LOVD.nl/PITX3. Thus, this article informs on key variants in transcription factor genes linked to cataract, aphakia, corneal opacity, glaucoma, microcornea, microphthalmia, anterior segment mesenchymal dysgenesis, and Ayme-Gripp syndrome, and facilitates their access through Web-based databases. © 2018 Wiley Periodicals, Inc.

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

    PubMed

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

    2017-04-01

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

  17. Alkaline Phosphatase Protects Lipopolysaccharide-Induced Early Pregnancy Defects in Mice

    PubMed Central

    Lei, Wei; Ni, Hua; Herington, Jennifer; Reese, Jeff; Paria, Bibhash C.

    2015-01-01

    Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women. PMID:25910276

  18. Alkaline phosphatase protects lipopolysaccharide-induced early pregnancy defects in mice.

    PubMed

    Lei, Wei; Ni, Hua; Herington, Jennifer; Reese, Jeff; Paria, Bibhash C

    2015-01-01

    Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women.

  19. Lanthony 15-Hue Desaturated Test for screening of early color vision defects in uncomplicated juvenile diabetes.

    PubMed

    Giusti, C

    2001-01-01

    To identify the most appropriate test for screening of early color vision abnormalities in uncomplicated juvenile diabetes. Enrolled in this study were 39 diabetic adolescents, characterized by optimal Early Treatment Diabetic Retinopathy Study criteria for visual acuity, transparent dioptric means and angiographically normal retinas. Color vision was examined with Standard Pseudoisochromatic Plates (Part 2, SPP2), Roth 28-Hue Test (R28), Farnsworth-Munsell 100-Hue Tests (FM100), and Lanthony 15-Hue Desaturated Test (L15). Color confusion score (CCS) and desaturation angle (DSAT) were measured on L15 only. Thirty-nine normal subjects served as a control group. Poor metabolic control was an exclusion criteria. CCS was significantly higher in the patients than in the controls (37.8 +/- 11.1 vs 0 +/- P < .001) and normal scores were found in only 4 diabetic patients. DSAT values were spread, not showing a well-defined axis of the defect. The results of FM100 were clinically reliable but affected by a longer execution time. R28 and SPP2 demonstrated a low sensitivity, as all patients scored normally with both tests. Impaired color vision is a common observation even in patients with uncomplicated juvenile diabetes. Our results indicate that L15 is the most suitable test for screening of early color vision abnormalities in these subjects.

  20. 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,…

  1. Teaching the Standards Is Developmentally Appropriate Practice: Strategies for Incorporating the Sociopolitical Dimension of DAP in Early Childhood Teaching

    ERIC Educational Resources Information Center

    Goldstein, Lisa S.

    2008-01-01

    Many early childhood practitioners in the U.S. are experiencing tension between their desire to offer students developmentally appropriate learning experiences and their obligation to teach the academic knowledge and skills mandated by their states. However, careful examination of the DAP guidelines' definition of culturally appropriate practice…

  2. The Positive Impact of Early Intervention for Children with Developmental Delays, Gestational Cocaine Exposure, and Co-Occurring Risk Factors

    ERIC Educational Resources Information Center

    Ullery, Mary Anne; Katz, Lynne

    2017-01-01

    This article examined transition rates of young children (n = 102) from an early intervention program at the Linda Ray Intervention Program (LRIP) who had documented developmental delays and co-occurring prenatal drug exposure often coupled with verified child maltreatment. Findings indicated that there was significant group improvement from…

  3. 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…

  4. An Annotated Bibliography of Some Recent Articles That Correlate with the Sewall Early Education Developmental Program (SEED).

    ERIC Educational Resources Information Center

    Jackson, Janice; Flamboe, Thomas C.

    The annotated bibliography contains approximately 110 references (1969-1976) of articles related to the Sewall Early Education Developmental Program. Entries are arranged alphabetically by author within the following seven topic areas: social emotional, gross motor, fine motor, adaptive reasoning, speech and language, feeding and dressing and…

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

    PubMed Central

    Ozernov-Palchik, Ola; Gaab, Nadine

    2016-01-01

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

  6. A Rare de novo Interstitial Duplication at 4p15.2 in a Boy with Severe Congenital Heart Defects, Limb Anomalies, Hypogonadism, and Global Developmental Delay.

    PubMed

    Liang, Liyang; Xie, Yingjun; Shen, Yiping; Yin, Qibin; Yuan, Haiming

    2016-01-01

    Proximal 4p deletion syndrome is a relatively rare genetic condition characterized by dysmorphic facial features, limb anomalies, minor congenital heart defects, hypogonadism, cafe-au-lait spots, developmental delay, tall and thin habitus, and intellectual disability. At present, over 20 cases of this syndrome have been published. However, duplication of the same region in proximal 4p has never been reported. Here, we describe a 2-year-5-month-old boy with severe congenital heart defects, limb anomalies, hypogonadism, distinctive facial features, pre- and postnatal developmental delay, and mild cognitive impairments. A de novo 4.5-Mb interstitial duplication at 4p15.2p15.1 was detected by chromosomal microarray analysis. Next-generation sequencing was employed and confirmed the duplication, but revealed no additional pathogenic variants. Several candidate genes in this interval responsible for the complex clinical phenotype were identified, such as RBPJ, STIM2, CCKAR, and LGI2. The results suggest a novel contiguous gene duplication syndrome. © 2016 S. Karger AG, Basel.

  7. RNA-sequencing of the sturgeon Acipenser baeri provides insights into expression dynamics of morphogenic differentiation and developmental regulatory genes in early versus late developmental stages.

    PubMed

    Song, Wei; Jiang, Keji; Zhang, Fengying; Lin, Yu; Ma, Lingbo

    2016-08-08

    Acipenser baeri, one of the critically endangered animals on the verge of extinction, is a key species for evolutionary, developmental, physiology and conservation studies and a standout amongst the most important food products worldwide. Though the transcriptome of the early development of A. baeri has been published recently, the transcriptome changes occurring in the transition from embryonic to late stages are still unknown. The aim of this work was to analyze the transcriptomes of embryonic and post-embryonic stages of A. baeri and identify differentially expressed genes (DEGs) and their expression patterns using mRNA collected from specimens at big yolk plug, wide neural plate and 64 day old sturgeon developmental stages for RNA-Seq. The paired-end sequencing of the transcriptome of samples of A. baeri collected at two early (big yolk plug (T1, 32 h after fertilization) and wide neural plate formation (T2, 45 h after fertilization)) and one late (T22, 64 day old sturgeon) developmental stages using Illumina Hiseq2000 platform generated 64039846, 64635214 and 75293762 clean paired-end reads for T1, T2 and T22, respectively. After quality control, the sequencing reads were de novo assembled to generate a set of 149,265 unigenes with N50 value of 1277 bp. Functional annotation indicated that a substantial number of these unigenes had significant similarity with proteins in public databases. Differential expression profiling allowed the identification of 2789, 12,819 and 10,824 DEGs from the respective T1 vs. T2, T1 vs. T22 and T2 vs. T22 comparisons. High correlation of DEGs' features was recorded among early stages while significant divergences were observed when comparing the late stage with early stages. GO and KEGG enrichment analyses revealed the biological processes, cellular component, molecular functions and metabolic pathways associated with identified DEGs. The qRT-PCR performed for candidate genes in specimens confirmed the validity of the RNA

  8. 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…

  9. Developmental Changes in Ultradian Sleep Cycles across Early Childhood: Preliminary Insights

    PubMed Central

    Lopp, Sean; Navidi, William; Achermann, Peter; LeBourgeois, Monique; Diniz Behn, Cecilia

    2017-01-01

    Nocturnal human sleep is composed of cycles between rapid eye movement (REM) sleep and non-REM (NREM) sleep. In adults, the structure of ultradian cycles between NREM and REM sleep is well characterized; however, less is known about the developmental trajectories of ultradian sleep cycles across early childhood. Cross-sectional studies indicate that the rapid ultradian cycling of active-quiet sleep in infancy shifts to a more adult-like pattern of NREM-REM sleep cycling by the school-age years, yet longitudinal studies elucidating the details of this transition are scarce. To address this gap, we examined ultradian cycling during nocturnal sleep following 13 h of prior wakefulness in 8 healthy children at 3 longitudinal points: 2Y (2.5-3.0 years of age), 3Y (3.5-4.0 years of age), and 5Y (5.5-6.0 years of age). We found that the length of ultradian cycles increased with age as a result of increased NREM sleep episode duration. In addition, we observed a significant decrease in the number of NREM sleep episodes as well as a nonsignificant trend for a decrease in the number of cycles with increasing age. Together, these findings suggest a concurrent change in which cycle duration increases and the number of cycles decreases across development. We also found that, consistent with data from adolescents and adults, the duration of NREM sleep episodes decreased with time since lights-off whereas the duration of REM sleep episodes increased over this time period. These results indicate the presence of circadian modulation of nocturnal sleep in preschool children. In addition to characterizing changes in ultradian cycling in healthy children ages 2 to 5 years, this work describes a developmental model that may provide insights into the emergence of normal adult REM sleep regulatory circuitry as well as potential trajectories of dysregulated ultradian cycles such as those associated with affective disorders. PMID:28088873

  10. Evaluation of right ventricular function in early period following transcatheter closure of atrial septal defect.

    PubMed

    Ağaç, Mustafa Tarık; Akyüz, Ali Rıza; Acar, Zeydin; Akdemir, Ramazan; Korkmaz, Levent; Kırış, Abdülkadir; Erkuş, Emre; Erkan, Hakan; Celik, Sükrü

    2012-03-01

    There is limited data on alterations in novel right ventricular (RV) function indices like tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity (TASV) after transcatheter atrial septal defect (ASD) closure. We aimed to evaluate RV function by echocardiography (ECG) with these novel indices in early period in patients with secundum-type ASD that was closed percutaneously. Patients were enrolled to study if they had secundum-type ASD that was suitable for percutaneous closure. Patient population consisted of 4 men and 16 women. Echocardiography was performed before and 1 month after closure. Mean age was 37 ± 16. Mean diameter of ASD and total atrial septum length measured by ECG were 19 ± 6 mm and 49 ± 7 mm, respectively. Mean diameter of defect in transesophageal echocardiography was 20 ± 6 mm. Stretched mean diameter in catheterization was 23 ± 6 mm. One month after closure, there were statistically significant decreases in RV end-diastolic diameters (43.3 ± 10.7 mm vs. 34.9 ± 5.5 mm; P < 0.001), RV/left ventricular (LV) end-diastolic diameter ratio (1.1 ± 0.3 vs. 0.87 ± 0.1; P < 0.001), TASV (16.9 ± 3.2 cm/sec vs. 14.3 ± 3.3 cm/sec; P < 0.05), early diastolic tricuspid annular velocity (15.3 ± 3.1 cm/sec vs. 13.4 ± 2.4 cm/sec P <0.05), late diastolic tricuspid annular velocity (16.2 ± 5.4 cm/sec vs. 14.3 ± 6.3 cm/sec; P < 0.05), and TAPSE (29.9 ± 6.2 mm vs. 22.4 ± 7.4 mm; P < 0.001). LV end-diastolic diameter (38.0 ± 6.9 mm and 40.0 ± 4.5 P < 0.05) was increased, whereas there was no change in LV ejection fraction. Closure of ASD by using Amplatzer devices led to decrease in right heart chamber size, tissue Doppler-derived tricuspid annular velocities and TAPSE in early period. © 2011, Wiley Periodicals, Inc.

  11. 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

  12. 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

  13. Developmental Defects in a Zebrafish Model for Muscular Dystrophies Associated with the Loss of Fukutin-Related Protein (FKRP)

    ERIC Educational Resources Information Center

    Thornhill, Paul; Bassett, David; Lochmuller, Hanns; Bushby, Kate; Straub, Volker

    2008-01-01

    A number of muscular dystrophies are associated with the defective glycosylation of [alpha]-dystroglycan and many are now known to result from mutations in a number of genes encoding putative or known glycosyltransferases. These diseases include severe forms of congenital muscular dystrophy (CMD) such as Fukuyama type congenital muscular dystrophy…

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

    PubMed

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

    2017-03-01

    The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Drosophila caspases involved in developmentally regulated programmed cell death of peptidergic neurons during early metamorphosis.

    PubMed

    Lee, Gyunghee; Wang, Zixing; Sehgal, Ritika; Chen, Chun-Hong; Kikuno, Keiko; Hay, Bruce; Park, Jae H

    2011-01-01

    A great number of obsolete larval neurons in the Drosophila central nervous system are eliminated by developmentally programmed cell death (PCD) during early metamorphosis. To elucidate the mechanisms of neuronal PCD occurring during this period, we undertook genetic dissection of seven currently known Drosophila caspases in the PCD of a group of interneurons (vCrz) that produce corazonin (Crz) neuropeptide in the ventral nerve cord. The molecular death program in the vCrz neurons initiates within 1 hour after pupariation, as demonstrated by the cytological signs of cell death and caspase activation. PCD was significantly suppressed in dronc-null mutants, but not in null mutants of either dredd or strica. A double mutation lacking both dronc and strica impaired PCD phenotype more severely than did a dronc mutation alone, but comparably to a triple dredd/strica/dronc mutation, indicating that dronc is a main initiator caspase, while strica plays a minor role that overlaps with dronc's. As for effector caspases, vCrz PCD requires both ice and dcp-1 functions, as they work cooperatively for a timely removal of the vCrz neurons. Interestingly, the activation of the Ice and Dcp-1 is not solely dependent on Dronc and Strica, implying an alternative pathway to activate the effectors. Two remaining effector caspase genes, decay and damm, found no apparent functions in the neuronal PCD, at least during early metamorphosis. Overall, our work revealed that vCrz PCD utilizes dronc, strica, dcp-1, and ice wherein the activation of Ice and Dcp-1 requires a novel pathway in addition to the initiator caspases.

  17. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. 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

  19. 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…

  20. 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.

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

    PubMed

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

    2014-12-01

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

  2. [Early complications following transcatheter occlusion of perimembranous ventricular septal defects in children].

    PubMed

    Li, Jun-jie; Zhang, Zhi-wei; Qian, Ming-yang; Wang, Hui-shen; Li, Yu-fen

    2006-11-01

    To evaluate the early complications during and after transcatheter closure of perimembranous ventricular septal defects (PMVSDs) in children. A total of 223 patients received transcatheter closure of PMVSDs from March 2002 to December 2005 in our hospital were included in this retrospective study. The overall complications rate was 26.9% (60/223). Major complications occurred in 9 patients (4.0%) including III degrees atrioventricular block (AVB) in 2 (0.9%), hemolysis in 3 (1.3%) and surgical interventions in 4 patients (1.8%) because of device malposition (1), mild aortic regurgitation (2) and device embolization (1) and all 4 patients recovered without further complications. The 2 patients with III degrees AVB were completely recovered to normal sinus rhythm after 7 days treatment with temporary pacemaker and corticosteroid. Hemolysis in 3 patients disappeared after corticosteroid treatment. Minor complications occurred in 51 patients (22.8%) including bundle branch block (BBB) in 37 (16.6%), first-degree AVB in 2 (0.9%), second-degree AVB in 1 (0.4%), new-onset mild aortic regurgitation in 5 (2.2%) and new-onset mild to moderate tricuspid regurgitation in 6 patients (2.6%). Except for right bundle branch blocks, other BBBs were treated with albumin and corticosteroid and completely recovered. No treatment was applied for new-onset valve regurgitations. There was no death in all 223 patients. Early complications post PMVSDs in children are mostly minor with good prognosis and the prognosis for major complications post PMVSDs is good after proper treatment.

  3. 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

  4. Malnutrition-related early childhood exposures and enamel defects in the permanent dentition: A longitudinal study from the Bolivian Amazon.

    PubMed

    Masterson, Erin E; Fitzpatrick, Annette L; Enquobahrie, Daniel A; Mancl, Lloyd A; Conde, Esther; Hujoel, Philippe P

    2017-10-01

    We investigated the relationship between early childhood malnutrition-related measures and subsequent enamel defects in the permanent dentition. This cohort study included 349 Amerindian adolescents (10-17 years, 52% male) from the Bolivian Amazon. Exposures included: stunted growth (height-for-age z-scores), underweight (weight-for-age z-scores), anemia (hemoglobin), acute inflammation (C-reactive protein) and parasitic infection (hookworm). We measured the occurrence (no/yes) and extent (<1/3, 1/3-2/3, >2/3) of enamel defects. We estimated associations between childhood exposures and enamel defect measures using log-binomial and multinomial logistic regression. The prevalence of an enamel defect characterized by an orange peel texture on a large central depression on the labial surface of the central maxillary incisors was 92.3%. During childhood (1-4 years), participants had a high prevalence of stunted growth (75.2%), anemia (56.9%), acute inflammation (39.1%), and hookworm infection (49.6%). We observed associations between childhood height-for-age (OR = 0.65; P = 0.028 for >2/3 extent vs. no EH) and gastrointestinal hookworm infection (OR = 3.43; P = 0.035 for >2/3 extent vs. no defects or <1/3 extent) with enamel defects. The study describes a possibly novel form of enamel hypoplasia and provides evidence for associations of malnutrition-related measures in early childhood, including stunted growth and parasitic helminth infection, with the observed enamel defects. © 2017 Wiley Periodicals, Inc.

  5. Detection of retinal nerve fiber layer defects on retinal fundus images for early diagnosis of glaucoma

    NASA Astrophysics Data System (ADS)

    Muramatsu, Chisako; Hayashi, Yoshinori; Sawada, Akira; Hatanaka, Yuji; Hara, Takeshi; Yamamoto, Tetsuya; Fujita, Hiroshi

    2010-01-01

    Retinal nerve fiber layer defect (NFLD) is a major sign of glaucoma, which is the second leading cause of blindness in the world. Early detection of NFLDs is critical for improved prognosis of this progressive, blinding disease. We have investigated a computerized scheme for detection of NFLDs on retinal fundus images. In this study, 162 images, including 81 images with 99 NFLDs, were used. After major blood vessels were removed, the images were transformed so that the curved paths of retinal nerves become approximately straight on the basis of ellipses, and the Gabor filters were applied for enhancement of NFLDs. Bandlike regions darker than the surrounding pixels were detected as candidates of NFLDs. For each candidate, image features were determined and the likelihood of a true NFLD was determined by using the linear discriminant analysis and an artificial neural network (ANN). The sensitivity for detecting the NFLDs was 91% at 1.0 false positive per image by using the ANN. The proposed computerized system for the detection of NFLDs can be useful to physicians in the diagnosis of glaucoma in a mass screening.

  6. Heat shock during early somitogenesis induces caudal vertebral column defects in Atlantic salmon (Salmo salar).

    PubMed

    Wargelius, Anna; Fjelldal, Per Gunnar; Hansen, Tom

    2005-07-01

    In several terrestrial vertebrates, heat shock (HS) during somitogenesis causes vertebral deformities. To determine if vertebral deformities can occur due to sudden temperature changes during early development in fish, Atlantic salmon embryos were HS treated during somitogenesis. Ten months later these individuals displayed a high prevalence of caudal vertebral column condensations (27-34%). The defects were located caudally of the abdominal cavity, displaying an even distribution in this region independent of time of HS. To determine if HS disturbed vertebral development during somitogenesis, two genes coding for markers of skeletal development were identified, namely, the secreted protein Shh (Sashh) and the transcription factor Twist (Satwist). These proteins are involved in the proliferation and specification of presumptive skeletal cells (sclerotome) in vertebrates. The spatial expression pattern of sashh and satwist in salmon indicated a functional conservation of these proteins. Furthermore, HS embryos displayed expressional disturbance in both sashh and satwist, indicating an effect of HS on sclerotomal cell patterning. However, the HS-protecting ability in embryos seems to be individually regulated because reduction in gene expression was not detected at all stages; in addition, HS did not induce somitic disturbance and vertebral deformity in all embryos.

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

    PubMed Central

    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

  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

    2015-05-06

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

  9. 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

  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. 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…

  12. 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…

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

    PubMed

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

    2016-12-01

    In this study, we verified nuclear transport activity of an artificial nuclear localization signal (aNLS) in medaka fish (Oryzias latipes). We generated a transgenic medaka strain expresses the aNLS tagged enhanced green fluorescent protein (EGFP) driven by a medaka beta-actin promoter. The aNLS-EGFP was accumulated in the nuclei of somatic tissues and yolk nuclei of oocytes, but undetectable in the spermatozoa. The fluorescent signal was observed from immediately after fertilization by a maternal contribution. Furthermore, male and female pronuclei were visualized in fertilized eggs, and nuclear dynamics of pronuclear fusion and subsequent cleavage were captured by time-lapse imaging. In contrast, SV40NLS exhibited no activity of nuclear transport in early embryos. In conclusion, the aNLS possesses a strong nuclear localization activity and is a useful probe for fluorescent observation of the pronuclei and nuclei in early developmental stage of medaka. © 2016 Japanese Society of Developmental Biologists.

  14. Developmental Structural Tooth Defects in Dogs – Experience From Veterinary Dental Referral Practice and Review of the Literature

    PubMed Central

    Boy, Sonja; Crossley, David; Steenkamp, Gerhard

    2016-01-01

    Developmental tooth abnormalities in dogs are uncommon in general veterinary practice but understanding thereof is important for optimal management in order to maintain masticatory function through preservation of the dentition. The purpose of this review is to discuss clinical abnormalities of the enamel and general anatomy of dog teeth encountered in veterinary dental referral practice and described in the literature. More than 900 referral cases are seen annually between the two referral practices. The basis of the pathogenesis, resultant clinical appearance, and the principles of management for each anomaly will be described. Future research should be aimed toward a more detailed analysis of these conditions so rarely described in the literature. PMID:26904551

  15. Developmental outcome after surgery in focal cortical dysplasia patients with early-onset epilepsy.

    PubMed

    Kimura, Nobusuke; Takahashi, Yukitoshi; Shigematsu, Hideo; Imai, Katsumi; Ikeda, Hiroko; Ootani, Hideyuki; Takayama, Rumiko; Mogami, Yukiko; Kimura, Noriko; Baba, Koichi; Matsuda, Kazumi; Tottori, Takayasu; Usui, Naotaka; Inoue, Yushi

    2014-12-01

    The purpose of this study was to investigate the developmental outcome after surgery for early-onset epilepsy in patients with focal cortical dysplasia (FCD). Among 108 patients with histopathologically confirmed FCD operated between 1985 and 2008, we selected 17 patients with epilepsy onset up to 3 years of age. Development was evaluated by the developmental quotient or intelligence quotient (DQ-IQ) and mental age was measured by the Mother-Child Counseling baby test or the Tanaka-Binet scale of intelligence. Postsurgical development outcome was evaluated by the changes in DQ-IQ and mental age as well as rate of increase in mental age (RIMA) after surgery. RIMA was calculated as the increase in mental age per chronological year (months/year; normal average rate: 12 months/year). Age at epilepsy onset of 17 patients ranged from 15 days to 36 months (mean±SD, 11.0±10.0 months). Age at surgery ranged from 18 to 145 months (75.1±32.4 months). Evaluation just before surgery showed that 13 of 17 (76.4%) patients had DQ-IQ below 70. Ten patients (58.8%) were seizure-free throughout the postsurgical follow-up period. After surgery, DQ-IQ was maintained within 10 points of the presurgical level in 13 patients (76.4%), and increased by more than 10 points in one patient (5.9%). After surgery, RIMA in patients with Engel's class I (7.5±3.8) was higher than patients with Engel's class II-IV (2.6±3.4) (unpaired t-test with Welch's correction, t=2.99, df=15, p=0.0092). RIMA was particularly low in two patients with spasm. In four patients with presurgical DQ-IQ<70, seizure-free after surgery and without spasm, DQ-IQ did not increase but RIMA improved from 3.6±2.8 before surgery to 6.9±2.5 months/year after surgery. RIMA became better from 2 years after surgery. In four patients with presurgical DQ-IQ≥70 and no spasm, two showed the same or higher RIMA than normal average after surgery. In 58.8% of FCD patients with early onset epilepsy, epilepsy surgery effectively

  16. Maternal ambient air pollution exposure preconception and during early gestation and offspring congenital orofacial defects

    PubMed Central

    Zhu, Yeyi; Zhang, Cuilin; Liu, Danping; Grantz, Katherine L.; Wallace, Maeve; Mendola, Pauline

    2015-01-01

    Background Maternal air pollution exposure has been related to orofacial clefts but the literature is equivocal. Potential chronic preconception effects have not been studied. Objectives Criteria air pollutant exposure during three months preconception and gestational weeks 3–8 was studied in relation to orofacial defects. Methods Among 188,102 live births and fetal deaths from the Consortium on Safe Labor (2002–2008), 63 had isolated cleft palate (CP) and 159 had isolated cleft lip with or without cleft palate (CL ± CP). Exposures were estimated using a modified Community Multiscale Air Quality model. Logistic regression with generalized estimating equations adjusted for site/region and maternal demographic, lifestyle and clinical factors calculated the odds ratio (OR) and 95% CI per interquartile increase in each pollutant. Results Preconception, carbon monoxide (CO; OR = 2.24; CI: 1.21, 4.16) and particulate matter (PM) ≤10 μm (OR = 1.72; CI: 1.12, 2.66) were significantly associated with CP, while sulfur dioxide (SO2) was associated with CL ± CP (OR = 1.93; CI: 1.16, 3.21). During gestational weeks 3–8, CO remained a significant risk for CP (OR = 2.74; CI: 1.62, 4.62) and nitrogen oxides (NOx; OR = 3.64; CI: 1.73, 7.66) and PM ≤2.5 μm (PM2.5; OR = 1.74; CI: 1.15, 2.64) were also related to the risk. Analyses by individual week revealed that positive associations of NOx and PM2.5 with CP were most prominent from weeks 3–6 and 3–5, respectively. Conclusions Exposure to several criteria air pollutants preconception and during early gestation was associated with elevated odds for CP, while CL ± CP was only associated with preconception SO2 exposure. PMID:26099933

  17. Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome–associated Sos1 mutation

    PubMed Central

    Chen, Peng-Chieh; Wakimoto, Hiroko; Conner, David; Araki, Toshiyuki; Yuan, Tao; Roberts, Amy; Seidman, Christine E.; Bronson, Roderick; Neel, Benjamin G.; Seidman, Jonathan G.; Kucherlapati, Raju

    2010-01-01

    Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, unique facial features, and congenital heart disease. About 10%–15% of individuals with NS have mutations in son of sevenless 1 (SOS1), which encodes a RAS and RAC guanine nucleotide exchange factor (GEF). To understand the role of SOS1 in the pathogenesis of NS, we generated mice with the NS-associated Sos1E846K gain-of-function mutation. Both heterozygous and homozygous mutant mice showed many NS-associated phenotypes, including growth delay, distinctive facial dysmorphia, hematologic abnormalities, and cardiac defects. We found that the Ras/MAPK pathway as well as Rac and Stat3 were activated in the mutant hearts. These data provide in vivo molecular and cellular evidence that Sos1 is a GEF for Rac under physiological conditions and suggest that Rac and Stat3 activation might contribute to NS phenotypes. Furthermore, prenatal administration of a MEK inhibitor ameliorated the embryonic lethality, cardiac defects, and NS features of the homozygous mutant mice, demonstrating that this signaling pathway might represent a promising therapeutic target for NS. PMID:21041952

  18. Prenatal exposure to disaster-related traumatic stress and developmental trajectories of temperament in early childhood: Superstorm Sandy pregnancy study.

    PubMed

    Zhang, Wei; Rajendran, Khushmand; Ham, Jacob; Finik, Jackie; Buthmann, Jessica; Davey, Kei; Pehme, Patricia M; Dana, Kathryn; Pritchett, Alexandra; Laws, Holly; Nomura, Yoko

    2018-07-01

    Little is known about the impact of prenatal maternal stress (PNMS) on the developmental trajectory of temperament and few studies have been able to incorporate a natural disaster as a quasi-experimental stressor. The current study investigated PNMS related to Superstorm Sandy ('Sandy'), a hurricane that struck the New York metropolitan area in October 2012, in terms of objective exposure during pregnancy, subjective stress reaction as assessed by maternal symptoms of post-traumatic stress, and their impact on the developmental changes in temperament during early childhood. A subsample of 318 mother-child dyads was drawn from the Stress in Pregnancy Study. Temperament was measured at 6, 12, 18, and 24 months of age. Objective exposure was associated with greater High-Intensity Pleasure, Approach, Perceptual Sensitivity and Fearfulness, but lower Cuddliness and Duration of Orientation at 6 months. Objective exposure and its interaction with subjective stress reaction predicted developmental changes in temperament. In particular, objective exposure was linked to greater increases in Activity Level but decreases in High-Intensity Pleasure, Approach, and Fearfulness. The combination of objective exposure and subjective stress reaction was also associated with greater increases in Activity Level. Temperament was measured solely via maternal report. Trimester-specific effects of Sandy on temperament were not examined. This is the first study to examine the effects of prenatal maternal exposure to a natural disaster on trajectories of early childhood temperament. Findings suggest that both objective stress exposure and subjective stress reaction in-utero predict developmental trajectories of temperament in early childhood. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Profile of referrals for early childhood developmental delay to ambulatory subspecialty clinics.

    PubMed

    Shevell, M I; Majnemer, A; Rosenbaum, P; Abrahamowicz, M

    2001-09-01

    The objective of this study was to determine the profile and pattern of referral to subspecialty clinics of young children with suspected developmental delay together with the factors prompting their referral. All children under 5 years of age referred to either developmental pediatrics or pediatric neurology clinics at a single tertiary hospital over an 18-month period were prospectively identified. Standardized demographic and referral information were collected at intake, final developmental delay subtype diagnosed was identified, and referring physicians were surveyed regarding factors prompting referral. A total of 224 children met study criteria. There was a marked male preponderance (166/224), especially among those with either cognitive or language delay. Two delay subtypes, global developmental delay and developmental language disorder, accounted for two thirds of the diagnoses made. For slightly more than one third of the children (75/224), the delay subtype diagnosed following specialty evaluation was different from that initially suspected by the referring physician. A mean delay of 15.5 months was observed for the cohort as a whole between initial parental concern and specialty assessment. For referring physicians, the major factor prompting referral was the severity of the observed delay. The most important aspects of the specialty evaluation according to referral sources were the identification of a possible etiology and confirmation of delay. A profile of referrals and the rationale thereof for a cohort of children with suspected developmental delay is presented that, although locale specific, has implications for service provision and training.

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

    PubMed Central

    GUL, HESNA; EROL, NESE; AKIN, DUYGU PAMIR; GULLU, BELGİN USTUN; AKCAKİN, 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. PMID:26891759

  1. Morphological and histomorphological structures of testes and ovaries in early developmental stages of the silkworm, Bombyx mori.

    PubMed

    Sakai, Hiroki; Kirino, Yohei; Katsuma, Susumu; Aoki, Fugaku; Suzuki, Masataka G

    2016-01-01

    The gonad develops as a testis in male or an ovary in female. In the silkworm, B. mori , little is known about testis and ovary in the embryonic stages and early larval stages. In this study, we performed morphological and histomorphological observations of ovaries and testes from the late embryonic stage to the 1st instar larval stage. Results obtained with lack of accurate information on sex of examined individuals may be misleading, thus we performed phenotypic observations of gonads by utilizing sex-limited strain that enables us to easily discriminate female embryos from male ones based on those egg colors. In testis, four testicular follicles were clearly observed in the testis at the first instar larval stage, and boundary layers were formed between the testicular follicles. At the late embryonic stage, the testis consisted of four testicular follicles, while the boundary layers were still obscure. In ovary, four ovarioles were easily recognizable in the ovary at the first instar larval stage, and boundary layers were formed between the ovarioles. However, in the late embryonic stage, it was quite difficult to identify four ovarioles. Morphological characteristics were almost similar between testis and ovary in early developmental stages. Our present study demonstrates that the most reliable difference between testis and ovary in early developmental stages is the attaching point of the duct. Formation and development of the duct may be sensitive to the sex-determining signal and display sexual dimorphism in early embryonic stages.

  2. 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.

  3. Divergence of developmental trajectories is triggered interactively by early social and ecological experience in a cooperative breeder

    PubMed Central

    Bohn, Lena; Oberhummer, Evelyne

    2017-01-01

    Cooperative breeders feature the highest level of social complexity among vertebrates. Environmental constraints foster the evolution of this form of social organization, selecting for both well-developed social and ecological competences. Cooperative breeders pursue one of two alternative social trajectories: delaying reproduction to care for the offspring of dominant breeders or dispersing early to breed independently. It is yet unclear which ecological and social triggers determine the choice between these alternatives and whether diverging developmental trajectories exist in cooperative vertebrates predisposing them to dispersal or philopatry. Here we experimentally reared juveniles of cooperatively breeding cichlid fish by varying the social environment and simulated predation threat in a two-by-two factorial long-term experiment. First, we show that individuals develop specialized behavioral competences, originating already in the early postnatal phase. Second, these specializations predisposed individuals to pursue different developmental trajectories and either to disperse early or to extend philopatry in adulthood. Thus, our results contrast with the proposition that social specializations in early ontogeny should be restricted to eusocial species. Importantly, social and ecological triggers were both required for the generation of divergent life histories. Our results thus confirm recent predictions from theoretical models that organisms should combine relevant information from different environmental cues to develop integrated phenotypes. PMID:29078289

  4. Volatile organic compounds from fungi isolated after hurricane katrina induce developmental defects and apoptosis in a Drosophila melanogaster model.

    PubMed

    Inamdar, Arati A; Bennett, Joan W

    2015-05-01

    In previous work, our laboratory developed a Drosophila model for studying the adverse effects of fungal volatile organic compounds (VOCs) emitted by growing cultures of molds. In this report, we have extended these studies and compared the toxic effects of fungal VOCs emitted from living cultures of four molds isolated after Hurricane Katrina from a flooded home in New Orleans. Strains of Aspergillus, Mucor, Penicillium, and Trichoderma were grown with wild-type larvae and the toxic effects of volatile products on the developmental stages of Drosophila larvae were evaluated. Furthermore, heterozygous mutants of Drosophila carrying the apoptotic genes, reaper and dronc, were used to assess the role of apoptosis in fungal VOCs mediated toxicity. Third-instar larvae of Drosophila carrying these apoptotic genes were exposed to fungal VOCs emitted from growing mold cultures for 10 days. The larval strains carrying apoptopic genes survived longer than the control wild type larvae; moreover, of those that survived, heterozygous reaper and dronc strains progressed to pupae and adult phases more rapidly, suggesting that fungal VOCs may induce apoptotic changes in flies. These data lend support to the use of Drosophila as an inexpensive and genetically versatile toxicological model to investigate the mechanistic basis for some of the human illnesses/symptoms associated with exposure to mold-contaminated indoor air, especially after hurricanes. © 2013 Wiley Periodicals, Inc.

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

    ERIC Educational Resources Information Center

    Trentacosta, Christopher J.; Shaw, Daniel S.

    2009-01-01

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

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

    PubMed

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

    2014-06-17

    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. © 2014 The Authors.

  7. 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

  8. Inherited partial direct duplication of 11q: First report and possible association with a midline developmental field defect

    SciT

    Witt, D.R.; Jenkins, L.; Pinheiro, S.

    1994-09-01

    A 36-year-old woman underwent amniocentesis for advanced maternal age. The fetal karyotype had an extra dark staining G band on the long arm of chromosome 11 with no other identifiable abnormalities. FISH studies using a chromosome 11 paint probe confirmed the origin of the extra band. The abnormality was identified as a partial duplication of 11q: 46,XX dir dup (11)(q13.5q21) or (q21q23.1). The specific duplicated band could not be identified with certainty. Detailed fetal sonograms were normal. Family studies revealed the identical duplication in the mother but normal karyotypes in both maternal grandparents. The mother had strabismus and a shortmore » tongue frenulum which required surgical correction. Menses occurred late in adolescence and complete development of secondary sexual characteristics was delayed until adulthood. An infertility evaluation revealed duplication of the uterus, cervix, and vagina. An evaluation for metorrhagia identified a pituitary adenoma which was resected. Her intelligence was normal. To our knowledge this is the first report of a heritable direct duplication of 11q. It is possible that one or more gene in the duplicated segment played a causal role in the pathophysiology of the patient`s anomalies through a disturbance of the so-called {open_quotes}midline developmental field{close_quotes}. Alternatively, the cytogenetic findings could be unrelated to the malformations. Rare instances of partial gain or loss of specific late-replicating heterochromatic regions without phenotypic effect have been reported. This region of 11q is also relatively late-replicating. This is consistent with previous reports suggesting a paucity of expressed genes in this 11q region. Molecular studies of the duplication are underway to determine the specific location and extent of duplication. Phenotypic evaluation of the patient`s baby will also be reported.« less

  9. Isolation and characterization of progenitor cells from surgically created - early healing alveolar defects in humans. A preliminary study.

    PubMed

    Sant'Ana, Adriana Campos Passanezi; Damante, Carla Andreotti; Martinez, Maria Alejandra Frias; Valdivia, Maria Alejandra Medina; Karam, Paula Stefânia Hage; de Oliveira, Flavia Amadeu; de Oliveira, Rodrigo Cardoso; Gasparoto, Thais Helena; Campanelli, Ana Paula; Zangrando, Mariana Schutzer Ragghianti; de Rezende, Maria Lúcia Rubo; Greghi, Sebastião Luiz Aguiar; Passanezi, Euloir

    2018-05-30

    The granulation tissue (GT) present in surgically-created early healing sockets has been considered as a possible source of osteoprogenitor cells for periodontal regeneration, as demonstrated in animal studies. However, the in vitro osteogenic properties of tissue removed from human surgically-created early healing alveolar defects (SC-EHAD) remains to be established, being that the aim of this study. Surgical defects were created in the edentulous ridge of two systemically healthy adults. The healing tissue present in these defects was removed 21 days later for the establishment of primary culture. The in vitro characteristics of the cultured cells were determined by Armelin method, MTT assay, immunohistochemistry, alkaline phosphatase (ALP) activity, mineralization assay and flow cytometry for detection of stem cells/osteoprogenitor cell markers. Cells were able to adhere to the plastic and assumed spindle-shaped morphology at earlier passages, changing to a cuboidal one with increasing passages. Differences in the proliferation rate were observed with increasing passages, suggesting osteogenic differentiation. ALP and mineralization activities were detected in conventional and osteogenic medium. Fresh samples of SC-EHAD tissue exhibited CD34 - and CD45 - phenotypes. Cells at later passages (14 th ) exhibited CD34 - , CD45 - , CD105 - , CD166 - and collagen type I + phenotype. Tissue removed from SC-EHAD is a possible source of progenitor cells. This article is protected by copyright. All rights reserved. © 2018 American Academy of Periodontology.

  10. Developmental programming: postnatal estradiol amplifies ovarian follicular defects induced by fetal exposure to excess testosterone and dihydrotestosterone in sheep.

    PubMed

    Veiga-Lopez, A; Wurst, A K; Steckler, T L; Ye, W; Padmanabhan, V

    2014-04-01

    Excess of prenatal testosterone (T) induces reproductive defects including follicular persistence. Comparative studies with T and dihydrotestosterone (DHT) have suggested that follicular persistence is programmed via estrogenic actions of T. This study addresses the androgenic and estrogenic contributions in programming follicular persistence. Because humans are exposed to estrogenic environmental steroids from various sources throughout their life span and postnatal insults may also induce organizational and/or activational changes, we tested whether continuous postnatal exposure to estradiol (E) will amplify effects of prenatal steroids on ovarian function. Pregnant sheep were treated with T, DHT, E, or ED (E and DHT) from days 30 to 90 of gestation. Postnatally, a subset of the vehicle (C), T, and DHT females received an E implant. Transrectal ultrasonography was performed in the first breeding season during a synchronized cycle to monitor ovarian follicular dynamics. As expected, number of ≥8 mm follicles was higher in the T versus C group. Postnatal E reduced the number of 4 to 8 mm follicles in the DHT group. Percentage of females bearing luteinized follicles and the number of luteinized follicles differed among prenatal groups. Postnatal E increased the incidence of subluteal cycles in the prenatal T-treated females. Findings from this study confirm previous findings of divergences in programming effects of prenatal androgens and estrogens. They also indicate that some aspects of follicular dynamics are subject to postnatal modulation as well as support the existence of an extended organizational period or the need for a second insult to uncover the previously programmed event.

  11. 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. © 2014 Society for Endocrinology.

  12. 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,…

  13. 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…

  14. 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…

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

    ERIC Educational Resources Information Center

    Fujinaga, Tamotsu; And Others

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

  16. 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…

  17. 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…

  18. Community College Developmental Education Services: Perspectives of Spanish-Speaking Latino Early Childhood Educators

    ERIC Educational Resources Information Center

    Eberly, John E.

    2018-01-01

    The purpose of this single-case study was to understand the perceptions of Latino Spanish-speaking English learners on the efficacy of developmental education services at a Western U.S. community college. The primary data collection method was in-depth individual interviews of a purposeful sample of nine successful students. Findings indicated…

  19. An Examination of the Relationship between a Child's Developmental Age and Early Literacy Learning

    ERIC Educational Resources Information Center

    Moran, Christine E.; Senseny, Karlen

    2016-01-01

    American students typically attend kindergarten at the chronological age (CA) of five and currently with the implementation of Common Core State Standards, there are expectations that children learn how to read in order to meet these academic standards, despite whether or not they are developmentally ready. This mixed methods study examined age…

  20. 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…

  1. Talk with Your Mother or Your Sibling? Developmental Changes in Early Family Conversations about Feelings.

    ERIC Educational Resources Information Center

    Brown, Jane R.; Dunn, Judy

    1992-01-01

    Developmental changes in the pattern of 50 families' conversations about feelings were examined when the families' second-born children were 33 and 47 months old. The total amount of talk and the frequency of talk about feelings between sibling pairs increased, whereas the amount of mother-child conversation and references to feelings decreased.…

  2. Individual and Developmental Differences in Disengagement of Fixation in Early Infancy.

    ERIC Educational Resources Information Center

    Frick, Janet E.; Colombo, John; Saxon, Terrill F.

    1999-01-01

    Investigated whether individual and developmental differences in look duration were correlated with latency to disengage fixation from a visual stimulus for 3- and 4-month olds. Found that look duration was correlated with disengagement latency. Three-month olds showed slower latencies than 4-month olds. Long-looking infants showed greater…

  3. 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…

  4. 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…

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

    ERIC Educational Resources Information Center

    Barbarin, Oscar A.

    2015-01-01

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

  6. Developmental tasks of early marriage: Barefoot in the Park (1967), Raising Arizona (1987), The Quiet Man (1952).

    PubMed

    Akhtar, Salman; Billinkoff, Zoe

    2011-06-01

    Using three Hollywood movies as a springboard, the authors offer a discussion of the psychosocial challenges faced by an individual entering a marital relationship. Keeping their attention on both intrapsychic and interpersonal factors, as well as the group matrix surrounding the couple, the authors discuss the subtleties of identity transformation, evolution of true mutuality, distance-related conflicts, and the deeper synthesis of affection and sensuality in the setting of early marriage. Their portrayal of this adult developmental phase is intended to help clinicians evolve greater empathy with newly married individuals.

  7. Early developmental influences on self-esteem trajectories from adolescence through adulthood: Impact of birth weight and motor skills.

    PubMed

    Poole, Kristie L; Schmidt, Louis A; Ferro, Mark A; Missiuna, Cheryl; Saigal, Saroj; Boyle, Michael H; Van Lieshout, Ryan J

    2018-02-01

    While the trajectory of self-esteem from adolescence to adulthood varies from person to person, little research has examined how differences in early developmental processes might affect these pathways. This study examined how early motor skill development interacted with preterm birth status to predict self-esteem from adolescence through the early 30s. We addressed this using the oldest known, prospectively followed cohort of extremely low birth weight (<1000 g) survivors (N = 179) and normal birth weight controls (N = 145) in the world, born between 1977 and 1982. Motor skills were measured using a performance-based assessment at age 8 and a retrospective self-report, and self-esteem was reported during three follow-up periods (age 12-16, age 22-26, and age 29-36). We found that birth weight status moderated the association between early motor skills and self-esteem. Stable over three decades, the self-esteem of normal birth weight participants was sensitive to early motor skills such that those with poorer motor functioning manifested lower self-esteem, while those with better motor skills manifested higher self-esteem. Conversely, differences in motor skill development did not affect the self-esteem from adolescence to adulthood in individuals born at extremely low birth weight. Early motor skill development may exert differential effects on self-esteem, depending on whether one is born at term or prematurely.

  8. Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development

    PubMed Central

    Ataca, Dalya; Caikovski, Marian; Piersigilli, Alessandra; Moulin, Alexandre; Benarafa, Charaf; Earp, Sarah E.; Guri, Yakir; Kostic, Corinne; Arsenivic, Yvan; Soininen, Raija; Apte, Suneel S.

    2016-01-01

    ABSTRACT The ADAMTS family comprises 19 secreted metalloproteinases that cleave extracellular matrix components and have diverse functions in numerous disease and physiological contexts. A number of them remain ‘orphan’ proteases and among them is ADAMTS18, which has been implicated in developmental eye disorders, platelet function and various malignancies. To assess in vivo function of ADAMTS18, we generated a mouse strain with inactivated Adamts18 alleles. In the C57Bl6/Ola background, Adamts18-deficient mice are born in a normal Mendelian ratio, and are viable but show a transient growth delay. Histological examination revealed a 100% penetrant eye defect resulting from leakage of lens material through the lens capsule occurring at embryonic day (E)13.5, when the lens grows rapidly. Adamts18-deficient lungs showed altered bronchiolar branching. Fifty percent of mutant females are infertile because of vaginal obstruction due to either a dorsoventral vaginal septum or imperforate vagina. The incidence of ovarian rete is increased in the mutant mouse strain. Thus, Adamts18 is essential in the development of distinct tissues and the new mouse strain is likely to be useful for investigating ADAMTS18 function in human disease, particularly in the contexts of infertility and carcinogenesis. PMID:27638769

  9. Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development.

    PubMed

    Ataca, Dalya; Caikovski, Marian; Piersigilli, Alessandra; Moulin, Alexandre; Benarafa, Charaf; Earp, Sarah E; Guri, Yakir; Kostic, Corinne; Arsenijevic, Yvan; Soininen, Raija; Apte, Suneel S; Brisken, Cathrin

    2016-11-15

    The ADAMTS family comprises 19 secreted metalloproteinases that cleave extracellular matrix components and have diverse functions in numerous disease and physiological contexts. A number of them remain 'orphan' proteases and among them is ADAMTS18, which has been implicated in developmental eye disorders, platelet function and various malignancies. To assess in vivo function of ADAMTS18, we generated a mouse strain with inactivated Adamts18 alleles. In the C57Bl6/Ola background, Adamts18-deficient mice are born in a normal Mendelian ratio, and are viable but show a transient growth delay. Histological examination revealed a 100% penetrant eye defect resulting from leakage of lens material through the lens capsule occurring at embryonic day (E)13.5, when the lens grows rapidly. Adamts18-deficient lungs showed altered bronchiolar branching. Fifty percent of mutant females are infertile because of vaginal obstruction due to either a dorsoventral vaginal septum or imperforate vagina. The incidence of ovarian rete is increased in the mutant mouse strain. Thus, Adamts18 is essential in the development of distinct tissues and the new mouse strain is likely to be useful for investigating ADAMTS18 function in human disease, particularly in the contexts of infertility and carcinogenesis. © 2016. Published by The Company of Biologists Ltd.

  10. Early developmental trajectories of number knowledge and math achievement from 4 to 10 years: Low-persistent profile and early-life predictors.

    PubMed

    Garon-Carrier, Gabrielle; Boivin, Michel; Lemelin, Jean-Pascal; Kovas, Yulia; Parent, Sophie; Séguin, Jean R; Vitaro, Frank; Tremblay, Richard E; Dionne, Ginette

    2018-06-01

    Little is known about the development of number knowledge (NK) and the antecedents of low-persistent NK profiles in early childhood. We documented the developmental trajectories of NK across the transition from preschool to elementary school, their predictive validity with respect to later math achievement, and the child and family early-life factors associated with low NK profiles. Children's NK was assessed four times at regular intervals between the ages 4 and 7 years in a large, representative population-based sample. Developmental trajectories of NK were established for 1597 children. These children were also assessed with respect to several features of their family environment at 5, 17, and 29 months, as well as their cognitive skills at age 41 months. Analyses revealed a best-fitting 4-trajectory model, characterized by Low-Increasing (10% of the children), Moderate-Increasing (39%), Moderate-Fast Increasing (32%) and High-Increasing (19%) groups. Children of these trajectory groups differed significantly with respect to math achievement at ages 8 and 10 years, with the Low-Increasing group persistently scoring lower than the other groups throughout these years. Children of Low-Increasing NK group were from household of lower income and father with low educational background, poorer early cognitive development, and more importantly, reduced visual-spatial skills and memory-span. Children displaying reduced cognitive abilities and impoverished living conditions early in life are at greater risk of low NK throughout late preschool and school entry, with ensuing difficulties in math achievement. They deserve early preventive attention to help alleviate later mathematic difficulties. Copyright © 2018 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  11. Early pregnancy exposure to antihistamines and risk of congenital heart defects: results of two case-control studies.

    PubMed

    Smedts, Huberdina P M; de Jonge, Linda; Bandola, Sarah J G; Baardman, Marlies E; Bakker, Marian K; Stricker, Bruno H C; Steegers-Theunissen, Régine P M

    2014-09-01

    We aimed to study the association between use of antihistamines in early pregnancy and congenital heart defects (CHD) in the offspring. Two case-control studies. HAVEN study, Erasmus MC, University Medical Centre, Rotterdam, and Eurocat Northern Netherlands (NNL), University Medical Center Groningen, Groningen, the Netherlands. We studied 361 children with CHD and 410 controls without congenital malformations from the HAVEN study and replicated the analyses in 445 children with CHD and 530 controls from the Eurocat NNL registry. Information about antihistamine use in early pregnancy and potential confounders was obtained from questionnaires postpartum. We calculated the association between antihistamines and CHD risk by multivariable logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (CI). In the HAVEN study, 25 of 771 mothers used antihistamines that were associated with an increased CHD risk (OR 3.0, 95% CI 1.2-7.3), particularly atrioventricular septal defects (AVSD) (OR 5.1, 95 % CI 1.3-20.5) and perimembranous ventricular septal defects (pVSD) (OR 5.1, 95% CI 1.8-14.4). Mothers with severe nausea who did not use antihistamines had a reduced risk (OR 0.7, 95% CI 0.5-0.98), whereas nauseous mothers using antihistamines showed an almost fivefold increased risk of pVSD (OR 4.8, 95% CI 1.1-21.8). The association between antihistamines and AVSD was confirmed in the Eurocat cohort (OR 3.5, 95% CI 1.4-8.7), but we could not replicate the association with overall CHD risk. We found a positive association between antihistamine use in early pregnancy and CHD risk, particularly AVSD, which seemed to be independent of nausea/vomiting.

  12. 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.

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

    PubMed Central

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

    2015-01-01

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

  14. Early life experience contributes to the developmental programming of depressive-like behaviour, neuroinflammation and oxidative stress.

    PubMed

    Réus, Gislaine Z; Fernandes, Gabrielly C; de Moura, Airam B; Silva, Ritele H; Darabas, Ana Caroline; de Souza, Thays G; Abelaira, Helena M; Carneiro, Celso; Wendhausen, Diogo; Michels, Monique; Pescador, Bruna; Dal-Pizzol, Felipe; Macêdo, Danielle S; Quevedo, João

    2017-12-01

    This study used an animal model of depression induced by maternal care deprivation (MCD) to investigate whether depressive behaviour, neuroinflammation and oxidative stress were underlying factors in developmental programming after early life stress. At postnatal days (PND) 20, 30, 40, and 60, individual subsets of animals were evaluated in behavioural tests and then euthanized to assess cytokine levels and oxidative stress parameters in the prefrontal cortex (PFC), hippocampus and serum. The results showed that MCD did not induce behavioural changes at PND 30 and 40. However, at PND 20 and 60, the rats displayed a depressive-like behaviour in the forced swimming test, without changes in locomotor spontaneous activity. In the brain and serum, the levels of pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α)) were increased, and the anti-inflammatory cytokine (interleukin-10) level was reduced throughout developmental programming (PND 20, 30, 40 and 60). Protein carbonyl levels increased in the brain at PND 30, 40 and 60. Superoxide dismutase (SOD) activity was decreased during all developmental programming phases evaluated in the brain. Catalase (CAT) activity was decreased at PND 20, 40 and 60 in the brain. Our results revealed that "critical episodes" in early life stressful events are able to induce behavioural alterations that persist into adulthood and can stimulate inflammation and oxidative damage in both central and peripheral systems, which are required for distinct patterns of resilience against psychiatric disorders later in life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Interdyad differences in early mother-infant face-to-face communication: real-time dynamics and developmental pathways.

    PubMed

    Lavelli, Manuela; Fogel, Alan

    2013-12-01

    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 with analyses performed dyad by dyad showed that most dyads go through 2 qualitatively different developmental phases of early face-to-face communication: After a phase of mutual attentiveness, mutual engagement begins in Weeks 7-8, with infant smiling and cooing bidirectionally linked with maternal mirroring. This gives rise to sequences of positive feedback that, by the 3rd month, dynamically stabilizes into innovative play routines. However, when there is a lack of bidirectional positive feedback between infant and maternal behaviors, and a lack of permeability of the early communicative patterns to incorporate innovations, the development of the mutual engagement phase is compromised. The findings contribute both to theories of relationship change processes and to clinical work with at-risk mother-infant interactions. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  16. 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

  17. Microspore Separation in the quartet 3 Mutants of Arabidopsis Is Impaired by a Defect in a Developmentally Regulated Polygalacturonase Required for Pollen Mother Cell Wall Degradation1

    PubMed Central

    Rhee, Seung Y.; Osborne, Erin; Poindexter, Patricia D.; Somerville, Chris R.

    2003-01-01

    Mutations in the QUARTET loci in Arabidopsis result in failure of microspore separation during pollen development due to a defect in degradation of the pollen mother cell wall during late stages of pollen development. Mutations in a new locus required for microspore separation, QRT3, were isolated, and the corresponding gene was cloned by T-DNA tagging. QRT3 encodes a protein that is approximately 30% similar to an endopolygalacturonase from peach (Prunus persica). The QRT3 protein was expressed in yeast (Saccharomyces cerevisiae) and found to exhibit polygalacturonase activity. In situ hybridization experiments showed that QRT3 is specifically and transiently expressed in the tapetum during the phase when microspores separate from their meiotic siblings. Immunohistochemical localization of QRT3 indicated that the protein is secreted from tapetal cells during the early microspore stage. Thus, QRT3 plays a direct role in degrading the pollen mother cell wall during microspore development. PMID:14551328

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

    PubMed

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

    2015-01-01

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

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

    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

  20. 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.

  1. Carbon nanotubes as VEGF carriers to improve the early vascularization of porcine small intestinal submucosa in abdominal wall defect repair

    PubMed Central

    Liu, Zhengni; Feng, Xueyi; Wang, Huichun; Ma, Jun; Liu, Wei; Cui, Daxiang; Gu, Yan; Tang, Rui

    2014-01-01

    Insufficient early vascularization in biological meshes, resulting in limited host tissue incorporation, is thought to be the primary cause for the failure of abdominal wall defect repair after implantation. The sustained release of exogenous angiogenic factors from a biocompatible nanomaterial might be a way to overcome this limitation. In the study reported here, multiwalled carbon nanotubes (MWNT) were functionalized by plasma polymerization to deliver vascular endothelial growth factor165 (VEGF165). The novel VEGF165-controlled released system was incorporated into porcine small intestinal submucosa (PSIS) to construct a composite scaffold. Scaffolds incorporating varying amounts of VEGF165-loaded functionalized MWNT were characterized in vitro. At 5 weight percent MWNT, the scaffolds exhibited optimal properties and were implanted in rats to repair abdominal wall defects. PSIS scaffolds incorporating VEGF165-loaded MWNT (VEGF–MWNT–PSIS) contributed to early vascularization from 2–12 weeks postimplantation and obtained more effective collagen deposition and exhibited improved tensile strength at 24 weeks postimplantation compared to PSIS or PSIS scaffolds, incorporating MWNT without VEGF165 loading (MWNT–PSIS). PMID:24648727

  2. A Taxonomy of Instructional Strategies in Early Childhood Education; Toward a Developmental Theory of Instructional Design.

    ERIC Educational Resources Information Center

    Vance, Barbara

    This paper suggests two steps in instructional deisgn for early childhood that can be derived from a recent major paper on instructional strategy taxonomy. These steps, together with the instructional design variables involved in each step, are reviewed relative to current research in child development and early education. The variables reviewed…

  3. 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…

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  5. Subacute developmental exposure of zebrafish to the organophosphate pesticide metabolite, chlorpyrifos-oxon, results in defects in Rohon-Beard sensory neuron development

    PubMed Central

    Jacobson, Saskia M.; Birkholz, Denise A.; McNamara, Marcy L.; Bharate, Sandip B.; George, Kathleen M.

    2010-01-01

    Organophosphate pesticides (OPs) are environmental toxicants known to inhibit the catalytic activity of acetylcholinesterase (AChE) resulting in hypercholinergic toxicity symptoms. In developing embryos, OPs have been hypothesized to affect both cholinergic and non-cholinergic pathways. In order to understand the neurological pathways affected by OP exposure during embryogenesis, we developed a subacute model of OP developmental exposure in zebrafish by exposing embryos to a dose of the OP metabolite chlorpyrifos oxon (CPO) that is non-lethal and significantly inhibited AChE enzymatic activity compared to control embryos (43% at 1 day post-fertilization (dpf) and 11% at 2 dpf). Phenotypic analysis of CPO-exposed embryos demonstrated that embryonic growth, as analyzed by gross morphology, was normal in 85% of treated embryos. Muscle fiber formation was similar to control embryos as analyzed by birefringence, and nicotinic acetylcholine receptor (nAChR) cluster formation was quantitatively similar to control embryos as analyzed by α-bungarotoxin staining. These results indicate that partial AChE activity during the early days of zebrafish development is sufficient for general development, muscle fiber, and nAChR development. Rohon-Beard (RB) sensory neurons exhibited aberrant peripheral axon extension and gene expression profiling suggests that several genes responsible for RB neurogenesis are down-regulated. Stability of CPO in egg water at 28.5 °C was determined by HPLC-UV-MS analysis which revealed that the CPO concentration used in our studies hydrolyzes in egg water with a half-life of one day. The result that developmental CPO exposure affected RB neurogenesis without affecting muscle fiber or nAChR cluster formation demonstrates that zebrafish are a strong model system for characterizing subtle neurological pathologies resulting from environmental toxicants. PMID:20701988

  6. Developmental toxicity of PAH mixtures in fish early life stages. Part I: adverse effects in rainbow trout.

    PubMed

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

    2014-12-01

    A new gravel-contact assay using rainbow trout, Oncorhynchus mykiss, embryos was developed to assess the toxicity of polycyclic aromatic hydrocarbons (PAHs) and other hydrophobic compounds. Environmentally realistic exposure conditions were mimicked with a direct exposure of eyed rainbow trout embryos incubated onto chemical-spiked gravels until hatching at 10 °C. Several endpoints were recorded including survival, hatching delay, hatching success, biometry, developmental abnormalities, and DNA damage (comet and micronucleus assays). This bioassay was firstly tested with two model PAHs, fluoranthene and benzo[a]pyrene. Then, the method was applied to compare the toxicity of three PAH complex mixtures characterized by different PAH compositions: a pyrolytic extract from a PAH-contaminated sediment (Seine estuary, France) and two petrogenic extracts from Arabian Light and Erika oils, at two environmental concentrations, 3 and 10 μg g(-1) sum of PAHs. The degree and spectrum of toxicity were different according to the extract considered. Acute effects including embryo mortality and decreased hatching success were observed only for Erika oil extract. Arabian Light and pyrolytic extracts induced mainly sublethal effects including reduced larvae size and hemorrhages. Arabian Light and Erika extracts both induced repairable DNA damage as revealed by the comet assay versus the micronucleus assay. The concentration and proportion of methylphenanthrenes and methylanthracenes appeared to drive the toxicity of the three PAH fractions tested, featuring a toxic gradient as follows: pyrolytic < Arabian Light < Erika. The minimal concentration causing developmental defects was as low as 0.7 μg g(-1) sum of PAHs, indicating the high sensitivity of the assay and validating its use for toxicity assessment of particle-bound pollutants.

  7. 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

  8. 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.

  9. Developmental disruption of medial prefrontal cortical GABAergic function by non-contingent cocaine exposure during early adolescence

    PubMed Central

    Cass, Daryn K.; Thomases, Daniel R.; Caballero, Adriana; Tseng, Kuei Y.

    2013-01-01

    Background Drug experimentation during adolescence is associated with increased risk of drug addiction relative to any other age group. To further our understanding on the neurobiology underlying such liability, we investigate how early adolescent cocaine experience impacts the overall medial prefrontal cortex (mPFC) network function in adulthood. Methods A non-contingent administration paradigm was used to assess the impact of early adolescent cocaine treatment (rats; postnatal days -PD- 35-40) on the overall inhibitory regulation of mPFC activity in adulthood (PD65-75) by means of histochemical and in vivo electrophysiological measures combined with pharmacological manipulations. Results Cocaine exposure during early adolescence yields a distinctive hyper-metabolic PFC state that was not observed in adult (PD75-80)-treated rats. Local field potential recordings expand upon these findings by showing that early adolescent cocaine exposure is associated with an attenuation of mPFC GABAergic inhibition evoked by ventral hippocampal stimulation at beta and gamma frequencies that endures throughout adulthood. Such cocaine-induced mPFC disinhibition was not observed in adult-exposed animals. Furthermore, the normal developmental upregulation of parvalbumin immunoreactivity observed in the mPFC from PD35 to PD65 is lacking following early adolescent cocaine treatment. Conclusion Our data indicate that repeated cocaine exposure during early adolescence can elicit a state of mPFC disinhibition resulting from a functional impairment of the local prefrontal GABAergic network that endures through adulthood. A lack of acquisition of prefrontal GABAergic function during adolescence could trigger long-term deficits in the mPFC that may increase the susceptibility for the onset of substance abuse and related psychiatric disorders. PMID:23558299

  10. Latent profiles of early developmental vulnerabilities in a New South Wales child population at age 5 years.

    PubMed

    Green, Melissa J; Tzoumakis, Stacy; Laurens, Kristin R; Dean, Kimberlie; Kariuki, Maina; Harris, Felicity; O'Reilly, Nicole; Chilvers, Marilyn; Brinkman, Sally A; Carr, Vaughan J

    2018-06-01

    Detecting the early emergence of childhood risk for adult mental disorders may lead to interventions for reducing subsequent burden of these disorders. We set out to determine classes of children who may be at risk for later mental disorder on the basis of early patterns of development in a population cohort, and associated exposures gleaned from linked administrative records obtained within the New South Wales Child Development Study. Intergenerational records from government departments of health, education, justice and child protection were linked with the Australian Early Development Census for a state population cohort of 67,353 children approximately 5 years of age. We used binary data from 16 subdomains of the Australian Early Development Census to determine classes of children with shared patterns of Australian Early Development Census-defined vulnerability using latent class analysis. Covariates, which included demographic features (sex, socioeconomic status) and exposure to child maltreatment, parental mental illness, parental criminal offending and perinatal adversities (i.e. birth complications, smoking during pregnancy, low birth weight), were examined hierarchically within latent class analysis models. Four classes were identified, reflecting putative risk states for mental disorders: (1) disrespectful and aggressive/hyperactive behaviour, labelled 'misconduct risk' ( N = 4368; 6.5%); (2) 'pervasive risk' ( N = 2668; 4.0%); (3) 'mild generalised risk' ( N = 7822; 11.6%); and (4) 'no risk' ( N = 52,495; 77.9%). The odds of membership in putative risk groups (relative to the no risk group) were greater among children from backgrounds of child maltreatment, parental history of mental illness, parental history of criminal offending, socioeconomic disadvantage and perinatal adversities, with distinguishable patterns of association for some covariates. Patterns of early childhood developmental vulnerabilities may provide useful indicators

  11. 77 FR 55605 - Early Warning Reporting, Foreign Defect Reporting, and Motor Vehicle and Equipment Recall...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-10

    ... requires quarterly reporting of early warning information: Production information; information on incidents... manufacturers, and other equipment manufacturers) and the annual production of the entity. The EWR information... vehicle type as part of [[Page 55608

  12. 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

  13. Right ventricular pressure response to exercise in adults with isolated ventricular septal defect closed in early childhood.

    PubMed

    Moller, Thomas; Lindberg, Harald; Lund, May Brit; Holmstrom, Henrik; Dohlen, Gaute; Thaulow, Erik

    2018-06-01

    We previously demonstrated an abnormally high right ventricular systolic pressure response to exercise in 50% of adolescents operated on for isolated ventricular septal defect. The present study investigated the prevalence of abnormal right ventricular systolic pressure response in 20 adult (age 30-45 years) patients who underwent surgery for early ventricular septal defect closure and its association with impaired ventricular function, pulmonary function, or exercise capacity. The patients underwent cardiopulmonary tests, including exercise stress echocardiography. Five of 19 patients (26%) presented an abnormal right ventricular systolic pressure response to exercise ⩾ 52 mmHg. Right ventricular systolic function was mixed, with normal tricuspid annular plane systolic excursion and fractional area change, but abnormal tricuspid annular systolic motion velocity (median 6.7 cm/second) and isovolumetric acceleration (median 0.8 m/second2). Left ventricular systolic and diastolic function was normal at rest as measured by the peak systolic velocity of the lateral wall and isovolumic acceleration, early diastolic velocity, and ratio of early diastolic flow to tissue velocity, except for ejection fraction (median 53%). The myocardial performance index was abnormal for both the left and right ventricle. Peak oxygen uptake was normal (mean z score -0.4, 95% CI -2.8-0.3). There was no association between an abnormal right ventricular systolic pressure response during exercise and right or left ventricular function, pulmonary function, or exercise capacity. Abnormal right ventricular pressure response is not more frequent in adult patients compared with adolescents. This does not support the theory of progressive pulmonary vascular disease following closure of left-to-right shunts.

  14. Reconstitution of wild type viral DNA in simian cells transfected with early and late SV40 defective genomes.

    PubMed

    O'Neill, F J; Gao, Y; Xu, X

    1993-11-01

    The DNAs of polyomaviruses ordinarily exist as a single circular molecule of approximately 5000 base pairs. Variants of SV40, BKV and JCV have been described which contain two complementing defective DNA molecules. These defectives, which form a bipartite genome structure, contain either the viral early region or the late region. The defectives have the unique property of being able to tolerate variable sized reiterations of regulatory and terminus region sequences, and portions of the coding region. They can also exchange coding region sequences with other polyomaviruses. It has been suggested that the bipartite genome structure might be a stage in the evolution of polyomaviruses which can uniquely sustain genome and sequence diversity. However, it is not known if the regulatory and terminus region sequences are highly mutable. Also, it is not known if the bipartite genome structure is reversible and what the conditions might be which would favor restoration of the monomolecular genome structure. We addressed the first question by sequencing the reiterated regulatory and terminus regions of E- and L-SV40 DNAs. This revealed a large number of mutations in the regulatory regions of the defective genomes, including deletions, insertions, rearrangements and base substitutions. We also detected insertions and base substitutions in the T-antigen gene. We addressed the second question by introducing into permissive simian cells, E- and L-SV40 genomes which had been engineered to contain only a single regulatory region. Analysis of viral DNA from transfected cells demonstrated recombined genomes containing a wild type monomolecular DNA structure. However, the complete defectives, containing reiterated regulatory regions, could often compete away the wild type genomes. The recombinant monomolecular genomes were isolated, cloned and found to be infectious. All of the DNA alterations identified in one of the regulatory regions of E-SV40 DNA were present in the recombinant

  15. Hepcidin, Cathelicidin-1 and IL-8 as immunological markers of responsiveness in early developmental stages of rainbow trout.

    PubMed

    Santana, Paula A; Guzmán, Fanny; Forero, Juan C; Luna, Omar F; Mercado, Luis

    2016-09-01

    During the early developmental stage of salmonids, high mortality occurs largely as a result of pathogens. These cause low immune competence in fry, producing disease, decreasing production and finally leading to economic losses. Therefore, the aim of this study was to characterise the developmental stages in which rainbow trout acquires immune response capability when challenged with LPS from Pseudomona aeruginosa for 8 h, studying the hepcidin, cathelicidin-1 and IL-8. Total RNA was extracted from fry at 34, 42, 56 and 66 days post hatching (dph). Hepcidin and cathelicidin-1 transcripts were detected only at days 34 and 42, whereas the IL-8 transcript was detected from day 34 to day 66. To analyse the protein expression in the fry, polyclonal anti-peptide antibodies were generated in rabbit. These three immune sera demonstrated the ability to recognise the whole molecule in biological samples. Immunofluorescence showed that skin, gills and intestine mainly responded to the LPS challenge, indicating that these portals of pathogen entry are capturing LPS. This study constitutes a valuable approach, since it has the potential to identify molecules with biological activity that can be used to evaluate the status of fry in culture. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Early Detection and Prevention of Mental Health Problems: Developmental Epidemiology and Systems of Support.

    PubMed

    Costello, E Jane

    2016-01-01

    This article reviews the role of developmental epidemiology in the prevention of child and adolescent mental disorders and the implications for systems of support. The article distinguishes between universal or primary prevention, which operates at the level of the whole community to limit risk exposure before the onset of symptoms, and secondary or targeted prevention, which operates by identifying those at high risk of developing a disorder. It discusses different aspects of time as it relates to risk for onset of disease, such as age at first exposure, duration of exposure, age at onset of first symptoms, and time until treatment. The study compares universal and targeted prevention, describing the systems needed to support each, and their unintended consequences.

  17. Single-cell RNA sequencing reveals developmental heterogeneity among early lymphoid progenitors.

    PubMed

    Alberti-Servera, Llucia; von Muenchow, Lilly; Tsapogas, Panagiotis; Capoferri, Giuseppina; Eschbach, Katja; Beisel, Christian; Ceredig, Rhodri; Ivanek, Robert; Rolink, Antonius

    2017-12-15

    Single-cell RNA sequencing is a powerful technology for assessing heterogeneity within defined cell populations. Here, we describe the heterogeneity of a B220 + CD117 int CD19 - NK1.1 - uncommitted hematopoietic progenitor having combined lymphoid and myeloid potential. Phenotypic and functional assays revealed four subpopulations within the progenitor with distinct lineage developmental potentials. Among them, the Ly6D + SiglecH - CD11c - fraction was lymphoid-restricted exhibiting strong B-cell potential, whereas the Ly6D - SiglecH - CD11c - fraction showed mixed lympho-myeloid potential. Single-cell RNA sequencing of these subsets revealed that the latter population comprised a mixture of cells with distinct lymphoid and myeloid transcriptional signatures and identified a subgroup as the potential precursor of Ly6D + SiglecH - CD11c - Subsequent functional assays confirmed that B220 + CD117 int CD19 - NK1.1 - single cells are, with rare exceptions, not bipotent for lymphoid and myeloid lineages. A B-cell priming gradient was observed within the Ly6D + SiglecH - CD11c - subset and we propose a herein newly identified subgroup as the direct precursor of the first B-cell committed stage. Therefore, the apparent multipotency of B220 + CD117 int CD19 - NK1.1 - progenitors results from underlying heterogeneity at the single-cell level and highlights the validity of single-cell transcriptomics for resolving cellular heterogeneity and developmental relationships among hematopoietic progenitors. © 2017 The Authors.

  18. Early developmental, temperamental and educational problems in 'substance use disorder' patients with and without ADHD. Does ADHD make a difference?

    PubMed

    Skutle, Arvid; Bu, Eli Torild Hellandsjø; Jellestad, Finn Konow; van Emmerik-van Oortmerssen, Katelijne; Dom, Geert; Verspreet, Sofie; Carpentier, Pieter Jan; Ramos-Quiroga, Josep Antoni; Franck, Johan; Konstenius, Maija; Kaye, Sharlene; Demetrovics, Zsolt; Barta, Csaba; Fatséas, Melina; Auriacombe, Marc; Johnson, Brian; Faraone, Stephen V; Levin, Frances R; Allsop, Steve; Carruthers, Susan; Schoevers, Robert A; Koeter, Maarten W J; van den Brink, Wim; Moggi, Franz; Møller, Merete; van de Glind, Geurt

    2015-12-01

    The prevalence of ADHD among patients with substance use disorder (SUD) is substantial. This study addressed the following research questions: Are early developmental, temperamental and educational problems overrepresented among SUD patients with ADHD compared to SUD patients without ADHD? Do this comorbid group receive early help for their ADHD, and are there signs of self-medicating with illicit central stimulants? An international, multi-centre cross-sectional study was carried out involving seven European countries, with 1205 patients in treatment for SUD. The mean age was 40 years and 27% of the sample was female. All participants were interviewed with the Mini International Neuropsychiatric Interview Plus and the Conners' Adult ADHD Diagnostic Interview for DSM-IV. SUD patients with ADHD ( n  = 196; 16.3% of the total sample) had a significantly slower infant development than SUD patients without ADHD ( n  = 1,009; 83.4%), had greater problems controlling their temperament, and had lower educational attainment. Only 24 (12%) of the current ADHD positive patients had been diagnosed and treated during childhood and/or adolescence. Finally, SUD patients with ADHD were more likely to have central stimulants or cannabis as their primary substance of abuse, whereas alcohol use was more likely to be the primary substance of abuse in SUD patients without ADHD. The results emphasize the importance of early identification of ADHD and targeted interventions in the health and school system, as well as in the addiction field.

  19. Preventing High-Risk Sexual Behavior in Early Adulthood with Family Interventions in Adolescence: Outcomes and Developmental Processes

    PubMed Central

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

    2013-01-01

    Adolescent study participants who engaged in a brief, family-centered intervention (the Family Check-Up; FCU) were later assessed for the intervention’s effects on high-risk sexual behavior (HRSB) in early adulthood (age 22). Participants (N = 998 adolescents and their families) were randomly assigned to a family-centered intervention in 6th grade and were offered a gated, multilevel intervention that included (a) a school-based family resource center, (b) the FCU, and (c) more intensive, family-based treatment. All services were voluntary, but high-risk families were actively recruited into the FCU. Approximately 23% of the intervention families engaged in the FCU and approximately 18% engaged in more intensive treatment. Using an intent-to-treat design, we found that the direct effect of the FCU on HRSB was not significant; however, an analysis of the developmental processes indicated that intervention families demonstrated improved family relationship quality when compared to control families, which in turn resulted in lower levels of HRSB in early adulthood. Further, the significant effect of family relationship quality on HRSB was mediated by differences in parental monitoring and early sexual activity, and these effects varied as a function of gender and ethnicity. Indirect effects of the FCU on HRSB were significant via multiple different pathways. The implications of these findings for enhancing the impact of family-centered interventions are discussed. PMID:23536124

  20. Demonstration of Parent Training to Address Early Self-Injury in Young Children with Intellectual and Developmental Delays.

    PubMed

    Fodstad, Jill C; Kirsch, Alexandra; Faidley, Micah; Bauer, Nerissa

    2018-06-20

    Individuals with intellectual and developmental disabilities (IDD) are at a high risk for engaging in self-injurious behavior (SIB). Prognosis is poor when SIB emerges early. Limited research exists on interventions teaching parents how to manage their young child's SIB. This investigation assessed the feasibility of adapting an applied behavior analytic parent training program with 11 parents of children 1-5 years of age with IDD and SIB. Quantitative and observational measures were used to assess outcomes; semi-structured interviews assessed caregiver satisfaction. Outcomes yielded preliminary data suggesting the adapted curriculum was feasible and acceptable to parents. Initial efficacy outcomes yielded decreases in SIB and observed negative parent-child interactions on pre- and post-measures. Qualitative data provided areas for further curriculum refinement.

  1. Early defect of transforming growth factor β1 formation in Huntington’s disease

    PubMed Central

    Battaglia, Giuseppe; Cannella, Milena; Riozzi, Barbara; Orobello, Sara; Maat-Schieman, Marion L; Aronica, Eleonora; Busceti, Carla Letizia; Ciarmiello, Andrea; Alberti, Silvia; Amico, Enrico; Sassone, Jenny; Sipione, Simonetta; Bruno, Valeria; Frati, Luigi; Nicoletti, Ferdinando; Squitieri, Ferdinando

    2011-01-01

    Abstract A defective expression or activity of neurotrophic factors, such as brain- and glial-derived neurotrophic factors, contributes to neuronal damage in Huntington’s disease (HD). Here, we focused on transforming growth factor-β (TGF-β1), a pleiotropic cytokine with an established role in mechanisms of neuroprotection. Asymptomatic HD patients showed a reduction in TGF-β1 levels in the peripheral blood, which was related to trinucleotide mutation length and glucose hypometabolism in the caudate nucleus. Immunohistochemical analysis in post-mortem brain tissues showed that TGF-β1 was reduced in cortical neurons of asymptomatic and symptomatic HD patients. Both YAC128 and R6/2 HD mutant mice showed a reduced expression of TGF-β1 in the cerebral cortex, localized in neurons, but not in astrocytes. We examined the pharmacological regulation of TGF-β1 formation in asymptomatic R6/2 mice, where blood TGF-β1 levels were also reduced. In these R6/2 mice, both the mGlu2/3 metabotropic glutamate receptor agonist, LY379268, and riluzole failed to increase TGF-β1 formation in the cerebral cortex and corpus striatum, suggesting that a defect in the regulation of TGF-β1 production is associated with HD. Accordingly, reduced TGF-β1 mRNA and protein levels were found in cultured astrocytes transfected with mutated exon 1 of the human huntingtin gene, and in striatal knock-in cell lines expressing full-length huntingtin with an expanded glutamine repeat. Taken together, our data suggest that serum TGF-β1 levels are potential biomarkers of HD development during the asymptomatic phase of the disease, and raise the possibility that strategies aimed at rescuing TGF-β1 levels in the brain may influence the progression of HD. PMID:20082658

  2. 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.

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

    PubMed

    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

    2016-05-01

    We sought to investigate the diagnostic yield and mutation spectrum in previously reported genes for early-onset epilepsy and disorders of severe developmental delay. 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. 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. 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. Early deprivation disruption of associative learning is a developmental pathway to depression and social problems.

    PubMed

    Sheridan, Margaret A; McLaughlin, Katie A; Winter, Warren; Fox, Nathan; Zeanah, Charles; Nelson, Charles A

    2018-06-07

    Exposure to psychosocial deprivation is associated with elevations in numerous forms of impairment throughout the life-course. Disruptions in associative learning may be a key mechanism through which adversity, particularly psychosocial deprivation, increases risk for impairment. Existing data consistent with this claim come entirely from correlational studies. Here, we present the first experimental evidence relating psychosocial deprivation and disruptions in multiple forms of associative learning. Using data from the Bucharest Early Intervention Project, we demonstrate that randomized placement into a family caregiving environment during the infant/toddler period as compared to prolonged institutional care normalizes two forms of associative learning in early adolescence: reward responsivity and implicit motor learning. These forms of associative learning significantly mediate the effect of institutional rearing on depressive symptoms and peer relationships. In sum, we provide evidence for a novel pathway linking early experience to psychopathology and peer relationships through basic associative learning mechanisms.

  5. 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…

  6. 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…

  7. Social Studies, Social Competence and Citizenship in Early Childhood Education: Developmental Principles Guide Appropriate Practice

    ERIC Educational Resources Information Center

    Kemple, Kristen M.

    2017-01-01

    The purpose of this article is to examine the nature of appropriate social studies education in the Kindergarten and Pre-Kindergarten years. The importance of social competence development as a basic foundation of the social studies in the early years of schooling is examined, with particular attention to the commonalities shared between goals and…

  8. 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…

  9. Developmental Trajectories of Cigarette Smoking from Adolescence to the Early Thirties: Personality and Behavioral Risk Factors

    PubMed Central

    Brook, David W.; Brook, Judith S.; Zhang, Chenshu; Whiteman, Martin; Cohen, Patricia; Finch, Stephen J.

    2013-01-01

    The purpose of this study was to identify distinct trajectories of cigarette smoking from ages 14 to 32, and to examine adolescent personality factors that distinguish trajectories of smoking behavior. Participants (N=975) were randomly selected and followed prospectively since 1975. Follow-up data on cigarette use and personality and behavioral attributes were collected at five points in time, using structured interviews given in private by trained interviewers. Of these subjects, 746 comprised the cohort used in this study. Growth mixture modeling identified five smoking trajectory groups: nonsmokers, occasional smokers, late starters, quitters, and heavy/continuous smokers. Adolescent personality and behavioral risk factors such as lower ego integration, more externalizing behavior, and lower educational aspirations distinguished the trajectory groups. No gender differences were noted. The findings supported the hypotheses indicating multiple distinct trajectory groups of smoking behavior. Smoking behavior appeared in early adolescence and most often continued into adulthood. Emotional difficulties (i.e., lower ego integration), externalizing behavior, and lower educational aspirations in early adolescence were associated both with smoking at an early age and with continuing to smoke into the thirties. To be more effective, smoking prevention programs should target personality and behavioral variations, before smoking becomes habitual, particularly focused on characteristics reflecting behavioral problems as manifested in emotional difficulties, externalizing behavior, and low educational aspirations in early adolescence. The implications for research, prevention, and treatment are discussed. PMID:18686175

  10. 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…

  11. 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…

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  13. 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…

  14. 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…

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

    ERIC Educational Resources Information Center

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

    2016-01-01

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

  16. 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…

  17. The Developmental Trajectories of Depressive Symptoms in Early Adolescence: An Examination of School-Related Factors

    ERIC Educational Resources Information Center

    Wu, Pei-Chen

    2017-01-01

    This study investigated the heterogeneity of depressive symptom trajectories and the roles of school-related factors in predicting the membership of different trajectories in a sample of early adolescents in Taiwan. In all, 870 junior high school students were followed for 3 years. Using growth mixture modeling, the study identified four distinct…

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

    PubMed

    McCoy, Dana Charles; Peet, Evan D; Ezzati, Majid; Danaei, Goodarz; Black, Maureen M; Sudfeld, Christopher R; Fawzi, Wafaie; Fink, Günther

    2016-06-01

    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. 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 ages 3 and 4 y), followed by

  19. Developmental Changes in Early Comprehension and Production of Drawings: Evidence From Two Socioeconomic Backgrounds.

    PubMed

    Salsa, Analía M; Vivaldi, Romina

    2017-01-01

    Two studies examined young children's comprehension and production of representational drawings across and within 2 socioeconomic strata (SES). Participants were 130 middle-SES (MSES) and low-SES (LSES) Argentine children, from 30 to 60 months old, given a task with 2 phases, production and comprehension. The production phase assessed free drawing and drawings from simple 3-dimensional objects (model drawing); the comprehension phase assessed children's understanding of an adult's line drawings of the objects. MSES children solved the comprehension phase of the task within the studied age range; representational production emerged first in model drawing (42 months) and later in free drawing (48 months). The same developmental pathway was observed in LSES children but with a clear asynchrony in the age of onset of comprehension and production: Children understood the symbolic nature of drawings at 42 months old and the first representational drawings were found at 60 months old. These results provide empirical evidence that support the crucial influence of social experiences by organizing and constraining graphic development.

  20. Early adolescent outcomes of joint developmental trajectories of problem behavior and IQ in childhood.

    PubMed

    Flouri, Eirini; Papachristou, Efstathios; Midouhas, Emily; Joshi, Heather; Ploubidis, George B; Lewis, Glyn

    2018-04-16

    General cognitive ability (IQ) and problem behavior (externalizing and internalizing problems) are variable and inter-related in children. However, it is unknown how they co-develop in the general child population and how their patterns of co-development may be related to later outcomes. We carried out this study to explore this. Using data from 16,844 Millennium Cohort Study children, we fitted three-parallel-process growth mixture models to identify joint developmental trajectories of internalizing, externalizing and IQ scores at ages 3-11 years. We then examined their associations with age 11 outcomes. We identified a typically developing group (83%) and three atypical groups, all with worse behavior and ability: children with improving behavior and low (but improving in males) ability (6%); children with persistently high levels of problems and low ability (5%); and children with worsening behavior and low ability (6%). Compared to typically developing children, the latter two groups were more likely to show poor decision-making, be bullies or bully victims, engage in antisocial behaviors, skip and dislike school, be unhappy and have low self-esteem. By contrast, children (especially males) in the improver group had outcomes that were similar to, or even better than, those of their typically developing peers. These findings encourage the development of interventions to target children with both cognitive and behavioral difficulties.

  1. Regional white matter development in very preterm infants: perinatal predictors and early developmental outcomes.

    PubMed

    Rogers, Cynthia E; Smyser, Tara; Smyser, Christopher D; Shimony, Joshua; Inder, Terrie E; Neil, Jeffrey J

    2016-01-01

    Preterm infants are at risk for white matter (WM) injury and adverse neurodevelopmental outcomes. Serial diffusion tensor magnetic resonance imaging data were obtained from very preterm infants (N = 78) born <30 wk gestation imaged up to four times from 26-42 wk postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with ≥2 scans (N = 50). Sixty-five children underwent neurodevelopmental testing at 2 y of age. FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum, and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with patent ductus arteriosus had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At 2 y of age, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent age. Better social-emotional competence was related to lower FA in the left cingulum bundle. This study demonstrates regional variability in the susceptibility/sensitivity of WM maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates.

  2. Early Orthodontic Tooth Movement into Regenerative Bony Defects: A Case Report.

    PubMed

    Tsai, Hui-Chen; Yao, Chung-Chen Jane; Wong, Man-Ying

    Early orthodontic tooth movement following regenerative surgery is controversial. In this case, during protraction of the maxillary right first premolar to substitute for the long-term missing maxillary right canine, Bio-Oss and Bio-Gide were used for lateral ridge augmentation at the area of the maxillary right lateral incisor and to cover the denuded surface at the buccal side of the first premolar. Orthodontic tooth movement (OTM) commenced 2 weeks after regenerative surgery. After 8 months, new bone formation was observed on the root surface of the first premolar during implant surgery. A cone beam computed tomography scan taken 1.5 years postsurgery revealed good maintenance of regenerative bone at the same site. This satisfactory outcome of early OTM following regenerative surgery suggests biomechanical stimulation may not jeopardize the regenerative effect.

  3. Nervous-Tissue-Specific Elimination of Microtubule-Actin Crosslinking Factor 1a Results in Multiple Developmental Defects in the Mouse Brain

    PubMed Central

    Goryunov, Dmitry; He, Cui-Zhen; Lin, Chyuan-Sheng; Leung, Conrad L.; Liem, Ronald K. H.

    2010-01-01

    The microtubule-actin crosslinking factor 1 (MACF1) is a ubiquitous cytoskeletal linker protein with multiple spliced isoforms expressed in different tissues. The MACF1a isoform contains microtubule and actin binding regions and is expressed at high levels in the nervous system. Macf1−/− mice are early embryonic lethal and hence the role of MACF1 in the nervous system could not be determined. We have specifically knocked out MACF1a in the developing mouse nervous system using Cre/loxP technology. Mutant mice died within 24–36 hrs after birth of apparent respiratory distress. Their brains displayed a disorganized cerebral cortex with a mixed layer structure, heterotopia in the pyramidal layer of the hippocampus, disorganized thalamocortical and corticofugal fibers, and aplastic anterior and hippocampal commissures. Embryonic neurons showed a defect in traversing the cortical plate. Our data suggest a critical role for MACF1 in neuronal migration that is dependent on its ability to interact with both microfilaments and microtubules. PMID:20170731

  4. Nervous-tissue-specific elimination of microtubule-actin crosslinking factor 1a results in multiple developmental defects in the mouse brain.

    PubMed

    Goryunov, Dmitry; He, Cui-Zhen; Lin, Chyuan-Sheng; Leung, Conrad L; Liem, Ronald K H

    2010-05-01

    The microtubule-actin crosslinking factor 1 (MACF1) is a ubiquitous cytoskeletal linker protein with multiple spliced isoforms expressed in different tissues. The MACF1a isoform contains microtubule and actin-binding regions and is expressed at high levels in the nervous system. Macf1-/- mice are early embryonic lethal and hence the role of MACF1 in the nervous system could not be determined. We have specifically knocked out MACF1a in the developing mouse nervous system using Cre/loxP technology. Mutant mice died within 24-36h after birth of apparent respiratory distress. Their brains displayed a disorganized cerebral cortex with a mixed layer structure, heterotopia in the pyramidal layer of the hippocampus, disorganized thalamocortical and corticofugal fibers, and aplastic anterior and hippocampal commissures. Embryonic neurons showed a defect in traversing the cortical plate. Our data suggest a critical role for MACF1 in neuronal migration that is dependent on its ability to interact with both microfilaments and microtubules. Copyright 2010 Elsevier Inc. All rights reserved.

  5. 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

  6. Epigenetic Vestiges of Early Developmental Adversity: Childhood Stress Exposure and DNA Methylation in Adolescence

    PubMed Central

    Essex, Marilyn J.; Boyce, W. Thomas; Hertzman, Clyde; Lam, Lucia L.; Armstrong, Jeffrey M.; Neumann, Sarah M.A.; Kobor, Michael S.

    2011-01-01

    Fifteen-year-old adolescents (N=109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents’ infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide (CpG) sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children’s early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children’s gender. To the authors’ knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents’ genomic DNA. PMID:21883162

  7. Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence.

    PubMed

    Essex, Marilyn J; Boyce, W Thomas; Hertzman, Clyde; Lam, Lucia L; Armstrong, Jeffrey M; Neumann, Sarah M A; Kobor, Michael S

    2013-01-01

    Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents' infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children's early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children's gender. To the authors' knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents' genomic DNA. © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.

  8. The Blind Child and His Parents: Congenital Visual Defect and the Repercussion of Family Attitudes on the Early Development of the Child.

    ERIC Educational Resources Information Center

    Lairy, G. C.; Harrison-Covello, A.

    Discussed are the effects of parental attitudes on the early development of the congenitally blind child. The disproportion between family reactions and the limitations of the handicap are attributed to symbolic aspects of blindness and previously existing pathological elements in the parents. Compared are developmental milestones (such as the…

  9. Early-stage valuation of medical devices: the role of developmental uncertainty.

    PubMed

    Girling, Alan; Young, Terry; Brown, Celia; Lilford, Richard

    2010-08-01

    At the concept stage, many uncertainties surround the commercial viability of a new medical device. These include the ultimate functionality of the device, the cost of producing it and whether, and at what price, it can be sold to a health-care provider (HCP). Simple assessments of value can be made by estimating such unknowns, but the levels of uncertainty may mean that their operational value for investment decisions is unclear. However, many decisions taken at the concept stage are reversible and will be reconsidered later before the product is brought to market. This flexibility can be exploited to enhance early-stage valuations. To develop a framework for valuing a new medical device at the concept stage that balances benefit to the HCP against commercial costs. This is done within a simplified stage-gated model of the development cycle for new products. The approach is intended to complement existing proposals for the evaluation of the commercial headroom available to new medical products. A model based on two decision gates can lead to lower bounds (underestimates) for product value that can serve to support a decision to develop the product. Quantifiable uncertainty that can be resolved before the device is brought to market will generally enhance early-stage valuations of the device, and this remains true even when some components of uncertainty cannot be fully described. Clinical trials and other evidence-gathering activities undertaken as part of the development process can contribute to early-stage estimates of value.

  10. 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

  11. Developmental Origins of Rumination in Middle Childhood: The Roles of Early Temperament and Positive Parenting.

    PubMed

    Schweizer, Tina H; Olino, Thomas M; Dyson, Margaret W; Laptook, Rebecca S; Klein, Daniel N

    2017-09-08

    Rumination, a thinking style characterized by a repetitive inward focus on negative cognitions, has been linked to internalizing disorders, particularly depression. Moreover, research suggests that rumination may be a cognitive vulnerability that predisposes individuals to psychopathology. Surprisingly little is known, however, about the etiology and development of rumination. The present study examined the role of specific components of child temperamental negative emotionality (sadness, fear, anger) and effortful control (inhibition), as well as parenting behaviors during early childhood on the development of rumination in middle childhood. Early childhood (age 3) temperament and parenting behaviors were assessed observationally and rumination was self-reported in middle childhood (age 9) in a large community sample (N = 425; 47.1% female). Two significant interactions emerged. First, temperamental anger interacted with inhibitory control (IC) such that high anger and low IC predicted higher levels of rumination, whereas low anger and low IC predicted lower levels of rumination. Second, IC interacted with parenting such that children with low IC and positive parenting had lower levels of rumination. In contrast, children with high IC reported similar levels of rumination regardless of parenting quality. Overall, these findings highlight the interplay of early IC with temperamental anger and positive parenting in the development of ruminative tendencies in middle childhood.

  12. Developmental treatment with bisphenol A or ethinyl estradiol causes few alterations on early preweaning measures.

    PubMed

    Ferguson, Sherry A; Law, Charles D; Abshire, Jordan S

    2011-11-01

    Because bisphenol A (BPA) exposure is nearly ubiquitous, increased knowledge of its potential effects on development will enable better risk assessment and regulatory guidance. Here, Sprague-Dawley rats were reared in low exogenous estrogen environments. After breeding at adulthood, dams were gavaged on gestational days (GDs) 6-21 with vehicle (VEH), 2.5 or 25.0 μg/kg/day BPA, or 5.0 or 10.0 μg/kg/day ethinyl estradiol (EE₂). Offspring were orally treated on postnatal days (PNDs) 1-21 with the same dose the dam received. Relative to the VEH group, dams of both EE₂-treated groups weighed less throughout gestation and lactation. PND 1 absolute anogenital distance and anogenital index were unaltered by any treatment. Ages at fur development and eye and ear opening were unaffected by any treatment. Despite a significant treatment effect, no group was significantly different from VEH in PNDs 3-6 righting latencies; although males had shorter latencies and all latencies decreased with age. PNDs 8-11 slant board behavior was unaffected by any treatment; however, males had shorter turning latencies and latencies decreased with age. Preweaning body weights of BPA- and EE₂-treated groups as well as naive controls were less than VEH. No treatment affected PND 21 whole or regional brain weights or levels of estradiol, testosterone, corticosterone, T3, T4, luteinizing hormone, ghrelin, or leptin. These results add to the literature indicating that developmental BPA treatment at these doses has no effects on gestational or lactational body weight, offspring anogenital distance, preweaning behaviors or hormone levels, and whole and regional brain weights measured at weaning.

  13. 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…

  14. 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…

  15. The Contribution of M.N. Skatkin to the Advancement of Didactic Ideas about the Developmental Role of Education (1950s to Early 1960s)

    ERIC Educational Resources Information Center

    Selivyorstova, E. N.

    2015-01-01

    The article analyzes the research that M.N. Skatkin conducted during the 1950s and early 1960s and describes its contribution to the elabortion of Russian teaching science approaches towards understanding of the developmental role of education. [This article was translated by Kenneth Cargill.

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

    ERIC Educational Resources Information Center

    De Feyter, Jessica Johnson; Winsler, Adam

    2009-01-01

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

  17. 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…

  18. 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,…

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

    PubMed

    Wagner, Norman; Müller, Hendrik; Viertel, Bruno

    2017-01-01

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

  20. 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

  1. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. 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

  3. 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

  4. Median network analysis of defectively sequenced entire mitochondrial genomes from early and contemporary disease studies.

    PubMed

    Bandelt, Hans-Jürgen; Yao, Yong-Gang; Bravi, Claudio M; Salas, Antonio; Kivisild, Toomas

    2009-03-01

    Sequence analysis of the mitochondrial genome has become a routine method in the study of mitochondrial diseases. Quite often, the sequencing efforts in the search of pathogenic or disease-associated mutations are affected by technical and interpretive problems, caused by sample mix-up, contamination, biochemical problems, incomplete sequencing, misdocumentation and insufficient reference to previously published data. To assess data quality in case studies of mitochondrial diseases, it is recommended to compare any mtDNA sequence under consideration to their phylogenetically closest lineages available in the Web. The median network method has proven useful for visualizing potential problems with the data. We contrast some early reports of complete mtDNA sequences to more recent total mtDNA sequencing efforts in studies of various mitochondrial diseases. We conclude that the quality of complete mtDNA sequences generated in the medical field in the past few years is somewhat unsatisfactory and may even fall behind that of pioneer manual sequencing in the early nineties. Our study provides a paradigm for an a posteriori evaluation of sequence quality and for detection of potential problems with inferring a pathogenic status of a particular mutation.

  5. Early reproductive developmental anatomy in Decaisnea (Lardizabalaceae) and its systematic implications.

    PubMed

    Wang, Hua-Feng; Friedman, Cynthia Ross; Zhu, Zhi-Xin; Qin, Hai-Ning

    2009-11-01

    Decaisnea insignis, known as 'dead man's fingers' (Lardizabalaceae), is widely distributed in China and the Himalayan foothill countries. This economically important plant, which is the only species in the genus, has not been the subject of any embryological studies aside from one brief, older paper that lacks micrographs. Data on Decaisnea are also important because its systematic position has been unstable since the genus was established in 1855. Therefore, the objectives of this study were: (a) to use modern microscopy to document early reproductive anatomical development in Decaisnea; and (b) to compare qualitatively these early embryological characters with allied taxa in a systematic context. Decaisnea insignis floral buds and inflorescences were regularly collected from Shaanxi Province, China and prepared for light microscopy. The embryological characters studied were qualitatively compared with those of allied taxa via a thorough examination of the existing literature. Early reproductive anatomy in Decaisnea was documented and novel revelations made. It was discovered that the pollen is shed when three-celled (not two-celled, as previously reported), and that endosperm formation is nuclear (not cellular or helobial, as previously reported). These two newly revealed embryological characters are not found in any other members of Lardizabalaceae. Furthermore, neither are persistent antipodal cells, which we confirmed to be present in Decaisnea. Decaisnea and other Lardizabalaceae characteristically have tetrasporangiate anthers, a secretory tapetum, simultaneous microsporocyte cytokinesis, primarily bitegmic, crassinucellate ovules, and a Polygonum type embryo sac. However, in the family, persistent antipodals, nuclear endosperm, and pollen shed at the three-celled stage are only found in Decaisnea. These embryological data prompted the suggestion that Decaisnea needs elevation above the level of genus.

  6. Early reproductive developmental anatomy in Decaisnea (Lardizabalaceae) and its systematic implications

    PubMed Central

    Wang, Hua-Feng; Friedman, Cynthia Ross; Zhu, Zhi-Xin; Qin, Hai-Ning

    2009-01-01

    Background and Aims Decaisnea insignis, known as ‘dead man's fingers’ (Lardizabalaceae), is widely distributed in China and the Himalayan foothill countries. This economically important plant, which is the only species in the genus, has not been the subject of any embryological studies aside from one brief, older paper that lacks micrographs. Data on Decaisnea are also important because its systematic position has been unstable since the genus was established in 1855. Therefore, the objectives of this study were: (a) to use modern microscopy to document early reproductive anatomical development in Decaisnea; and (b) to compare qualitatively these early embryological characters with allied taxa in a systematic context. Methods Decaisnea insignis floral buds and inflorescences were regularly collected from Shaanxi Province, China and prepared for light microscopy. The embryological characters studied were qualitatively compared with those of allied taxa via a thorough examination of the existing literature. Key Results Early reproductive anatomy in Decaisnea was documented and novel revelations made. It was discovered that the pollen is shed when three-celled (not two-celled, as previously reported), and that endosperm formation is nuclear (not cellular or helobial, as previously reported). These two newly revealed embryological characters are not found in any other members of Lardizabalaceae. Furthermore, neither are persistent antipodal cells, which we confirmed to be present in Decaisnea. Conclusions Decaisnea and other Lardizabalaceae characteristically have tetrasporangiate anthers, a secretory tapetum, simultaneous microsporocyte cytokinesis, primarily bitegmic, crassinucellate ovules, and a Polygonum type embryo sac. However, in the family, persistent antipodals, nuclear endosperm, and pollen shed at the three-celled stage are only found in Decaisnea. These embryological data prompted the suggestion that Decaisnea needs elevation above the level of genus

  7. Early interventions for youths at high risk for bipolar disorder: a developmental approach.

    PubMed

    Benarous, Xavier; Consoli, Angèle; Milhiet, Vanessa; Cohen, David

    2016-03-01

    In recent decades, ongoing research programmes on primary prevention and early identification of bipolar disorder (BD) have been developed. The aim of this article is to review the principal forms of evidence that support preventive interventions for BD in children and adolescents and the main challenges associated with these programmes. We performed a literature review of the main computerised databases (MEDLINE, PUBMED) and a manual search of the literature relevant to prospective and retrospective studies of prodromal symptoms, premorbid stages, risk factors, and early intervention programmes for BD. Genetic and environmental risk factors of BD were identified. Most of the algorithms used to measure the risk of developing BD and the early interventions programmes focused on the familial risk. The prodromal signs varied greatly and were age dependent. During adolescence, depressive episodes associated with genetic or environmental risk factors predicted the onset of hypomanic/manic episodes over subsequent years. In prepubertal children, the lack of specificity of clinical markers and difficulties in mood assessment were seen as impeding preventive interventions at these ages. Despite encouraging results, biomarkers have not thus far been sufficiently validated in youth samples to serve as screening tools for prevention. Additional longitudinal studies in youths at high risk of developing BD should include repeated measures of putative biomarkers. Staging models have been developed as an integrative approach to specify the individual level of risk based on clinical (e.g. prodromal symptoms and familial history of BD) and non-clinical (e.g. biomarkers and neuroimaging) data. However, there is still a lack of empirically validated studies that measure the benefits of using these models to design preventive intervention programmes.

  8. Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats.

    PubMed

    van der Stok, Johan; Lozano, Daniel; Chai, Yoke Chin; Amin Yavari, Saber; Bastidas Coral, Angela P; Verhaar, Jan A N; Gómez-Barrena, Enrique; Schrooten, Jan; Jahr, Holger; Zadpoor, Amir A; Esbrit, Pedro; Weinans, Harrie

    2015-05-01

    A promising bone graft substitute is porous titanium. Porous titanium, produced by selective laser melting (SLM), can be made as a completely open porous and load-bearing scaffold that facilitates bone regeneration through osteoconduction. In this study, the bone regenerative capacity of porous titanium is improved with a coating of osteostatin, an osteoinductive peptide that consists of the 107-111 domain of the parathyroid hormone (PTH)-related protein (PTHrP), and the effects of this osteostatin coating on bone regeneration were evaluated in vitro and in vivo. SLM-produced porous titanium received an alkali-acid-heat treatment and was coated with osteostatin through soaking in a 100 nM solution for 24 h or left uncoated. Osteostatin-coated scaffolds contained ∼0.1 μg peptide/g titanium, and in vitro 81% was released within 24 h. Human periosteum-derived osteoprogenitor cells cultured on osteostatin-coated scaffolds did not induce significant changes in osteogenic (alkaline phosphatase [ALP], collagen type 1 [Col1], osteocalcin [OCN], runt-related transcription factor 2 [Runx2]), or angiogenic (vascular endothelial growth factor [VEGF]) gene expression; however, it resulted in an upregulation of osteoprotegerin (OPG) gene expression after 24 h and a lower receptor activator of nuclear factor kappa-B ligand (RankL):OPG mRNA ratio. In vivo, osteostatin-coated, porous titanium implants increased bone regeneration in critical-sized cortical bone defects (p=0.005). Bone regeneration proceeded until 12 weeks, and femurs grafted with osteostatin-coated implants and uncoated implants recovered, respectively, 66% and 53% of the original femur torque strength (97±31 and 77±53 N·mm, not significant). In conclusion, the osteostatin coating improved bone regeneration of porous titanium. This effect was initiated after a short burst release and might be related to the observed in vitro upregulation of OPG gene expression by osteostatin in osteoprogenitor

  9. Developmental Associations Between Conduct Problems and Expressive Language in Early Childhood: A Population-Based Study.

    PubMed

    Girard, Lisa-Christine; Pingault, Jean-Baptiste; Doyle, Orla; Falissard, Bruno; Tremblay, Richard E

    2016-08-01

    Conduct problems have been associated with poor language development, however the direction of this association in early childhood remains unclear. This study examined the longitudinal directional associations between conduct problems and expressive language ability. Children enrolled in the UK Millennium Cohort Study (N = 14, 004; 50.3 % boys) were assessed at 3 and 5 years of age. Parent reports of conduct problems and standardised assessments of expressive language were analyzed using cross-lagged modeling. Conduct problems at 3 years was associated with poorer expressive language at 5 years and poorer expressive language at 3 years was associated with increased conduct problems by 5 years. The results support reciprocal associations, rather than a specific unidirectional path, which is commonly found with samples of older children. The emergence of problems in either domain can thus negatively impact upon the other over time, albeit the effects were modest. Studies examining the effects of intervention targeting conduct problems and language acquisition prior to school entry may be warranted in testing the efficacy of prevention programmes related to conduct problems and poor language ability early in childhood.

  10. Entorhinal cortical defects in Tg2576 mice are present as early as 2–4 months of age

    PubMed Central

    Duffy, Áine M.; Morales-Corraliza, Jose; Bermudez-Hernandez, Keria M.; Schaner, Michael J.; Magagna-Poveda, Alejandra; Mathews, Paul M.; Scharfman, Helen E.

    2014-01-01

    The entorhinal cortex (EC) is one of the first brain areas to display neuropathology in Alzheimer’s disease (AD). A mouse model which simulates amyloid-β (Aβ) neuropathology, the Tg2576 mouse, was used to address these early changes. Here we show EC abnormalities occur in 2–4 month-old Tg2576 mice, an age prior to β-amyloid deposition and where previous studies suggest that there are few behavioral impairments. First we show, using sandwich ELISA, that soluble human Aβ40 and Aβ42 are detectable in the EC of 2-month-old Tg2576 mice prior to β-amyloid deposition. We then demonstrate that 2–4 month-old Tg2576 mice are impaired at object placement, an EC-dependent cognitive task. Next we show that defects in NeuN expression and myelin uptake occur in the superficial layers of the EC in 2–4-month-old Tg2576 mice. In slices from Tg2576 mice that contained the EC, there were repetitive field potentials evoked by a single stimulus to the underlying white matter, and a greater response to reduced extracellular magnesium ([Mg2+]o), suggesting increased excitability. However, deep layer neurons in Tg2576 mice had longer latencies to antidromic activation than wild type mice. The results show changes in the EC at early ages, and suggest that altered excitability occurs before extensive plaque pathology. PMID:25109765

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

    PubMed

    Ju, Soyoung; Lee, Yanghee

    2018-02-01

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

  12. Neighborhood poverty and early transition to sexual activity in young adolescents: a developmental ecological approach.

    PubMed

    Dupéré, Véronique; Lacourse, Eric; Willms, J Douglas; Leventhal, Tama; Tremblay, Richard E

    2008-01-01

    This study examined how the link between neighborhood poverty and the timing of sexual initiation varies as a function of age, gender, and background characteristics. A sample of N = 2,596 predominately White Canadian adolescents from the National Longitudinal Survey of Children and Youth was used. Sexual initiations occurring between 12 and 15 years old were considered. Results showed that younger adolescent females who lived in poor neighborhoods and who had a history of conduct problems were more likely to report early sexual activity. Peer characteristics partly accounted for this susceptibility. Among adolescent males, no direct neighborhood effects were found, but those who had combined risks at multiple levels appeared more vulnerable. The theoretical and practical implications of these findings are discussed.

  13. Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas

    PubMed Central

    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.

    2015-01-01

    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

  14. 78 FR 51381 - Early Warning Reporting, Foreign Defect Reporting, and Motor Vehicle and Equipment Recall...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-20

    ...NHTSA is adopting amendments to certain provisions of the early warning reporting (EWR) rule and the regulations governing motor vehicle and equipment safety recalls. The amendments to the EWR rule require light vehicle manufacturers to specify the vehicle type and the fuel and/or propulsion system type in their reports and add new component categories of stability control systems for light vehicles, buses, emergency vehicles, and medium-heavy vehicle manufacturers, and forward collision avoidance, lane departure prevention, and backover prevention for light vehicle manufacturers. These amendments will also require light vehicle manufacturers to segregate their Service Brake EWR data into two new discrete component categories. In addition, NHTSA will require motor vehicle manufacturers to report their annual list of substantially similar vehicles via the Internet. As to safety recalls, we will now require certain manufacturers to provide a VIN-based recalls lookup tool on their Web site or the Web site of a third party; require the submission of recalls reports and information via the Internet; and require adjustments to the required content of the owner notification letters and envelopes required to be issued to owners and purchasers of recalled vehicles and equipment.

  15. Early neurotrophic pharmacotherapy rescues developmental delay and Alzheimer’s-like memory deficits in the Ts65Dn mouse model of Down syndrome

    PubMed Central

    Kazim, Syed Faraz; Blanchard, Julie; Bianchi, Riccardo; Iqbal, Khalid

    2017-01-01

    Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer’s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS in utero, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3β) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model. PMID:28368015

  16. An exploratory analysis of the relationship between ambient ozone and particulate matter concentrations during early pregnancy and selected birth defects in Texas

    EPA Science Inventory

    Background: Associations between ozone (O3) and fine particulate matter (PM2.5) concentrations and birth outcomes have been previously demonstrated. We perform an exploratory analysis of O3 and PM2.5 concentrations during early pregnancy and multiple types of birth defects. Met...

  17. Developmental Trajectories of Anxiety Symptoms in Early Adolescence: The Influence of Anxiety Sensitivity

    PubMed Central

    Allan, Nicholas P.; Capron, Daniel W.; Lejuez, Carl W.; Reynolds, Elizabeth K.; MacPherson, Laura; Schmidt, Norman B.

    2014-01-01

    Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity has been identified as an important risk factor in the development of anxiety psychopathology. This study prospectively examined the development of anxiety symptoms in a sample of 277 adolescents (Mage=11.52; 44 % female, 56 % male) over a 3 year period including the influence of anxiety sensitivity on this development. Further, this study investigated whether there were distinct classes of adolescents based on their anxiety symptom trajectories and including anxiety sensitivity as a predictor. Consistent with other reports, findings indicated an overall decline in anxiety symptoms over time in the sample. However, three classes of adolescents were found with distinct anxiety symptom trajectories and anxiety sensitivity was an important predictor of class membership. Adolescents with elevated anxiety sensitivity scores were more likely to be classified as having high and increasing anxiety symptoms over time versus having moderate to low and decreasing anxiety symptoms over time. There are important implications for identification of adolescents and children who are at risk for the development of an anxiety disorder. PMID:24062146

  18. Developmental trajectories of anxiety symptoms in early adolescence: the influence of anxiety sensitivity.

    PubMed

    Allan, Nicholas P; Capron, Daniel W; Lejuez, Carl W; Reynolds, Elizabeth K; MacPherson, Laura; Schmidt, Norman B

    2014-05-01

    Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity has been identified as an important risk factor in the development of anxiety psychopathology. This study prospectively examined the development of anxiety symptoms in a sample of 277 adolescents (M age = 11.52; 44 % female, 56 % male) over a 3 year period including the influence of anxiety sensitivity on this development. Further, this study investigated whether there were distinct classes of adolescents based on their anxiety symptom trajectories and including anxiety sensitivity as a predictor. Consistent with other reports, findings indicated an overall decline in anxiety symptoms over time in the sample. However, three classes of adolescents were found with distinct anxiety symptom trajectories and anxiety sensitivity was an important predictor of class membership. Adolescents with elevated anxiety sensitivity scores were more likely to be classified as having high and increasing anxiety symptoms over time versus having moderate to low and decreasing anxiety symptoms over time. There are important implications for identification of adolescents and children who are at risk for the development of an anxiety disorder.

  19. Ion currents involved in oocyte maturation, fertilization and early developmental stages of the ascidian Ciona intestinalis.

    PubMed

    Tosti, Elisabetta; Gallo, Alessandra; Silvestre, Francesco

    2011-01-01

    Electrophysiological techniques were used to study the role of ion currents in the ascidian Ciona intestinalis oocyte plasma membrane during different stages of growth, meiosis, fertilization and early development. Three stages of immature oocytes were discriminated in the ovary, with the germinal vesicle showing specific different features of growth and maturation. Stage-A (pre-vitellogenic) oocytes exhibited the highest L-type calcium current activity and were incompetent for meiosis resumption. Stage-B (vitellogenic) oocytes showed a progressive disappearance of calcium currents and the first appearance of sodium currents that remained high during the maturation process, up to the post-vitellogenic stage-C oocytes. The latter had acquired meiotic competence, undergoing spontaneous in vitro maturation and interacting with the spermatozoon. However, fertilized oocytes did not produce normal larvae, suggesting that cytoplasmic maturation may affect embryo development. In mature oocytes at the metaphase I stage, sodium currents were present and remained high up to the zygote stage. Oocytes fertilized in the absence of sodium showed significant reduction of the fertilization current amplitude and high development of anomalous "rosette" embryos. Current amplitudes became negligible in embryos at the 2- and 4-cell stage, whereas resumption of all the current activities occurred at the 8-cell embryo. Taken together, these results suggest: (i) an involvement of L-type calcium currents in initial oocyte meiotic progression and growth; (ii) a role of sodium currents at fertilization; (iii) a role of the fertilization current in ensuring normal embryo development. Copyright © 2011 Wiley Periodicals, Inc.

  20. The alternative Medicago truncatula defense proteome of ROS—defective transgenic roots during early microbial infection

    PubMed Central

    Kiirika, Leonard M.; Schmitz, Udo; Colditz, Frank

    2014-01-01

    ROP-type GTPases of plants function as molecular switches within elementary signal transduction pathways such as the regulation of ROS synthesis via activation of NADPH oxidases (RBOH-respiratory burst oxidase homolog in plants). Previously, we reported that silencing of the Medicago truncatula GTPase MtROP9 led to reduced ROS production and suppressed induction of ROS-related enzymes in transgenic roots (MtROP9i) infected with pathogenic (Aphanomyces euteiches) and symbiotic microorganisms (Glomus intraradices, Sinorhizobium meliloti). While fungal infections were enhanced, S. meliloti infection was drastically impaired. In this study, we investigate the temporal proteome response of M. truncatula MtROP9i transgenic roots during the same microbial interactions under conditions of deprived potential to synthesize ROS. In comparison with control roots (Mtvector), we present a comprehensive proteomic analysis using sensitive MS protein identification. For four early infection time-points (1, 3, 5, 24 hpi), 733 spots were found to be different in abundance: 213 spots comprising 984 proteins (607 unique) were identified after S. meliloti infection, 230 spots comprising 796 proteins (580 unique) after G. intraradices infection, and 290 spots comprising 1240 proteins (828 unique) after A. euteiches infection. Data evaluation by GelMap in combination with a heatmap tool allowed recognition of key proteome changes during microbial interactions under conditions of hampered ROS synthesis. Overall, the number of induced proteins in MtROP9i was low as compared with controls, indicating a dual function of ROS in defense signaling as well as alternative response patterns activated during microbial infection. Qualitative analysis of induced proteins showed that enzymes linked to ROS production and scavenging were highly induced in control roots, while in MtROP9i the majority of proteins were involved in alternative defense pathways such as cell wall and protein degradation. PMID

  1. Early prenatal exposure to air pollution and its associations with birth defects in a state-wide birth cohort from North Carolina.

    PubMed

    Vinikoor-Imler, Lisa C; Davis, J Allen; Meyer, Robert E; Luben, Thomas J

    2013-10-01

    Few studies have examined the potential relationship between air pollution and birth defects. The objective of this study was to investigate whether maternal exposure to particulate matter (PM2.5 ) and ozone (O3 ) during pregnancy is associated with birth defects among women living throughout North Carolina. Information on maternal and infant characteristics was obtained from North Carolina birth certificates and health service data (2003-2005) and linked with information on birth defects from the North Carolina Birth Defects Monitoring Program. The 24-hr PM2.5 and O3 concentrations were estimated using a hierarchical Bayesian model of air pollution generated by combining modeled air pollution predictions from the U.S. Environmental Protection Agency's Community Multi-Scale Air Quality model with air monitor data from the Environmental Protection Agency's Air Quality System. Maternal residence was geocoded and assigned pollutant concentrations averaged over weeks 3 to 8 of gestation. Binomial regression was performed and adjusted for potential confounders. No association was observed between either PM2.5 or O3 concentrations and most birth defects. Positive effect estimates were observed between air pollution and microtia/anotia and lower limb deficiency defects, but the 95% confidence intervals were wide and included the null. Overall, this study suggested a possible relationship between air pollution concentration during early pregnancy and certain birth defects (e.g., microtia/anotia, lower limb deficiency defects), although this study did not have the power to detect such an association. The risk for most birth defects does not appear to be affected by ambient air pollution. Copyright © 2013 Wiley Periodicals, Inc.

  2. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. 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. © 2012 Blackwell Publishing Ltd.

  4. Characterization and developmental expression of genes encoding the early carotenoid biosynthetic enzymes in Citrus paradisi Macf.

    PubMed

    Costa, Marcio G C; Moreira, Cristina D; Melton, John R; Otoni, Wagner C; Moore, Gloria A

    2012-02-01

    In the present study, the full-length cDNA sequences of PSY, PDS, and ZDS, encoding the early carotenoid biosynthetic enzymes in the carotenoid pathway of grapefruit (Citrus paradisi), were isolated and characterized for the first time. CpPSY contained a 1311-bp open reading frame (ORF) encoding a polypeptide of 436 amino acids, CpPDS contained a 1659-bp ORF encoding a polypeptide of 552 amino acids, and CpZDS contained a 1713-bp ORF encoding a polypeptide of 570 amino acids. Phylogenetic analysis indicated that CpPSY shares homology with PSYs from Citrus, tomato, pepper, Arabidopsis, and the monocot PSY1 group, while CpPDS and CpZDS are most closely related to orthologs from Citrus and tomato. Expression analysis revealed fluctuations in CpPSY, CpPDS, and CpZDS transcript abundance and a non-coordinated regulation between the former and the two latter genes during fruit development in albedo and juice vesicles of white ('Duncan') and red ('Flame') grapefruits. A 3× higher upregulation of CpPSY expression in juice vesicles of red-fleshed 'Flame' as compared to white-fruited 'Duncan' was observed in the middle stages of fruit development, which correlates with the well documented accumulation pattern of lycopene in red grapefruit. Together with previous data, our results suggest that the primary mechanism controlling lycopene accumulation in red grapefruit involves the transcriptional upregulation of CpPSY, which controls the flux into the carotenoid pathway, and the downregulated expression of CpLCYB2, which controls the step of cyclization of lycopene in chromoplasts during fruit ripening. A correlation between CpPSY expression and fruit color evolution in red grapefruit is demonstrated.

  5. [Cost effectiveness of mass orthoptic screening in kindergarten for early detection of developmental vision disorders].

    PubMed

    König, H H; Barry, J C; Leidl, R; Zrenner, E

    2000-04-01

    Orthoptic screening in the kindergarten is one option to improve early detection of amblyopia in children aged 3 years. The purpose of this study was to analyse the cost-effectiveness of such a screening programme in Germany. Based on data from the literature and own experience gained from orthoptic screening in kindergarten a decision-analytic model was developed. According to the model, all children in kindergarten, aged 3 years, who had not been treated for amblyopia before, were subjected to an orthoptic examination. Non-cooperative children were reexamined in kindergarten after one year. Children with positive test results were examined by an ophthalmologist for diagnosis. Effects were measured by the number of newly diagnosed cases of amblyopia, non-obvious strabismus and amblyogenic refractive errors. Direct costs were estimated from a third-party payer perspective. The influence of uncertain model parameters was tested by sensitivity analysis. In the base analysis the cost per orthoptic screening test was DM 15.39. Examination by an ophthalmologist cost DM 71.20. The total cost of the screening programme in all German kindergartens was DM 6.1 million. With a 1.5% age-specific prevalence of undiagnosed cases, a sensitivity of 95% and a specificity of 98%, a total of 4,261 new cases would be detected. The cost-effectiveness ratio was DM 1,421 per case detected. Sensitivity analysis showed considerable influence of prevalence and specificity on the cost-effectiveness ratio. It was more cost-effective to re-screen non-cooperative children in kindergarten than to have them examined by an ophthalmologist straight-away. The decision-analytic model showed stable results which may serve as a basis for discussion on the implementation of orthoptic screening and for planning a field study.

  6. Is early adulthood a critical developmental stage for psychosis proneness? A survey of delusional ideation in normal subjects.

    PubMed

    Verdoux, H; van Os, J; Maurice-Tison, S; Gay, B; Salamon, R; Bourgeois, M

    1998-02-09

    It has been hypothesized that late adolescence and early adulthood might be a brain developmental stage favoring the clinical expression of psychotic symptoms in psychiatric or neurological diseases. The aim of the present survey was to examine the relationship between age and delusional ideation in a sample of subjects with no psychiatric disorder. The survey was carried out with the Aquitaine Sentinel Network of general practitioners. Consecutive practice attenders were invited to complete the PDI-21 (Peters Delusional Inventory 21 items), a self-report questionnaire designed to measure delusional ideation in the normal population. The study concerned 444 patients who had no lifetime history of psychiatric disorder and who completed the PDI-21. A principal component analysis of the PDI-21 items was performed in order to identify delusional dimensions. An age-related decrease in the likelihood to report delusional ideas was found, younger subjects scoring higher on most dimensions of delusional ideation, such as 'persecution', 'thought disturbance', 'grandiosity' and 'paranormal beliefs'. 'Religiosity' was the only dimension positively associated with age. The results suggest that there may be a physiological neurodevelopmental stage favouring the expression of psychosis proneness in normal subjects, and support the hypothesis that the association between age and positive psychotic symptoms in functional and organic psychoses may be linked to the interaction between normal brain maturational processes and cerebral abnormalities involved in the aetiology of functional and organic psychoses.

  7. Substance use changes and social role transitions: proximal developmental effects on ongoing trajectories from late adolescence through early adulthood.

    PubMed

    Staff, Jeremy; Schulenberg, John E; Maslowsky, Julie; Bachman, Jerald G; O'Malley, Patrick M; Maggs, Jennifer L; Johnston, Lloyd D

    2010-11-01

    Substance use changes rapidly during late adolescence and early adulthood. This time in the life course is also dense with social role changes, as role changes provide dynamic context for individual developmental change. Using nationally representative, multiwave longitudinal data from age 18 to 28, we examine proximal links between changes in social roles and changes in substance use during the transition to adulthood. We find that changes in family roles, such as marriage, divorce, and parenthood, have clear and consistent associations with changes in substance use. With some notable exceptions, changes in school and work roles have weaker effects on changes in substance use compared to family roles. Changes in socializing (i.e., nights out for fun and recreation) and in religiosity were found to mediate the relationship of social role transitions to substance use. Two time-invariant covariates, socioeconomic background and heavy adolescent substance use, predicted social role status, but did not moderate associations, as within-person links between social roles and substance use were largely equivalent across groups. This paper adds to the cascading effects literature by considering how, within individuals, more proximal variations in school, work, and family roles relate to variations in substance use, and which roles appear to be most influential in precipitating changes in substance use during the transition to adulthood.

  8. Substance Use Changes and Social Role Transitions: Proximal Developmental Effects on Ongoing Trajectories from Late Adolescence through Early Adulthood*

    PubMed Central

    Staff, Jeremy; Schulenberg, John E.; Maslowsky, Julie; Bachman, Jerald G.; O’Malley, Patrick M.; Maggs, Jennifer L.; Johnston, Lloyd D.

    2010-01-01

    Substance use changes rapidly during late adolescence and early adulthood. Not coincidentally, this time in the life course is also dense with social role changes, as role changes provide dynamic context for individual developmental change. Using nationally representative, multiwave longitudinal data from age 18 to 28, we examine proximal links between changes in social roles and changes in substance use during the transition to adulthood. We find that changes in family roles, such as marriage, divorce, and parenthood, have clear and consistent associations with changes in substance use. With some notable exceptions, changes in school and work roles have weaker effects on changes in substance use compared to family roles. Changes in socializing (i.e., nights out for fun and recreation) and in religiosity were found to mediate the relationship of social role transitions to substance use. Two time- invariant covariates, socioeconomic background and heavy adolescent substance use, predicted social role status, but did not moderate associations, as within-person links between social roles and substance use were largely equivalent across groups. This paper adds to the cascading effects literature by considering how, within individuals, more proximal variations in school, work, and family roles relate to variations in substance use; and which roles appear to be most influential in precipitating changes in substance use during the transition to adulthood. PMID:20883590

  9. Developmental insights from early mammalian embryos and core signaling pathways that influence human pluripotent cell growth and differentiation.

    PubMed

    Chen, Kevin G; Mallon, Barbara S; Johnson, Kory R; Hamilton, Rebecca S; McKay, Ronald D G; Robey, Pamela G

    2014-05-01

    Human pluripotent stem cells (hPSCs) have two potentially attractive applications: cell replacement-based therapies and drug discovery. Both require the efficient generation of large quantities of clinical-grade stem cells that are free from harmful genomic alterations. The currently employed colony-type culture methods often result in low cell yields, unavoidably heterogeneous cell populations, and substantial chromosomal abnormalities. Here, we shed light on the structural relationship between hPSC colonies/embryoid bodies and early-stage embryos in order to optimize current culture methods based on the insights from developmental biology. We further highlight core signaling pathways that underlie multiple epithelial-to-mesenchymal transitions (EMTs), cellular heterogeneity, and chromosomal instability in hPSCs. We also analyze emerging methods such as non-colony type monolayer (NCM) and suspension culture, which provide alternative growth models for hPSC expansion and differentiation. Furthermore, based on the influence of cell-cell interactions and signaling pathways, we propose concepts, strategies, and solutions for production of clinical-grade hPSCs, stem cell precursors, and miniorganoids, which are pivotal steps needed for future clinical applications. Published by Elsevier B.V.

  10. 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. © The Author 2014. Published by Oxford University Press. All rights reserved. For

  11. The zerovalent iron nanoparticle causes higher developmental toxicity than its oxidation products in early life stages of medaka fish.

    PubMed

    Chen, Pei-Jen; Wu, Wan-Lin; Wu, Kevin Chia-Wen

    2013-08-01

    Nanoscale zerovalent iron (nZVI)-mediated oxidation reaction is increasingly being used for enhanced treatment of water or wastewater processes; however, the fate and eco-toxicological effects of nZVI in the surface aquifer remain unclear. We investigated bioaccumulation and lethal-to-sublethal toxic effects on early life development of Japanese medaka (Oryzias latipes) with 7-day exposure to 25-200 mg/L of well-characterized solutions containing carboxymethyl cellulose (CMC)-stabilized nZVI (CMC-nZVI), nanoscale iron oxide (nFe3O4) or ferrous ion [Fe(II)aq]. The CMC-nZVI solution had the greatest acute mortality and developmental toxic effects in embryos, with lesser and the least effects with Fe(II)aq and nFe3O4. The toxicity of CMC-nZVI was ascribed to its high reactivity in the oxygenic solution, which led to a combination of hypoxia and production of reactive oxygen species (ROS) and Fe(II)aq. nFe3O4 (50-100 mg/L) was more bioavailable to embryos and bioaccmulative in hatchlings than suspended CMC-nZVI. The antioxidant balance was differentially altered by induced intracellular ROS in hatchlings with all 3 iron species. We revealed causal toxic effects of nZVI and its oxidized products in early life stages of medaka fish using different organizational levels of biomarker assays. The toxicity results implicate a potential eco-toxicological impact of nZVI on the aquatic environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Early language impairments and developmental pathways of emotional problems across childhood.

    PubMed

    Yew, Shaun Goh Kok; O'Kearney, Richard

    2015-01-01

    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. To examine the link between early language status (language impaired (LI), typical language (TL)) and the pattern and predictors of growth in emotional difficulties from school entry to the start of high school in a large cohort of Australian children. Unconditional latent growth curves of emotional difficulties were modelled across four waves (ages 4-5, 6-7, 8-9 and 10-11) using data from 1627 boys (280 LI, 1347 TL) and 1609 girls (159 LI, 1450 TL). Conditional latent growth curves estimated the main effects of LI on the severity and slope of growth in emotional problems. Simultaneous multiple regression tested the interaction between language status and the other predictors of the development of emotional symptoms. LI predicted a significant persistent elevation in severity of emotional difficulties across childhood among boys (d = 0.33-0.57) and girls (d = 0.25-0.39) but was not associated with their growth. LI moderated the association between hostile parenting and the severity of emotional symptoms for boys and the effect of socioeconomic status (SES) and temperamental sociability on the linear and quadratic growth of emotional problems for girls but had no impact on the influence of other predictors. There is no effect of LI on the characteristic rate and shape of growth in emotional symptoms across childhood although LI children maintain elevated severities of emotional difficulties. The associations between child reactivity, peer problems, prosocial behaviours, maternal distress and parental warmth and the development of emotional difficulties were the same for LI and TL children. LI enhanced the influence of hostile parenting on a higher severity of emotional symptoms for boys and of lower SES on a faster rate of development of emotional symptoms for

  13. Specific subpopulations of hypothalamic leptin receptor-expressing neurons mediate the effects of early developmental leptin receptor deletion on energy balance.

    PubMed

    Rupp, Alan C; Allison, Margaret B; Jones, Justin C; Patterson, Christa M; Faber, Chelsea L; Bozadjieva, Nadejda; Heisler, Lora K; Seeley, Randy J; Olson, David P; Myers, Martin G

    2018-06-06

    To date, early developmental ablation of leptin receptor (LepRb) expression from circumscribed populations of hypothalamic neurons (e.g., arcuate nucleus (ARC) Pomc- or Agrp-expressing cells) has only minimally affected energy balance. In contrast, removal of LepRb from at least two large populations (expressing vGat or Nos1) spanning multiple hypothalamic regions produced profound obesity and metabolic dysfunction. Thus, we tested the notion that the total number of leptin-responsive hypothalamic neurons (rather than specific subsets of cells with a particular molecular or anatomical signature) subjected to early LepRb deletion might determine energy balance. We generated new mouse lines deleted for LepRb in ARC Ghrh Cre neurons or in Htr2c Cre neurons (representing roughly half of all hypothalamic LepRb neurons, distributed across many nuclei). We compared the phenotypes of these mice to previously-reported models lacking LepRb in Pomc, Agrp, vGat or Nos1 cells. The early developmental deletion of LepRb from vGat or Nos1 neurons produced dramatic obesity, but deletion of LepRb from Pomc, Agrp, Ghrh, or Htr2c neurons minimally altered energy balance. Although early developmental deletion of LepRb from known populations of ARC neurons fails to substantially alter body weight, the minimal phenotype of mice lacking LepRb in Htr2c cells suggests that the phenotype that results from early developmental LepRb deficiency depends not simply upon the total number of leptin-responsive hypothalamic LepRb cells. Rather, specific populations of LepRb neurons must play particularly important roles in body energy homeostasis; these as yet unidentified LepRb cells likely reside in the DMH. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

  14. Percutaneous device closure of atrial septal defect results in very early and sustained changes of right and left heart function.

    PubMed

    Monfredi, Oliver; Luckie, Matthew; Mirjafari, Hoda; Willard, Terence; Buckley, Helen; Griffiths, Linda; Clarke, Bernard; Mahadevan, Vaikom S

    2013-08-20

    To investigate the echocardiographic effects of percutaneous closure of secundum atrial septal defect (ASD) in adults and assess which pre-closure parameters predict good response to closure. ASD is a common congenital heart disease often undiscovered until adulthood. ASD closure has been revolutionized by the use of percutaneous devices. The effects of these procedures on echocardiographic parameters are not well characterized. Patients undergoing percutaneous device closure of ASD between June 2007 and June 2009 had 3 sequential echocardiograms reviewed: pre-procedure, immediate post-procedure (24 hours) and 6-8 weeks post-procedure. Significant changes from baseline were investigated using paired t-test/1-way ANOVA. Pearson correlation (2-tailed) tests were used to categorize patients as 'good responders' to closure in terms of selected parameters. 129 echocardiograms in 43 consecutive patients were included. Remodeling of both ventricles occurred immediately following ASD closure and was sustained. Right ventricular (RV) diameter in diastole decreased by 13.5% and 19.3% compared to baseline at 24 hours and 6-8 weeks post-closure, respectively (p<0.05); Left ventricular (LV) diameter in diastole increased by 8.5% and 15.6%, respectively (p<0.05). Functional parameters of the RV also demonstrated early and sustained decreases (TAPSE decreased by 8.3% and 17% compared to baseline at 24 hours and 6-8 weeks post-closure, respectively (p<0.05)). Smaller RV baseline diameter appeared to predict good response to closure. Percutaneous ASD closure has immediate, sustained benefits on multiple echocardiographic parameters. Good responders have smaller RV at baseline, suggesting early closure is preferable. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. periostin Null Mice Exhibit Dwarfism, Incisor Enamel Defects, and an Early-Onset Periodontal Disease-Like Phenotype

    PubMed Central

    Rios, Hector; Koushik, Shrinagesh V.; Wang, Haiyan; Wang, Jian; Zhou, Hong-Ming; Lindsley, Andrew; Rogers, Rhonda; Chen, Zhi; Maeda, Manabu; Kruzynska-Frejtag, Agnieszka; Feng, Jian Q.; Conway, Simon J.

    2005-01-01

    Periostin was originally identified as an osteoblast-specific factor and is highly expressed in the embryonic periosteum, cardiac valves, placenta, and periodontal ligament as well as in many adult cancerous tissues. To investigate its role during development, we generated mice that lack the periostin gene and replaced the translation start site and first exon with a lacZ reporter gene. Surprisingly, although periostin is widely expressed in many developing organs, periostin-deficient (perilacZ) embryos are grossly normal. Postnatally, however, ∼14% of the nulls die before weaning and all of the remaining perilacZ nulls are severely growth retarded. Skeletal analysis revealed that trabecular bone in adult homozygous skeletons was sparse, but overall bone growth was unaffected. Furthermore, by 3 months, the nulls develop an early-onset periodontal disease-like phenotype. Unexpectedly, these mice also show a severe incisor enamel defect, although there is no apparent change in ameloblast differentiation. Significantly, placing the perilacZ nulls on a soft diet that alleviated mechanical strain on the periodontal ligament resulted in a partial rescue of both the enamel and periodontal disease-like phenotypes. Combined, these data suggest that a healthy periodontal ligament is required for normal amelogenesis and that periostin is critically required for maintenance of the integrity of the periodontal ligament in response to mechanical stresses. PMID:16314533

  16. Prevalence of suspected developmental delays in early infancy: results from a regional population-based longitudinal study.

    PubMed

    Valla, Lisbeth; Wentzel-Larsen, Tore; Hofoss, Dag; Slinning, Kari

    2015-12-17

    Prevalence estimates on suspected developmental delays (SDD) in young infants are scarce and a necessary first step for planning an early intervention. We investigated the prevalence of SDD at 4, 6 and 12 months, in addition to associations of SDD with gender, prematurity and maternal education. This study is based on a Norwegian longitudinal sample of 1555 infants and their parents attending well-baby clinics for regular health check-ups. Moreover, parents completed the Norwegian translation of the Ages and Stages Questionnaires (ASQ) prior to the check-up, with a corrected gestational age being used to determine the time of administration for preterm infants. Scores ≤ the established cut-offs in one or more of the five development areas: communication, gross motor, fine motor, problem solving and personal-social, which defined SDD for an infant were reported. Chi-square tests were performed for associations between the selected factors and SDD. According to established Norwegian cut-off points, the overall prevalence of SDD in one or more areas was 7.0 % (10.3 % US cut-off) at 4 months, 5.7 % (12.3 % US cut-off) at 6 months and 6.1 % (10.3 % US cut-off) at 12 months. The highest prevalence of SDD was in the gross motor area at all three time points. A gestational age of < 37 weeks revealed a significant association with the communication SDD at 4 months, and with the fine motor and personal social SDD at 6 months. Gender was significantly associated with the fine motor and problem solving SDD at 4 months and personal- social SDD at 6 months: as more boys than girls were delayed. No significant associations were found between maternal education and the five developmental areas of the ASQ. Our findings indicate prevalence rates of SDD between 5.7 and 7.0 % in Norwegian infants between 4 and 12 months of age based on the Norwegian ASQ cut-off points (10.3-12.3 %, US cut-off points). During the first year of life, delay is most frequent

  17. Early results of immediate repair of obstetric third-degree tears: 65% are completely asymptomatic despite persistent sphincter defects in 61%.

    PubMed

    Hayes, J; Shatari, T; Toozs-Hobson, P; Busby, K; Pretlove, S; Radley, S; Keighley, M

    2007-05-01

    The outcome of immediate repair of obstetric third-degree tears is poorly documented. Immediate repair may give better functional results than delayed repair because scarring is reduced. This aim of this prospective study was to examine the early outcome of immediate repair of third-degree tears. A total of 121 women who had immediate repair of obstetric third-degree tears underwent interview, anal ultrasonography and anorectal physiology. At review, 79 (65%) were completely asymptomatic (score = 0), 23 (19%), had minor flatus incontinence or mild urgency causing no compromise to their quality of life (score 1-4), and 19 (16%) had clinically embarrassing faecal incontinence (score 5-24). Thirty-nine (32%) had an intact internal anal sphincter (IAS) and external anal sphincter (EAS) (i.e. a successful repair), eight (7%) had a defect in the IAS alone but the EAS was intact (i.e. a successful repair but a residual IAS defect), 43 (35%) had a residual defect in the EAS alone (IAS intact) and 31 (26%) had a persistent defect in the IAS and EAS. Residual defects in either or both of the sphincters were associated with a significantly higher incidence of abnormal resting and squeeze anal pressures. Anal manometry had no correlation with symptoms. The highest proportion of severe incontinence was in those with an IAS defect alone (37%) and when there was a residual IAS and EAS defect (24%). Only 2 of 39 (5%) with an intact IAS and EAS had severe incontinence and only 8 of 43 (18%) with a residual EAS defect alone had severe faecal incontinence. These results indicate a good outcome following immediate repair of third-degree obstetric tears and emphasize the role of the IAS in providing continence.

  18. 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…

  19. Getting Ready for College: An Implementation and Early Impacts Study of Eight Texas Developmental Summer Bridge Programs

    ERIC Educational Resources Information Center

    Wathington, Heather D.; Barnett, Elisabeth A.; Weissman, Evan; Teres, Jedediah; Pretlow, Joshua; Nakanishi, Aki

    2011-01-01

    In 2007, the Texas Higher Education Coordinating Board (THECB) funded 22 colleges to establish developmental summer bridge programs. Aimed at providing an alternative to traditional developmental education, these programs involve intensive remedial instruction in math, reading, and/or writing and college preparation content for students entering…

  20. Getting Ready for College: An Implementation and Early Impacts Study of Eight Texas Developmental Summer Bridge Programs. Executive Summary

    ERIC Educational Resources Information Center

    Wathington, Heather D.; Barnett, Elisabeth A.; Weissman, Evan; Teres, Jedediah; Pretlow, Joshua; Nakanishi, Aki

    2011-01-01

    In 2007, the Texas Higher Education Coordinating Board (THECB) funded 22 colleges to establish developmental summer bridge programs. Aimed at providing an alternative to traditional developmental education, these programs involve intensive remedial instruction in math, reading, and/or writing and college preparation content for students entering…

  1. Getting Ready for College: An Implementation and Early Impacts Study of Eight Texas Developmental Summer Bridge Programs. NCPR Brief

    ERIC Educational Resources Information Center

    Wathington, Heather D.; Barnett, Elisabeth A.; Weissman, Evan; Teres, Jedediah; Pretlow, Joshua; Nakanishi, Aki

    2011-01-01

    In 2009, the National Center for Postsecondary Research (NCPR) launched an evaluation of eight developmental summer bridge programs in Texas to assess whether these programs reduce the need for developmental coursework and improve student outcomes in college. The evaluation uses an experimental design to measure the effects of these programs on…

  2. Diagnostic Classification 0-3: Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood.

    ERIC Educational Resources Information Center

    Zero to Three: National Center for Infants, Toddlers and Families, Washington, DC.

    The diagnostic framework presented in this manual seeks to address the need for a systematic, multi-disciplinary, developmentally based approach to the classification of mental health and developmental difficulties in the first 4 years of life. An introduction discusses clinical approaches to assessment and diagnosis, gives an overview of the…

  3. Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood. Diagnostic Classification: 0-3.

    ERIC Educational Resources Information Center

    Wieder, Serena, Ed.

    The diagnostic framework presented in this manual seeks to address the need for a systematic, multidisciplinary, developmentally based approach to the classification of mental health and developmental difficulties in the first 4 years of life. An introduction discusses clinical approaches to assessment and diagnosis, gives an overview of the…

  4. METROPOLITAN ATLANTA DEVELOPMENTAL DISABILITIES PROGRAM (MADDSP)

    EPA Science Inventory

    To address the problem of developmental disabilities among children, CDC, the former Division of Birth Defects and Developmental Disabilities, which was funded by the Agency for Toxic Substances and Disease Registry (ATSDR), and the Georgia Department of Human Resources, initiate...

  5. 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

  6. Is MSAFP still a useful test for detecting open neural tube defects and ventral wall defects in the era of first-trimester and early second-trimester fetal anatomical ultrasounds?

    PubMed

    Roman, Ashley S; Gupta, Simi; Fox, Nathan S; Saltzman, Daniel; Klauser, Chad K; Rebarber, Andrei

    2015-01-01

    To evaluate whether maternal serum α-fetoprotein (MSAFP) improves the detection rate for open neural tube defects (ONTDs) and ventral wall defects (VWD) in patients undergoing first-trimester and early second-trimester fetal anatomical survey. A cohort of women undergoing screening between 2005 and 2012 was identified. All patients were offered an ultrasound at between 11 weeks and 13 weeks and 6 days of gestational age for nuchal translucency/fetal anatomy followed by an early second-trimester ultrasound at between 15 weeks and 17 weeks and 6 days of gestational age for fetal anatomy and MSAFP screening. All cases of ONTD and VWD were identified via query of billing and reporting software. Sensitivity and specificity for detection of ONTD/VWD were calculated, and groups were compared using the Fisher exact test, with p < 0.05 as significance. A total of 23,790 women met the criteria for inclusion. Overall, 15 cases of ONTD and 17 cases of VWD were identified; 100% of cases were diagnosed by ultrasound prior to 18 weeks' gestation; none were diagnosed via MSAFP screening (p < 0.001). First-trimester and early second-trimester ultrasound had 100% sensitivity and 100% specificity for diagnosing ONTD/VWD. Ultrasound for fetal anatomy during the first and early second trimester detected 100% of ONTD/VWD in our population. MSAFP is not useful as a screening tool for ONTD and VWD in the setting of this ultrasound screening protocol. © 2014 S. Karger AG, Basel.

  7. Developmental trends in alcohol use initiation and escalation from early- to middle-adolescence: Prediction by urgency and trait affect

    PubMed Central

    Spillane, Nichea S.; Merrill, Jennifer E.; Jackson, Kristina M.

    2016-01-01

    Studies on adolescent drinking have not always been able to distinguish between initiation and escalation of drinking, because many studies include samples in which initiation has already occurred; hence initiation and escalation are often confounded. The present study draws from a dual-process theoretical framework to investigate: if changes in the likelihood of drinking initiation and escalation are predicted by a tendency towards rash action when experiencing positive and negative emotions (positive and negative urgency); and whether trait positive and negative affect moderate such effects. Alcohol naïve adolescents (n=944; age: M=12.16, SD=.96; 52% female) completed 6 semi-annual assessments of trait urgency and affect (wave-1) and alcohol use (waves 2–6). A two-part random-effects model was used to estimate changes in the likelihood of any alcohol use vs. escalation in the volume of use amongst initiators. Main effects suggest a significant association between positive affect and change in level of alcohol use amongst initiators, such that lower positive affect predicted increased alcohol involvement. This main effect was qualified by a significant interaction between positive urgency and positive affect predicting changes in the escalation of drinking, such that the effect of positive urgency was augmented for those high on trait positive affect, though only at extremely high levels of positive affect. Results suggest risk factors in the development of drinking depend on whether initiation or escalation is investigated. A more nuanced understanding of the early developmental phases of alcohol involvement can inform prevention and intervention efforts. PMID:27031086

  8. 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

  9. 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.

  10. Automated detection of nerve fiber layer defects on retinal fundus images using fully convolutional network for early diagnosis of glaucoma

    NASA Astrophysics Data System (ADS)

    Watanabe, Ryusuke; Muramatsu, Chisako; Ishida, Kyoko; Sawada, Akira; Hatanaka, Yuji; Yamamoto, Tetsuya; Fujita, Hiroshi

    2017-03-01

    Early detection of glaucoma is important to slow down progression of the disease and to prevent total vision loss. We have been studying an automated scheme for detection of a retinal nerve fiber layer defect (NFLD), which is one of the earliest signs of glaucoma on retinal fundus images. In our previous study, we proposed a multi-step detection scheme which consists of Gabor filtering, clustering and adaptive thresholding. The problems of the previous method were that the number of false positives (FPs) was still large and that the method included too many rules. In attempt to solve these problems, we investigated the end-to-end learning system without pre-specified features. A deep convolutional neural network (DCNN) with deconvolutional layers was trained to detect NFLD regions. In this preliminary investigation, we investigated effective ways of preparing the input images and compared the detection results. The optimal result was then compared with the result obtained by the previous method. DCNN training was carried out using original images of abnormal cases, original images of both normal and abnormal cases, ellipse-based polar transformed images, and transformed half images. The result showed that use of both normal and abnormal cases increased the sensitivity as well as the number of FPs. Although NFLDs are visualized with the highest contrast in green plane, the use of color images provided higher sensitivity than the use of green image only. The free response receiver operating characteristic curve using the transformed color images, which was the best among seven different sets studied, was comparable to that of the previous method. Use of DCNN has a potential to improve the generalizability of automated detection method of NFLDs and may be useful in assisting glaucoma diagnosis on retinal fundus images.

  11. Defective expression of apoptosis-related molecules in multiple sclerosis patients is normalized early after autologous haematopoietic stem cell transplantation.

    PubMed

    de Oliveira, G L V; Ferreira, A F; Gasparotto, E P L; Kashima, S; Covas, D T; Guerreiro, C T; Brum, D G; Barreira, A A; Voltarelli, J C; Simões, B P; Oliveira, M C; de Castro, F A; Malmegrim, K C R

    2017-03-01

    Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts. In the BEAM group, BAK, BIK, BIM EL , FAS, FASL, A1, BCL2, BCLX L , CFLIP L and CIAP2 genes were up-regulated after AHSCT. With the exception of BIK, BIM EL and A1, all genes reached levels similar to controls at day + 720 post-transplantation. Furthermore, in these patients, we observed increased CD8 + Fas + T cell frequencies after AHSCT when compared to baseline. In the CY group, we observed increased BAX, BCLW, CFLIP L and CIAP1 and decreased BIK and BID gene expressions after transplantation. At day + 720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLX L and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At 1 year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the re-establishment of immune tolerance during the first 2 years post-transplantation. © 2016 British Society for Immunology.

  12. Efficacy of a sheet combined with fibrin glue in repair of pleural defect at the early phase after lung surgery in a canine model.

    PubMed

    Sakai, Takashi; Matsutani, Noriyuki; Kanai, Eiichi; Yamauchi, Yoshikane; Uehara, Hirofumi; Iinuma, Hisae; Kawamura, Masafumi

    2018-02-01

    Polyglycolic acid and oxidized regenerated cellulose have been widely used as a sealant for repairing pulmonary air leakage during respiratory surgery. However, fundamental research of these materials has not been sufficiently conducted. Therefore, we conducted studies to assess the pressure resistance ability of these materials using a canine visceral pleural defect model at the early phase. The 6-mm circular defect and the 12-mm square defect were created on the visceral pleura of anesthetized beagles. These defects were then repaired using one of four methods: method A using polyglycolic acid and fibrin glue; method B using oxidized regenerated cellulose and fibrin glue; method C using oxidized regenerated cellulose; method D using fibrin glue. Airway pressure was measured as bursting pressure when air leakage from the repaired areas occurred at 5 min, 3 h, and 24 h after repair. For the 6-mm circle defect, method A showed higher bursting pressures than the other methods at 5 min and 3 h (p < 0.05); method B showed higher than methods C and D at 5 min and 3 h (p < 0.05). For the 12-mm square defect, method A showed higher bursting pressures than the other methods at all time points (p < 0.05). Moreover, method B showed higher than method C at 24 h (p < 0.05). Visceral pleural repairs using polyglycolic acid combined with fibrin glue showed the highest bursting pressure. Oxidized regenerated cellulose combined with fibrin glue showed sufficiently high bursting pressure in repair of small 6-mm circular defects.

  13. Early IGF-1 primes visual cortex maturation and accelerates developmental switch between NKCC1 and KCC2 chloride transporters in enriched animals.

    PubMed

    Baroncelli, Laura; Cenni, Maria Cristina; Melani, Riccardo; Deidda, Gabriele; Landi, Silvia; Narducci, Roberta; Cancedda, Laura; Maffei, Lamberto; Berardi, Nicoletta

    2017-02-01

    Environmental enrichment (EE) has a remarkable impact on brain development. Continuous exposure to EE from birth determines a significant acceleration of visual system maturation both at retinal and cortical levels. A pre-weaning enriched experience is sufficient to trigger the accelerated maturation of the visual system, suggesting that factors affected by EE during the first days of life might prime visual circuits towards a faster development. The search for such factors is crucial not only to gain a better understanding of the molecular hierarchy of brain development but also to identify molecular pathways amenable to be targeted to correct atypical brain developmental trajectories. Here, we showed that IGF-1 levels are increased in the visual cortex of EE rats as early as P6 and this is a crucial event for setting in motion the developmental program induced by EE. Early intracerebroventricular (i.c.v.) infusion of IGF-1 in standard rats was sufficient to mimic the action of EE on visual acuity development, whereas blocking IGF-1 signaling by i.c.v. injections of the IGF-1 receptor antagonist JB1 prevented the deployment of EE effects. Early IGF-1 decreased the ratio between the expression of NKCC1 and KCC2 cation/chloride transporters, and the reversal potential for GABA A R-driven Cl - currents (E Cl ) was shifted toward more negative potentials, indicating that IGF-1 is a crucial factor in accelerating the maturation of GABAergic neurotransmission and promoting the developmental switch of GABA polarity from excitation to inhibition. In addition, early IGF-1 promoted a later occurring increase in its own expression, suggesting a priming effect of early IGF-1 in driving post-weaning cortical maturation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 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

  15. Developmental profiles of progesterone receptor transcripts and molecular responses to gestagen exposure during Silurana tropicalis early development.

    PubMed

    Thomson, Paisley; Langlois, Valerie S

    2018-05-18

    Environmental gestagens are an emerging class of contaminants that have been recently measured in surface water and can interfere with reproduction in aquatic vertebrates. Gestagens include endogenous progestogens, such as progesterone (P4), which bind P4-receptors and have critically important roles in vertebrate physiology and reproduction. Gestagens also include synthetic progestins, which are components of human and veterinary drugs, such as melengestrol acetate (MGA). Endogenous progestogens are essential in the regulation of reproduction in mammalian species, but the role of P4 in amphibian larval development remains unclear. This project aims to understand the roles and the regulatory mechanisms of P4 in amphibians and to assess the consequences of exposures to environmental gestagens on the P4-receptor signaling pathways in frogs. Here, we established the developmental profiles of the P4 receptors: the intracellular progesterone receptor (ipgr), the membrane progesterone receptor β (mpgrβ), and the progesterone receptor membrane component 1 (pgrmc1) in Western clawed frog (Silurana tropicalis) embryos using real-time qPCR. P4-receptor mRNAs were detected throughout embryogenesis. Transcripts for ipgr and pgrmc1 were detected in embryos at Nieuwkoop and Faber (NF) stage 2 and 7, indicative of maternal transfer of mRNA. We also assessed the effects of P4 and MGA exposure in embryonic and early larval development. Endocrine responses were evaluated through transcript analysis of a suite of gene targets of interest, including: ipgr, mpgrβ, pgrmc1, androgen receptor (ar), estrogen receptor α (erα), follicle stimulating hormone β (fshβ), prolactin (prl), and the steroid 5-alpha reductase family (srd5α1, 2, and 3). Acute exposure (NF 12-46) to P4 caused a 2- to 5-fold change increase of ipgr, mpgrβ, pgrmc1, and ar mRNA levels at the environmentally relevant concentration of 195 ng/L P4. Acute exposure to MGA induced a 56% decrease of srd5α3 at 1140

  16. MOTHERS AND FATHERS TOGETHER: CONTRASTS IN PARENTING ACROSS PRESCHOOL TO EARLY SCHOOL AGE IN CHILDREN WITH DEVELOPMENTAL DELAYS

    PubMed Central

    Crnic, Keith; Arbona, Anita Pedersen y; Baker, Bruce; Blacher, Jan

    2009-01-01

    Much of our understanding of families and parenting of children with intellectual disabilities (ID) reflects the thoughts, beliefs, attitudes, and behaviors of mothers with relatively little focus on the ways in which fathers contribute to and are affected by this unique context. In this chapter, we address the importance of fathers as a source of critical developmental influence, and contrast fathers and mothers of children with ID along three important dimensions of parent functioning (stress, well-being, and interactive behavior). The contrasts explore the developmental trajectories of these parenting constructs over time from the perspective of an emerging new complexity in conceptual models of family and parent adaptation. Data from the Collaborative Family Study are used to explore paternal and maternal stress, well-being, and behavior across the preschool through transition to school-age developmental period, and findings are discussed within the context of the broader literature in each area. PMID:20224748

  17. [Early application of the antibiotic-laden bone cement (ALBC) combined with the external fixation support in treating the open fractures of lower limbs complicated with bone defect].

    PubMed

    Xiao, Jian; Mao, Zhao-Guang; Zhu, Hui-Hua; Guo, Liang

    2017-03-25

    To discuss the curative effect of the early application of the antibiotic-laden bone cement (ALBC) combined with the external fixation support in treating the open fractures of lower limbs complicated with bone defect. From December 2013 to January 2015, 36 cases of lower limb open comminuted fractures complicated with bone defects were treated by the vancomycin ALBC combined with the external fixation support, including 26 males and 10 females with an average age of 38.0 years old ranging from 19 to 65 years old. The included cases were all open fractures of lower limbs complicated with bone defects with different degree of soft tissue injuries. Among them, 25 cases were tibial fractures, 11 cases were femoral fractures. The radiographs indicated a presence of bone defects, which ranged from 3.0 to 6.1 cm with an average of 4.0 cm. The Gustilo classification of open fractures:24 cases were type IIIA, 12 cases were typr IIIB. The percentage of wound infection, bone grafting time, fracture healing time and postoperative joint function of lower limb were observed. The function of injured limbs was evaluated at 1 month after the clinical healing of fracture based on Paley evaluation criterion. All cases were followed up for 3 to 24 months with an average of (6.0±3.0) months. The wound surface was healed well, neither bone infections nor unhealed bone defects were presented. The reoperation of bone grafting was done at 6 weeks after the patients received an early treatment with ALBC, some of them were postponed to 8 weeks till the approximate healing of fractures, the treatment course lasted for 4 to 8 months with an average of(5.5±1.5) months. According to Paley and other grading evaluations of bone and function, there were 27 cases as excellent, 5 cases as good, 3 cases as ordinary. The ALBC combined with external fixation support was an effective method for early treatment to treat the traumatic lower limb open fractures complicated with bone defects. This method

  18. The impact of youth, family, peer and neighborhood risk factors on developmental trajectories of risk involvement from early through middle adolescence.

    PubMed

    Wang, Bo; Deveaux, Lynette; Li, Xiaoming; Marshall, Sharon; Chen, Xinguang; Stanton, Bonita

    2014-04-01

    Few studies have analyzed the development course beginning in pre-/early adolescence of overall engagement in health-risk behaviors and associated social risk factors that place individuals in different health-risk trajectories through mid-adolescence. The current longitudinal study identified 1276 adolescents in grade six and followed them for three years to investigate their developmental trajectories of risk behaviors and to examine the association of personal and social risk factors with each trajectory. Group-based trajectory modeling was applied to identify distinctive trajectory patterns of risk behaviors. Multivariate multinomial logistic regression analyses were performed to examine the effects of the personal and social risk factors on adolescents' trajectories. Three gender-specific behavioral trajectories were identified for males (55.3% low-risk, 37.6% moderate-risk, increasing, and 7.1% high-risk, increasing) and females (41.4% no-risk, 53.4% low-risk, increasing and 5.2% moderate to high-risk, increasing). Sensation-seeking, family, peer, and neighborhood factors at baseline predicted following the moderate-risk, increasing trajectory and the high-risk, increasing trajectory in males; these risk factors predicted following the moderate to high-risk, increasing trajectory in females. The presence of all three social risk factors (high-risk neighborhood, high-risk peers and low parental monitoring) had a dramatic impact on increased probability of being in a high-risk trajectory group. These findings highlight the developmental significance of early personal and social risk factors on subsequent risk behaviors in early to middle adolescence. Future adolescent health behavior promotion interventions might consider offering additional prevention resources to pre- and early adolescent youth who are exposed to multiple contextual risk factors (even in the absence of risk behaviors) or youth who are early-starters of delinquency and substance use behaviors

  19. Birth Defects

    MedlinePlus

    ... both. Some birth defects like cleft lip or neural tube defects are structural problems that can be ... during pregnancy is a key factor in causing neural tube defects. For most birth defects, the cause ...

  20. A comparative view of early development in the corals Favia lizardensis, Ctenactis echinata, and Acropora millepora - morphology, transcriptome, and developmental gene expression.

    PubMed

    Okubo, Nami; Hayward, David C; Forêt, Sylvain; Ball, Eldon E

    2016-02-29

    Research into various aspects of coral biology has greatly increased in recent years due to anthropogenic threats to coral health including pollution, ocean warming and acidification. However, knowledge of coral early development has lagged. The present paper describes the embryonic development of two previously uncharacterized robust corals, Favia lizardensis (a massive brain coral) and Ctenactis echinata (a solitary coral) and compares it to that of the previously characterized complex coral, Acropora millepora, both morphologically and in terms of the expression of a set of key developmental genes. Illumina sequencing of mixed age embryos was carried out, resulting in embryonic transcriptomes consisting of 40605 contigs for C.echinata (N50 = 1080 bp) and 48536 contigs for F.lizardensis (N50 = 1496 bp). The transcriptomes have been annotated against Swiss-Prot and were sufficiently complete to enable the identification of orthologs of many key genes controlling development in bilaterians. Developmental series of images of whole mounts and sections reveal that the early stages of both species contain a blastocoel, consistent with their membership of the robust clade. In situ hybridization was used to examine the expression of the developmentally important genes brachyury, chordin and forkhead. The expression of brachyury and forkhead was consistent with that previously reported for Acropora and allowed us to confirm that the pseudo-blastopore sometimes seen in robust corals such as Favia spp. is not directly associated with gastrulation. C.echinata chordin expression, however, differed from that seen in the other two corals. Embryonic transcriptomes were assembled for the brain coral Favia lizardensis and the solitary coral Ctenactis echinata. Both species have a blastocoel in their early developmental stages, consistent with their phylogenetic position as members of the robust clade. Expression of the key developmental genes brachyury, chordin and

  1. Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: Prevention with folic acid

    PubMed Central

    Sarmah, Swapnalee; Marrs, James A.

    2014-01-01

    BACKGROUND Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known. RESULTS Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbed multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions. CONCLUSIONS Our results indicate that ethanol exposure interrupted divergent cardiac morphogenesis events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects. PMID:23832875

  2. 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 Central

    SOTO, TIMOTHY; KISS, IVY GISERMAN; CARTER, ALICE S.

    2018-01-01

    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

  3. Post-natal myogenic and adipogenic developmental

    PubMed Central

    Konings, Gonda; van Weeghel, Michel; van den Hoogenhof, Maarten MG; Gijbels, Marion; van Erk, Arie; Schoonderwoerd, Kees; van den Bosch, Bianca; Dahlmans, Vivian; Calis, Chantal; Houten, Sander M; Misteli, Tom

    2011-01-01

    A-type lamins are a major component of the nuclear lamina. Mutations in the LMNA gene, which encodes the A-type lamins A and C, cause a set of phenotypically diverse diseases collectively called laminopathies. While adult LMNA null mice show various symptoms typically associated with laminopathies, the effect of loss of lamin A/C on early post-natal development is poorly understood. Here we developed a novel LMNA null mouse (LMNAGT−/−) based on genetrap technology and analyzed its early post-natal development. We detect LMNA transcripts in heart, the outflow tract, dorsal aorta, liver and somites during early embryonic development. Loss of A-type lamins results in severe growth retardation and developmental defects of the heart, including impaired myocyte hypertrophy, skeletal muscle hypotrophy, decreased amounts of subcutaneous adipose tissue and impaired ex vivo adipogenic differentiation. These defects cause death at 2 to 3 weeks post partum associated with muscle weakness and metabolic complications, but without the occurrence of dilated cardiomyopathy or an obvious progeroid phenotype. Our results indicate that defective early post-natal development critically contributes to the disease phenotypes in adult laminopathies. PMID:21818413

  4. The influence of early intervention, informal support and the family environment on trajectories of competence for fathers raising children with developmental disabilities.

    PubMed

    Crossman, Morgan K; Parish, Susan L; Hauser-Cram, Penny; Garcia, Dolores Acevedo; Warfield, Marji Erickson

    2018-05-21

    Scant research disentangles the relationship between parenting competence, early intervention (EI) services, the family environment and informal support among fathers of children with developmental disabilities. (1) To determine the trajectory of parental competence for fathers of children with DD from age 3 to age 15. (2) Controlling for child and family characteristics, determine the main effects of the family environment, informal support, and EI services on paternal competence when their child with a developmental disability was age 3. (3) To determine whether there were lasting effects of the family environment, informal support, and the EI service system on differences in paternal competence over time. This study used multilevel modeling to analyze longitudinal data from 93 American fathers from the Early Intervention Collaborative Study. There was no significant change over time in paternal competence after controlling for various covariates. Fathers who initially reported low levels of competence when their child was three reported continuously lower competence over time. Family relationships, positive supports, and perceived helpfulness of home visits were significant predictors of paternal competence at age three. Implications for programs and policy include developing and adopting rigorous ways to measure and carefully monitor service provision, including assessments of paternal competence, family relationships and informal supports at the start of early intervention, and fostering continuous collaborations between providers, researchers and clinicians to address challenges in data collection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Early Effects of Responsivity Education/Prelinguistic Milieu Teaching for Children with Developmental Delays and Their Parents

    ERIC Educational Resources Information Center

    Fey, Marc E.; Warren, Steven F.; Brady, Nancy; Finestack, Lizbeth H.; Bredin-Oja, Shelley L.; Fairchild, Martha; Sokol, Shari; Yoder, Paul J.

    2006-01-01

    Purpose: To evaluate the efficacy of a 6-month course of responsivity education/prelinguistic milieu teaching (RE/PMT) for children with developmental delay and RE/PMT's effects on parenting stress in a randomized clinical trial. Method: Fifty-one children, age 24-33 months, with no more than 10 expressive words or signs, were randomly assigned to…

  6. 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…

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect.

    PubMed

    Vogelaar, Ingrid P; Ligtenberg, Marjolijn J L; van der Post, Rachel S; de Voer, Richarda M; Kets, C Marleen; Jansen, Trees J G; Jacobs, Liesbeth; Schreibelt, Gerty; de Vries, I Jolanda M; Netea, Mihai G; Hoogerbrugge, Nicoline

    2016-04-01

    Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88. Immunological assays on peripheral blood mononuclear cells revealed an impaired immune response upon stimulation with Candida albicans, characterized by a defective production of the cytokine interleukin-17. Our data suggest that a genetic defect in MYD88 results in an impaired immune response and may increase gastric cancer risk.

  12. Mutation of the Membrane-Associated M1 Protease APM1 Results in Distinct Embryonic and Seedling Developmental Defects in Arabidopsis[C][W

    PubMed Central

    Peer, Wendy Ann; Hosein, Fazeeda N.; Bandyopadhyay, Anindita; Makam, Srinivas N.; Otegui, Marisa S.; Lee, Gil-Je; Blakeslee, Joshua J.; Cheng, Yan; Titapiwatanakun, Boosaree; Yakubov, Bahktiyor; Bangari, Bharat; Murphy, Angus S.

    2009-01-01

    Aminopeptidase M1 (APM1), a single copy gene in Arabidopsis thaliana, encodes a metallopeptidase originally identified via its affinity for, and hydrolysis of, the auxin transport inhibitor 1-naphthylphthalamic acid (NPA). Mutations in this gene result in haploinsufficiency. Loss-of-function mutants show irregular, uncoordinated cell divisions throughout embryogenesis, affecting the shape and number of cotyledons and the hypophysis, and is seedling lethal at 5 d after germination due to root growth arrest. Quiescent center and cell cycle markers show no signals in apm1-1 knockdown mutants, and the ground tissue specifiers SHORTROOT and SCARECROW are misexpressed or mislocalized. apm1 mutants have multiple, fused cotyledons and hypocotyls with enlarged epidermal cells with cell adhesion defects. apm1 alleles show defects in gravitropism and auxin transport. Gravistimulation decreases APM1 expression in auxin-accumulating root epidermal cells, and auxin treatment increases expression in the stele. On sucrose gradients, APM1 occurs in unique light membrane fractions. APM1 localizes at the margins of Golgi cisternae, plasma membrane, select multivesicular bodies, tonoplast, dense intravacuolar bodies, and maturing metaxylem cells. APM1 associates with brefeldin A–sensitive endomembrane structures and the plasma membrane in cortical and epidermal cells. The auxin-related phenotypes and mislocalization of auxin efflux proteins in apm1 are consistent with biochemical interactions between APM1 and NPA. PMID:19531600

  13. Developmental milestones record

    MedlinePlus

    ... in the early years is to follow your child's development. Most parents also watch for different milestones. Talk ... child's provider if you have concerns about your child's development. Closely watching a "checklist" or calendar of developmental ...

  14. Suppression of OsKu80 results in defects in developmental growth and increased telomere length in rice (Oryza sativa L.).

    PubMed

    Byun, Mi Young; Cui, Li Hua; Kim, Woo Taek

    2015-12-25

    The Ku70-Ku80 heterodimer plays a critical role in the maintenance of genomic stability in humans and yeasts. In this report, we identified and characterized OsKu80 in rice, a model monocot crop. OsKu80 forms a heterodimer with OsKu70 in yeast and plant cells, as demonstrated by yeast two-hybrid, in vivo co-immunoprecipitation, and bimolecular fluorescence complementation assays. RNAi-mediated knock-down T3 transgenic rice plants (Ubi:RNAi-OsKu80) displayed a retarded growth phenotype at the post-germination stage. In addition, the Ubi:RNAi-OsKu80 knock-down progeny exhibited noticeably increased telomere length as compared to wild-type rice. These results are discussed with the idea that OsKu80 plays a role in developmental growth and telomere length regulation in rice plants. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Low-Dose Alkylphenol Exposure Promotes Mammary Epithelium Alterations and Transgenerational Developmental Defects, But Does Not Enhance Tumorigenic Behavior of Breast Cancer Cells

    PubMed Central

    Chamard-Jovenin, Clémence; Thiebaut, Charlène; Chesnel, Amand; Bresso, Emmanuel; Morel, Chloé; Smail-Tabbone, Malika; Devignes, Marie-Dominique; Boukhobza, Taha; Dumond, Hélène

    2017-01-01

    Fetal and neonatal exposure to long-chain alkylphenols has been suspected to promote breast developmental disorders and consequently to increase breast cancer risk. However, disease predisposition from developmental exposures remains unclear. In this work, human MCF-10A mammary epithelial cells were exposed in vitro to a low dose of a realistic (4-nonylphenol + 4-tert-octylphenol) mixture. Transcriptome and cell-phenotype analyses combined to functional and signaling network modeling indicated that long-chain alkylphenols triggered enhanced proliferation, migration ability, and apoptosis resistance and shed light on the underlying molecular mechanisms which involved the human estrogen receptor alpha 36 (ERα36) variant. A male mouse-inherited transgenerational model of exposure to three environmentally relevant doses of the alkylphenol mix was set up in order to determine whether and how it would impact on mammary gland architecture. Mammary glands from F3 progeny obtained after intrabuccal chronic exposure of C57BL/6J P0 pregnant mice followed by F1–F3 male inheritance displayed an altered histology which correlated with the phenotypes observed in vitro in human mammary epithelial cells. Since cellular phenotypes are similar in vivo and in vitro and involve the unique ERα36 human variant, such consequences of alkylphenol exposure could be extrapolated from mouse model to human. However, transient alkylphenol treatments combined to ERα36 overexpression in mammary epithelial cells were not sufficient to trigger tumorigenesis in xenografted Nude mice. Therefore, it remains to be determined if low-dose alkylphenol transgenerational exposure and subsequent abnormal mammary gland development could account for an increased breast cancer susceptibility. PMID:29109696

  16. 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. © 2014 Wiley Periodicals, Inc.

  17. 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...

  18. A framework for evaluating developmental defects at the cellular level: An example from ten maize anther mutants using morphological and molecular data.

    PubMed

    Egger, Rachel L; Walbot, Virginia

    2016-11-01

    In seed plants, anthers are critical for sexual reproduction, because they foster both meiosis and subsequent pollen development of male germinal cells. Male-sterile mutants are analyzed to define steps in anther development. Historically the major topics in these studies are meiotic arrest and post-meiotic gametophyte failure, while relatively few studies focus on pre-meiotic defects of anther somatic cells. Utilizing morphometric analysis we demonstrate that pre-meiotic mutants can be impaired in anticlinal or periclinal cell division patterns and that final cell number in the pre-meiotic anther lobe is independent of cell number changes of individual differentiated somatic cell types. Data derived from microarrays and from cell wall NMR analyses allow us to further refine our understanding of the onset of phenotypes. Collectively the data highlight that even minor deviations from the correct spatiotemporal pattern of somatic cell proliferation can result in male sterility in Zea mays. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. 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…

  20. Examining the social determinants of children's developmental health: protocol for building a pan-Canadian population-based monitoring system for early childhood development.

    PubMed

    Guhn, Martin; Janus, Magdalena; Enns, Jennifer; Brownell, Marni; Forer, Barry; Duku, Eric; Muhajarine, Nazeem; Raos, Rob

    2016-04-29

    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. 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 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 development action and policies, using the database as a tool

  1. Bad habits and bad genes: early 20th-century eugenic attempts to eliminate syphilis and associated "defects" from the United States.

    PubMed

    Wilson, Philip K

    2003-01-01

    American eugenists in the early 20th century distinguished "degenerates," including syphilitics, prostitutes, alcoholics and criminals, from the "normal" population by their particular bad habits. From eugenists' viewpoint, these bad habits were derived from bad character, a flaw that stemmed from an individual's bad genes. This essay explores how eugenists during this period characterized syphilitics and those with associated character "defects" in terms of heredity. Additionally, it examines the methods eugenists most frequently advocated to rectify these bad habits. These methods included marriage restriction, immigration control and reproductive sterilization. Overall, eugenists directed their efforts not so much at the "degenerate" as at his or her germ line.

  2. The AtRbx1 protein is part of plant SCF complexes, and its down-regulation causes severe growth and developmental defects.

    PubMed

    Lechner, Esther; Xie, Daoxin; Grava, Sandrine; Pigaglio, Emmanuelle; Planchais, Severine; Murray, James A H; Parmentier, Yves; Mutterer, Jerome; Dubreucq, Bertrand; Shen, Wen-Hui; Genschik, Pascal

    2002-12-20

    Recently in yeast and animal cells, one particular class of ubiquitin ligase (E3), called the SCF, was demonstrated to regulate diverse processes including cell cycle and development. In plants SCF-dependent proteolysis is also involved in different developmental and hormonal regulations. To further investigate the function of SCF, we characterized at the molecular level the Arabidopsis RING-H2 finger protein AtRbx1. We demonstrated that the plant gene is able to functionally complement a yeast knockout mutant strain and showed that AtRbx1 protein interacts physically with at least two members of the Arabidopsis cullin family (AtCul1 and AtCul4). AtRbx1 also associates with AtCul1 and the Arabidopsis SKP1-related proteins in planta, indicating that it is part of plant SCF complexes. AtRbx1 mRNAs accumulate in various tissues of the plant, but at higher levels in tissues containing actively dividing cells. Finally to study the function of the gene in planta, we either overexpressed AtRbx1 or reduced its expression by a dsRNA strategy. Down-regulation of AtRbx1 impaired seedling growth and development, indicating that the gene is essential in plants. Furthermore, the AtRbx1-silenced plants showed a reduced level of AtCul1 protein, but accumulated higher level of cyclin D3.

  3. Developmental progression to early adult binge drinking and marijuana use from worsening versus stable trajectories of adolescent attention deficit/hyperactivity disorder and delinquency.

    PubMed

    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

    2015-05-01

    To examine the association between developmental trajectories of inattention, hyperactivity-impulsivity and delinquency through childhood and adolescence (ages 8-16 years) and subsequent binge drinking and marijuana use in early adulthood (age 21 years). 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. 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. A total of 579 children with DSM-IV ADHD combined type, aged 7.0 and 9.9 years at baseline (mean = 8.5, SD = 0.80). 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 (mean age 21 years). 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, all P-values <0.05), even when symptom levels in stable trajectories were high. Worsening inattention symptoms and delinquency during adolescence are were associated with higher levels of early adult substance use; this pattern may reflect a developmental course of vulnerability to elevated substance use in early adulthood. © 2015 Society for the Study of Addiction.

  4. Partial trisomy 3p and partial monosomy 11q associated with atrial septal defect, cleft palate, and developmental delay: a case report.

    PubMed

    Tan, E-C; Lim, E; Cham, B; Knight, L; Ng, I

    2011-01-01

    Unbalanced translocation involving both chromosome 3p duplication and 11q deletion in the same patient is extremely rare; only 1 live-born case was reported previously. This karyotype was also detected during prenatal diagnosis of 2 different pregnancies in a Taiwanese family which were both terminated. In all 3 cases, only standard karyotyping was done to detect the abnormal karyotypes. Here, we report a 4-year-old boy with cleft palate, atrial septal defect, and hypotonia with gross and fine motor delay. Oligonucleotide-based array comparative genomic hybridization showed copy number gain from 3pter to 3p24.2 (approximately 24.5 Mb) and copy number loss from 11q25 to 11qter (approximately 5.8 Mb). This de novo unbalanced translocation event involving a terminal 3p duplication and a terminal 11q deletion provides candidate genes for further investigation of dosage effect leading to the patient's multiple phenotypic abnormalities. Genotype-phenotype correlation is difficult to make in this case due to the large number of genes involved. However, the description of such cases together with precise gene-level mapping of chromosomal breakpoints will add to further refinement of candidate genes to be investigated for terminal imbalances in 3p and 11q when more similar cases are reported. Copyright © 2011 S. Karger AG, Basel.

  5. The Role of Omega-3 Fatty Acids in Developmental Psychopathology: A Systematic Review on Early Psychosis, Autism, and ADHD

    PubMed Central

    Nobile, Maria; Ciappolino, Valentina; Delvecchio, Giuseppe; Tesei, Alessandra; Turolo, Stefano; Crippa, Alessandro; Mazzocchi, Alessandra; Altamura, Carlo A.; Brambilla, Paolo

    2017-01-01

    In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of ω-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far. PMID:29207548

  6. 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.…

  7. Effect of W self-implantation and He plasma exposure on early-stage defect and bubble formation in tungsten

    NASA Astrophysics Data System (ADS)

    Thompson, M.; Drummond, D.; Sullivan, J.; Elliman, R.; Kluth, P.; Kirby, N.; Riley, D.; Corr, C. S.

    2018-06-01

    To determine the effect of pre-existing defects on helium-vacancy cluster nucleation and growth, tungsten samples were self-implanted with 1 MeV tungsten ions at varying fluences to induce radiation damage, then subsequently exposed to helium plasma in the MAGPIE linear plasma device. Positron annihilation lifetime spectroscopy was performed both immediately after self-implantation, and again after plasma exposure. After self-implantation vacancies clusters were not observed near the sample surface (<30 nm). At greater depths (30–150 nm) vacancy clusters formed, and were found to increase in size with increasing W-ion fluence. After helium plasma exposure in the MAGPIE linear plasma device at ~300 K with a fluence of 1023 He-m‑2, deep (30–150 nm) vacancy clusters showed similar positron lifetimes, while shallow (<30 nm) clusters were not observed. The intensity of positron lifetime signals fell for most samples after plasma exposure, indicating that defects were filling with helium. The absence of shallow clusters indicates that helium requires pre-existing defects in order to drive vacancy cluster growth at 300 K. Further samples that had not been pre-damaged with W-ions were also exposed to helium plasma in MAGPIE across fluences from 1  ×  1022 to 1.2  ×  1024 He-m‑2. Samples exposed to fluences up to 1  ×  1023 He-m‑2 showed no signs of damage. Fluences of 5  ×  1023 He-m‑2 and higher showed significant helium-cluster formation within the first 30 nm, with positron lifetimes in the vicinity 0.5–0.6 ns. The sample temperature was significantly higher for these higher fluence exposures (~400 K) due to plasma heating. This higher temperature likely enhanced bubble formation by significantly increasing the rate interstitial helium clusters generate vacancies, which is we suspect is the rate-limiting step for helium-vacancy cluster/bubble nucleation in the absence of pre-existing defects.

  8. CHEMICAL PRIORITIZATION FOR DEVELOPMENTAL ...

    EPA Pesticide Factsheets

    Defining a predictive model of developmental toxicity from in vitro and high-throughput screening (HTS) assays can be limited by the availability of developmental defects data. ToxRefDB (www.epa.gov/ncct/todrefdb) was built from animal studies on data-rich environmental chemicals, and has been used as an anchor for predictive modeling of ToxCast™ data. Scaling to thousands of untested chemicals requires another approach. ToxPlorer™ was developed as a tool to query and extract specific facts about defined biological entities from the open scientific literature and to coherently synthesize relevant knowledge about relationships, pathways and processes in toxicity. Here, we investigated the specific application of ToxPlorer to weighting HTS assay targets for relevance to developmental defects as defined in the literature. First, we systemically analyzed 88,193 Pubmed abstracts selected by bulk query using harmonized terminology for 862 developmental endpoints (www.devtox.net) and 364,334 dictionary term entities in our VT-KB (virtual tissues knowledgebase). We specifically focused on entities corresponding to genes/proteins mapped across of >500 ToxCast HTS assays. The 88,193 devtox abstracts mentioned 244 gene/protein entities in an aggregated total of ~8,000 occurrences. Each of the 244 assays was scored and weighted by the number of devtox articles and relevance to developmental processes. This score was used as a feature for chemical prioritization by Toxic

  9. Mutations in MYB3R1 and MYB3R4 Cause Pleiotropic Developmental Defects and Preferential Down-Regulation of Multiple G2/M-Specific Genes in Arabidopsis1[C][W

    PubMed Central

    Haga, Nozomi; Kobayashi, Kosuke; Suzuki, Takamasa; Maeo, Kenichiro; Kubo, Minoru; Ohtani, Misato; Mitsuda, Nobutaka; Demura, Taku; Nakamura, Kenzo; Jürgens, Gerd; Ito, Masaki

    2011-01-01

    R1R2R3-Myb proteins represent an evolutionarily conserved class of Myb family proteins important for cell cycle regulation and differentiation in eukaryotic cells. In plants, this class of Myb proteins are believed to regulate the transcription of G2/M phase-specific genes by binding to common cis-elements, called mitosis-specific activator (MSA) elements. In Arabidopsis (Arabidopsis thaliana), MYB3R1 and MYB3R4 act as transcriptional activators and positively regulate cytokinesis by activating the transcription of KNOLLE, which encodes a cytokinesis-specific syntaxin. Here, we show that the double mutation myb3r1 myb3r4 causes pleiotropic developmental defects, some of which are due to deficiency of KNOLLE whereas other are not, suggesting that multiple target genes are involved. Consistently, microarray analysis of the double mutant revealed altered expression of many genes, among which G2/M-specific genes showed significant overrepresentation of the MSA motif and a strong tendency to be down-regulated by the double mutation. Our results demonstrate, on a genome-wide level, the importance of the MYB3R-MSA pathway for regulating G2/M-specific transcription. In addition, MYB3R1 and MYB3R4 may have diverse roles during plant development by regulating G2/M-specific genes with various functions as well as genes possibly unrelated to the cell cycle. PMID:21862669

  10. Maturity-associated variation in change of direction and dribbling speed in early pubertal years and 5-year developmental changes in young soccer players.

    PubMed

    Valente-Dos-Santos, J; Coelho-E-Silva, M J; Vaz, V; Figueiredo, A J; Capranica, L; Sherar, L B; Elferink-Gemser, M T; Malina, R M

    2014-06-01

    The purpose of the current study was to assess the developmental changes in change of direction and dribbling speed in youth soccer players taking into account skeletal age (SA), maturity status, body size, estimated fat mass, aerobic endurance, lower limb explosive strength and annual volume of training. Eighty-three male soccer players aged 10-15 years (SA) at baseline were annually followed over 5 years, resulting in an average 4.4 observations per player. After testing for multicollinearity, multi-level regression modeling was used to examine the longitudinal developmental changes on change of direction and dribbling speed. Maturity-associated variability was significant in change of direction and also dribbling speed among young soccer players aged 12-14 years with better scores being performed by late maturers. Moreover, the predicted longitudinal scores for change of direction and dribbling speed improved with SA (P<0.01), SA2 (P<0.01) and skeletal maturity status entered as an additional developmental predictor (P<0.05). Estimated fat-free mass (P<0.01), aerobic endurance (P<0.01) and lower limb strength (P<0.01) were additional predictors in both models. The soccer-specific skill, dibbling speed, was also explained by annual volume of training (P<0.05). Skeletal maturity status explains inter-individual variability on maximal short-term run performances with and without the ball possession at early ages of participation in competitive soccer. The effects tend to persist across ages combined with longitudinal changes in body composition and functional fitness. In the particular case of the ball test, annual volume of training was also a longitudinal performance predictor.

  11. In vitro expansion impaired the stemness of early passage mesenchymal stem cells for treatment of cartilage defects

    PubMed Central

    Jiang, Tongmeng; Xu, Guojie; Wang, Qiuyan; Yang, Lihui; Zheng, Li; Zhao, Jinmin; Zhang, Xingdong

    2017-01-01

    In vitro cultured autologous mesenchymal stem cells (MSCs) within passage 5 have been approved for clinical application in stem cell-based treatment of cartilage defects. However, their chondrogenic potential has not yet been questioned or verified. In this study, the chondrogenic potential of bone marrow MSCs at passage 3 (P3 BMSCs) was investigated both in cartilage repair and in vitro, with freshly isolated bone marrow mononuclear cells (BMMNCs) as controls. The results showed that P3 BMSCs were inferior to BMMNCs not only in their chondrogenic differentiation ability but also as candidates for long-term repair of cartilage defects. Compared with BMMNCs, P3 BMSCs presented a decay in telomerase activity and a change in chromosomal morphology with potential anomalous karyotypes, indicating senescence. In addition, interindividual variability in P3 BMSCs is much higher than in BMMNCs, demonstrating genomic instability. Interestingly, remarkable downregulation in cell cycle, DNA replication and mismatch repair (MMR) pathways as well as in multiple genes associated with telomerase activity and chromosomal stability were found in P3 BMSCs. This result indicates that telomerase and chromosome anomalies might originate from expansion, leading to impaired stemness and pluripotency of stem cells. In vitro culture and expansion are not recommended for cell-based therapy, and fresh BMMNCs are the first choice. PMID:28569773

  12. Developmental Toxicity of the Organic Fraction from Hydraulic Fracturing Flowback and Produced Waters to Early Life Stages of Zebrafish ( Danio rerio).

    PubMed

    He, Yuhe; Sun, Chenxing; Zhang, Yifeng; Folkerts, Erik J; Martin, Jonathan W; Goss, Greg G

    2018-03-20

    Hydraulic fracturing (HF) has emerged as a major recovery method of unconventional oil and gas reservoirs and concerns have been raised regarding the environmental impact of releases of Flowback and Produced Water (FPW) to aquatic ecosystems. To investigate potential effects of HF-FPW on fish embryo development, HF-FPW samples were collected from two different wells and the organic fractions were isolated from both aqueous and particle phases to eliminate the confounding effects of high salinity. Each organic extract was characterized by non-target analysis with HPLC-Orbitrap-MS, with targeted analysis for polycyclic aromatic hydrocarbons provided as markers of petroleum-affected water. The organic profiles differed between samples, including PAHs and alkyl PAHs, and major substances identified by non-target analysis included polyethylene glycols, alkyl ethoxylates, octylphenol ethoxylates, and other high molecular weight (C 49-79 ) ethylene oxide polymeric material. Zebrafish embryos were exposed to various concentrations of FPW organic extracts to investigate acute (7-day) and developmental toxicity in early life stages. The acute toxicity (LD 50 ) of the extracted FPW fractions ranged from 2.8× to 26× the original organic content. Each extracted FPW fraction significantly increased spinal malformation, pericardial edema, and delayed hatch in exposed embryos and altered the expression of a suite of target genes related to biotransformation, oxidative stress, and endocrine-mediation in developing zebrafish embryos. These results provide novel information on the variation of organic profiles and developmental toxicity among different sources and fractions of HF-FPWs.

  13. 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

  14. Arrhythmias after transcatheter closure of perimembranous ventricular septal defects with a modified double-disk occluder: early and long-term results.

    PubMed

    Li, Pan; Zhao, Xian-xian; Zheng, Xing; Qin, Yong-wen

    2012-07-01

    With the development of interventional techniques and devices, transcatheter closure of perimembranous ventricular septal defect has been widely performed. However, there has been a lack of long-term follow-up results about postoperative ECG changes of PmVSD patients. We report our experience of early and late arrhythmias after transcatheter closure of PmVSD with a modified double-disk occluder (MDVO). We performed a retrospective review of 79 patients (47 males, 32 females) between September 2002 and May 2007 who underwent transcatheter closure of perimembranous ventricular septal defect. Symmetric and asymmetric PmVSD occluders were used. The diameter of the evaluated defects ranged from 3 to 12 mm, as measured by TTE and 3 to 15 mm by left ventriculography. Most cases of PmVSD were treated successfully with a single procedure, resulting in a successful closure rate of 97% (77/79 patients). There was no death in any of the patients. After the operation, 79 patients were followed-up for a range of 10-76 months (35.3 ± 17.4 months). In this series, 11 cases of incomplete right bundle branch block and five cases of complete right bundle branch block occurred during the early period after operation. During long-term follow-up, these issues declined in prevalence to five and four cases, respectively. Moreover, reversible third-degree AVB occurred during closure or after the procedure, and two of the three patients with reversible AVB received a temporary heart pacemaker implantation. These patients recovered 1 h, 6 days, and 9 days later, respectively. During 10-76 months of follow-up, no complications occurred in any of the patients, including residual shunt, severe aortic valve, or tricuspid valve regurgitation. Device closure of perimembranous ventricular septal defects with a modified double-disk occluder (MDVO) resulted in excellent closure rates and acceptably low arrhythmia rates.

  15. Long-term Associations of an Early Corrected Ventricular Septal Defect and Stress Systems of Child and Mother at Primary School Age.

    PubMed

    Stonawski, Valeska; Vollmer, Laura; Köhler-Jonas, Nicola; Rohleder, Nicolas; Golub, Yulia; Purbojo, Ariawan; Moll, Gunther H; Heinrich, Hartmut; Cesnjevar, Robert A; Kratz, Oliver; Eichler, Anna

    2017-01-01

    Ventricular septal defect (VSD) is the most common congenital heart defect, with larger VSDs typically being corrected with an open-heart surgery during infancy. Long-term consequences of a VSD-corrective surgery on stress systems of child and mother are still unknown. The aim of the present study is to investigate the associations of an early corrected VSD and diurnal cortisol release of child and mother. 26 children (12 boys) between 6 and 9 years old, who underwent surgery for an isolated VSD within the first 3 years of life, and their mothers participated in the study. Their diurnal cortisol profiles were compared to a sex-, age-, and socioeconomic status-matched healthy control group. Within the VSD group, associations between cortisol and characteristics of surgery and hospitalization were investigated. Child and mother psychopathological symptoms were considered as a possible interfering mechanism of altered cortisol profiles. Diurnal cortisol profiles of children with an early corrected VSD did not differ from those of controls. However, mothers of affected children exhibited higher cortisol levels in the morning ( p  < 0.001, [Formula: see text]) and a steeper diurnal cortisol slope ( p  = 0.016, [Formula: see text]) than mothers of healthy children. Results indicate a favorable development of children with an early corrected VSD, in terms of comparable diurnal cortisol profiles with healthy controls, according to a comparable mother-rated psychopathology. Mothers of affected children reveal altered diurnal cortisol levels, without differences in self-rated psychopathology. This divergence should be clarified in future research.

  16. 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.

  17. 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

  18. 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

  19. Feasibility of a Team Approach to Complex Congenital Heart Defect Neurodevelopmental Follow-Up: Early Experience of a Combined Cardiology/Neonatal Intensive Care Unit Follow-Up Program.

    PubMed

    Chorna, Olena; Baldwin, H Scott; Neumaier, Jamie; Gogliotti, Shirley; Powers, Deborah; Mouvery, Amanda; Bichell, David; Maitre, Nathalie L

    2016-07-01

    Infants with complex congenital heart disease are at high risk for poor neurodevelopmental outcomes. However, implementation of dedicated congenital heart disease follow-up programs presents important infrastructure, personnel, and resource challenges. We present the development, implementation, and retrospective review of 1- and 2-year outcomes of a Complex Congenital Heart Defect Neurodevelopmental Follow-Up program. This program was a synergistic approach between the Pediatric Cardiology, Cardiothoracic Surgery, Pediatric Intensive Care, and Neonatal Intensive Care Unit Follow-Up teams to provide a feasible and responsible utilization of existing infrastructure and personnel, to develop and implement a program dedicated to children with congenital heart disease. Trained developmental testers administered the Ages and Stages Questionnaire-3 over the phone to the parents of all referred children at least once between 6 and 12 months' corrected age. At 18 months' corrected age, all children were scheduled in the Neonatal Intensive-Care Unit Follow-Up Clinic for a visit with standardized neurological exams, Bayley III, multidisciplinary therapy evaluations and continued follow-up. Of the 132 patients identified in the Cardiothoracic Surgery database and at discharge from the hospital, a total number of 106 infants were reviewed. A genetic syndrome was identified in 23.4% of the population. Neuroimaging abnormalities were identified in 21.7% of the cohort with 12.8% having visibly severe insults. As a result, 23 (26.7%) received first-time referrals for early intervention services, 16 (13.8%) received referrals for new services in addition to their existing ones. We concluded that utilization of existing resources in collaboration with established programs can ensure targeted neurodevelopmental follow-up for all children with complex congenital heart disease. © 2016 American Heart Association, Inc.

  20. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice.

    PubMed

    Jonscher, Karen R; Stewart, Michael S; Alfonso-Garcia, Alba; DeFelice, Brian C; Wang, Xiaoxin X; Luo, Yuhuan; Levi, Moshe; Heerwagen, Margaret J R; Janssen, Rachel C; de la Houssaye, Becky A; Wiitala, Ellen; Florey, Garrett; Jonscher, Raleigh L; Potma, Eric O; Fiehn, Oliver; Friedman, Jacob E

    2017-04-01

    Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity or Western-style diet (WD) increases steatosis and oxidative stress in fetal liver and is associated with lifetime disease risk in the offspring. Pyrroloquinoline quinone (PQQ) is a natural antioxidant found in soil, enriched in human breast milk, and essential for development in mammals. We investigated whether a supplemental dose of PQQ, provided prenatally in a mouse model of diet-induced obesity during pregnancy, could protect obese offspring from progression of NAFLD. PQQ treatment given pre- and postnatally in WD-fed offspring had no effect on weight gain but increased metabolic flexibility while reducing body fat and liver lipids, compared with untreated obese offspring. Indices of NAFLD, including hepatic ceramide levels, oxidative stress, and expression of proinflammatory genes ( Nos2 , Nlrp3 , Il6 , and Ptgs2 ), were decreased in WD PQQ-fed mice, concomitant with increased expression of fatty acid oxidation genes and decreased Pparg expression. Notably, these changes persisted even after PQQ withdrawal at weaning. Our results suggest that supplementation with PQQ, particularly during pregnancy and lactation, protects offspring from WD-induced developmental programming of hepatic lipotoxicity and may help slow the advancing epidemic of NAFLD in the next generation.-Jonscher, K. R., Stewart, M. S., Alfonso-Garcia, A., DeFelice, B. C., Wang, X. X., Luo, Y., Levi, M., Heerwagen, M. J. R., Janssen, R. C., de la Houssaye, B. A., Wiitala, E., Florey, G., Jonscher, R. L., Potma, E. O., Fiehn, O. Friedman, J. E. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice. © FASEB.

  1. 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

  2. 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…

  3. "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…

  4. Incorporating Family Assessment and Individualized Family Service Plans into Early Intervention Programs: A Developmental, Decision Making Process.

    ERIC Educational Resources Information Center

    Kochanek, Thomas T.; Friedman, Donna Haig

    The monograph presents essential components of a decision making sequence used to incorporate formalized family assessment and service planning procedures into two existing early intervention programs in Massachusetts. The 1-year effort used a consultant to: (1) redefine screening and assessment processes to include both child and family centered…

  5. 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...

  6. 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…

  7. Chemotherapeutic-Induced Cardiovascular Dysfunction: Physiological Effects, Early Detection—The Role of Telomerase to Counteract Mitochondrial Defects and Oxidative Stress

    PubMed Central

    Quryshi, Nabeel; Norwood Toro, Laura E.; Ait-Aissa, Karima; Kong, Amanda; Beyer, Andreas M.

    2018-01-01

    Although chemotherapeutics can be highly effective at targeting malignancies, their ability to trigger cardiovascular morbidity is clinically significant. Chemotherapy can adversely affect cardiovascular physiology, resulting in the development of cardiomyopathy, heart failure and microvascular defects. Specifically, anthracyclines are known to cause an excessive buildup of free radical species and mitochondrial DNA damage (mtDNA) that can lead to oxidative stress-induced cardiovascular apoptosis. Therefore, oncologists and cardiologists maintain a network of communication when dealing with patients during treatment in order to treat and prevent chemotherapy-induced cardiovascular damage; however, there is a need to discover more accurate biomarkers and therapeutics to combat and predict the onset of cardiovascular side effects. Telomerase, originally discovered to promote cellular proliferation, has recently emerged as a potential mechanism to counteract mitochondrial defects and restore healthy mitochondrial vascular phenotypes. This review details mechanisms currently used to assess cardiovascular damage, such as C-reactive protein (CRP) and troponin levels, while also unearthing recently researched biomarkers, including circulating mtDNA, telomere length and telomerase activity. Further, we explore a potential role of telomerase in the mitigation of mitochondrial reactive oxygen species and maintenance of mtDNA integrity. Telomerase activity presents a promising indicator for the early detection and treatment of chemotherapy-derived cardiac damage. PMID:29534446

  8. Birth Defects Research and Tracking

    MedlinePlus

    ... least one month before getting pregnant and during early pregnancy lowers the risk of having a baby with ... 2017) Key Findings: Use of Pain Medicine During Early Pregnancy May Be Related To Birth Defects A study ...