Sample records for potential developmental effects

  1. 76 FR 55391 - Notice of Postponement of Release of Draft NTP Monograph on Potential Developmental Effects of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Notice of Postponement of Release of Draft NTP Monograph on Potential Developmental Effects of Cancer Chemotherapy During Pregnancy and Panel Meeting To Peer... NTP Monograph on Potential Developmental Effects of Cancer Chemotherapy during Pregnancy and the peer...

  2. Fired up or burned out? How developmental challenge differentially impacts leader behavior.

    PubMed

    Courtright, Stephen H; Colbert, Amy E; Choi, Daejeong

    2014-07-01

    Leadership development research has largely drawn on experiential and enactive learning theories to explore the positive effects of developmental challenge on leaders. In contrast, we examined potential positive and negative effects of developmental challenge (i.e., challenging job assignments) on leader behavior through an alternative theoretical lens--transactional stress theory. We predicted, on one hand, that developmental challenge may be associated with higher leader engagement and transformational leadership behavior; however, developmental challenge also has the potential to be associated with higher leader emotional exhaustion and laissez-faire leadership behavior. We further proposed that leadership self-efficacy (LSE) moderates these potential effects of developmental challenge and helps explain why leaders react either positively or negatively to developmental challenge. We tested our hypotheses in a sample of 153 leaders and 631 direct reports at a Fortune 500 company. Findings supported positive relationships among developmental challenge, leader engagement, and transformational leadership. However, we also found support for significant relationships among developmental challenge, emotional exhaustion, and laissez-faire leadership. Additionally, leaders lower in LSE were more likely to encounter the negative effects of developmental challenge by experiencing increased emotional exhaustion and displaying laissez-faire leadership behaviors. Our study contributes to theory and practice by elucidating a "dark side" of developmental challenge, identifying LSE as a moderator of the negative effects of developmental challenge, identifying antecedents of transformational and laissez-faire leadership behaviors, and investigating demands and stress in leadership roles.

  3. 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...

  4. The developmental potential of parthenogenetic and somatic cell nuclear-transferred rat oocytes in vitro.

    PubMed

    Mizumoto, Shigetoshi; Kato, Yoko; Tsunoda, Yukio

    2008-12-01

    We examined the optimal conditions for somatic cell nuclear transfer (SCNT) in rat oocytes. First, we compared the effects of two types of inhibitors of spontaneous activation, MG132 and demecolcine, on the developmental potential of parthenogenetic oocytes. The potential of activated oocytes to develop into blastocysts significantly decreased 2 h after oocyte recovery (77% vs. 7%). The developmental potential of oocytes preserved in MG132-supplemented medium for 1 to 4 h was high (62% to 77%), but the potential of those preserved in demecolcine-supplemented medium for 3 and 4 h was low (77% vs. 41% and 37%, respectively). Second, the effect of the duration of parthenogenetic activation on the developmental potential was examined. When oocytes preserved in MG132 for 4 h were treated with 10 mM strontium for 5 or 6 h, the potential of activated oocytes to develop into blastocysts was high (78% and 70%, respectively). Using the optimal conditions for parthenogenetic activation, we examined the potential of rat enucleated oocytes receiving cumulus cells to develop into blastocysts. In contrast to parthenogenotes, the potential of SCNT rat oocytes to develop into blastocysts was low (2%) even if then oocytes were treated with the histone deacetylation inhibitor trichostatin A. The reason for the low developmental potential of rat SCNT oocytes is discussed.

  5. A risk assessment of topical tretinoin as a potential human developmental toxin based on animal and comparative human data.

    PubMed

    Johnson, E M

    1997-03-01

    Although topically applied all-trans-retinoic acid (tretinoin) undergoes minimal absorption and adds negligibly to normal endogenous levels, its safety in humans is occasionally questioned because oral ingestion of retinoids at therapeutic levels is known to entail teratogenic risks. To assess the actual potential for developmental toxicity from treatment with topical tretinoin. Risk assessments were conducted on four known human developmental toxicants (valproic acid, methotrexate, thalidomide, and isotretinoin) and a potential developmental toxicant (acetylsalicylic acid). The margin of safety for each chemical was calculated from the ratio of animal no-observed adverse effect levels to human lowest-observed adverse effect levels or estimated exposure doses. The derived safety margin of more than 100 for topical tretinoin (with 2% absorption) contrasted sharply with the near unity values for valproic acid, methotrexate, thalidomide, and isotretinoin and was larger than that for acetylsalicylic acid. These data support other epidemiologic and animal data that topical tretinoin is not a potential human developmental toxicant.

  6. Developmental Changes in Memory Encoding: Insights from Event-Related Potentials

    ERIC Educational Resources Information Center

    Rollins, Leslie; Riggins, Tracy

    2013-01-01

    The aim of the present study was to investigate developmental changes in encoding processes between 6-year-old children and adults using event-related potentials (ERPs). Although episodic memory ("EM") effects have been reported in both children and adults at retrieval and subsequent memory effects have been established in adults, no…

  7. An Empowerment Framework for Latinx Students in Developmental Education

    ERIC Educational Resources Information Center

    Doran, Erin E.

    2017-01-01

    While developmental education in community colleges has the potential to prepare students for college-level work, its effectiveness and need is often questioned. Further, while Latinx students are overrepresented in developmental courses, there is a dearth of literature on their experiences in such courses and how to effectively serve their needs…

  8. Effects of nuclear transfer procedures on ES cell cloning efficiency in the mouse.

    PubMed

    Yabuuchi, Akiko; Yasuda, Yoshiko; Kato, Yoko; Tsunoda, Yukio

    2004-04-01

    Enucleated oocytes receiving mouse embryonic stem (ES) cells develop into fertile young. The developmental potential to young is low, however, and the rate of postnatal death is high. We examined the effect of various nuclear transfer procedures on the in vitro and in vivo developmental potential of nuclear-transferred oocytes. The potential of oocytes receiving ES cells at M phase to develop into blastocysts after fusion by Sendai virus was high compared with that after direct injection (67% vs. 30%). The developmental potential of oocytes receiving ES cells at the M phase is higher than that of oocytes receiving ES cells at the G(1) phase (30-67% vs. 2-5%). Developmental ability to live young was low in all groups (0-4%). Different activation protocols affected the potential to develop into blastocysts to a different extent (27-62%), but did not affect the potential to develop into live young (0-3%). The present study demonstrated that the various conditions examined did not affect the potential of nuclear-transferred oocytes receiving ES cells to develop into live young or the incidence of postnatal death.

  9. A review of developmental and reproductive toxicity of CS2 and H2 S generated by the pesticide sodium tetrathiocarbonate.

    PubMed

    Silva, Marilyn

    2013-04-01

    Sodium tetrathiocarbonate (STTC) is an example of a pesticide that when prepared for use in aqueous solution releases two toxic products carbon disulfide (CS2 ) (active ingredient) and hydrogen sulfide (H2 S) in ambient air in equimolar concentrations resulting in potential exposure to workers and bystanders. CS2 and H2 S are pollutants that are generated from several pesticides as well as in industrial settings. Registrant submitted reports and open literature studies for STTC, CS2 and H2 S were reviewed. Previous reports suggest that CS2 was a concern as a developmental and reproductive toxicant. H2 S was also examined since it is a neurotoxicant and potentially harmful to developing fetuses. STTC did not induce developmental or reproductive effects in animal studies. CS2 was a developmental neurobehavioral toxin in rat pups (inhalation no observed effect level [NOEL]=0.01 ppm). Reproductive effects occurred in male and female factory workers after CS2 exposure (NOEL=1 ppm). H2 S had developmental effects in rats at doses at or above those observed for nasal pathology (NOEL=10 ppm) but was not a reproductive or developmental toxin in humans. The database for CS2 indicates a strong potential for developmental neurotoxicity in animals at low doses but it is lacking in acceptable, well-performed studies. There is also a lack of studies performed with CS2 and H2 S as a mixture. © 2013 Wiley Periodicals, Inc.

  10. Assessment of Mouse Germinal Vesicle Stage Oocyte Quality by Evaluating the Cumulus Layer, Zona Pellucida, and Perivitelline Space

    PubMed Central

    Liu, Ying-Lei; Chen, Ying; Zhou, Cheng-Jie; Wu, Sha-Na; Shen, Jiang-Peng; Liang, Cheng-Guang

    2014-01-01

    To improve the outcome of assisted reproductive technology (ART) for patients with ovulation problems, it is necessary to retrieve and select germinal vesicle (GV) stage oocytes with high developmental potential. Oocytes with high developmental potential are characterized by their ability to undergo proper maturation, fertilization, and embryo development. In this study, we analyzed morphological traits of GV stage mouse oocytes, including cumulus cell layer thickness, zona pellucida thickness, and perivitelline space width. Then, we assessed the corresponding developmental potential of each of these oocytes and found that it varies across the range measured for each morphological trait. Furthermore, by manipulating these morphological traits in vitro, we were able to determine the influence of morphological variation on oocyte developmental potential. Manually altering the thickness of the cumulus layer showed strong effects on the fertilization and embryo development potentials of oocytes, whereas manipulation of zona pellucida thickness effected the oocyte maturation potential. Our results provide a systematic detailed method for selecting GV stage oocytes based on a morphological assessment approach that would benefit for several downstream ART applications. PMID:25144310

  11. DEVELOPMENTAL AGE EFFECTS ON TISSUE DISPOSITION OF BDE 47 IN MICE

    EPA Science Inventory

    Public health concern for polybrominated diphenyl ethers (PBDEs) has focused on potential hazardous effects resulting from exposure to infants and young children because of previous studies reporting adverse developmental effects in rodent studies. This study investigated distrib...

  12. Maternally Mediated Developmental Toxicity

    EPA Science Inventory

    The current practice for the assessment of an agent’s potential effects on the developing embryo/fetus includes administration of high, maternally toxic doses to pregnant laboratory animals. For most agents evaluated, developmental effects occur concomitant with maternal toxicity...

  13. Maternally Mediated Developmental Toxicity

    EPA Science Inventory

    The current practice for the assessment of an agent’s potential effects on the developing embryo/fetus includes administration of high, maternally toxic doses to pregnant laboratory animals. For most agents evaluated, developmental effects occur concomitant with maternal to...

  14. N-acetyl-L-cysteine pre-treatment protects cryopreserved bovine spermatozoa from reactive oxygen species without compromising the in vitro developmental potential of intracytoplasmic sperm injection embryos.

    PubMed

    Pérez, L; Arias, M E; Sánchez, R; Felmer, R

    2015-12-01

    Excess of reactive oxygen species (ROS) on in vitro embryo production systems negatively affects the quality and developmental potential of embryos, as result of a decreased sperm quality and increased DNA fragmentation. This issue is of major importance in assisted fertilisation procedures such as intracytoplasmic sperm injection (ICSI), because this technique does not allow the natural selection of competent spermatozoa, and therefore, DNA-damaged spermatozoa might be used to fertilise an egg. The aim of this study was to investigate a new strategy to prevent the potential deleterious effect of ROS on cryopreserved bovine spermatozoa. We evaluated the effect of a sperm pre-treatment with different concentrations of N-acetyl-L-cysteine (NAC) on ROS production, viability and DNA fragmentation and assessed the effect of this treatment on the in vitro developmental potential and quality of embryos generated by ICSI. The results show a strong scavenging effect of 1 and 10 mm NAC after exposure of spermatozoa to a ROS inducer, without compromising the viability and DNA integrity. Importantly, in vitro developmental potential and quality of embryos generated by ICSI with spermatozoa treated with NAC were not affected, confirming the feasibility of using this treatment before an ICSI cycle. © 2015 Blackwell Verlag GmbH.

  15. Effects of the SAFE Children preventive intervention on developmental trajectories of attention-deficit/hyperactivity disorder symptoms.

    PubMed

    Fowler, Patrick J; Henry, David B; Schoeny, Michael; Gorman-Smith, Deborah; Tolan, Patrick H

    2014-11-01

    This study examined whether a family-based preventive intervention for inner-city children entering the first grade could alter the developmental course of attention-deficit/hyperactivity disorder (ADHD) symptoms. Participants were 424 families randomly selected and randomly assigned to a control condition (n = 192) or Schools and Families Educating Children (SAFE) Children (n = 232). SAFE Children combined family-focused prevention with academic tutoring to address multiple developmental-ecological needs. A booster intervention provided in the 4th grade to randomly assigned children in the initial intervention (n =101) evaluated the potential of increasing preventive effects. Follow-up occurred over 5 years with parents and teachers reporting on attention problems. Growth mixture models identified multiple developmental trajectories of ADHD symptoms. The initial phase of intervention placed children on more positive developmental trajectories for impulsivity and hyperactivity, demonstrating the potential for ADHD prevention in at-risk youth, but the SAFE Children booster had no additional effect on trajectory or change in ADHD indicators.

  16. In vitro approaches to screening and prioritization of chemicals for potential developmental neurotoxicity

    EPA Science Inventory

    Characterization of the potential adverse effects is lacking for tens of thousands of chemicals that are present in the environment, and characterization of developmental neurotoxicity (DNT) hazard lags behind that of other adverse outcomes (e.g. hepatotoxicity). This is due in p...

  17. In vitro approaches to screening and prioritizing chemicals for potential developmental neurotoxicity

    EPA Science Inventory

    Characterization of the potential adverse effects is lacking for tens of thousands of chemicals that are present in the environment, and characterization of developmental neurotoxicity (DNT) hazard lags behind that of other adverse outcomes (e.g. hepatotoxicity). This is due in p...

  18. USING THE MEDAKA EMBRYO ASSAY TO INVESTIGATE DEVELOPMENTAL ETHANOL TOXICITY.

    EPA Science Inventory

    Ethanol (EtOH) is a well-known developmental toxicant that produces a range of abnormal phenotypes. While the toxic potential of developmental EtOH exposure is well characterized, the effect of the timing of exposure on the extent of toxicity remains unknown. Fish models such as ...

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Yi; Wei, Wei; Wang, Yuan

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism onmore » long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and hypothyroidism. - Highlights: • Neurotoxicity of developmental hypothyroxinemia impaired LTP. • Decreased activation of PI3K signaling contributed to LTP impairments. • The recovery of TH after the developmental period did not prevent LTP impairments. • ID diet successfully induced neurotoxicity of developmental hypothyroxinemia.« less

  20. EVALUATION OF POTENTIAL DEVELOPMENTAL NEUROTOXICITY OF ORGANOTINS.

    EPA Science Inventory

    Organotins, including monomethyltin (MMT), dimethyltin (DMT), and dibutyltin (DBT), are widely used as heat stabilizers in PVC and CPVC piping, which results in their presence in drinking water supplies. Concern for developmental neurotoxic effects were raised by published findi...

  1. The Potential Contribution of Advanced Imaging Techniques to Developmental Neurotoxicity Risk Assessment

    EPA Science Inventory

    Neuropathologic assessment provides critical data essential to developmental neurotoxicity risk assessment. There are a number of objectives in conducting a neuropathologic assessment to effectively support risk assessment. These include a comprehensive assessment of the adult an...

  2. Effortful Control Mediates Associations of Fetal Growth with Hyperactivity and Behavioural Problems in 7- to 9-Year-Old Children

    ERIC Educational Resources Information Center

    Schlotz, Wolff; Jones, Alexander; Godfrey, Keith M.; Phillips, David I. W.

    2008-01-01

    Background: Inverse associations of fetal growth with behavioural problems in childhood have been repeatedly reported, suggesting long-term effects of the prenatal developmental environment on behaviour later in life. However, no study so far has examined effects on temperament and potential developmental pathways. Temperamental traits may be…

  3. The relationship of maternal and fetal toxicity in developmental toxicology bioassays with notes on the biological significance of the "no observed adverse effect level".

    EPA Science Inventory

    Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects and include dose levels that induce maternal toxicity. The work reported here was undertaken to evaluate the relationship of maternal and fetal toxicity. It co...

  4. Estimating disturbance effects from military training using developmental instability and physiological measures of plant stress

    USGS Publications Warehouse

    Duda, J.J.; Freeman, D.C.; Brown, M.L.; Graham, J.H.; Krzysik, A.J.; Emlen, J.M.; Zak, J.C.; Kovacic, D.A.

    2004-01-01

    We used developmental instability, water potential, and variable fluorescence to determine if populations of winged sumac (Rhus copallinum) were being negatively effected by military training disturbance. We established nine sites that represented a land-use disturbance gradient with three impact levels (low, medium, and high), the effects mostly due to mechanized infantry training maneuvers. Although mean values of developmental instability, water potential, and variable fluorescence differed significantly among sites, the patterns did not consistently differentiate sites relative to the disturbance gradient. At the population level, some measures of developmental instability and variable fluorescence were positively correlated. All nine sites consisted of habitat mosaics, with the abundance of higher quality habitat patches and canopy gaps closely related to habitat impacts. It may be that R. copallinum is selecting similar micro-environments at all sites and therefore minimizing inter-site variation in stress measures, despite large differences in overall habitat condition. Our results call for caution in developing ecological indicators using the response of physiological and morphological measures from a single plant species. ?? 2003 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2012-01-01

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

  6. Simulated developmental and reproductive impacts on amphibian populations and implications for assessing long-term effects

    EPA Science Inventory

    Fish endpoints measured in early life stage toxicity tests are often used as representative of larval amphibian sensitivity in Ecological Risk Assessment (ERA). This application potentially overlooks the impact of developmental delays on amphibian metamorphosis, and thereby red...

  7. Location negative priming effects in children with developmental dyslexia: An event-related potential study.

    PubMed

    Ma, Yujun; Wang, Enguo; Yuan, Tian; Zhao, Guo Xiang

    2016-08-01

    As the reading process is inseparable from working memory, inhibition, and other higher cognitive processes, the deep cognitive processing defects that are associated with dyslexia may be due to defective distraction inhibition systems. In this study, we used event-related potential technology to explore the source of negative priming effects in children with developmental dyslexia and in a group of healthy children for comparison. We found that the changes in the average response times in the negative priming and control conditions were consistent across the two groups, while the negative priming effects differed significantly between the groups. The magnitude of the negative priming effect was significantly different between the two groups, with the magnitude being significantly higher in the control group than it was in the developmental dyslexia group. These results indicate that there are deficits in distraction inhibition in children with developmental dyslexia. In terms of the time course of processing, inhibition deficits in the dyslexia group appeared during early-stage cognition selection and lasted through the response selection phase. Regarding the cerebral cortex locations, early-stage cognition selection was mainly located in the parietal region, while late-stage response selection was mainly located in the frontal and central regions. The results of our study may help further our understanding of the intrinsic causes of developmental dyslexia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Developmental instability analysis of BKD-infected spring Chinook salmon (Onchorhynchus tshawytscha) prior to seawater exposure

    USGS Publications Warehouse

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

    1997-01-01

    Stress in organisms results in energy dissipation, making developmental pathways less stable. Effects of chronic stress, manifested as small random departures from phenotypic symmetry, reflect developmental instability, are considered to be epigenetic and an effect produced by compromised fitness. Instability is detectable and effectively interpreted among sites or populations if samples are collected randomly, the stressor is present throughout character development, characters are identified accurately and excessive mortality does not erase the existence of developmental instability. Bacterial kidney disease (BKD) is a chronic systemic disease in salmonids that, after vertical transmission from parent to egg, persists and spreads throughout ontogeny, potentially affecting developmental processes. Because levels of progeny infection reflect parental infection levels, groups of offspring from parents with high and low levels of BKD infection can be compared to assess the effects of disease-mediated developmental stress. Analyses of fluctuating asymmetry in five bilateral characters were inconclusive, but significant reductions in the proportion of unusable scales, in the number of circulus errors, and in the directional asymmetry of branchiostegal rays were observed in fish from the high-BKD group. This group also contained individuals of significantly larger size. These results are opposite to those expected from traditional developmental instability theory in suggesting that surviving high-BKD fish have greater developmental stability. This reversal appears to be produced by selective mortality having a greater effect than sublethal stress in altering developmental instability patterns. These results are discussed with respect to size selectivity, heterosis and the assumptions supporting developmental instability as a tool for detecting chronic sublethal stress.

  9. Developmental neurotoxicants in e-waste: an emerging health concern.

    PubMed

    Chen, Aimin; Dietrich, Kim N; Huo, Xia; Ho, Shuk-mei

    2011-04-01

    Electronic waste (e-waste) has been an emerging environmental health issue in both developed and developing countries, but its current management practice may result in unintended developmental neurotoxicity in vulnerable populations. To provide updated information about the scope of the issue, presence of known and suspected neurotoxicants, toxicologic mechanisms, and current data gaps, we conducted this literature review. We reviewed original articles and review papers in PubMed and Web of Science regarding e-waste toxicants and their potential developmental neurotoxicity. We also searched published reports of intergovernmental and governmental agencies and nongovernmental organizations on e-waste production and management practice. We focused on the potential exposure to e-waste toxicants in vulnerable populations-that is, pregnant women and developing children-and neurodevelopmental outcomes. In addition, we summarize experimental evidence of developmental neurotoxicity and mechanisms. In developing countries where most informal and primitive e-waste recycling occurs, environmental exposure to lead, cadmium, chromium, polybrominated diphenyl ethers, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons is prevalent at high concentrations in pregnant women and young children. Developmental neurotoxicity is a serious concern in these regions, but human studies of adverse effects and potential mechanisms are scarce. The unprecedented mixture of exposure to heavy metals and persistent organic pollutants warrants further studies and necessitates effective pollution control measures. Pregnant women and young children living close to informal e-waste recycling sites are at risk of possible perturbations of fetus and child neurodevelopment.

  10. An overview of butanol-induced developmental neurotoxicity and the potential mechanisms related to these observed effects.

    PubMed

    Bale, Ambuja S; Lee, Janice S

    2016-01-01

    The purpose of this article is to briefly review the published literature on the developmental neurotoxic effects, including potential mechanisms, of four butanols: n-butanol, sec-butanol, tert-butanol, isobutanol, and identify data gaps and research needs for evaluation of human health risks in this area. Exposure potential to these four butanols is considerable given the high production volume (>1 billion lb) of n- and tert-butanol and moderate production volumes (100-500 million lb) of sec- and isobutanol. With the impetus to derive cleaner gasoline blends, butanols are being considered for use as fuel oxygenates. Notable signs of neurotoxicity and developmental neurotoxicity have been observed in some studies where laboratory animals (rodents) were gestationally exposed to n- or tert-butanol. Mechanistic data relevant to the observed developmental neurotoxicity endpoints were also reviewed to hypothesize potential mechanisms associated with the developmental neurotoxicity outcome. Data from the related and highly characterized alcohol, ethanol, were included to examine consistencies between this compound and the four butanols. It is widely known that alcohols, including butanols, interact with several ion channels and modulate the function of these targets following both acute and chronic exposures. In addition, n- and sec-butanol have been demonstrated to inhibit fetal rat brain astroglial cell proliferation. Further, rat pups exposed to n-butanol in utero were also reported to have significant increases in brain levels of dopamine and serotonin, but decreases in serotonin levels were noted with gestational exposure to tert-butanol. tert-Butanol was reported to inhibit muscarinic receptor-stimulated phosphoinositide metabolism which has been hypothesized to be a possible target for the neurotoxic effects of ethanol during brain development. The mechanistic data for the butanols support developmental neurotoxicity that has been observed in some of the rodent studies. However, careful studies evaluating the neurobehavior of developing pups in sensitive strains, as well as characterizing the plausible mechanisms involved, need to be conducted in order to further elucidate the neurodevelopmental effects of butanols for risk evaluation. Published by Elsevier Inc.

  11. Relationships of maternal and fetal weight changes in developmental toxicology bioassays

    EPA Science Inventory

    Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects in the embryo/fetus. Guidelines require the inclusion of a dose level(s) that induces “overt maternal toxicity”. The common occurrence of dose levels at which ...

  12. PERSPECTIVES ON THE CONCERN FOR AND MANAGEMENT OF PRENATAL CHEMICAL EXPOSURE AND POSTNATAL EFFECTS

    EPA Science Inventory

    This paper was presented as the introduction to a session on the history and epidemiology of prenatal chemical exposure. lthough teratology and developmental toxicology had its experimental beginnings in the early part of this century, the potential for human developmental toxici...

  13. A systematic evaluation of chemicals in hydraulic-fracturing fluids and wastewater for reproductive and developmental toxicity.

    PubMed

    Elliott, Elise G; Ettinger, Adrienne S; Leaderer, Brian P; Bracken, Michael B; Deziel, Nicole C

    2017-01-01

    Hydraulic-fracturing fluids and wastewater from unconventional oil and natural gas development contain hundreds of substances with the potential to contaminate drinking water. Challenges to conducting well-designed human exposure and health studies include limited information about likely etiologic agents. We systematically evaluated 1021 chemicals identified in hydraulic-fracturing fluids (n=925), wastewater (n=132), or both (n=36) for potential reproductive and developmental toxicity to triage those with potential for human health impact. We searched the REPROTOX database using Chemical Abstract Service registry numbers for chemicals with available data and evaluated the evidence for adverse reproductive and developmental effects. Next, we determined which chemicals linked to reproductive or developmental toxicity had water quality standards or guidelines. Toxicity information was lacking for 781 (76%) chemicals. Of the remaining 240 substances, evidence suggested reproductive toxicity for 103 (43%), developmental toxicity for 95 (40%), and both for 41 (17%). Of these 157 chemicals, 67 had or were proposed for a federal water quality standard or guideline. Our systematic screening approach identified a list of 67 hydraulic fracturing-related candidate analytes based on known or suspected toxicity. Incorporation of data on potency, physicochemical properties, and environmental concentrations could further prioritize these substances for future drinking water exposure assessments or reproductive and developmental health studies.

  14. Strategies to avoid the loss of developmental potential in more than 200 million children in the developing world.

    PubMed

    Engle, Patrice L; Black, Maureen M; Behrman, Jere R; Cabral de Mello, Meena; Gertler, Paul J; Kapiriri, Lydia; Martorell, Reynaldo; Young, Mary Eming

    2007-01-20

    This paper is the third in the Child Development Series. The first paper showed that more than 200 million children under 5 years of age in developing countries do not reach their developmental potential. The second paper identified four well-documented risks: stunting, iodine deficiency, iron deficiency anaemia, and inadequate cognitive stimulation, plus four potential risks based on epidemiological evidence: maternal depression, violence exposure, environmental contamination, and malaria. This paper assesses strategies to promote child development and to prevent or ameliorate the loss of developmental potential. The most effective early child development programmes provide direct learning experiences to children and families, are targeted toward younger and disadvantaged children, are of longer duration, high quality, and high intensity, and are integrated with family support, health, nutrition, or educational systems and services. Despite convincing evidence, programme coverage is low. To achieve the Millennium Development Goals of reducing poverty and ensuring primary school completion for both girls and boys, governments and civil society should consider expanding high quality, cost-effective early child development programmes.

  15. Army and Marine Corps Active Protection System (APS) Efforts

    DTIC Science & Technology

    2016-08-30

    safe enough for operational use, the benefits of MAPS relative to non-developmental efforts, MAPS’ impacts on NDI APS performance and costs, the Army’s...APSs Effective and Safe Enough for Operational Use? .............................. 24 What are the Benefits of MAPS Relative to Non-Developmental...corrosion—which will also factor into their eventual APS plans. Potential issues for Congress include whether current NDI APSs are effective and

  16. Developmental Status and Intimacy in Adult Survivors of Childhood Cancer.

    ERIC Educational Resources Information Center

    Zevon, Michael A.; Corn, Barbara; Lowrie, Geoffrey; Green, Daniel M.

    Whereas aggressive multimodal therapies are responsible for improved survival rates of children and adolescents diagnosed with cancer, concern has grown regarding the potential for adverse and delayed developmental effects resulting from these treatments. In light of this concern, this study assessed 207 adult survivors of childhood cancer in…

  17. Development of a high-throughput screening assay for chemical effects on proliferation and viability of immortalized human neural progenitor cells

    EPA Science Inventory

    There is considerable public concern that the majority of commercial chemicals have not been evaluated for their potential to cause developmental neurotoxicity. Although several chemicals are assessed annually under the current developmental neurotoxicity guidelines, time, resour...

  18. Developmental Hypothyroidism Reduces the Expression of Activity-Dependent Plasticity Genes in Denate Gyrus of the Adult Following Long Term Potentiation

    EPA Science Inventory

    Disruption of thyroid hormone (TH) is a known effect of environmental contaminants. Neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been implicated in brain dysfunction resulting from severe developmental TH insufficiency. Neuro...

  19. Maternal and fetal toxicity in developmental toxicology bioassays: Weight changes and their biological significance

    EPA Science Inventory

    Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects in the embryo/fetus. Guidelines call for the inclusion of a dose level(s) that induces “overt maternal toxicity.” The possibility that general maternal toxicit...

  20. Insects as test systems for assessing the potential role of microgravity in biological development and evolution.

    PubMed

    Vernós, I; Carratalá, M; González-Jurado, J; Valverde, J R; Calleja, M; Domingo, A; Vinós, J; Cervera, M; Marco, R

    1989-01-01

    Gravity and radiation are undoubtedly the two major environmental factors altered in space. Gravity is a weak force, which creates a permanent potential field acting on the mass of biological systems and their cellular components, strongly reduced in space flights. Developmental systems, particularly at very early stages, provide the larger cellular compartments known, where the effects of alterations in the size of the gravity vector on living organisms can be more effectively tested. The insects, one of the more highly evolved classes of animals in which early development occurs in a syncytial embryo, are systems particularly well suited to test these effects and the specific developmental mechanisms affected. Furthermore, they share some basic features such as small size, short life cycles, relatively high radio-resistance, etc. and show a diversity of developmental strategies and tempos advantageous in experiments of this type in space. Drosophila melanogaster, the current biological paradigm to study development, with so much genetic and evolutionary background available, is clearly the reference organism for these studies. The current evidence on the effects of the physical parameters altered in space flights on insect development indicate a surprising correlation between effects seen on the fast developing and relatively small Drosophila embryo and the more slowly developing and large Carausius morosus system. In relation to the issue of the importance of developmental and environmental constraints in biological evolution, still the missing link in current evolutionary thinking, insects and space facilities for long-term experiments could provide useful experimental settings where to critically assess how development and evolution may be interconnected. Finally, it has to be pointed out that since there are experimental data indicating a possible synergism between microgravity and space radiation, possible effects of space radiation should be taken into account in the planning and evaluation of experiments designed to test the potential role of microgravity on biological developmental and evolution.

  1. Transgenerational developmental programming.

    PubMed

    Aiken, Catherine E; Ozanne, Susan E

    2014-01-01

    The concept of developmental programming suggests that the early life environment influences offspring characteristics in later life, including the propensity to develop diseases such as the metabolic syndrome. There is now growing evidence that the effects of developmental programming may also manifest in further generations without further suboptimal exposure. This review considers the evidence, primarily from rodent models, for effects persisting to subsequent generations, and evaluates the mechanisms by which developmental programming may be transmitted to further generations. In particular, we focus on the potential role of the intrauterine environment in contributing to a developmentally programmed phenotype in subsequent generations. The literature was systematically searched at http://pubmed.org and http://scholar.google.com to identify published findings regarding transgenerational (F2 and beyond) developmental programming effects in human populations and animal models. Transmission of programming effects is often viewed as a form of epigenetic inheritance, either via the maternal or paternal line. Evidence exists for both germline and somatic inheritance of epigenetic modifications which may be responsible for phenotypic changes in further generations. However, there is increasing evidence for the role of both extra-genomic components of the zygote and the interaction of the developing conceptus with the intrauterine environment in propagating programming effects. The contribution of a suboptimal reproductive tract environment or maternal adaptations to pregnancy may be critical to inheritance of programming effects via the maternal line. As the effects of age exacerbate the programmed metabolic phenotype, advancing maternal age may increase the likelihood of developmental programming effects being transmitted to further generations. We suggest that developmental programming effects could be propagated through the maternal line de novo in generations beyond F2 as a consequence of development in a suboptimally developed intrauterine tract and not necessarily though directly transmitted epigenetic mechanisms.

  2. Developmental Neurotoxicants in E-Waste: An Emerging Health Concern

    PubMed Central

    Chen, Aimin; Dietrich, Kim N.; Huo, Xia; Ho, Shuk-mei

    2011-01-01

    Objective Electronic waste (e-waste) has been an emerging environmental health issue in both developed and developing countries, but its current management practice may result in unintended developmental neurotoxicity in vulnerable populations. To provide updated information about the scope of the issue, presence of known and suspected neurotoxicants, toxicologic mechanisms, and current data gaps, we conducted this literature review. Data sources We reviewed original articles and review papers in PubMed and Web of Science regarding e-waste toxicants and their potential developmental neurotoxicity. We also searched published reports of intergovernmental and governmental agencies and nongovernmental organizations on e-waste production and management practice. Data extraction We focused on the potential exposure to e-waste toxicants in vulnerable populations—that is, pregnant women and developing children—and neurodevelopmental outcomes. In addition, we summarize experimental evidence of developmental neurotoxicity and mechanisms. Data synthesis In developing countries where most informal and primitive e-waste recycling occurs, environmental exposure to lead, cadmium, chromium, polybrominated diphenyl ethers, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons is prevalent at high concentrations in pregnant women and young children. Developmental neurotoxicity is a serious concern in these regions, but human studies of adverse effects and potential mechanisms are scarce. The unprecedented mixture of exposure to heavy metals and persistent organic pollutants warrants further studies and necessitates effective pollution control measures. Conclusions Pregnant women and young children living close to informal e-waste recycling sites are at risk of possible perturbations of fetus and child neurodevelopment. PMID:21081302

  3. Post-Larval Developmental Trajectory of Zebrafish Fry is Altered by Exposure to T3 or T4 Analogues

    EPA Science Inventory

    The thyroid axis plays a key role in development. While the impacts of perturbing thyroid axis development and/or function are documented in embryonic and larval zebrafish, the effects on developmental milestones at later life stages are not well-delineated. To assess potential l...

  4. Clinical Outcomes of Behavioral Treatments for Pica in Children with Developmental Disabilities

    ERIC Educational Resources Information Center

    Call, Nathan A.; Simmons, Christina A.; Mevers, Joanna E.; Alvarez, Jessica P.

    2015-01-01

    Pica is a potentially deadly form of self-injurious behavior most frequently exhibited by individuals with developmental and intellectual disabilities. Research indicates that pica can be decreased with behavioral interventions; however, the existing literature reflects treatment effects for small samples (n = 1-4) and the overall success of such…

  5. Acute and Developmental Behavioral Effects of Flame ...

    EPA Pesticide Factsheets

    As polybrominated diphenyl ethers are phased out, numerous compounds are emerging as potential replacement flame retardants for use in consumer and electronic products. Little is known, however, about the neurobehavioral toxicity of these replacements. This study evaluated the neurobehavioral effects of acute or developmental exposure to t-butylphenyl diphenyl phosphate (BPDP), 2-ethylhexyl diphenyl phosphate (EHDP), isodecyl diphenyl phosphate (IDDP), isopropylated phenyl phosphate (IPP), tricresyl phosphate (TMPP; also abbreviated TCP), triphenyl phosphate (TPHP; also abbreviated TPP), tetrabromobisphenol A (TBBPA), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloroisopropyl) phosphate (TDCIPP; also abbreviated TDCPP), tri-o-cresyl phosphate (TOCP), and 2,2-,4,4’-tetrabromodiphenyl ether (BDE-47) in zebrafish (Danio rerio) larvae. Larvae (n≈24 per dose per compound) were exposed to test compounds (0.4 - 120 µM) at sub-teratogenic concentrations either developmentally or acutely, and locomotor activity was assessed at 6 days post fertilization. When given developmentally, all chemicals except BPDP, IDDP and TBBPA produced behavioral effects. When given acutely, all chemicals produced behavioral effects, with TPHP, TBBPA, EHDP, IPP, and BPDP eliciting the most effects at the most concentrations. The results indicate that these replacement flame retardants may have developmental or pharmacological effects on the vertebrate nervous system. This study

  6. Effect of the timing of the first cleavage on the developmental potential of nuclear-transferred mouse oocytes receiving embryonic stem cells.

    PubMed

    Kobayashi, T; Kato, Y; Tsunoda, Y

    2004-09-01

    The present study examined whether the timing of the first cleavage has an effect on the in vitro and in vivo developmental potential of nuclear-transferred mouse oocytes receiving embryonic stem cells. First, the timing of the first cleavage and the developmental potential of nuclear-transferred oocytes were examined every hour from 12 to 24 h after the start of culture and compared with in vitro-fertilized oocytes. The developmental potential of in vitro-fertilized oocytes decreased gradually according to the time required for cleavage (84% (32/38) for 15 h to 50% (1/2) for 20 h), but intermediate-cleaved (15-16 h) nuclear-transferred oocytes had a higher potential to develop into blastocysts (55% (17/31) to 67% (45/67) versus 0-43% (6/14)]. Second the nuclear-transferred oocytes were divided into three groups according to the timing of the first cleavage; each group was cultured to blastocysts in vitro, and then transferred to recipients. The potential of intermediate-cleaved oocytes (15-16 h) to develop into blastocysts was significantly higher than fast-cleaved (before 15 h) and slow-cleaved (after 16 h) oocytes (65, 46, and 37%). The proportion of fetuses on Day 10.5 of pregnancy was highest in the intermediate-cleaved group (4 versus 2 and 1%, respectively) and a full-term fetus was obtained from this group. The present study demonstrated that the timing of the first cleavage could be used to determine the potential of nuclear-transferred oocytes with embryonic stem cells to develop to the blastocyst stage in vitro, but not to determine post-implantation viability after transfer to recipients.

  7. Acute, subchronic, and developmental toxicological properties of lubricating oil base stocks.

    PubMed

    Dalbey, Walden E; McKee, Richard H; Goyak, Katy Olsavsky; Biles, Robert W; Murray, Jay; White, Russell

    2014-01-01

    Lubricating oil base stocks (LOBs) are substances used in the manufacture of finished lubricants and greases. They are produced from residue remaining after atmospheric distillation of crude oil that is subsequently fractionated by vacuum distillation and additional refining steps. Initial LOB streams that have been produced by vacuum distillation but not further refined may contain polycyclic aromatic compounds (PACs) and may present carcinogenic hazards. In modern refineries, LOBs are further refined by multistep processes including solvent extraction and/or hydrogen treatment to reduce the levels of PACs and other undesirable constituents. Thus, mildly (insufficiently) refined LOBs are potentially more hazardous than more severely (sufficiently) refined LOBs. This article discusses the evaluation of LOBs using statistical models based on content of PACs; these models indicate that insufficiently refined LOBs (potentially carcinogenic LOBs) can also produce systemic and developmental effects with repeated dermal exposure. Experimental data were also obtained in ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and seven dermal developmental toxicity studies with sufficiently refined LOBs (noncarcinogenic and commonly marketed) in which no observed adverse effect levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d with dermal exposures, typically the highest dose tested. Results in both oral and inhalation developmental toxicity studies were similar. This absence of toxicologically relevant findings was consistent with lower PAC content of sufficiently refined LOBs. Based on data on reproductive organs with repeated dosing and parameters in developmental toxicity studies, sufficiently refined LOBs are likely to have little, if any, effect on reproductive parameters.

  8. 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.

  9. Metabolomics approach reveals metabolic disorders and potential biomarkers associated with the developmental toxicity of tetrabromobisphenol A and tetrachlorobisphenol A

    NASA Astrophysics Data System (ADS)

    Ye, Guozhu; Chen, Yajie; Wang, Hong-Ou; Ye, Ting; Lin, Yi; Huang, Qiansheng; Chi, Yulang; Dong, Sijun

    2016-10-01

    Tetrabromobisphenol A and tetrachlorobisphenol A are halogenated bisphenol A (H-BPA), and has raised concerns about their adverse effects on the development of fetuses and infants, however, the molecular mechanisms are unclear, and related metabolomics studies are limited. Accordingly, a metabolomics study based on gas chromatography-mass spectrometry was employed to elucidate the molecular developmental toxicology of H-BPA using the marine medaka (Oryzias melastigmas) embryo model. Here, we revealed decreased synthesis of nucleosides, amino acids and lipids, and disruptions in the TCA (tricarboxylic acid) cycle, glycolysis and lipid metabolism, thus inhibiting the developmental processes of embryos exposed to H-BPA. Unexpectedly, we observed enhanced neural activity accompanied by lactate accumulation and accelerated heart rates due to an increase in dopamine pathway and a decrease in inhibitory neurotransmitters following H-BPA exposure. Notably, disorders of the neural system, and disruptions in glycolysis, the TCA cycle, nucleoside metabolism, lipid metabolism, glutamate and aspartate metabolism induced by H-BPA exposure were heritable. Furthermore, lactate and dopa were identified as potential biomarkers of the developmental toxicity of H-BPA and related genetic effects. This study has demonstrated that the metabolomics approach is a useful tool for obtaining comprehensive and novel insights into the molecular developmental toxicity of environmental pollutants.

  10. Sub-lethal and lethal toxicities of elevated CO2 on embryonic, juvenile, and adult stages of marine medaka Oryzias melastigma.

    PubMed

    Lee, Changkeun; Kwon, Bong-Oh; Hong, Seongjin; Noh, Junsung; Lee, Junghyun; Ryu, Jongseong; Kang, Seong-Gil; Khim, Jong Seong

    2018-06-06

    The potential leakage from marine CO 2 storage sites is of increasing concern, but few studies have evaluated the probable adverse effects on marine organisms. Fish, one of the top predators in marine environments, should be an essential representative species used for water column toxicity testing in response to waterborne CO 2 exposure. In the present study, we conducted fish life cycle toxicity tests to fully elucidate CO 2 toxicity mechanism effects. We tested sub-lethal and lethal toxicities of elevated CO 2 concentrations on marine medaka (Oryzias melastigma) at different developmental stages. At each developmental stage, the test species was exposed to varying concentrations of gaseous CO 2 (control air, 5%, 10%, 20%, and 30%), with 96 h of exposure at 0-4 d (early stage), 4-8 d (middle stage), and 8-12 d (late stage). Sub-lethal and lethal effects, including early developmental delays, cardiac edema, tail abnormalities, abnormal pigmentation, and mortality were monitored daily during the 14 d exposure period. At the embryonic stage, significant sub-lethal and lethal effects were observed at pH < 6.30. Hypercapnia can cause long-term and/or delayed developmental embryonic problems, even after transfer back to clean seawater. At fish juvenile and adult stages, significant mortality was observed at pH < 5.70, indicating elevated CO 2 exposure might cause various adverse effects, even during short-term exposure periods. It should be noted the early embryonic stage was found more sensitive to CO 2 exposure than other developmental stages of the fish life cycle. Overall, the present study provided baseline information for potential adverse effects of high CO 2 concentration exposure on fish developmental processes at different life cycle stages in marine ecosystems. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Using zebrafish in systems toxicology for developmental toxicity testing.

    PubMed

    Nishimura, Yuhei; Inoue, Atsuto; Sasagawa, Shota; Koiwa, Junko; Kawaguchi, Koki; Kawase, Reiko; Maruyama, Toru; Kim, Soonih; Tanaka, Toshio

    2016-01-01

    With the high cost and the long-term assessment of developmental toxicity testing in mammals, the vertebrate zebrafish has become a useful alternative model organism for high-throughput developmental toxicity testing. Zebrafish is also very favorable for the 3R perspective in toxicology; however, the methodologies used by research groups vary greatly, posing considerable challenges to integrative analysis. In this review, we discuss zebrafish developmental toxicity testing, focusing on the methods of chemical exposure, the assessment of morphological abnormalities, housing conditions and their effects on the production of healthy embryos, and future directions. Zebrafish as a systems toxicology model has the potential to elucidate developmental toxicity pathways, and to provide a sound basis for human health risk assessments. © 2015 Japanese Teratology Society.

  12. The Effect of Different Cooking Methods on Phenolics and Vitamin C in Developmentally Young Potato Tubers

    USDA-ARS?s Scientific Manuscript database

    New potatoes (also known as “baby” or “early” potatoes) are harvested at a young developmental age and have higher concentrations of many phytonutrients than mature tubers. A better assessment of the potential of new potatoes in the diet and their suitability as targets for further nutritional enhan...

  13. Dorsal Stream Deficits Suggest Hidden Dyslexia among Deaf Poor Readers: Correlated Evidence from Reduced Perceptual Speed and Elevated Coherent Motion Detection Thresholds

    ERIC Educational Resources Information Center

    Samar, V.J.; Parasnis, I.

    2005-01-01

    Prelingual deafness and developmental dyslexia have confounding developmental effects on reading acquisition. Therefore, standard reading assessment methods for diagnosing dyslexia in hearing people are ineffective for use with deaf people. Recently, Samar, Parasnis, and Berent (2002) reported visual evoked potential evidence that deaf poor…

  14. Introduction: digital games as a context for cognitive development, learning, and developmental research.

    PubMed

    Blumberg, Fran C; Fisch, Shalom M

    2013-01-01

    The authors present reasons why developmental psychologists should care about children's and adolescents' digital game play. These reasons may be identified as: a) digital game play is an integral aspect of children's and adolescents' lives; b) digital game play contributes to learning and cognitive development; and c) developmental research has the potential to contribute to effective educational game design. The authors expand on these reasons with the goal of introducing or reintroducing to developmental psychologists a rich and very relevant context in which to examine children's and adolescents' applied cognitive development. Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.

  15. Earmuff restricts progenitor cell potential by attenuating the competence to respond to self-renewal factors.

    PubMed

    Janssens, Derek H; Komori, Hideyuki; Grbac, Daniel; Chen, Keng; Koe, Chwee Tat; Wang, Hongyan; Lee, Cheng-Yu

    2014-03-01

    Despite expressing stem cell self-renewal factors, intermediate progenitor cells possess restricted developmental potential, which allows them to give rise exclusively to differentiated progeny rather than stem cell progeny. Failure to restrict the developmental potential can allow intermediate progenitor cells to revert into aberrant stem cells that might contribute to tumorigenesis. Insight into stable restriction of the developmental potential in intermediate progenitor cells could improve our understanding of the development and growth of tumors, but the mechanisms involved remain largely unknown. Intermediate neural progenitors (INPs), generated by type II neural stem cells (neuroblasts) in fly larval brains, provide an in vivo model for investigating the mechanisms that stably restrict the developmental potential of intermediate progenitor cells. Here, we report that the transcriptional repressor protein Earmuff (Erm) functions temporally after Brain tumor (Brat) and Numb to restrict the developmental potential of uncommitted (immature) INPs. Consistently, endogenous Erm is detected in immature INPs but undetectable in INPs. Erm-dependent restriction of the developmental potential in immature INPs leads to attenuated competence to respond to all known neuroblast self-renewal factors in INPs. We also identified that the BAP chromatin-remodeling complex probably functions cooperatively with Erm to restrict the developmental potential of immature INPs. Together, these data led us to conclude that the Erm-BAP-dependent mechanism stably restricts the developmental potential of immature INPs by attenuating their genomic responses to stem cell self-renewal factors. We propose that restriction of developmental potential by the Erm-BAP-dependent mechanism functionally distinguishes intermediate progenitor cells from stem cells, ensuring the generation of differentiated cells and preventing the formation of progenitor cell-derived tumor-initiating stem cells.

  16. Phenotypic screening for developmental neurotoxicity ...

    EPA Pesticide Factsheets

    There are large numbers of environmental chemicals with little or no available information on their toxicity, including developmental neurotoxicity. Because of the resource-intensive nature of traditional animal tests, high-throughput (HTP) methods that can rapidly evaluate chemicals for the potential to affect the developing brain are being explored. Typically, HTP screening uses biochemical and molecular assays to detect the interaction of a chemical with a known target or molecular initiating event (e.g., the mechanism of action). For developmental neurotoxicity, however, the mechanism(s) is often unknown. Thus, we have developed assays for detecting chemical effects on the key events of neurodevelopment at the cellular level (e.g., proliferation, differentiation, neurite growth, synaptogenesis, network formation). Cell-based assays provide a test system at a level of biological complexity that encompasses many potential neurotoxic mechanisms. For example, phenotypic assessment of neurite outgrowth at the cellular level can detect chemicals that target kinases, ion channels, or esterases at the molecular level. The results from cell-based assays can be placed in a conceptual framework using an Adverse Outcome Pathway (AOP) which links molecular, cellular, and organ level effects with apical measures of developmental neurotoxicity. Testing a wide range of concentrations allows for the distinction between selective effects on neurodevelopmental and non-specific

  17. Prenatal stress and development: beyond the single cause and effect paradigm.

    PubMed

    Hamlin, Heather J

    2012-12-01

    Our awareness of the causes of stress-induced developmental dysfunction has increased dramatically over the past decade, and it is becoming increasingly clear that a number of factors can have considerable impacts on the developing fetus. Although there is a tendency in investigations of developmental teratogens to attribute specific causes to adverse fetal outcomes, it is important we recognize that for most developmental dysfunctions it is unlikely a single cause, but yet a series of environmental insults combined with genetic predisposition that ultimately leads to a disease state. Nonetheless, a number of developmental teratogens, such as maternal psychological stress and chemical exposures, have been shown to increase the likelihood of developmental defects. These defects can manifest during development, leading to observable birth defects, or could become evident long after birth, even into adulthood. In addition, epigenetic mutations in the germline can alter the phenotype of successive generations through transgenerational inheritance, and in this way environmental factors can alter the developmental outcomes and disease predispositions of future generations. Understanding this complexity is essential to interpretations of causality in the studies of stress-induced developmental dysfunction and needs to be fully considered to more effectively interpret potential outcomes. Copyright © 2013 Wiley Periodicals, Inc.

  18. Evaluating the Effects of Chemicals on Nervous System Development

    EPA Pesticide Factsheets

    There are thousands of chemicals that lack data on their potential effects on neurodevelopment. EPA is developing New Approach Methods to evaluate these chemicals for developmental neurotoxicity hazard.

  19. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ema, Makoto, E-mail: ema-makoto@aist.go.jp; Gamo, Masashi; Honda, Kazumasa

    We summarized significant effects reported in the literature on the developmental toxicity of engineered nanomaterials (ENMs) in rodents. The developmental toxicity of ENMs included not only structural abnormalities, but also death, growth retardation, and behavioral and functional abnormalities. Most studies were performed on mice using an injection route of exposure. Teratogenic effects were indicated when multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), and TiO{sub 2}-nanoparticles were administered to mice during early gestation. Reactive oxygen species levels were increased in placentas and malformed fetuses and their placentas after prenatal exposure to MWCNTs and SWCNTs, respectively. The pre- and postnatal mortalitiesmore » and growth retardation in offspring increased after prenatal exposure to ENMs. Histopathological and functional abnormalities were also induced in placentas after prenatal exposure to ENMs. Maternal exposure to ENMs induced behavioral alterations, histopathological and biochemical changes in the central nervous system, increased susceptibility to allergy, transplacental genotoxicity, and vascular, immunological, and reproductive effects in offspring. The size- and developmental stage-dependent placental transfer of ENMs was noted after maternal exposure. Silver accumulated in the visceral yolk sac after being injected with Ag-NPs during early gestation. Although currently available data has provided initial information on the potential developmental toxicity of ENMs, that on the developmental toxicity of ENMs is still very limited. Further studies using well-characterized ENMs, state-of the-art study protocols, and appropriate routes of exposure are required in order to clarify these developmental effects and provide information suitable for risk assessments of ENMs. - Highlights: • We review the developmental toxicity studies of engineered nanomaterials (ENMs). • Various developmental endpoints have been reported after exposure to ENMs. • Physico-chemical properties of ENMs are determinants of the developmental toxicity. • Oxidative stress/inflammation may be involved in the developmental toxicity of ENMs. • Further developmental toxicity studies of ENMs are needed to fill a data gap.« less

  20. Using Animation in Microsoft PowerPoint to Enhance Engagement and Learning in Young Learners with Developmental Delay

    ERIC Educational Resources Information Center

    Parette, Howard P., Jr.; Hourcade, Jack; Blum, Craig

    2011-01-01

    Over the past decade, a wide array of instructional technology applications have found their way into early intervention settings. Of particular importance to young learners who evidence developmental delays or are at risk for school failure are those technologies with the potential to more effectively teach basic emergent literacy skills: (1)…

  1. Prediction of the developmental toxicity hazard potential of halogenated drinking water disinfection by-products tested by the in vitro hydra assay

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fu, L.J.; Johnson, E.M.; Newman, L.M.

    A series of seven randomly selected potential halogenated water disinfection by-products were evaluated in vitro by the hydra assay to determine their developmental toxicity hazard potential. For six of the chemicals tested by this assay (dibromoacetonitrile; trichloroacetonitrile; 2-chlorophenol; 2,4,6-trichlorophenol; trichloroacetic acid; dichloroacetone) it was predicted that they would be generally equally toxic to both adult and embryonic mammals when studied by means of standard developmental toxicity teratology tests. However, the potential water disinfection by-product chloroacetic acid (CA) was determined to be over eight times more toxic to the embryonic developmental portion of the assay than it was to the adults.more » Because of this potential selectivity, CA is a high-priority item for developmental toxicity tests in pregnant mammals to confirm or refute its apparent unique developmental hazard potential and/or to establish a NOAEL by the route of most likely human exposure.« less

  2. NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines.

    PubMed

    2005-07-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for amphetamines to cause adverse effects on reproduction and development in humans. Amphetamines evaluated were D- and D,L-amphetamine and methamphetamine. Amphetamine is approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD) in persons over 3 years of age and narcolepsy; methamphetamine is approved for the treatment of ADHD in persons 6 years of age and older and for short-term treatment of obesity. Amphetamines were selected for evaluation because of 1) widespread usage in children, 2) availability of developmental studies in children and experimental animals, and 3) public concern about the effect of this stimulant on child development. The results of this evaluation on amphetamines are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Methylphenidate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to methylphenidate on human development and reproduction. First, there is some concern for developmental effects, specifically for potential neurobehavioral alterations, from prenatal amphetamine exposure in humans both in therapeutic and non-therapeutic settings. After prenatal exposure to therapeutic doses of amphetamine, rat pups demonstrated neurobehavioral alterations. Data from human and animal studies were judged insufficient for an evaluation of the effect of amphetamine exposure on growth and other related developmental effects. Second, there is concern for methamphetamine-induced adverse developmental effects, specifically on growth and neurobehavioral development, in therapeutic and non-therapeutic settings. This conclusion is based on evidence from studies in experimental animals that prenatal and postnatal exposures to methamphetamine produce neurobehavioral alterations, small litter size, and low birth weight. Results from studies in humans suggest that methamphetamine may cause low birth weight and shortened gestation, but study confounders such as possible multiple drug usage prevent a definite conclusion. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).

  3. Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells

    PubMed Central

    Choi, Jiho; Huebner, Aaron J; Clement, Kendell; Walsh, Ryan M; Savol, Andrej; Lin, Kaixuan; Gu, Hongcang; Di Stefano, Bruno; Brumbaugh, Justin; Kim, Sang-Yong; Sharif, Jafar; Rose, Christopher M.; Mohammad, Arman; Odajima, Junko; Charron, Jean; Shioda, Toshi; Gnirke, Andreas; Gygi, Steven; Koseki, Haruhiko; Sadreyev, Ruslan I.; Xiao, Andrew; Meissner, Alexander; Hochedlinger, Konrad

    2018-01-01

    Concomitant activation of the Wnt pathway and suppression of Mapk signaling by two small molecules in the presence of LIF (2i/L) induces a naïve state in mouse embryonic stem cells (ESCs) that resembles the inner cell mass (ICM) of the pre-implantation embryo1. Since the ICM exists only transiently in vivo, it remains unclear how sustained propagation of naïve ESCs in vitro affects their stability and functionality. Here we show that prolonged culture of male ESCs in 2i/L results in irreversible epigenetic and genomic changes that impair their developmental potential. Additionally, we find that female ESCs cultured in conventional serum/LIF (S/L) media phenocopy male ESCs cultured in 2i/L. Mechanistically, we demonstrate that Mek1/2 inhibition is predominantly responsible for these effects, in part through downregulation of DNA methyltransferases and their associated cofactors. Finally, we show that replacement of the Mek1/2 inhibitor with a Src inhibitor preserves the epigenetic and genomic integrity as well as developmental potential of ESCs. Taken together, our data suggest that, while short-term suppression of Mek1/2 in ESCs helps maintain an ICM-like epigenetic state, prolonged suppression results in irreversible changes that compromise their developmental potential. PMID:28746311

  4. Differential Immunotoxicity Induced by Two Different Windows of Developmental Trichloroethylene Exposure

    PubMed Central

    Gilbert, Kathleen M.; Woodruff, William; Blossom, Sarah J.

    2014-01-01

    Developmental exposure to environmental toxicants may induce immune system alterations that contribute to adult stage autoimmune disease. We have shown that continuous exposure of MRL+/+ mice to trichloroethylene (TCE) from gestational day (GD) 0 to postnatal day (PND) 49 alters several aspects of CD4+ T cell function. This window of exposure corresponds to conception-adolescence/young adulthood in humans. More narrowly defining the window of TCE developmental exposure causes immunotoxicity that would establish the stage at which avoidance and/or intervention would be most effective. The current study divided continuous TCE exposure into two separate windows, namely, gestation only (GD0 to birth (PND0)) and early-life only (PND0-PND49). The mice were examined for specific alterations in CD4+ T cell function at PND49. One potentially long-lasting effect of developmental exposure, alterations in retrotransposon expression indicative of epigenetic alterations, was found in peripheral CD4+ T cells from both sets of developmentally exposed mice. Interestingly, certain other effects, such as alterations in thymus cellularity, were only found in mice exposed to TCE during gestation. In contrast, expansion of memory/activation cell subset of peripheral CD4+ T cells were only found in mice exposed to TCE during early life. Different windows of developmental TCE exposure can have different functional consequences. PMID:24696780

  5. Thermal plasticity of growth and development varies adaptively among alternative developmental pathways.

    PubMed

    Kivelä, Sami M; Svensson, Beatrice; Tiwe, Alma; Gotthard, Karl

    2015-09-01

    Polyphenism, the expression of discrete alternative phenotypes, is often a consequence of a developmental switch. Physiological changes induced by a developmental switch potentially affect reaction norms, but the evolution and existence of alternative reaction norms remains poorly understood. Here, we demonstrate that, in the butterfly Pieris napi (Lepidoptera: Pieridae), thermal reaction norms of several life history traits vary adaptively among switch-induced alternative developmental pathways of diapause and direct development. The switch was affected both by photoperiod and temperature, ambient temperature during late development having the potential to override earlier photoperiodic cues. Directly developing larvae had higher development and growth rates than diapausing ones across the studied thermal gradient. Reaction norm shapes also differed between the alternative developmental pathways, indicating pathway-specific selection on thermal sensitivity. Relative mass increments decreased linearly with increasing temperature and were higher under direct development than diapause. Contrary to predictions, population phenology did not explain trait variation or thermal sensitivity, but our experimental design probably lacks power for finding subtle phenology effects. We demonstrate adaptive differentiation in thermal reaction norms among alternative phenotypes, and suggest that the consequences of an environmentally dependent developmental switch primarily drive the evolution of alternative thermal reaction norms in P. napi. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  6. Linking Prenatal Maternal Adversity to Developmental Outcomes in Infants: The Role of Epigenetic Pathways

    PubMed Central

    Monk, Catherine; Spicer, Julie; Champagne, Frances A.

    2013-01-01

    Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with consequences for risk of psychopathology. Though the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally-induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this review, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and here we review findings illustrating prenatal-postnatal interplay and the developmental and epigenetic consequences of postnatal mother-infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress. PMID:23062303

  7. Potential of chromium(III) picolinate for reproductive or developmental toxicity following exposure of male CD-1 mice prior to mating.

    PubMed

    McAdory, DeAna; Rhodes, Nicholas R; Briggins, Felicia; Bailey, Melissa M; Di Bona, Kristin R; Goodwin, Craig; Vincent, John B; Rasco, Jane F

    2011-12-01

    Chromium(III) picolinate, [Cr(pic)(3)], is a commonly used nutritional supplement in humans, which has also been approved for use in animals. Health concerns have arisen over the use of [Cr(pic)(3)]. At high [Cr(pic)(3)] doses, developmental toxicity tests in female mice have shown a higher litter incidence of split cervical arch in exposed fetuses, but this was not consistently reproducible. In the current study, male CD-1 mice were used to further assess the potential for reproductive or developmental toxicity. Four weeks prior to mating, the males were fed a diet providing 200 mg/kg/day [Cr(pic)(3)] for comparison with untreated controls. Females were not treated. Each male was mated with two females, which were sacrificed on gestation day 17, and their litters were examined for adverse effects. Mating and fertility indices were not significantly altered by treatment. Male exposure to [Cr(pic)(3)] also had no effect on prenatal mortality, fetal weight, or gross or skeletal morphology. These results suggest that paternal dietary exposure to chromium(III) picolinate has little potential for adverse reproductive effects, even at exposure levels considerably higher than expected human exposures from nutritional supplements (1 mg of Cr per day or less).

  8. Hazard-Ranking of Agricultural Pesticides for Chronic Health Effects in Yuma County, Arizona

    PubMed Central

    Sugeng, Anastasia J.; Beamer, Paloma I.; Lutz, Eric A.; Rosales, Cecilia B.

    2013-01-01

    With thousands of pesticides registered by the United States Environmental Protection Agency, it not feasible to sample for all pesticides applied in agricultural communities. Hazard-ranking pesticides based on use, toxicity, and exposure potential can help prioritize community-specific pesticide hazards. This study applied hazard-ranking schemes for cancer, endocrine disruption, and reproductive/developmental toxicity in Yuma County, Arizona. An existing cancer hazard-ranking scheme was modified, and novel schemes for endocrine disruption and reproductive/developmental toxicity were developed to rank pesticide hazards. The hazard-ranking schemes accounted for pesticide use, toxicity, and exposure potential based on chemical properties of each pesticide. Pesticides were ranked as hazards with respect to each health effect, as well as overall chronic health effects. The highest hazard-ranked pesticides for overall chronic health effects were maneb, metam sodium, trifluralin, pronamide, and bifenthrin. The relative pesticide rankings were unique for each health effect. The highest hazard-ranked pesticides differed from those most heavily applied, as well as from those previously detected in Yuma homes over a decade ago. The most hazardous pesticides for cancer in Yuma County, Arizona were also different from a previous hazard-ranking applied in California. Hazard-ranking schemes that take into account pesticide use, toxicity, and exposure potential can help prioritize pesticides of greatest health risk in agricultural communities. This study is the first to provide pesticide hazard-rankings for endocrine disruption and reproductive/developmental toxicity based on use, toxicity, and exposure potential. These hazard-ranking schemes can be applied to other agricultural communities for prioritizing community-specific pesticide hazards to target decreasing health risk. PMID:23783270

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

    PubMed

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

    2018-04-02

    SummaryThe objective of the study was to investigate the effect of l-ergothioneine (l-erg) (5 mM or 10 mM) supplementation in maturation medium on the developmental potential and OCTN1-dependant l-erg-mediated (10 mM) change in mRNA abundance of apoptotic (Bcl2, Bax, Casp3 and PCNA) and antioxidant (GPx, SOD1, SOD2 and CAT) genes in sheep oocytes and developmental stages of embryos produced in vitro. Oocytes matured with l-erg (10 mM) reduced their embryo toxicity by decreasing intracellular ROS and increasing intracellular GSH in matured oocytes that in turn improved developmental potential, resulting in significantly (P < 0.05) higher percentages of cleavage (53.72% vs 38.86, 46.56%), morulae (34.36% vs 20.62, 25.84%) and blastocysts (14.83% vs 6.98, 9.26%) compared with other lower concentrations (0 mM and 5 mM) of l-erg without change in maturation rate. l-Erg (10 mM) treatment did not influence the mRNA abundance of the majority of apoptotic and antioxidant genes studied in the matured oocytes and developmental stages of embryo. A gene expression study found that the SLC22A4 gene that encodes OCTN1, an integral membrane protein and specific transporter of l-erg was not expressed in oocytes and developmental stages of embryos. Therefore it was concluded from the study that although there was improvement in the developmental potential of sheep embryos by l-erg supplementation in maturation medium, there was no change in the expression of the majority of the genes studied due to the absence of the SLC22A4 gene in oocytes and embryos that encode OCTN1, which is responsible for transportation of l-erg across the membrane to alter gene expression.

  10. Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms.

    PubMed

    Bayliss, D A; Viana, F; Talley, E M; Berger, A J

    1997-11-01

    Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and (2) the inhibition of a calcium-dependent spike after hyperpolarization (AHP) by 5-HT and its effect on firing behavior. Potential functional consequences on HM behavior of these different neurotransmitter effects is discussed. In addition, we describe postnatal changes in transmitter effects and suggest potential cellular mechanisms to explain those developmental changes. Most of the data discussed are derived from in vitro electrophysiological recordings performed in preparations from neonatal and adult rats.

  11. Effect of the timing of first cleavage on in vitro developmental potential of nuclear-transferred bovine oocytes receiving cumulus and fibroblast cells.

    PubMed

    Amarnath, Dasari; Kato, Yoko; Tsunoda, Yukio

    2007-06-01

    The aim of the present study was to examine whether cumulus and fibroblast cell nuclear-transferred oocytes, which have high and low potential to develop into normal calves, respectively, are different in terms of in their patterns of timing of first cleavage and in their relationships between timing of first cleavage and in vitro developmental potential. The timing of first cleavage was similar in both types of nuclear-transferred and in vitro fertilized oocytes. More than 86% of the oocytes cleaved within 24 h after activation or in vitro fertilization; these oocytes contributed to more than 98% of the total number of blastocysts in all three groups. The potential of oocytes that cleaved at different intervals to develop into blastocysts differed among the groups. The developmental potential of the cumulus cell nuclear-transferred oocytes and in vitro fertilized oocytes decreased with the increase in time required for cleavage. Fibroblast cell nuclear-transferred oocytes that cleaved at 20 h, an intermediate cleaving time, had higher potential to develop into blastocysts. The results of the present study suggest that the type of donor nucleus used for nuclear transfer affects the timing of first cleavage.

  12. Effects of Exercise Intervention on Event-Related Potential and Task Performance Indices of Attention Networks in Children with Developmental Coordination Disorder

    ERIC Educational Resources Information Center

    Tsai, Chia-Liang; Wang, Chun-Hao; Tseng, Yu-Ting

    2012-01-01

    The study investigated whether 10-week soccer training can benefit the inhibitory control and neuroelectric indices in children with developmental coordination disorder (DCD). Fifty-one children were divided into groups of typically developing (TD, n = 21), DCD-training (n = 16), and DCD non-training (n=14) individuals using the for Children test,…

  13. Novel quantitative methods for characterization of chemical induced functional alteration in developing neuronal cultures

    EPA Science Inventory

    ABSTRACT BODY: Thousands of chemicals lack adequate testing for adverse effects on nervous system development, stimulating research into alternative methods to screen chemicals for potential developmental neurotoxicity. Microelectrode arrays (MEA) collect action potential spiking...

  14. A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity

    PubMed Central

    Costa, Lucio G.; de Laat, Rian; Tagliaferri, Sara; Pellacani, Claudia

    2013-01-01

    Polybrominated diphenyl ethers (PBDEs), extensively used in the past few decades as flame retardants in a variety of consumer products, have become world-wide persistent environmental pollutants. Levels in North America are usually higher than those in Europe and Asia, and body burden is 3 to 9-fold higher in infants and toddlers than in adults. The latter has raised concern for potential developmental toxicity and neurotoxicity of PBDEs. Experimental studies in animals and epidemiological observations in humans suggest that PBDEs may be developmental neurotoxicants. Pre- and/or post-natal exposure to PBDEs may cause long-lasting behavioral abnormalities, particularly in the domains of motor activity and cognition. The mechanisms underlying the developmental neurotoxic effects of PBDEs are not known, though several hypotheses have been put forward. One general mode of action relates to the ability of PBDEs to impair thyroid hormone homeostasis, thus indirectly affecting the developing brain. An alternative or additional mode of action involves a direct effect of PBDEs on nervous system cells; PBDEs can cause oxidative stress-related damage (DNA damage, mitochondrial dysfunction, apoptosis), and interfere with signal transduction (particularly calcium signaling), and with neurotransmitter systems. Important issues such as bioavailability and metabolism of PBDEs, extrapolation of results to low level of exposures, and the potential effects of interactions among PBDE congeners and between PBDEs and other contaminants also need to be taken into account. PMID:24270005

  15. Characteristics, correlates, and outcomes of childhood and adolescent depressive disorders

    PubMed Central

    Rao, Uma; Chen, Li-Ann

    2009-01-01

    Depressive illness beginning early in life can have serious developmental and functional consequences. Therefore, understanding the disorder during this developmental stage is critical for determining its etiology and course, as well as for deveiopinq effective intervention straieqies. This paper summarizes current knoviedqe reqardinq the etiology, phenomenoiogy, correlates, natural course, and consequences of unipolar depression in children and adolescents. Using adult depression as a framevork, the unique aspects of childhood and adolescence are considered in order to better understand depression within a developmental context. The data suggest that the clinical presentation, correlates, and natural course of depression are remarkably similar across the lifespan. There are, however, important developmental differences. Specifically, the familial and psychological context in which depression develops in youngsters is associated with variability in the frequency and nature of depressive symptoms and comorbid conditions among children and adolescents. Maturational differences have also been identified in the neurobiological correlates of depression. These developmental differences may be associated with the observed variability in clinical response to treatment and longitudinal course. Characterization of the developmental differences will be helpful in developing more specific and effective interventions for youngsters, thereby allowing them to reach their full potential as adults. PMID:19432387

  16. Insects as test systems for assessing the potential role of microgravity in biological development and evolution

    NASA Astrophysics Data System (ADS)

    Vernós, I.; Carratalá, M.; González-Jurado, J.; Valverde, J. R.; Calleja, M.; Domingo, A.; Vinós, J.; Cervera, M.; Marco, R.

    Gravity and radiation are undoubtedly the two major environmental factors altered in space. Gravity is a weak force, which creates a permanent potential field acting on the mass of biological systems and their cellular components, strongly reduced in space flights. Developmental systems, particularly at very early stages, provide the larger cellular compartments known, where the effects of alterations in the size of the gravity vector on living organisms can be more effectively tested. The insects, one of the more highly evolved classes of animals in which early development occurs in a syncytial embryo, are systems particularly well suited to test these effects and the specific developmental mechanisms affected. Furthermore, they share some basic features such as small size, short life cycles, relatively high radio-resistance, etc. and show a diversity of developmental strategies and tempos advantageous in experiments of this type in space. Drosophila melanogaster, the current biological paradigm to study development, with so much genetic and evolutionary background available, is clearly the reference organism for these studies. The current evidence on the effects of the physical parameters altered in space flights on insect development indicate a surprising correlation between effects seen on the fast developing and relatively small Drosophila embryo and the more slowly developing and large Carausius morosus system. In relation to the issue of the importance of developmental and environmental constraints in biological evolution, still the missing link in current evolutionary thinking, insects and space facilities for long-term experiments could provide useful experimental settings where to critically assess how development and evolution may be interconnected. Finally, it has to be pointed out that since there are experimental data indicating a possible synergism between microgravity and space radiation, possible effects of space radiation should be taken into account in the planning and evaluation of experiments designed to test the potential role of microgravity on biological development and evolution.

  17. Holistic face training enhances face processing in developmental prosopagnosia

    PubMed Central

    Cohan, Sarah; Nakayama, Ken

    2014-01-01

    Prosopagnosia has largely been regarded as an untreatable disorder. However, recent case studies using cognitive training have shown that it is possible to enhance face recognition abilities in individuals with developmental prosopagnosia. Our goal was to determine if this approach could be effective in a larger population of developmental prosopagnosics. We trained 24 developmental prosopagnosics using a 3-week online face-training program targeting holistic face processing. Twelve subjects with developmental prosopagnosia were assessed before and after training, and the other 12 were assessed before and after a waiting period, they then performed the training, and were then assessed again. The assessments included measures of front-view face discrimination, face discrimination with view-point changes, measures of holistic face processing, and a 5-day diary to quantify potential real-world improvements. Compared with the waiting period, developmental prosopagnosics showed moderate but significant overall training-related improvements on measures of front-view face discrimination. Those who reached the more difficult levels of training (‘better’ trainees) showed the strongest improvements in front-view face discrimination and showed significantly increased holistic face processing to the point of being similar to that of unimpaired control subjects. Despite challenges in characterizing developmental prosopagnosics’ everyday face recognition and potential biases in self-report, results also showed modest but consistent self-reported diary improvements. In summary, we demonstrate that by using cognitive training that targets holistic processing, it is possible to enhance face perception across a group of developmental prosopagnosics and further suggest that those who improved the most on the training task received the greatest benefits. PMID:24691394

  18. Developmental Toxicity of Nanoparticles on the Brain.

    PubMed

    Umezawa, Masakazu; Onoda, Atsuto; Takeda, Ken

    2017-01-01

    The toxicity of nanoparticles (nanotoxicology) is being investigated to understand both the health impacts of atmospheric ultrafine particles-the size of which is a fraction (<0.1 μm aerodynamic diameter) of that of PM 2.5 (<2.5 μm diameter)-and the safer use of engineered nanomaterials. Developmental toxicity of nanoparticles has been studied since their transfer from pregnant body to fetal circulation and offspring body was first reported. Here we reviewed the developmental toxicity of nanoparticles on the brain, one of the most important organs in maintenance of mental health and high quality of life. Recently the dose- and size-dependency of transplacental nanoparticle transfer to the fetus was reported. It is important to understand both the mechanism of direct effect of nanoparticles transferred to the fetus and offspring and the indirect effect mediated by induction of oxidative stress and inflammation in the pregnant body. Locomotor activity, learning and memory, motor coordination, and social behavior were reported as potential neurobehavioral targets of maternal nanoparticle exposure. Histopathologically, brain perivascular cells, including perivascular macrophages and surrounding astrocytes, have an important role in waste clearance from the brain parenchyma. They are potentially the most sensitive target of maternal exposure to low-dose nanoparticles. Further investigations will show the detailed mechanism of developmental toxicity of nanoparticles and preventive strategies against intended and unintended nanoparticle exposure. This knowledge will contribute to the safer design of nanoparticles through the development of sensitive and quantitative endpoints for prediction of their developmental toxicity.

  19. Ecological and life-history factors influencing the evolution of maternal antibody allocation: a phylogenetic comparison

    PubMed Central

    Addison, BriAnne; Klasing, Kirk C.; Robinson, W. Douglas; Austin, Suzanne H.; Ricklefs, Robert E.

    2009-01-01

    Maternally derived yolk antibodies provide neonates with immune protection in early life at negligible cost to mothers. However, developmental effects on the neonate's future immunity are potentially costly and thus could limit yolk antibody deposition. The benefits to neonatal immunity must be balanced against costs, which may depend on neonate vulnerability to pathogens, developmental trajectories and the immunological strategies best suited to a species' pace of life. We measured yolk antibodies and life-history features of 23 species of small Neotropical birds and assessed the evidence for each of several hypotheses for life history and ecological effects on the evolution of yolk antibody levels. Developmental period and yolk antibodies are negatively related, which possibly reflect the importance of humoral immune priming through antigen exposure, and selection to avoid autoimmunity, in species with a slower pace of life. There is also a strong relationship between body size and yolk antibody concentration, suggesting that larger species are architecturally equipped to produce and transfer higher concentrations of antibodies. These results suggest that developmental effects of maternally derived antibodies, such as imprinting effects on B-cell diversity or autoimmune effects, are important and deserve more consideration in future research. PMID:19710063

  20. Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells.

    PubMed

    Choi, Jiho; Huebner, Aaron J; Clement, Kendell; Walsh, Ryan M; Savol, Andrej; Lin, Kaixuan; Gu, Hongcang; Di Stefano, Bruno; Brumbaugh, Justin; Kim, Sang-Yong; Sharif, Jafar; Rose, Christopher M; Mohammad, Arman; Odajima, Junko; Charron, Jean; Shioda, Toshi; Gnirke, Andreas; Gygi, Steven; Koseki, Haruhiko; Sadreyev, Ruslan I; Xiao, Andrew; Meissner, Alexander; Hochedlinger, Konrad

    2017-08-10

    Concomitant activation of the Wnt pathway and suppression of Mapk signalling by two small molecule inhibitors (2i) in the presence of leukaemia inhibitory factor (LIF) (hereafter termed 2i/L) induces a naive state in mouse embryonic stem (ES) cells that resembles the inner cell mass (ICM) of the pre-implantation embryo. Since the ICM exists only transiently in vivo, it remains unclear how sustained propagation of naive ES cells in vitro affects their stability and functionality. Here we show that prolonged culture of male mouse ES cells in 2i/L results in irreversible epigenetic and genomic changes that impair their developmental potential. Furthermore, we find that female ES cells cultured in conventional serum plus LIF medium phenocopy male ES cells cultured in 2i/L. Mechanistically, we demonstrate that the inhibition of Mek1/2 is predominantly responsible for these effects, in part through the downregulation of DNA methyltransferases and their cofactors. Finally, we show that replacement of the Mek1/2 inhibitor with a Src inhibitor preserves the epigenetic and genomic integrity as well as the developmental potential of ES cells. Taken together, our data suggest that, although short-term suppression of Mek1/2 in ES cells helps to maintain an ICM-like epigenetic state, prolonged suppression results in irreversible changes that compromise their developmental potential.

  1. The use of repetition suppression paradigms in developmental cognitive neuroscience.

    PubMed

    Nordt, Marisa; Hoehl, Stefanie; Weigelt, Sarah

    2016-07-01

    Repetition suppression paradigms allow a more detailed look at brain functioning than classical paradigms and have been applied vigorously in adult cognitive neuroscience. These paradigms are well suited for studies in the field of developmental cognitive neuroscience as they can be applied without collecting a behavioral response and across all age groups. Furthermore, repetition suppression paradigms can be employed in various neuroscience techniques, such as functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), electroencephalography (EEG) and magnetoencephalography (MEG). In the present article we review studies using repetition suppression paradigms in developmental cognitive neuroscience covering the age range from infancy to adolescence. Our first goal is to point out characteristics of developmental repetition suppression effects. In doing so, we discuss the relationship of the direction of repetition effects (suppression vs enhancement) with developmental factors, and address the question how the direction of repetition effects might be related to looking-time effects in behavioral infant paradigms, the most prominently used behavioral measure in infant research. To highlight the potential of repetition suppression paradigms, our second goal is to provide an overview on the insights recently obtained by applying repetition paradigms in neurodevelopmental studies, including research on children with autism spectrum disorders (ASDs). We conclude that repetition suppression paradigms are valuable tools for investigating neurodevelopmental processes, while at the same time we highlight the necessity for further studies that disentangle methodological and developmental factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Hazard-ranking of agricultural pesticides for chronic health effects in Yuma County, Arizona.

    PubMed

    Sugeng, Anastasia J; Beamer, Paloma I; Lutz, Eric A; Rosales, Cecilia B

    2013-10-01

    With thousands of pesticides registered by the United States Environmental Protection Agency, it not feasible to sample for all pesticides applied in agricultural communities. Hazard-ranking pesticides based on use, toxicity, and exposure potential can help prioritize community-specific pesticide hazards. This study applied hazard-ranking schemes for cancer, endocrine disruption, and reproductive/developmental toxicity in Yuma County, Arizona. An existing cancer hazard-ranking scheme was modified, and novel schemes for endocrine disruption and reproductive/developmental toxicity were developed to rank pesticide hazards. The hazard-ranking schemes accounted for pesticide use, toxicity, and exposure potential based on chemical properties of each pesticide. Pesticides were ranked as hazards with respect to each health effect, as well as overall chronic health effects. The highest hazard-ranked pesticides for overall chronic health effects were maneb, metam-sodium, trifluralin, pronamide, and bifenthrin. The relative pesticide rankings were unique for each health effect. The highest hazard-ranked pesticides differed from those most heavily applied, as well as from those previously detected in Yuma homes over a decade ago. The most hazardous pesticides for cancer in Yuma County, Arizona were also different from a previous hazard-ranking applied in California. Hazard-ranking schemes that take into account pesticide use, toxicity, and exposure potential can help prioritize pesticides of greatest health risk in agricultural communities. This study is the first to provide pesticide hazard-rankings for endocrine disruption and reproductive/developmental toxicity based on use, toxicity, and exposure potential. These hazard-ranking schemes can be applied to other agricultural communities for prioritizing community-specific pesticide hazards to target decreasing health risk. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Emerging Environmental Contaminants: What’s New

    EPA Science Inventory

    Much has been achieved in the way of environmental protection over the last 30 years. However, as we learn more, new concerns arise; for example, potential adverse health effects (e.g., cancer, reproductive and developmental effects, and endocrine disruption), bioaccumulation, an...

  4. Perceived Effectiveness of Internal Executive Coaching Engagements by Participants in a High Potential Leadership Development Program

    ERIC Educational Resources Information Center

    Figlar, Marilyn Elizabeth Kraus

    2014-01-01

    The field of executive coaching has grown in popularity as a developmental tool for leaders. With the potential for a leadership continuity gap and the desire for organizations to strengthen leadership talent pools to prepare for succession planning, there is a need for empirical research regarding the effectiveness of executive coaching. The aim…

  5. Woodland in Practical Skills Therapeutic Education

    ERIC Educational Resources Information Center

    Mata, Paula; Gibons, Kenneth; Mata, Fernando

    2016-01-01

    Modern urban life provides less opportunities to contact with nature, which is a potential cause of developmental deviances in children. We investigated the potential therapeutic effect of woodlands, within the context of Practical Skills Therapeutic Education at the Ruskin Mill College, UK. Data on physical and emotional perceptions were…

  6. AN OCCUPATIONAL REPRODUCTIVE RESEARCH AGENDA FOR THE THIRD MILLENNIUM

    EPA Science Inventory

    There is a significant public health concern about the potential effects of occupational exposure to toxic substances on reproductive outcomes. Several toxicants with reported reproductive and developmental effects are still in regular commercial or therapeutic use and thus prese...

  7. OVERVIEW AND EVALUATION OF NEUROBEHAVIORAL EFFECTS OF FLAME RETARDANTS IN LABORATORY ANIMALS.

    EPA Science Inventory

    Polybrominated diphenyl ether (PBDE) flame retardants are used worldwide and have been detected in numerous environmental, including human, samples. Concern has been raised regarding their potential developmental neurotoxic effects. There is an emerging literature on behavioral...

  8. Knowing when to assist: developmental issues in lifelong assistive robotics.

    PubMed

    Demiris, Yiannis

    2009-01-01

    Children and adults with sensorimotor disabilities can significantly increase their autonomy through the use of assistive robots. As the field progresses from short-term, task-specific solutions to long-term, adaptive ones, new challenges are emerging. In this paper a lifelong methodological approach is presented, that attempts to balance the immediate context-specific needs of the user, with the long-term effects that the robot's assistance can potentially have on the user's developmental trajectory.

  9. Gestational Hyperandrogenism in Developmental Programming

    PubMed Central

    Hakim, Christopher; Padmanabhan, Vasantha

    2017-01-01

    Androgen excess (hyperandrogenism) is a common endocrine disorder affecting women of reproductive age. The potential causes of androgen excess in women include polycystic ovary syndrome, congenital adrenal hyperplasia (CAH), adrenal tumors, and racial disparity among many others. During pregnancy, luteoma, placental aromatase deficiency, and fetal CAH are additional causes of gestational hyperandrogenism. The present report reviews the various phenotypes of hyperandrogenism during pregnancy and its origin, pathophysiology, and the effect of hyperandrogenism on the fetal developmental trajectory and offspring consequences. PMID:27967205

  10. PROPYLTHIOURACIL (PTU)-INDUCED HYPOTHYROIDISM: EFFECTS ON SYNAPTIC TRANSMISSION AND LONG TERM POTENTIATION IN HIPPOCAMPAL SLICES.

    EPA Science Inventory

    Concern has been raised over endocrine effects of some classes of environmental chemicals. Severe hypothyroidism during critical periods of brain developmental leads to alterations in hippocampal structure, learning deficits, yet neurophysiological properties of the hippocampus...

  11. USING PEA AND SOYBEAN IN DEVELOPMENTAL TESTS FOR NON-TARGET PLANT EFFECTS

    EPA Science Inventory

    Current tests required for pesticide registration do not investigate the potential effects of chemical exposure on plant development. The tests investigate only seedling emergence and early growth. Previous research has shown that significant impacts can occur to plant developm...

  12. Reproductive and Developmental Toxicity of Formaldehyde: A Systematic Review

    PubMed Central

    Duong, Anh; Steinmaus, Craig; McHale, Cliona M.; Vaughan, Charles P.; Zhang, Luoping

    2011-01-01

    Formaldehyde, the recently classified carcinogen and ubiquitous environmental contaminant, has long been suspected of causing adverse reproductive and developmental effects, but previous reviews were inconclusive, due in part, to limitations in the design of many of the human population studies. In the current review, we systematically evaluated evidence of an association between formaldehyde exposure and adverse reproductive and developmental effects, in human populations and in vivo animal studies, in the peer-reviewed literature. The mostly retrospective human studies provided evidence of an association of maternal exposure with adverse reproductive and developmental effects. Further assessment of this association by meta-analysis revealed an increased risk of spontaneous abortion (1.76, 95% CI 1.20–2.59, p=0.002) and of all adverse pregnancy outcomes combined (1.54, 95% CI 1.27–1.88, p<0.001), in formaldehyde-exposed women, although differential recall, selection bias, or confounding cannot be ruled out. Evaluation of the animal studies including all routes of exposure, doses and dosing regimens studied, suggested positive associations between formaldehyde exposure and reproductive toxicity, mostly in males. Potential mechanisms underlying formaldehyde-induced reproductive and developmental toxicities, including chromosome and DNA damage (genotoxicity), oxidative stress, altered level and/or function of enzymes, hormones and proteins, apoptosis, toxicogenomic and epigenomic effects (such as DNA methylation), were identified. To clarify these associations, well-designed molecular epidemiologic studies, that include quantitative exposure assessment and diminish confounding factors, should examine both reproductive and developmental outcomes associated with exposure in males and females. Together with mechanistic and animal studies, this will allow us to better understand the systemic effect of formaldehyde exposure. PMID:21787879

  13. Short-term developmental effects and potential mechanisms of azoxystrobin in larval and adult zebrafish (Danio rerio).

    PubMed

    Cao, Fangjie; Wu, Peizhuo; Huang, Lan; Li, Hui; Qian, Le; Pang, Sen; Qiu, Lihong

    2018-05-01

    Previous study indicated that azoxystrobin had high acute toxicity to zebrafish, and larval zebrafish were more sensitive to azoxystrobin than adult zebrafish. The objective of the present study was to investigate short-term developmental effects and potential mechanisms of azoxystrobin in larval and adult zebrafish. After zebrafish embryos and adults were exposed to 0.01, 0.05 and 0.20 mg/L azoxystrobin (equal to 25, 124 and 496 nM azoxystrobin, respectively) for 8 days, the lethal effect, physiological responses, liver histology, mitochondrial ultrastructure, and expression alteration of genes related to mitochondrial respiration, oxidative stress, cell apoptosis and innate immune response were determined. The results showed that there was no significant effect on larval and adult zebrafish after exposure to 0.01 mg/L azoxystrobin. However, increased ROS, MDA concentration and il1b in larval zebrafish, as well as increased il1b, il8 and cxcl-c1c in adult zebrafish were induced after exposure to 0.05 mg/L azoxystrobin. Reduced mitochondrial complex III activity and ATP concentration, increased SOD activity, ROS and MDA concentration, decreased cytb, as well as increased sod1, sod2, cat, il1b, il8 and cxcl-c1c were observed both in larval and adult zebrafish after exposure to 0.20 mg/L azoxystrobin; meanwhile, increased p53, bax, apaf1 and casp9, alteration of liver histology and mitochondrial ultrastructure in larval zebrafish, and alteration of mitochondrial ultrastructure in adult zebrafish were also induced. The results demonstrated that azoxytrobin induced short-term developmental effects on larval zebrafish and adult zebrafish, including mitochondrial dysfunction, oxidative stress, cell apoptosis and innate immune response. Statistical analysis indicated that azoxystrobin induced more negative effects on larval zebrafish, which might be the reason for the differences of developmental toxicity between larval and adult zebrafish caused by azoxystrobin. These results provided a new insight into potential mechanisms of azoxystrobin in larval zebrafish and adult zebrafish. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Developmental mechanisms underlying variation in craniofacial disease and evolution.

    PubMed

    Fish, Jennifer L

    2016-07-15

    Craniofacial disease phenotypes exhibit significant variation in penetrance and severity. Although many genetic contributions to phenotypic variation have been identified, genotype-phenotype correlations remain imprecise. Recent work in evolutionary developmental biology has exposed intriguing developmental mechanisms that potentially explain incongruities in genotype-phenotype relationships. This review focuses on two observations from work in comparative and experimental animal model systems that highlight how development structures variation. First, multiple genetic inputs converge on relatively few developmental processes. Investigation of when and how variation in developmental processes occurs may therefore help predict potential genetic interactions and phenotypic outcomes. Second, genetic mutation is typically associated with an increase in phenotypic variance. Several models outlining developmental mechanisms underlying mutational increases in phenotypic variance are discussed using Satb2-mediated variation in jaw size as an example. These data highlight development as a critical mediator of genotype-phenotype correlations. Future research in evolutionary developmental biology focusing on tissue-level processes may help elucidate the "black box" between genotype and phenotype, potentially leading to novel treatment, earlier diagnoses, and better clinical consultations for individuals affected by craniofacial anomalies. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. An approach to finding teaching moments on families and child development in Disney films.

    PubMed

    Guerrero, Anthony P S

    2015-04-01

    In the interest of finding "teaching moments in film" for psychiatric education and education on child development, the author describes an approach to analyzing Disney--and potentially other children's films--based on specifically observing family structure at the beginning and ending of the story, developmental stage and gender of the protagonist, the developmental crisis, and the external change agent and/or stressor. The author considered a convenience sample of ten popular Disney films. A wide variety of family structures and developmental stages and challenges were observed in the reviewed films. A matrix approach such as the one illustrated may help psychiatric educators to select effective teaching moments from Disney and other children's films.

  16. Social Media and Mentoring in Biomedical Research Faculty Development.

    PubMed

    Teruya, Stacey Alan; Bazargan-Hejazi, Shahrzad

    2014-09-01

    To determine how effective and collegial mentoring in biomedical research faculty development may be implemented and facilitated through social media. The authors reviewed the literature for objectives, concerns, and limitations of career development for junior research faculty. They tabularized these as developmental goals, and aligned them with relevant social media strengths and capabilities facilitated through traditional and/or peer mentoring. The authors derived a model in which social media is leveraged to achieve developmental goals reflected in independent and shared projects, and in the creation and expansion of support and research networks. Social media may be successfully leveraged and applied in achieving developmental goals for biomedical research faculty, and potentially for those in other fields and disciplines.

  17. 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.

  18. Sperm-derived factors enhance the in vitro developmental potential of haploid parthenotes.

    PubMed

    Nair, Ramya; Aboobacker, Shahin; Mutalik, Srinivas; Kalthur, Guruprasad; Adiga, Satish Kumar

    2017-12-01

    Parthenotes are characterized by poor in vitro developmental potential either due to the ploidy status or the absence of paternal factors. In the present study, we demonstrate the beneficial role of sperm-derived factors (SDF) on the in vitro development of mouse parthenotes. Mature (MII) oocytes collected from superovulated Swiss albino mice were activated using strontium chloride (SrCl2) in the presence or absence of various concentrations of SDF in M16 medium. The presence of SDF in activation medium did not have any significant influence on the activation rate. However, a significant increase in the developmental potential of the embryos and increased blastocyst rate (P < 0.01) was observed at 50 µg/ml concentration. Furthermore, the activated oocytes from this group exhibited early cleavage and cortical distribution of cortical granules that was similar to that of normally fertilized zygotes. Culturing 2-cell stage parthenotes in the presence of SDF significantly improved the developmental potential (P < 0.05) indicating that they also play a significant role in embryo development. In conclusion, artificial activation of oocytes with SDF can improve the developmental potential of parthenotes in vitro.

  19. THE INFLUENCE OF PRESESSION FACTORS IN THE ASSESSMENT OF DEVIANT AROUSAL

    PubMed Central

    Reyes, Jorge R; Vollmer, Timothy R; Hall, Astrid

    2011-01-01

    Three adult male sex offenders with developmental disabilities participated in an evaluation of presession factors that may influence levels of sexual arousal measured with a penile plethysmograph. We evaluated the effects of presession masturbation (1 participant) and arousal-suppression strategies (2 participants). Results showed that presession masturbation lowered arousal levels and both participants suppressed arousal to varying degrees. These outcomes suggest the potential for consideration and manipulation of presession factors as treatment components for sex offenders with developmental disabilities. PMID:22219524

  20. Pre- and Postnatal Exposure to Low Dose Glufosinate Ammonium Induces Autism-Like Phenotypes in Mice

    PubMed Central

    Laugeray, Anthony; Herzine, Ameziane; Perche, Olivier; Hébert, Betty; Aguillon-Naury, Marine; Richard, Olivier; Menuet, Arnaud; Mazaud-Guittot, Séverine; Lesné, Laurianne; Briault, Sylvain; Jegou, Bernard; Pichon, Jacques; Montécot-Dubourg, Céline; Mortaud, Stéphane

    2014-01-01

    Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 – two genes implicated in autism-like deficits – was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods. PMID:25477793

  1. Developmental plasticity: Friend or foe?

    PubMed

    Michels, Karin B

    2017-01-01

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

  2. Investigation of repeated dose (90 day) oral toxicity, reproductive/developmental toxicity and mutagenic potential of 'Calebin A'.

    PubMed

    Majeed, Muhammed; Nagabhushanam, Kalyanam; Natarajan, Sankaran; Bani, Sarang; Pandey, Anjali; Karri, Suresh Kumar

    2015-01-01

    The present work investigated repeated dose and reproductive toxicity of Calebin A in Wistar rats. A study for assessing the mutagenic potential of Calebin A through an AMES test is also described. Calebin A was orally administered to groups of 10 male and/or 10 female Wistar rats each, assigned to three dose levels (20, 50 and 100 mg/kg/body weight) once daily for 90 consecutive days. None of the animals in any of the treatment/control groups exhibited any abnormal clinical signs/behavioral changes, reproductive as well as developmental parameters, or gross and microscopic changes in both male and female rats. Calebin A was also evaluated for its ability to induce reverse mutations at selected loci of Salmonella typhimurium in the presence and absence of Aroclor 1254 induced rat liver S9 cell lines. In conclusion, 100 mg/kg/d of Calebin A is not likely to produce any significant toxic effects in male and female Wistar rats and no reproductive or developmental toxicity was observed at the same dose and hence Calebin A at 100 mg/kg was determined as "No Observed Adverse Effect Level (NOAEL)" under the test conditions.

  3. Effects of medicinal compounds on the differentiation of the eukaryotic microorganism dictyostelium discoideum: can this model be used as a screening test for reproductive toxicity in humans?

    PubMed

    Dannat, K; Tillner, J; Winckler, T; Weiss, M; Eger, K; Dingermann, T

    2003-03-01

    Dictyostelium discoideum is a single-cell, eukaryotic microorganism that can undergo multicellular development in order to produce dormant spores. We investigated the capacity of D. discoideum to be used as a rapid screening system for potential developmental toxicity of compounds under development as pharmaceuticals. We used a set of four transgenic D. discoideum strains that expressed a reporter gene under the control of promoters that are active at certain time periods and in distinct cell types during D. discoideum development. We found that teratogens such as valproic acid, tretinoin, or thalidomide interfered to various extents with D. discoideum development, and had different effects on prestalk and prespore cell-specific reporter gene expression. Phenytoin was inactive in this assay, which may point to limitations in metabolization of the compound in Dictyostelium required to exert developmental toxicity. D. discoideum cell culture is cheap and easy to handle compared to mammalian cell cultures or animal teratogenicity models. Although the Dictyostelium-based assay described in this report may not securely predict the teratogenic potential of these drugs in humans, this organism may be qualified for rapid large-scale screenings of synthetic compounds under development as new pharmaceuticals for their potential to interfere with developmental processes and thus help to reduce the amount of teratogenicity tests in animal models.

  4. Utility of Small Animal Models of Developmental Programming.

    PubMed

    Reynolds, Clare M; Vickers, Mark H

    2018-01-01

    Any effective strategy to tackle the global obesity and rising noncommunicable disease epidemic requires an in-depth understanding of the mechanisms that underlie these conditions that manifest as a consequence of complex gene-environment interactions. In this context, it is now well established that alterations in the early life environment, including suboptimal nutrition, can result in an increased risk for a range of metabolic, cardiovascular, and behavioral disorders in later life, a process preferentially termed developmental programming. To date, most of the mechanistic knowledge around the processes underpinning development programming has been derived from preclinical research performed mostly, but not exclusively, in laboratory mouse and rat strains. This review will cover the utility of small animal models in developmental programming, the limitations of such models, and potential future directions that are required to fully maximize information derived from preclinical models in order to effectively translate to clinical use.

  5. More than Just Convenient: The Scientific Merits of Homogeneous Convenience Samples

    PubMed Central

    Jager, Justin; Putnick, Diane L.; Bornstein, Marc H.

    2017-01-01

    Despite their disadvantaged generalizability relative to probability samples, non-probability convenience samples are the standard within developmental science, and likely will remain so because probability samples are cost-prohibitive and most available probability samples are ill-suited to examine developmental questions. In lieu of focusing on how to eliminate or sharply reduce reliance on convenience samples within developmental science, here we propose how to augment their advantages when it comes to understanding population effects as well as subpopulation differences. Although all convenience samples have less clear generalizability than probability samples, we argue that homogeneous convenience samples have clearer generalizability relative to conventional convenience samples. Therefore, when researchers are limited to convenience samples, they should consider homogeneous convenience samples as a positive alternative to conventional or heterogeneous) convenience samples. We discuss future directions as well as potential obstacles to expanding the use of homogeneous convenience samples in developmental science. PMID:28475254

  6. Negative priming in a numerical Piaget-like task as evidenced by ERP.

    PubMed

    Daurignac, Elsa; Houdé, Olivier; Jouvent, Roland

    2006-05-01

    Inhibition is a key executive function in adults and children for the acquisition and expression of cognitive abilities. Using event-related potentials in a priming adaptation of a Piaget-like numerical task taken from developmental psychology, we report a negative priming effect in adults measured just after the cognitive inhibition of a misleading strategy, the visuospatial length-equals-number bias. This effect was determined in the N200 information processing stage through increased N200 amplitude. We show here that for accuracy in numerical quantification, the adult brain still had to control the child-like cognition biases that are stored in a kind of "developmental memory."

  7. Neurophysiological assessment of auditory, peripheral nerve, somatosensory, and visual system functions after developmental exposure to ethanol vapors.

    PubMed

    Boyes, William K; Degn, Laura L; Martin, Sheppard A; Lyke, Danielle F; Hamm, Charles W; Herr, David W

    2014-01-01

    Ethanol-blended gasoline entered the market in response to demand for domestic renewable energy sources, and may result in increased inhalation of ethanol vapors in combination with other volatile gasoline constituents. It is important to understand potential risks of inhalation of ethanol vapors by themselves, and also as a baseline for evaluating the risks of ethanol combined with a complex mixture of hydrocarbon vapors. Because sensory dysfunction has been reported after developmental exposure to ethanol, we evaluated the effects of developmental exposure to ethanol vapors on neurophysiological measures of sensory function as a component of a larger project evaluating developmental ethanol toxicity. Pregnant Long-Evans rats were exposed to target concentrations 0, 5000, 10,000, or 21,000 ppm ethanol vapors for 6.5h/day over GD9-GD20. Sensory evaluations of male offspring began between PND106 and PND128. Peripheral nerve function (compound action potentials, nerve conduction velocity (NCV)), somatosensory (cortical and cerebellar evoked potentials), auditory (brainstem auditory evoked responses), and visual evoked responses were assessed. Visual function assessment included pattern elicited visual evoked potentials (VEPs), VEP contrast sensitivity, and electroretinograms recorded from dark-adapted (scotopic), light-adapted (photopic) flashes, and UV flicker and green flicker. No consistent concentration-related changes were observed for any of the physiological measures. The results show that gestational exposure to ethanol vapor did not result in detectable changes in peripheral nerve, somatosensory, auditory, or visual function when the offspring were assessed as adults. Published by Elsevier Inc.

  8. Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and rats.

    PubMed

    Welsch, Frank; Elswick, Barbara; James, R Arden; Marr, Melissa C; Myers, Christina B; Tyl, Rochelle W

    2003-01-01

    This evaluation was part of a much more comprehensive testing program to characterize the mammalian toxicity potential of the gasoline oxygenator additive tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency mandate. A developmental toxicity hazard identification study was conducted by TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant CD(Sprague-Dawley) rats and CD-1 mice, 25 animals per group, inhaled TAME vapors containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6-16 (mice) or 6-19 (rats). The developmental toxicity hazard potential was evaluated following the study design draft guidelines and end points proposed by the United States Environmental Protection Agency. Based on maternal body weight changes during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using the criterion of near-term fetal body weights. In mice, more profound developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At the highest concentration, mouse litters revealed more late fetal deaths, significantly reduced fetal body weights per litter and increased incidences of cleft palate (classified as an external malformation), as well as enlarged lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse fetuses also exhibited an increased incidence of cleft palate and the dam body weights were reduced. Therefore, the NOAEL for the mouse maternal and developmental toxicity was 250 ppm under the conditions of this study. Copyright 2003 John Wiley & Sons, Ltd.

  9. Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from The Endocrine Society

    PubMed Central

    Brown, T. R.; Doan, L. L.; Gore, A. C.; Skakkebaek, N. E.; Soto, A. M.; Woodruff, T. J.; Vom Saal, F. S.

    2012-01-01

    An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive “safe” dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures. PMID:22733974

  10. 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...

  11. Effects of Professional Development on Preschool Teachers' Use of Embedded Instruction Practices

    ERIC Educational Resources Information Center

    Snyder, Patricia; Hemmeter, Mary Louise; McLean, Mary; Sandall, Susan; McLaughlin, Tara; Algina, James

    2018-01-01

    We conducted a randomized controlled potential efficacy trial to examine effects of two variants of the Tools for Teachers (TfT) professional development (PD) intervention on preschool teachers' implementation of embedded instruction practices and children's developmental and learning outcomes. Thirty-six preschool teachers recruited from three…

  12. RODENT AND HUMAN NEUROPROGENITOR CELLS FOR HIGH-CONTENT SCREENS OF CHEMICAL EFFECTS ON PROLIFERATION AND APOPTOSIS

    EPA Science Inventory

    The objective of these experiments is to develop high-throughput screens for proliferation and apoptosis in order to compare rodent and human neuroprogenitor cell responses to potential developmental neurotoxicants. Effects of 4 chemicals on proliferation and apoptosis in mouse c...

  13. ASSESSMENT OF CHEMICAL EFFECTS ON NEURITE OUTGROWTH, NEURONAL POLARIZATION AND SYNAPTOGENESIS IN RAT CORTICAL NEURONS USING HIGH CONTENT IMAGE ANALYSIS

    EPA Science Inventory

    There is a need for efficient, cost-effective methods for screening and prioritization of potential developmental neurotoxicants. One approach uses in vitro cell culture models that can recapitulate the critical processes of nervous system development. In vitro, primary cultures ...

  14. Developmental Effects of Incentives on Response Inhibition

    ERIC Educational Resources Information Center

    Geier, Charles F.; Luna, Beatriz

    2012-01-01

    Inhibitory control and incentive processes underlie decision making, yet few studies have explicitly examined their interaction across development. Here, the effects of potential rewards and losses on inhibitory control in 64 adolescents (13- to 17-year-olds) and 42 young adults (18- to 29-year-olds) were examined using an incentivized antisaccade…

  15. Multigeneration reproductive and developmental toxicity study of bar gene inserted into genetically modified potato on rats.

    PubMed

    Rhee, Gyu Seek; Cho, Dae Hyun; Won, Yong Hyuck; Seok, Ji Hyun; Kim, Soon Sun; Kwack, Seung Jun; Lee, Rhee Da; Chae, Soo Yeong; Kim, Jae Woo; Lee, Byung Mu; Park, Kui Lea; Choi, Kwang Sik

    2005-12-10

    Each specific protein has an individual gene encoding it, and a foreign gene introduced to a plant can be used to synthesize a new protein. The identification of potential reproductive and developmental toxicity from novel proteins produced by genetically modified (GM) crops is a difficult task. A science-based risk assessment is needed in order to use GM crops as a conventional foodstuff. In this study, the specific characteristics of GM food and low-level chronic exposure were examined using a five-generation animal study. In each generation, rats were fed a solid pellet containing 5% GM potato and non-GM potato for 10 wk prior to mating in order to assess the potential reproductive and developmental toxic effects. In the multigeneration animal study, there were no GM potato-related changes in body weight, food consumption, reproductive performance, and organ weight. Polymerase chain reaction (PCR) was carried out using extracted genomic DNA to examine the possibility of gene persistence in the organ tissues after a long-term exposure to low levels of GM feed. In each generation, the gene responsible for bar was not found in any of the reproductive organs of the GM potato-treated male and female rats, and the litter-related indexes did not show any genetically modified organism (GMO)-related changes. The results suggest that genetically modified crops have no adverse effects on the multigeneration reproductive-developmental ability.

  16. 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.

  17. Pleiotropy in the wild: the dormancy gene DOG1 exerts cascading control on life cycles.

    PubMed

    Chiang, George C K; Barua, Deepak; Dittmar, Emily; Kramer, Elena M; de Casas, Rafael Rubio; Donohue, Kathleen

    2013-03-01

    In the wild, organismal life cycles occur within seasonal cycles, so shifts in the timing of developmental transitions can alter the seasonal environment experienced subsequently. Effects of genes that control the timing of prior developmental events can therefore be magnified in the wild because they determine seasonal conditions experienced by subsequent life stages, which can influence subsequent phenotypic expression. We examined such environmentally induced pleiotropy of developmental-timing genes in a field experiment with Arabidopsis thaliana. When studied in the field under natural seasonal variation, an A. thaliana seed-dormancy gene, Delay Of Germination 1 (DOG1), was found to influence not only germination, but also flowering time, overall life history, and fitness. Flowering time of the previous generation, in turn, imposed maternal effects that altered germination, the effects of DOG1 alleles, and the direction of natural selection on these alleles. Thus under natural conditions, germination genes act as flowering genes and potentially vice versa. These results illustrate how seasonal environmental variation can alter pleiotropic effects of developmental-timing genes, such that effects of genes that regulate prior life stages ramify to influence subsequent life stages. In this case, one gene acting at the seed stage impacted the entire life cycle. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  18. Exposure of children with developmental delay to social determinants of poor health: cross-sectional case record review study.

    PubMed

    Emerson, E; Brigham, P

    2015-03-01

    Research on child development in general has highlighted the importance that the family environment plays in mediating the pathway between exposure to low socio-economic position (SEP) and child well-being. While child developmental models in intellectual disability have highlighted the interplay between social context, family environment and child development, little empirical work has attempted to formally evaluate the evidence in support of specific mediating pathways between low SEP and child outcomes. Secondary analysis of cross-sectional confidentialized needs analysis data collected in three Primary Care Trusts in England covering a total population of 1.25 million people. Case record reviews were undertaken for 46 023 households, 2236 (4.9%) of which contained a child in the target age range with developmental delay. Children with developmental delay, when compared with their non-disabled peers, were at significantly increased risk of poorer health outcomes and of being exposed to a wide range of social determinants of poor health. Controlling for between-group differences in exposure to social determinants of poor health reduced the risk of developmental delay being associated with poorer health outcomes by 45% for behaviour problems and 89% for risk of significant harm. For children with developmental delay, parenting difficulties appears to play a particularly significant role in partially mediating the effects of low SEP. The findings of the present study point to the potential effectiveness of family-focused early intervention to prevent the emergence and escalation of behavioural difficulties and health problems in children with developmental delay. © 2014 John Wiley & Sons Ltd.

  19. Social Media and Mentoring in Biomedical Research Faculty Development

    PubMed Central

    Teruya, Stacey Alan; Bazargan-Hejazi, Shahrzad

    2015-01-01

    Purpose To determine how effective and collegial mentoring in biomedical research faculty development may be implemented and facilitated through social media. Method The authors reviewed the literature for objectives, concerns, and limitations of career development for junior research faculty. They tabularized these as developmental goals, and aligned them with relevant social media strengths and capabilities facilitated through traditional and/or peer mentoring. Results The authors derived a model in which social media is leveraged to achieve developmental goals reflected in independent and shared projects, and in the creation and expansion of support and research networks. Conclusions Social media may be successfully leveraged and applied in achieving developmental goals for biomedical research faculty, and potentially for those in other fields and disciplines. PMID:26120494

  20. Assessing the Developmental Neurotoxicity of 27 ...

    EPA Pesticide Factsheets

    Assessing the Developmental Neurotoxicity of 27 Organophosphorus Pesticides Using a Zebrafish Behavioral Assay, Waalkes, M., Hunter, D.L., Jarema, K., Mundy, W., and S. Padilla. The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize organophosphorus pesticides for developmental neurotoxicity. As such, we are exploring a behavioral testing paradigm that can assess the effects of sublethal and subteratogenic concentrations of developmental neurotoxicants on zebrafish (Danio rerio). This in vivo assay quantifies the locomotor response to light stimuli under tandem light and dark conditions in a 96-well plate using a video tracking system on 6 day post fertilization zebrafish larvae. Each of twenty-seven organophosphorus pesticides was tested for their developmental neurotoxic potential by exposing zebrafish embryos/larvae to the pesticide at several concentrations (≤ 100 μM nominal concentration) during the first five days of development, followed by 24 hours of depuration and then behavioral testing. Approximately 22% of the chemicals (Acephate, Dichlorvos, Diazoxon, Bensulide,Tribufos, Tebupirimfos) did not produce any behavioral changes after developmental exposure, while many (Malaoxon Fosthiazate, Dimethoate, Dicrotophos, Ethoprop, Malathion, Naled, Diazinon, Methamidophos, Terbufos, Trichlorfon, Phorate, Pirimiphos-methyl, Profenofos, Z-Tetrachlorvinphos, Chlorpyrifos, Coumaphos, Phosmet, Omethoate) produced changes in swi

  1. From Mice to Men: research models of developmental programming

    PubMed Central

    Rabadán-Diehl, C.; Nathanielsz, P.

    2012-01-01

    Developmental programming can be defined as a response to a specific challenge to the mammalian organism during a critical developmental time window that alters the trajectory of development with persistent effects on offspring phenotype and predisposition to future illness. We focus on the need for studies in relevant, well-characterized animal models in the context of recent research discoveries on the challenges, mechanisms and outcomes of developmental programming. We discuss commonalities and differences in general principles of developmental programming as they apply to several species, including humans. The consequences of these differences are discussed. Obesity, metabolic disorders and cardiovascular diseases are associated with the highest percentage of morbidity and mortality worldwide. Although many of the causes are associated with lifestyle, high-energy diets and lack of physical activity, recent evidence has linked developmental programming to the epidemic of metabolic diseases. A better understanding of comparative systems physiology of mother, fetus and neonate using information provided by rapid advances in molecular biology has the potential to improve the lifetime health of future generations by providing better women’s health, diagnostic tools and preventative and therapeutic interventions in individuals exposed during their development to programming influences. PMID:23525085

  2. Current Development in Reproductive Toxicity Testing of Pesticides

    EPA Science Inventory

    A protocol to evaluate the potential developmental and reproductive effects of test chemicals has been developed by the Life Stages Task Force of the International Life Sciences Institute (ILSI)/Health and Environmental Sciences Institute (HESI) Agricultural Chemical Safety Asses...

  3. 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.

  4. 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

  5. Extracurricular activity participation moderates impact of family and school factors on adolescents' disruptive behavioural problems.

    PubMed

    Driessens, Corine M E F

    2015-11-11

    The prevalence of problem behaviours among British adolescents has increased in the past decades. Following Erikson's psychosocial developmental theory and Bronfenbrenner's developmental ecological model, it was hypothesized that youth problem behaviour is shaped in part by social environment. The aim of this project was to explore potential protective factors within the social environment of British youth's for the presentation of disruptive behavioural problems. This study used secondary data from the Longitudinal Study of Young People in England, a cohort study of secondary school students. These data were analysed with generalized estimation equations to take the correlation between the longitudinal observations into account. Three models were built. The first model determined the effect of family, school, and extracurricular setting on presentation of disruptive behavioural problems. The second model expanded the first model by assuming extracurricular activities as protective factors that moderated the interaction between family and school factors with disruptive behavioural problems. The third model described the effect of prior disruptive behaviour on current disruptive behaviour. Associations were found between school factors, family factors, involvement in extracurricular activities and presence of disruptive behavioural problems. Results from the second generalized estimating equation (GEE) logistic regression models indicated that extracurricular activities buffered the impact of school and family factors on the presence of disruptive behavioural problems. For instance, participation in sports activities decreased the effect of bullying on psychological distress. Results from the third model indicated that prior acts of disruptive behaviour reinforced current disruptive behaviour. This study supports Erikson's psychosocial developmental theory and Bronfenbrenner's developmental ecological model; social environment did influence the presence of disruptive behavioural problems for British adolescents. The potential of extracurricular activities to intervention strategies addressing disruptive behavioural problems of adolescents is discussed.

  6. Relative Age Effects in Women's Rugby Union From Developmental Leagues to World Cup Tournaments.

    PubMed

    Lemez, Srdjan; MacMahon, Clare; Weir, Patricia

    2016-01-01

    Annual age cohort groupings promote relative age effects (RAEs), which often, inadvertently, create participation and attainment biases between relatively older and younger players within the same age cohort. In a globally evolving sport, women's rugby team selection practices may potentially bypass qualified players as a result of maturational differences. Our study examined the prevalence of RAEs in women's rugby union. Player data (age range = 4-21+ years) were gathered from the 2006 and 2010 Rugby World Cups (n = 498) and from Canadian (n = 1,497) and New Zealand (NZ; n = 13,899) developmental rugby leagues. Although no evidence of an RAE was found in the World Cup samples, chi-square analyses identified some typical and atypical patterns of RAEs at the developmental levels (w ≥ .3). Younger developmental groups displayed a typical RAE patterning with a greater representation of older players (Canadian 13-year-olds, w = .58; NZ 4-year-olds, w = .35), whereas older developmental groups displayed an atypical RAE patterning with a greater representation of younger players (Canadian 19-year-olds, w = .58; NZ 17-year-olds, w = .32). Further, a traditional RAE emerged in the Canadian 11- to 15-year-old age group, χ2(3) = 10.92, p < .05, w = .30. The lack of homogeneity of traditional RAEs across the sample questions the existence of a single, clear RAE in women's rugby. Some evidence of participation inequalities at the developmental levels suggests that further RAE research in more varied sociocultural contexts may be necessary.

  7. Developmental manganese neurotoxicity in rats: Cognitive deficits in allocentric and egocentric learning and memory.

    PubMed

    Amos-Kroohs, Robyn M; Davenport, Laurie L; Atanasova, Nina; Abdulla, Zuhair I; Skelton, Matthew R; Vorhees, Charles V; Williams, Michael T

    Manganese (Mn) is an essential element but neurotoxic at higher exposure levels. The effects of Mn overexposure (MnOE) on hippocampal and striatal-dependent learning and memory in rats were tested in combination with iron deficiency (FeD) and developmental stress that often co-occur with MnOE. Moderate FeD affects up to 15% of U.S. children and developmental stress is common in lower socio-economic areas where MnOE occurs. Pregnant Sprague-Dawley rats and their litters were housed in cages with or without (barren cage (BAR)) standard bedding from embryonic day (E)7 to postnatal day (P)28. Dams were fed a 90% FeD or iron sufficient (FeS) diet from E15-P28. Within each litter, separate offspring were treated with 100mg/kg Mn (MnOE) or vehicle (VEH) by gavage on alternate days from P4-28. Offspring were tested as adults in the Morris and Cincinnati water mazes. FeD and developmental stress interactively impaired spatial learning in the Morris water maze. Developmental stress and MnOE impaired learning and memory in both mazes. MnOE resulted in reduced CA1 hippocampal long-term potentiation (LTP) and increased levels of α-synuclein. Preweaning MnOE resulted in cognitive deficits on multiple domains of learning and memory accompanied by impaired LTP and α-synuclein changes, effects worsened by developmental stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Developmental origins of inflammatory and immune diseases

    PubMed Central

    Chen, Ting; Liu, Han-xiao; Yan, Hui-yi; Wu, Dong-mei; Ping, Jie

    2016-01-01

    Epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exert a profound influence on physiological function and risk of diseases in adult life. The concepts of the ‘developmental programming’ and Developmental Origins of Health and Diseases (DOHaD) have become well accepted and have been applied across almost all fields of medicine. Adverse intrauterine environments may have programming effects on the crucial functions of the immune system during critical periods of fetal development, which can permanently alter the immune function of offspring. Immune dysfunction may in turn lead offspring to be susceptible to inflammatory and immune diseases in adulthood. These facts suggest that inflammatory and immune disorders might have developmental origins. In recent years, inflammatory and immune disorders have become a growing health problem worldwide. However, there is no systematic report in the literature on the developmental origins of inflammatory and immune diseases and the potential mechanisms involved. Here, we review the impacts of adverse intrauterine environments on the immune function in offspring. This review shows the results from human and different animal species and highlights the underlying mechanisms, including damaged development of cells in the thymus, helper T cell 1/helper T cell 2 balance disturbance, abnormal epigenetic modification, effects of maternal glucocorticoid overexposure on fetal lymphocytes and effects of the fetal hypothalamic–pituitary–adrenal axis on the immune system. Although the phenomena have already been clearly implicated in epidemiologic and experimental studies, new studies investigating the mechanisms of these effects may provide new avenues for exploiting these pathways for disease prevention. PMID:27226490

  9. Environmental Impact on Vascular Development Predicted by High-Throughput Screening

    PubMed Central

    Judson, Richard S.; Reif, David M.; Sipes, Nisha S.; Singh, Amar V.; Chandler, Kelly J.; DeWoskin, Rob; Dix, David J.; Kavlock, Robert J.; Knudsen, Thomas B.

    2011-01-01

    Background: Understanding health risks to embryonic development from exposure to environmental chemicals is a significant challenge given the diverse chemical landscape and paucity of data for most of these compounds. High-throughput screening (HTS) in the U.S. Environmental Protection Agency (EPA) ToxCast™ project provides vast data on an expanding chemical library currently consisting of > 1,000 unique compounds across > 500 in vitro assays in phase I (complete) and Phase II (under way). This public data set can be used to evaluate concentration-dependent effects on many diverse biological targets and build predictive models of prototypical toxicity pathways that can aid decision making for assessments of human developmental health and disease. Objective: We mined the ToxCast phase I data set to identify signatures for potential chemical disruption of blood vessel formation and remodeling. Methods: ToxCast phase I screened 309 chemicals using 467 HTS assays across nine assay technology platforms. The assays measured direct interactions between chemicals and molecular targets (receptors, enzymes), as well as downstream effects on reporter gene activity or cellular consequences. We ranked the chemicals according to individual vascular bioactivity score and visualized the ranking using ToxPi (Toxicological Priority Index) profiles. Results: Targets in inflammatory chemokine signaling, the vascular endothelial growth factor pathway, and the plasminogen-activating system were strongly perturbed by some chemicals, and we found positive correlations with developmental effects from the U.S. EPA ToxRefDB (Toxicological Reference Database) in vivo database containing prenatal rat and rabbit guideline studies. We observed distinctly different correlative patterns for chemicals with effects in rabbits versus rats, despite derivation of in vitro signatures based on human cells and cell-free biochemical targets, implying conservation but potentially differential contributions of developmental pathways among species. Follow-up analysis with antiangiogenic thalidomide analogs and additional in vitro vascular targets showed in vitro activity consistent with the most active environmental chemicals tested here. Conclusions: We predicted that blood vessel development is a target for environmental chemicals acting as putative vascular disruptor compounds (pVDCs) and identified potential species differences in sensitive vascular developmental pathways. PMID:21788198

  10. TRIENNIAL REPRODUCTION SYMPOSIUM: Developmental programming of fertility.

    PubMed

    Reynolds, L P; Vonnahme, K A

    2016-07-01

    The 2015 Triennial Reproduction Symposium focused on developmental programming of fertility. The topics covered during the morning session included the role of the placenta in programming of fetal growth and development, effects of feeding system and level of feeding during pregnancy on the annual production cycle and lifetime productivity of heifer offspring, effects of litter size and level of socialization postnatally on reproductive performance of pigs, effects of postnatal dietary intake on maturation of the hypothalamic-pituitary-gonadal axis and onset of puberty in heifers, effects of housing systems on growth performance and reproductive efficiency of gilts, and effects of energy balance on sexual differentiation in rodent models. The morning session concluded with presentation of the American Society of Animal Science L. E. Casida Award for Excellence in Graduate Education to Dr. Michael Smith from the University of Missouri, Columbia, who shared his philosophy of graduate education. The afternoon session included talks on the role of epigenetic modifications in developmental programming and transgenerational inheritance of reproductive dysfunction, effects of endocrine disrupting compounds on fetal development and long-term physiology of the individual, and potential consequences of real-life exposure to environmental contaminants on reproductive health. The symposium concluded with a summary talk and the posing of 2 questions to the audience. From an evolutionary standpoint, programming and epigenetic events must be adaptive; when do they become maladaptive? If there are so many environmental factors that induce developmental programming, are we doomed, and if not, what is or are the solution or solutions?

  11. Absolute and proportional measures of potential markers of rehearsal, and their implications for accounts of its development

    PubMed Central

    Jarrold, Christopher; Danielsson, Henrik; Wang, Xiaoli

    2015-01-01

    Previous studies of the development of phonological similarity and word length effects in children have shown that these effects are small or absent in young children, particularly when measured using visual presentation of the memoranda. This has often been taken as support for the view that young children do not rehearse. The current paper builds on recent evidence that instead suggests that absent phonological similarity and word length effects in young children reflects the same proportional cost of these effects in children of all ages. Our aims are to explore the conditions under which this proportional scaling account can reproduce existing developmental data, and in turn suggest ways that future studies might measure and model phonological similarity and word length effects in children. To that end, we first fit a single mathematical function through previously reported data that simultaneously captures absent and negative proportional effects of phonological similarity in young children plus constant proportional similarity effects in older children. This developmental function therefore provides the benchmark that we seek to re-produce in a series of subsequent simulations that test the proportional scaling account. These simulations reproduce the developmental function well, provided that they take into account the influence of floor effects and of measurement error. Our simulations suggest that future empirical studies examining these effects in the context of the development of rehearsal need to take into account proportional scaling. They also provide a demonstration of how proportional costs can be explored, and of the possible developmental functions associated with such an analysis. PMID:25852615

  12. Recent Insights Into Molecular Mechanisms of Propofol-Induced Developmental Neurotoxicity: Implications for the Protective Strategies.

    PubMed

    Bosnjak, Zeljko J; Logan, Sarah; Liu, Yanan; Bai, Xiaowen

    2016-11-01

    Mounting evidence has demonstrated that general anesthetics could induce developmental neurotoxicity, including acute widespread neuronal cell death, followed by long-term memory and learning abnormalities. Propofol is a commonly used intravenous anesthetic agent for the induction and maintenance of anesthesia and procedural and critical care sedation in children. Compared with other anesthetic drugs, little information is available on its potential contributions to neurotoxicity. Growing evidence from multiple experimental models showed a similar neurotoxic effect of propofol as observed in other anesthetic drugs, raising serious concerns regarding pediatric propofol anesthesia. The aim of this review is to summarize the current findings of propofol-induced developmental neurotoxicity. We first present the evidence of neurotoxicity from animal models, animal cell culture, and human stem cell-derived neuron culture studies. We then discuss the mechanism of propofol-induced developmental neurotoxicity, such as increased cell death in neurons and oligodendrocytes, dysregulation of neurogenesis, abnormal dendritic development, and decreases in neurotrophic factor expression. Recent findings of complex mechanisms of propofol action, including alterations in microRNAs and mitochondrial fission, are discussed as well. An understanding of the toxic effect of propofol and the underlying mechanisms may help to develop effective novel protective or therapeutic strategies for avoiding the neurotoxicity in the developing human brain.

  13. The Translational Role of Diffusion Tensor Image Analysis in Animal Models of Developmental Pathologies

    PubMed Central

    Oguz, Ipek; McMurray, Matthew S.; Styner, Martin; Johns, Josephine M.

    2013-01-01

    Diffusion Tensor Magnetic Resonance Imaging (DTI) has proven itself a powerful technique for clinical investigation of the neurobiological targets and mechanisms underlying developmental pathologies. The success of DTI in clinical studies has demonstrated its great potential for understanding translational animal models of clinical disorders, and preclinical animal researchers are beginning to embrace this new technology to study developmental pathologies. In animal models, genetics can be effectively controlled, drugs consistently administered, subject compliance ensured, and image acquisition times dramatically increased to reduce between-subject variability and improve image quality. When pairing these strengths with the many positive attributes of DTI, such as the ability to investigate microstructural brain organization and connectivity, it becomes possible to delve deeper into the study of both normal and abnormal development. The purpose of this review is to provide new preclinical investigators with an introductory source of information about the analysis of data resulting from small animal DTI studies to facilitate the translation of these studies to clinical data. In addition to an in depth review of translational analysis techniques, we present a number of relevant clinical and animal studies using DTI to investigate developmental insults in order to further illustrate techniques and to highlight where small animal DTI could potentially provide a wealth of translational data to inform clinical researchers. PMID:22627095

  14. School-Based Early Childhood Centers: Secrets of Success from Early Innovators.

    ERIC Educational Resources Information Center

    Jewett, Janet L.; Katzev, Aphra

    School-based early childhood centers have the potential for responding effectively to a broad range of child and family needs and to society's demands for more effective schools. They have four defining features: (1) implementation of quality programs and developmentally appropriate practices for young children through age eight; (2) families as…

  15. Relative Age Effects in Women's Rugby Union from Developmental Leagues to World Cup Tournaments

    ERIC Educational Resources Information Center

    Lemez, Srdjan; MacMahon, Clare; Weir, Patricia

    2016-01-01

    Annual age cohort groupings promote relative age effects (RAEs), which often, inadvertently, create participation and attainment biases between relatively older and younger players within the same age cohort. In a globally evolving sport, women's rugby team selection practices may potentially bypass qualified players as a result of maturational…

  16. Strategic Planning Evaluation of Creating a New Professional Association

    ERIC Educational Resources Information Center

    Arendale, David; Barrow, Hilda; Carpenter, Kathy; Hodges, Russ; McGrath, Jane; Newell, Pat; Norton, Jan

    2007-01-01

    Creating a new professional association to more effectively serve both current and potential new members has been the focus of the College Reading and Learning Association/National Association for Developmental (CRLA/NADE) Working Group. The group considered not only the issue of effectiveness, but also the merits of expanding the mission and…

  17. CHLORPYRIFOS DEVELOPMENTAL NEUROTOXICITY: INTERACTION WITH GLUCOCORTICOIDS IN PC12 CELLS

    PubMed Central

    Slotkin, Theodore A.; Card, Jennifer; Seidler, Frederic J.

    2012-01-01

    Prenatal coexposures to glucocorticoids and organophosphate pesticides are widespread. Glucocorticoids are elevated by maternal stress and are commonly given in preterm labor; organophosphate exposures are virtually ubiquitous. We used PC12 cells undergoing neurodifferentiation in order to assess whether dexamethasone enhances the developmental neurotoxicity of chlorpyrifos, focusing on concentrations relevant to human exposures. By themselves, each agent reduced the number of cells and the combined exposure elicited a correspondingly greater effect than with either agent alone. There was no general cytotoxicity, as cell growth was actually enhanced, and again, the combined treatment evoked greater cellular hypertrophy than with the individual compounds. The effects on neurodifferentiation were more complex. Chlorpyrifos alone had a promotional effect on neuri to genesis whereas dexamethasone impaired it; combined treatment showed an overall impairment greater than that seen with dexamethasone alone. The effect of chlorpyrifos on differentiation into specific neurotransmitter phenotypes was shifted by dexamethasone. Either agent alone promoted differentiation into the dopaminergic phenotype at the expense of the cholinergic phenotype. However, in dexamethasone-primed cells, chlorpyrifos actually enhanced cholinergic neurodifferentiation instead of suppressing this phenotype. Our results indicate that developmental exposure to glucocorticoids, either in the context of stress or the therapy of preterm labor, could enhance the developmental neurotoxicity of organophosphates and potentially of other neurotoxicants, as well as producing neurobehavioral outcomes distinct from those seen with either individual agent. PMID:22796634

  18. Neurotoxic effects of perfluoroalkylated compounds: mechanisms of action and environmental relevance.

    PubMed

    Mariussen, Espen

    2012-09-01

    Perfluoroalkylated compounds (PFCs) are used in fire-fighting foams, treatment of clothes, carpets and leather products, and as lubricants, pesticides, in paints and medicine. Recent developments in chemical analysis have revealed that fluorinated compounds have become ubiquitously spread and are regarded as a potential threats to the environment. Due to the carbon-fluorine bond, which has a very high bond strength, these chemicals are extremely persistent towards degradation and some PFCs have a potential for bioaccumulation in organisms. Of particular concern has been the developmental toxicity of PFOS and PFOA, which has been manifested in rodent studies as high mortality of prenatally exposed newborn rats and mice within 24 h after delivery. The nervous system appears to be one of the most sensitive targets of environmental contaminants. The serious developmental effects of PFCs have lead to the upcoming of studies that have investigated neurotoxic effects of these substances. In this review the major findings of the neurotoxicity of the main PFCs and their suggested mechanisms of action are presented. The neurotoxic effects are discussed in light of other toxic effects of PFCs to indicate the significance of PFCs as neurotoxicants. The main findings are that PFCs may induce neurobehavioral effects, particularly in developmentally exposed animals. The effects are, however, subtle and inconclusive and are often induced at concentrations where other toxic effects also are expected. Mechanistic studies have shown that PFCs may affect the thyroid system, influence the calcium homeostasis, protein kinase C, synaptic plasticity and cellular differentiation. Compared to other environmental toxicants the human blood levels of PFCs are high and of particular concern is that susceptible groups may be exposed to a cocktail of substances that in combination reach harmful concentrations.

  19. Predictions of developmental neurotoxicity potential of TDCPP

    EPA Science Inventory

    Tris(1 ,3-dichloro-2-propyl)phosphate (TDCPP) is an organophosphate flame retardant with widespread usage and documented human exposures through food, inhalation, dust ingestion, and breast milk. Concern for neurodevelopmental effects in infants and children has been raised by fi...

  20. Effects of perfluorinated chemicals on adipocyte development

    EPA Science Inventory

    Obesity is a growing concern in the US population. Current interest is high in the role played by environmental factors called obesogens that may contribute to obesity through developmental exposure. One class of potential obesogens is the family of perfluorinated chemicals used ...

  1. Kohlberg for Chaplains: A Theory of Moral Development.

    ERIC Educational Resources Information Center

    Zappone, Katherine E.

    1978-01-01

    Explains how Lawrence Kohlberg's cognitive developmental approach to moral education presents military chaplains with a potentially effective method of education. Cautions chaplains to recognize the differences between Kohlberg's philosophical/psychological ethics and Christian morality. Journal availability: see SO 506 875. (DB)

  2. Is Intake of Flavonoid-Based Food Supplements During Pregnancy Safe for the Developing Child? A Literature Review.

    PubMed

    Barenys, Marta; Masjosthusmann, Stefan; Fritsche, Ellen

    2017-01-01

    Due to potential health benefits and the general assumption that natural products are safe, there is an increasing trend in the general population - including pregnant women - to supplement their diet with flavonoid-based food supplements. In addition, preclinical studies aim to prevent developmental adverse effects induced by toxic substances, infections, maternal or genetic diseases of the unborn child by administration of flavonoids at doses far above those reached by normal diets. Because these substances do not undergo classical risk assessment processes, our aim was to review the available literature on the potential adverse effects of maternal diet supplementation with flavonoid-based products for the developing child. A systematic literature search was performed in three databases and screened following four exclusion criteria. Selected studies were classified into two groups: 1. Studies on the developmental toxicity of single flavonoids in vitro or in animals in vivo, and 2. Studies on the developmental toxicity of single flavonoids or on flavonoid-mixtures in humans. The data collected indicate that there is a concern for the safety of some flavonoids within realistic human exposure scenarios. This concern is accompanied by a tremendous lack of studies on safety of these compounds during development making definite safety decisions impossible. Besides studies of survival, especially the more specific developmental processes like nervous system development need to be addressed experimentally. Before new high-dose, flavonoid-based therapeutic strategies are developed for pregnant women further research on the safety of these compounds is clearly needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. The red tide toxin, brevetoxin, induces embryo toxicity and developmental abnormalities.

    PubMed Central

    Kimm-Brinson, K L; Ramsdell, J S

    2001-01-01

    Brevetoxins are lipophilic polyether toxins produced by the red tide dinoflagellate Gymnodinium breve, and their neurotoxic effects on adult animals have been documented. In this study, we characterized adverse developmental effects of brevetoxin-1 (PbTx-1) using an exposure paradigm that parallels the maternal oocyte transfer of toxin. Medaka fish (Oryzias latipes) embryos were exposed to PbTx-1 via microinjection of toxin reconstituted in a triolein oil droplet. Embryos microinjected with doses of 0.1-8.0 ng/egg (ppm) of brevetoxin-1 exhibited pronounced muscular activity (hyperkinesis) after embryonic day 4. Upon hatching, morphologic abnormalities were commonly found in embryos at the following lowest adverse effect levels: 1.0-3.0 ppm, lateral curvature of the spinal column; 3.1-3.4 ppm, herniation of brain meninges through defects in the skull; and 3.4-4.0 ppm, malpositioned eye. Hatching abnormalities were also commonly observed at brevetoxin doses of 2.0 ppm and higher with head-first, as opposed to the normal tail-first, hatching, and doses > 4.1 ng/egg produced embryos that developed but failed to hatch. Given the similarity of developmental processes found between higher and lower vertebrates, teratogenic effects of brevetoxins have the potential to occur among different phylogenetic classes. The observation of developmental abnormalities after PbTx-1 exposure identifies a new spectrum of adverse effects that may be expected to occur following exposure to G. breve red tide events. PMID:11335186

  4. DNA methylation at differentially methylated regions of imprinted genes is resistant to developmental programming by maternal nutrition

    PubMed Central

    Ivanova, Elena; Chen, Jian-Hua; Segonds-Pichon, Anne; Ozanne, Susan E.; Kelsey, Gavin

    2012-01-01

    The nutritional environment in which the mammalian fetus or infant develop is recognized as influencing the risk of chronic diseases, such as type 2 diabetes and hypertension, in a phenomenon that has become known as developmental programming. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, because epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. One class of genes that has been considered a potential target or mediator of programming events is imprinted genes, because these genes critically depend upon epigenetic modifications for correct expression and because many imprinted genes have roles in controlling fetal growth as well as neonatal and adult metabolism. In this study, we have used an established model of developmental programming—isocaloric protein restriction to female mice during gestation or lactation—to examine whether there are effects on expression and DNA methylation of imprinted genes in the offspring. We find that although expression of some imprinted genes in liver of offspring is robustly and sustainably changed, methylation of the differentially methylated regions (DMRs) that control their monoallelic expression remains largely unaltered. We conclude that deregulation of imprinting through a general effect on DMR methylation is unlikely to be a common factor in developmental programming. PMID:22968513

  5. Screening for Developmental Neurotoxicants using In Vitro "Brain on a Chip" Cultures

    EPA Science Inventory

    Currently there are thousands of chemicals in the environment that have not been screened for their potential to cause developmental neurotoxicity (DNT). The use of microelectrode array (MEA) technology allows for simultaneous extracellular measurement of action potential (spike)...

  6. Growth hormone combined with child-specific motor training improves motor development in infants with Prader-Willi syndrome: a randomized controlled trial.

    PubMed

    Reus, Linda; Pelzer, Ben J; Otten, Barto J; Siemensma, Elbrich P C; van Alfen-van der Velden, Janielle A A E M; Festen, Dederieke A M; Hokken-Koelega, Anita C S; Nijhuis-van der Sanden, Maria W G

    2013-10-01

    Although severe motor problems in infants with Prader-Willi syndrome (PWS) are striking, motor development has never been studied longitudinally and the results of growth hormone (GH) treatment on motor development are contradictory. The authors studied whether GH treatment can enhance the effect of physical training on motor development in infants with PWS. Twenty-two infants were followed for two years during a randomized controlled trial. The treatment and control groups began GH after baseline or following a control period, respectively. Both groups followed a child-specific physical training program. Motor performance was measured every three months. Multi-level regression analysis revealed that motor development differed significantly between infants (p<.001), and this could be partially explained by baseline motor developmental level (p<.01). GH treatment enhanced the effects of child-specific physical training on both motor developmental rate and motor developmental potential. Moreover, this effect was more pronounced when GH treatment was initiated at a younger age. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity (ACDC) Assay: Book Chapter

    EPA Science Inventory

    There are thousands of environmental chemicals for which there is limited toxicological information, motivating the development and application of in vitro systems to profile the biological effects of xenobiotic exposure and predict their potential developmental hazard. An adher...

  8. Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity (ACDC) assay-Book Chapter*

    EPA Science Inventory

    There are thousands of environmental chemicals for which there is limited toxicological information, motivating the development and application of in vitro systems to profile the biological effects of xenobiotic exposure and predict their potential developmental hazard. An adhere...

  9. Concentrations and trends of Perfluorinated chemicals in potential indoor sources from 2007 through 2011 in the US

    EPA Science Inventory

    Certain perfluorinated chemicals in consumer products have been associated with developmental toxicity and other adverse health effects. Temporal trends in the concentrations of selected perfluorinated chemicals (PFCs), including perfluorooctanoic acid (PFOA) and other perfluoroc...

  10. A Systems-Level Approach to Characterizing Effects of ENMs in Terrestrial Organisms and Ecosystems

    EPA Science Inventory

    Engineered nanomaterials (ENMs) represent a new regulatory challenge because of their unique properties and their potential to interact with ecological organisms at various developmental stages, in numerous environmental compartments. Traditional toxicity tests have proven to be...

  11. Strengths of Farming Communities in Fostering Resilience in Children.

    ERIC Educational Resources Information Center

    Larson, Nancy C.; Dearmont, Melissa

    2002-01-01

    Explores the unique values and characteristics of rural communities and farm families, particularly individual, family, and community factors that may protect children from potentially negative developmental effects of chronic stress or adversity. Considers community strengths in supporting children's healthy development. Identifies implications…

  12. Teaching and Technologies for Human Development.

    ERIC Educational Resources Information Center

    Chickering, Arthur W.; Payne, Carla; Poitras, Gail

    2001-01-01

    Discusses the potential of emerging communication and information technologies in terms of human development. Topics include distinctions between training and education, instrumental and developmental purposes, and differentiation and integration; developmental stages theory; a leadership seminar based on developmental stages; and uses of…

  13. II. MORE THAN JUST CONVENIENT: THE SCIENTIFIC MERITS OF HOMOGENEOUS CONVENIENCE SAMPLES.

    PubMed

    Jager, Justin; Putnick, Diane L; Bornstein, Marc H

    2017-06-01

    Despite their disadvantaged generalizability relative to probability samples, nonprobability convenience samples are the standard within developmental science, and likely will remain so because probability samples are cost-prohibitive and most available probability samples are ill-suited to examine developmental questions. In lieu of focusing on how to eliminate or sharply reduce reliance on convenience samples within developmental science, here we propose how to augment their advantages when it comes to understanding population effects as well as subpopulation differences. Although all convenience samples have less clear generalizability than probability samples, we argue that homogeneous convenience samples have clearer generalizability relative to conventional convenience samples. Therefore, when researchers are limited to convenience samples, they should consider homogeneous convenience samples as a positive alternative to conventional (or heterogeneous) convenience samples. We discuss future directions as well as potential obstacles to expanding the use of homogeneous convenience samples in developmental science. © 2017 The Society for Research in Child Development, Inc.

  14. Strategies for Reversing the Effects of Metabolic Disorders Induced as a Consequence of Developmental Programming

    PubMed Central

    Vickers, M. H.; Sloboda, D. M.

    2012-01-01

    Obesity and the metabolic syndrome have reached epidemic proportions worldwide with far-reaching health care and economic implications. The rapid increase in the prevalence of these disorders suggests that environmental and behavioral influences, rather than genetic causes, are fueling the epidemic. The developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal, and early infant phases of life and the subsequent development of metabolic disorders in later life. In particular, the impact of poor maternal nutrition on susceptibility to later life metabolic disease in offspring is now well documented. Several studies have now shown, at least in experimental animal models, that some components of the metabolic syndrome, induced as a consequence of developmental programming, are potentially reversible by nutritional or targeted therapeutic interventions during windows of developmental plasticity. This review will focus on critical windows of development and possible therapeutic avenues that may reduce metabolic and obesogenic risk following an adverse early life environment. PMID:22783205

  15. Determining Developmental Education Effectiveness in Math

    ERIC Educational Resources Information Center

    May, Joseph E.

    2017-01-01

    One of the most problematic issues facing community colleges is developmental education. In the last decade, more research has been conducted examining developmental education. The purpose of this study was to evaluate the effectiveness of developmental math in a rural community college setting. Is developmental math an effective intervention?…

  16. Why developmental niche construction is not selective niche construction: and why it matters.

    PubMed

    Stotz, Karola

    2017-10-06

    In the last decade, niche construction has been heralded as the neglected process in evolution. But niche construction is just one way in which the organism's interaction with and construction of the environment can have potential evolutionary significance. The constructed environment does not just select for , it also produces new variation. Nearly 3 decades ago, and in parallel with Odling-Smee's article 'Niche-constructing phenotypes', West and King introduced the 'ontogenetic niche' to give the phenomena of exo genetic inheritance a formal name. Since then, a range of fields in the life sciences and medicine has amassed evidence that parents influence their offspring by means other than DNA (parental effects), and proposed mechanisms for how heritable variation can be environmentally induced and developmentally regulated. The concept of 'developmental niche construction' (DNC) elucidates how a diverse range of mechanisms contributes to the transgenerational transfer of developmental resources. My most central of claims is that whereas the selective niche of niche construction theory is primarily used to explain the active role of the organism in its selective environment, DNC is meant to indicate the active role of the organism in its developmental environment. The paper highlights the differences between the construction of the selective and the developmental niche, and explores the overall significance of DNC for evolutionary theory.

  17. Variation in developmental time affects mating success and Allee effects

    Treesearch

    Christelle Robinet; Andrew Liebhold; David Gray

    2007-01-01

    A fundamental question in biological conservation and invasion biology is why do some populations go extinct? Allee effects, notably those caused by mate location failure, are potentially key factors leading to the extinction of sparse populations. Several previous studies have focused on the inability of males and females to locate each other in space when populations...

  18. Gene Expression Changes in Developing Zebrafish as Potential Markers for Rapid Developmental Neurotoxicity Screening

    EPA Science Inventory

    Sparse information exists on many chemicals to guide developmental neurotoxicity (DNT) risk assessments. As DNT testing using rodents is laborious and expensive, alternative species such as zebrafish are being adapted for toxicity screening. Assessing the DNT potential of chem...

  19. High developmental potential in vitro and in vivo of cattle embryos cloned without micromanipulators

    PubMed Central

    Rodríguez, Lleretny; Navarrete, Felipe I.; Tovar, Heribelt; Cox, José F.

    2008-01-01

    Purpose In order to simplify cloning, a new method that does not require micromanipulators was used. We aimed to evaluate the developmental potential of two bovine cell lines upon cloning. Materials and methods In vitro matured bovine oocytes, were released from zona pellucida, enucleated, fused to foetal or adult somatic donor cells. The reconstructed embryos were reprogrammed, activated and cultured until blastocyst stage. No micromanipulators were used. Blastocyst rate and quality was scored. Some expanded (d7) blastocysts were transferred to recipient cattle and collected back at d17 to assess elongation. Results High developmental potential in vitro of cloned embryos to expanded (d7) blastocysts was achieved (52.6%). In one cell line, 65.7% of blastocysts was scored. Most blastocysts (87.4%) were graded as excellent. In vivo development to elongation (day-17) in temporary recipient cows also showed a high developmental potential (11/18 transferred blastocysts elongated). Conclusions Hand-made cloning is an efficient alternative for cloning in cattle. PMID:18205035

  20. Dose–response analysis of phthalate effects on gene expression in rat whole embryo culture

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Robinson, Joshua F.; Department of Toxicogenomics, Maastricht University, Maastricht; Verhoef, Aart

    2012-10-01

    The rat postimplantation whole embryo culture (WEC) model serves as a potential screening tool for developmental toxicity. In this model, cultured rat embryos are exposed during early embryogenesis and evaluated for morphological effects. The integration of molecular-based markers may lead to improved objectivity, sensitivity and predictability of WEC in assessing developmental toxic properties of compounds. In this study, we investigated the concentration-dependent effects of two phthalates differing in potency, mono(2-ethylhexyl) phthalate (MEHP) and monomethyl phthalate (MMP, less toxic), on the transcriptome in WEC to examine gene expression in relation with dysmorphogenesis. MEHP was more potent than MMP in inducing genemore » expression changes as well as changes on morphology. MEHP induced significant enrichment of cholesterol/lipid/steroid (CLS) metabolism and apoptosis pathways which was associated with developmental toxicity. Regulation of genes within CLS metabolism pathways represented the most sensitive markers of MEHP exposure, more sensitive than classical morphological endpoints. As shown in direct comparisons with toxicogenomic in vivo studies, alterations in the regulation of CLS metabolism pathways has been previously identified to be associated with developmental toxicity due to phthalate exposure in utero. Our results support the application of WEC as a model to examine relative phthalate potency through gene expression and morphological responses. Additionally, our results further define the applicability domain of the WEC model for developmental toxicological investigations. -- Highlights: ► We examine the effect of two phthalates on gene expression and morphology in WEC. ► MEHP is more potent than MMP in inducing gene expression changes and dysmorphogenesis. ► MEHP significantly disrupts cholesterol metabolism pathways in a dose-dependent manner. ► Specific phthalate-related mechanisms in WEC are relevant to mechanisms in vivo.« less

  1. Developmental origins of inflammatory and immune diseases.

    PubMed

    Chen, Ting; Liu, Han-Xiao; Yan, Hui-Yi; Wu, Dong-Mei; Ping, Jie

    2016-08-01

    Epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exert a profound influence on physiological function and risk of diseases in adult life. The concepts of the 'developmental programming' and Developmental Origins of Health and Diseases (DOHaD) have become well accepted and have been applied across almost all fields of medicine. Adverse intrauterine environments may have programming effects on the crucial functions of the immune system during critical periods of fetal development, which can permanently alter the immune function of offspring. Immune dysfunction may in turn lead offspring to be susceptible to inflammatory and immune diseases in adulthood. These facts suggest that inflammatory and immune disorders might have developmental origins. In recent years, inflammatory and immune disorders have become a growing health problem worldwide. However, there is no systematic report in the literature on the developmental origins of inflammatory and immune diseases and the potential mechanisms involved. Here, we review the impacts of adverse intrauterine environments on the immune function in offspring. This review shows the results from human and different animal species and highlights the underlying mechanisms, including damaged development of cells in the thymus, helper T cell 1/helper T cell 2 balance disturbance, abnormal epigenetic modification, effects of maternal glucocorticoid overexposure on fetal lymphocytes and effects of the fetal hypothalamic-pituitary-adrenal axis on the immune system. Although the phenomena have already been clearly implicated in epidemiologic and experimental studies, new studies investigating the mechanisms of these effects may provide new avenues for exploiting these pathways for disease prevention. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Berberine exposure triggers developmental effects on planarian regeneration

    PubMed Central

    Balestrini, Linda; Isolani, Maria Emilia; Pietra, Daniele; Borghini, Alice; Bianucci, Anna Maria; Deri, Paolo; Batistoni, Renata

    2014-01-01

    The mechanisms of action underlying the pharmacological properties of the natural alkaloid berberine still need investigation. Planarian regeneration is instrumental in deciphering developmental responses following drug exposure. Here we report the effects of berberine on regeneration in the planarian Dugesia japonica. Our findings demonstrate that this compound perturbs the regenerative pattern. By real-time PCR screening for the effects of berberine exposure on gene expression, we identified alterations in the transcriptional profile of genes representative of different tissues, as well as of genes involved in extracellular matrix (ECM) remodeling. Although berberine does not influence cell proliferation/apoptosis, our experiments prove that this compound causes abnormal regeneration of the planarian visual system. Potential berberine-induced cytotoxic effects were noticed in the intestine. Although we were unable to detect abnormalities in other structures, our findings, sustained by RNAi-based investigations, support the possibility that berberine effects are critically linked to anomalous ECM remodeling in treated planarians. PMID:24810466

  3. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    PubMed

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  4. Developmental Programming and Endocrine Disruptor Effects on Reproductive Neuroendocrine Systems

    PubMed Central

    Gore, Andrea C.

    2009-01-01

    The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted. PMID:18394690

  5. Acute and Developmental Behavioral Effects of Flame Retardants and Related Chemicals in Zebrafish

    EPA Science Inventory

    As polybrominated diphenyl ethers are phased out, numerous compounds are emerging as potential replacement flame retardants for use in consumer and electronic products. Little is known, however, about the neurobehavioral toxicity of these replacements. This study evaluated the ne...

  6. DEVELOPMENTAL EXPOSURE TO POLYBROMINATED DIPHENYL ETHERS DOES NOT ALTER SYNAPTIC TRANSMISSION AND LTP IN HIPPOCAMPUS.

    EPA Science Inventory

    Polybrominated diphenyl ether (PDE) flame retardants bioaccumulate in the environment, in wildlife, and in humans. Concern has been raised over potential thyrotoxic effects of this class of xenobiotics. Severe hypothyroidism during critical periods of brain development leads to...

  7. DIRECT AND PHOTOACTIVATED TOXICITY OF A COMPLEX PETROLEUM MIXTURE: A COMPARISON OF SOLUBILIZATION METHODS

    EPA Science Inventory

    This work addresses several issues associated with the toxicity of a complex petroleum mixture (combined kerosene/diesel and crude oil), including developmental effects and early lifestage mortality, method of solubilization, and potential photo-activated and photo-modified toxic...

  8. Active Learning: The Way Children Construct Knowledge.

    ERIC Educational Resources Information Center

    Hohmann, Mary; Weikart, David P.

    2002-01-01

    The High/Scope approach to early childhood education promotes the belief that active learning is fundamental to the development of human potential and occurs most effectively in settings that provide developmentally appropriate learning opportunities. Describes five ingredients of active learning (materials, manipulation, choice, language from…

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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

  10. A combined event-related potential and neuropsychological investigation of developmental dyscalculia.

    PubMed

    Soltész, Fruzsina; Szucs, Dénes; Dékány, Judit; Márkus, Attila; Csépe, Valéria

    2007-05-01

    Adolescents with developmental dyscalculia (DD) but no other impairments were examined with neuropsychological tests and with event-related brain potentials (ERPs). A matched control group and an adult control group were tested as well. Behavioural and ERP markers of the magnitude representation were examined in a task where subjects decided whether visually presented Hindu-Arabic digits were smaller or larger than 5. There was a normal behavioural numerical distance effect (better performance for digits closer to the reference number than for digits further away from it) in DD. This suggests that semantic magnitude relations depend on a phenomenologically (nearly) normal magnitude representation in DD, at least in the range of single-digit numbers. However, minor discrepancies between DD subjects and controls suggest that the perception of the magnitude of single digits may be slightly impaired in DD. Early ERP distance effects were similar in DD and in control subjects. In contrast, between 400 and 440 ms there was a focused right-parietal ERP distance effect in controls, but not in DD. This suggests that early, more automatic processing of digits was similar in both groups, and between-group processing differences arose later, during more complex controlled processing. This view is supported by signs of decelerated executive functioning in developmental dyscalculia. Further, DD subjects did not differ from controls in general mental rotation and in body parts knowledge, but were markedly impaired in mental finger rotation, finger knowledge, and tactile performance.

  11. Developmental and Evolutionary History Affect Survival in Stressful Environments

    PubMed Central

    Hopkins, Gareth R.; Brodie, Edmund D.; French, Susannah S.

    2014-01-01

    The world is increasingly impacted by a variety of stressors that have the potential to differentially influence life history stages of organisms. Organisms have evolved to cope with some stressors, while with others they have little capacity. It is thus important to understand the effects of both developmental and evolutionary history on survival in stressful environments. We present evidence of the effects of both developmental and evolutionary history on survival of a freshwater vertebrate, the rough-skinned newt (Taricha granulosa) in an osmotically stressful environment. We compared the survival of larvae in either NaCl or MgCl2 that were exposed to salinity either as larvae only or as embryos as well. Embryonic exposure to salinity led to greater mortality of newt larvae than larval exposure alone, and this reduced survival probability was strongly linked to the carry-over effect of stunted embryonic growth in salts. Larval survival was also dependent on the type of salt (NaCl or MgCl2) the larvae were exposed to, and was lowest in MgCl2, a widely-used chemical deicer that, unlike NaCl, amphibian larvae do not have an evolutionary history of regulating at high levels. Both developmental and evolutionary history are critical factors in determining survival in this stressful environment, a pattern that may have widespread implications for the survival of animals increasingly impacted by substances with which they have little evolutionary history. PMID:24748021

  12. 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

  13. Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung

    PubMed Central

    Bhandari, Vineet; Choo-Wing, Rayman; Lee, Chun G.; Yusuf, Kamran; Nedrelow, Jonathan H.; Ambalavanan, Namasivayam; Malkus, Herbert; Homer, Robert J.; Elias, Jack A.

    2008-01-01

    Vascular endothelial growth factor (VEGF) is known to have a pivotal role in lung development and in a variety of pathologic conditions in the adult lung. Our earlier studies have shown that NO is a critical mediator of VEGF-induced vascular and extravascular effects in the adult murine lung. As significant differences have been reported in the cytokine responses in the adult versus the neonatal lung, we hypothesized that there may be significant differences in VEGF-induced alterations in the developing as opposed to the mature lung. Furthermore, nitric oxide (NO) mediation of these VEGF-induced effects may be developmentally regulated. Using a novel externally regulatable lung-targeted transgenic murine model, we found that VEGF-induced pulmonary hemorrhage was mediated by NO-dependent mechanisms in adults and newborns. VEGF enhanced surfactant production in adults as well as increased surfactant and lung development in newborns, via an NO-independent mechanism. While the enhanced survival in hyperoxia in the adult was partly NO-dependent, there was enhanced hyperoxia-induced lung injury in the newborn. In addition, human amniotic fluid VEGF levels correlated positively with surfactant phospholipids. Tracheal aspirate VEGF levels had an initial spike, followed by a decline, and then a subsequent rise, in human neonates with an outcome of bronchopulmonary dysplasia or death. Our data show that VEGF can have injurious as well as potentially beneficial developmental effects, of which some are NO dependent, others NO independent. This opens up the possibility of selective manipulation of any VEGF-based intervention using NO inhibitors for maximal potential clinical benefit. PMID:18441284

  14. Developmental regulation of NO-mediated VEGF-induced effects in the lung.

    PubMed

    Bhandari, Vineet; Choo-Wing, Rayman; Lee, Chun G; Yusuf, Kamran; Nedrelow, Jonathan H; Ambalavanan, Namasivayam; Malkus, Herbert; Homer, Robert J; Elias, Jack A

    2008-10-01

    Vascular endothelial growth factor (VEGF) is known to have a pivotal role in lung development and in a variety of pathologic conditions in the adult lung. Our earlier studies have shown that NO is a critical mediator of VEGF-induced vascular and extravascular effects in the adult murine lung. As significant differences have been reported in the cytokine responses in the adult versus the neonatal lung, we hypothesized that there may be significant differences in VEGF-induced alterations in the developing as opposed to the mature lung. Furthermore, nitric oxide (NO) mediation of these VEGF-induced effects may be developmentally regulated. Using a novel externally regulatable lung-targeted transgenic murine model, we found that VEGF-induced pulmonary hemorrhage was mediated by NO-dependent mechanisms in adults and newborns. VEGF enhanced surfactant production in adults as well as increased surfactant and lung development in newborns, via an NO-independent mechanism. While the enhanced survival in hyperoxia in the adult was partly NO-dependent, there was enhanced hyperoxia-induced lung injury in the newborn. In addition, human amniotic fluid VEGF levels correlated positively with surfactant phospholipids. Tracheal aspirate VEGF levels had an initial spike, followed by a decline, and then a subsequent rise, in human neonates with an outcome of bronchopulmonary dysplasia or death. Our data show that VEGF can have injurious as well as potentially beneficial developmental effects, of which some are NO dependent, others NO independent. This opens up the possibility of selective manipulation of any VEGF-based intervention using NO inhibitors for maximal potential clinical benefit.

  15. The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals

    PubMed Central

    Stel, Jente

    2015-01-01

    Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans. PMID:26241072

  16. The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals.

    PubMed

    Stel, Jente; Legler, Juliette

    2015-10-01

    Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.

  17. Unhappy (and Happy) in Their Own Way: A Developmental Psychopathology Perspective on Quality of Life for Families Living with Developmental Disability with and without Autism

    ERIC Educational Resources Information Center

    Gardiner, Emily; Iarocci, Grace

    2012-01-01

    Research on families living with developmental disability generally and autism specifically is dominated by a deficit view that elicits an elaborate representation of problems and risks without the benefit of considering families' potential for adaptation and resilience. A central tenet of developmental psychopathology is that the study of…

  18. Developmental Demands of Cognitive Behavioral Therapy for Depression in Children and Adolescents: Cognitive, Social, and Emotional Processes.

    PubMed

    Garber, Judy; Frankel, Sarah A; Herrington, Catherine G

    2016-01-01

    Although some treatments for depression in children and adolescents have been found to be efficacious, the effects sizes have tended to be modest. Thus, there is considerable room to improve upon existing depression treatments. Some children may respond poorly because they do not yet have the cognitive, social, or emotional maturity needed to understand and apply the skills being taught in therapy. Therefore, treatments for depression may need to be tailored to match children's ability to both comprehend and implement the therapeutic techniques. This review outlines the steps needed for such developmental tailoring: (a) Specify the skills being taught in depression treatments; (b) identify what cognitive, social, and emotional developmental abilities are needed to attain these skills; (c) describe the normative developmental course of these skills and how to determine a child's developmental level; and (d) use this information to design an individualized treatment plan. Possible approaches to intervening include: alter the therapy to meet the child's level of development, train the child on the skills needed to engage in the therapy, or apply a dynamic assessment approach that integrates evaluation into treatment and measures children's current abilities as well as their potential.

  19. Bet-hedging as a complex interaction among developmental instability, environmental heterogeneity, dispersal, and life-history strategy.

    PubMed

    Scheiner, Samuel M

    2014-02-01

    One potential evolutionary response to environmental heterogeneity is the production of randomly variable offspring through developmental instability, a type of bet-hedging. I used an individual-based, genetically explicit model to examine the evolution of developmental instability. The model considered both temporal and spatial heterogeneity alone and in combination, the effect of migration pattern (stepping stone vs. island), and life-history strategy. I confirmed that temporal heterogeneity alone requires a threshold amount of variation to select for a substantial amount of developmental instability. For spatial heterogeneity only, the response to selection on developmental instability depended on the life-history strategy and the form and pattern of dispersal with the greatest response for island migration when selection occurred before dispersal. Both spatial and temporal variation alone select for similar amounts of instability, but in combination resulted in substantially more instability than either alone. Local adaptation traded off against bet-hedging, but not in a simple linear fashion. I found higher-order interactions between life-history patterns, dispersal rates, dispersal patterns, and environmental heterogeneity that are not explainable by simple intuition. We need additional modeling efforts to understand these interactions and empirical tests that explicitly account for all of these factors.

  20. Laser surgery of zebrafish (Danio rerio) embryos using femtosecond laser pulses: Optimal parameters for exogenous material delivery, and the laser's effect on short- and long-term development

    PubMed Central

    Kohli, Vikram; Elezzabi, Abdulhakem Y

    2008-01-01

    Background Femtosecond (fs) laser pulses have recently received wide interest as an alternative tool for manipulating living biological systems. In various model organisms the excision of cellular components and the intracellular delivery of foreign exogenous materials have been reported. However, the effect of the applied fs laser pulses on cell viability and development has yet to be determined. Using the zebrafish (Danio rerio) as our animal model system, we address both the short- and long-term developmental changes following laser surgery on zebrafish embryonic cells. Results An exogenous fluorescent probe, fluorescein isothiocyanate (FITC), was successfully introduced into blastomere cells and found to diffuse throughout all developing cells. Using the reported manipulation tool, we addressed whether the applied fs laser pulses induced any short- or long-term developmental effects in embryos reared to 2 and 7 days post-fertilization (dpf). Using light microscopy and scanning electron microscopy we compared key developmental features of laser-manipulated and control samples, including the olfactory pit, dorsal, ventral and pectoral fins, notochord, pectoral fin buds, otic capsule, otic vesicle, neuromast patterning, and kinocilia of the olfactory pit rim and cristae of the lateral wall of the ear. Conclusion In our study, no significant differences in hatching rates and developmental morphologies were observed in laser-manipulated samples relative to controls. This tool represents an effective non-destructive technique for potential medical and biological applications. PMID:18230185

  1. The application of latent curve analysis to testing developmental theories in intervention research.

    PubMed

    Curran, P J; Muthén, B O

    1999-08-01

    The effectiveness of a prevention or intervention program has traditionally been assessed using time-specific comparisons of mean levels between the treatment and the control groups. However, many times the behavior targeted by the intervention is naturally developing over time, and the goal of the treatment is to alter this natural or normative developmental trajectory. Examining time-specific mean levels can be both limiting and potentially misleading when the behavior of interest is developing systematically over time. It is argued here that there are both theoretical and statistical advantages associated with recasting intervention treatment effects in terms of normative and altered developmental trajectories. The recently developed technique of latent curve (LC) analysis is reviewed and extended to a true experimental design setting in which subjects are randomly assigned to a treatment intervention or a control condition. LC models are applied to both artificially generated and real intervention data sets to evaluate the efficacy of an intervention program. Not only do the LC models provide a more comprehensive understanding of the treatment and control group developmental processes compared to more traditional fixed-effects models, but LC models have greater statistical power to detect a given treatment effect. Finally, the LC models are modified to allow for the computation of specific power estimates under a variety of conditions and assumptions that can provide much needed information for the planning and design of more powerful but cost-efficient intervention programs for the future.

  2. Event-Related Potentials Reveal Anomalous Morphosyntactic Processing in Developmental Dyslexia

    ERIC Educational Resources Information Center

    Cantiani, Chiara; Lorusso, Maria Luisa; Perego, Paolo; Molteni, Massimo; Guasti, Maria Teresa

    2013-01-01

    In the light of the literature describing oral language difficulties in developmental dyslexia (DD), event-related potentials were used in order to compare morphosyntactic processing in 16 adults with DD (aged 20-28 years) and unimpaired controls. Sentences including subject-verb agreement violations were presented auditorily, with grammaticality…

  3. GLUCOCORTICOID RECEPTOR REGULATION IN THE RAT EMBRYO: A POTENTIAL SITE FOR DEVELOPMENTAL TOXICITY?

    EPA Science Inventory

    Glucocorticoid receptor regulation in the rat embryo: a potential site for developmental toxicity?

    Ghosh B, Wood CR, Held GA, Abbott BD, Lau C.

    National Research Council, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

  4. The Changing Role of Pediatric Well-Child Care

    ERIC Educational Resources Information Center

    Kuo, Alice A.; Inkelas, Moira

    2007-01-01

    Identifying potential developmental and behavioral problems during the first 3 years of life is an important factor in promoting a child's healthy development. The early identification of a potential developmental or behavioral problem leads to further evaluation and possible diagnosis or treatment if needed. Pediatric health care professionals…

  5. Psychological Resources of Adults with Developmental Dyslexia

    ERIC Educational Resources Information Center

    Lockiewicz, Marta; Bogdanowicz, Katarzyna M.; Bogdanowicz, Marta

    2014-01-01

    The aim of our study was to describe specific psychological resources of adults with developmental dyslexia and compare them with psychological resources of adults without developmental dyslexia. Potential differences were analyzed in visual-spatial, creative, and motivational abilities. No evidence was found for either creative, or visuospatial…

  6. IN VITRO ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY: USE OF MICROELECTRODE ARRAYS TO MEASURE FUNCTIONAL CHANGES IN NEURONAL NETWORK ONTOGENY

    EPA Science Inventory

    Because the Developmental Neurotoxicity Testing Battery requires large numbers of animals and is expensive, development of in vitro approaches to screen chemicals for potential developmental neurotoxicity is a high priority. Many proposed approaches for screening are biochemical,...

  7. In Vitro Assessment of Developmental Neurotoxicity: Use of Microelectrode Arrays to Measure Functional Changes in Neuronal Network Ontogeny*

    EPA Science Inventory

    Because the Developmental Neurotoxicity Testing Guidelines require large numbers of animals and is expensive, development of in vitro approaches to screen chemicals for potential developmental neurotoxicity is a high priority. Many proposed approaches for screening are biochemica...

  8. An occupational reproductive research agenda for the third millennium.

    PubMed Central

    Lawson, Christina C; Schnorr, Teresa M; Daston, George P; Grajewski, Barbara; Marcus, Michele; McDiarmid, Melissa; Murono, Eisuke; Perreault, Sally D; Schrader, Steven M; Shelby, Michael

    2003-01-01

    There is a significant public health concern about the potential effects of occupational exposure to toxic substances on reproductive outcomes. Several toxicants with reported reproductive and developmental effects are still in regular commercial or therapeutic use and thus present potential exposure to workers. Examples of these include heavy metals, organic solvents, pesticides and herbicides, and sterilants, anesthetic gases, and anticancer drugs used in health care. Many other substances are suspected of producing reproductive or developmental toxicity but lack sufficient data. Progress has been limited in identifying hazards and quantifying their potencies and in separating the contribution of these hazards from other etiologic factors. Identifying the causative agents, mechanisms by which they act, and any potential target populations, present the opportunity to intervene and protect the reproductive health of workers. The pace of laboratory studies to identify hazards and to underpin the biologic plausibility of effects in humans has not matched the pace at which new chemicals are introduced into commerce. Though many research challenges exist today, recent technologic and methodologic advances have been made that allow researchers to overcome some of these obstacles. The objective of this article is to recommend future directions in occupational reproductive health research. By bridging interdisciplinary gaps, the scientific community can work together to improve health and reduce adverse outcomes. PMID:12676620

  9. Development of PBPK Models for Gasoline in Adult and Pregnant Rats and their Fetuses

    EPA Science Inventory

    Concern for potential developmental effects of exposure to gasoline-ethanol blends has grown along with their increased use in the US fuel supply. Physiologically-based pharmacokinetic (PBPK) models for these complex mixtures were developed to address dosimetric issues related to...

  10. Developmental neurotoxicity testing in vitro: Models for assessing chemical effects on neurite outgrowth

    EPA Science Inventory

    In vitro models may be useful for the rapid toxicological screening of large numbers of chemicals for their potential to produce toxicity. Such screening could facilitate prioritization of resources needed for in vivo toxicity testing towards those chemicals most likely to resul...

  11. BIRTH DEFECTS RISK ASSOCIATED WITH MATERNAL SPORT FISH CONSUMPTION: POTENTIAL EFFECT MODIFICATION BY SEX OF OFFSPRING

    EPA Science Inventory

    Contaminated sport fish consumption may result in exposure to various reproductive and developmental toxicants, including pesticides and other suspected endocrine disruptors. We investigated the relation between maternal sport fish meals and risk of major birth defects among infa...

  12. Foundations in Elementary Education: Overview.

    ERIC Educational Resources Information Center

    Hohmann, Charles

    The cornerstone of the High/Scope approach to early elementary education is the belief that active learning is fundamental to the full development of human potential and that active learning occurs most effectively in settings that provide developmentally appropriate learning opportunities. This guide and accompanying videotape are intended to…

  13. Home Environment Quality Mediates the Effects of an Early Intervention on Children's Social-Emotional Development in Rural Pakistan

    ERIC Educational Resources Information Center

    Finch, Jenna E.; Obradovic, Jelena; Yousafzai, Aisha

    2016-01-01

    Over 200 million children under the age of 5 are not fulfilling their developmental potential due to poverty, poor health, and lack of cognitive stimulation. Experiences in early childhood have long term-effects on brain development and thus the cognitive and social-emotional skills that promote children's school success. Further, early childhood…

  14. Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia.

    PubMed

    Ewing, Samuel G; Grace, Anthony A

    2013-02-01

    Existing antipsychotic drugs are most effective at treating the positive symptoms of schizophrenia but their relative efficacy is low and they are associated with considerable side effects. In this study deep brain stimulation of the ventral hippocampus was performed in a rodent model of schizophrenia (MAM-E17) in an attempt to alleviate one set of neurophysiological alterations observed in this disorder. Bipolar stimulating electrodes were fabricated and implanted, bilaterally, into the ventral hippocampus of rats. High frequency stimulation was delivered bilaterally via a custom-made stimulation device and both spectral analysis (power and coherence) of resting state local field potentials and amplitude of auditory evoked potential components during a standard inhibitory gating paradigm were examined. MAM rats exhibited alterations in specific components of the auditory evoked potential in the infralimbic cortex, the core of the nucleus accumbens, mediodorsal thalamic nucleus, and ventral hippocampus in the left hemisphere only. DBS was effective in reversing these evoked deficits in the infralimbic cortex and the mediodorsal thalamic nucleus of MAM-treated rats to levels similar to those observed in control animals. In contrast stimulation did not alter evoked potentials in control rats. No deficits or stimulation-induced alterations were observed in the prelimbic and orbitofrontal cortices, the shell of the nucleus accumbens or ventral tegmental area. These data indicate a normalization of deficits in generating auditory evoked potentials induced by a developmental disruption by acute high frequency, electrical stimulation of the ventral hippocampus. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Deep brain stimulation of the ventral hippocampus restores deficits in processing of auditory evoked potentials in a rodent developmental disruption model of schizophrenia

    PubMed Central

    Ewing, Samuel G.; Grace, Anthony A.

    2012-01-01

    Existing antipsychotic drugs are most effective at treating the positive symptoms of schizophrenia, but their relative efficacy is low and they are associated with considerable side effects. In this study deep brain stimulation of the ventral hippocampus was performed in a rodent model of schizophrenia (MAM-E17) in an attempt to alleviate one set of neurophysiological alterations observed in this disorder. Bipolar stimulating electrodes were fabricated and implanted, bilaterally, into the ventral hippocampus of rats. High frequency stimulation was delivered bilaterally via a custom-made stimulation device and both spectral analysis (power and coherence) of resting state local field potentials and amplitude of auditory evoked potential components during a standard inhibitory gating paradigm were examined. MAM rats exhibited alterations in specific components of the auditory evoked potential in the infralimbic cortex, the core of the nucleus accumbens, mediodorsal thalamic nucleus, and ventral hippocampus in the left hemisphere only. DBS was effective in reversing these evoked deficits in the infralimbic cortex and the mediodorsal thalamic nucleus of MAM-treated rats to levels similar to those observed in control animals. In contrast stimulation did not alter evoked potentials in control rats. No deficits or stimulation-induced alterations were observed in the prelimbic and orbitofrontal cortices, the shell of the nucleus accumbens or ventral tegmental area. These data indicate a normalization of deficits in generating auditory evoked potentials induced by a developmental disruption by acute high frequency, electrical stimulation of the ventral hippocampus. PMID:23269227

  16. 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.

  17. 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.

  18. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johnson, E.M.

    Human reproduction and development is a cycle of interdependent events. Virtually all of its phases have been shown to be the primary target of one or more non-mutagenic exogenous agents. Such agents interfere with certain of the countless epigenetic or ontogenic events essential for normal completion of the cycle. Mutagens disrupt this cycle at some points, but the overwhelming majority of reproductive and developmental toxins are not mutagenic. As in all aspects of toxicology, the reproductive and developmental effects of chemicals are determined by the intrinsic nature of the chemical, the quantity of the chemical exposure, the duration of exposuremore » and the stage of the cycle at which it occurs. Signs of reproductive toxicity range from reduced fertility to spontaneous abortion. Adverse effects on the conceptus are categorized as functional deficits, developmental retardation, structural abnormality and death. One or more of these is anticipated to occur as a result of excess exposure to most chemicals. Although the degree of hazard and risk potential can be calculated in each instance, chemicals differ markedly in their ability to interfere with reproduction and/or development. Standardized methods for reproductive and developmental toxicity safety evaluation are available for detecting adverse effects upon any aspect of reproduction and development. Data currently available establish that these state-of-the-art tests conducted in laboratory animals are often highly predictive of the type of adverse effect a particular chemical will have in humans, as well as the exposure level at which it will occur. By adding a modest safety factor to the no-observed-effect-level of well-executed animal studies, safe human exposure levels can be established. 40 references.« less

  19. Developmental Neurotoxicity of Pyrethroid Insecticides: Critical Review and Future Research Needs

    PubMed Central

    Shafer, Timothy J.; Meyer, Douglas A.; Crofton, Kevin M.

    2005-01-01

    Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system. PMID:15687048

  20. Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs.

    PubMed

    Shafer, Timothy J; Meyer, Douglas A; Crofton, Kevin M

    2005-02-01

    Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system.

  1. Potential of DCT/SCDT in Addressing Two Elusive Themes of Mental Health Counseling.

    ERIC Educational Resources Information Center

    Borders, L. DiAnne

    1994-01-01

    Responds to previous article by Rigazio-DiGilio on Developmental Counseling and Therapy and Systemic Cognitive-Developmental Therapy as two integrative models that unify individual, family, and network treatment within coconstructive-developmental framework. Considers extent to which model breaks impasse in integrating development into counseling…

  2. 40 CFR 798.4900 - Developmental toxicity study.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... study is designed to provide information on the potential hazard to the unborn which may arise from... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Developmental toxicity study. 798.4900... Developmental toxicity study. (a) Purpose. In the assessment and evaluation of the toxic characteristics of a...

  3. 40 CFR 798.4900 - Developmental toxicity study.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... study is designed to provide information on the potential hazard to the unborn which may arise from... 40 Protection of Environment 33 2012-07-01 2012-07-01 false Developmental toxicity study. 798.4900... Developmental toxicity study. (a) Purpose. In the assessment and evaluation of the toxic characteristics of a...

  4. 40 CFR 798.4900 - Developmental toxicity study.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... study is designed to provide information on the potential hazard to the unborn which may arise from... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Developmental toxicity study. 798.4900... Developmental toxicity study. (a) Purpose. In the assessment and evaluation of the toxic characteristics of a...

  5. 40 CFR 798.4900 - Developmental toxicity study.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... study is designed to provide information on the potential hazard to the unborn which may arise from... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Developmental toxicity study. 798.4900... Developmental toxicity study. (a) Purpose. In the assessment and evaluation of the toxic characteristics of a...

  6. 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

  7. Identity processes and personality traits and types in adolescence: directionality of effects and developmental trajectories.

    PubMed

    Luyckx, Koen; Teppers, Eveline; Klimstra, Theo A; Rassart, Jessica

    2014-08-01

    Personality traits are hypothesized to be among the most important factors contributing to individual differences in identity development. However, longitudinal studies linking Big Five personality traits to contemporary identity models (in which multiple exploration and commitment processes are distinguished) are largely lacking. To gain more insight in the directionality of effect and the developmental interdependence of the Big Five and identity processes as forwarded in multilayered personality models, the present study assessed personality and identity in 1,037 adolescents 4 times over a period of 3 years. First, using cross-lagged path analysis, Big Five traits emerged as consistent predictors of identity exploration processes, whereas only one significant path from identity exploration to the Big Five was found. Second, using latent class growth analysis, 3 Big Five trajectory classes were identified, resembling the distinctions typically made between resilients, overcontrollers, and undercontrollers. These classes were characterized by different initial levels and (to a lesser extent) rates of change in commitment and exploration processes. In sum, important developmental associations linking personality traits to identity processes were uncovered, emphasizing the potential role of personality traits in identity development. Developmental implications and suggestions for future research are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  8. 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 zebrafish embryos and larvae, which highlights the need to evaluate the potential eco-toxicity of these manufactured nanomaterials (MNMs).

  9. Performance and Durability Assessment of Two Emission Control Technologies Installed on a Legacy High-Speed Marine Diesel Engine

    DTIC Science & Technology

    2015-11-05

    program investigated cost- effective technologies to reduce emissions from legacy marine engines. High-speed, high-population engine models in both...respectively) were driven by health effects and environmental impacts. The U.S. Navy assessed its contribution to the domestic marine emission inventory...greatest potential. A laboratory developmental assessment was followed by a shipboard evaluation. Effective technology concepts applied to high

  10. The Root Cause of Post-Traumatic and Developmental Stress Disorder (Phase 1)

    DTIC Science & Technology

    2015-04-01

    effects accentuates fear behavior (abstract) Our previous experiments demonstrated that systemic depletion of serotonin (5-hydroxytryptamine, 5- HT ...potentiated fear behaviors. However, the effects of isolated depletion of 5- HT in the LA, and the molecular mechanisms underlying enhanced glutamatergic...susceptible to the effects of severe stress. Previous findings from our lab support the existence of an anatomical phenotype related to the 5HTTLPR serotonin

  11. Quantitative assessment of developmental levels in overarm throwing using wearable inertial sensing technology.

    PubMed

    Grimpampi, Eleni; Masci, Ilaria; Pesce, Caterina; Vannozzi, Giuseppe

    2016-09-01

    Motor proficiency in childhood has been recently recognised as a public health determinant, having a potential impact on the physical activity level and possible sedentary behaviour of the child later in life. Among fundamental motor skills, ballistic skills assessment based on in-field quantitative observations is progressively needed in the motor development community. The aim of this study was to propose an in-field quantitative approach to identify different developmental levels in overarm throwing. Fifty-eight children aged 5-10 years performed an overarm throwing task while wearing three inertial sensors located at the wrist, trunk and pelvis level and were then categorised using a developmental sequence of overarm throwing. A set of biomechanical parameters were defined and analysed using multivariate statistics to evaluate whether they can be used as developmental indicators. Trunk and pelvis angular velocities and time durations before the ball release showed increasing/decreasing trends with increasing developmental level. Significant differences between developmental level pairs were observed for selected biomechanical parameters. The results support the suitability and feasibility of objective developmental measures in ecological learning contexts, suggesting their potential supportiveness to motor learning experiences in educational and youth sports training settings.

  12. Assessment of chemical effects on neurite outgrowth in PC12 cells using high content screening

    EPA Science Inventory

    Identification of chemicals that pose a hazard to the developing nervous system is the first step in reducing human exposure and preventing health risks to infants and children. In response to the need for more efficient methods to identify potential developmental neurotoxicants,...

  13. 76 FR 21368 - Evaluation of the Potential Developmental Effects of Cancer Chemotherapy During Pregnancy: Call...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... Cancer Chemotherapy During Pregnancy: Call for Information and Nomination of Scientific Experts AGENCY... chemotherapy during pregnancy. CERHR invites the submission of information about ongoing studies or upcoming publications on the pregnancy outcomes and long- term health of offspring exposed to cancer chemotherapy agents...

  14. Economically Disadvantaged Children's Transitions into Elementary School: Linking Family Processes, School Contexts, and Educational Policy

    ERIC Educational Resources Information Center

    Crosnoe, Robert; Cooper, Carey E.

    2010-01-01

    Working from a core perspective on the developmental implications of economic disadvantage, this study attempted to identify "family-based" mechanisms of economic effects on early learning and their potential "school-based" remedies. Multilevel analysis of the Early Childhood Longitudinal Study-Kindergarten Cohort revealed that…

  15. NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A

    EPA Science Inventory

    The National Toxicology Program (NTP)1 established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of the CERHR is to provide timely, unbiased, scientifically sound evaluations of the potential for adverse effects on reproduction...

  16. Using Motivational Interviewing to Address College Client Alcohol Abuse

    ERIC Educational Resources Information Center

    Scholl, Mark B.; Schmitt, Dorothy M.

    2009-01-01

    Motivational Interviewing (MI; W. R. Miller & S. Rollnick, 2002) is presented as a potentially effective counseling strategy for assisting traditionally aged college students in reducing their problematic, heavy alcohol use. MI's congruence with two developmental theories--Self-Determination Theory (R. M. Ryan & E. L. Deci, 2000) and…

  17. MAMMARY GLAND DEVELOPMENT AS A SENSITIVE END-POINT FOLLOWING ACUTE PERNATAL EXPOSURE TO A LOW DOSE ATRAZINE METABOLITE MIXTURE IN FEMALE LONG EVANS RATS

    EPA Science Inventory

    In order to characterize the potential developmental effects of atrazine (ATR) metabolites at low doses, an environmentally-based mixture (EBM) of ATR and its metabolites hydroxyatrazine, diaminochlorotriazine, deethylatrazine, and deisopropylatrazine was formulated based on surv...

  18. DEVELOPMENT OF AN OBJECTIVE AND QUANTIFIABLE TERATOLOGICAL SCREEN FOR USE IN ZEBRAFISH LARVAE.

    EPA Science Inventory

    To address EPA’s need to prioritize large numbers of chemicals for testing, a rapid, cost-effective in vivo screen for potential developmental toxicity using an alternative vertebrate species (zebrafish;Danio rerio) has been developed. A component of that screen is the observatio...

  19. Current Trends in Sexuality and Aging: An Update for Counselors.

    ERIC Educational Resources Information Center

    Capuzzi, Dave; Friel, Susan Eileen

    1990-01-01

    Considers effects of physiological and psychological factors on aging and sexuality and addresses the needs of special population groups, such as single older persons and those residing in institutions. Discusses the importance of a holistic and developmental framework that stresses potential for personal growth, intimacy, and sensual enjoyment…

  20. Comparison of Chemical-induced Changes in Proliferation and Apoptosis in Human and Mouse Neuroprogenitor Cells.***

    EPA Science Inventory

    There is a need to develop rapid and efficient models to screen chemicals for their potential to cause developmental neurotoxicity. Use of in vitro neuronal models, including human cells, is one approach that allows for timely, cost-effective toxicity screening. The present study...

  1. COMPARISON OF CHEMICAL-INDUCED CHANGES IN PROLIFERATION AND APOPTOSIS IN HUMAN AND MOUSE NEUROPROGENITOR CELLS.

    EPA Science Inventory

    There is a need to develop rapid and efficient models for screening chemicals for their potential to cause developmental neurotoxicity. Use of in vitro neuronal models, including human cells, is one approach that allows for timely, cost-effective toxicity screening. The present s...

  2. Comparative Developmental Toxicity of Flavonoids Using an Integrative Zebrafish System

    PubMed Central

    Bugel, Sean M.; Bonventre, Josephine A.; Tanguay, Robert L.

    2016-01-01

    Flavonoids are a large, structurally diverse class of bioactive naturally occurring chemicals commonly detected in breast milk, soy based infant formulas, amniotic fluid, and fetal cord blood. The potential for pervasive early life stage exposures raises concerns for perturbation of embryogenesis, though developmental toxicity and bioactivity information is limited for many flavonoids. Therefore, we evaluated a suite of 24 flavonoid and flavonoid-like chemicals using a zebrafish embryo-larval toxicity bioassay—an alternative model for investigating developmental toxicity of environmentally relevant chemicals. Embryos were exposed to 1–50 µM of each chemical from 6 to 120 h postfertilization (hpf), and assessed for 26 adverse developmental endpoints at 24, 72, and 120 hpf. Behavioral changes were evaluated in morphologically normal animals at 24 and 72 hpf, at 120 hpf using a larval photomotor response (LPR) assay. Gene expression was comparatively evaluated for all compounds for effects on biomarker transcripts indicative of AHR (cyp1a) and ER (cyp19a1b, esr1, lhb, vtg) pathway bioactivity. Overall, 15 of 24 flavonoids elicited adverse effects on one or more of the developmental or behavioral endpoints. Hierarchical clustering and principle component analyses compared toxicity profiles and identified 3 distinct groups of bioactive flavonoids. Despite robust induction of multiple estrogen-responsive biomarkers, co-exposure with ER and GPER antagonists did not ameliorate toxicity, suggesting ER-independence and alternative modes of action. Taken together, these studies demonstrate that development is sensitive to perturbation by bioactive flavonoids in zebrafish that are not related to traditional estrogen receptor mode of action pathways. This integrative zebrafish platform provides a useful framework for evaluating flavonoid developmental toxicity and hazard prioritization. PMID:27492224

  3. Why developmental niche construction is not selective niche construction: and why it matters

    PubMed Central

    2017-01-01

    In the last decade, niche construction has been heralded as the neglected process in evolution. But niche construction is just one way in which the organism's interaction with and construction of the environment can have potential evolutionary significance. The constructed environment does not just select for, it also produces new variation. Nearly 3 decades ago, and in parallel with Odling-Smee's article ‘Niche-constructing phenotypes', West and King introduced the ‘ontogenetic niche’ to give the phenomena of exogenetic inheritance a formal name. Since then, a range of fields in the life sciences and medicine has amassed evidence that parents influence their offspring by means other than DNA (parental effects), and proposed mechanisms for how heritable variation can be environmentally induced and developmentally regulated. The concept of ‘developmental niche construction’ (DNC) elucidates how a diverse range of mechanisms contributes to the transgenerational transfer of developmental resources. My most central of claims is that whereas the selective niche of niche construction theory is primarily used to explain the active role of the organism in its selective environment, DNC is meant to indicate the active role of the organism in its developmental environment. The paper highlights the differences between the construction of the selective and the developmental niche, and explores the overall significance of DNC for evolutionary theory. PMID:28839923

  4. Developmental neurotoxicity of different pesticides in PC-12 cells in vitro.

    PubMed

    Christen, Verena; Rusconi, Manuel; Crettaz, Pierre; Fent, Karl

    2017-06-15

    The detection of developmental neurotoxicity (DNT) of chemicals has high relevance for protection of human health. However, DNT of many pesticides is only little known. Furthermore, validated in vitro systems for assessment of DNT are not well established. Here we employed the rat phaeochromocytoma cell line PC-12 to evaluate DNT of 18 frequently used pesticides of different classes, including neonicotinoids, pyrethroids, organophosphates, organochlorines, as well as quaternary ammonium compounds, the organic compound used in pesticides, piperonyl butoxide, as well as the insect repellent diethyltoluamide (DEET). We determined the outgrowth of neurites in PC-12 cells co-treated with nerve growth factor and different concentrations of biocides for 5days. Furthermore, we determined transcriptional alterations of selected genes that may be associated with DNT, such as camk2α and camk2β, gap-43, neurofilament-h, tubulin-α and tubulin-β. Strong and dose- dependent inhibition of neurite outgrowth was induced by azamethiphos and chlorpyrifos, and dieldrin and heptachlor, which was correlated with up-regulation of gap-43. No or only weak effects on neurite outgrowth and transcriptional alterations occurred for neonicotinoids acetamiprid, clothianidin, imidacloprid and thiamethoxam, the pyrethroids λ-cyhalothrin, cyfluthrin, deltamethrin, and permethrin, the biocidal disinfectants C12-C14-alkyl(ethylbenzyl)dimethylammonium (BAC), benzalkonium chloride and barquat (dimethyl benzyl ammonium chloride), and piperonyl butoxide and DEET. Our study confirms potential developmental neurotoxicity of some pesticides and provides first evidence that azamethiphos has the potential to act as a developmental neurotoxic compound. We also demonstrate that inhibition of neurite outgrowth and transcriptional alterations of gap-43 expression correlate, which suggests the employment of gap-43 expression as a biomarker for detection and initial evaluation of potential DNT of chemicals. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Is decabromodiphenyl ether (BDE-209) a developmental neurotoxicant?

    PubMed Central

    Costa, Lucio G.; Giordano, Gennaro

    2011-01-01

    Polybrominated diphenyl ether (PBDE) flame retardants have become ubiquitous environmental pollutants. The relatively higher body burden in toddlers and children has reaised concern for their potential developmental neurotoxicity, which has been suggested by animal studies, in vitro experiments, and recent human epidemiological evidence. While lower brominated PBDEs have been banned in several countries, the fully brominated decaBDE (BDE-209) is still utilized, though manufacturers will discontinue production in the U.S.A. in 2013. The recent decision by the U.S. Environmental Protection Agency to base the Reference Dose (RfD) for BDE-209 on a developmental neurotoxicity study has generated some controversy. Because of its bulky configuration, BDE-209 is poorly absorbed and does not easily penetrate the cell wall. Its acute and chronic toxicities are relatively low, with the liver and the thyroid as the primary targets, though there is some evidence of carcinogenicity. A few animal studies have indicated that BDE-209 may cause developmental neurotoxicity, affecting motor and cognitive domains, as seen for other PBDEs. Limited in vivo and in vitro studies have also evidenced effects of BDE-209 on thyroid hormone homeostasis and direct effects on nervous cells, again similar to what found with other lower brominated PBDEs. In contrast, a recent developmental neurotoxicity study, carried out according to international guidelines, has provided no evidence of adverse effects on neurodevelopment, and this should be considered in a future re-evaluation of BDE-209. While estimated exposure to BDE-209 in children is believed to be several orders of magnitude below the most conservative RfD proposed by the USEPA, questions remain on the extent and relevance of BDE-209 metabolism to lower brominated PBDEs in the environment and in humans. PMID:21182867

  6. Evaluation of Epidemiology and Animal Data for Risk Assessment: Chlorpyrifos Developmental Neurobehavioral Outcomes

    PubMed Central

    Li, Abby A.; Lowe, Kimberly A.; McIntosh, Laura J.; Mink, Pamela J.

    2012-01-01

    Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring. PMID:22401178

  7. Present and future of developmental neuropsychopharmacology.

    PubMed

    Arango, Celso

    2015-05-01

    The field of child and adolescent psychiatry has always lagged behind adult psychiatry. With recent evidence that the vast majority of mental disorders, even when they emerge in adulthood, cause abnormal neurodevelopment and resultant emphasis on prevention and early intervention, there is a need to put child psychiatry at the top of the agenda in mental health research. This should also be the case for developmental neuropsychopharmacology. The target of drug discovery should shift toward a population younger than the one that is typically included in clinical trials. This is not only a matter of trying to replicate what has been found in individuals with mature brains; it is about searching for new strategies that address developing brains while the therapeutic window for their effect is still open. At present, major concerns in developmental psychopharmacology are over-prescription rates and use of psychotropic medications for conditions with a particularly underdeveloped evidence base, as well as adverse effects, especially potentially life-shortening cardiometabolic effects and suicidal ideation. The future of research in this area should focus on the use of drugs for primary and secondary prevention that would modify abnormal brain development. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  8. Development and modulation of intrinsic membrane properties control the temporal precision of auditory brain stem neurons.

    PubMed

    Franzen, Delwen L; Gleiss, Sarah A; Berger, Christina; Kümpfbeck, Franziska S; Ammer, Julian J; Felmy, Felix

    2015-01-15

    Passive and active membrane properties determine the voltage responses of neurons. Within the auditory brain stem, refinements in these intrinsic properties during late postnatal development usually generate short integration times and precise action-potential generation. This developmentally acquired temporal precision is crucial for auditory signal processing. How the interactions of these intrinsic properties develop in concert to enable auditory neurons to transfer information with high temporal precision has not yet been elucidated in detail. Here, we show how the developmental interaction of intrinsic membrane parameters generates high firing precision. We performed in vitro recordings from neurons of postnatal days 9-28 in the ventral nucleus of the lateral lemniscus of Mongolian gerbils, an auditory brain stem structure that converts excitatory to inhibitory information with high temporal precision. During this developmental period, the input resistance and capacitance decrease, and action potentials acquire faster kinetics and enhanced precision. Depending on the stimulation time course, the input resistance and capacitance contribute differentially to action-potential thresholds. The decrease in input resistance, however, is sufficient to explain the enhanced action-potential precision. Alterations in passive membrane properties also interact with a developmental change in potassium currents to generate the emergence of the mature firing pattern, characteristic of coincidence-detector neurons. Cholinergic receptor-mediated depolarizations further modulate this intrinsic excitability profile by eliciting changes in the threshold and firing pattern, irrespective of the developmental stage. Thus our findings reveal how intrinsic membrane properties interact developmentally to promote temporally precise information processing. Copyright © 2015 the American Physiological Society.

  9. Auditory temporal perceptual learning and transfer in Chinese-speaking children with developmental dyslexia.

    PubMed

    Zhang, Manli; Xie, Weiyi; Xu, Yanzhi; Meng, Xiangzhi

    2018-03-01

    Perceptual learning refers to the improvement of perceptual performance as a function of training. Recent studies found that auditory perceptual learning may improve phonological skills in individuals with developmental dyslexia in alphabetic writing system. However, whether auditory perceptual learning could also benefit the reading skills of those learning the Chinese logographic writing system is, as yet, unknown. The current study aimed to investigate the remediation effect of auditory temporal perceptual learning on Mandarin-speaking school children with developmental dyslexia. Thirty children with dyslexia were screened from a large pool of students in 3th-5th grades. They completed a series of pretests and then were assigned to either a non-training control group or a training group. The training group worked on a pure tone duration discrimination task for 7 sessions over 2 weeks with thirty minutes per session. Post-tests immediately after training and a follow-up test 2 months later were conducted. Analyses revealed a significant training effect in the training group relative to non-training group, as well as near transfer to the temporal interval discrimination task and far transfer to phonological awareness, character recognition and reading fluency. Importantly, the training effect and all the transfer effects were stable at the 2-month follow-up session. Further analyses found that a significant correlation between character recognition performance and learning rate mainly existed in the slow learning phase, the consolidation stage of perceptual learning, and this effect was modulated by an individuals' executive function. These findings indicate that adaptive auditory temporal perceptual learning can lead to learning and transfer effects on reading performance, and shed further light on the potential role of basic perceptual learning in the remediation and prevention of developmental dyslexia. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. High-throughput Screening of ToxCast" Phase I Chemicals in an Embryonic Stem Cell Assay Reveals Potential Disruption of a Critical Developmental Signaling Pathway

    EPA Science Inventory

    Little is known about the developmental toxicity of the expansive chemical landscape in existence today. Significant efforts are being made to apply novel methods to predict developmental activity of chemicals utilizing high-throughput screening (HTS) and high-content screening (...

  11. Developmental Education's Impact on Students' Academic Self-Concept and Self-Efficacy

    ERIC Educational Resources Information Center

    Martin, Kimberly; Goldwasser, Molly; Harris, Eugenia

    2017-01-01

    Students who are enrolled in developmental courses often persist at lower rates than students who enter college prepared for college-level work. This phenomenon has been attributed to numerous potential factors, including the psychological impact of assignment to developmental courses. This study examines the impact of enrollment in multiple…

  12. Predictors of Externalizing Behavior Problems in Early Elementary-Aged Children: The Role of Family and Home Environments

    ERIC Educational Resources Information Center

    Price, Joseph M.; Chiapa, Amanda; Walsh, Natalia Escobar

    2013-01-01

    As children enter elementary school they display behavioral orientations that reveal potential developmental trajectories. Developmental transitions offer unique opportunities for examining developmental pathways and the factors that influence emerging pathways. The primary goal of this investigation was to examine characteristics of family and…

  13. Moving at the Speed of Potential: A Mixed-Methods Study of Accelerating Developmental Students in a California Community College

    ERIC Educational Resources Information Center

    Parks, Paula L.

    2014-01-01

    Most developmental community college students are not completing the composition sequence successfully. This mixed-methods study examined acceleration as a way to help developmental community college students complete the composition sequence more quickly and more successfully. Acceleration is a curricular redesign that includes challenging…

  14. Predictors of Self-Determination in Postsecondary Education for Students with Intellectual and Developmental Disabilities

    ERIC Educational Resources Information Center

    Shogren, Karrie A.; Wehmeyer, Michael L.; Shaw, Leslie A.; Grigal, Meg; Hart, Debra; Smith, Frank A.; Khamsi, Sheida

    2018-01-01

    Given the increasing enrollment of students with intellectual and developmental disabilities in postsecondary education and the potential impact of self-determination on postsecondary outcomes, this study analyzed data on the self-determination status of students with intellectual and developmental disabilities completing their first year of a…

  15. Public Health Emergency Planning for Children in Chemical, Biological, Radiological, and Nuclear (CBRN) Disasters

    PubMed Central

    Bartenfeld, Michael T.; Peacock, Georgina; Griese, Stephanie E.

    2015-01-01

    Children represent nearly a quarter of the US population, but their unique needs in chemical, biological, radiological, and nuclear (CBRN) emergencies may not be well understood by public health and emergency management personnel or even clinicians. Children are different from adults physically, developmentally, and socially. These characteristics have implications for providing care in CBRN disasters, making resulting illness in children challenging to prevent, identify, and treat. This article discusses these distinct physical, developmental, and social traits and characteristics of children in the context of the science behind exposure to, health effects from, and treatment for the threat agents potentially present in CBRN incidents. PMID:25014894

  16. Nature, nurture, and development: from evangelism through science toward policy and practice.

    PubMed

    Rutter, Michael

    2002-01-01

    During the second half of the 20th century there was an immense increase in both empirical findings on, and conceptual understanding of, the effects of nature, nurture, and developmental processes on psychological functioning--both normal and abnormal. Unfortunately, the good science has also been accompanied by excessive polarizing claims and by unwarranted extrapolations. This article provides a summary review of the real gains in knowledge, outlines some of the misleading claims, and notes the potential for research and for science-led improvements in policies and practice. The need to bring about a better interpretation of genetic, psychosocial, and developmental research strategies and theoretical concepts is emphasized.

  17. Predictive Models of Cognitive Outcomes of Developmental Insults

    NASA Astrophysics Data System (ADS)

    Chan, Yupo; Bouaynaya, Nidhal; Chowdhury, Parimal; Leszczynska, Danuta; Patterson, Tucker A.; Tarasenko, Olga

    2010-04-01

    Representatives of Arkansas medical, research and educational institutions have gathered over the past four years to discuss the relationship between functional developmental perturbations and their neurological consequences. We wish to track the effect on the nervous system by developmental perturbations over time and across species. Except for perturbations, the sequence of events that occur during neural development was found to be remarkably conserved across mammalian species. The tracking includes consequences on anatomical regions and behavioral changes. The ultimate goal is to develop a predictive model of long-term genotypic and phenotypic outcomes that includes developmental insults. Such a model can subsequently be fostered into an educated intervention for therapeutic purposes. Several datasets were identified to test plausible hypotheses, ranging from evoked potential datasets to sleep-disorder datasets. An initial model may be mathematical and conceptual. However, we expect to see rapid progress as large-scale gene expression studies in the mammalian brain permit genome-wide searches to discover genes that are uniquely expressed in brain circuits and regions. These genes ultimately control behavior. By using a validated model we endeavor to make useful predictions.

  18. Chitosan nanoparticles and their Tween 80 modified counterparts disrupt the developmental profile of zebrafish embryos.

    PubMed

    Yuan, Zhongyue; Li, Ying; Hu, Yulan; You, Jian; Higashisaka, Kazuma; Nagano, Kazuya; Tsutsumi, Yasuo; Gao, Jianqing

    2016-12-30

    Chitosan nanoparticles (CS-NPs) and their Tween 80 modified counterparts (TmCS-NPs) are among the most commonly used brain-targeted vehicles. However, their potential developmental toxicity is poorly understood. In this study, zebrafish embryos are introduced as an in vivo platform. Both NPs showed a dose-dependent increase in developmental toxicity (decreased hatching rate, increased mortality and incidences of malformation). Neurobehavioral changes included decreased spontaneous movement in TmCS-NP treated embryos and hyperactive effect in CS-NP treated larvae. Both NPs remarkably inhibited axonal development of primary and secondary motor neurons, and affected the muscle structure. Overall, this study demonstrated that CS-NPs and TmCS-NPs could affect embryonic development, disrupt neurobehavior of zebrafish larvae and affect muscle and neuron development, suggesting more attention on biodegradable chitosan nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Cutaneous wound healing: recruiting developmental pathways for regeneration.

    PubMed

    Bielefeld, Kirsten A; Amini-Nik, Saeid; Alman, Benjamin A

    2013-06-01

    Following a skin injury, the damaged tissue is repaired through the coordinated biological actions that constitute the cutaneous healing response. In mammals, repaired skin is not identical to intact uninjured skin, however, and this disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development. Improving our understanding of the molecular pathways that are involved in these processes is essential to generate new therapies for wound healing complications. Here we focus on the roles of several key developmental signaling pathways (Wnt/β-catenin, TGF-β, Hedgehog, Notch) in mammalian cutaneous wound repair, and compare this to their function in skin development. We discuss the varying responses to cutaneous injury across the taxa, ranging from complete regeneration to scar tissue formation. Finally, we outline how research into the role of developmental pathways during skin repair has contributed to current wound therapies, and holds potential for the development of more effective treatments.

  20. Evaluation of developmental toxicity studies of glyphosate with attention to cardiovascular development.

    PubMed

    Kimmel, Gary L; Kimmel, Carole A; Williams, Amy L; DeSesso, John M

    2013-02-01

    The herbicide glyphosate has undergone multiple safety tests for developmental toxicity in rats and rabbits. The European Commission's 2002 review of available glyphosate data discusses specific heart defects observed in several individual rabbit developmental toxicity studies, but describes the evidence for a potential causal relationship as equivocal. The present assessment was undertaken to analyze the current body of information generated from seven unpublished rabbit studies in order to determine if glyphosate poses a risk for cardiovascular malformations. In addition, the results of six unpublished developmental toxicity studies in rats were considered. Five of the seven rabbit studies (dose range: 10-500 mg/kg/day) were GLP- and testing guideline-compliant for the era in which the studies were performed; a sixth study predated testing and GLP guidelines, but generally adhered to these principles. The seventh study was judged inadequate. In each of the adequate studies, offspring effects occurred only at doses that also caused maternal toxicity. An integrated evaluation of the six adequate studies, using conservative assumptions, demonstrated that neither the overall malformation rate nor the incidence of cardiovascular malformations increased with dose up to the point where severe maternal toxicity was observed (generally ≥150 mg/kg/day). Random occurrences of cardiovascular malformations were observed across all dose groups (including controls) and did not exhibit a dose-response relationship. In the six rat studies (dose range: 30-3500 mg/kg/day), a low incidence of sporadic cardiovascular malformations was reported that was clearly not related to treatment. In summary, assessment of the entire body of the developmental toxicity data reviewed fails to support a potential risk for increased cardiovascular defects as a result of glyphosate exposure during pregnancy.

  1. Targeting Developmental Pathways: The Achilles Heel of Cancer?

    PubMed

    Dempke, Wolfram C M; Fenchel, Klaus; Uciechowski, Peter; Chevassut, Timothy

    2017-01-01

    Developmental pathways (e.g., Notch, Hippo, Hedgehog, Wnt, and TGF-β/BMP/FGF) are networks of genes that act co-ordinately to establish the body plan, and disruptions of genes in one pathway can have effects in related pathways and may result in serious dysmorphogenesis or cancer. Interestingly, all developmental pathways are highly conserved cell signalling systems present in almost all multicellular organisms. In addition, they have a crucial role in cell proliferation, apoptosis, differentiation, and finally in organ development. Of note, almost all of these pathways promote oncogenesis through synergistic associations with the Hippo signalling pathway, and several lines of evidence have also indicated that these pathways (e.g., Wnt/β-catenin) may be implicated in checkpoint inhibitor resistance (e.g., CTLA-4, PD-1, and PD-L1). Since Notch inhibition in vivo results in partial loss of its stemness features such as self-renewal, chemoresistance, invasive and migratory potential, and tumorigenesis, these highly conserved developmental pathways are regarded as being critical for regulation of self-renewal in both embryonic and adult stem cells and hence are likely to be implicated in the maintenance of cancer stem cells. Many small molecules are currently in preclinical and early clinical development, and only two compounds are approved for treatment of advanced or metastatic basal cell carcinoma (vismodegib and sonidegib). Furthermore, therapeutic targeting of cancer stem cells using drugs that disrupt activated developmental pathways may also represent an attractive strategy that is potentially relevant to many types of malignancy, notably blood cancers, where the evidence for leukaemia stem cells is well established. Future work will hopefully pave the way for the development of new strategies for targeting these pervasive oncogenic pathways. © 2017 S. Karger AG, Basel.

  2. Fibroblast Growth Factor 10 Enhances the Developmental Efficiency of Somatic Cell Nuclear Transfer Embryos by Accelerating the Kinetics of Cleavage During In Vitro Maturation.

    PubMed

    Son, Yeo-Jin; Lee, Seung-Eun; Park, Yun-Gwi; Jeong, Sang-Gi; Shin, Min-Young; Kim, Eun-Young; Park, Se-Pill

    2018-06-01

    Somatic cell nuclear transfer (SCNT) is required for the generation of transgenic animals as disease models. During the in vitro development of SCNT embryos, the quality of matured oocytes is one of the major factors regulating the developmental potential of embryos. Time-lapse monitoring systems are new tools that assess the developmental capacity of embryos for use in embryo transfer. In this study, we investigated the effect of fibroblast growth factor 10 (FGF 10) on the developmental potential of SCNT embryos. After the in vitro maturation (IVM) of oocytes in IVM medium containing 10 ng/mL FGF 10 (10 F), the polar body extrusion rate was significantly higher than in the control. However, there was no difference in the percentage of fused embryos between the groups. The cleavage and blastocyst formation rates of embryos were significantly increased in the 10 F compared with the control. In addition, the total cell number was higher and the apoptotic index was lower in the 10 F than control at day 7. The messenger RNA (mRNA) expression of genes involved in apoptosis (baculoviral inhibitor of apoptosis repeat containing 5 [BIRC5] and caspase 3 [CASP3]) and development (octamer-binding transcription factor 4 [POU5F1] and sex determining region Y box 2 [SOX2]) increased after 10 F treatment. Furthermore, the kinetics of the first cleavage was faster and the percentage of embryos at cell block was significantly lower in the 10 F group than in the control. These results demonstrate that exposure of oocytes to FGF 10 during IVM promotes developmental competence.

  3. Evaluation of developmental toxicity studies of glyphosate with attention to cardiovascular development

    PubMed Central

    Kimmel, Gary L.; Kimmel, Carole A.; Williams, Amy L.

    2013-01-01

    The herbicide glyphosate has undergone multiple safety tests for developmental toxicity in rats and rabbits. The European Commission’s 2002 review of available glyphosate data discusses specific heart defects observed in several individual rabbit developmental toxicity studies, but describes the evidence for a potential causal relationship as equivocal. The present assessment was undertaken to analyze the current body of information generated from seven unpublished rabbit studies in order to determine if glyphosate poses a risk for cardiovascular malformations. In addition, the results of six unpublished developmental toxicity studies in rats were considered. Five of the seven rabbit studies (dose range: 10–500 mg/kg/day) were GLP- and testing guideline-compliant for the era in which the studies were performed; a sixth study predated testing and GLP guidelines, but generally adhered to these principles. The seventh study was judged inadequate. In each of the adequate studies, offspring effects occurred only at doses that also caused maternal toxicity. An integrated evaluation of the six adequate studies, using conservative assumptions, demonstrated that neither the overall malformation rate nor the incidence of cardiovascular malformations increased with dose up to the point where severe maternal toxicity was observed (generally ≥150 mg/kg/day). Random occurrences of cardiovascular malformations were observed across all dose groups (including controls) and did not exhibit a dose–response relationship. In the six rat studies (dose range: 30–3500 mg/kg/day), a low incidence of sporadic cardiovascular malformations was reported that was clearly not related to treatment. In summary, assessment of the entire body of the developmental toxicity data reviewed fails to support a potential risk for increased cardiovascular defects as a result of glyphosate exposure during pregnancy. PMID:23286529

  4. Developmental toxicity and alteration of gene expression in zebrafish embryos exposed to PFOS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shi Xiongjie; Graduate School of the Chinese Academy of Sciences, Beijing 100039; Du Yongbing

    2008-07-01

    Perfluorooctanesulfonate (PFOS) is a persistent organic pollutant, the potential toxicity of which is causing great concern. In the present study, we employed zebrafish embryos to investigate the developmental toxicity of this compound. Four-hour post-fertilization (hpf) zebrafish embryos were exposed to 0.1, 0.5, 1, 3 and 5 mg/L PFOS. Hatching was delayed and hatching rates as well as larval survivorship were significantly reduced after the embryos were exposed to 1, 3 and 5 mg/L PFOS until 132 hpf. The fry displayed gross developmental malformations, including epiboly deformities, hypopigmentation, yolk sac edema, tail and heart malformations and spinal curvature upon exposure tomore » PFOS concentrations of 1 mg/L or greater. Growth (body length) was significantly reduced in the 3 and 5 mg/L PFOS-treated groups. To test whether developmental malformation was mediated via apoptosis, flow cytometry analysis of DNA content, acridine orange staining and TUNEL assay was used. These techniques indicated that more apoptotic cells were present in the PFOS-treated embryos than in the control embryos. Certain genes related to cell apoptosis, p53 and Bax, were both significantly up-regulated upon exposure to all the concentrations tested. In addition, we investigated the effects of PFOS on marker genes related to early thyroid development (hhex and pax8) and genes regulating the balance of androgens and estrogens (cyp19a and cyp19b). For thyroid development, the expression of hhex was significantly up-regulated at all concentrations tested, whereas pax8 expression was significantly up-regulated only upon exposure to lower concentrations of PFOS (0.1, 0.5, 1 mg/L). The expression of cyp19a and of cyp19b was significantly down-regulated at all exposure concentrations. The overall results indicated that zebrafish embryos constitute a reliable model for testing the developmental toxicity of PFOS, and the gene expression patterns in the embryos were able to reveal some potential mechanisms of developmental toxicity.« less

  5. Characterization of a complex chromosomal rearrangement using chromosome, FISH, and microarray assays in a girl with multiple congenital abnormalities and developmental delay.

    PubMed

    Hemmat, Morteza; Yang, Xiaojing; Chan, Patricia; McGough, Robert A; Ross, Leslie; Mahon, Loretta W; Anguiano, Arturo L; Boris, Wang T; Elnaggar, Mohamed M; Wang, Jia-Chi J; Strom, Charles M; Boyar, Fatih Z

    2014-01-01

    Complex chromosomal rearrangements (CCRs) are balanced or unbalanced structural rearrangements involving three or more cytogenetic breakpoints on two or more chromosomal pairs. The phenotypic anomalies in such cases are attributed to gene disruption, superimposed cryptic imbalances in the genome, and/or position effects. We report a 14-year-old girl who presented with multiple congenital anomalies and developmental delay. Chromosome and FISH analysis indicated a highly complex chromosomal rearrangement involving three chromosomes (3, 7 and 12), seven breakpoints as a result of one inversion, two insertions, and two translocations forming three derivative chromosomes. Additionally, chromosomal microarray study (CMA) revealed two submicroscopic deletions at 3p12.3 (467 kb) and 12q13.12 (442 kb). We postulate that microdeletion within the ROBO1 gene at 3p12.3 may have played a role in the patient's developmental delay, since it has potential activity-dependent role in neurons. Additionally, factors other than genomic deletions such as loss of function or position effects may also contribute to the abnormal phenotype in our patient.

  6. Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj

    Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophinmore » (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA damage.« less

  7. Developmental Changes in Error Monitoring: An Event-Related Potential Study

    ERIC Educational Resources Information Center

    Wiersema, Jan R.; van der Meere, Jacob J.; Roeyers, Herbert

    2007-01-01

    The aim of the study was to investigate the developmental trajectory of error monitoring. For this purpose, children (age 7-8), young adolescents (age 13-14) and adults (age 23-24) performed a Go/No-Go task and were compared on overt reaction time (RT) performance and on event-related potentials (ERPs), thought to reflect error detection…

  8. Effects of trichostatin A on In vitro development and DNA methylation level of the satellite I region of swamp buffalo (Bubalus bubalis) cloned embryos.

    PubMed

    Srirattana, Kanokwan; Ketudat-Cairns, Mariena; Nagai, Takashi; Kaneda, Masahiro; Parnpai, Rangsun

    2014-01-01

    Trichostatin A (TSA), a histone deacetylase inhibitor, has been widely used to improve the cloning efficiency in several species. This brings our attention to investigation of the effects of TSA on developmental potential of swamp buffalo cloned embryos. Swamp buffalo cloned embryos were produced by electrical pulse fusion of male swamp buffalo fibroblasts with swamp buffalo enucleated oocytes. After fusion, reconstructed oocytes were treated with 0, 25 or 50 nM TSA for 10 h. The results showed that there was no significant difference in the rates of fusion (82-85%), cleavage (79-84%) and development to the 8-cell stage (59-65%) among treatment groups. The highest developmental rates to the morula and blastocyst stages of embryos were found in the 25 nM TSA-treated group (42.7 and 30.1%, respectively). We also analyzed the DNA methylation level in the satellite I region of donor cells and in in vitro fertilized (IVF) and cloned embryos using the bisulfite DNA sequencing method. The results indicated that the DNA methylation levels in cloned embryos were significantly higher than those of IVF embryos but approximately similar to those of donor cells. Moreover, there was no significant difference in the methylation level among TSA-treated and untreated cloned embryos. Thus, TSA treatments at 25 nM for 10 h could enhance the in vitro developmental potential of swamp buffalo cloned embryos, but no beneficial effect on the DNA methylation level was observed.

  9. Effects of Trichostatin A on In Vitro Development and DNA Methylation Level of the Satellite I Region of Swamp Buffalo (Bubalus bubalis) Cloned Embryos

    PubMed Central

    SRIRATTANA, Kanokwan; KETUDAT-CAIRNS, Mariena; NAGAI, Takashi; KANEDA, Masahiro; PARNPAI, Rangsun

    2014-01-01

    Trichostatin A (TSA), a histone deacetylase inhibitor, has been widely used to improve the cloning efficiency in several species. This brings our attention to investigation of the effects of TSA on developmental potential of swamp buffalo cloned embryos. Swamp buffalo cloned embryos were produced by electrical pulse fusion of male swamp buffalo fibroblasts with swamp buffalo enucleated oocytes. After fusion, reconstructed oocytes were treated with 0, 25 or 50 nM TSA for 10 h. The results showed that there was no significant difference in the rates of fusion (82–85%), cleavage (79–84%) and development to the 8-cell stage (59–65%) among treatment groups. The highest developmental rates to the morula and blastocyst stages of embryos were found in the 25 nM TSA-treated group (42.7 and 30.1%, respectively). We also analyzed the DNA methylation level in the satellite I region of donor cells and in in vitro fertilized (IVF) and cloned embryos using the bisulfite DNA sequencing method. The results indicated that the DNA methylation levels in cloned embryos were significantly higher than those of IVF embryos but approximately similar to those of donor cells. Moreover, there was no significant difference in the methylation level among TSA-treated and untreated cloned embryos. Thus, TSA treatments at 25 nM for 10 h could enhance the in vitro developmental potential of swamp buffalo cloned embryos, but no beneficial effect on the DNA methylation level was observed. PMID:24909601

  10. Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity

    PubMed Central

    Johnson, S. A.; Painter, M. S.; Javurek, A. B.; Ellersieck, M. R.; Wiedmeyer, C. E.; Thyfault, J. P.; Rosenfeld, C. S.

    2016-01-01

    Endocrine disrupting chemicals (EDC) have received considerable attention as potential obesogens. Past studies examining obesogenic potential of one widespread EDC, bisphenol A (BPA), have generally focused on metabolic and adipose tissue effects. However, physical inactivity has been proposed to be a leading cause of obesity. A paucity of studies has considered whether EDC, including BPA, affects this behavior. To test whether early exposure to BPA and ethinyl estradiol (EE, estrogen present in birth control pills) results in metabolic and such behavioral disruptions, California mice developmentally exposed to BPA and EE were tested as adults for energy expenditure (indirect calorimetry), body composition (echoMRI) and physical activity (measured by beam breaks and voluntary wheel running). Serum glucose and metabolic hormones were measured. No differences in body weight or food consumption were detected. BPA-exposed females exhibited greater variation in weight than females in control and EE groups. During the dark and light cycles, BPA females exhibited a higher average respiratory quotient than control females, indicative of metabolizing carbohydrates rather than fats. Various assessments of voluntary physical activity in the home cage confirmed that during the dark cycle, BPA and EE-exposed females were significantly less active in this setting than control females. Similar effects were not observed in BPA or EE-exposed males. No significant differences were detected in serum glucose, insulin, adiponectin and leptin concentrations. Results suggest that females developmentally exposed to BPA exhibit decreased motivation to engage in voluntary physical activity and altered metabolism of carbohydrates v. fats, which could have important health implications. PMID:26378919

  11. Psychological Stress on Female Mice Diminishes the Developmental Potential of Oocytes: A Study Using the Predatory Stress Model

    PubMed Central

    Liu, Yu-Xiang; Cheng, Ya-Nan; Miao, Yi-Long; Wei, De-Li; Zhao, Li-Hua; Luo, Ming-Jiu; Tan, Jing-He

    2012-01-01

    Although the predatory stress experimental protocol is considered more psychological than the restraint protocol, it has rarely been used to study the effect of psychological stress on reproduction. Few studies exist on the direct effect of psychological stress to a female on developmental competence of her oocytes, and the direct effect of predatory maternal stress on oocytes has not been reported. In this study, a predatory stress system was first established for mice with cats as predators. Beginning 24 h after injection of equine chorionic gonadotropin, female mice were subjected to predatory stress for 24 h. Evaluation of mouse responses showed that the predatory stress system that we established increased anxiety-like behaviors and plasma cortisol concentrations significantly and continuously while not affecting food and water intake of the mice. In vitro experiments showed that whereas oocyte maturation and Sr2+ activation or fertilization were unaffected by maternal predatory stress, rate of blastocyst formation and number of cells per blastocyst decreased significantly in stressed mice compared to non-stressed controls. In vivo embryo development indicated that both the number of blastocysts recovered per donor mouse and the average number of young per recipient after embryo transfer of blastocysts with similar cell counts were significantly lower in stressed than in unstressed donor mice. It is concluded that the predatory stress system we established was both effective and durative to induce mouse stress responses. Furthermore, predatory stress applied during the oocyte pre-maturation stage significantly impaired oocyte developmental potential while exerting no measurable impact on nuclear maturation, suggesting that cytoplasmic maturation of mouse oocytes was more vulnerable to maternal stress than nuclear maturation. PMID:23118931

  12. Sex-Dependent Effects of Developmental Lead Exposure on the Brain.

    PubMed

    Singh, Garima; Singh, Vikrant; Sobolewski, Marissa; Cory-Slechta, Deborah A; Schneider, Jay S

    2018-01-01

    The role of sex as an effect modifier of developmental lead (Pb) exposure has until recently received little attention. Lead exposure in early life can affect brain development with persisting influences on cognitive and behavioral functioning, as well as, elevated risks for developing a variety of diseases and disorders in later life. Although both sexes are affected by Pb exposure, the incidence, manifestation, and severity of outcomes appears to differ in males and females. Results from epidemiologic and animal studies indicate significant effect modification by sex, however, the results are not consistent across studies. Unfortunately, only a limited number of human epidemiological studies have included both sexes in independent outcome analyses limiting our ability to draw definitive conclusions regarding sex-differentiated outcomes. Additionally, due to various methodological differences across studies, there is still not a good mechanistic understanding of the molecular effects of lead on the brain and the factors that influence differential responses to Pb based on sex. In this review, focused on prenatal and postnatal Pb exposures in humans and animal models, we discuss current literature supporting sex differences in outcomes in response to Pb exposure and explore some of the ideas regarding potential molecular mechanisms that may contribute to sex-related differences in outcomes from developmental Pb exposure. The sex-dependent variability in outcomes from developmental Pb exposure may arise from a combination of complex factors, including, but not limited to, intrinsic sex-specific molecular/genetic mechanisms and external risk factors including sex-specific responses to environmental stressors which may act through shared epigenetic pathways to influence the genome and behavioral output.

  13. Sex-Dependent Effects of Developmental Lead Exposure on the Brain

    PubMed Central

    Singh, Garima; Singh, Vikrant; Sobolewski, Marissa; Cory-Slechta, Deborah A.; Schneider, Jay S.

    2018-01-01

    The role of sex as an effect modifier of developmental lead (Pb) exposure has until recently received little attention. Lead exposure in early life can affect brain development with persisting influences on cognitive and behavioral functioning, as well as, elevated risks for developing a variety of diseases and disorders in later life. Although both sexes are affected by Pb exposure, the incidence, manifestation, and severity of outcomes appears to differ in males and females. Results from epidemiologic and animal studies indicate significant effect modification by sex, however, the results are not consistent across studies. Unfortunately, only a limited number of human epidemiological studies have included both sexes in independent outcome analyses limiting our ability to draw definitive conclusions regarding sex-differentiated outcomes. Additionally, due to various methodological differences across studies, there is still not a good mechanistic understanding of the molecular effects of lead on the brain and the factors that influence differential responses to Pb based on sex. In this review, focused on prenatal and postnatal Pb exposures in humans and animal models, we discuss current literature supporting sex differences in outcomes in response to Pb exposure and explore some of the ideas regarding potential molecular mechanisms that may contribute to sex-related differences in outcomes from developmental Pb exposure. The sex-dependent variability in outcomes from developmental Pb exposure may arise from a combination of complex factors, including, but not limited to, intrinsic sex-specific molecular/genetic mechanisms and external risk factors including sex-specific responses to environmental stressors which may act through shared epigenetic pathways to influence the genome and behavioral output. PMID:29662502

  14. Developmental Demands of Cognitive Behavioral Therapy for Depression in Children and Adolescents: Cognitive, Social, and Emotional Processes

    PubMed Central

    Garber, Judy; Frankel, Sarah A.; Herrington, Catherine G.

    2017-01-01

    Although some treatments for depression in children and adolescents have been found to be efficacious, the effects sizes have tended to be modest. Thus, there is considerable room to improve upon existing depression treatments. Some children may respond poorly because they do not yet have the cognitive, social, or emotional maturity needed to understand and apply the skills being taught in therapy. Therefore, treatments for depression may need to be tailored to match children’s ability to both comprehend and implement the therapeutic techniques. This paper outlines the steps needed for such developmental tailoring: (1) specify the skills being taught in depression treatments; (2) identify what cognitive, social, and emotional developmental abilities are needed to attain these skills; (3) describe the normative developmental course of these skills, and how to determine a child’s developmental level; and (4) use this information to design an individualized treatment plan. Possible approaches to intervening include: alter the therapy to meet the child’s level of development, train the child on the skills needed to engage in the therapy, or apply a dynamic assessment approach that integrates evaluation into treatment and measures children’s potential as well as their current abilities. PMID:27019397

  15. Improving student dentist competencies and perception of difficulty in delivering care to children with developmental disabilities using a virtual patient module.

    PubMed

    Kleinert, Harold L; Sanders, Carla; Mink, John; Nash, David; Johnson, Jeff; Boyd, Sara; Challman, Sandra

    2007-02-01

    An interactive, multimedia, virtual patient module was designed and developed on compact disc (CD-ROM) to address the need for student dentists to increase their competence and decrease their perception of difficulty in caring for children with developmental disabilities. A development team consisting of pediatric dentistry faculty members, parents of children with developmental disabilities, an individual with a developmental disability, and educational specialists developed an interactive virtual patient case. The case involved a ten-year-old child with Down syndrome presenting with a painful tooth. Student dentists were required to make decisions regarding proper interactions with the child, as well as appropriate clinical procedures throughout the case. Differences in perceived difficulty level and knowledge change were measured, as well as the student dentists' overall satisfaction with the learning experience. Significant results were obtained in both perceived difficulty level and knowledge-based measures for student dentists. Participants reported overall satisfaction with the modules. Preparing student dentists to provide sensitive and competent care for children with developmental disabilities is a critical need within dentistry. This study demonstrated that an interactive, multimedia (CD-ROM), virtual patient learning module for student dentists is potentially an effective tool in meeting this need.

  16. The adolescent parent: A dual developmental crisis.

    PubMed

    Sadler, L S; Catrone, C

    1983-06-01

    This paper examines salient developmental characteristics of adolescents and beginning parents. In the case of many teenage parents, specific developmental tasks of adolescence affect and may potentially conflict with the tasks of early parenthood. A conceptual framework is presented which describes this conflict and serves as the basis for examining and explaining certain unique behaviors observed in young adolescent parents.

  17. Adverse Childhood Experiences and Suicide Attempts: The Mediating Influence of Personality Development and Problem Behaviors.

    PubMed

    Perez, Nicholas M; Jennings, Wesley G; Piquero, Alex R; Baglivio, Michael T

    2016-08-01

    Adverse childhood experiences, comprised of forms of maltreatment and certain dysfunctional household environments, can affect the development of a child in a variety of different ways. This multitude of developmental changes may subsequently produce compounding harmful effects on the child's life and increase acutely maladaptive outcomes, including adolescent suicidal behavior. This study uses data collected from 2007 to 2012 for 64,329 Florida Department of Juvenile Justice youth (21.67 % female, 42.88 % African American, and 15.37 % Hispanic) to examine the direct and indirect effects of adverse childhood experiences on suicide attempts. Using a generalized structural equation model, the effects of adverse childhood experience scores are estimated on suicidal behavior through pathways of certain aspects of a child's personality development (aggression and impulsivity), as well as adolescent problem behaviors (school difficulties and substance abuse). The results show that a large proportion of the relationship between childhood adversity and suicide is mediated by the aforementioned individual characteristics, specifically through the youth's maladaptive personality development. These results suggest that, if identified early enough, the developmental issues for these youth could potentially be addressed in order to thwart potential suicidal behavior.

  18. Effectiveness of a low-cost virtual reality system for children with developmental delay: a preliminary randomised single-blind controlled trial.

    PubMed

    Salem, Yasser; Gropack, Stacy Jaffee; Coffin, Dale; Godwin, Ellen M

    2012-09-01

    Physical and occupational therapists have started to use the Nintendo Wii™ gaming system with adults and children as part of their regular treatment. Despite the growing use of the Wii and trend towards evidence-based practice, limited evidence is available on the effectiveness of virtual reality using the Wii for children with developmental delay. The purpose of this study was to determine the feasibility and preliminary effectiveness of a low-cost gaming system for young children with developmental delay. Single-blind, randomised controlled trial. Forty children with developmental delay (age 39 to 58 months) who attended a segregated or integrated preschool participated in this study. All children's parents read and signed an informed consent form approved by the institutional review board. Children were assigned at random to an experimental (Wii) group (n=20) or a control group (n=20). Two weekly sessions for 10 weeks using Nintendo Wii Sports™ and Nintendo Wii Fit™, including balance, strength training and aerobics games. Participants were evaluated 1 week before and 1 week after the programme by a blinded investigator. Primary outcomes were gait speed, timed up and go test, single leg stance test, five-times-sit-to-stand test, timed up and down stairs test, 2-minute walk test and grip strength. The Gross Motor Function Measure (GMFM) was used to assess gross motor skills. The two groups were homogenous regarding all parameters at baseline. The Wii training was feasible and enjoyable for those in the experimental group. There were no adverse effects or injuries reported over 267 training sessions. Comparison of groups following the intervention indicated that the experimental group showed significant improvements compared with the control group in single leg stance test {mean difference 1.03 [standard deviation (SD) 1.7], 95% confidence interval (CI) 0.2 to 1.9; P=0.017}, right grip strength [mean difference 1.11 (SD 1.84), 95% CI 0.15 to 2.06; P=0.024] and left grip strength [mean difference 0.90 (SD 1.67), 95% CI 0.03 to 1.77; P=0.043]. Although changes in other outcome measures were not significant between the study groups, there were trends towards greater improvements in the experimental group compared with the control group. This study supports use of the Wii as a feasible, safe and potentially effective therapeutic tool to augment the rehabilitation of young children with developmental delay. The potential application of the Wii to increase the intensity of therapy or as a rehabilitation tool in children's homes and rural settings is an area worthy of investigation. The promising results of this study suggest that further studies are warranted to validate the potential benefits of a low-cost commercially available gaming system as a treatment strategy to supplement rehabilitation of children with disabilities. Copyright © 2012 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  19. Developmental Neurotoxicity Study of Dietary Bisphenol A in Sprague-Dawley Rats

    PubMed Central

    Stump, Donald G.; Beck, Melissa J.; Radovsky, Ann; Garman, Robert H.; Freshwater, Lester L.; Sheets, Larry P.; Marty, M. Sue; Waechter, John M.; Dimond, Stephen S.; Van Miller, John P.; Shiotsuka, Ronald N.; Beyer, Dieter; Chappelle, Anne H.; Hentges, Steven G.

    2010-01-01

    This study was conducted to determine the potential of bisphenol A (BPA) to induce functional and/or morphological effects to the nervous system of F1 offspring from dietary exposure during gestation and lactation according to the Organization for Economic Cooperation and Development and U.S. Environmental Protection Agency guidelines for the study of developmental neurotoxicity. BPA was offered to female Sprague-Dawley Crl:CD (SD) rats (24 per dose group) and their litters at dietary concentrations of 0 (control), 0.15, 1.5, 75, 750, and 2250 ppm daily from gestation day 0 through lactation day 21. F1 offspring were evaluated using the following tests: detailed clinical observations (postnatal days [PNDs] 4, 11, 21, 35, 45, and 60), auditory startle (PNDs 20 and 60), motor activity (PNDs 13, 17, 21, and 61), learning and memory using the Biel water maze (PNDs 22 and 62), and brain and nervous system neuropathology and brain morphometry (PNDs 21 and 72). For F1 offspring, there were no treatment-related neurobehavioral effects, nor was there evidence of neuropathology or effects on brain morphometry. Based on maternal and offspring body weight reductions, the no-observed-adverse-effect level (NOAEL) for systemic toxicity was 75 ppm (5.85 and 13.1 mg/kg/day during gestation and lactation, respectively), with no treatment-related effects at lower doses or nonmonotonic dose responses observed for any parameter. There was no evidence that BPA is a developmental neurotoxicant in rats, and the NOAEL for developmental neurotoxicity was 2250 ppm, the highest dose tested (164 and 410 mg/kg/day during gestation and lactation, respectively). PMID:20164145

  20. Bereavement: Applying Erikson's Theory of Psychosocial Development to College Students.

    ERIC Educational Resources Information Center

    Floerchinger, Debra S.

    One of the developmental challenges that a college student may have to face is the death of a significant other, friend, spouse, relative, child, or parent. This article reviews the literature on the potential effects of bereavement on a college student with respect to Erik Erikson's stage six of psychosocial development (intimacy versus…

  1. Using developing cortical cultures on microelectrode arrays to identify and prioritize compounds based on changes in network formation

    EPA Science Inventory

    Characterization of the potential adverse effects is lacking for tens of thousands of chemicals that are present in the environment, and characterization of developmental neurotoxicity (DNT) hazard lags behind that of other adverse outcomes (e.g. hepatotoxicity). This is due in p...

  2. Brief Report: Agreement between Parents and Day-Care Professionals on Early Symptoms Associated with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Larsen, Kenneth; Aasland, Astrid; Diseth, Trond H.

    2018-01-01

    Early identification of Autism Spectrum Disorders (ASD) has the potential to elicit effective early intervention, improving children's level of functioning and developmental trajectories as well as reducing parental stress. Multiple sources of information, including several informants may facilitate early identification. This study examined the…

  3. The Role of Psychological and Developmental Science in Efforts to Improve Teacher Quality

    ERIC Educational Resources Information Center

    Rimm-Kaufman, Sara E.; Hamre, Bridget K.

    2010-01-01

    Background: Theory, methods, and knowledge gained from years of study in psychological science and human development apply to the understanding and improvement of teacher quality and, ultimately, student achievement and social and emotional outcomes. With these applications, educational research has stronger potential to make more effective and…

  4. An Evaluation of ToxCast Angiogenic Disruptors for Effects on Mitochondrial Bioactivity Profiles (Teratology Society Annual Meeting)

    EPA Science Inventory

    Angiogenesis is a critical developmental process and a potential target for chemical teratogenesis. Over one-tenth of the Tox21 library of 10,000 compounds have been shown to disrupt mitochondrial function [Attene-Ramos et al., 2015]. Previous studies utilizing ToxCast chemicals ...

  5. The Influence of Parental Separation and Divorce on Adolescent Academic Achievement: Developmental Issues.

    ERIC Educational Resources Information Center

    Nisivoccia, Joseph Dominick

    Parental separation and divorce can have a critically adverse effect on the academic performance and achievement of adolescent students. The psychological and social disadvantages can significantly interfere with students reaching their full potential for success in school. Information is provided on the scope of divorce in society and its…

  6. [Effect of TSA and VPA treatment on long-tailed macaque (Macaca fascicularis)-pig interspecies somatic cell nuclear transfer].

    PubMed

    Qin, Zu-Xing; Huang, Gao-Bo; Luo, Jun; Ning, Shu-Fang; Lu, Sheng-Sheng; Lu, Ke-Huan

    2012-03-01

    Long-tailed macaque-pig interspecies somatic cell nuclear transfer (iSCNT) is beneficial to yield embryonic stem cells from iSCNT embryos with similar genetic background as human, which can be used as materials for medical and basic research. The primary objective of this study was to investigate the effects of concentrations and treatment duration of two histone deacetylase inhibitors-Trichostatin A (TSA) and Valproic acid (VPA) and two different embryo culture media (PZM-3 and HECM-10) on the in vitro development of iSCNT embryos. The results suggested that when PZM-3 was used as the embryo culture medium, the blastocyst rate of 10 nmol/L TSA treatment for 48 h was significantly higher than the control group (22.78% vs 9.86%, P< 0.05). However, neither in PZM-3 nor in HECM-10, 2-10 mmol/L VPA treatment did not increase the in vitro developmental potential of iSCNT embryos. It was concluded that TSA treatment could enhance the in vitro developmental potential of long-tailed macaque-pig iSCNT embryos.

  7. Long-term reproductive and behavioral toxicity of anthracene to fish in the presence of solar ultraviolet radiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hall, A.T.; Oris, J.T.

    1994-12-31

    The long-term, low-level effects of anthracene in the presence of solar ultraviolet radiation (SUVR) were examined in the fathead minnow (Pimephales promelas). Adult fish exposed to anthracene exhibited reduced egg laying capacity, with altered oocyte maturation as a potential mechanism of action. Eggs and larvae maternally exposed to anthracene exhibited reduced hatching success and severe developmental abnormalities when incubated under SUVR. The combination of reduced egg output and developmental effects resulted in an inhibition in reproductive capacity in the range of 70--100%. Maternal transfer of anthracene to eggs was efficient; the BCF was 717 for maternally exposed eggs. However, anthracenemore » deputation from eggs after oviposition with only maternal PAH exposure was rapid; anthracene half-life from eggs equaled 1.3 days. Exposure to anthracene under SUVR altered locomotor activity patterns in fathead minnows by inducing hyperactivity or hypoactivity during the light or dark phases of the photoperiod, respectively. Altered activity patterns indicated potential effects of anthracene on the nervous system and/or pineal gland. These alterations disrupted normal activity patterns and reproductive behaviors, and thus have major implications on a fish`s ability to survive and reproduce. Anthracene, a model phototoxic PAH, has many potential sites of toxic action, and any organism exposed to such contaminants will be an considerable SUVR-enhanced risk in the environment.« less

  8. DEVELOPMENTAL LEAD (PB) EXPOSURE REDUCES THE ABILITY OF THE NNDA ANTAGONIST MK801 TO SUPPRESS LONG-TERM POTENTIATION (LTP) IN THE RAT DENTATE GYRUS, IN VIVO

    EPA Science Inventory

    Chronic developmental lead (Pb) exposure increases the threshold and enhances decay of long-term potentiation (LTP) in the dentate gyrus of the hippocampal formation. MK-801 and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype impair induction of LT...

  9. TOWARDS REFINED USE OF TOXICITY DATA IN ...

    EPA Pesticide Factsheets

    In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants. In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

  10. Life-Long Implications of Developmental Exposure to Environmental Stressors: New Perspectives.

    PubMed

    Grandjean, Philippe; Barouki, Robert; Bellinger, David C; Casteleyn, Ludwine; Chadwick, Lisa H; Cordier, Sylvaine; Etzel, Ruth A; Gray, Kimberly A; Ha, Eun-Hee; Junien, Claudine; Karagas, Margaret; Kawamoto, Toshihiro; Paige Lawrence, B; Perera, Frederica P; Prins, Gail S; Puga, Alvaro; Rosenfeld, Cheryl S; Sherr, David H; Sly, Peter D; Suk, William; Sun, Qi; Toppari, Jorma; van den Hazel, Peter; Walker, Cheryl L; Heindel, Jerrold J

    2015-10-01

    The Developmental Origins of Health and Disease (DOHaD) paradigm is one of the most rapidly expanding areas of biomedical research. Environmental stressors that can impact on DOHaD encompass a variety of environmental and occupational hazards as well as deficiency and oversupply of nutrients and energy. They can disrupt early developmental processes and lead to increased susceptibility to disease/dysfunctions later in life. Presentations at the fourth Conference on Prenatal Programming and Toxicity in Boston, in October 2014, provided important insights and led to new recommendations for research and public health action. The conference highlighted vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous "reprogramming" of the genome, thereby potentially resulting in transgenerational effects. Stem cells can also be targets of environmental stressors, thus paving another way for effects that may last a lifetime. Current testing paradigms do not allow proper characterization of risk factors and their interactions. Thus, relevant exposure levels and combinations for testing must be identified from human exposure situations and outcome assessments. Testing of potential underpinning mechanisms and biomarker development require laboratory animal models and in vitro approaches. Only few large-scale birth cohorts exist, and collaboration between birth cohorts on a global scale should be facilitated. DOHaD-based research has a crucial role in establishing factors leading to detrimental outcomes and developing early preventative/remediation strategies to combat these risks.

  11. Infant Neurobehavioral Development

    PubMed Central

    Lester, Barry M.; Miller, Robin J.; Hawes, Katheleen; Salisbury, Amy; Bigsby, Rosemarie; Sullivan, Mary C.; Padbury, James F.

    2011-01-01

    The trend toward single-room neonatal intensive care units (NICUs) is increasing; however scientific evidence is, at this point, mostly anecdotal. This is a critical time to assess the impact of the single-room NICU on improving medical and neurobehavioral outcomes of the preterm infant. We have developed a theoretical model that may be useful in studying how the change from an open-bay NICU to a single-room NICU could affect infant medical and neurobehavioral outcome. The model identifies mediating factors that are likely to accompany the change to a single-room NICU. These mediating factors include family centered care, developmental care, parenting and family factors, staff behavior and attitudes, and medical practices. Medical outcomes that plan to be measured are sepsis, length of stay, gestational age at discharge, weight gain, illness severity, gestational age at enteral feeding, and necrotizing enterocolitis (NEC). Neurobehavioral outcomes include the NICU Network Neurobehavioral Scale (NNNS) scores, sleep state organization and sleep physiology, infant mother feeding interaction scores, and pain scores. Preliminary findings on the sample of 150 patients in the open-bay NICU showed a “baseline” of effects of family centered care, developmental care, parent satisfaction, maternal depression, and parenting stress on the neurobehavioral outcomes of the newborn. The single-room NICU has the potential to improve the neurobehavioral status of the infant at discharge. Neurobehavioral assessment can assist with early detection and therefore preventative intervention to maximize developmental outcome. We also present an epigenetic model of the potential effects of maternal care on improving infant neurobehavioral status. PMID:21255702

  12. Effects of perfluorooctanoic acid (PFOA) on expression of ...

    EPA Pesticide Factsheets

    PPARs regulate metabolism and can be activated by environmental contaminants such as perfluorooctanoic acid (PFOA). PFOA induces neonatal mortality, developmental delay, and growth deficits in mice. Studies in genetically altered mice showed that PPARa is required for PFOA-induced developmental toxicity. In this study, pregnant CD-1 mice were dosed orally from GD1-17 with water or 5 mg PFO/kg to examine PPARa, PPARß, and PPARy expression and profile the effects of PFOA on PPAR-regulated genes. Prenatal and postnatal liver, heart, adrenal, kidney, intestine, stomach, lung, spleen, and thymus were collected at various developmental ages. RNA and protein were examined using qPCR and Western blot analysis. PPAR expression varied with age in all tissues, and in liver PPARa and PPARy expression correlated with nutritional changes as the pups matured. As early as GD14, PFOA affected expression of genes involved in lipid and glucose homeostatic control. The metabolic disruption produced by PFOA may contribute to poor postnatal survival and persistent weight deficits of neonates This paper represents the continuing efforts at ORD, in response to the call for assistance from OPPTS, to investigate the potential developmental toxicities of perfluoroalkyl acids (PFAA). Perfluorooctanoic acid (PFOA) is a compound which persists and is found ubiquitously in the environment, wildlife and humans. Studies in our laboratory using an in vitro transfected cell model showed that PFO

  13. Multivariate dynamical modelling of structural change during development.

    PubMed

    Ziegler, Gabriel; Ridgway, Gerard R; Blakemore, Sarah-Jayne; Ashburner, John; Penny, Will

    2017-02-15

    Here we introduce a multivariate framework for characterising longitudinal changes in structural MRI using dynamical systems. The general approach enables modelling changes of states in multiple imaging biomarkers typically observed during brain development, plasticity, ageing and degeneration, e.g. regional gray matter volume of multiple regions of interest (ROIs). Structural brain states follow intrinsic dynamics according to a linear system with additional inputs accounting for potential driving forces of brain development. In particular, the inputs to the system are specified to account for known or latent developmental growth/decline factors, e.g. due to effects of growth hormones, puberty, or sudden behavioural changes etc. Because effects of developmental factors might be region-specific, the sensitivity of each ROI to contributions of each factor is explicitly modelled. In addition to the external effects of developmental factors on regional change, the framework enables modelling and inference about directed (potentially reciprocal) interactions between brain regions, due to competition for space, or structural connectivity, and suchlike. This approach accounts for repeated measures in typical MRI studies of development and aging. Model inversion and posterior distributions are obtained using earlier established variational methods enabling Bayesian evidence-based comparisons between various models of structural change. Using this approach we demonstrate dynamic cortical changes during brain maturation between 6 and 22 years of age using a large openly available longitudinal paediatric dataset with 637 scans from 289 individuals. In particular, we model volumetric changes in 26 bilateral ROIs, which cover large portions of cortical and subcortical gray matter. We account for (1) puberty-related effects on gray matter regions; (2) effects of an early transient growth process with additional time-lag parameter; (3) sexual dimorphism by modelling parameter differences between boys and girls. There is evidence that the regional pattern of sensitivity to dynamic hidden growth factors in late childhood is similar across genders and shows a consistent anterior-posterior gradient with strongest impact to prefrontal cortex (PFC) brain changes. Finally, we demonstrate the potential of the framework to explore the coupling of structural changes across a priori defined subnetworks using an example of previously established resting state functional connectivity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Bisphenol A alternatives in thermal paper from the Netherlands, Spain, Sweden and Norway. Screening and potential toxicity.

    PubMed

    Björnsdotter, Maria K; Jonker, Willem; Legradi, Jessica; Kool, Jeroen; Ballesteros-Gómez, Ana

    2017-12-01

    Thermal paper contains potentially toxic additives, such as bisphenol A (BPA), as a common color developer. Because of its known endocrine disrupting effects, structural analogues to BPA, such as bisphenol S (BPS), D-8 and Pergafast 201, have been used as alternatives, but little is known about the presence and toxicological effects of alternatives other than BPS. In this study, thermal paper is screened by direct probe ambient mass spectrometry (rapid pre-screening method not requiring sample preparation) and by liquid chromatography (LC) with high resolution time-of flight (TOF-MS) mass spectrometry. Cash receipts and other thermal paper products (cinema tickets, boarding passes and luggage tags) were analyzed. Besides BPA and BPS, other developers only recently reported (Pergafast 201, D-8) or to the best of our knowledge not reported before (D-90, TGSA, BPS-MAE) were frequently found as well as some related unreported impurities (2,4-BPS that is a BPS related impurity and a TGSA related impurity). To gain some insight into the potential estrogenicity of the detected developers, a selection of extracts was further analyzed using a LC-nanofractionation platform in combination with cell-based bioassay testing. These preliminary results seems to indicate very low or absence of estrogenic activity for Pergafast 201, D-8, D-90, TGSA and BPS-MAE in comparison to BPA and BPS, although further dose-response tests with authentic standards are required to confirm these results. Compounds for which standards were available were also tested for developmental toxicity and neurotoxicity using zebrafish (Danio rerio) embryos. TGSA and D-8 induced similar teratogenic effects as BPA in zebrafish embryos. BPS and 2,4-BPS did not induce any developmental effects but 2,4-BPS did alter the locomotor activity at the tested concentration. Our findings suggest that the alternatives used as alternatives to BPA (except BPS) might not be estrogenic. However, TGSA and D-8 showed abnormal developmental effects similar to BPA. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Testing for developmental neurotoxicity using a battery of in vitro assays for key cellular events in neurodevelopment.

    PubMed

    Harrill, Joshua A; Freudenrich, Theresa; Wallace, Kathleen; Ball, Kenneth; Shafer, Timothy J; Mundy, William R

    2018-04-05

    Medium- to high-throughput in vitro assays that recapitulate the critical processes of nervous system development have been proposed as a means to facilitate rapid testing and identification of chemicals which may affect brain development. In vivo neurodevelopment is a complex progression of distinct cellular processes. Therefore, batteries of in vitro assays that model and quantify effects on a variety of neurodevelopmental processes have the potential to identify chemicals which may affect brain development at different developmental stages. In the present study, the results of concentration-response screening of 67 reference chemicals in a battery of high content imaging and microplate reader-based assays that evaluate neural progenitor cell proliferation, neural proginitor cell apoptosis, neurite initiation/outgrowth, neurite maturation and synaptogenesis are summarized and compared. The assay battery had a high degree of combined sensitivity (87%) for categorizing chemicals known to affect neurodevelopment as active and a moderate degree of combined specificity (71%) for categorizing chemicals not associated with affects on neurodevelopment as inactive. The combined sensitivity of the assay battery was higher compared to any individual assay while the combined specificity of the assay battery was lower compared to any individual assay. When selectivity of effects for a neurodevelopmental endpoint as compared to general cytotoxicity was taken into account, the combined sensitivity of the assay battery decreased (68%) while the combined specificity increased (93%). The identity and potency of chemicals identified as active varied across the assay battery, underscoring the need for use of a combination of diverse in vitro models to comprehensively screen chemicals and identify those which potentially affect neurodevelopment. Overall, these data indicate that a battery of assays which address many different processes in nervous system development may be used to identify potential developmental neurotoxicants and to distinguish specific from generalized cytotoxic effects with a high degree of success. Published by Elsevier Inc.

  16. Neurophysiological assessment of auditory, peripheral nerve, somatosensory, and visual system function after developmental exposure to gasoline, E15, and E85 vapors.

    PubMed

    Herr, David W; Freeborn, Danielle L; Degn, Laura; Martin, Sheppard A; Ortenzio, Jayna; Pantlin, Lara; Hamm, Charles W; Boyes, William K

    2016-01-01

    The use of gasolines blended with a range of ethanol concentrations may result in inhalation of vapors containing a variable combination of ethanol with other volatile gasoline constituents. The possibility of exposure and potential interactions between vapor constituents suggests the need to evaluate the possible risks of this complex mixture. Previously we evaluated the effects of developmental exposure to ethanol vapors on neurophysiological measures of sensory function as a component of a larger project evaluating developmental ethanol toxicity. Here we report an evaluation using the same battery of sensory function testing in offspring of pregnant dams exposed during gestation to condensed vapors of gasoline (E0), gasoline blended with 15% ethanol (E15) or gasoline blended with 85% ethanol (E85). Pregnant Long-Evans rats were exposed to target concentrations 0, 3000, 6000, or 9000 ppm total hydrocarbon vapors for 6.5h/day over GD9 - GD20. Sensory evaluations of male offspring began as adults. The electrophysiological testing battery included tests of: peripheral nerve (compound action potentials, nerve conduction velocity [NCV]), somatosensory (cortical and cerebellar evoked potentials), auditory (brainstem auditory evoked responses), and visual functions. Visual function assessment included pattern elicited visual evoked potentials (VEP), VEP contrast sensitivity, dark-adapted (scotopic) electroretinograms (ERGs), light-adapted (photopic) ERGs, and green flicker ERGs. The results included sporadic statistically significant effects, but the observations were not consistently concentration-related and appeared to be statistical Type 1 errors related to multiple dependent measures evaluated. The exposure concentrations were much higher than can be reasonably expected from typical exposures to the general population during refueling or other common exposure situations. Overall the results indicate that gestational exposure of male rats to ethanol/gasoline vapor combinations did not cause detectable changes in peripheral nerve, somatosensory, auditory, or visual function when the offspring were assessed as adults. Published by Elsevier Inc.

  17. Avoiding the Potential Pitfalls of Using Negative Priming Tasks in Developmental Studies: Assessing Inhibitory Control in Children, Adolescents, and Adults

    ERIC Educational Resources Information Center

    Pritchard, Verena E.; Neumann, Ewald

    2009-01-01

    Despite being ignored, visual distractors often produce traceable negative priming (NP) effects that can be used to investigate inhibitory processes. Robust NP effects are typically found with young adults, but not with children. Using 2 different NP tasks, the authors compared NP in 5 different age groups spanning 5 to 25 years of age. The 1st…

  18. Can Nucleoli Be Markers of Developmental Potential in Human Zygotes?

    PubMed

    Fulka, Helena; Kyogoku, Hirohisa; Zatsepina, Olga; Langerova, Alena; Fulka, Josef

    2015-11-01

    In 1999, Tesarik and Greco reported that they could predict the developmental potential of human zygotes from a single static evaluation of their pronuclei. This was based on the distribution and number of specific nuclear organelles - the nucleoli. Recent studies in mice show that nucleoli play a key role in parental genome restructuring after fertilization, and that interfering with this process may lead to developmental failure. These studies thus support the Tesarik-Greco evaluation as a potentially useful method for selecting high-quality embryos in human assisted reproductive technologies. In this opinion article we discuss recent evidence linking nucleoli to parental genome reprogramming, and ask whether nucleoli can mirror or be used as representative markers of embryonic parameters such as chromosome content or DNA fragmentation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Media use by children younger than 2 years.

    PubMed

    Brown, Ari

    2011-11-01

    In 1999, the American Academy of Pediatrics (AAP) issued a policy statement addressing media use in children. The purpose of that statement was to educate parents about the effects that media--both the amount and the content--may have on children. In one part of that statement, the AAP recommended that "pediatricians should urge parents to avoid television viewing for children under the age of two years." The wording of the policy specifically discouraged media use in this age group, although it is frequently misquoted by media outlets as no media exposure in this age group. The AAP believed that there were significantly more potential negative effects of media than positive ones for this age group and, thus, advised families to thoughtfully consider media use for infants. This policy statement reaffirms the 1999 statement with respect to media use in infants and children younger than 2 years and provides updated research findings to support it. This statement addresses (1) the lack of evidence supporting educational or developmental benefits for media use by children younger than 2 years, (2) the potential adverse health and developmental effects of media use by children younger than 2 years, and (3) adverse effects of parental media use (background media) on children younger than 2 years.

  20. Developmental origins of non-communicable disease: Implications for research and public health

    PubMed Central

    2012-01-01

    This White Paper highlights the developmental period as a plastic phase, which allows the organism to adapt to changes in the environment to maintain or improve reproductive capability in part through sustained health. Plasticity is more prominent prenatally and during early postnatal life, i.e., during the time of cell differentiation and specific tissue formation. These developmental periods are highly sensitive to environmental factors, such as nutrients, environmental chemicals, drugs, infections and other stressors. Nutrient and toxicant effects share many of the same characteristics and reflect two sides of the same coin. In both cases, alterations in physiological functions can be induced and may lead to the development of non-communicable conditions. Many of the major diseases – and dysfunctions – that have increased substantially in prevalence over the last 40 years seem to be related in part to developmental factors associated with either nutritional imbalance or exposures to environmental chemicals. The Developmental Origins of Health and Disease (DOHaD) concept provides significant insight into new strategies for research and disease prevention and is sufficiently robust and repeatable across species, including humans, to require a policy and public health response. This White Paper therefore concludes that, as early development (in utero and during the first years of postnatal life) is particularly sensitive to developmental disruption by nutritional factors or environmental chemical exposures, with potentially adverse consequences for health later in life, both research and disease prevention strategies should focus more on these vulnerable life stages. PMID:22715989

  1. Embracing the Potential of Play for Children on the Autism Spectrum: Facilitating the Earliest Stages of Developmental Integration

    ERIC Educational Resources Information Center

    Gerber, Sima

    2017-01-01

    In this article, the breadth and depth of play as an integrating process for children with developmental challenges are explored. The fact that play is a source of developmental growth suggests that its role in intervention with children with language and communication disorders cannot be overstated. Several contemporary play-based intervention…

  2. Magnetic resonance imaging (MRI) evaluation of developmental delay in pediatric patients.

    PubMed

    Ali, Althaf S; Syed, Naziya P; Murthy, G S N; Nori, Madhavi; Abkari, Anand; Pooja, B K; Venkateswarlu, J

    2015-01-01

    Developmental delay is defined as significant delay in one or more developmental domains. Magnetic Resonance Imaging (MRI) is the best modality to investigate such patients. Evaluation of a child with developmental delay is important not only because it allows early diagnosis and treatment but also helpful for parental counseling regarding the outcome of their child and to identify any possible risk of recurrence in the siblings. Thus this study was undertaken to evaluate the developmental delay in Indian children which will help the clinicians in providing an estimation of the child's ultimate developmental potential and organize specific treatment requirement and also relieve parental apprehension. To study the prevalence of normal and abnormal MRI in pediatric patients presenting with developmental delay and further categorize the abnormal MRI based on its morphological features. It is a prospective, observational & descriptive study of MRI Brain in 81 paediatric patients (46 Males and 35 Females), aged between three months to 12 years; presenting with developmental delay in Deccan College of Medical Sciences, Hyderabad; over a period of three years (Sept 2011 to Sept 2014). MRI brain was done on 1.5T Siemens Magnetom Essenza & 0.35T Magnetom C with appropriate sequences and planes after making the child sleep/sedated/ anesthetized. Various anatomical structures like Ventricles, Corpus callosum, etc were systematically assessed. The MRI findings were divided into various aetiological subgroups. Normal MRI findings were seen in 32% cases and 68% had abnormal findings of which the proportion of Traumatic/ Neurovascular Diseases, Congenital & Developmental, Metabolic and Degenerative, neoplastic and non specific were 31%, 17%, 10%, 2.5% and 7.5% respectively. The ventricles and white matter mainly the corpus callosum were the most commonly affected anatomical structures. The diagnostic yield was found to be 68% and higher yield was seen in patients presenting with developmental delay plus. The clinical diagnosis of developmental delay should not be the end point, but rather a springboard for an effective search for causal factors. MRI is the best investigation with a high yield in such patients.

  3. Magnetic Resonance Imaging (MRI) Evaluation of Developmental Delay in Pediatric Patients

    PubMed Central

    Syed, Naziya P.; Murthy, G.S.N.; Nori, Madhavi; Abkari, Anand; Pooja, B.K.; Venkateswarlu, J.

    2015-01-01

    Introduction: Developmental delay is defined as significant delay in one or more developmental domains. Magnetic Resonance Imaging (MRI) is the best modality to investigate such patients. Evaluation of a child with developmental delay is important not only because it allows early diagnosis and treatment but also helpful for parental counseling regarding the outcome of their child and to identify any possible risk of recurrence in the siblings. Thus this study was undertaken to evaluate the developmental delay in Indian children which will help the clinicians in providing an estimation of the child’s ultimate developmental potential and organize specific treatment requirement and also relieve parental apprehension. Aims and Objectives: To study the prevalence of normal and abnormal MRI in pediatric patients presenting with developmental delay and further categorize the abnormal MRI based on its morphological features. Materials and Methods: It is a prospective, observational & descriptive study of MRI Brain in 81 paediatric patients (46 Males and 35 Females), aged between three months to 12 years; presenting with developmental delay in Deccan College of Medical Sciences, Hyderabad; over a period of three years (Sept 2011 to Sept 2014). MRI brain was done on 1.5T Siemens Magnetom Essenza & 0.35T Magnetom C with appropriate sequences and planes after making the child sleep/sedated/ anesthetized. Various anatomical structures like Ventricles, Corpus callosum, etc were systematically assessed. The MRI findings were divided into various aetiological subgroups. Results: Normal MRI findings were seen in 32% cases and 68% had abnormal findings of which the proportion of Traumatic/ Neurovascular Diseases, Congenital & Developmental, Metabolic and Degenerative, neoplastic and non specific were 31%, 17%, 10%, 2.5% and 7.5% respectively. The ventricles and white matter mainly the corpus callosum were the most commonly affected anatomical structures. The diagnostic yield was found to be 68% and higher yield was seen in patients presenting with developmental delay plus. Conclusion: The clinical diagnosis of developmental delay should not be the end point, but rather a springboard for an effective search for causal factors. MRI is the best investigation with a high yield in such patients. PMID:25738057

  4. Developmental programming: interaction between prenatal BPA and postnatal overfeeding on cardiac tissue gene expression in female sheep

    PubMed Central

    Koneva, LA; Vyas, AK; McEachin, RC; Puttabyatappa, M; H-S, Wang; Sartor, MA; Padmanabhan, V

    2017-01-01

    Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known. mRNA-seq of myocardium was performed on four groups of four female sheep to assess the effects of prenatal BPA exposure, postnatal overfeeding and their interaction on gene transcription, pathway perturbations and functional effects. The effects of prenatal exposure to BPA, postnatal overfeeding, and prenatal BPA with postnatal overfeeding all resulted in transcriptional changes (85–141 significant differentially expressed genes). Although the effects of prenatal BPA and postnatal overfeeding did not involve dysregulation of many of the same genes, they affected a remarkably similar set of biological pathways. Furthermore, an additive or synergistic effect was not found in the combined treatment group, but rather prenatal BPA treatment led to a partial reversal of the effects of overfeeding alone. Many genes previously known to be affected by BPA and involved in obesity, hypertension, or heart disease were altered following these treatments, and AP-1, EGR1, and EGFR were key hubs affected by BPA and/or overfeeding. PMID:28079927

  5. Onto-clust--a methodology for combining clustering analysis and ontological methods for identifying groups of comorbidities for developmental disorders.

    PubMed

    Peleg, Mor; Asbeh, Nuaman; Kuflik, Tsvi; Schertz, Mitchell

    2009-02-01

    Children with developmental disorders usually exhibit multiple developmental problems (comorbidities). Hence, such diagnosis needs to revolve on developmental disorder groups. Our objective is to systematically identify developmental disorder groups and represent them in an ontology. We developed a methodology that combines two methods (1) a literature-based ontology that we created, which represents developmental disorders and potential developmental disorder groups, and (2) clustering for detecting comorbid developmental disorders in patient data. The ontology is used to interpret and improve clustering results and the clustering results are used to validate the ontology and suggest directions for its development. We evaluated our methodology by applying it to data of 1175 patients from a child development clinic. We demonstrated that the ontology improves clustering results, bringing them closer to an expert generated gold-standard. We have shown that our methodology successfully combines an ontology with a clustering method to support systematic identification and representation of developmental disorder groups.

  6. Developmental neurotoxicity of different pesticides in PC-12 cells in vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Christen, Verena

    The detection of developmental neurotoxicity (DNT) of chemicals has high relevance for protection of human health. However, DNT of many pesticides is only little known. Furthermore, validated in vitro systems for assessment of DNT are not well established. Here we employed the rat phaeochromocytoma cell line PC-12 to evaluate DNT of 18 frequently used pesticides of different classes, including neonicotinoids, pyrethroids, organophosphates, organochlorines, as well as quaternary ammonium compounds, the organic compound used in pesticides, piperonyl butoxide, as well as the insect repellent diethyltoluamide (DEET). We determined the outgrowth of neurites in PC-12 cells co-treated with nerve growth factor andmore » different concentrations of biocides for 5 days. Furthermore, we determined transcriptional alterations of selected genes that may be associated with DNT, such as camk2α and camk2β, gap-43, neurofilament-h, tubulin-α and tubulin-β. Strong and dose- dependent inhibition of neurite outgrowth was induced by azamethiphos and chlorpyrifos, and dieldrin and heptachlor, which was correlated with up-regulation of gap-43. No or only weak effects on neurite outgrowth and transcriptional alterations occurred for neonicotinoids acetamiprid, clothianidin, imidacloprid and thiamethoxam, the pyrethroids λ-cyhalothrin, cyfluthrin, deltamethrin, and permethrin, the biocidal disinfectants C12-C14-alkyl(ethylbenzyl)dimethylammonium (BAC), benzalkonium chloride and barquat (dimethyl benzyl ammonium chloride), and piperonyl butoxide and DEET. Our study confirms potential developmental neurotoxicity of some pesticides and provides first evidence that azamethiphos has the potential to act as a developmental neurotoxic compound. We also demonstrate that inhibition of neurite outgrowth and transcriptional alterations of gap-43 expression correlate, which suggests the employment of gap-43 expression as a biomarker for detection and initial evaluation of potential DNT of chemicals. - Highlights: • The developmental neurotoxicity (DNT) of biocides is poorly known. • We assessed different classes of biocides for DNT in PC-12 cells. • DNT was shown by neurite outgrowth (NOG) and transcriptional changes. • Azamethiphos, chlorpyrifos, dieldrin and heptachlor showed DNT. • NOG correlated with induction of gap-43 which is an important determinant for DNT.« less

  7. Deficits of Visuospatial Attention with Reflexive Orienting Induced by Eye-Gazed Cues in Children with Developmental Coordination Disorder in the Lower Extremities: An Event-Related Potential Study

    ERIC Educational Resources Information Center

    Tsai, Chia-Liang; Pan, Chien-Yu; Chang, Yu-Kai; Wang, Chun-Hao; Tseng, Ko-Da

    2010-01-01

    The present study aims to investigate and compare the behavioral performance and event-related potentials (ERPs) measures in children with developmental coordination disorder (DCD) and typically developing (TD) children when performing the visuospatial attention task with reflexive orienting. Thirty children with DCD and 30 TD children were…

  8. Infant Reminders Alter Sympathetic Reactivity and Reduce Couple Hostility at the Transition to Parenthood

    ERIC Educational Resources Information Center

    Mosek-Eilon, Vered; Hirschberger, Gilad; Kanat-Maymon, Yaniv; Feldman, Ruth

    2013-01-01

    The transition to parenthood marks an important developmental stage in adult life, associated with unique challenges to the partners' conflict dialogue in the formation of the family unit. Utilizing a biobehavioral experimental design, we examined the potential positive effects of the infant on the couple's conflict discussion. One…

  9. The Effect of a Basic Home Stimulation Programme on the Development of Young Children Infected with HIV

    ERIC Educational Resources Information Center

    Potterton, Joanne; Stewart, Aimee; Cooper, Peter; Becker, Pieter

    2010-01-01

    Aims: The human immunodeficiency virus (HIV) potentially causes a significant encephalopathy and resultant developmental delay in infected children. The aim of this study was to determine whether a home-based intervention programme could have an impact on the neurodevelopmental status of children infected with HIV. Method: A longitudinal,…

  10. Increases in Global and Domain Specific Self-Esteem Following a 10 Day Developmental Voyage

    ERIC Educational Resources Information Center

    Grocott, Andrew C.; Hunter, John A.

    2009-01-01

    Although positive effects are often reported, research assessing the impact of Adventure Education and Outward Bound programmes on self-esteem is fraught with methodological weaknesses pertaining to an emphasis on scales assessing global self-esteem, a lack of follow-up measures to assess the potential long-term benefits of such programmes and…

  11. Developmental regulation of neuroligin genes in Japanese rice fish (oryzias latipes) embryogenesis maintains the rhythym during ethanol-in

    USDA-ARS?s Scientific Manuscript database

    Although prenatal alcohol exposure is the potential cause of fetal alcohol spectrum disorder (FASD) in humans, the molecular mechanism(s) of FASD is yet unknown. We have used Japanese rice fish (Oryzias latipes) embryogenesis as an animal model of FASD and reported that this model has effectively ge...

  12. Di-Isobutyl Phthalate (DIBP) Hazard Identification [Abstract ...

    EPA Pesticide Factsheets

    The hazard potential for DIBP is being evaluated as part of EPA’s Integrated Risk Information System (IRIS) Toxicological Review. DIBP is a plasticizer that confers flexibility and durability in industrial and consumer products. A literature search identified a relatively small epidemiology and animal toxicology database for DIBP. The epidemiological database includes studies that assessed the relationship between urinary concentrations of the DIBP metabolite mono-isobutyl phthalate (MIBP)and developmental, neurodevelopmental, immunological or breast cancer outcomes. There is limited support for associations between MIBP and inflammatory biomarker levels and decreased masculine play behavior. The animal toxicological database includes studies that assessed “phthalate syndrome” male reproductive developmental endpoints after in utero DIBP exposure. Data from the largest developmental study, Saillenfait et al. (2008), shows changes in anogenital distance, male reproductive organ weights, and litter incidence of phthalate syndrome endpoints in the lower dose range after early gestational exposure. Other studies observed increased fetal mortality, male postnatal and adult growth decrements, decreased fetal testicular testosterone and changes in expression of genes in androgen production pathways. The developmental reproductive effects observed in animal studies are consistent with the reduced testicular testosterone mode of action that is well-characterize

  13. Computational Modeling and Simulation of Developmental ...

    EPA Pesticide Factsheets

    Standard practice for assessing developmental toxicity is the observation of apical endpoints (intrauterine death, fetal growth retardation, structural malformations) in pregnant rats/rabbits following exposure during organogenesis. EPA’s computational toxicology research program (ToxCast) generated vast in vitro cellular and molecular effects data on >1858 chemicals in >600 high-throughput screening (HTS) assays. The diversity of assays has been increased for developmental toxicity with several HTS platforms, including the devTOX-quickPredict assay from Stemina Biomarker Discovery utilizing the human embryonic stem cell line (H9). Translating these HTS data into higher order-predictions of developmental toxicity is a significant challenge. Here, we address the application of computational systems models that recapitulate the kinematics of dynamical cell signaling networks (e.g., SHH, FGF, BMP, retinoids) in a CompuCell3D.org modeling environment. Examples include angiogenesis (angiodysplasia) and dysmorphogenesis. Being numerically responsive to perturbation, these models are amenable to data integration for systems Toxicology and Adverse Outcome Pathways (AOPs). The AOP simulation outputs predict potential phenotypes based on the in vitro HTS data ToxCast. A heuristic computational intelligence framework that recapitulates the kinematics of dynamical cell signaling networks in the embryo, together with the in vitro profiling data, produce quantitative predic

  14. Linking Biological and Cognitive Aging: Toward Improving Characterizations of Developmental Time

    PubMed Central

    DeCarlo, Correne A.; Dixon, Roger A.

    2011-01-01

    Objectives. Chronological age is the most frequently employed predictor in life-span developmental research, despite repeated assertions that it is best conceived as a proxy for true mechanistic changes that influence cognition across time. The present investigation explores the potential that selected functional biomarkers may contribute to the more effective conceptual and operational definitions of developmental time. Methods. We used data from the Victoria Longitudinal Study to explore both static and dynamic biological or physiological markers that arguably influence process-specific mechanisms underlying cognitive changes in late life. Multilevel models were fit to test the dynamic coupling between change in theoretically relevant biomarkers (e.g., grip strength, pulmonary function) and change in select cognitive measures (e.g., executive function, episodic and semantic memory). Results. Results showed that, independent of the passage of developmental time (indexed as years in study), significant time-varying covariation was observed linking corresponding declines for select cognitive outcomes and biological markers. Discussion. Our findings support the interpretation that cognitive decline is not due to chronological aging per se but rather reflects multiple causal factors from a broad range of biological and physical health domains that operate along the age continuum. PMID:21743053

  15. Child Health, Developmental Plasticity, and Epigenetic Programming

    PubMed Central

    Feil, R.; Constancia, M.; Fraga, M.; Junien, C.; Carel, J.-C.; Boileau, P.; Le Bouc, Y.; Deal, C. L.; Lillycrop, K.; Scharfmann, R.; Sheppard, A.; Skinner, M.; Szyf, M.; Waterland, R. A.; Waxman, D. J.; Whitelaw, E.; Ong, K.; Albertsson-Wikland, K.

    2011-01-01

    Plasticity in developmental programming has evolved in order to provide the best chances of survival and reproductive success to the organism under changing environments. Environmental conditions that are experienced in early life can profoundly influence human biology and long-term health. Developmental origins of health and disease and life-history transitions are purported to use placental, nutritional, and endocrine cues for setting long-term biological, mental, and behavioral strategies in response to local ecological and/or social conditions. The window of developmental plasticity extends from preconception to early childhood and involves epigenetic responses to environmental changes, which exert their effects during life-history phase transitions. These epigenetic responses influence development, cell- and tissue-specific gene expression, and sexual dimorphism, and, in exceptional cases, could be transmitted transgenerationally. Translational epigenetic research in child health is a reiterative process that ranges from research in the basic sciences, preclinical research, and pediatric clinical research. Identifying the epigenetic consequences of fetal programming creates potential applications in clinical practice: the development of epigenetic biomarkers for early diagnosis of disease, the ability to identify susceptible individuals at risk for adult diseases, and the development of novel preventive and curative measures that are based on diet and/or novel epigenetic drugs. PMID:20971919

  16. Alpha7 nicotinic acetylcholine receptors targeted by cholinergic developmental neurotoxicants: nicotine and chlorpyrifos.

    PubMed

    Slotkin, Theodore A; Southard, Matthew C; Adam, Stacey J; Cousins, Mandy M; Seidler, Frederic J

    2004-09-30

    Alpha7 nicotinic acetylcholine receptors (nAChRs) play a role in axonogenesis, synaptogenesis and synaptic plasticity, and are therefore potential targets for developmental neurotoxicants. We administered nicotine to neonatal rats during discrete periods spanning the onset and peak of axonogenesis/synaptogenesis, focusing on three brain regions with disparate distributions of cell bodies and neural projections: brainstem, forebrain and cerebellum. Nicotine treatment on postnatal days (PN) 1-4 had little or no effect on alpha7 nAChRs but treatment during the second (PN11-14) or third (PN21-24) weeks elicited significant decrements in receptor expression in brainstem and cerebellum, regions containing cell bodies that project to the forebrain. Exposure to chlorpyrifos, a neurotoxicant pesticide that acts partially through cholinergic mechanisms, also elicited deficits in alpha7 nAChRs during the second postnatal week but not the first week. For both nicotine and chlorpyrifos, the effects on alpha7 nAChRs were distinct from those on the alpha4beta2 subtype. Continuous prenatal nicotine exposure, which elicits subsequent, postnatal deficits in axonogenesis and synaptogenesis, also produced delayed-onset changes in alpha7 nAChRs, characterized by reductions in the forebrain and upregulation in the brainstem and cerebellum, a pattern consistent with impaired axonogenesis/synaptogenesis and reactive sprouting. Males were more sensitive to the persistent effects of prenatal nicotine exposure on alpha7 nAChRs, a pattern that mimics neurobehavioral deficits resulting from this treatment. The present findings reinforce the mechanistic involvement of alpha7 nAChRs in the actions of developmental neurotoxicants, and its biomarker potential for neuroteratogens that target neuritic outgrowth.

  17. 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.

  18. An integrated model of academic self-concept development: Academic self-concept, grades, test scores, and tracking over 6 years.

    PubMed

    Marsh, Herbert W; Pekrun, Reinhard; Murayama, Kou; Arens, A Katrin; Parker, Philip D; Guo, Jiesi; Dicke, Theresa

    2018-02-01

    Our newly proposed integrated academic self-concept model integrates 3 major theories of academic self-concept formation and developmental perspectives into a unified conceptual and methodological framework. Relations among math self-concept (MSC), school grades, test scores, and school-level contextual effects over 6 years, from the end of primary school through the first 5 years of secondary school (a representative sample of 3,370 German students, 42 secondary schools, 50% male, M age at grade 5 = 11.75) support the (1) internal/external frame of reference model: Math school grades had positive effects on MSC, but the effects of German grades were negative; (2) reciprocal effects (longitudinal panel) model: MSC was predictive of and predicted by math test scores and school grades; (3) big-fish-little-pond effect: The effects on MSC were negative for school-average achievement based on 4 indicators (primary school grades in math and German, school-track prior to the start of secondary school, math test scores in the first year of secondary school). Results for all 3 theoretical models were consistent across the 5 secondary school years: This supports the prediction of developmental equilibrium. This integration highlights the robustness of support over the potentially volatile early to middle adolescent period; the interconnectedness and complementarity of 3 ASC models; their counterbalancing strengths and weaknesses; and new theoretical, developmental, and substantive implications at their intersections. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  19. Developmental effects of antiepileptic drugs and the need for improved regulations

    PubMed Central

    Loring, David W.

    2016-01-01

    Antiepileptic drugs (AEDs) are among the most common teratogenic drugs prescribed to women of childbearing age. AEDs can induce both anatomical (malformations) and behavioral (cognitive/behavioral deficits) teratogenicity. Only in the last decade have we begun to truly discriminate differential AED developmental effects. Fetal valproate exposure carries a special risk for both anatomical and behavioral teratogenic abnormalities, but the mechanisms and reasons for individual variability are unknown. Intermediate anatomical risks exist for phenobarbital and topiramate. Several AEDs (e.g., lamotrigine and levetiracetam) appear to possess low risks for both anatomical and behavioral teratogenesis. Despite advances in the past decade, our knowledge of the teratogenic risks for most AEDs and the underlying mechanisms remain inadequate. Further, the long-term effects of AEDs in neonates and older children remain uncertain. The pace of progress is slow given the lifelong consequences of diminished developmental outcomes, exposing children unnecessarily to potential adverse effects. It is imperative that new approaches be employed to determine risks more expediently. Our recommendations include a national reporting system for congenital malformations, federal funding of the North American AED Pregnancy Registry, routine meta-analyses of cohort studies to detect teratogenic signals, monitoring of AED prescription practices for women, routine preclinical testing of all new AEDs for neurodevelopmental effects, more specific Food and Drug Administration requirements to establish differential AED cognitive effects in children, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms for AED-induced anatomical and behavioral teratogenesis. PMID:26519545

  20. Developmental Effects and Estrogenicity of Bisphenol A Alternatives in a Zebrafish Embryo Model.

    PubMed

    Mu, Xiyan; Huang, Ying; Li, Xuxing; Lei, Yunlei; Teng, Miaomiao; Li, Xuefeng; Wang, Chengju; Li, Yingren

    2018-03-06

    In order to understand the negative effects of bisphenol A (BPA) alternatives comprehensively, zebrafish embryos were used to assess the lethality, developmental effects, and estrogenic activity of bisphenol analogues. The in silico estrogenic activities of bisphenol analogues were assayed by binding simulation. According to our results, the lethality of bisphenol analogues decreased in order of bisphenol AF (BPAF) > BPA > bisphenol F (BPF) > bisphenol S (BPS). BPAF and BPF induced significant effects on zebrafish embryos, including decreased heart rate, hatching inhibition, and teratogenic effects. The binding potentials of bisphenol analogues toward zebrafish ERs (zfERS) decreased in the following order: BPAF > BPA > BPF > BPS. Among the three subtypes of zfERs, zfERβ2 showed the highest binding activity toward the bisphenols, followed by zfERα and zfERβ1. In vivo estrogenic activity tests showed that BPAF, BPA, and BPF significantly enhanced the protein levels of ERα along with the mRNA levels of esr1, esr2a, esr2b, and vtg1 in zebrafish embryos. Esr2b showed the strongest response to BPAF and BPA exposure among the three esrs. In contrast, BPS did not significantly regulate ER protein level or ER transcription. In conclusion, BPAF showed the highest lethality, developmental effects, and estrogenic activity (both in silico and in vivo) followed by BPA and BPF. BPS showed the weakest toxicity and estrogenic activity. zfERβ2 might act as the main target among the three ER subtypes of zebrafish after exposure to BPAF and BPA.

  1. Play and the older child: developmental and clinical opportunities.

    PubMed

    Meersand, Pamela

    2009-01-01

    This paper examines the meaning and function of pretend play in older children. First, a review of the widely accepted developmental sequences, growth-promoting potential, and analytic uses of play for younger children is provided. Then the possible role for play in later childhood is explored through the presentation of Sarah, a twelve-year-old girl in analysis, whose play appeared to provide both clinical and developmental benefits. The suggestion is made to soften the existing developmental line for play in order to allow for its role with preadolescent children.

  2. Developmental programming of energy balance regulation: is physical activity more 'programmable' than food intake?

    PubMed

    Zhu, Shaoyu; Eclarinal, Jesse; Baker, Maria S; Li, Ge; Waterland, Robert A

    2016-02-01

    Extensive human and animal model data show that environmental influences during critical periods of prenatal and early postnatal development can cause persistent alterations in energy balance regulation. Although a potentially important factor in the worldwide obesity epidemic, the fundamental mechanisms underlying such developmental programming of energy balance are poorly understood, limiting our ability to intervene. Most studies of developmental programming of energy balance have focused on persistent alterations in the regulation of energy intake; energy expenditure has been relatively underemphasised. In particular, very few studies have evaluated developmental programming of physical activity. The aim of this review is to summarise recent evidence that early environment may have a profound impact on establishment of individual propensity for physical activity. Recently, we characterised two different mouse models of developmental programming of obesity; one models fetal growth restriction followed by catch-up growth, and the other models early postnatal overnutrition. In both studies, we observed alterations in body-weight regulation that persisted to adulthood, but no group differences in food intake. Rather, in both cases, programming of energy balance appeared to be due to persistent alterations in energy expenditure and spontaneous physical activity (SPA). These effects were stronger in female offspring. We are currently exploring the hypothesis that developmental programming of SPA occurs via induced sex-specific alterations in epigenetic regulation in the hypothalamus and other regions of the central nervous system. We will summarise the current progress towards testing this hypothesis. Early environmental influences on establishment of physical activity are likely an important factor in developmental programming of energy balance. Understanding the fundamental underlying mechanisms in appropriate animal models will help determine whether early life interventions may be a practical approach to promote physical activity in man.

  3. TOWARDS REFINED USE OF TOXICITY DATA IN STATISTICALLY BASED SAR MODELS FOR DEVELOPMENTAL TOXICITY.

    EPA Science Inventory

    In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

  4. Predictive Modeling of Developmental Toxicity

    EPA Science Inventory

    The use of alternative methods in conjunction with traditional in vivo developmental toxicity testing has the potential to (1) reduce cost and increase throughput of testing the chemical universe, (2) prioritize chemicals for further targeted toxicity testing and risk assessment,...

  5. AGCVIII Kinases: at the crossroads of cellular signaling

    USDA-ARS?s Scientific Manuscript database

    AGCVIII kinases regulate diverse developmental and cellular processes in plants. As putative mediators of secondary messengers, AGCVIII kinases potentially integrate developmental and environmental cues into specific cellular responses through substrate phosphorylation. Here we discuss the functiona...

  6. Lifelong disturbance of serotonin transporter functioning results in fear learning deficits: Reversal by blockade of CRF1 receptors.

    PubMed

    Bijlsma, Elisabeth Y; Hendriksen, Hendrikus; Baas, Johanna M P; Millan, Mark J; Groenink, Lucianne

    2015-10-01

    The inability to associate aversive events with relevant cues (i.e. fear learning) may lead to maladaptive anxiety. To further study the role of the serotonin transporter (SERT) in fear learning, classical fear conditioning was studied in SERT knockout rats (SERT(-/-)) using fear potentiation of the startle reflex. Next, fear acquisition and concomitant development of contextual conditioned fear were monitored during training. To differentiate between developmental and direct effects of reduced SERT functioning, effects of acute and chronic SSRI treatment were studied in adult rats. Considering the known interactions between serotonin and corticotropin-releasing factor (CRF), we studied the effect of the CRFR1 antagonist CP154,526 on behavioral changes observed and determined CRF1 receptor levels in SERT(-/-) rats. SERT(-/-) showed blunted fear potentiation and enhanced contextual fear, which resulted from a deficit in fear acquisition. Paroxetine treatment did not affect acquisition or expression of fear-potentiated startle, suggesting that disturbed fear learning in SERT(-/-) results from developmental changes and not from reduced SERT functioning. Although CRF1 receptor levels did not differ significantly between genotypes, CP154,526 treatment normalized both cue- and contextual fear in SERT(-/-) during acquisition, but not expression of fear-potentiated startle. The disrupted fear acquisition and concomitant increase in contextual conditioned fear-potentiated startle fear in SERT(-/-) resembles the associative learning deficit seen in patients with panic disorder and suggests that normal SERT functioning is crucial for the development of an adequate fear neuro-circuitry. Moreover, the normalization of fear acquisition by CP154,526 suggests a role for central CRF signaling in the generalization of fear. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  7. The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy.

    PubMed

    Villaluz, Mel Michel; Lomax, Lysa Boissé; Jadhav, Trupti; Cross, J Helen; Scheffer, Ingrid E

    2018-07-01

    Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1 month, 3 months, 6 months, 1 year, and 2 years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3 months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology. © 2018 Mac Keith Press.

  8. Characterization of a complex chromosomal rearrangement using chromosome, FISH, and microarray assays in a girl with multiple congenital abnormalities and developmental delay

    PubMed Central

    2014-01-01

    Complex chromosomal rearrangements (CCRs) are balanced or unbalanced structural rearrangements involving three or more cytogenetic breakpoints on two or more chromosomal pairs. The phenotypic anomalies in such cases are attributed to gene disruption, superimposed cryptic imbalances in the genome, and/or position effects. We report a 14-year-old girl who presented with multiple congenital anomalies and developmental delay. Chromosome and FISH analysis indicated a highly complex chromosomal rearrangement involving three chromosomes (3, 7 and 12), seven breakpoints as a result of one inversion, two insertions, and two translocations forming three derivative chromosomes. Additionally, chromosomal microarray study (CMA) revealed two submicroscopic deletions at 3p12.3 (467 kb) and 12q13.12 (442 kb). We postulate that microdeletion within the ROBO1 gene at 3p12.3 may have played a role in the patient’s developmental delay, since it has potential activity-dependent role in neurons. Additionally, factors other than genomic deletions such as loss of function or position effects may also contribute to the abnormal phenotype in our patient. PMID:25478007

  9. Optical Coherence Tomography for Brain Imaging and Developmental Biology

    PubMed Central

    Men, Jing; Huang, Yongyang; Solanki, Jitendra; Zeng, Xianxu; Alex, Aneesh; Jerwick, Jason; Zhang, Zhan; Tanzi, Rudolph E.; Li, Airong; Zhou, Chao

    2016-01-01

    Optical coherence tomography (OCT) is a promising research tool for brain imaging and developmental biology. Serving as a three-dimensional optical biopsy technique, OCT provides volumetric reconstruction of brain tissues and embryonic structures with micrometer resolution and video rate imaging speed. Functional OCT enables label-free monitoring of hemodynamic and metabolic changes in the brain in vitro and in vivo in animal models. Due to its non-invasiveness nature, OCT enables longitudinal imaging of developing specimens in vivo without potential damage from surgical operation, tissue fixation and processing, and staining with exogenous contrast agents. In this paper, various OCT applications in brain imaging and developmental biology are reviewed, with a particular focus on imaging heart development. In addition, we report findings on the effects of a circadian gene (Clock) and high-fat-diet on heart development in Drosophila melanogaster. These findings contribute to our understanding of the fundamental mechanisms connecting circadian genes and obesity to heart development and cardiac diseases. PMID:27721647

  10. Developmental origins of epigenetic transgenerational inheritance

    PubMed Central

    Hanson, Mark A.; Skinner, Michael K.

    2016-01-01

    Abstract Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective. PMID:27390622

  11. Hearing-Impaired/Developmentally Disabled Persons in the United States: Definitions, Causes, Effects, and Prevalence Estimates

    ERIC Educational Resources Information Center

    Stewart, Larry G.

    1978-01-01

    Information is presented on the definition, causes, effects and population estimates for developmental disabilities; and a tentative hypothesis regarding the hearing impaired/developmentally disabled is set forth. (CL)

  12. 77 FR 48995 - Draft National Toxicology Program (NTP) Monograph on Developmental Effects and Pregnancy Outcomes...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... Program (NTP) Monograph on Developmental Effects and Pregnancy Outcomes Associated With Cancer Chemotherapy Use During Pregnancy; Request for Comments; Peer Review Panel Meeting AGENCY: Division of the... Monograph on Developmental Effects and Pregnancy Outcomes Associated with Cancer Chemotherapy Use during...

  13. Infant developmental milestones and adult intelligence: A 34-year follow-up.

    PubMed

    Flensborg-Madsen, Trine; Mortensen, Erik Lykke

    2015-07-01

    A number of studies suggest a positive association between faster infant motor development and intellectual function in childhood and adolescence. However, studies investigating the relationship between infant motor development and intelligence in adulthood are lacking. To investigate whether age at achievement of 12 motor developmental milestones was associated with adult intelligence and to evaluate the influence of sex, parental social status, parity, mother's cigarette consumption in the last trimester, gestational age, birthweight, and birth length on this association. Mothers of 9125 children of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the child's first year of life. A subsample of the cohort comprising 1155 individuals participated in a follow-up when they were aged 20-34 years and were administered the Wechsler Adult Intelligence Scale (WAIS). Associations between motor developmental milestones and IQ were analysed by multiple linear regression adjusting for potential confounding factors. Later acquisition of infant developmental milestones was associated with lower subsequent IQ, and the majority of significant associations were found for Performance IQ. Correlations were generally small (r < 0.10), but significant interactions were found between parental social status and age of attaining developmental milestones, with associations being significantly stronger in the offspring of lower social status parents. The effects remained significant after adjusting for possible confounding factors. This is the first study to find significant interactions with parental social status, thereby suggesting that associations between early motor development and intelligence are stronger in infants of low social status parents. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Reprogramming: A Preventive Strategy in Hypertension Focusing on the Kidney

    PubMed Central

    Tain, You-Lin; Joles, Jaap A.

    2015-01-01

    Adulthood hypertension can be programmed in response to a suboptimal environment in early life. However, developmental plasticity also implies that one can prevent hypertension in adult life by administrating appropriate compounds during early development. We have termed this reprogramming. While the risk of hypertension has been assessed in many mother-child cohorts of human developmental programming, interventions necessary to prove causation and provide a reprogramming strategy are lacking. Since the developing kidney is particularly vulnerable to environmental insults and blood pressure is determined by kidney function, renal programming is considered key in developmental programming of hypertension. Common pathways, whereby both genetic and acquired developmental programming converge into the same phenotype, have been recognized. For instance, the same reprogramming interventions aimed at shifting nitric oxide (NO)-reactive oxygen species (ROS) balance, such as perinatal citrulline or melatonin supplements, can be protective in both genetic and developmentally programmed hypertension. Furthermore, a significantly increased expression of gene Ephx2 (soluble epoxide hydrolase) was noted in both genetic and acquired animal models of hypertension. Since a suboptimal environment is often multifactorial, such common reprogramming pathways are a practical finding for translation to the clinic. This review provides an overview of potential clinical applications of reprogramming strategies to prevent programmed hypertension. We emphasize the kidney in the following areas: mechanistic insights from human studies and animal models to interpret programmed hypertension; identified risk factors of human programmed hypertension from mother-child cohorts; and the impact of reprogramming strategies on programmed hypertension from animal models. It is critical that the observed effects on developmental reprogramming in animal models are replicated in human studies. PMID:26712746

  15. Training the Brain: Practical Applications of Neural Plasticity From the Intersection of Cognitive Neuroscience, Developmental Psychology, and Prevention Science

    PubMed Central

    Bryck, Richard L.; Fisher, Philip A.

    2012-01-01

    Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this paper, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. PMID:21787037

  16. Training the brain: practical applications of neural plasticity from the intersection of cognitive neuroscience, developmental psychology, and prevention science.

    PubMed

    Bryck, Richard L; Fisher, Philip A

    2012-01-01

    Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this article, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  17. Calmodulin point mutations affect Drosophila development and behavior.

    PubMed

    Nelson, H B; Heiman, R G; Bolduc, C; Kovalick, G E; Whitley, P; Stern, M; Beckingham, K

    1997-12-01

    Calmodulin (CAM) is recognized as a major intermediary in intracellular calcium signaling, but as yet little is known of its role in developmental and behavioral processes. We have generated and studied mutations to the endogenous Cam gene of Drosophila melanogaster that change single amino acids within the protein coding region. One of these mutations produces a striking pupal lethal phenotype involving failure of head eversion. Various mutant combinations produce specific patterns of ectopic wing vein formation or melanotic scabs on the cuticle. Anaphase chromosome bridging is also seen as a maternal effect during the early embryonic nuclear divisions. In addition, specific behavioral defects such as poor climbing and flightlessness are detected among these mutants. Comparisons with other Drosophila mutant phenotypes suggests potential CAM targets that may mediate these developmental and behavioral effects, and analysis of the CAM crystal structure suggests the structural consequences of the individual mutations.

  18. Calmodulin Point Mutations Affect Drosophila Development and Behavior

    PubMed Central

    Nelson, H. B.; Heiman, R. G.; Bolduc, C.; Kovalick, G. E.; Whitley, P.; Stern, M.; Beckingham, K.

    1997-01-01

    Calmodulin (CAM) is recognized as a major intermediary in intracellular calcium signaling, but as yet little is known of its role in developmental and behavioral processes. We have generated and studied mutations to the endogenous Cam gene of Drosophila melanogaster that change single amino acids within the protein coding region. One of these mutations produces a striking pupal lethal phenotype involving failure of head eversion. Various mutant combinations produce specific patterns of ectopic wing vein formation or melanotic scabs on the cuticle. Anaphase chromosome bridging is also seen as a maternal effect during the early embryonic nuclear divisions. In addition, specific behavioral defects such as poor climbing and flightlessness are detected among these mutants. Comparisons with other Drosophila mutant phenotypes suggests potential CAM targets that may mediate these developmental and behavioral effects, and analysis of the CAM crystal structure suggests the structural consequences of the individual mutations. PMID:9409836

  19. Refining the application of direct embryogenesis in sugarcane: Effect of the developmental phase of leaf disc explants and the timing of DNA transfer on transformation efficiency.

    PubMed

    Snyman, S J; Meyer, G M; Richards, J M; Haricharan, N; Ramgareeb, S; Huckett, B I

    2006-10-01

    A rapid in vitro protocol using direct somatic embryogenesis and microprojectile bombardment was investigated to establish the developmental phases most suitable for efficient sugarcane transformation. Immature leaf roll disc explants with and without pre-emergent inflorescence tissue were compared. It was shown that for effective transformation to occur, explants should be cultured for several days to allow initiation of embryo development prior to bombardment. Leaf roll discs with pre-emergent inflorescences showed a higher degree of embryogenic competence than non-flowering explants, and transformation efficiency was higher when explants containing floral initials were bombarded. Despite the occurrence of high numbers of phenotypically negative plants, combining the use of inflorescent leaf roll discs with direct embryogenic regeneration has the potential to improve the speed and efficiency of transgenesis in sugarcane.

  20. NTP-CERHR monograph on the potential human reproductive and developmental effects of hydroxyurea.

    PubMed

    2008-10-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for hydroxyurea to cause adverse effects on reproduction and development in humans. Hydroxyurea is a drug used to treat cancer, sickle cell disease, and thalassemia. It is the only treatment for sickle cell disease in children, aside from blood transfusion and, in severe cases, hematopoietic stem cell transplantation. Hydroxyurea is FDA-approved for use in adults with sickle cell anemia to reduce the frequency of painful crises and the need for blood transfusions. Hydroxyurea may be given to children and adults with sickle cell disease for an extended period of time or for repeated cycles of therapy. Treatment with hydroxyurea is associated with known side effects such as cytotoxicity and myelosuppression, and hydroxyurea is genotoxic (can damage DNA). CERHR selected hydroxyurea for evaluation because of: its increasing use for treatment of sickle cell disease in children and adults, knowledge that it inhibits DNA synthesis and is cytotoxic, and published evidence of reproductive and developmental toxicity in rodents. The results of this evaluation are published in the NTP-CERHR Monograph on Hydroxyurea, which includes the NTP Brief and Expert Panel Report on the Reproductive and Developmental Toxicity of Hydroxyurea. Additional information related to the evaluation process, including public comments received on the draft NTP Brief and the final expert panel report, are available on the CERHR website (http:// cerhr.niehs.nih.gov/). See hydroxyurea under "CERHR Chemicals" on the homepage or go directly to http://cerhr.niehs.nih.gov/chemicals/hydroxyurea/hydroxyurea-eval.html). The NTP reached the following conclusions on the possible effects of exposure to hydroxyurea on human reproduction or development. The possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. The NTP expresses serious concern that exposure of men to therapeutic doses of hydroxyurea may adversely affect sperm production. This level of concern is for all males who have reached puberty. The NTP concurs with the Expert Panel that there is concern that exposure of pregnant women to hydroxyurea may result in birth defects, abnormalities of fetal growth, or abnormal postnatal development in offspring. The NTP concurs with the Expert Panel that there is minimal concern that exposure of children to therapeutic doses of hydroxyurea at 5 -15 years of age will adversely affect growth. NTP will transmit the NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Hydroxyurea to federal and state agencies, interested parties, and the public and make it available in electronic PDF format on the CERHR web site (http://cerhr niehs nih gov) and in printed text or CD from CERHR.

  1. Effects of Ordinary and Adaptive Toys on Pre-School Children with Developmental Disabilities

    ERIC Educational Resources Information Center

    Hsieh, Hsieh-Chun

    2008-01-01

    Toys help children in mastering developmental tasks. This study investigated toy effect on children with developmental disabilities as they engage in using ordinary and adaptive toys. A single-subject design was used to identify the effects on their toy play abilities. Differences in toy effects between playing ordinary and adaptive toys were…

  2. Abnormal electroretinogram associated with developmental brain anomalies.

    PubMed Central

    Cibis, G W; Fitzgerald, K M

    1995-01-01

    PURPOSE: We have encountered abnormal ERGs associated with optic nerve hypoplasia, macular, optic nerve and chorioretinal colobomata and developmental brain anomalies. Brain anomalies include cortical dysgenesis, lissencephaly, porencephaly, cerebellar and corpus callosum hypoplasia. We describe six exemplar cases. METHODS: Scotopic and photopic ERGs adherent to international standards were performed as well as photopic ERGs to long-duration stimuli. CT or MRI studies were also done. The ERGs were compared to age-matched normal control subjects. RESULTS: ERG changes include reduced amplitude b-waves to blue and red stimuli under scotopic testing conditions. Implicit times were often delayed. The photopic responses also showed reduced amplitude a- and b-waves with implicit time delays. The long-duration photopic ERG done in one case shows attenuation of both ON- and OFF-responses. CONCLUSIONS: Common underlying developmental genetic or environmental unifying casualties are speculated to be at fault in causing these cases of associated retinal and brain abnormalities. No single etiology is expected. Multiple potential causes acting early in embryogenesis effecting neuronal induction, migration and differentiation are theorized. These occur at a time when brain and retinal cells are sufficiently undifferentiated to be similarly effected. We call these cases examples of Brain Retina Neuroembryodysgenesis (BRNED). Homeobox and PAX genes with global neuronal developmental influences are gene candidates to unify the observed disruption of brain and retinal cell development. The ERG can provide a valuable clinical addition in understanding and ultimately classifying these disorders. Images FIGURE 1 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 PMID:8719676

  3. 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.

  4. DEVELOPMENTAL HYPOTHYROIDISM ALTERS SYNAPTIC TRANSMISSION IN DENTATE GYRUS AND AREA CA1 OF HIPPOCAMPUS.

    EPA Science Inventory

    Hypothyroidism during critical periods of brain developmental leads to learning deficits and alterations in hippocampal structure. Neurophysiological properties of the hippocampus, however, have not been well characterized. The present study examined field potentials evoked in...

  5. DEVELOPMENT AND EVALUATION OF IN VITRO IMAGING TECHNIQUES USED TO SCREEN AGENTS THAT AFFECT NEURONAL DIFFERENTIATION.

    EPA Science Inventory

    Testing chemicals for potential developmental neurotoxicity is an issue of regulatory concern. Developmental vulnerability is determined by pharmacokinetic and pharmacodynamic differences between developing and adult animals. These pharmacokinetic and pharmacodynamic factors dete...

  6. A systematic evaluation of the potential effects of trichloroethylene exposure on cardiac development.

    PubMed

    Makris, Susan L; Scott, Cheryl Siegel; Fox, John; Knudsen, Thomas B; Hotchkiss, Andrew K; Arzuaga, Xabier; Euling, Susan Y; Powers, Christina M; Jinot, Jennifer; Hogan, Karen A; Abbott, Barbara D; Hunter, E Sidney; Narotsky, Michael G

    2016-10-01

    The 2011 EPA trichloroethylene (TCE) IRIS assessment, used developmental cardiac defects from a controversial drinking water study in rats (Johnson et al. [51]), along with several other studies/endpoints to derive reference values. An updated literature search of TCE-related developmental cardiac defects was conducted. Study quality, strengths, and limitations were assessed. A putative adverse outcome pathway (AOP) construct was developed to explore key events for the most commonly observed cardiac dysmorphologies, particularly those involved with epithelial-mesenchymal transition (EMT) of endothelial origin (EndMT); several candidate pathways were identified. A hypothesis-driven weight-of-evidence analysis of epidemiological, toxicological, in vitro, in ovo, and mechanistic/AOP data concluded that TCE has the potential to cause cardiac defects in humans when exposure occurs at sufficient doses during a sensitive window of fetal development. The study by Johnson et al. [51] was reaffirmed as suitable for hazard characterization and reference value derivation, though acknowledging study limitations and uncertainties. Published by Elsevier Inc.

  7. Action potential broadening in a presynaptic channelopathy

    NASA Astrophysics Data System (ADS)

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

    2016-07-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.

  8. Effect of mercury and cadmium on early life stages of Java medaka (Oryzias javanicus): a potential tropical test fish.

    PubMed

    Ismail, Ahmad; Yusof, Shahrizad

    2011-01-01

    Several organisms have been used as indicators, bio-monitoring agents or test organisms in ecotoxicological studies. A close relative of the well established Japanese medaka, the Java medaka (Oryzias javanicus), has the potential to be a test organism. The fish is native to the estuaries of the Malaysian Peninsula, Thailand, Indonesia and Singapore. In this study, newly fertilised eggs were exposed to different concentrations of Cd and Hg. Observations were done on the development of the embryos. Exposure to low levels of Cd and Hg (0.01-0.05 ppm) resulted in several developmental disorders that led to death. Exposure to ≥1.0 ppm Cd resulted in immediate developmental arrest. The embryos of Java medaka showed tolerance to a certain extent when exposed to ≥1.0 ppm Hg compared to Cd. Based on the sensitivity of the embryos, Java medaka is a suitable test organism for ecotoxicology in the tropical region. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Children's concepts of physical illness: a review and critique of the cognitive-developmental literature.

    PubMed

    Burbach, D J; Peterson, L

    1986-01-01

    Cognitive-developmental studies relevant to children's concepts of physical illness are reviewed and critiqued. Although numerous methodological weaknesses make firm conclusions difficult, most data appear to suggest that children's concepts of illness do evolve in a systematic and predictable sequence consistent with Piaget's theory of cognitive development. Methodological weaknesses identified include poor description of samples, assessment instruments, and procedures; lack of control over potential observer bias, expectancy effects, and other confounding variables; and minimal attention to reliability and validity issues. Increased methodological rigor and a further explication of the specific and unique ways in which children's concepts of illness develop over the course of cognitive development could substantially increase the value of these studies for professionals in pediatric health care settings.

  10. The two fold role of oxytocin in social developmental disorders: A cause and a remedy?

    PubMed

    Lefevre, Arthur; Sirigu, Angela

    2016-04-01

    Oxytocin is widely used by obstetricians to induce or facilitate labor. The long lasting consequences of oxytocin administration remain however unknown. Here, we discuss recent evidence suggesting a link between oxytocin labor induction and developmental social impairments such as autism spectrum disorders (ASD). Because these associations are methodologically questionable, we provide a review of animal studies investigating the long term effects of neonatal injection of oxytocin to shed light on the biological mechanisms that mediate the contribution of early oxytocin supplementation on the development of social impairments. In contrast to this potential negative impact on development, oxytocin has been shown to ameliorate social skills of ASD patients. However, results of chronic oxytocin administration from animal experiments are contradictory. We also review recent studies looking at chronic oxytocin effects in animal and in humans. Obstetric and psychiatric uses of exogenous oxytocin both impact on oxytocinergic neurotransmission but the effects may be sharply dissimilar. Copyright © 2016. Published by Elsevier Ltd.

  11. Developmental programming: Interaction between prenatal BPA and postnatal overfeeding on cardiac tissue gene expression in female sheep.

    PubMed

    Koneva, L A; Vyas, A K; McEachin, R C; Puttabyatappa, M; Wang, H-S; Sartor, M A; Padmanabhan, V

    2017-01-01

    Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known. mRNA-seq of myocardium was performed on four groups of four female sheep to assess the effects of prenatal BPA exposure, postnatal overfeeding and their interaction on gene transcription, pathway perturbations and functional effects. The effects of prenatal exposure to BPA, postnatal overfeeding, and prenatal BPA with postnatal overfeeding all resulted in transcriptional changes (85-141 significant differentially expressed genes). Although the effects of prenatal BPA and postnatal overfeeding did not involve dysregulation of many of the same genes, they affected a remarkably similar set of biological pathways. Furthermore, an additive or synergistic effect was not found in the combined treatment group, but rather prenatal BPA treatment led to a partial reversal of the effects of overfeeding alone. Many genes previously known to be affected by BPA and involved in obesity, hypertension, or heart disease were altered following these treatments, and AP-1, EGR1, and EGFR were key hubs affected by BPA and/or overfeeding. Environ. Mol. Mutagen. 58:4-18, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Understanding Race and Gender Differences in Delinquent Acts and Alcohol and Marijuana Use: A Developmental Analysis of Initiation

    ERIC Educational Resources Information Center

    Williams, James Herbert; Van Dorn, Richard A.; Ayers, Charles D.; Bright, Charlotte L.; Abbott, Robert D.; Hawkins, J. David

    2007-01-01

    Guided by social development constructs, this article investigates race and gender differences in the initiation of various types of delinquent behavior and alcohol and marijuana use among African American and Caucasian adolescents in grades 7 through 12. In addition, this study examined the potential direct or indirect effects of parental…

  13. 76 FR 51034 - Availability of Draft NTP Monograph on Potential Developmental Effects of Cancer Chemotherapy...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... Cancer Chemotherapy During Pregnancy (available at http://ntp.niehs.nih.gov/go/36639 ) that will be peer... the NTP Web site ( http://ntp.niehs.nih.gov/go/36639 ) or may be requested in hardcopy from the....gov/go/36639 ) by October 12, 2011, to facilitate access to the NIEHS campus. A photo ID is required...

  14. Adapting a Developmental Screening Measure: Exploring the Effects of Language and Culture on a Parent-Completed SocialEmotional Screening Test

    ERIC Educational Resources Information Center

    Chen, Chieh-Yu; Chen, Ching-I; Squires, Jane; Bian, Xiaoyan; Heo, Kay H.; Filgueiras, Alberto; Kalinina, Svetlana; Samarina, Larissa; Ermolaeva, Evgeniya; Xie, Huichao; Yu, Ting-Ying; Wu, Pei-Fang; Landeira-Fernandez, Jesus

    2017-01-01

    Ages & Stages Questionnaires: Social-Emotional (ASQ:SE) is a widely used screening instrument for detecting social-emotional difficulties in infants and young children. To use a screening instrument across cultures and countries, it is necessary to identify potential item-level biases and ensure item equivalence. This study investigated the…

  15. Current and future needs for developmental toxicity testing.

    PubMed

    Makris, Susan L; Kim, James H; Ellis, Amy; Faber, Willem; Harrouk, Wafa; Lewis, Joseph M; Paule, Merle G; Seed, Jennifer; Tassinari, Melissa; Tyl, Rochelle

    2011-10-01

    A review is presented of the use of developmental toxicity testing in the United States and international regulatory assessment of human health risks associated with exposures to pharmaceuticals (human and veterinary), chemicals (agricultural, industrial, and environmental), food additives, cosmetics, and consumer products. Developmental toxicology data are used for prioritization and screening of pharmaceuticals and chemicals, for evaluating and labeling of pharmaceuticals, and for characterizing hazards and risk of exposures to industrial and environmental chemicals. The in vivo study designs utilized in hazard characterization and dose-response assessment for developmental outcomes have not changed substantially over the past 30 years and have served the process well. Now there are opportunities to incorporate new technologies and approaches to testing into the existing assessment paradigm, or to apply innovative approaches to various aspects of risk assessment. Developmental toxicology testing can be enhanced by the refinement or replacement of traditional in vivo protocols, including through the use of in vitro assays, studies conducted in alternative nonmammalian species, the application of new technologies, and the use of in silico models. Potential benefits to the current regulatory process include the ability to screen large numbers of chemicals quickly, with the commitment of fewer resources than traditional toxicology studies, and to refine the risk assessment process through an enhanced understanding of the mechanisms of developmental toxicity and their relevance to potential human risk. As the testing paradigm evolves, the ability to use developmental toxicology data to meet diverse critical regulatory needs must be retained. © 2011 Wiley Periodicals, Inc.

  16. Effects of ordinary and adaptive toys on pre-school children with developmental disabilities.

    PubMed

    Hsieh, Hsieh-Chun

    2008-01-01

    Toys help children in mastering developmental tasks. This study investigated toy effect on children with developmental disabilities as they engage in using ordinary and adaptive toys. A single-subject design was used to identify the effects on their toy play abilities. Differences in toy effects between playing ordinary and adaptive toys were examined. Three special education teachers chose ordinary toys and modified ordinary toys. Modified ordinary toys, i.e., adaptive toys, were designed according to the individual disabilities of participating children, treatment goals, and the toy types. Three children with developmental disabilities from pre-schools in Taiwan were enrolled. Appropriate participation of three pre-schoolers increased dramatically in playing adaptive toys during intervention phase. The toy effects demonstrate that when using adaptive toys, children with developmental disabilities may response better during toy play sessions.

  17. Interpersonal Stress Regulation and the Development of Anxiety Disorders: An Attachment-Based Developmental Framework

    PubMed Central

    Nolte, Tobias; Guiney, Jo; Fonagy, Peter; Mayes, Linda C.; Luyten, Patrick

    2011-01-01

    Anxiety disorders represent a common but often debilitating form of psychopathology in both children and adults. While there is a growing understanding of the etiology and maintenance of these disorders across various research domains, only recently have integrative accounts been proposed. While classical attachment history has been a traditional core construct in psychological models of anxiety, contemporary attachment theory has the potential to integrate neurobiological and behavioral findings within a multidisciplinary developmental framework. The current paper proposes a modern attachment theory-based developmental model grounded in relevant literature from multiple disciplines including social neuroscience, genetics, neuroendocrinology, and the study of family factors involved in the development of anxiety disorders. Recent accounts of stress regulation have highlighted the interplay between stress, anxiety, and activation of the attachment system. This interplay directly affects the development of social–cognitive and mentalizing capacities that are acquired in the interpersonal context of early attachment relationships. Early attachment experiences are conceptualized as the key organizer of a complex interplay between genetic, environmental, and epigenetic contributions to the development of anxiety disorders – a multifactorial etiology resulting from dysfunctional co-regulation of fear and stress states. These risk-conferring processes are characterized by hyperactivation strategies in the face of anxiety. The cumulative allostatic load and subsequent “wear and tear” effects associated with hyperactivation strategies converge on the neural pathways of anxiety and stress. Attachment experiences further influence the development of anxiety as potential moderators of risk factors, differentially impacting on genetic vulnerability and relevant neurobiological pathways. Implications for further research and potential treatments are outlined. PMID:21960962

  18. Mobile social network services for families with children with developmental disabilities.

    PubMed

    Chou, Li-Der; Lai, Nien-Hwa; Chen, Yen-Wen; Chang, Yao-Jen; Yang, Jyun-Yan; Huang, Lien-Fu; Chiang, Wen-Ling; Chiu, Hung-Yi; Shin, Haw-Yun

    2011-07-01

    As Internet technologies evolve, their applications have changed various aspects of human life. Here, we attempt to examine their potential impact on services for families with developmentally delayed children. Our research is thus designed to utilize wireless mobile communication technologies, location services, and search technology in an effort to match families of specific needs with potential care providers. Based on the investigation conducted by our counselors, this paper describes a platform for smooth communication between professional communities and families with children with developmental disabilities (CDD). This research also looks into the impact of management of mobile social network services and training on the operation of these services. Interaction opportunities, care, and support to families with CDD are introduced.

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

    PubMed

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

    2017-05-01

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

  20. Effect of triiodothyronine on developmental competence of bovine oocytes.

    PubMed

    Costa, N N; Cordeiro, M S; Silva, T V G; Sastre, D; Santana, P P B; Sá, A L A; Sampaio, R V; Santos, S S D; Adona, P R; Miranda, M S; Ohashi, O M

    2013-09-01

    Developmental competence of in vitro-matured bovine oocytes is a limiting factor in production of embryos in vitro. Several studies have suggested a potential positive effect of thyroid hormones on cultured oocytes and/or their supporting cells. Therefore, the aim of the present study was to ascertain whether medium supplementation with triiodothyronine (T3) improved subsequent developmental competence of in vitro-matured bovine oocytes. For this purpose, we first documented (using reverse transcription PCR) that whereas bovine cumulus cells expressed both thyroid hormone receptor (TR)-α and TRβ, immature bovine oocytes expressed TRα only. Thereafter, to test the effects of TH on developmental competence, abattoir-derived oocytes were matured in vitro in a medium containing 0, 25, 50, or 100 nM T3 and subjected to in vitro fertilization. Embryo quality was evaluated by assessing cleavage and blastocyst rates, morphological quality, development kinetics, and total cell number on Day 8 of culture. Notably, addition of 50 or 100 nM T3 to the in vitro maturation medium increased (P < 0.05) the rate of hatched blastocysts on the eighth day of culture, as compared with other groups (62.4 ± 11.7, 53.1 ± 16.3, and 32.4 ± 5.3, respectively). Next, the relative expression levels of genes related to embryo quality POU-domain transcription factor (POU5F1) and glucose transporter-1 (GLUT 1) were compared between in vivo- and in vitro-produced blastocysts. On the basis of the previous experiments, IVP embryos originating from oocytes that were matured in vitro in the presence or absence of 50 nM T3 were evaluated. The treatment had no effect (P > 0.05) on gene expression. We concluded that supplementation of bovine oocyte in vitro maturation medium with T3 may have a beneficial effect on the kinetics of embryo development. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Amphibian metamorphosis as a model for studying endocrine disruption on vertebrate development: effect of bisphenol A on thyroid hormone action.

    PubMed

    Heimeier, Rachel A; Shi, Yun-Bo

    2010-09-01

    Thyroid hormone (TH) is essential for proper development in vertebrates. TH deficiency during gestation and early postnatal development produces severe neurological, skeletal, metabolism and growth abnormalities. It is therefore important to consider environmental chemicals that may interfere with TH signaling. Exposure to environmental contaminants that disrupt TH action may underlie the increasing incidence of human developmental disorders worldwide. One contaminant of concern is the xenoestrogen bisphenol A (BPA), a chemical widely used to manufacture polycarbonate plastics and epoxy resins. The difficulty in studying uterus-enclosed mammalian embryos has hampered the analysis on the direct effects of BPA during vertebrate development. As TH action at the cellular level is highly conserved across vertebrate species, amphibian metamorphosis serves as an important TH-dependent in vivo vertebrate model for studying potential contributions of BPA toward human developmental disorders. Using Xenopus laevis as a model, we and others have demonstrated the inhibitory effects of BPA exposure on metamorphosis. Genome-wide gene expression analysis revealed that surprisingly, BPA primarily targets the TH-signaling pathway essential for metamorphosis in Xenopus laevis. Given the importance of the genomic effects of TH during metamorphosis and the conservation in its regulation in higher vertebrates, these observations suggest that the effect of BPA in human embryogenesis is through the inhibition of the TH pathway and warrants further investigation. Our findings further argue for the critical need to use in vivo animal models coupled with systematic molecular analysis to determine the developmental effects of endocrine disrupting compounds. Published by Elsevier Inc.

  2. Chronic Intranasal Oxytocin Causes Long-term Impairments in Partner Preference Formation in Male Prairie Voles

    PubMed Central

    Bales, Karen L.; Perkeybile, Allison M.; Conley, Olivia G.; Lee, Meredith H.; Guoynes, Caleigh D.; Downing, Griffin M.; Yun, Catherine R.; Solomon, Marjorie; Jacob, Suma; Mendoza, Sally P.

    2012-01-01

    Background Oxytocin (OT) is a hormone shown to be involved in social bonding in animal models. Intranasal OT is currently in clinical trials for use in disorders such as autism and schizophrenia. We examined long-term effects of intranasal OT given developmentally in the prairie vole (Microtus ochrogaster), a socially monogamous rodent, often used as an animal model to screen drugs that have therapeutic potential for social disorders. Methods We treated voles with one of three dosages of intranasal OT, or saline, from day 21 (weaning) through day 42 (sexual maturity). We examined both social behavior immediately following administration, as well as long-term changes in social and anxiety behavior after treatment ceased. Group sizes varied from 8 to 15 voles (n = 89 voles total). Results Treatment with OT resulted in acute increases in social behavior in males with familiar partners, as seen in humans. However, long-term developmental treatment with low doses of intranasal OT resulted in a deficit in partner preference behavior (a reduction of contact with a familiar opposite-sex partner, used to index pair-bond formation) by males. Conclusions Long-term developmental treatment with OT may show results different to those predicted by short-term studies, as well as significant sex differences and dosage effects. Further animal study is crucial to determining safe and effective strategies for use of chronic intranasal OT, especially during development. PMID:23079235

  3. Comparison of glucose metabolism in in vivo- and in vitro-matured tammar wallaby oocytes and its relationship to developmental potential following intracytoplasmic sperm injection.

    PubMed

    Magarey, Genevieve M; Mate, Karen E

    2004-01-01

    Although marsupial oocytes undergo nuclear maturation in vitro, there is, at present, no indication of their developmental potential, largely owing to the lack of in vitro fertilisation and related technologies for marsupials. Glucose metabolism has proven a useful indicator of oocyte cytoplasmic maturation and developmental potential in several eutherian species. Therefore, the aims of the present study were to compare: (1) the rates of glycolysis and glucose oxidation in immature, in vitro-matured and in vivo-matured tammar wallaby oocytes; and (2) the metabolic rate of individual oocytes with their ability to form pronuclei after intracytoplasmic sperm injection. The rates of glycolysis measured in immature (2.18 pmol oocyte(-1) h(-1)), in vitro- matured (0.93 pmol oocyte(-1) h(-1)) and in vivo-matured tammar wallaby oocytes (0.54 pmol oocyte(-1) h(-1)) were within a similar range to values obtained in eutherian species. However, unlike the trend observed in eutherian oocytes, the glycolytic rate was significantly higher in immature oocytes compared with either in vivo- or in vitro-matured oocytes (P < 0.001) and significantly higher in in vitro-matured oocytes compared with in vivo-matured oocytes (P < 0.001). No relationship was identified between glucose metabolism and the developmental capacity of oocytes after intracytoplasmic sperm injection when assessed after 17-19 h. Oocytes that became fertilised (two pronuclei) or activated (one or more pronucleus) were not distinguished from others by their metabolic rates. Longer culture after intracytoplasmic sperm injection (e.g. blastocyst stage) may show oocyte glucose metabolism to be predictive of developmental potential; however, culture to the single-cell stage did not reveal any significant differences in normally developing embryos.

  4. Significant improvement of pig cloning efficiency by treatment with LBH589 after somatic cell nuclear transfer.

    PubMed

    Jin, Jun-Xue; Li, Suo; Gao, Qing-Shan; Hong, Yu; Jin, Long; Zhu, Hai-Ying; Yan, Chang-Guo; Kang, Jin-Dan; Yin, Xi-Jun

    2013-10-01

    The low success rate of animal cloning by somatic cell nuclear transfer (SCNT) associates with epigenetic aberrancy, including the abnormal acetylation of histones. Altering the epigenetic status by histone deacetylase inhibitors (HDACi) enhances the developmental potential of SCNT embryos. In the current study, we examined the effects of LBH589 (panobinostat), a novel broad-spectrum HDACi, on the nuclear reprogramming and development of pig SCNT embryos in vitro. In experiment 1, we compared the in vitro developmental competence of nuclear transfer embryos treated with different concentrations of LBH589. Embryos treated with 50 nM LBH589 for 24 hours showed a significant increase in the rate of blastocyst formation compared with the control or embryos treated with 5 or 500 nM LBH589 (32.4% vs. 11.8%, 12.1%, and 10.0%, respectively, P < 0.05). In experiment 2, we examined the in vitro developmental competence of nuclear transfer embryos treated with 50 nM LBH589 for various intervals after activation and 6-dimethylaminopurine. Embryos treated for 24 hours had higher rates of blastocyst formation than the other groups. In experiment 3, when the acetylation of H4K12 was examined in SCNT embryos treated for 6 hours with 50 nM LBH589 by immunohistochemistry, the staining intensities of these proteins in LBH589-treated SCNT embryos were significantly higher than in the control. In experiment 4, LBH589-treated nuclear transfer and control embryos were transferred into surrogate mothers, resulting in three (100%) and two (66.7%) pregnancies, respectively. In conclusion, LBH589 enhances the nuclear reprogramming and developmental potential of SCNT embryos by altering the epigenetic status and expression, and increasing blastocyst quality. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  5. Oral supplements of inulin during gestation offsets rotenone-induced oxidative impairments and neurotoxicity in maternal and prenatal rat brain.

    PubMed

    Krishna, Gokul; Muralidhara

    2018-05-25

    Environmental insults including pesticide exposure and their entry into the immature brain are of increased concern due to their developmental neurotoxicity. Several lines of evidence suggest that maternal gut microbiota influences in utero fetal development via modulation of host's microbial composition with prebiotics. Hence we examined the hypothesis if inulin (IN) supplements during pregnancy in rats possess the potential to alleviate brain oxidative response and mitochondrial deficits employing a developmental model of rotenone (ROT) neurotoxicity. Initially, pregnant Sprague-Dawley rats were gavaged during gestational days (GDs) 6-19 with 0 (control), 10 (low), 30 (mid) or 50 (high) mg/kg bw/day of ROT to recapitulate developmental effects on general fetotoxicity (assessed by the number of fetuses, fetal body and placental weights), markers of oxidative stress and cholinergic activities in maternal brain regions and whole fetal-brain. Secondly, dams orally supplemented with inulin (2×/day, 2 g/kg/bw) on GD 0-21 were administered ROT (50 mg/kg, GD 6-19). IN supplements increased maternal cecal bacterial numbers that significantly corresponded with improved exploratory-related behavior among ROT administered rats. In addition, IN supplements improved fetal and placental weight on GD 19. IN diminished gestational ROT-induced increased reactive oxygen species levels, protein and lipid peroxidation biomarkers, and cholinesterase activity in maternal brain regions (cortex, cerebellum, and striatum) and fetal brain. Moreover, in the maternal cortex, mitochondrial assessment revealed IN protected against ROT-induced reduction in NADH cytochrome c oxidoreductase and ATPase activities. These data suggest a potential role for indigestible oligosaccharides in reducing oxidative stress-mediated developmental origins of neurodegenerative disorders. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  6. Maturation experiments reveal bias in the fossil record of feathers

    NASA Astrophysics Data System (ADS)

    McNamara, Maria; Field, Daniel

    2016-04-01

    The evolutionary history of birds and feathers is a major focus in palaeobiology and evolutionary biology. Diverse exceptionally preserved birds and feathered dinosaurs from Jurassic and Cretaceous biotas in China have provided pivotal evidence of early feathers and feather-like integumentary features, but the true nature of many of these fossil soft tissues is still debated. Interpretations of feathers at intermediate developmental stages (i.e. Stages II, III and IV) and of simple quill-like (Stage I) feathers are particularly controversial. This reflects key uncertainties relating to the preservation potential of feathers at different evolutionary-developmental stages, and to the relative preservation potential of diagnostic features of Stage I feathers and hair. To resolve these issues, we used high pressure-high temperature autoclave experiments to simulate the effects of burial on modern feathers from the Black Coucal (Centropus grilii) and Common Starling (Sturnus vulgaris), and on human hair. Our results reveal profound differences in the recalcitrance of feathers of different types during maturation: Stage I and Stage V feathers retain diagnostic morphological and ultrastructural details following maturation, whereas other feather types do not. Further, the morphology and arrangement of certain ultrastructural features diagnostic of Stages III and IV, e.g. barbules, are preferentially lost during maturation. These results indicate a pervasive bias in the fossil record of feathers, whereby preservation of feathers at Stages I and V is favored. Critical stages in the evolution of feathers, i.e. Stages II, III and IV, are less likely to be preserved and more likely to be misinterpreted as feathers at earlier developmental stages. Our discovery has major implications for our understanding of the fidelity of the fossil record of feathers and provides a framework for testing the significance of putative examples of fossil feathers at different developmental stages.

  7. NCT and Culture-Conscious Developmental Science

    ERIC Educational Resources Information Center

    Downing-Wilson, Deborah; Pelaprat, Etienne; Rosero, Ivan; Vadeboncoeur, Jennifer; Packer, Martin; Cole, Michael

    2013-01-01

    The authors share the belief that there is great potential for developmental science in bringing the ideas of Niche Construction Theory (NCT), as developed in evolutionary biology, into conversation with Vygotskian-inspired theories such as cultural-historical and activity theories, distributed cognition, and embodied cognition, although from…

  8. The Dynamic Lift of Developmental Process

    ERIC Educational Resources Information Center

    Smith, Linda B.; Breazeal, Cynthia

    2007-01-01

    What are the essential properties of human intelligence, currently unparalleled in its power relative to other biological forms and relative to artificial forms of intelligence? We suggest that answering this question depends critically on understanding developmental process. This paper considers three principles potentially essential to building…

  9. Screening for Developmental Neurotoxicity; What Role Can Zebrafish Play?

    EPA Science Inventory

    There are so many chemicals in use today. How can we screen those chemicals for potential developmental neurotoxicity? The zebrafish larval assay with behavioral assessments may prove useful for that chemical screen. This talk presents data from our laboratory as well as others t...

  10. DEVELOPMENTAL TOXICITY OF ATRAZINE METABOLITES IN FISCHER 344 RATS

    EPA Science Inventory

    Previously we have shown that atrazine, a commonly used herbicide, causes full-litter resorption (FLR) in Fischer 344 rats at 50 mg/kg. In this study, we tested four atrazine metabolites for their potential to cause FLR and developmental toxicity. Desethylatrazine (DEA), desis...

  11. Optimization of high-throughput nanomaterial developmental toxicity testing in zebrafish embryos

    EPA Science Inventory

    Nanomaterial (NM) developmental toxicities are largely unknown. With an extensive variety of NMs available, high-throughput screening methods may be of value for initial characterization of potential hazard. We optimized a zebrafish embryo test as an in vivo high-throughput assay...

  12. [Theoretical Development and Research Trends in Developmental Care].

    PubMed

    Wang, Yu-Wen; Chang, Ying-Ju

    2015-10-01

    The Newborn Individualized Developmental Care and Assessment Program (NIDCAP), based on the Synactive Theory, is applied to improve brain development in premature and illness infants within a supportive environment. The NIDCAP has been used widely in the clinical setting. The aim of this article was to systematically review research published between 2000 and 2013 that relates to the evidence and application of developmental care. Most studies support the effectiveness of developmental care in terms of facilitating the healthy growth of premature infants, reducing oxygen dependence, reducing hospitalization times, and improving neurodevelopmental outcomes at two years of age. However, research results related to the effects of developmental care on neurodevelopmental outcomes from 2 years old to school age are not consistent. The heterogeneity of interventions, outcome indicators, and measurements in studies may contribute to these mixed results. In addition, as developmental care has been applied for many years, the contamination of participants in the supportive environment should be considered. Based on current evidence, neonatal healthcare professionals must recognize the core value of developmental care in dealing with premature infants and their families. In order to provide effective interventions for infants, further research is needed to assess the comparative effects of the single intervention and the holistic approach in developmental care.

  13. Variation in chemical composition and allelopathic potential of mixoploid Trigonella foenum-graecum L. with developmental stages.

    PubMed

    Omezzine, Faten; Bouaziz, Mohamed; Simmonds, Monique S J; Haouala, Rabiaa

    2014-04-01

    This study was conducted to evaluate the influence of developmental stages (vegetative, flowering and fruiting) of mixoploid fenugreek aerial parts on their chemical composition and allelopathic potential, assessed on lettuce germination and seedling growth. Aqueous and organic extracts significantly delayed germination, reduced its rate and affected seedling growth. Ethyl acetate and methanol extracts of aerial parts harvested at vegetative stage were the most toxic for lettuce germination and seedling growth, respectively. LC-MS/MS analysis of T. foenum-graecum aerial parts methanolic extract showed nine different flavonol glycosides (quercetin and kaempferol glucosides). Chemical composition of aerial parts differed with the developmental stage; indeed, at the vegetative and fruiting stages, analysis revealed the presence of 9 compounds as compared to only 6 compounds at the flowering stage. Thus, it is necessary to follow the qualitative changes of allelochemicals production at different developmental stages to identify the most productive one. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Lack of genetic interaction between Tbx20 and Tbx3 in early mouse heart development.

    PubMed

    Gavrilov, Svetlana; Harvey, Richard P; Papaioannou, Virginia E

    2013-01-01

    Members of the T-box family of transcription factors are important regulators orchestrating the complex regionalization of the developing mammalian heart. Individual mutations in Tbx20 and Tbx3 cause distinct congenital heart abnormalities in the mouse: Tbx20 mutations result in failure of heart looping, developmental arrest and lack of chamber differentiation, while hearts of Tbx3 mutants progress further, loop normally but show atrioventricular convergence and outflow tract defects. The two genes have overlapping areas of expression in the atrioventricular canal and outflow tract of the heart but their potential genetic interaction has not been previously investigated. In this study we produced compound mutants to investigate potential genetic interactions at the earliest stages of heart development. We find that Tbx20; Tbx3 double heterozygous mice are viable and fertile with no apparent abnormalities, while double homozygous mutants are embryonic lethal by midgestation. Double homozygous mutant embryos display abnormal cardiac morphogenesis, lack of heart looping, expression patterns of cardiac genes and time of death that are indistinguishable from Tbx20 homozygous mutants. Prior to death, the double homozygotes show an overall developmental delay similar to Tbx3 homozygous mutants. Thus the effects of Tbx20 are epistatic to Tbx3 in the heart but Tbx3 is epistatic to Tbx20 with respect to developmental delay.

  15. Development and spindle formation in rat somatic cell nuclear transfer (SCNT) embryos in vitro using porcine recipient oocytes.

    PubMed

    Sugawara, Atsushi; Sugimura, Satoshi; Hoshino, Yumi; Sato, Eimei

    2009-08-01

    Cloning that uses somatic cell nuclear transfer (SCNT) technology with gene targeting could be a potential alternative approach to obtain valuable rat models. In the present study, we determined the developmental competence of rat SCNT embryos constructed using murine and porcine oocytes at metaphase II (MII). Further, we assessed the effects of certain factors, such as: (i) the donor cell type (fetal fibroblasts or cumulus cells); and (ii) premature chromosome condensation (PCC) with normal spindle formation, on the developmental competence of rat interspecies SCNT (iSCNT) embryos. iSCNT embryos that had been constructed using porcine oocytes developed to the blastocyst stage, while those embryos made using murine MII oocytes did not. Rat iSCNT embryos constructed with green fluorescent protein (GFP)-expressing fetal fibroblasts injected into porcine oocytes showed considerable PCC with a normal bipolar spindle formation. The total cell number of iSCNT blastocyst derived from GFP-expressing fetal fibroblasts was higher than the number derived from cumulus cells. In addition, these embryos expressed GFP at the blastocyst stage. This paper is the first report to show that rat SCNT embryos constructed using porcine MII oocytes have the potential to develop to the blastocyst stage in vitro. Thus the iSCNT technique, when performed using porcine MII oocytes, could provide a new bioassay system for the evaluatation of the developmental competence of rat somatic cells.

  16. MicroRNAs in Breastmilk and the Lactating Breast: Potential Immunoprotectors and Developmental Regulators for the Infant and the Mother

    PubMed Central

    Alsaweed, Mohammed; Hartmann, Peter E.; Geddes, Donna T.; Kakulas, Foteini

    2015-01-01

    Human milk (HM) is the optimal source of nutrition, protection and developmental programming for infants. It is species-specific and consists of various bioactive components, including microRNAs, small non-coding RNAs regulating gene expression at the post-transcriptional level. microRNAs are both intra- and extra-cellular and are present in body fluids of humans and animals. Of these body fluids, HM appears to be one of the richest sources of microRNA, which are highly conserved in its different fractions, with milk cells containing more microRNAs than milk lipids, followed by skim milk. Potential effects of exogenous food-derived microRNAs on gene expression have been demonstrated, together with the stability of milk-derived microRNAs in the gastrointestinal tract. Taken together, these strongly support the notion that milk microRNAs enter the systemic circulation of the HM fed infant and exert tissue-specific immunoprotective and developmental functions. This has initiated intensive research on the origin, fate and functional significance of milk microRNAs. Importantly, recent studies have provided evidence of endogenous synthesis of HM microRNA within the human lactating mammary epithelium. These findings will now form the basis for investigations of the role of microRNA in the epigenetic control of normal and aberrant mammary development, and particularly lactation performance. PMID:26529003

  17. Limbic control of aggression in the cat.

    PubMed

    Adamec, R E; Stark-Adamec, C I

    1983-01-01

    Over a decade of work by Flynn and colleagues has delineated a network of limbic circuits which function to modulate the expression of predatory aggression and defence in the cat, and aspects of this work are reviewed. In particular, Flynn's work revealed a circuit involving the basomedial amygdala which functions to suppress attack, and at the same time facilitates defence. A second circuit, involving the ventral hippocampus, is involved in attack facilitation. Studies relating stable differences in excitability in these two circuits to developmentally determined behavioural dispositions toward aggression or defence are summarized. Finally, the impact of experimentally induced limbic seizures on interictally maintained expression of aggression and defence behaviourally, and on limbic excitability are reviewed. Taken together, the data indicate that the behavioural balance of attack and defence is under the tonic control of opponent limbic circuits, which are themselves biased in a measureable manner. Developmental studies indicate that adult defensiveness is determined early in life, so early as to suggest some pre-programmed neuro-developmental process. Experimentally induced seizures alter behaviour lastingly, producing an increase in defensive disposition. At the same time there is an equally lasting potentiation of interictal transmission of neural activity from the amygdala to the hypothalamus. Moreover, seizures may reduce interictal transmission of activity through the ventral hippocampus by potentiating recurrent inhibition. These effects of seizures are of interest since seizures reproduce naturally occurring differences in limbic excitability seen in naturally defensive cats.

  18. Simultaneous mapping of membrane voltage and calcium in zebrafish heart in vivo reveals chamber-specific developmental transitions in ionic currents

    PubMed Central

    Hou, Jennifer H.; Kralj, Joel M.; Douglass, Adam D.; Engert, Florian; Cohen, Adam E.

    2014-01-01

    The cardiac action potential (AP) and the consequent cytosolic Ca2+ transient are key indicators of cardiac function. Natural developmental processes, as well as many drugs and pathologies change the waveform, propagation, or variability (between cells or over time) of these parameters. Here we apply a genetically encoded dual-function calcium and voltage reporter (CaViar) to study the development of the zebrafish heart in vivo between 1.5 and 4 days post fertilization (dpf). We developed a high-sensitivity spinning disk confocal microscope and associated software for simultaneous three-dimensional optical mapping of voltage and calcium. We produced a transgenic zebrafish line expressing CaViar under control of the heart-specific cmlc2 promoter, and applied ion channel blockers at a series of developmental stages to map the maturation of the action potential in vivo. Early in development, the AP initiated via a calcium current through L-type calcium channels. Between 90 and 102 h post fertilization (hpf), the ventricular AP switched to a sodium-driven upswing, while the atrial AP remained calcium driven. In the adult zebrafish heart, a sodium current drives the AP in both the atrium and ventricle. Simultaneous voltage and calcium imaging with genetically encoded reporters provides a new approach for monitoring cardiac development, and the effects of drugs on cardiac function. PMID:25309445

  19. Simultaneous mapping of membrane voltage and calcium in zebrafish heart in vivo reveals chamber-specific developmental transitions in ionic currents.

    PubMed

    Hou, Jennifer H; Kralj, Joel M; Douglass, Adam D; Engert, Florian; Cohen, Adam E

    2014-01-01

    The cardiac action potential (AP) and the consequent cytosolic Ca(2+) transient are key indicators of cardiac function. Natural developmental processes, as well as many drugs and pathologies change the waveform, propagation, or variability (between cells or over time) of these parameters. Here we apply a genetically encoded dual-function calcium and voltage reporter (CaViar) to study the development of the zebrafish heart in vivo between 1.5 and 4 days post fertilization (dpf). We developed a high-sensitivity spinning disk confocal microscope and associated software for simultaneous three-dimensional optical mapping of voltage and calcium. We produced a transgenic zebrafish line expressing CaViar under control of the heart-specific cmlc2 promoter, and applied ion channel blockers at a series of developmental stages to map the maturation of the action potential in vivo. Early in development, the AP initiated via a calcium current through L-type calcium channels. Between 90 and 102 h post fertilization (hpf), the ventricular AP switched to a sodium-driven upswing, while the atrial AP remained calcium driven. In the adult zebrafish heart, a sodium current drives the AP in both the atrium and ventricle. Simultaneous voltage and calcium imaging with genetically encoded reporters provides a new approach for monitoring cardiac development, and the effects of drugs on cardiac function.

  20. Tretinoin: a review of the nonclinical developmental toxicology experience.

    PubMed

    Kochhar, D M; Christian, M S

    1997-03-01

    Tretinoin has been thoroughly evaluated for its potential as an embryofetal developmental toxicant. Oral tretinoin produces developmental anomalies in animal models; the minimal teratogenic dose is consistently 2.5 to 10 mg/kg. In contrast, topical application does not induce developmental malformations in laboratory animals. A structurally related compound, isotretinoin, is a potent toxicant in humans and animals; the lowest systemic dose that induces fetal anomalies varies more than 100-fold depending on the model. Oral isotretinoin is a more potent developmental toxicant than oral tretinoin in monkeys. Between-drug differences in the metabolism and transplacental transfer of the two retinoids account for the differences in toxicant potency. Pharmacokinetic studies reveal that absorption of tretinoin from the skin is poor and yields maternal plasma concentrations below the developmentally toxic threshold established after oral administration. Analysis of outcomes of developmental toxicology and pharmacokinetic studies suggests that the human risk of fetal anomalies is negligible after therapeutic application of topical tretinoin.

  1. Consumption habits of pregnant women and implications for developmental biology: a survey of predominantly Hispanic women in California.

    PubMed

    Santiago, Sarah E; Park, Grace H; Huffman, Kelly J

    2013-07-01

    Healthy post-pregnancy outcomes are contingent upon an informed regimen of prenatal care encouraging healthy maternal consumption habits. In this article, we describe aspects of maternal intake of food, drink, and medication in a population of predominantly Hispanic women in Southern California. Potential implications for unhealthy prenatal dietary choices are discussed. The Food, Beverage, and Medication Intake Questionnaire (FBMIQ) measures common practices of maternal consumption during pregnancy. The FBMIQ was administered to English and Spanish speaking pregnant and recently pregnant (36 weeks pregnant - 8 weeks post-partum) women over the age of 18 who were receiving care from a private medical group in Downey CA. A total of 200 women completed the FBMIQ. Consumption habits of healthy foods and beverages, unhealthy foods, unhealthy beverages, and medication are characterized in this article. Data indicate widespread consumption of fresh fruit, meats, milk and juice and indicate most women used prenatal vitamin supplements. Studies in developmental neuroscience have shown that certain substances may cause teratogenic effects on the fetus when ingested by the mother during pregnancy. Those potentially harmful substances included in our study were Bisphenol-A (BPA), methylmercury, caffeine, alcohol and certain medications. Our results show that a proportion of the women surveyed in our study consumed BPA, methylmercury, caffeine, alcohol, and certain medications at varied levels during pregnancy. This represents an interesting finding and suggests a disconnect between scientific data and general recommendations provided to pregnant mothers by obstetricians. The results of our study demonstrate that a proportion of pregnant women consume substances that are potentially teratogenic and may impact the health and well being of the offspring. It is important to appraise healthy and unhealthy consumption habits in order to encourage healthy practices and alleviate future effects of preventable, toxin-induced developmental issues. Prenatal advising should discourage the consumption of dangerous foods, beverages, and medications that women commonly report eating during pregnancy.

  2. Consumption habits of pregnant women and implications for developmental biology: a survey of predominantly Hispanic women in California

    PubMed Central

    2013-01-01

    Background Healthy post-pregnancy outcomes are contingent upon an informed regimen of prenatal care encouraging healthy maternal consumption habits. In this article, we describe aspects of maternal intake of food, drink, and medication in a population of predominantly Hispanic women in Southern California. Potential implications for unhealthy prenatal dietary choices are discussed. Methods The Food, Beverage, and Medication Intake Questionnaire (FBMIQ) measures common practices of maternal consumption during pregnancy. The FBMIQ was administered to English and Spanish speaking pregnant and recently pregnant (36 weeks pregnant - 8 weeks post-partum) women over the age of 18 who were receiving care from a private medical group in Downey CA. Results A total of 200 women completed the FBMIQ. Consumption habits of healthy foods and beverages, unhealthy foods, unhealthy beverages, and medication are characterized in this article. Data indicate widespread consumption of fresh fruit, meats, milk and juice and indicate most women used prenatal vitamin supplements. Studies in developmental neuroscience have shown that certain substances may cause teratogenic effects on the fetus when ingested by the mother during pregnancy. Those potentially harmful substances included in our study were Bisphenol-A (BPA), methylmercury, caffeine, alcohol and certain medications. Our results show that a proportion of the women surveyed in our study consumed BPA, methylmercury, caffeine, alcohol, and certain medications at varied levels during pregnancy. This represents an interesting finding and suggests a disconnect between scientific data and general recommendations provided to pregnant mothers by obstetricians. Conclusions The results of our study demonstrate that a proportion of pregnant women consume substances that are potentially teratogenic and may impact the health and well being of the offspring. It is important to appraise healthy and unhealthy consumption habits in order to encourage healthy practices and alleviate future effects of preventable, toxin-induced developmental issues. Prenatal advising should discourage the consumption of dangerous foods, beverages, and medications that women commonly report eating during pregnancy. PMID:23815874

  3. Developmental Changes in the Effects of Presentation Mode on the Storage and Retrieval of Noun Pairs in Children's Recognition Memory.

    ERIC Educational Resources Information Center

    Kee, Daniel W.; And Others

    Four problems in children's paired-associate memory were addressed: (1) reappraisal of the presumed developmental trend in presentation mode effect during grade-school years, (2) identification of the locus of this developmental effect, (3) evaluation of the influence of combined presentation (verbal plus pictorial) relative to pictorial…

  4. Developmental regulation of neuroligin genes in Japanese ricefish (Oryzias latipes) embryogenesis maintains the rhythm during ethanol-induced fetal alcohol spectrum disorder.

    PubMed

    Haron, Mona H; Khan, Ikhlas A; Dasmahapatra, Asok K

    2014-01-01

    Although prenatal alcohol exposure is the potential cause of fetal alcohol spectrum disorder (FASD) in humans, the molecular mechanism(s) of FASD is yet unknown. We have used Japanese ricefish (Oryzias latipes) embryogenesis as an animal model of FASD and reported that this model has effectively generated several phenotypic features in the cardiovasculature and neurocranial cartilages by developmental ethanol exposure which is analogous to human FASD phenotypes. As FASD is a neurobehavioral disorder, we are searching for a molecular target of ethanol that alters neurological functions. In this communication, we have focused on neuroligin genes (nlgn) which are known to be active at the postsynaptic side of both excitatory and inhibitory synapses of the central nervous system. There are six human NLGN homologs of Japanese ricefish reported in public data bases. We have partially cloned these genes and analyzed their expression pattern during normal development and also after exposing the embryos to ethanol. Our data indicate that the expression of all six nlgn genes in Japanese ricefish embryos is developmentally regulated. Although ethanol is able to induce developmental abnormalities in Japanese ricefish embryogenesis comparable to the FASD phenotypes, quantitative real-time PCR (qPCR) analysis of nlgn mRNAs indicate unresponsiveness of these genes to ethanol. We conclude that the disruption of the developmental rhythm of Japanese ricefish embryogenesis by ethanol that leads to FASD may not affect the nlgn gene expression at the message level. © 2013.

  5. Seeking mathematics success for college students: a randomized field trial of an adapted approach

    NASA Astrophysics Data System (ADS)

    Gula, Taras; Hoessler, Carolyn; Maciejewski, Wes

    2015-11-01

    Many students enter the Canadian college system with insufficient mathematical ability and leave the system with little improvement. Those students who enter with poor mathematics ability typically take a developmental mathematics course as their first and possibly only mathematics course. The educational experiences that comprise a developmental mathematics course vary widely and are, too often, ineffective at improving students' ability. This trend is concerning, since low mathematics ability is known to be related to lower rates of success in subsequent courses. To date, little attention has been paid to the selection of an instructional approach to consistently apply across developmental mathematics courses. Prior research suggests that an appropriate instructional method would involve explicit instruction and practising mathematical procedures linked to a mathematical concept. This study reports on a randomized field trial of a developmental mathematics approach at a college in Ontario, Canada. The new approach is an adaptation of the JUMP Math program, an explicit instruction method designed for primary and secondary school curriculae, to the college learning environment. In this study, a subset of courses was assigned to JUMP Math and the remainder was taught in the same style as in the previous years. We found consistent, modest improvement in the JUMP Math sections compared to the non-JUMP sections, after accounting for potential covariates. The findings from this randomized field trial, along with prior research on effective education for developmental mathematics students, suggest that JUMP Math is a promising way to improve college student outcomes.

  6. Inhibition of O-linked N-acetylglucosamine transferase activity in PC12 cells - A molecular mechanism of organophosphate flame retardants developmental neurotoxicity.

    PubMed

    Gu, Yuxin; Yang, Yu; Wan, Bin; Li, Minjie; Guo, Liang-Hong

    2018-06-01

    Organophosphate flame retardants (OPFRs), as alternatives of brominated flame retardants, can cause neurodevelopmental effects similar to organophosphate pesticides. However, the molecular mechanisms underlying the toxicity remain elusive. O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) regulates numerous neural processes through the O-GlcNAcylation modification of nuclear and cytoplasmic proteins. In this study, we aimed to investigate the molecular mechanisms accounting for the developmental neurotoxicity of OPFRs by identifying potential targets of OPFRs and the attendant effects. Twelve OPFRs were evaluated for inhibition of OGT activity using an electrochemical biosensor. Their potency differed with substituent groups. The alkyl group substituted OPFRs had no inhibitory effect. Instead, the six OPFRs substituted with aromatic or chlorinated alkyl groups inhibited OGT activity significantly, with tri-m-cresyl phosphate (TCrP) being the strongest. The six OPFRs (0-100 μM exposure) also inhibited OGT activity in PC12 cells and decreased protein O-GlcNAcylation level. Inhibition of OGT by OPFRs might be involved in the subsequent toxic effects, including intracellular reactive oxygen species (ROS), calcium level, as well as cell proliferation and autophagy. Molecular docking of the OGT/OPFR complexes provided rationales for the difference in their structure-dependent inhibition potency. Our findings may provide a new biological target of OPFRs in their neurotoxicological actions, which might be a major molecular mechanism of OPFRs developmental neurotoxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Developmental programming of the metabolic syndrome - critical windows for intervention

    PubMed Central

    Vickers, Mark H

    2011-01-01

    Metabolic disease results from a complex interaction of many factors, including genetic, physiological, behavioral and environmental influences. The recent rate at which these diseases have increased suggests that environmental and behavioral influences, rather than genetic causes, are fuelling the present epidemic. In this context, the developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal and early infant phases of life and the subsequent development of adult obesity and the metabolic syndrome. Although the mechanisms are yet to be fully elucidated, this programming was generally considered an irreversible change in developmental trajectory. Recent work in animal models suggests that developmental programming of metabolic disorders is potentially reversible by nutritional or targeted therapeutic interventions during the period of developmental plasticity. This review will discuss critical windows of developmental plasticity and possible avenues to ameliorate the development of postnatal metabolic disorders following an adverse early life environment. PMID:21954418

  8. Effects of a dolphin interaction program on children with autism spectrum disorders – an exploratory research

    PubMed Central

    2012-01-01

    Background Interaction programs involving dolphins and patients with various pathologies or developmental disorders (e.g., cerebral palsy, intellectual impairment, autism, atopic dermatitis, post-traumatic stress disorder, depression) have stimulated interest in their beneficial effects and therapeutic potential. However, the true effects observed in different clinical and psycho-educational setups are still controversial. Results An evaluation protocol consisting of the Childhood Autism Rating Scale (CARS), Psychoeducational Profile-Revised (PEP-R), Autism Treatment Evaluation Checklist (ATEC), Theory of Mind Tasks (ToM Tasks) and a custom-made Interaction Evaluation Grid (IEG) to evaluate behavioural complexity during in-pool interactions was applied to 10 children diagnosed with Autism Spectrum Disorders. The ATEC, ToM Tasks and CARS results show no benefits of the dolphin interaction program. Interestingly, the PEP-R suggests some statistically significant effects on ‘Overall development score’, as well as on their ‘Fine motor development’, ‘Cognitive performance’ and ‘Cognitive verbal development’. Also, a significant evolution in behavioural complexity was shown by the IEG. Conclusions This study does not support significant developmental progress resulting from the dolphin interaction program. PMID:22537536

  9. Developmental Effects of Incentives on Response Inhibition

    PubMed Central

    Geier, Charles F.; Luna, Beatriz

    2012-01-01

    Inhibitory control and incentive processes underlie decision-making, yet few studies have explicitly examined their interaction across development. Here, the effects of potential rewards and losses on inhibitory control in sixty-four adolescents (13-17-year-olds) and forty-two young adults (18-29-year-olds) were examined using an incentivized antisaccade task. Notably, measures were implemented to minimize age-related differences in reward valuation and potentially confounding motivation effects. Incentives affected antisaccade metrics differently across the age groups. Younger adolescents generated more errors than adults on reward trials, but all groups performed well on loss trials. Adolescent saccade latencies also differed from adults across the range of reward trials. Overall, results suggest persistent immaturities in the integration of reward and inhibitory control processes across adolescence. PMID:22540668

  10. 47 CFR 22.401 - Description and purposes of developmental authorizations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... technical suitability of antenna locations for stations in the Public Mobile Services; (b) Experimentation leading to the potential development of a new Public Mobile Service or technology; or, (c) Stations... CARRIER SERVICES PUBLIC MOBILE SERVICES Developmental Authorizations § 22.401 Description and purposes of...

  11. The potential of AOP networks for reproductive and developmental toxicity assay development

    EPA Science Inventory

    Historically, the prediction of reproductive and early developmental toxicity has largely relied on the use of animals. The Adverse Outcome Pathway (AOP) framework forms a basis for the development of new non-animal test methods. It also provides biological context for mechanisti...

  12. DOSIMETRY AND REPRODUCTIVE/DEVELOPMENTAL STUDY DESIGN AND INTERPRETATION FOR RISK OR SAFETY ASSESSMENT

    EPA Science Inventory

    Increasingly reproductive and developmental toxicity studies are utilized in assessing the potential for adverse affects in pregnant women, nursing infants, and children. These studies largely have been utilized based upon the dose to the mother due to the complexity of describin...

  13. Trajectories of cognitive development during adolescence among youth at-risk for schizophrenia.

    PubMed

    Dickson, Hannah; Cullen, Alexis E; Jones, Rebecca; Reichenberg, Abraham; Roberts, Ruth E; Hodgins, Sheilagh; Morris, Robin G; Laurens, Kristin R

    2018-04-23

    Among adults with schizophrenia, evidence suggests that premorbid deficits in different cognitive domains follow distinct developmental courses during childhood and adolescence. The aim of this study was to delineate trajectories of adolescent cognitive functions prospectively among different groups of youth at-risk for schizophrenia, relative to their typically developing (TD) peers. Using linear mixed models adjusted for sex, ethnicity, parental occupation and practice effects, cognitive development between ages 9 and 16 years was compared for youth characterised by a triad of well-replicated developmental antecedents of schizophrenia (ASz; N = 32) and youth with a least one affected relative with schizophrenia or schizoaffective disorder (FHx; N = 29), relative to TD youth (N = 45). Participants completed measures of IQ, scholastic achievement, memory and executive function at three time-points, separated by approximately 24-month intervals. Compared to TD youth, both ASz and FHx youth displayed stable developmental deficits in verbal working memory and inhibition/switching executive functions. ASz youth additionally presented with stable deficits in measures of vocabulary (IQ), word reading, numerical operations, and category fluency executive function, and a slower rate of growth (developmental lag) on spelling from 9 to 16 years than TD peers. Conversely, faster rates of growth relative to TD peers (developmental delay) were observed on visual and verbal memory, and on category fluency executive function (ASz youth only) and on matrix reasoning (IQ) and word reading (FHx youth only). These differential patterns of deviation from normative adolescent cognitive development among at-risk youth imply potential for cognitive rehabilitation targeting of specific cognitive deficits at different developmental phases. © 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

  14. Techtalk: How Technology Has Changed Developmental Education.

    ERIC Educational Resources Information Center

    Caverly, David C.; MacDonald, Lucy

    2003-01-01

    Discusses how technology has changed higher education and how it is important to teach developmental students to effectively use technology to become better students and more effective workers. Describes a variety of portable devices and learning strategy applications. Recommends that developmental educators seriously consider the use of Personal…

  15. A REVIEW OF HUMAN STUDIES ON THE REPRODUCTIVE AND DEVELOPMENTAL EFFECTS OF PESTICIDE EXPOSURE

    EPA Science Inventory

    Many pesticides cxause reproductive or developmental toxicity at high doses in animal models, but effects in humans at environmental exposure levels are difficult to assess. Human data on reproductive and developmental outcomes for currently used pesticides may help to define ris...

  16. BRAIN AND BLOOD TIN LEVELS IN A DEVELOPMENTAL NEUROTOXICITY STUDY OF DIBUTYLTIN.

    EPA Science Inventory

    Dibutyltin (DBT), a widely used plastic stabilizer, is detected in the environment and human tissues. While teratological and developmental effects are known, we could find no published report of DBT effects on the developing nervous system. As part of a developmental neurotoxi...

  17. Subliminal trauma reminders impact neural processing of cognitive control in adults with developmental earthquake trauma: a preliminary report.

    PubMed

    Du, Xue; Li, Yu; Ran, Qian; Kim, Pilyoung; Ganzel, Barbara L; Liang, GuangSheng; Hao, Lei; Zhang, Qinglin; Meng, Huaqing; Qiu, Jiang

    2016-03-01

    Little is known about the effects of developmental trauma on the neural basis of cognitive control among adults who do not have posttraumatic stress disorder. To examine this question, we used functional magnetic resonance imaging to compare the effect of subliminal priming with earthquake-related images on attentional control during a Stroop task in survivors of the 2008 Wenchuan earthquake in China (survivor group, survivors were adolescents at the time of the earthquake) and in matched controls (control group). We found that the survivor group showed greater activation in the left ventral anterior cingulate cortex (vACC) and the bilateral parahippocampal gyrus during the congruent versus incongruent condition, as compared to the control group. Depressive symptoms were positively correlated with left vACC activation during the congruent condition. Moreover, psychophysiological interaction results showed that the survivor group had stronger functional connectivity between the left parahippocampal gyrus and the left vACC than the control group under the congruent-incongruent condition. These results suggested that trauma-related information was linked to abnormal activity in brain networks associated with cognitive control (e.g., vACC-parahippocampal gyrus). This may be a potential biomarker for depression following developmental trauma, and it may also provide a mechanism linking trauma reminders with depression.

  18. Developmental song learning as a model to understand neural mechanisms that limit and promote the ability to learn.

    PubMed

    London, Sarah E

    2017-11-20

    Songbirds famously learn their vocalizations. Some species can learn continuously, others seasonally, and still others just once. The zebra finch (Taeniopygia guttata) learns to sing during a single developmental "Critical Period," a restricted phase during which a specific experience has profound and permanent effects on brain function and behavioral patterns. The zebra finch can therefore provide fundamental insight into features that promote and limit the ability to acquire complex learned behaviors. For example, what properties permit the brain to come "on-line" for learning? How does experience become encoded to prevent future learning? What features define the brain in receptive compared to closed learning states? This piece will focus on epigenomic, genomic, and molecular levels of analysis that operate on the timescales of development and complex behavioral learning. Existing data will be discussed as they relate to Critical Period learning, and strategies for future studies to more directly address these questions will be considered. Birdsong learning is a powerful model for advancing knowledge of the biological intersections of maturation and experience. Lessons from its study not only have implications for understanding developmental song learning, but also broader questions of learning potential and the enduring effects of early life experience on neural systems and behavior. Copyright © 2017. Published by Elsevier B.V.

  19. Effect of maternal exposure to tributyltin on reproduction of the pearl oyster (Pinctada fucata martensii).

    PubMed

    Inoue, Suguru; Oshima, Yuji; Nagai, Kiyohito; Yamamoto, Takashi; Go, Jyoji; Kai, Norihisa; Honjo, Tsuneo

    2004-05-01

    We examined the effect of tributyltin (TBT) on reproduction of the pearl oyster (Pinctada fucata martensii). In a maternal exposure test, five female pearl oysters were exposed to TBT at measured concentrations of 0 (control), 0.092, or 0.191 microg/L at 25 degreesC for one week, and the embryo developmental success (the ratio of normal D-larvae to all larvae) was measured. The embryo developmental success was significantly decreased in the 0.191-microg/L treatment group (65.5%) compared to that in the control group (82.5%; p = 0.031). Concentrations of TBT in the ovary reached 0.088 microg/g in the 0.191-microg/L treatment group. In a waterborne exposure test, inseminated eggs were exposed to TBT at measured concentrations of 0 (control), 0.020, 0.045, 0.091, 0.192, or 0.374 microg/L for 24 h. The embryo developmental success also was significantly decreased in the 0.192-microg/L treatment group (78.3%; p = 0.020) and no development at all was observed in the 0.374-microg/L treatment group compared with that in the control group (95.4%). These results clearly demonstrate that TBT accumulating in the bodies of bivalves has the potential to inhibit reproduction.

  20. Developmental Implications for Prenatal Exposure to Environmental Toxins: Consumption Habits of Pregnant Women and Prenatal Nicotine Exposure in a Mouse Model

    NASA Astrophysics Data System (ADS)

    Santiago, Sarah Emily

    This dissertation provides a discussion of the effects of maternal consumption of environmental toxins, and will hopefully contribute to the prevention and understanding of developmental disorders and physiological deficits. Developing systems are particularly susceptible to toxic insults, and small changes in utero can result in long-term deficits. Chapter one of this dissertation reviews the potential teratogenicity of nicotine, alcohol, caffeine, MeHg, PCBs, BPA, and tap water contaminants, so as to characterize the current body of literature detailing the effects and implications of prenatal exposure to toxins. In chapter two, research on maternal consumption habits is presented, with an emphasis on commonly-consumed, potentially-teratogenic substances. Occurrences and frequencies of maternal intake of healthy and unhealthy foods, beverages, and medications in a population of predominantly Hispanic women in Southern California were assessed using the Food, Beverage, and Medication Intake Questionnaire (FBMIQ). The described study reveals that a proportion of pregnant women consumed BPA, MeHg, caffeine, and alcohol at varied levels during pregnancy. The following chapters provide an in-depth analysis of the postnatal effects of a particular neuroteratogen, nicotine, which has been shown to impart various detrimental postnatal effects on exposed offspring. A CD-1 mouse model of prenatal nicotine exposure (PNE) was used to analyze aspects of the brain and neocortex that may underly some of the cognitive and behavioral phenotypes seen with PNE. Analyses included postnatal measurements of brain weight, brain widths and lengths, development of neocortical circuitry, and cortical thickness measures. Exposed mice were found to exhibit reduced brain and body weights at birth, a phenotype that recovered by postnatal day 10. No changes in neocortical circuity or thickness in sensory and motor areas were found. PNE also resulted in persistent behavioral effects, including increased anxiety and deficits in sensorimotor integration abilities, in six month old females. Such analyses describe immediate and long-lasting postnatal effects of prenatal nicotine exposure, underscoring the importance of abstaining from nicotine during pregnancy. Hopefully, the works detailed in this dissertation will provide a foundation upon which future researchers can build a better understanding of how prenatal exposures contribute to developmental deficits.

  1. Normal composite face effects in developmental prosopagnosia.

    PubMed

    Biotti, Federica; Wu, Esther; Yang, Hua; Jiahui, Guo; Duchaine, Bradley; Cook, Richard

    2017-10-01

    Upright face perception is thought to involve holistic processing, whereby local features are integrated into a unified whole. Consistent with this view, the top half of one face appears to fuse perceptually with the bottom half of another, when aligned spatially and presented upright. This 'composite face effect' reveals a tendency to integrate information from disparate regions when faces are presented canonically. In recent years, the relationship between susceptibility to the composite effect and face recognition ability has received extensive attention both in participants with normal face recognition and participants with developmental prosopagnosia. Previous results suggest that individuals with developmental prosopagnosia may show reduced susceptibility to the effect suggestive of diminished holistic face processing. Here we describe two studies that examine whether developmental prosopagnosia is associated with reduced composite face effects. Despite using independent samples of developmental prosopagnosics and different composite procedures, we find no evidence for reduced composite face effects. The experiments yielded similar results; highly significant composite effects in both prosopagnosic groups that were similar in magnitude to the effects found in participants with normal face processing. The composite face effects exhibited by both samples and the controls were greatly diminished when stimulus arrangements were inverted. Our finding that the whole-face binding process indexed by the composite effect is intact in developmental prosopagnosia indicates that other factors are responsible for developmental prosopagnosia. These results are also inconsistent with suggestions that susceptibility to the composite face effect and face recognition ability are tightly linked. While the holistic process revealed by the composite face effect may be necessary for typical face perception, it is not sufficient; individual differences in face recognition ability likely reflect variability in multiple sequential processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Developmental effects of magnetic field (50 Hz) in combination with ionizing radiation and chemical teratogens.

    PubMed

    Pafková, H; Jerábek, J; Tejnorová, I; Bednár, V

    1996-11-01

    The influence of a 50 Hz magnetic field (MF) on avian and mammalian embryogenesis, the MF level and vector, as well as the effect of exposure to MF (50 Hz, 10 mT) in combination with X-rays has been recently reported [2,3]. No significant alterations of chick or rat embryogenesis were found after repeated exposures to 50 Hz MF at 10 mT or 6 microT or with different vectors. However, X-ray chick embryotoxicity was significantly affected by repeated exposures of developing organisms to MF. A strong dependence of effect on the type of interaction was revealed. A decrease of X-ray induced teratogenicity was observed when MF preceded X-ray exposure (indirect interaction), while MF exposure applied immediately after X-ray radiation (direct interaction) non-significantly potentiated adverse developmental effects of ionizing radiation. This study deals with the effects of MF in combination with insulin or tetracycline. Exposure of chick embryos to MF influenced the sensitivity of embryonic morphogenetic systems to the subsequently administered chemical teratogens, insulin and/or tetracycline. A protective effect of MF was detected similarly as in the case of indirect interaction with ionizing radiation.

  3. Gene networks, occlusal clocks, and functional patches: new understanding of pattern and process in the evolution of the dentition.

    PubMed

    Polly, P David

    2015-05-01

    Our understanding of the evolution of the dentition has been transformed by advances in the developmental biology, genetics, and functional morphology of teeth, as well as the methods available for studying tooth form and function. The hierarchical complexity of dental developmental genetics combined with dynamic effects of cells and tissues during development allow for substantial, rapid, and potentially non-linear evolutionary changes. Studies of selection on tooth function in the wild and evolutionary functional comparisons both suggest that tooth function and adaptation to diets are the most important factors guiding the evolution of teeth, yet selection against random changes that produce malocclusions (selectional drift) may be an equally important factor in groups with tribosphenic dentitions. These advances are critically reviewed here.

  4. Application study of filamentary composites in a commercial jet aircraft fuselage

    NASA Technical Reports Server (NTRS)

    Johnson, R. W.; June, R. R.

    1972-01-01

    A study of applications of filamentary composite materials to aircraft fuselage structure was performed. General design criteria were established and material studies conducted using the 727-200 forebody as the primary structural component. Three design approaches to the use of composites were investigated: uniaxial reinforcement of metal structure, uniaxial and biaxial reinforcement of metal structure, and an all-composite design. Materials application studies for all three concepts were conducted on fuselage shell panels, keel beam, floor beams, floor panels, body frames, fail-safe straps, and window frames. Cost benefit studies were conducted and developmental program costs estimated. On the basis of weight savings, cost effectiveness, developmental program costs, and potential for early application on commercial aircraft, the unaxial design is recommended for a 5-year flight service evaluation program.

  5. Conservation Evo-Devo: Preserving Biodiversity by Understanding Its Origins.

    PubMed

    Campbell, Calum S; Adams, Colin E; Bean, Colin W; Parsons, Kevin J

    2017-10-01

    Unprecedented rates of species extinction increase the urgency for effective conservation biology management practices. Thus, any improvements in practice are vital and we suggest that conservation can be enhanced through recent advances in evolutionary biology, specifically advances put forward by evolutionary developmental biology (i.e., evo-devo). There are strong overlapping conceptual links between conservation and evo-devo whereby both fields focus on evolutionary potential. In particular, benefits to conservation can be derived from some of the main areas of evo-devo research, namely phenotypic plasticity, modularity and integration, and mechanistic investigations of the precise developmental and genetic processes that determine phenotypes. Using examples we outline how evo-devo can expand into conservation biology, an opportunity which holds great promise for advancing both fields. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Students' Perceptions of Effective Teaching Strategies in a Developmental Writing Course

    ERIC Educational Resources Information Center

    Dorsey, Carrie S.

    2014-01-01

    This dissertation explores student perceptions of effective teaching strategies in a developmental writing course and their perspectives of how well the course prepared them for the freshman college composition course. Three research questions guided the study. Research Question 1 asked which teaching strategies developmental writing students…

  7. Goldilocks' Determination of What New In Vivo Data are "Just Right" for Different Common Drug Development Scenarios, Part 1.

    PubMed

    Bowman, Christopher J; Chapin, Robert E

    2016-08-01

    As alternative models and scientific advancements improve the ability to predict developmental toxicity, the challenge is how to best use this information to support safe use of pharmaceuticals in humans. While in vivo experimental data are often expected, there are other important considerations that drive the impact of developmental toxicity data to human risk assessment and product labeling. These considerations include three key elements: (1) the drug's likelihood of producing off-target toxicities, (2) risk tolerance of adverse effects based on indication and patient population, and (3) how much is known about the effects of modulating the target in pregnancy and developmental biology. For example, there is little impact or value of a study in pregnant monkeys to inform the risk assessment for a highly specific monoclonal antibody indicated for a life-threatening indication against a target known to be critical for pregnancy maintenance and fetal survival. In contrast, a small molecule to a novel biological target for a chronic lifestyle indication would warrant more safety data than simply in vitro studies and a literature review. Rather than accounting for innumerable theoretical possibilities surrounding each potential submission's profile, we consolidated most of the typical situations into eight possible scenarios across these three elements, and present a discussion of these scenarios here. We hope that this framework will facilitate a rational approach to determining what new information is required to inform developmental toxicity risk of pharmaceuticals in context of the specific needs of each program while reducing animal use where possible. © 2016 Wiley Periodicals, Inc.

  8. Ultraviolet Photolysis of Chlorpyrifos: Developmental Neurotoxicity Modeled in PC12 Cells

    PubMed Central

    Slotkin, Theodore A.; Seidler, Frederic J.; Wu, Changlong; MacKillop, Emiko A.; Linden, Karl G.

    2009-01-01

    Background Ultraviolet photodegradation products from pesticides form both in the field and during water treatment. Objectives We evaluated the photolytic breakdown of the organophosphate pesticide chlorpyrifos (CPF) in terms of both the chemical entities generated by low-pressure ultraviolet C irradiation and their potential as developmental neurotoxicants. Methods We separated by-products using high-performance liquid chromatography and characterized them by gas chromatography/mass spectrometry. We assessed neurotoxicity in neuronotypic PC12 cells, both in the undifferentiated state and during differentiation. Results Photodegradation of CPF in methanol solution generated CPF oxon and trichloropyridinol, products known to retain developmental neurotoxicant actions, as well as a series of related organophosphate and phosphorothionate derivatives. Exposure conditions that led to 50% degradation of CPF thus did not reduce developmental neurotoxicity. The degradation mixture inhibited DNA synthesis in undifferentiated cells to the same extent as native CPF. In differentiating cells, the products likewise retained the full ability to elicit shortfalls in cell number and corresponding effects on cell growth and neurite formation. When the exposure was prolonged to the point where 70% of the CPF was degraded, the adverse effects on PC12 cells were no longer evident; however, these conditions were sufficiently severe to generate toxic products from the methanol vehicle. Conclusions Our results indicate that field conditions or remediation treatments that degrade a significant proportion of the CPF do not necessarily produce inactive products and, indeed, may elicit formation of even more toxic chemicals that are more water soluble and thus have greater field mobility than CPF itself. PMID:19337505

  9. Citrinin induces apoptosis via a mitochondria-dependent pathway and inhibition of survival signals in embryonic stem cells, and causes developmental injury in blastocysts

    PubMed Central

    Chan, Wen-Hsiung

    2007-01-01

    The mycotoxin CTN (citrinin), a natural contaminant in foodstuffs and animal feeds, has cytotoxic and genotoxic effects on various mammalian cells. CTN is known to cause cell injury, including apoptosis, but the precise regulatory mechanisms of CTN action, particularly in stem cells and embryos, are currently unclear. In the present paper, I report that CTN has cytotoxic effects on mouse embryonic stem cells and blastocysts, and is associated with defects in their subsequent development, both in vitro and in vivo. Experiments in embryonic stem cells (ESC-B5) showed that CTN induces apoptosis via ROS (reactive oxygen species) generation, increased Bax/Bcl-2 ratio, loss of MMP (mitochondrial membrane potential), induction of cytochrome c release, and activation of caspase 3. In this model, CTN triggers cell death via inactivation of the HSP90 [a 90 kDa isoform of the HSP (heat-shock protein) family proteins]/multichaperone complex and subsequent degradation of Ras and Raf-1, further inhibiting anti-apoptotic processes, such as the Ras→ERK (extracellular-signal-regulated kinase) signal transduction pathway. In addition, CTN causes early developmental injury in mouse ESCs and blastocysts in vitro. Lastly, using an in vivo mouse model, I show that consumption of drinking water containing 10 μM CTN results in blastocyst apoptosis and early embryonic developmental injury. Collectively, these findings show for the first time that CTN induces ROS and mitochondria-dependent apoptotic processes, inhibits Ras→ERK survival signalling via inactivation of the HSP90/multichaperone complex, and causes developmental injury in vivo. PMID:17331071

  10. Disrupted white matter connectivity underlying developmental dyslexia: A machine learning approach.

    PubMed

    Cui, Zaixu; Xia, Zhichao; Su, Mengmeng; Shu, Hua; Gong, Gaolang

    2016-04-01

    Developmental dyslexia has been hypothesized to result from multiple causes and exhibit multiple manifestations, implying a distributed multidimensional effect on human brain. The disruption of specific white-matter (WM) tracts/regions has been observed in dyslexic children. However, it remains unknown if developmental dyslexia affects the human brain WM in a multidimensional manner. Being a natural tool for evaluating this hypothesis, the multivariate machine learning approach was applied in this study to compare 28 school-aged dyslexic children with 33 age-matched controls. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging were acquired to extract five multitype WM features at a regional level: white matter volume, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) classifier achieved an accuracy of 83.61% using these MRI features to distinguish dyslexic children from controls. Notably, the most discriminative features that contributed to the classification were primarily associated with WM regions within the putative reading network/system (e.g., the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamocortical projections, and corpus callosum), the limbic system (e.g., the cingulum and fornix), and the motor system (e.g., the cerebellar peduncle, corona radiata, and corticospinal tract). These results were well replicated using a logistic regression classifier. These findings provided direct evidence supporting a multidimensional effect of developmental dyslexia on WM connectivity of human brain, and highlighted the involvement of WM tracts/regions beyond the well-recognized reading system in dyslexia. Finally, the discriminating results demonstrated a potential of WM neuroimaging features as imaging markers for identifying dyslexic individuals. © 2016 Wiley Periodicals, Inc.

  11. Effects of postnatal ethanol exposure at different developmental phases on neurotrophic factors and phosphorylated proteins on signal transductions in rat brain.

    PubMed

    Tsuji, Ryozo; Fattori, Vittorio; Abe, Shin-ichi; Costa, Lucio G; Kobayashi, Kumiko

    2008-01-01

    Exposure to ethanol during development induces severe brain damage resulting in a number of CNS dysfunctions including microencephaly and mental retardation in humans and in laboratory animals. The most vulnerable period to ethanol neurotoxicity coincides with the peak of brain growth spurt. Recently, neurotrophic factors and/or their signal transduction pathways have been reported as a potential relevant target for the developmental neurotoxicity of ethanol. The present studies were designed to investigate the effects of ethanol given in various developmental phases during the brain growth spurt in rats. Rat pups were assigned to the three treatment groups and treated with 5 g/kg of ethanol for three days, on postnatal days (PND) 2-4, 6-8 or 13-15. Whole brain weights were reduced only in the PND 6-8 group concurrently with the reduction of GDNF mRNA in cortex in this group. BDNF mRNA expression was reduced in both the PND 6-8 and 13-15 groups, while mRNA expressions of NT-3 and NGF were unchanged in all three groups. Phospho-Akt level was mostly reduced in the PND 6-8 group. Both phospho-MAPK and p-70S6 kinase levels were decreased in all groups whereas no changes were observed in either phospho-PKCzeta or CREB level. The phosphorylation of Akt was immediately inhibited after single administration of ethanol, and its inhibition was correlated with variations in blood ethanol concentration. These findings suggest that GDNF and the phosphorylation of Akt play a possible key role in the ethanol-induced developmental neurotoxicity.

  12. Working Memory and Mathematics: A Review of Developmental, Individual Difference, and Cognitive Approaches

    ERIC Educational Resources Information Center

    Raghubar, Kimberly P.; Barnes, Marcia A.; Hecht, Steven A.

    2010-01-01

    Working memory refers to a mental workspace, involved in controlling, regulating, and actively maintaining relevant information to accomplish complex cognitive tasks (e.g. mathematical processing). Despite the potential relevance of a relation between working memory and math for understanding developmental and individual differences in…

  13. Learning to BREATHE: An Intervention to Foster Mindfulness in Adolescence

    ERIC Educational Resources Information Center

    Broderick, Patricia C.; Frank, Jennifer L.

    2014-01-01

    During adolescence, young people are traversing exciting and also challenging stages in their development. Mindfulness, if taught in a developmentally appropriate way, has the potential to be an asset in adolescents' lives. Developmentally appropriate approaches of mindfulness intervention during adolescence need to consider adolescents'…

  14. Advocacy, a Role for DD Councils.

    ERIC Educational Resources Information Center

    Paul, James, L., Ed.; And Others

    The advocacy role of state developmental disabilities councils is examined in the monograph. It is explained that the material was gathered from a 1974 conference in Winter Park, Colorado. Topics addressed include the potential for advocacy, a personal perspective on developmental disabilities from a cerebral palsied adult, planning and evaluating…

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

    USDA-ARS?s Scientific Manuscript database

    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...

  16. Evolutionary Developmental Psychology: Contributions from Comparative Research with Nonhuman Primates

    ERIC Educational Resources Information Center

    Maestripieri, Dario; Roney, James R.

    2006-01-01

    Evolutionary developmental psychology is a discipline that has the potential to integrate conceptual approaches to the study of behavioral development derived from psychology and biology as well as empirical data from humans and animals. Comparative research with animals, and especially with nonhuman primates, can provide evidence of adaptation in…

  17. Developmental Coordination Disorder and Reported Enjoyment of Physical Education in Children

    ERIC Educational Resources Information Center

    Cairney, John; Hay, John; Mandigo, James; Wade, Terrance; Faught, Brent E.; Flouris, Andreas

    2007-01-01

    Children with developmental coordination disorder (DCD) are less likely to enjoy participating in physical education (PE) than children without motor coordination difficulties. However, no studies have attempted to quantify this relationship or examine potentially modifiable mediating variables. Using a large sample (N = 590) of children (aged 9…

  18. Computerised Attention Training for Children with Intellectual and Developmental Disabilities: A Randomised Controlled Trial

    ERIC Educational Resources Information Center

    Kirk, Hannah E.; Gray, Kylie M.; Ellis, Kirsten; Taffe, John; Cornish, Kim M.

    2016-01-01

    Background: Children with intellectual and developmental disabilities (IDD) experience heightened attention difficulties which have been linked to poorer cognitive, academic and social outcomes. Although, increasing research has focused on the potential of computerised cognitive training in reducing attention problems, limited studies have…

  19. Computational Modeling and Simulation of Developmental Toxicity: what can we learn from a virtual embryo? (RIVM, Brussels)

    EPA Science Inventory

    Developmental and Reproductive Toxicity (DART) testing is important for assessing the potential consequences of drug and chemical exposure on human health and well-being. Complexity of pregnancy and the reproductive cycle makes DART testing challenging and costly for traditional ...

  20. Predictors and Moderators of Psychological Distress in Mothers of Children with Pervasive Developmental Disorders

    ERIC Educational Resources Information Center

    Tobing, Lauren E.; Glenwick, David S.

    2006-01-01

    This study explored potential predictors of psychological distress and moderators of the relation between parenting stress and psychological distress in mothers of children with pervasive developmental disorders (PDDs). Ninety-seven mothers of children diagnosed with autism spectrum disorders completed measures assessing children's functional…

  1. Bridging Developmental Systems Theory and Evolutionary Psychology Using Dynamic Optimization

    ERIC Educational Resources Information Center

    Frankenhuis, Willem E.; Panchanathan, Karthik; Clark Barrett, H.

    2013-01-01

    Interactions between evolutionary psychologists and developmental systems theorists have been largely antagonistic. This is unfortunate because potential synergies between the two approaches remain unexplored. This article presents a method that may help to bridge the divide, and that has proven fruitful in biology: dynamic optimization. Dynamic…

  2. The Developmental Approach to School Readiness.

    ERIC Educational Resources Information Center

    Ogletree, Earl J.

    In the United States, a psychometric psychology dominates the thinking of educators. For traditional, political, and social reasons, developmental psychology rarely informs educational practices. This is the case even though studies show that the inducing of cognitive learning before a child is ready will reduce the child's learning potential and…

  3. Techtalk: "Second Life" and Developmental Education

    ERIC Educational Resources Information Center

    Burgess, Melissa L.; Caverly, David C.

    2009-01-01

    In our previous two columns, we discussed the potential for using blogs and wikis with developmental education (DE) students. Another Web 2.0 technology, virtual environments like "Second Life", provides a virtual world where residents create avatars (three-dimensional [3-D] self-representations) and navigate around an online environment (Caverly,…

  4. Crystallizing Conditions, Developmental Advance and Education. First Annual Report.

    ERIC Educational Resources Information Center

    Feldman, David

    This research report outlines progress made in the development of a conceptual framework (called "crystallization") which is intended to explain the conditions found to be critical to the child's potential for developmental change. The research completed and proposed on crystallization has centered around four main areas of activity: (1)…

  5. CATV in Central Appalachia: A Feasibility Study.

    ERIC Educational Resources Information Center

    Marchese, Lamar

    This document examines the problems and potentials that cable televisions have in public service, with a view toward understanding CATV's growth and how that growth relates to the developmental and educational needs of the Appalachian Region. Six developmental districts in Appalachia were chosen for intensive study. A team of consultants was…

  6. ERPs and Eye Movements Reflect Atypical Visual Perception in Pervasive Developmental Disorder

    ERIC Educational Resources Information Center

    Kemner, Chantal; van Engeland, Herman

    2006-01-01

    Many studies of eye tracking or event-related brain potentials (ERPs) in subjects with Pervasive Developmental Disorder (PDD) have yielded inconsistent results on attentional processing. However, recent studies have indicated that there are specific abnormalities in early processing that are probably related to perception. ERP amplitudes in…

  7. Neural Progenitor Cells as Models for High-Throughput Screens of Developmental Neurotoxicity: State of the Science

    EPA Science Inventory

    In vitro, high-throughput approaches have been widely recommended as an approach to screen chemicals for the potential to cause developmental neurotoxicity and prioritize them for additional testing. The choice of cellular models for such an approach will have important ramificat...

  8. An Evaluation of a Stimulus Preference Assessment of Auditory Stimuli for Adolescents with Developmental Disabilities

    ERIC Educational Resources Information Center

    Horrocks, Erin; Higbee, Thomas S.

    2008-01-01

    Previous researchers have used stimulus preference assessment (SPA) methods to identify salient reinforcers for individuals with developmental disabilities including tangible, leisure, edible and olfactory stimuli. In the present study, SPA procedures were used to identify potential auditory reinforcers and determine the reinforcement value of…

  9. Audiovisual Speech Integration in Pervasive Developmental Disorder: Evidence from Event-Related Potentials

    ERIC Educational Resources Information Center

    Magnee, Maurice J. C. M.; de Gelder, Beatrice; van Engeland, Herman; Kemner, Chantal

    2008-01-01

    Background: Integration of information from multiple sensory sources is an important prerequisite for successful social behavior, especially during face-to-face conversation. It has been suggested that communicative impairments among individuals with pervasive developmental disorders (PDD) might be caused by an inability to integrate synchronously…

  10. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Butyl Phthalate (DBP).

    PubMed

    2003-04-01

    TThe National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-n-butyl phthalate (DBP) to cause adverse effects on reproduction and development in humans. DBP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates Expert Panel. These phthalates were selected for evaluation because of high production volume, extent of human exposures, use in children's products, and/or published evidence of reproductive or developmental toxicity. Unlike many phthalates, DBP is not currently used as a plasticizer in polyvinyl chloride plastics. DBP is a component of latex adhesives and is used in cosmetics and other personal care products, as a plasticizer in cellulose plastics, and as a solvent for dyes. The results of this evaluation on DBP are published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Di-n-Butyl Phthalate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to DBP on human development and reproduction. First, although DBP could possibly affect human reproduction and development if exposures are sufficiently high, the NTP concludes that there is negligible concern for reproductive toxicity in exposed adults. Second, the NTP concludes that there is minimal concern for developmental effects when pregnant women are exposed to DBP levels estimated by the panel (2-10 mug/kg body weight/day). There is no direct evidence that exposure of people to DBP adversely affects reproduction or development, but studies reviewed by the expert panel show that oral exposure to high doses of DBP (>/=100 mg/kg body weight/day) may adversely affect the prenatal and early postnatal development in rodents. Finally, based on exposure estimates in women of reproductive age, the NTP concludes that there is some concern for DBP causing adverse effects to human development, particularly development of the male reproductive system. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available electronically in PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).

  11. Epigenetics and the Developmental Origins of Health and ...

    EPA Pesticide Factsheets

    Epigenetic programming is likely to be an important mechanism underlying the lasting influence of the developmental environment on lifelong health, a concept known as the Developmental Origins of Health and Disease (DOHaD). DNA methylation, posttranslational histone protei n modifications, noncoding RNAs and recruited protein complexes are elements of the epigenetic regulation of gene transcription. These heritable but reversible changes in gene function are dynamic and labile during specific stages of the reproductive cycle and development. Epigenetic marks may be maintained throughout an individual's lifespan and can alter the life-long risk of disease; the nature of these epigenetic marks and their potential alteration by environmental factors is an area of active research. This chapter provides an overview of epigenetic regulation, particularly as it occurs as an essential component of embryo-fetal development. In this chapter we will present key features of DNA methylation and histone protein modifications, including the enzymes involved and the effects of these modifications on gene transcription. We will discuss the interplay of these dynamic modifications and the emerging role of noncoding RNAs in epigenetic gene regulation.

  12. Improved reading measures in adults with dyslexia following transcranial direct current stimulation treatment.

    PubMed

    Heth, Inbahl; Lavidor, Michal

    2015-04-01

    To better understand the contribution of the dorsal system to word reading, we explored transcranial direct current stimulation (tDCS) effects when adults with developmental dyslexia received active stimulation over the visual extrastriate area MT/V5, which is dominated by magnocellular input. Stimulation was administered in 5 sessions spread over two weeks, and reading speed and accuracy as well as reading fluency were assessed before, immediately after, and a week after the end of the treatment. A control group of adults with developmental dyslexia matched for age, gender, reading level, vocabulary and block-design WAIS-III sub-tests and reading level was exposed to the same protocol but with sham stimulation. The results revealed that active, but not sham stimulation, significantly improved reading speed and fluency. This finding suggests that the dorsal stream may play a role in efficient retrieval from the orthographic input lexicon in the lexical route. It also underscores the potential of tDCS as an intervention tool for improving reading speed, at least in adults with developmental dyslexia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. The developmental effects of extremely low frequency electric fields on visual and somatosensory evoked potentials in adult rats.

    PubMed

    Gok, Deniz Kantar; Akpinar, Deniz; Hidisoglu, Enis; Ozen, Sukru; Agar, Aysel; Yargicoglu, Piraye

    2016-01-01

    The purpose of our study was to investigate the developmental effects of extremely low frequency electric fields (ELF-EFs) on visual evoked potentials (VEPs) and somatosensory-evoked potentials (SEPs) and to examine the relationship between lipid peroxidation and changes of these potentials. In this context, thiobarbituric acid reactive substances (TBARS) levels were determined as an indicator of lipid peroxidation. Wistar albino female rats were divided into four groups; Control (C), gestational (prenatal) exposure (Pr), gestational+ postnatal exposure (PP) and postnatal exposure (Po) groups. Pregnant rats of Pr and PP groups were exposed to 50 Hz electric field (EF) (12 kV/m; 1 h/day), while those of C and Po groups were placed in an inactive system during pregnancy. Following parturition, rats of PP and Po groups were exposed to ELF-EFs whereas rats of C and Pr groups were kept under the same experimental conditions without being exposed to any EF during 68 days. On postnatal day 90, rats were prepared for VEP and SEP recordings. The latencies of VEP components in all experimental groups were significantly prolonged versus C group. For SEPs, all components of PP group, P2, N2 components of Pr group and P1, P2, N2 components of Po group were delayed versus C group. As brain TBARS levels were significantly increased in Pr and Po groups, retina TBARS levels were significantly elevated in all experimental groups versus C group. In conclusion, alterations seen in evoked potentials, at least partly, could be explained by lipid peroxidation in the retina and brain.

  14. DEVELOPMENTAL TOXICOLOGY EVALUATIONS -- ISSUES WITH INCLUDING NEUROTOXICOLOGY AND IMMUNOTOXICOLOGY ASSESSMENTS IN REPRODUCTIVE TOXICOLOGY STUDIES

    EPA Science Inventory

    Developmental and reproductive toxixology (DART) has routinely been a part of safety assessment. Attention is now focused on the effects of chemicals on the developing nervous and immune systems. This focus on developmental neurotoxicology (DNT) and developmental immunotoxicolo...

  15. Developmental Effects of the ToxCast™ Phase I and Phase II Chemicals in Caenorhabditis elegans and Corresponding Responses in Zebrafish, Rats, and Rabbits

    PubMed Central

    Boyd, Windy A.; Smith, Marjolein V.; Co, Caroll A.; Pirone, Jason R.; Rice, Julie R.; Shockley, Keith R.; Freedman, Jonathan H.

    2015-01-01

    Background: Modern toxicology is shifting from an observational to a mechanistic science. As part of this shift, high-throughput toxicity assays are being developed using alternative, nonmammalian species to prioritize chemicals and develop prediction models of human toxicity. Methods: The nematode Caenorhabditis elegans (C. elegans) was used to screen the U.S. Environmental Protection Agency’s (EPA’s) ToxCast™ Phase I and Phase II libraries, which contain 292 and 676 chemicals, respectively, for chemicals leading to decreased larval development and growth. Chemical toxicity was evaluated using three parameters: a biologically defined effect size threshold, half-maximal activity concentration (AC50), and lowest effective concentration (LEC). Results: Across both the Phase I and Phase II libraries, 62% of the chemicals were classified as active ≤ 200 μM in the C. elegans assay. Chemical activities and potencies in C. elegans were compared with those from two zebrafish embryonic development toxicity studies and developmental toxicity data for rats and rabbits. Concordance of chemical activity was higher between C. elegans and one zebrafish assay across Phase I chemicals (79%) than with a second zebrafish assay (59%). Using C. elegans or zebrafish to predict rat or rabbit developmental toxicity resulted in balanced accuracies (the average value of the sensitivity and specificity for an assay) ranging from 45% to 53%, slightly lower than the concordance between rat and rabbit (58%). Conclusions: Here, we present an assay that quantitatively and reliably describes the effects of chemical toxicants on C. elegans growth and development. We found significant overlap in the activity of chemicals in the ToxCast™ libraries between C. elegans and zebrafish developmental screens. Incorporating C. elegans toxicological assays as part of a battery of in vitro and in vivo assays provides additional information for the development of models to predict a chemical’s potential toxicity to humans. Citation: Boyd WA, Smith MV, Co CA, Pirone JR, Rice JR, Shockley KR, Freedman JH. 2016. Developmental effects of the ToxCast™ Phase I and II chemicals in Caenorhabditis elegans and corresponding responses in zebrafish, rats, and rabbits. Environ Health Perspect 124:586–593; http://dx.doi.org/10.1289/ehp.1409645 PMID:26496690

  16. Role of the pre- and post-natal environment in developmental programming of health and productivity.

    PubMed

    Reynolds, Lawrence P; Caton, Joel S

    2012-05-06

    The concept that developmental insults (for example, poor pre- or postnatal nutrition) can have long-term consequences on health and well-being of the offspring has been termed developmental programming. In livestock, developmental programming affects production traits, including growth, body composition, and reproduction. Although low birth weight was used as a proxy for compromised fetal development in the initial epidemiological studies, based on controlled studies using livestock and other animal models in the last two decades we now know that developmental programming can occur independently of any effects on birth weight. Studies in humans, rodents, and livestock also have confirmed the critical role of the placenta in developmental programming. In addition, the central role of epigenetic regulation in developmental programming has been confirmed. Lastly, relatively simple therapeutic/management strategies designed to 'rescue' placental development and function are being developed to minimize the effects of developmental programming on health and productivity of humans, livestock, and other mammals. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits

    PubMed Central

    Abbott, D.H.; Levine, J.E.; Dumesic, D.A.

    2017-01-01

    Genetics-based studies of women with polycystic ovary syndrome (PCOS) implicate >20 PCOS risk genes that collectively account for <10% of PCOS. Clinicians now consider that either rare alleles or non-genetic, potentially epigenetic, developmental origins may contribute key pathogenic components to >90% of PCOS cases. Animal models convincingly demonstrate excess fetal testosterone exposure in females as a reliable, epigenetic, developmental origin for PCOS-like traits. In particular, nonhuman primates (NHPs) provide the most faithful emulation of PCOS-like pathophysiology, likely because of close similarities to humans in genomic, developmental, reproductive and metabolic characteristics, as well as aging. Recent appreciation of potential molecular mechanisms contributing to enhanced LH action in both PCOS women (GWAS-based) and PCOS-like monkeys (DNA methylation-based) suggest commonality in pathogenic origins. This review examines the translational relevance of NHP studies to PCOS, identifying characteristics of newborn females at risk for PCOS-like traits and potential prepubertal treatment interventions to ameliorate PCOS onset. PMID:27426126

  18. Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

    PubMed

    Bolton, Helen; Graham, Sarah J L; Van der Aa, Niels; Kumar, Parveen; Theunis, Koen; Fernandez Gallardo, Elia; Voet, Thierry; Zernicka-Goetz, Magdalena

    2016-03-29

    Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.

  19. Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits.

    PubMed

    Abbott, David H; Levine, Jon E; Dumesic, Daniel A

    2016-01-01

    Genetics-based studies of women with polycystic ovary syndrome (PCOS) implicate >20 PCOS risk genes that collectively account for <10% of PCOS. Clinicians now consider that either rare alleles or non-genetic, potentially epigenetic, developmental origins may contribute key pathogenic components to >90% of PCOS cases. Animal models convincingly demonstrate excess fetal testosterone exposure in females as a reliable, epigenetic, developmental origin for PCOS-like traits. In particular, nonhuman primates (NHPs) provide the most faithful emulation of PCOS-like pathophysiology, likely because of close similarities to humans in genomic, developmental, reproductive and metabolic characteristics, as well as aging. Recent appreciation of potential molecular mechanisms contributing to enhanced LH action in both PCOS women (GWAS-based) and PCOS-like monkeys (DNA methylation-based) suggest commonality in pathogenic origins. This review examines the translational relevance of NHP studies to PCOS, identifying characteristics of newborn females at risk for PCOS-like traits and potential prepubertal treatment interventions to ameliorate PCOS onset.

  20. Infant formula supplementation with long-chain polyunsaturated fatty acids has no effect on Bayley developmental scores at 18 months of age--IPD meta-analysis of 4 large clinical trials.

    PubMed

    Beyerlein, Andreas; Hadders-Algra, Mijna; Kennedy, Katherine; Fewtrell, Mary; Singhal, Atul; Rosenfeld, Eva; Lucas, Alan; Bouwstra, Hylco; Koletzko, Berthold; von Kries, Rüdiger

    2010-01-01

    To find out whether supplementation of formula milk by long-chain polyunsaturated fatty acids (LCPUFA) affects neurodevelopment at 18 months of age in term or preterm infants by an individual patient data (IPD) meta-analysis. Data of 870 children from 4 large randomised clinical trials for formula milk with and without LCPUFAs allowed for assessing the effect of LCPUFA with adjustment for potential confounders and extensive subgroup analysis on prematurity, LCPUFA source, and dosage. Any additional clinical trials examining the effect of LCPUFA supplementation on Bayley Scales of Infant Development at 18 months were regarded as relevant. Two relevant studies were identified by MEDLINE, but were not available to us. An IPD meta-analysis was performed with subgroup analyses by preterm delivery, very low birth weight (<1500 g), trials with higher amounts of docosahexaenoic acid (DHA) and arachidonic acid (AA), and specific sources of LCPUFA. The sample size of 870 children was sufficient to detect clinically relevant differences in Bayley Scales even in subgroups. There were no significant differences in mental or psychomotor developmental indexes between LCPUFA-supplemented and control groups for all children or in subgroups. This was confirmed with adjustment for the possible confounders: sex, gestational age, birth weight, maternal age, and maternal smoking. The adjusted mean differences in mental developmental index and psychomotor developmental index for all of the children were -0.8 (95% confidence interval -2.8 to 1.2) and -1.0 (-2.7 to 0.7), respectively. These data based on considerable sample size provide substantial evidence that LCPUFA supplementation of infant formula does not have a clinically meaningful effect on the neurodevelopment as assessed by Bayley scores at 18 months. Inclusion of all relevant data should not have led to differing conclusions except, possibly, for very-low-birth-weight infants.

  1. Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure

    PubMed Central

    Balaraman, Sridevi; Idrus, Nirelia M.; Miranda, Rajesh C.; Thomas, Jennifer D.

    2017-01-01

    Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol’s developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol’s long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4–9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4–21. On PD 22, subjects were sacrificed, and RNA isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was normalized with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p<0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p<0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by ethanol. These findings have important implications for the mechanisms by which choline may serve as a potential treatment for FASD. PMID:28433422

  2. Flight performance in the altricial zebra finch: Developmental effects and reproductive consequences.

    PubMed

    Crino, Ondi L; Klaassen van Oorschot, Brett; Crandell, Kristen E; Breuner, Creagh W; Tobalske, Bret W

    2017-04-01

    The environmental conditions animals experience during development can have sustained effects on morphology, physiology, and behavior. Exposure to elevated levels of stress hormones (glucocorticoids, GCs) during development is one such condition that can have long-term effects on animal phenotype. Many of the phenotypic effects of GC exposure during development (developmental stress) appear negative. However, there is increasing evidence that developmental stress can induce adaptive phenotypic changes. This hypothesis can be tested by examining the effect of developmental stress on fitness-related traits. In birds, flight performance is an ideal metric to assess the fitness consequences of developmental stress. As fledglings, mastering takeoff is crucial to avoid bodily damage and escape predation. As adults, takeoff can contribute to mating and foraging success as well as escape and, thus, can affect both reproductive success and survival. We examined the effects of developmental stress on flight performance across life-history stages in zebra finches ( Taeniopygia guttata ). Specifically, we examined the effects of oral administration of corticosterone (CORT, the dominant avian glucocorticoid) during development on ground-reaction forces and velocity during takeoff. Additionally, we tested for associations between flight performance and reproductive success in adult male zebra finches. Developmental stress had no effect on flight performance at all ages. In contrast, brood size (an unmanipulated variable) had sustained, negative effects on takeoff performance across life-history stages with birds from small broods performing better than birds from large broods. Flight performance at 100 days posthatching predicted future reproductive success in males; the best fliers had significantly higher reproductive success. Our results demonstrate that some environmental factors experienced during development (e.g. clutch size) have stronger, more sustained effects than others (e.g. GC exposure). Additionally, our data provide the first link between flight performance and a direct measure of reproductive success.

  3. 29 CFR 1952.232 - Completion of developmental steps and certification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Completion of developmental steps and certification. 1952... § 1952.232 Completion of developmental steps and certification. (a) In accordance with the requirements... plan received certification, effective February 8, 1980, as having completed all developmental steps...

  4. Designing Meaningful Developmental Reform. Research Overview

    ERIC Educational Resources Information Center

    Jaggars, Shanna Smith; Hodara, Michelle; Stacey, Georgia West

    2013-01-01

    This practitioner packet is designed to help community college administrators implement reforms to developmental education at their colleges. It reviews common impediments to developmental reform and presents data that supports directions colleges can take to create a system of developmental education that might serve students more effectively.…

  5. What Happens to Students Placed into Developmental Education? A Meta-Analysis of Regression Discontinuity Studies

    ERIC Educational Resources Information Center

    Valentine, Jeffrey C.; Konstantopoulos, Spyros; Goldrick-Rab, Sara

    2017-01-01

    This article reports a systematic review and meta-analysis of studies that use regression discontinuity to examine the effects of placement into developmental education. Results suggest that placement into developmental education is associated with effects that are negative, statistically significant, and substantively large for three outcomes:…

  6. Cognitive Effects of Air Pollution Exposures and Potential Mechanistic Underpinnings

    PubMed Central

    Allen, J.L.; Klocke, C.; Morris-Schaffer, K.; Conrad, K.; Sobolewski, M.; Cory-Slechta, D.A.

    2017-01-01

    Purpose of review This review sought to address the potential for air pollutants to impair cognition and mechanisms by which that might occur. Recent findings Air pollution has been associated with deficits in cognitive functions across a wide range of epidemiological studies, both with developmental and adult exposures. Studies in animal models are significantly more limited in number, with somewhat inconsistent findings to date for measures of learning, but show more consistent impairments for short term memory. Potential contributory mechanisms include oxidative stress/inflammation, altered levels of dopamine and/or glutamate and changes in synaptic plasticity/structure. Summary Epidemiological studies are consistent with adverse effects of air pollutants on cognition, but additional studies and better phenotypic characterization are needed for animal models, including more precise delineation of specific components of cognition that are affected, as well as definitions of critical exposure periods for such effects and the components of air pollution responsible. This would permit development of more circumscribed hypotheses as to potential behavioral and neurobiological mechanisms. PMID:28435996

  7. Developmental milestones among Aboriginal children in Canada

    PubMed Central

    Findlay, Leanne; Kohen, Dafna; Miller, Anton

    2014-01-01

    BACKGROUND: Windows of achievement provide age ranges for the attainment of early developmental skills. Group-specific research is warranted given that development may be influenced by social or cultural factors. OBJECTIVES: To examine developmental milestones for Inuit, Métis and off-reserve First Nation children in Canada, based on developmental domains collected from the 2006 Aboriginal Children’s Survey. Sociodemographic and health predictors of risk for developmental delay were also examined. RESULTS: The ranges in which children achieve certain developmental milestones are presented. Gross motor and self-help skills were found to be achieved earlier (across the three Aboriginal groups), whereas language skills were achieved slightly later than in Canadian children in general. Furthermore, health factors (eg, low birth weight, chronic health conditions) were associated with late achievement of developmental outcomes even when sociodemographic characteristics were considered. CONCLUSIONS: Findings suggest that the timing of milestone achievement may differ for Aboriginal children, highlighting the importance of establishing culturally specific norms and standards rather than relying on those derived from general populations. This information may be useful for practitioners and parents interested in identifying the age ranges for development, as well as age ranges indicating potential for developmental risk and opportunities for early intervention among Aboriginal children. PMID:24855426

  8. Developmental outcome, including setback, in young children with severe visual impairment.

    PubMed

    Dale, Naomi; Sonksen, Patricia

    2002-09-01

    This study retrospectively investigated the developmental perspective of 69 children (40 males, 29 females) with 'potentially simple' congenital disorders of the peripheral visual system: development was examined in the context of degree of visual impairment. Developmental and visual assessments were carried out at 10 to 16 months (Time 1) and 27 to 54 months of age (Time 2). Participants were grouped according to (1) visual status: profound visual impairment (PVI), severe visual impairment (SVI); (2) developmental status on the Reynell-Zinkin scales. A majority of the sample showed normal development on all subscales (62% Time 1, 57% Time 2). Those with PVI were more developmentally vulnerable than SVI with a greater incidence of (1) uneven developmental profile at Time 1 (48% PVI, 16% SVI); (2) global learning difficulties at Time 2 (37% PVI, 0% SVI); (3) delay on individual subscales at Time 2 (p<0.02 PVI versus SVI); (4) deceleration (verbal comprehension 74% PVI, 24% SVI, sensorimotor understanding 70% PVI, 27% SVI); and (5) severe developmental setback (33% PVI, 7% SVI). Risk factors of visual level, age, and sex for poor developmental outcome in infants with visual impairment were established.

  9. Language used in interaction during developmental science instruction

    NASA Astrophysics Data System (ADS)

    Avenia-Tapper, Brianna

    The coordination of theory and evidence is an important part of scientific practice. Developmental approaches to instruction, which make the relationship between the abstract and the concrete a central focus of students' learning activity, provide educators with a unique opportunity to strengthen students' coordination of theory and evidence. Therefore, developmental approaches may be a useful instructional response to documented science achievement gaps for linguistically diverse students. However, if we are to leverage the potential of developmental instruction to improve the science achievement of linguistically diverse students, we need more information on the intersection of developmental science instruction and linguistically diverse learning contexts. This manuscript style dissertation uses discourse analysis to investigate the language used in interaction during developmental teaching-learning in three linguistically diverse third grade classrooms. The first manuscript asks how language was used to construct ascension from the abstract to the concrete. The second manuscript asks how students' non-English home languages were useful (or not) for meeting the learning goals of the developmental instructional program. The third manuscript asks how students' interlocutors may influence student choice to use an important discourse practice--justification--during the developmental teaching-learning activity. All three manuscripts report findings relevant to the instructional decisions that teachers need to make when implementing developmental instruction in linguistically diverse contexts.

  10. Effects of exposure to azaarenes on emergence and mouthpart development in the midge Chironomus riparius (Diptera: Chironomidae)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bleeker, E.A.J.; Leslie, H.A.; Groenendijk, D.

    1999-08-01

    Adverse effects of azaarenes on emergence and mouthpart development of the midge Chironomus riparius were analyzed using six closely related three-ringed isomers and metabolites. Effects on growth rate were examined by comparing the average day of emergence of exposed midges with that of controls. Fluctuating asymmetry (FA) in the pecten epipharyngis was examined as a measure of developmental abnormality. Delayed emergence was found at concentrations as low as 2% of the acute LC50, so emergence day appears to be a useful sensitive parameter to quantity life cycle effects. No differences in FA were found between exposed and control larvae, although,more » in other studies, all compounds have been proven to be genotoxic. The differences in FA were found between exposed and control larvae, although, in other studies, all compounds have been proven to be genotoxic. The differences in the genotoxic and FA-inducing properties of these compounds indicate that different mechanisms are involved in expressing these adverse effects. This study also illustrates that the choice of the morphological parameter strongly influences the results of developmental disturbance analyses and thus the risk qualification of a potentially hazardous compound.« less

  11. The dynamic lift of developmental process.

    PubMed

    Smith, Linda B; Breazeal, Cynthia

    2007-01-01

    What are the essential properties of human intelligence, currently unparalleled in its power relative to other biological forms and relative to artificial forms of intelligence? We suggest that answering this question depends critically on understanding developmental process. This paper considers three principles potentially essential to building human-like intelligence: the heterogeneity of the component processes, the embedding of development in a social world, and developmental processes that change the cognitive system as a function of the history of soft-assemblies of these heterogeneous processes in specific tasks. The paper uses examples from human development and from developmental robotics to show how these processes also may underlie biological intelligence and enable us to generate more advanced forms of artificial intelligence.

  12. Perceptions of societal developmental hierarchies in Europe and beyond: A Bulgarian Perspective

    PubMed Central

    Melegh, Attila; Thornton, Arland; Philipov, Dimiter; Young-DeMarco, Linda

    2012-01-01

    We examine how ordinary citizens in Bulgaria view the developmental levels of European countries and certain states outside of Europe. Our research is motivated by the understanding that scholars and policy makers have for centuries used developmental hierarchies to characterize countries and that this perception of differential development has shaped interactions among different groups, countries and regions. We expect that views of such developmental hierarchies and models have great potential for influencing demographic and family behavior and political and cultural identities of ordinary people. Using data from a 2009 survey in Bulgaria we document that developmental hierarchies are widely perceived in Bulgaria, but are distributed differentially by age, education, and degree of urbanization. We also consider internal mechanisms underlying this hierarchical understanding of development and how hierarchical understandings may be related to national identities. PMID:23807821

  13. Recruitment strategies should not be randomly selected: empirically improving recruitment success and diversity in developmental psychology research

    PubMed Central

    Sugden, Nicole A.; Moulson, Margaret C.

    2015-01-01

    Psychological and developmental research have been critiqued for the lack of diversity of research samples. Because differences in culture, race, and ethnicity can influence participant behavior, limited diversity limits the generalizability of the findings. These differences may also impact how participants behave in response to recruitment attempts, which suggests that recruitment itself may be leveraged to increase sample diversity. The goal of the current study was to determine what factors, within a recruitment interaction, could be leveraged to increase success and diversity when recruiting families with children for developmental research. Study 1 found three factors influenced success: (1) recruitment was more successful when other potential participants were also interested (i.e., recruiters were busy), (2) recruiters of particular races were more successful than recruiters of other races, and (3) differences in success were related to what the recruiter said to engage the potential participant (i.e., the script). The latter two factors interacted, suggesting some recruiters were using less optimal scripts. To improve success rates, study 2 randomly assigned scripts to recruiters and encouraged them to recruit more vigorously during busy periods. Study 2 found that two factors influenced success: (1) some scripts were more successful than others and (2) we were more successful at recruiting non-White potential participants than White participants. These two interacted, with some scripts being more successful with White and other scripts being more successful with non-White families. This intervention significantly increased recruitment success rate by 8.1% and the overall number of families recruited by 15.3%. These findings reveal that empirically evaluating and tailoring recruitment efforts based on the most successful strategies is effective in boosting diversity through increased participation of children from non-White families. PMID:25972829

  14. The Effect of Observing Response Procedures on the Reduction of Over-Selectivity in a Match to Sample Task: Immediate but Not Long Term Benefits

    ERIC Educational Resources Information Center

    Broomfield, Laura; McHugh, Louise; Reed, Phil

    2008-01-01

    Stimulus over-selectivity occurs when only one of potentially many aspects of the environment comes to control behavior. In three experiments, adult participants with no developmental disabilities were trained and tested in a match to samples (MTS) paradigm. Participants in Experiment 1 were assigned to one of two conditions, which differed on…

  15. Neurobehavioral Impairments Caused by Developmental Imidacloprid Exposure in Zebrafish

    PubMed Central

    Crosby, Emily B.; Bailey, Jordan M.; Oliveri, Anthony N.; Levin, Edward D.

    2015-01-01

    BACKGROUND Neonicotinoid insecticides are becoming more widely applied as organophosphate (OP) insecticides are decreasing in use. Because of their relative specificity to insect nicotinic receptors, they are thought to have reduced risk of neurotoxicity in vertebrates. However, there is scant published literature concerning the neurobehavioral effects of developmental exposure of vertebrates to neonicotinoids. METHODS Using zebrafish, we investigated the neurobehavioral effects of developmental exposure to imidacloprid, a prototypic neonicotinoid pesticide. Nicotine was also administered for comparison. Zebrafish were exposed via immersion in aqueous solutions containing 45 μM or 60 μM of imidacloprid or nicotine (or vehicle control) from 4 h to 5 d post fertilization. The functional effects of developmental exposure to both imidacloprid and nicotine were assessed in larvae using an activity assay and during adolescence and adulthood using a battery of neurobehavioral assays, including assessment of sensorimotor response and habituation in a tactile startle test, novel tank swimming, and shoaling behavior. RESULTS In larvae, developmental imidacloprid exposure at both doses significantly decreased swimming activity. The 5D strain of zebrafish were more sensitive to both nicotine and imidacloprid than the AB* strain. In adolescent and adult fish, developmental exposure to imidacloprid significantly decreased novel tank exploration and increased sensorimotor response to startle stimuli. While nicotine did not affect novel tank swimming, it increased sensorimotor response to startle stimuli at the low dose. No effects of either compound were found on shoaling behavior or habituation to a startling stimulus. DISCUSSION Early developmental exposure to imidacloprid has both early-life and persisting effects on neurobehavioral function in zebrafish. Its developmental neurotoxicity should be further investigated. PMID:25944383

  16. A study of associations between early DHA status and fatty acid desaturase (FADS) SNP and developmental outcomes in children of obese mothers.

    PubMed

    Andersen, Karina R; Harsløf, Laurine B S; Schnurr, Theresia M; Hansen, Torben; Hellgren, Lars I; Michaelsen, Kim F; Lauritzen, Lotte

    2017-01-01

    DHA from diet or endogenous synthesis has been proposed to affect infant development, however, results are inconclusive. In this study, we aim to verify previously observed fatty acid desaturase gene cluster (FADS) SNP-specific associations with erythrocyte DHA status in 9-month-old children and sex-specific association with developmental outcomes. The study was performed in 166 children (55 % boys) of obese mothers. Erythrocyte fatty acid composition was analysed in blood-samples obtained at 9 months of age, and developmental outcomes assessed by the Ages and Stages Questionnaire at 3 years. Erythrocyte DHA level ranged from 4·4 to 9·9 % of fatty acids, but did not show any association with FADS SNP or other potential determinants. Regression analysis showed associations between erythrocyte DHA and scores for personal-social skills (β 1·8 (95 % CI 0·3, 3·3), P=0·019) and problem solving (β 3·4 (95 % CI 1·2, 5·6), P=0·003). A tendency was observed for an association in opposite direction between minor alleles (G-variant) of rs1535 and rs174575 and personal-social skills (P=0·062 and 0·068, respectively), which became significant when the SNP were combined based on their previously observed effect on erythrocyte DHA at 9 months of age (β 2·6 (95 % CI 0·01, 5·1), P=0·011). Sex-SNP interaction was indicated for rs174575 genotype on fine motor scores (P=0·016), due to higher scores among minor allele carrying girls (P=0·043), whereas no effect was seen among boys. In conclusion, DHA-increasing FADS SNP and erythrocyte DHA status were consistently associated with improved personal-social skills in this small cohort of children of obese mothers irrespective of sex, but the sample was too small to verify potential sex-specific effects.

  17. Understanding Social Anxiety Disorder in Adolescents and Improving Treatment Outcomes: Applying the Cognitive Model of Clark and Wells (1995).

    PubMed

    Leigh, Eleanor; Clark, David M

    2018-04-13

    Social anxiety disorder is a condition characterised by a marked and persistent fear of being humiliated or scrutinised by others. Age-of-onset data point to adolescence as a developmentally sensitive period for the emergence of the condition, at a time when the peer group becomes increasingly important. Social anxiety in adolescence is associated with considerable impairment that persists through to adulthood. There are clear potential benefits to delivering effective interventions during adolescence. However, there is limited evidence on the specific efficacy of available therapies. This is in contrast to adults, for whom we have interventions with very specific treatment effects. One such treatment is individual cognitive therapy. Cognitive therapy is based on the cognitive model of social anxiety proposed by Clark and Wells (in: Heimberg, Leibowitz, Hope, Scheiber (eds) Social phobia: diagnosis, assessment and treatment, The Guilford Press, New York, 1995). The present review examines the potential application of this adult cognitive model to the understanding of adolescent social anxiety and considers additional adolescent-specific factors that need to be accommodated. It is suggested that a developmentally sensitive adoption of the cognitive model of social anxiety disorder (Clark and Wells 1995) for adolescents may lead to better treatment outcomes.

  18. Developmental delay in the Amazon: The social determinants and prevalence among rural communities in Peru

    PubMed Central

    Alnasser, Yossef

    2017-01-01

    The consequences of poor child development are becoming increasingly recognized. Programs are being put in place around the world to improve child development by providing healthy and stimulating environments for children. However, these programs often have limited reach and little is known about the prevalence of developmental delay in under-developed communities. The current study set-out to better understand the prevalence of developmental delay in rural communities in the Amazon region of Peru. Also, it explores social determinants that are associated with any delay. Cross-sectional study by evaluating developmental delay in children under 4 years utilizing Ages and Stages Questionnaire (ASQ-3). Additionally, conducting a social determinants questionnaire answered by caretakers to identify social drivers for developmental delay. The data was analyzed with multi-variant analysis to measure association. The prevalence of developmental delay in the Amazonian communities was 26.7% (19.3% in communication, 11.4% in gross motor skills, 8% in both) (N = 596). The multivariate logistic regression analysis revealed significant associations between developmental delay and; level of education (OR 0.64, p = 0.009), age of mother during child’s birth (OR 0.96, p = 0.002), visits by community health agents (OR 0.73, p = 0.013), and river as primary water source (OR 2.39, p = 0.001). The social determinants questionnaire revealed that 39% of the mothers had their first child before the age of 17, nearly half stopped going to school before the age of 12 (52%), 29% gave birth at home, 13% breast fed for less than 7 months, and 50% of the children had diarrhea in the last month. There is still a great need to improve the conditions for child development in the Amazon region of Peru. One-fourth of the children suffer from developmental delay, which will likely impede their potentials for life unless something is done. The impact of education, age of mother at birth of the child, community health agents, and access to clean drinking water were important findings. Improvements can be made in these areas to create a large, cost-effective impact on the well-being of the communities. PMID:29023517

  19. Developmental delay in the Amazon: The social determinants and prevalence among rural communities in Peru.

    PubMed

    Westgard, Christopher; Alnasser, Yossef

    2017-01-01

    The consequences of poor child development are becoming increasingly recognized. Programs are being put in place around the world to improve child development by providing healthy and stimulating environments for children. However, these programs often have limited reach and little is known about the prevalence of developmental delay in under-developed communities. The current study set-out to better understand the prevalence of developmental delay in rural communities in the Amazon region of Peru. Also, it explores social determinants that are associated with any delay. Cross-sectional study by evaluating developmental delay in children under 4 years utilizing Ages and Stages Questionnaire (ASQ-3). Additionally, conducting a social determinants questionnaire answered by caretakers to identify social drivers for developmental delay. The data was analyzed with multi-variant analysis to measure association. The prevalence of developmental delay in the Amazonian communities was 26.7% (19.3% in communication, 11.4% in gross motor skills, 8% in both) (N = 596). The multivariate logistic regression analysis revealed significant associations between developmental delay and; level of education (OR 0.64, p = 0.009), age of mother during child's birth (OR 0.96, p = 0.002), visits by community health agents (OR 0.73, p = 0.013), and river as primary water source (OR 2.39, p = 0.001). The social determinants questionnaire revealed that 39% of the mothers had their first child before the age of 17, nearly half stopped going to school before the age of 12 (52%), 29% gave birth at home, 13% breast fed for less than 7 months, and 50% of the children had diarrhea in the last month. There is still a great need to improve the conditions for child development in the Amazon region of Peru. One-fourth of the children suffer from developmental delay, which will likely impede their potentials for life unless something is done. The impact of education, age of mother at birth of the child, community health agents, and access to clean drinking water were important findings. Improvements can be made in these areas to create a large, cost-effective impact on the well-being of the communities.

  20. Issues in Sexuality for Individuals with Developmental Disabilities: Myths, Misconceptions, and Mistreatment

    ERIC Educational Resources Information Center

    Irvine, Angela

    2005-01-01

    The myths and misconceptions surrounding the topic of sexuality and people with developmental disabilities were examined to better understand the detrimental effects they were having on the sexual health of individuals with developmental disabilities. Persons with developmental disabilities are often infantilised and viewed as asexual. This…

  1. 29 CFR 1952.352 - Completion of developmental steps and certification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Completion of developmental steps and certification. 1952... § 1952.352 Completion of developmental steps and certification. (a) Implementation of the Arizona... certified, effective September 18, 1981 as having completed all developmental steps specified in the plan as...

  2. Strategies for Teaching Developmental Mathematics Students at the College Level

    ERIC Educational Resources Information Center

    Swaincott Kautz, Natalie Lynn

    2016-01-01

    The purpose of this investigation was to identify strategies used by effective instructors of developmental mathematics, and to discover the perceptions developmental mathematics students have about these strategies. While there are research projects focusing solely on developmental mathematics achievement, this study fills a need by incorporating…

  3. BDE 49 and developmental toxicity in zebrafish

    PubMed Central

    McClain, Valerie; Stapleton, Heather M.; Gallagher, Evan

    2011-01-01

    The polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardants. Human health concerns of these agents have largely centered upon their potential to elicit reproductive and developmental effects. Of the various congeners, BDE 49 (2,2’,4,5’-tetrabromodiphenyl ether) has been poorly studied, despite the fact that it is often detected in the tissues of fish and wildlife species. Furthermore, we have previously shown that BDE 49 is a metabolic debromination product of BDE 99 hepatic metabolism in salmon, carp and trout, underscoring the need for a better understanding of biological effects. In the current study, we investigated the developmental toxicity of BDE 49 using the zebrafish (Danio rerio) embryo larval model. Embryo and larval zebrafish were exposed to BDE 49 at either 5 hours post fertilization (hpf) or 24 hpf and monitored for developmental and neurotoxicity. Exposure to BDE 49 at concentrations of 4 µM- 32 µM caused a dose-dependent loss in survivorship at 6 days post fertilization (dpf). Morphological impairments were observed prior to the onset of mortality, the most striking of which included severe dorsal curvatures of the tail. The incidence of dorsal tail curvatures was dose and time dependent. Exposure to BDE 49 caused cardiac toxicity as evidenced by a significant reduction in zebrafish heart rates at 6 dpf but not earlier, suggesting that cardiac toxicity was non-specific and associated with physiological stress. Neurobehavioral injury from BDE 49 was evidenced by an impairment of touch-escape responses observed at 5 dpf. Our results indicate that BDE 49 is a developmental toxicant in larval zebrafish that can cause morphological abnormalities and adversely affect neurobehavior. The observed toxicities from BDE 49 were similar in scope to those previously reported for the more common tetrabrominated congener, BDE 47, and also for other lower brominated PBDEs, suggest that these compounds may share similarities in risk to aquatic species. PMID:21951712

  4. Inhalation developmental toxicology studies: Acetonitrile in rats. Final report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mast, T.J.; Weigel, R.J.; Westerberg, R.B.

    1994-02-01

    The potential for acetonitrile to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 100, 400, or 1200 ppM acetonitrile, 6 hours/day, 7 days/week. Exposure of rats to these concentrations of acetonitrile resulted in mortality in the 1200 ppM group (2/33 pregnant females; 1/10 non-pregnant females). However, there were no treatment-related effects upon body weights or reproduction indices at any exposure level, nor was there a significant increase in the incidence of fetal malformations or variations. The only effect observed in the fetuses was a slight, but not statiscally significant, exposure-correlated increase in the incidence of supernumerary ribs.more » Determination of acetonitrile and cyanide concentrations in maternal rat blood showed that acetonitrile concentration in the blood increased with exposure concentration for all exposed maternal rats. Detectable amounts of cyanide in the blood were found only in the rats exposed to 1200 ppM acetonitrile ({approximately}2 {mu}g cyanide/g of blood).« less

  5. Effect of semolina-jaggery diet on survival and development of Drosophila melanogaster.

    PubMed

    Chattopadhyay, Debarati; James, Joel; Roy, Debasish; Sen, Soumadeep; Chatterjee, Rishita; Thirumurugan, Kavitha

    2015-01-01

    Drosophila melanogaster is an ideal model organism for developmental studies. This study tests the potential of semolina-jaggery (SJ) diet as a new formulation for bulk rearing of flies. Semolina and jaggery are organic products obtained from wheat endosperm and cane sugar, respectively. Semolina is a rich source of carbohydrates and protein. Jaggery has a high content of dietary sugars. Moreover, preparation of semolina jaggery diet is cost-effective and easy. Thus, the current study aimed to compare survival and developmental parameters of flies fed the SJ diet to flies fed the standard cornmeal-sugar-yeast (CSY) diet. SJ diet enhanced survival of flies without affecting fecundity; male flies showed increased resistance to starvation. A higher number of flies emerged at F2 and F3 generation when fed the SJ diet than when fed the control CSY diet. SJ diet did not increase fly body weight and lipid percentage. Therefore, SJ diet can be used for bulk rearing of healthy flies at par with the standard cornmeal-sugar-yeast diet.

  6. Global perspectives on the sexual and reproductive health of adolescents: patterns, prevention, and potential.

    PubMed

    Bearinger, Linda H; Sieving, Renee E; Ferguson, Jane; Sharma, Vinit

    2007-04-07

    Worldwide, societal shifts and behavioural patterns exacerbated by unique developmental vulnerabilities create a confluence of factors that place today's adolescents at heightened risks for poor health outcomes. Country-level data show that continued investment in effective prevention and treatment strategies is essential to protect adolescents' sexual and reproductive health. Whereas strategies must be tailored to the developmental needs of this age group and their social contexts, effective approaches are multifaceted. All adolescents need access to quality youth-friendly services provided by clinicians trained to work with this population. Sex education programmes should offer accurate, comprehensive information while building skills for negotiating sexual behaviours. Girls and boys also need equal access to youth development programmes that connect them with supportive adults and with educational and economic opportunities. Although progress has been made since the 1994 International Conference on Population and Development, adolescents continue to be disproportionately burdened by threats to their sexual and reproductive health.

  7. Comparison of a teratogenic transcriptome-based predictive test based on human embryonic versus inducible pluripotent stem cells.

    PubMed

    Shinde, Vaibhav; Perumal Srinivasan, Sureshkumar; Henry, Margit; Rotshteyn, Tamara; Hescheler, Jürgen; Rahnenführer, Jörg; Grinberg, Marianna; Meisig, Johannes; Blüthgen, Nils; Waldmann, Tanja; Leist, Marcel; Hengstler, Jan Georg; Sachinidis, Agapios

    2016-12-30

    Human embryonic stem cells (hESCs) partially recapitulate early embryonic three germ layer development, allowing testing of potential teratogenic hazards. Because use of hESCs is ethically debated, we investigated the potential for human induced pluripotent stem cells (hiPSCs) to replace hESCs in such tests. Three cell lines, comprising hiPSCs (foreskin and IMR90) and hESCs (H9) were differentiated for 14 days. Their transcriptome profiles were obtained on day 0 and day 14 and analyzed by comprehensive bioinformatics tools. The transcriptomes on day 14 showed that more than 70% of the "developmental genes" (regulated genes with > 2-fold change on day 14 compared to day 0) exhibited variability among cell lines. The developmental genes belonging to all three cell lines captured biological processes and KEGG pathways related to all three germ layer embryonic development. In addition, transcriptome profiles were obtained after 14 days of exposure to teratogenic valproic acid (VPA) during differentiation. Although the differentially regulated genes between treated and untreated samples showed more than 90% variability among cell lines, VPA clearly antagonized the expression of developmental genes in all cell lines: suppressing upregulated developmental genes, while inducing downregulated ones. To quantify VPA-disturbed development based on developmental genes, we estimated the "developmental potency" (D p ) and "developmental index" (D i ). Despite differences in genes deregulated by VPA, uniform D i values were obtained for all three cell lines. Given that the D i values for VPA were similar for hESCs and hiPSCs, D i can be used for robust hazard identification, irrespective of whether hESCs or hiPSCs are used in the test systems.

  8. Neurobehavioral assessment of children and adolescents attending a developmental disabilities clinic.

    PubMed

    Brasić, James Robert; Barnett, Jacqueline Y; Kowalik, S; Tsaltas, Margaret Owen; Ahmad, Raheela

    2004-12-01

    Although the risk of the eventual development of tardive dyskinesia and other persistent adverse effects of neuroleptics is high, among adults with mental retardation and other developmental disabilities, neuroleptics may ameliorate dyskinesias, aggression, and inattention. The effects of traditional neuroleptics on a comparable population of children and adolescents with mental retardation and other developmental disabilities are unknown. The objective of this study was to develop an assessment battery to describe the effects of traditional neuroleptics on the behavior and movements of a small sample of children and adolescents with mental retardation and other developmental disabilities. 13 children and adolescents aged 6 to 16 years attending a developmental disabilities clinic were evaluated utilizing a Movement Assessment Battery to measure behavior and motions. Five subjects took traditional neuroleptic medications. Trained raters can reliably assess the movements and behaviors of children and adolescents with multiple handicaps. Children and adolescents with developmental disabilities may be vulnerable to experience functional impairment and akathisia, tics, and other dyskinesias when administered traditional neuroleptic medications.

  9. The Teacher Advisor Program: An Innovative Approach to School Guidance.

    ERIC Educational Resources Information Center

    Myrick, Robert D.; And Others

    The Teacher Advisor Program (TAP) is an innovative developmental approach to counseling that directly involves teachers as advisors to 18 to 20 students, with whom they meet both individually and in group sessions. An introductory chapter that cites the need for a developmental approach to counseling in contemporary schools and the potential role…

  10. Cortical Response Variability as a Developmental Index of Selective Auditory Attention

    ERIC Educational Resources Information Center

    Strait, Dana L.; Slater, Jessica; Abecassis, Victor; Kraus, Nina

    2014-01-01

    Attention induces synchronicity in neuronal firing for the encoding of a given stimulus at the exclusion of others. Recently, we reported decreased variability in scalp-recorded cortical evoked potentials to attended compared with ignored speech in adults. Here we aimed to determine the developmental time course for this neural index of auditory…

  11. Counseling and Psychotherapy as Moral and Spiritual Practice: Facing a Major Paradigm Shift.

    ERIC Educational Resources Information Center

    Ivey, Allen E.; Rigazio-DiGilio, Sandra A.

    1992-01-01

    Comments on article by Blakeney and Blakeney in which they offer metatheoretical perspective for counseling and therapy that gives primacy to developmental issues and to understanding worldview of client. Goes on to further demonstrate holistic and integrative nature and potential of Blakeney framework, using Developmental Counseling and Therapy…

  12. A Developmental Model for Educational Planning: Democratic Rationalities and Dispositions

    ERIC Educational Resources Information Center

    Hess, Michael; Johnson, Jerry; Reynolds, Sharon

    2014-01-01

    The Developmental Democratic Planning (DDP) model frames educational planning as a process that extends beyond the immediate focus of a particular planning effort to acknowledge and cultivate the potential of all members of the organization to fulfill their roles as active participants in the democratic life of the organization. The DDP model…

  13. An Outline on Psychotropic Drug Use in the Developmentally Disabled Patient. Monograph #102.

    ERIC Educational Resources Information Center

    Vander Zanden, Jeanne A.

    This introduction to basic principles of psychotropic drug use in developmentally disabled patients is intended to provide personnel working in the field with information on appropriate clinical use as well as potential risks. Presented in outline form, information is provided on five classes of psychotropic drugs: antipsychotics; antidepressants;…

  14. Evaluation of 1066 ToxCast Chemicals in a human stem cell assay for developmental toxicity (SOT)

    EPA Science Inventory

    To increase the diversity of assays used to assess potential developmental toxicity, the ToxCast chemical library was screened in the Stemina devTOX quickPREDICT assay using human embryonic stem (hES) cells. A model for predicting teratogenicity was based on a training set of 23 ...

  15. Enhancing Children's Acceptance of Diverse Peers: Interaction Patterns in Two Mainstreamed Multicultural Day Care Centers.

    ERIC Educational Resources Information Center

    Swadener, Elizabeth Blue

    For one school year, the classroom and playground social behaviors of normally developing and developmentally delayed children were analyzed for the occurrence of interactions across gender, across race and ethnicity, and across developmental condition. The potential impact of teachers' nonsexist language, and encouragement of interaction among…

  16. Enhancing Resilience in Youth through a 10-Day Developmental Voyage

    ERIC Educational Resources Information Center

    Hayhurst, Jill; Hunter, John A.; Kafka, Sarah; Boyes, Mike

    2015-01-01

    The present study sought to examine the potential for resilience to be enhanced in a group of youth participating in a developmental voyage, and to identify the factors that contribute to increased resilience following the voyage. Two studies are reported. Study 1 revealed that voyage participants experienced increased resilience over the course…

  17. Community and Videos: An Action Plan to Increase Success Rates in California Community College Developmental Mathematics

    ERIC Educational Resources Information Center

    Long, Gary W.

    2010-01-01

    Success rates in California community college developmental mathematics courses have hovered around 50% for decades. These gatekeeper courses have prevented many students from earning college degrees. Since community college is the starting point for the majority of California's potential college graduates and the majority of these students…

  18. Sources of Developmental Change in the Efficiency of Information Search

    ERIC Educational Resources Information Center

    Ruggeri, Azzurra; Lombrozo, Tania; Griffiths, Thomas L.; Xu, Fei

    2016-01-01

    Children are active learners: they learn not only from the information people offer and the evidence they happen to observe, but by actively seeking information. However, children's information search strategies are typically less efficient than those of adults. In two studies, we isolate potential sources of developmental change in how children…

  19. 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…

  20. Special Education Teachers Attitudes toward Teaching Sex Education to Students with Developmental Disabilities

    ERIC Educational Resources Information Center

    Hampton, Carolann

    2017-01-01

    The attitudes and opinions of special education teachers may potentially reveal insight as to how and why teachers choose to include sex education in their curriculum for self-contained special education classrooms designed to serve students with developmental disabilities. The main objective in developing this study was to gather information…

  1. Automated Detection of Repetitive Motor Behaviors as an Outcome Measurement in Intellectual and Developmental Disabilities

    ERIC Educational Resources Information Center

    Gilchrist, Kristin H.; Hegarty-Craver, Meghan; Christian, Robert B.; Grego, Sonia; Kies, Ashley C.; Wheeler, Anne C.

    2018-01-01

    Repetitive sensory motor behaviors are a direct target for clinical treatment and a potential treatment endpoint for individuals with intellectual or developmental disabilities. By removing the burden associated with video annotation or direct observation, automated detection of stereotypy would allow for longer term monitoring in ecologic…

  2. Caregiver Strain and Sensory Features in Children with Autism Spectrum Disorder and Other Developmental Disabilities

    ERIC Educational Resources Information Center

    Kirby, Anne V.; White, Tamira J.; Baranek, Grace T.

    2015-01-01

    Caring for children with disabilities contributes to increased levels of parent stress or caregiver strain. However, the potential relationship of sensory features to strain among caregivers of children with autism spectrum disorder (ASD) and other developmental disabilities (DD) is unknown. Sensory features include overreactions, underreactions,…

  3. Developmental Status and Social-Emotional Functioning of Young Children Experiencing Homelessness

    ERIC Educational Resources Information Center

    Haskett, Mary E.; Armstrong, Jenna Montgomery; Tisdale, Jennifer

    2016-01-01

    The developmental status and social-emotional functioning of young children who are homeless has received inadequate attention in spite of high rates of homelessness among families with young children and the potentially negative impact of homelessness and associated stressors on children's well-being. The aim of this study was to gain…

  4. Developmental neurotoxicity and autism: A potential link between indoor neuroactive pollutants and the curious birth order risk factor.

    PubMed

    Gray, Wesley A; Billock, Vincent A

    2017-11-01

    Epidemiological and demographic studies find an increased risk of autism among first-borns. Toxicological studies show that some semi-volatile substances found in infant products produce adverse effects in neural and endocrine systems of animals, including behavioral and developmental effects. Several factors elevate the exposure of human infants to these chemicals. The highest exposures found in infants are comparable to the exposures that induce neural toxicity in animals. A review of these literatures suggests a linking hypothesis that could bridge the epidemiological and toxicological lines of evidence: an infant's exposure to neuroactive compounds emitted by infant products is increased by product newness and abundance; exposure is likely maximized for first-born children in families that can afford new products. Exposure is reduced for subsequently-born children who reuse these now neuroactive-depleted products. The presence of neuroactive chemical emissions from infant products has implications for birth-order effects and for other curious risk factors in autism, including gender, socioeconomic status, and season-of-birth risk factors. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  5. Effect of sensory adaptation on anxiety of children with developmental disabilities: a new approach.

    PubMed

    Shapiro, Michele; Melmed, Raphael N; Sgan-Cohen, Harold D; Parush, Shula

    2009-01-01

    The aim of this study was to evaluate the effect of a sensory-adapted dental environment (SADE) on anxiety, relaxation, and cooperation of children with developmental disabilities (CDDs). Pharmacological treatment has been widely used to reduce anxiety, but nonpharmacological methods may be similarly effective. The standardized clinical situation chosen was a dental hygiene cleaning. A SADE was structured. Sixteen CDDs participated in an open cross-over intervention trial measuring behavioral and psychophysiological variables. There was a substantial increase in relaxation and cooperation in the SADE as opposed to the regular dental environment (RDE). This was reflected by: mean duration of anxious behaviors (SADE = 9.04 minutes vs. RDE = 23.44 minutes; P < .01); mean magnitude of anxious behaviors (SADE = 8.49 vs. RDE = 15.50; P < .01); cooperation levels (SADE = 331 vs. RDE = 1.94; P < .01); mean electrodermal activity (EDA; SADE = 1230 vs. RDE = 446; P < .001); and difference in degree of relaxation by EDA (SADE=2014 vs. RDE=763; P < .004). The findings indicate the potential importance of considering the sensory-adapted environment as a preferable dental environment for this population.

  6. Developmental risk and young children's regulatory strategies: predicting behavior problems at age five.

    PubMed

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

    2011-04-01

    Children with early developmental delays are at heightened risk for behavior problems and comorbid psychopathology. This study examined the trajectories of regulatory capabilities and their potentially mediating role in the development of behavior problems for children with and without early developmental delays. A sample of 231 children comprised of 137 typically developing children and 94 children with developmental delays were examined during mildly frustrating laboratory tasks across the preschool period (ages 3-5). Results indicated that children with delays had greater use of maladaptive strategies (distraction, distress venting) and lower use of adaptive strategies (constructive coping) than typically developing children. For both groups, strategies had similar rates of growth across time; maladaptive strategies decreased and adaptive strategies increased. The intercept of strategy use, but not the slope, was found to mediate the relation between developmental risk and externalizing behaviors. Findings support that dysregulation, rather than the developmental risk, may be responsible for the high levels of comorbid psychopathology.

  7. Endocrine, teratogenic and neurotoxic effects of cyanobacteria detected by cellular in vitro and zebrafish embryos assays.

    PubMed

    Jonas, Adam; Scholz, Stefan; Fetter, Eva; Sychrova, Eliska; Novakova, Katerina; Ortmann, Julia; Benisek, Martin; Adamovsky, Ondrej; Giesy, John P; Hilscherova, Klara

    2015-02-01

    Cyanobacteria contain various types of bioactive compounds, which could cause adverse effects on organisms. They are released into surface waters during cyanobacterial blooms, but there is little information on their potential relevance for effects in vivo. In this study presence of bioactive compounds was characterized in cyanobacteria Microcystis aeruginosa (Chroococcales), Planktothrix agardhii (Oscillatoriales) and Aphanizomenon gracile (Nostocales) with selected in vitro assays. The in vivo relevance of detected bioactivities was analysed using transgenic zebrafish embryos tg(cyp19a1b-GFP). Teratogenic potency was assessed by analysis of developmental disorders and effects on functions of the neuromuscular system by video tracking of locomotion. Estrogenicity in vitro corresponded to 0.95-54.6 ng estradiol equivalent(g dry weight (dw))(-1). In zebrafish embryos, estrogenic effects could not be detected potentially because they were masked by high toxicity. There was no detectable (anti)androgenic/glucocorticoid activity in any sample. Retinoid-like activity was determined at 1-1.3 μg all-trans-retinoic acid equivalent(g dw)(-1). Corresponding to the retinoid-like activity A. gracile extract also caused teratogenic effects in zebrafish embryos. Furthermore, exposure to biomass extracts at 0.3 gd wL(-1) caused increase of body length in embryos. There were minor effects on locomotion caused by 0.3 gd wL(-1)M. aeruginosa and P. agardhii extracts. The traditionally measured cyanotoxins microcystins did not seem to play significant role in observed effects. This indicates importance of other cyanobacterial compounds at least towards some species or their developmental phases. More attention should be paid to activity of retinoids, estrogens and other bioactive substances in phytoplankton using in vitro and in vivo bioassays. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. (Eco)toxicological effects of 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) in zebrafish (Danio rerio) and permanent fish cell cultures.

    PubMed

    Vincze, Krisztina; Gehring, Martin; Braunbeck, Thomas

    2014-01-01

    2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) is a high-production volume chemical used in paper, ink, pesticide, and adhesive industries as a wetting and anti-foaming agent. The physicochemical properties and slow biodegradation rate of TMDD indicate a low bioaccumulation potential but a high prevalence in the environment. As a consequence, TMDD has been detected in several European rivers in the nanogram per liter and lower microgram per liter range; however, its environmental risk to aquatic organisms is considered low. Recent studies almost exclusively focused on acute effects by TMDD, little is known about cytotoxic and genotoxic effects, reproduction and developmental toxicity, endocrine disruption, and any kind of long-term toxicity and carcinogenicity so far. The present study aims to provide more specific baseline information on the ecotoxicological effects of TMDD in fish. For this end, cyto- and genotoxicity assays were carried out in vitro with the permanent fish cell line RTL-W1; in addition, in vivo studies were conducted with the early life stages of zebrafish (Danio rerio) in order to fill the data gaps in developmental toxicity and endocrine disruption. TMDD showed a cytotoxic and slight genotoxic potential in fish cell lines; moreover, various sublethal and lethal effects could be detected in developing zebrafish embryos. There was no evidence of endocrine-disrupting effects by TMDD; however, mortality following prolonged exposure to TMDD during fish sexual development test was clearly higher than mortality in the fish embryo test after 96-h exposure. Our results thus confirmed previous findings of laboratory screening tests, suggesting short-term toxic effects of TMDD in the intermediate, and long-term effects in the lower milligram per liter range.

  9. Effects of cadmium, manganese, and lead on locomotor activity and neurexin 2a expression in zebrafish.

    PubMed

    Tu, Hongwei; Fan, Chengji; Chen, Xiaohui; Liu, Jiaxian; Wang, Bin; Huang, Zhibin; Zhang, Yiyue; Meng, Xiaojing; Zou, Fei

    2017-08-01

    The synaptic adhesion protein Neurexin 2a (Nrxn2a) plays a key role in neuronal development and is associated with cognitive functioning and locomotor behavior. Although low-level metal exposure poses a potential risk to the human nervous system, especially during the developmental stages, little is known about the effects of metal exposures on nrxn2a expression during embryonic development. We therefore exposed wild-type zebrafish embryos/larvae to cadmium (CdCl 2 ), manganese (MnCl 2 ), and lead ([CH 3 COO] 2 Pb), to determine their effect on mortality, malformation, and hatching rate. Concentrations of these metals in zebrafish were detected by inductively coupled plasma mass spectrometry analysis. Locomotor activity of zebrafish larvae was analyzed using a video-track tracking system. Expression of nrxn2a was assessed by in situ hybridization and quantitative polymerase chain reaction. The results showed that mortality, malformation, and bioaccumulation increased as the exposure dosages and duration increased. Developmental exposure to these metals significantly reduced larval swim distance and velocity. The nrxn2aa and nrxn2ab genes were expressed in the central nervous system and downregulated by almost all of the 3 metals, especially Pb. These data demonstrate that exposure to metals downregulates nrxn2a in the zebrafish model system, and this is likely linked to concurrent developmental processes. Environ Toxicol Chem 2017;36:2147-2154. © 2017 SETAC. © 2017 SETAC.

  10. Drugs of abuse in pregnancy, poor neonatal development, and future neurodegeneration. Is oxidative stress the culprit?

    PubMed

    Neri, Margherita; Bello, Stefania; Turillazzi, Emanuela; Riezzo, Irene

    2015-01-01

    The abuse of licit and illicit drugs is a worldwide issue that is a cause for concern in pregnant women. It may lead to complications in pregnancy that may affect the mother, fetus, and /or neonate. The effects of any substance on the developing embryo and fetus are dependent upon dosing, timing, duration of drug exposure, and the extent of drug distribution. Teratogenic effects have been described when exposure takes place during the embryonic stage; however drugs have subtle effects, including abnormal growth and/or maturation, alterations in neurotransmitters and their receptors, and brain organization. The mechanisms by which intrauterine exposure to many substances may result in neuronal injury have not been completely elucidated. Oxidative stress and epigenetic changes have been recently implicated in the pathogenesis of long - term adverse health sequelae, and neuro-developmental impairment in the offspring of addicted mothers. Transgenerational epigenetics may also explain the alarming datum that developmental abnormalities, impairment in learning and memory, and attention deficit can occur even in the absence of direct fetal exposure, when drugs are consumed prior to conception. There is a growing body of evidence demonstrating a link between redox state unbalance, epigenetic markers, developmental anomalies, and neurodegeneration. The reviewed literature data uphold redox homeostasis disruption as an important factor in the pathogenesis of drug of abuse- induced neurodegeneration, and highlight the potential for new therapies that could prevent neurodegeneration through antioxidant and epigenetic modulatory mechanisms. This therefore reveals important targets for novel neuroprotective strategies.

  11. Somatoform Pain: A developmental theory and translational research review

    PubMed Central

    Landa, Alla; Peterson, Bradley S.; Fallon, Brian A.

    2013-01-01

    Somatoform pain is a highly prevalent, debilitating condition and a tremendous public health problem. Effective treatments for somatoform pain are urgently needed. The etiology of this condition is, however, still unknown. On the basis of a review of recent basic and clinical research, we propose one potential mechanisms of symptom formation in somatoform pain and a developmental theory of its pathogenesis. The emerging evidence from animal and human studies in developmental neurobiology, cognitive-affective neuroscience, psychoneuroimmunology, genetics, epigenetics, and clinical and treatment studies of somatoform pain all point to the existence of a shared physical and social pain neural system. Research findings also show that non-optimal early experiences interact with genetic predispositions to influence the development of this shared system and ability to regulate it in an effective way. Interpersonal affect regulation between infant and caregiver is crucial for the optimal development of these brain circuits. The aberrant development of this shared neural system during infancy, childhood and adolescence, therefore, may ultimately lead to an increased sensitivity to physical and social pain and to problems with their regulation in adulthood. The authors critically review translational research findings that support this theory and discuss its clinical and research implications. Specifically, the proposed theory and reviewed research suggest that psychotherapeutic and/or pharmacologic interventions that foster the development of affect regulation capacities in an interpersonal context will also serve to more effectively modulate aberrantly activated neural pain circuits and thus be of particular benefit in the treatment of somatoform pain. PMID:22929064

  12. Developmental neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical models and potential mechanisms

    PubMed Central

    Burke, Richard D.; Todd, Spencer W.; Lumsden, Eric; Mullins, Roger J.; Mamczarz, Jacek; Fawcett, William P.; Gullapalli, Rao P.; Randall, William R.; Pereira, Edna F. R.; Albuquerque, Edson X.

    2017-01-01

    Organophosphorus (OP) insecticides are pest-control agents heavily used worldwide. Unfortunately, they are also well known for the toxic effects that they can trigger in humans. Clinical manifestations of an acute exposure of humans to OP insecticides include a well-defined cholinergic crisis that develops as a result of the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh). Prolonged exposures to levels of OP insecticides that are insufficient to trigger signs of acute intoxication, which are hereafter referred to as subacute exposures, have also been associated with neurological deficits. In particular, epidemiological studies have reported statistically significant correlations between prenatal subacute exposures to OP insecticides, including chlorpyrifos, and neurological deficits that range from cognitive impairments to tremors in childhood. The primary objectives of this article are: (i) to address the short- and long-term neurological issues that have been associated with acute and subacute exposures of humans to OP insecticides, especially early in life (ii) to discuss the translational relevance of animal models of developmental exposure to OP insecticides, and (iii) to review mechanisms that are likely to contribute to the developmental neurotoxicity of OP insecticides. Most of the discussion will be focused on chlorpyrifos, the top-selling OP insecticide in the United States and throughout the world. These points are critical for the identification and development of safe and effective interventions to counter and/or prevent the neurotoxic effects of these chemicals in the developing brain. PMID:28791702

  13. Developmental toxicity of prenatal exposure to toluene.

    PubMed

    Bowen, Scott E; Hannigan, John H

    2006-01-01

    Organic solvents have become ubiquitous in our environment and are essential for industry. Many women of reproductive age are increasingly exposed to solvents such as toluene in occupational settings (ie, long-term, low-concentration exposures) or through inhalant abuse (eg, episodic, binge exposures to high concentrations). The risk for teratogenic outcome is much less with low to moderate occupational solvent exposure compared with the greater potential for adverse pregnancy outcomes, developmental delays, and neurobehavioral problems in children born to women exposed to high concentrations of abused organic solvents such as toluene, 1,1,1-trichloroethane, xylenes, and nitrous oxide. Yet the teratogenic effects of abuse patterns of exposure to toluene and other inhalants remain understudied. We briefly review how animal models can aid substantially in clarifying the developmental risk of exposure to solvents for adverse biobehavioral outcomes following abuse patterns of use and in the absence of associated health problems and co-drug abuse (eg, alcohol). Our studies also begin to establish the importance of dose (concentration) and critical perinatal periods of exposure to specific outcomes. The present results with our clinically relevant animal model of repeated, brief, high-concentration binge prenatal toluene exposure demonstrate the dose-dependent effect of toluene on prenatal development, early postnatal maturation, spontaneous exploration, and amphetamine-induced locomotor activity. The results imply that abuse patterns of toluene exposure may be more deleterious than typical occupational exposure on fetal development and suggest that animal models are effective in studying the mechanisms and risk factors of organic solvent teratogenicity.

  14. Effects of a Developmental Boot Camp: Improving Student Performance on a College Placement Test

    ERIC Educational Resources Information Center

    Hill, Heather H.

    2012-01-01

    Nationwide, students are entering college unprepared for college-level work. Recent high school graduates are placing into developmental courses at an alarming rate. The purpose of this research study is to examine the effect of a developmental boot camp on standardized placement test scores of students enrolling at a community college in North…

  15. The Effects of a Developmentally Appropriate Music and Movement Program on Motor Performance

    ERIC Educational Resources Information Center

    Zachopoulou, E.; Tsapakidou, A.; Derri, V.

    2004-01-01

    Basic motor skills development is achieved through the implementation of different types of physical education programs. The purpose of this study was to investigate and to compare the effect of a developmentally appropriate music and movement program and of a developmentally appropriate physical education program on the development of jumping and…

  16. Effective Oocyte Vitrification and Survival Techniques for Bovine Somatic Cell Nuclear Transfer

    PubMed Central

    Park, Min Jee; Lee, Seung Eun; Lee, Jun Beom; Jeong, Chang Jin

    2015-01-01

    Abstract Bovine somatic cell nuclear transfer (SCNT) using vitrified–thawed (VT) oocytes has been studied; however, the cloning efficiency of these oocytes is not comparable with that of nonvitrified (non-V) fresh oocytes. This study sought to optimize the survival and cryopreservation of VT oocytes for SCNT. Co-culture with feeder cells that had been preincubated for 15 h significantly improved the survival of VT oocytes and their in vitro developmental potential following SCNT in comparison to co-culture with feeder cells that had been preincubated for 2, 5, or 24 h (p<0.05). Spindle assessment via the Oosight Microscopy Imaging System and microtubule staining revealed that vitrified metaphase II oocytes (VT group) were not suitable for SCNT. However, enucleating and/or activating oocytes prior to freezing enhanced their developmental potential and suitability for SCNT. The cloning efficiency of the enucleated–activated–vitrified–thawed (EAVT) group (21.6%) was better than that of the other vitrification groups [enucleated–vitrified–thawed (EVT) group, 13.7%; VT group, 15.0%; p<0.05] and was comparable with that of the non-V group (25.9%). The reactive oxygen species level was significantly lower in the EAVT group than in the other vitrification groups (p<0.05). mRNA levels of maternal genes (ZAR1, BMP15, and NLRP5) and a stress gene (HSF1) were lower in the vitrification groups than in the non-V group (p<0.05), whereas the level of phospho-p44/42 mitogen-activated protein kinase did not differ among the groups. Among the vitrification groups, blastocysts in the EAVT group had the best developmental potential, as judged by their high mRNA expression of developmental potential–related genes (POU5f1, Interferon-tau, and SLC2A5) and their low expression of proapoptotic (CASP3) and stress (Hsp70) genes. This study demonstrates that SCNT using bovine frozen–thawed oocytes can be successfully achieved using optimized vitrification and co-culture techniques. PMID:25984830

  17. Developmental Cognitive Neuroscience of Adolescent Sexual Risk and Alcohol Use

    PubMed Central

    Ryman, Sephira G.; Gillman, Arielle S.; Weiland, Barbara J.; Thayer, Rachel E.; Bryan, Angela D.

    2018-01-01

    Human adolescents engage in very high rates of unprotected sex. This behavior has a high potential for unintended, serious, and sustained health consequences including HIV/AIDS. Despite these serious health consequences, we know little about the neural and cognitive factors that influence adolescents’ decision-making around sex, and their potential overlap with behaviorally co-occurring risk behaviors, including alcohol use. Thus, in this review, we evaluate the developmental neuroscience of sexual risk and alcohol use for human adolescents with an eye to relevant prevention and intervention implications. PMID:26290051

  18. Reproductive and developmental effects of disinfection by-products in drinking water.

    PubMed Central

    Reif, J S; Hatch, M C; Bracken, M; Holmes, L B; Schwetz, B A; Singer, P C

    1996-01-01

    Recent epidemiologic studies have reported associations between the consumption of chlorinated drinking water and reproductive and developmental effects. Here we review the available epidemiologic data, assess the hazard potential posed by exposure to disinfection by-products, identify critical data gaps, and offer recommendations for further research. The epidemiologic evidence supporting associations between exposure to water disinfection by-products (DBPs) and adverse pregnancy outcomes is sparse, and positive findings should be interpreted cautiously. The methods used during the early stages of research in this area have been diverse. Variability in exposure assessment and endpoints makes it difficult to synthesize or combine the available data. Exposure misclassification and unmeasured confounding may have lead to bias in risk estimation. Future studies of reproductive outcome and exposure to chlorinated water should use improved methods for exposure assessment to 1) assure selection of appropriate exposure markers, 2) assess seasonal and annual fluctuations in DBPs, 3) assess variability within the distribution system, and 4) assess exposure through multiple routes such as bathing and showering, as well as consumption. Population-based studies should be conducted to evaluate male and female fertility, conception delay, growth retardation, and specific birth defects. The reproductive and developmental effects of exposure to DBPs could be efficiently explored in ongoing investigations by incorporating valid exposure markers and relevant questionnaire information. Future studies should make use of naturally occurring variability in the concentrations of DBPs and may incorporate biomarkers of exposure and effect in their design. Epidemiologic investigations should be conducted in parallel with laboratory-based and animal studies in a coordinated, multidisciplinary approach. PMID:8930546

  19. Screening for Developmental Neurotoxicity Using PC12 Cells: Comparisons of Organophosphates with a Carbamate, an Organochlorine, and Divalent Nickel

    PubMed Central

    Slotkin, Theodore A.; MacKillop, Emiko A.; Ryde, Ian T.; Tate, Charlotte A.; Seidler, Frederic J.

    2007-01-01

    Background In light of the large number of chemicals that are potential developmental neurotoxicants, there is a need to develop rapid screening techniques. Objectives We exposed undifferentiated and differentiating neuronotypic PC12 cells to different organophosphates (chlorpyrifos, diazinon, parathion), a carbamate (physostigmine), an organochlorine (dieldrin), and a metal (divalent nickel; Ni2+) and examined indices of cell replication and differentiation for both short- and long-term exposures. Results In undifferentiated cells, all the agents inhibited DNA synthesis, with the greatest effect for diazinon, but physostigmine eventually produced the largest deficits in the total number of cells after prolonged exposure. The onset of differentiation intensified the adverse effects on DNA synthesis and changed the rank order in keeping with a shift away from noncholinergic mechanisms and toward cholinergic mechanisms. Differentiation also worsened the effects of each agent on cell number after prolonged exposure, whereas cell growth was not suppressed, nor were there any effects on viability as assessed with trypan blue. Nevertheless, differentiating cells displayed signs of oxidative stress from all of the test compounds except Ni2+, as evidenced by measurements of lipid peroxidation. Finally, all of the toxicants shifted the transmitter fate of the cells away from the cholinergic phenotype and toward the catecholaminergic phenotype. Conclusions These studies point out the feasibility of developing cell-based screening methods that enable the detection of multiple end points that may relate to mechanisms associated with developmental neurotoxicity, revealing some common targets for disparate agents. PMID:17366826

  20. Similarities in temperature-dependent gene expression plasticity across timescales in threespine stickleback (Gasterosteus aculeatus).

    PubMed

    Metzger, David C H; Schulte, Patricia M

    2018-04-14

    Phenotypic plasticity occurs at a variety of timescales, but little is known about the degree to which plastic responses at different timescales are associated with similar underlying molecular processes, which is critical for assessing the effects of plasticity on evolutionary trajectories. To address this issue, we identified differential gene expression in response to developmental temperature in the muscle transcriptome of adult threespine stickleback (Gasterosteus aculeatus) exposed to 12, 18 and 24°C until hatch and then held at 18°C for 9 months and compared these results to differential gene expression in response to adult thermal acclimation in stickleback developed at 18°C and then acclimated to 5 and 25°C as adults. Adult thermal acclimation affected the expression of 7,940 and 7,015 genes in response to cold and warm acclimation, respectively, and 4,851 of these genes responded in both treatments. In contrast, the expression of only 33 and 29 genes was affected by cold and warm development, respectively. The majority of the genes affected by developmental temperature were also affected by adult acclimation temperature. Many genes that were differentially expressed as a result of adult acclimation were associated with previously identified temperature-dependent effects on DNA methylation patterns, suggesting a role of epigenetic mechanisms in regulating gene expression plasticity during acclimation. Taken together, these results demonstrate similarities between the persistent effects of developmental plasticity on gene expression and the effects of adult thermal acclimation, emphasizing the potential for mechanistic links between plasticity acting at these different life stages. © 2018 John Wiley & Sons Ltd.

  1. Preimplantation development of somatic cell cloned embryos in the common marmoset (Callithrix jacchus).

    PubMed

    Sotomaru, Yusuke; Hirakawa, Reiko; Shimada, Akiko; Shiozawa, Seiji; Sugawara, Ayako; Oiwa, Ryo; Nobukiyo, Asako; Okano, Hideyuki; Tamaoki, Norikazu; Nomura, Tatsuji; Hiyama, Eiso; Sasaki, Erika

    2009-12-01

    The somatic cell nuclear transfer technique has been applied to various mammals to produce cloned animals; however, a standardized method is not applicable to all species. We aimed here to develop optimum procedures for somatic cell cloning in nonhuman primates, using common marmosets. First, we confirmed that parthenogenetic activation of in vitro matured oocytes was successfully induced by electrical stimulation (three cycles of 150 V/mm, 50 microsec x 2, 20 min intervals), and this condition was applied to the egg activation procedure in the subsequent experiments. Next, nuclear transfer to recipient enucleated oocytes was performed 1 h before, immediately after, or 1 h after egg activation treatment. The highest developmental rate was observed when nuclear transfer was performed 1 h before activation, but none of the cloned embryos developed beyond the eight-cell stage. To investigate the causes of the low developmental potential of cloned embryos, a study was performed to determine whether the presence of metaphase II (MII) chromosome in recipient ooplasm has an effect on developmental potential. As a result, only tetraploid cloned embryos produced by transferring a donor cell into a recipient bearing the MII chromosome developed into blastocysts (66.7%). In contrast, neither parthenogenetic embryos nor cloned embryos (whether diploid or tetraploid) produced using enucleated oocytes developed past the eight-cell stage. These results suggest that MII chromosome, or cytoplasm proximal to the MII chromosome, plays a major role in the development of cloned embryos in common marmosets.

  2. Developmental neurotoxicity of succeeding generations of insecticides

    PubMed Central

    Abreu-Villaça, Yael; Levin, Edward D.

    2016-01-01

    Insecticides are by design toxic. They must be toxic to effectively kill target species of insects. Unfortunately, they also have off-target toxic effects that can harm other species, including humans. Developmental neurotoxicity is one of the most prominent off-target toxic risks of insecticides. Over the past seven decades several classes of insecticides have been developed, each with their own mechanisms of effect and toxic side effects. This review covers the developmental neurotoxicity of the succeeding generations of insecticides including organochlorines, organophosphates, pyrethroids, carbamates and neonicotinoids. The goal of new insecticide development is to more effectively kill target species with fewer toxic side effects on non-target species. From the experience with the developmental neurotoxicity caused by the generations of insecticides developed in the past advice is offered how to proceed with future insecticide development to decrease neurotoxic risk. PMID:27908457

  3. Developmental Toxicity

    EPA Science Inventory

    This chapter provides an overview the developmental toxicity resulting from exposure to perfluorinated alkyl acids (PFAAs). The majority of studies of PFAA-induced developmental toxicity have examined effects of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) a...

  4. CAD mutations and uridine-responsive epileptic encephalopathy.

    PubMed

    Koch, Johannes; Mayr, Johannes A; Alhaddad, Bader; Rauscher, Christian; Bierau, Jörgen; Kovacs-Nagy, Reka; Coene, Karlien L M; Bader, Ingrid; Holzhacker, Monika; Prokisch, Holger; Venselaar, Hanka; Wevers, Ron A; Distelmaier, Felix; Polster, Tilman; Leiz, Steffen; Betzler, Cornelia; Strom, Tim M; Sperl, Wolfgang; Meitinger, Thomas; Wortmann, Saskia B; Haack, Tobias B

    2017-02-01

    Unexplained global developmental delay and epilepsy in childhood pose a major socioeconomic burden. Progress in defining the molecular bases does not often translate into effective treatment. Notable exceptions include certain inborn errors of metabolism amenable to dietary intervention. CAD encodes a multifunctional enzyme involved in de novo pyrimidine biosynthesis. Alternatively, pyrimidines can be recycled from uridine. Exome sequencing in three families identified biallelic CAD mutations in four children with global developmental delay, epileptic encephalopathy, and anaemia with anisopoikilocytosis. Two died aged 4 and 5 years after a neurodegenerative disease course. Supplementation of the two surviving children with oral uridine led to immediate cessation of seizures in both. A 4-year-old female, previously in a minimally conscious state, began to communicate and walk with assistance after 9 weeks of treatment. A 3-year-old female likewise showed developmental progress. Blood smears normalized and anaemia resolved. We establish CAD as a gene confidently implicated in this neurometabolic disorder, characterized by co-occurrence of global developmental delay, dyserythropoietic anaemia and seizures. While the natural disease course can be lethal in early childhood, our findings support the efficacy of uridine supplementation, rendering CAD deficiency a treatable neurometabolic disorder and therefore a potential condition for future (genetic) newborn screening. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. The Newborn Individualized Developmental Care and Assessment Program (NIDCAP) with Kangaroo Mother Care (KMC): Comprehensive Care for Preterm Infants

    PubMed Central

    Als, Heidelise; McAnulty, Gloria B.

    2014-01-01

    State-of-the-art Newborn Intensive Care Units (NICUs), instrumental in the survival of high-risk and ever-earlier-born preterm infants, often have costly human repercussions. The developmental sequelae of newborn intensive care are largely misunderstood. Developed countries eager to export their technologies must also transfer the knowledge-base that encompasses all high-risk and preterm infants’ personhood as well as the neuro-essential importance of their parents. Without such understanding, the best medical care, while assuring survival jeopardizes infants’ long-term potential and deprives parents of their critical role. Exchanging the womb for the NICU environment at a time of rapid brain growth compromises preterm infants’ early development, which results in long-term physical and mental health problems and developmental disabilities. The Newborn Individualized Developmental Care and Assessment Program (NIDCAP) aims to prevent the iatrogenic sequelae of intensive care and to maintain the intimate connection between parent and infant, one expression of which is Kangaroo Mother Care. NIDCAP embeds the infant in the natural parent niche, avoids over-stimulation, stress, pain, and isolation while it supports self-regulation, competence, and goal orientation. Research demonstrates that NIDCAP improves brain development, functional competence, health, and life quality. It is cost effective, humane, and ethical, and promises to become the standard for all NICU care. PMID:25473384

  6. The Newborn Individualized Developmental Care and Assessment Program (NIDCAP) with Kangaroo Mother Care (KMC): Comprehensive Care for Preterm Infants.

    PubMed

    Als, Heidelise; McAnulty, Gloria B

    2011-08-01

    State-of-the-art Newborn Intensive Care Units (NICUs), instrumental in the survival of high-risk and ever-earlier-born preterm infants, often have costly human repercussions. The developmental sequelae of newborn intensive care are largely misunderstood. Developed countries eager to export their technologies must also transfer the knowledge-base that encompasses all high-risk and preterm infants' personhood as well as the neuro-essential importance of their parents. Without such understanding, the best medical care, while assuring survival jeopardizes infants' long-term potential and deprives parents of their critical role. Exchanging the womb for the NICU environment at a time of rapid brain growth compromises preterm infants' early development, which results in long-term physical and mental health problems and developmental disabilities. The Newborn Individualized Developmental Care and Assessment Program (NIDCAP) aims to prevent the iatrogenic sequelae of intensive care and to maintain the intimate connection between parent and infant, one expression of which is Kangaroo Mother Care. NIDCAP embeds the infant in the natural parent niche, avoids over-stimulation, stress, pain, and isolation while it supports self-regulation, competence, and goal orientation. Research demonstrates that NIDCAP improves brain development, functional competence, health, and life quality. It is cost effective, humane, and ethical, and promises to become the standard for all NICU care.

  7. Minimizing Noise in Pediatric Task-Based functional MRI; Adolescents with Developmental Disabilities and Typical Development

    PubMed Central

    Fassbender, Catherine; Muhkerjee, Prerona; Schweitzer, Julie B.

    2017-01-01

    Functional Magnetic Resonance Imaging (fMRI) represents a powerful tool with which to examine brain functioning and development in typically developing pediatric groups as well as children and adolescents with clinical disorders. However, fMRI data can be highly susceptible to misinterpretation due to the effects of excessive levels of noise, often related to head motion. Imaging children, especially with developmental disorders, requires extra considerations related to hyperactivity, anxiety and the ability to perform and maintain attention to the fMRI paradigm. We discuss a number of methods that can be employed to minimize noise, in particular movement-related noise. To this end we focus on strategies prior to, during and following the data acquisition phase employed primarily within our own laboratory. We discuss the impact of factors such as experimental design, screening of potential participants and pre-scan training on head motion in our adolescents with developmental disorders and typical development. We make some suggestions that may minimize noise during data acquisition itself and finally we briefly discuss some current processing techniques that may help to identify and remove noise in the data. Many advances have been made in the field of pediatric imaging, particularly with regard to research involving children with developmental disorders. Mindfulness of issues such as those discussed here will ensure continued progress and greater consistency across studies. PMID:28130195

  8. The Effectiveness of Aligned Developmental Feedback on the Overhand Throw in Third-Grade Students

    ERIC Educational Resources Information Center

    Cohen, Rona; Goodway, Jacqueline D.; Lidor, Ronnie

    2012-01-01

    Background: To improve student performance, teachers need to evaluate the developmental level of the child and to deliver feedback statements that correspond with the student's ability to process the information delivered. Therefore, feedback aligned with the developmental level of the child (aligned developmental feedback--ADF) is sometimes…

  9. Effective Developmental Math Instructional Practices That Facilitate Learning and Academic Success of Community College Students

    ERIC Educational Resources Information Center

    Little, Pamela Hilson

    2017-01-01

    The purpose of the qualitative study was to discover instructional practices used by developmental math instructors that facilitate learning and academic success of students in developmental math courses at select community colleges in Alabama in order to generate improved instructional practices in the developmental education field. Emergent data…

  10. 29 CFR 1952.262 - Completion of developmental steps and certification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Completion of developmental steps and certification. 1952... § 1952.262 Completion of developmental steps and certification. (a) In accordance with § 1952.263(a), the... effective January 13, 1981 as having completed all developmental steps specified in the plan as approved on...

  11. Comparing rat and rabbit embryo-fetal developmental toxicity studies for 379 pharmaceuticals: On systemic dose and developmental effects (Critical Reviews in Toxicology)

    EPA Science Inventory

    A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental adverse ef...

  12. Does Developmental Education Improve Labor Market Outcomes? Evidence from Two States. A CAPSEE Working Paper

    ERIC Educational Resources Information Center

    Hodara, Michelle; Xu, Di

    2014-01-01

    Nationally, about two thirds of community college students are referred to developmental education. Thus far, research on the effectiveness of developmental education has focused on students' academic outcomes; in this paper, we examine the economic consequences of developmental education for students. Using longitudinal student-unit record data…

  13. Developmental post-natal stress can alter the effects of pre-natal stress on the adult redox balance.

    PubMed

    Marasco, Valeria; Spencer, Karen A; Robinson, Jane; Herzyk, Pawel; Costantini, David

    2013-09-15

    Across diverse vertebrate taxa, stressful environmental conditions during development can shape phenotypic trajectories of developing individuals, which, while adaptive in the short-term, may impair health and survival in adulthood. Regardless, the long-lasting benefits or costs of early life stress are likely to depend on the conditions experienced across differing stages of development. Here, we used the Japanese quail (Coturnix coturnix japonica) to experimentally manipulate exposure to stress hormones in developing individuals. We tested the hypothesis that interactions occurring between pre- and post-natal developmental periods can induce long-term shifts on the adult oxidant phenotype in non-breeding sexually mature individuals. We showed that early life stress can induce long-term alterations in the basal antioxidant defences. The magnitude of these effects depended upon the timing of glucocorticoid exposure and upon interactions between the pre- and post-natal stressful stimuli. We also found differences among tissues with stronger effects in the erythrocytes than in the brain in which the long-term effects of glucocorticoids on antioxidant biomarkers appeared to be region-specific. Recent experimental work has demonstrated that early life exposure to stress hormones can markedly reduce adult survival (Monaghan et al., 2012). Our results suggest that long-term shifts in basal antioxidant defences might be one of the potential mechanisms driving such accelerated ageing processes and that post-natal interventions during development may be a potential tool to shape the effects induced by pre-natally glucococorticoid-exposed phenotypes. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Safety and side effects of ayahuasca in humans--an overview focusing on developmental toxicology.

    PubMed

    dos Santos, Rafael Guimarães

    2013-01-01

    Despite being relatively well studied from a botanical, chemical, and (acute) pharmacological perspective, little is known about the possible toxic effects of ayahuasca (an hallucinogenic brew used for magico-ritual purposes) in pregnant women and in their children, and the potential toxicity of long-term ayahuasca consumption. It is the main objective of the present text to do an overview of the risks and possible toxic effects of ayahuasca in humans, reviewing studies on the acute ayahuasca administration to humans, on the possible risks associated with long-term consumption by adults and adolescents, and on the possible toxic effects on pregnant animals and in their offspring. Acute ayahuasca administration, as well as long-term consumption of this beverage, does not seem to be seriously toxic to humans. Although some nonhuman developmental studies suggested possible toxic effects of ayahuasca or of some of its alkaloids, the limited human literature on adolescents exposed to ayahuasca as early as in the uterus reports no serious toxic effects of the ritual consumption of the brew. Researchers must take caution when extrapolating nonhuman data to humans and more data are needed in basic and human research before a definite opinion can be made regarding the possible toxic effects of ayahuasca in pregnant women and in their children.

  15. Bridging the gap between empirical results, actual strategies, and developmental programs in soccer.

    PubMed

    Figueiredo, António J; Gonçalves, Carlos E; Tessitore, Antonio

    2014-05-01

    Being one of the most prominent globalized sports, soccer played at club, national, and continental levels has a relevant societal role. At present, the specific competencies, interests, and languages of the different actors involved in the selection, development, and support of long-lasting careers of players might limit opportunities for potential talented players. Unless the cultural environment of soccer resolves the gaps between empirical results and actual soccer strategies, scientific discussion relating to the effectiveness of talent selection and development remains limited. This commentary is intended to highlight the need for developmental programs to prepare soccer personnel for a transdisciplinary dialogue, which could foster a future development of this sport. Finally, in considering the wide soccer-related employment opportunities at local, national, and international levels, the need for a clear qualification framework is crucial.

  16. Mothers and infants exposed to intimate partner violence compensate.

    PubMed

    Letourneau, Nicole; Morris, Catherine Young; Secco, Loretta; Stewart, Miriam; Hughes, Jean; Critchley, Kim

    2013-01-01

    Reasons for the developmental variability in children exposed to intimate partner violence (IPV) are unclear and under studied. This article presents exploratory findings on (a) the potential impact of IPV on mother-child relationships and child development and (b) the association between these maternal-child relationship impacts and child development. The fit of findings with compensatory, spillover, and compartmentalization hypotheses was explored. Participants were 49 mothers and 51 children younger than 3 years of age affected by IPV. Data were collected on maternal-child interactions, child development, social support, difficult life circumstances, family functioning, child temperament, and parental depression. The findings suggested developmental impacts on children in the sample, along with children's high sensitivity and responsiveness to their caregivers. Although some spillover effects were observed, the predominant observation was of mothers and infants compensating for exposure to IPV in their interactions.

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

    PubMed

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

    2011-03-01

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

  18. Neurobehavioral impairments caused by developmental imidacloprid exposure in zebrafish.

    PubMed

    Crosby, Emily B; Bailey, Jordan M; Oliveri, Anthony N; Levin, Edward D

    2015-01-01

    Neonicotinoid insecticides are becoming more widely applied as organophosphate (OP) insecticides are decreasing in use. Because of their relative specificity to insect nicotinic receptors, they are thought to have reduced risk of neurotoxicity in vertebrates. However, there is scant published literature concerning the neurobehavioral effects of developmental exposure of vertebrates to neonicotinoids. Using zebrafish, we investigated the neurobehavioral effects of developmental exposure to imidacloprid, a prototypic neonicotinoid pesticide. Nicotine was also administered for comparison. Zebrafish were exposed via immersion in aqueous solutions containing 45 μM or 60 μM of imidacloprid or nicotine (or vehicle control) from 4h to 5d post fertilization. The functional effects of developmental exposure to both imidacloprid and nicotine were assessed in larvae using an activity assay and during adolescence and adulthood using a battery of neurobehavioral assays, including assessment of sensorimotor response and habituation in a tactile startle test, novel tank swimming, and shoaling behavior. In larvae, developmental imidacloprid exposure at both doses significantly decreased swimming activity. The 5D strains of zebrafish were more sensitive to both nicotine and imidacloprid than the AB* strain. In adolescent and adult fish, developmental exposure to imidacloprid significantly decreased novel tank exploration and increased sensorimotor response to startle stimuli. While nicotine did not affect novel tank swimming, it increased sensorimotor response to startle stimuli at the low dose. No effects of either compound were found on shoaling behavior or habituation to a startling stimulus. Early developmental exposure to imidacloprid has both early-life and persisting effects on neurobehavioral function in zebrafish. Its developmental neurotoxicity should be further investigated. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Associations between prenatal, childhood, and adolescent stress and variations in white-matter properties in young men.

    PubMed

    Jensen, Sarah K G; Pangelinan, Melissa; Björnholm, Lassi; Klasnja, Anja; Leemans, Alexander; Drakesmith, Mark; Evans, C J; Barker, Edward D; Paus, Tomáš

    2017-10-21

    Previous studies have shown that both pre- and post-natal adversities, the latter including exposures to stress during childhood and adolescence, explain variation in structural properties of white matter (WM) in the brain. While previous studies have examined effects of independent stress exposures within one developmental period, such as childhood, we examine effects of stress across development using data from a prospective longitudinal study. More specifically, we ask how stressful events during prenatal development, childhood, and adolescence relate to variation in WM properties in early adulthood in young men recruited from a birth cohort. Using data from 393 mother-son pairs from a community-based birth cohort from England (Avon Longitudinal Study of Parents and Children), we examined how stressful life events relate to variation in different structural properties of WM in the corpus callosum and across the whole brain in early adulthood in men aged 18-21 years. We distinguish between stress occurring during three developmental periods: a) prenatal maternal stress, b) postnatal stress within the first four years of life, c) stress during adolescence (age 12-16 years). To obtain a comprehensive quantification of variation in WM, we assess structural properties of WM using four different measures, namely fractional anisotropy (FA), mean diffusivity (MD), magnetization transfer ratio (MTR) and myelin water fraction (MWF). The developmental model shows that prenatal stress is associated with lower MTR and MWF in the genu and/or splenium of the corpus callosum, and with lower MTR in global (lobar) WM. Stress during early childhood is associated with higher MTR in the splenium, and stress during adolescence is associated with higher MTR in the genu and lower MD in the splenium. We see no associations between postnatal stress and variation in global (lobar) WM. The current study found evidence for independent effects of stress on WM properties during distinct neurodevelopmental periods. We speculate that these independent effects are due to differences in the developmental processes unfolding at different developmental time points. We suggest that associations between prenatal stress and WM properties may relate to abnormalities in neurogenesis, affecting the number and density of axons, while postnatal stress may interfere with processes related to myelination or radial growth of axons. Potential consequences of prenatal glucocorticoid exposure should be considered in obstetric care. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Adolescents, peers, and motor vehicles: the perfect storm?

    PubMed

    Allen, Joseph P; Brown, B Bradford

    2008-09-01

    Motor-vehicle crashes are a leading cause of death among teenagers and in many instances appear linked to negative peer influences on adolescent driving behavior. This article examines a range of developmental and structural factors that potentially increase the risks associated with adolescent driving. Developmental risk factors for adolescents include a propensity toward engaging in deviant and risky behavior, a desire to please peers, and the potential cost to an adolescent of alienating peers with his or her behavior while driving. Structural features of the driving situation that create risks for negative peer influences on driving behavior include the inability of adolescents to look at peers who may be pressuring them, divided attention, the need to behave in a conventional manner among peers who may not value conventional behavior, and the lack of accountability by peers for the effects of any risky driving they promote. A range of potential peer influences are considered, including passive and active distraction and direct disruption of driving, as well as more positive influences, such as peer modeling of good driving behavior and positive reinforcement of good driving. Although the range of risk factors created by peers is large, this range presents a number of promising targets for intervention to improve teen driving safety.

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