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Sample records for developmentally related alterations

  1. Altered cortical expression of GABA-related genes in schizophrenia: illness progression vs developmental disturbance.

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    Hoftman, Gil D; Volk, David W; Bazmi, H Holly; Li, Siyu; Sampson, Allan R; Lewis, David A

    2015-01-01

    Schizophrenia is a neurodevelopmental disorder with altered expression of GABA-related genes in the prefrontal cortex (PFC). However, whether these gene expression abnormalities reflect disturbances in postnatal developmental processes before clinical onset or arise as a consequence of clinical illness remains unclear. Expression levels for 7 GABA-related transcripts (vesicular GABA transporter [vGAT], GABA membrane transporter [GAT1], GABAA receptor subunit α1 [GABRA1] [novel in human and monkey cohorts], glutamic acid decarboxylase 67 [GAD67], parvalbumin, calretinin, and somatostatin [previously reported in human cohort, but not in monkey cohort]) were quantified in the PFC from 42 matched pairs of schizophrenia and comparison subjects and from 49 rhesus monkeys ranging in age from 1 week postnatal to adulthood. Levels of vGAT and GABRA1, but not of GAT1, messenger RNAs (mRNAs) were lower in the PFC of the schizophrenia subjects. As previously reported, levels of GAD67, parvalbumin, and somatostatin, but not of calretinin, mRNAs were also lower in these subjects. Neither illness duration nor age accounted for the levels of the transcripts with altered expression in schizophrenia. In monkey PFC, developmental changes in expression levels of many of these transcripts were in the opposite direction of the changes observed in schizophrenia. For example, mRNA levels for vGAT, GABRA1, GAD67, and parvalbumin all increased with age. Together with published reports, these findings support the interpretation that the altered expression of GABA-related transcripts in schizophrenia reflects a blunting of normal postnatal development changes, but they cannot exclude a decline during the early stages of clinical illness. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Study on frequency of dental developmental alterations in a Mexican school-based population.

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    Ledesma-Montes, C; Garcés-Ortíz, M; Salcido-García, J-F; Hernández-Flores, F

    2016-05-01

    The aim of this study was to know the distribution of dental developmental alterations in the population requesting stomatological attention at the Admission and Diagnosis Clinic of our institution in Mexico City. We reviewed the archives and selected those files with developmental dental alterations. Analyzed data were diagnoses, age, gender, location and number of involved teeth. Of the 3.522 patients reviewed, 179 (5.1%) harbored 394 developmental dental alterations. Of them, 45.2% were males and 54.8% were females with a mean age of 16.7 years. The most common were supernumeraries, dental agenesia and dilaceration. Adults were 30.7% of the patients with dental developmental alterations. In them, the most common lesions were agenesia and supernumeraries. Mesiodens was the most frequently found supernumerary teeth (14.7%). Our finding that 30.7% of the affected patients were adults is an undescribed and unusually high proportion of patients that have implications on planning and prognosis of their stomatological treatment.

  3. Study on frequency of dental developmental alterations in a MEXICAN school-based population

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    Ledesma Montes, Constantino; Garcés Ortíz, Maricela; Salcido García, Juan Francisco; Hernández Flores, Florentino

    2016-01-01

    Background The aim of this study was to know the distribution of dental developmental alterations in the population requesting stomatological attention at the Admission and Diagnosis Clinic of our institution in Mexico City. Material and Methods We reviewed the archives and selected those files with developmental dental alterations. Analyzed data were diagnoses, age, gender, location and number of involved teeth. Results Of the 3.522 patients reviewed, 179 (5.1%) harbored 394 developmental de...

  4. Developmental Bisphenol A Exposure Modulates Immune-Related Diseases

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    Xu, Joella; Huang, Guannan; Guo, Tai L.

    2016-01-01

    Bisphenol A (BPA), used in polycarbonate plastics and epoxy resins, has a widespread exposure to humans. BPA is of concern for developmental exposure resulting in immunomodulation and disease development due to its ability to cross the placental barrier and presence in breast milk. BPA can use various mechanisms to modulate the immune system and affect diseases, including agonistic and antagonistic effects on many receptors (e.g., estrogen receptors), epigenetic modifications, acting on cell signaling pathways and, likely, the gut microbiome. Immune cell populations and function from the innate and adaptive immune system are altered by developmental BPA exposure, including decreased T regulatory (Treg) cells and upregulated pro- and anti-inflammatory cytokines and chemokines. Developmental BPA exposure can also contribute to the development of type 2 diabetes mellitus, allergy, asthma and mammary cancer disease by altering immune function. Multiple sclerosis and type 1 diabetes mellitus may also be exacerbated by BPA, although more research is needed. Additionally, BPA analogs, such as bisphenol S (BPS), have been increasing in use, and currently, little is known about their immune effects. Therefore, more studies should be conducted to determine if developmental exposure BPA and its analogs modulate immune responses and lead to immune-related diseases. PMID:29051427

  5. Developmental Bisphenol A Exposure Modulates Immune-Related Diseases

    Directory of Open Access Journals (Sweden)

    Joella Xu

    2016-09-01

    Full Text Available Bisphenol A (BPA, used in polycarbonate plastics and epoxy resins, has a widespread exposure to humans. BPA is of concern for developmental exposure resulting in immunomodulation and disease development due to its ability to cross the placental barrier and presence in breast milk. BPA can use various mechanisms to modulate the immune system and affect diseases, including agonistic and antagonistic effects on many receptors (e.g., estrogen receptors, epigenetic modifications, acting on cell signaling pathways and, likely, the gut microbiome. Immune cell populations and function from the innate and adaptive immune system are altered by developmental BPA exposure, including decreased T regulatory (Treg cells and upregulated pro- and anti-inflammatory cytokines and chemokines. Developmental BPA exposure can also contribute to the development of type 2 diabetes mellitus, allergy, asthma and mammary cancer disease by altering immune function. Multiple sclerosis and type 1 diabetes mellitus may also be exacerbated by BPA, although more research is needed. Additionally, BPA analogs, such as bisphenol S (BPS, have been increasing in use, and currently, little is known about their immune effects. Therefore, more studies should be conducted to determine if developmental exposure BPA and its analogs modulate immune responses and lead to immune-related diseases.

  6. Altered morphology of the nucleus accumbens in persistent developmental stuttering.

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    Neef, Nicole E; Bütfering, Christoph; Auer, Tibor; Metzger, F Luise; Euler, Harald A; Frahm, Jens; Paulus, Walter; Sommer, Martin

    2018-03-01

    Neuroimaging studies in persistent developmental stuttering repeatedly report altered basal ganglia functions. Together with thalamus and cerebellum, these structures mediate sensorimotor functions and thus represent a plausible link between stuttering and neuroanatomy. However, stuttering is a complex, multifactorial disorder. Besides sensorimotor functions, emotional and social-motivational factors constitute major aspects of the disorder. Here, we investigated cortical and subcortical gray matter regions to study whether persistent developmental stuttering is also linked to alterations of limbic structures. The study included 33 right-handed participants who stutter and 34 right-handed control participants matched for sex, age, and education. Structural images were acquired using magnetic resonance imaging to estimate volumetric characteristics of the nucleus accumbens, hippocampus, amygdala, pallidum, putamen, caudate nucleus, and thalamus. Volumetric comparisons and vertex-based shape comparisons revealed structural differences. The right nucleus accumbens was larger in participants who stutter compared to controls. Recent theories of basal ganglia functions suggest that the nucleus accumbens is a motivation-to-movement interface. A speaker intends to reach communicative goals, but stuttering can derail these efforts. It is therefore highly plausible to find alterations in the motivation-to-movement interface in stuttering. While behavioral studies of stuttering sought to find links between the limbic and sensorimotor system, we provide the first neuroimaging evidence of alterations in the limbic system. Thus, our findings might initialize a unified neurobiological framework of persistent developmental stuttering that integrates sensorimotor and social-motivational neuroanatomical circuitries. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Developmental Hypothyroidism Alters Brain-Derived Neurotrophic Factor (BDNF) Expression in Adulthood.

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    Severe developmental thyroid hormone (TH) insufficiency results in alterations in brain structure/function and lasting behavioral impairments. Environmental toxicants reduce circulating levels of TH, but the disruption is modest and the doseresponse relationships of TH and neuro...

  8. Vascular Alterations Underlie Developmental Problems Manifested in Cloned Cattle before or after Birth

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    Favaron, Phelipe Oliveira; dos Santos, Caio Rodrigues; Alberto, Miryan Lanca; Meirelles, Flavio Vieira; Miglino, Maria Angelica

    2015-01-01

    Although assisted reproductive techniques are commonly applied in humans and animals, they are frequently associated with major developmental deficits and reduced viability. To explore abnormalities associated with cloning or nuclear transfer (NT) as the most invasive of these methods, we used a bovine model to characterize abnormalities. Detailed necropsy examinations were done on 13 calves that died soon after birth; in addition, we included data from embryos and fetuses (produced by NT) that terminated prematurely. Bovine clones that survived until the neonatal period differed quantitatively and qualitatively from in-vivo-derived cattle. Although alterations affected a variety of organs (e.g. heart, lung and liver), there was a clear association with abberant vascular developmental during the early intrauterine phase. Therefore, we concluded that vascular problems were key alterations induced by cloning (presumably via epigenetic modifications). PMID:25584533

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

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    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...

  10. Eco-Evo-Devo: developmental symbiosis and developmental plasticity as evolutionary agents.

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    Gilbert, Scott F; Bosch, Thomas C G; Ledón-Rettig, Cristina

    2015-10-01

    The integration of research from developmental biology and ecology into evolutionary theory has given rise to a relatively new field, ecological evolutionary developmental biology (Eco-Evo-Devo). This field integrates and organizes concepts such as developmental symbiosis, developmental plasticity, genetic accommodation, extragenic inheritance and niche construction. This Review highlights the roles that developmental symbiosis and developmental plasticity have in evolution. Developmental symbiosis can generate particular organs, can produce selectable genetic variation for the entire animal, can provide mechanisms for reproductive isolation, and may have facilitated evolutionary transitions. Developmental plasticity is crucial for generating novel phenotypes, facilitating evolutionary transitions and altered ecosystem dynamics, and promoting adaptive variation through genetic accommodation and niche construction. In emphasizing such non-genomic mechanisms of selectable and heritable variation, Eco-Evo-Devo presents a new layer of evolutionary synthesis.

  11. Developmental exposure to Passiflora incarnata induces behavioural alterations in the male progeny.

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    Bacchi, André D; Ponte, Bianca; Vieira, Milene L; de Paula, Jaqueline C C; Mesquita, Suzana F P; Gerardin, Daniela C C; Moreira, Estefânia G

    2013-01-01

    Passiflora incarnata is marketed in many countries as a phytomedicine and is prescribed mainly as a sedative and anxiolytic. Even though the directions of most marketed phytomedicines recommend them to be used under medical supervision, reproductive and developmental studies are sparse and not mandatory for regulatory purposes. To evaluate the reproductive and developmental toxicity of P. incarnata, Wistar female rats were gavaged with 30 or 300 mg kg(-1) of this herb from gestational Day (GD) 0 to postnatal Day (PND) 21. P. incarnata treatment did not influence dams' bodyweight or food intake or their reproductive performance (post-implantation loss, litter size, litter weight). There was also no influence on the physical development of pups (bodyweight gain, day of vaginal opening or preputial separation) or their behaviour in the open-field at PND 22, 35 and 75. Sexual behaviour was disrupted in adult male pups exposed to 300 mg kg(-1) of P. incarnata; in this group, only 3 out of 11 pups were sexually competent. This behavioural disruption was not accompanied by alterations in plasma testosterone levels, reproductive-related organs and glands weights or sperm count. It is hypothesised that aromatase inhibition may be involved in the observed effect.

  12. Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia.

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    Kesby, James P; Cui, Xiaoying; Burne, Thomas H J; Eyles, Darryl W

    2013-01-01

    Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

  13. Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia

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    James P. Kesby

    2013-07-01

    Full Text Available Schizophrenia is a heterogeneous group of disorders with unknown aetiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesised that abnormal dopamine signalling in the adult patient may result from altered dopamine signalling during foetal brain development. Environmental and genetic risk factors can be modelled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the aetiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD deficiency. DVD-deficient adult rats display an altered behavioural profile in response to dopamine releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters dopamine metabolism in the developing brain. We speculate such alterations in foetal brain development may change the trajectory of dopamine neuron ontogeny to induce the behavioural abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in dopamine ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

  14. Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain.

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    Kesby, James P; Turner, Karly M; Alexander, Suzanne; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

    2017-11-01

    Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat

  15. Gender-related response in open-field activity following developmental nicotine exposure in rats.

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    Romero, Roland D; Chen, Wei-Jung A

    2004-08-01

    Smoking during pregnancy may lead to low birthweight and behavioral alterations in the offspring. In this study, the effects of developmental nicotine exposure on the somatic growth of the offspring and the behavioral performance in the open-field test were examined. Sprague-Dawley female rats were implanted with nicotine (35 mg for 21-day time release; NIC 35) or placebo pellets on gestational day (GD) 8 (postblastocyst implantation). A normal control group with no pellet implant was also included. There was a significantly higher maternal weight gain in the placebo group possibly due to a larger litter size. However, there were no significant differences in body weights among all three treatment groups for male and female offspring. The amount of activity, measured by the total number of crossings in the open-field test, indicated a gender difference in baseline level and pattern of ambulatory activity, with less activity (lower number of crossings) in male offspring and an increase in the activity of the female offspring as a function of testing day. The increase in the ambulatory activity of the female offspring was observed in the placebo and normal, but not the NIC 35 group suggesting that developmental nicotine exposure interferes with open-field activity, and this behavioral alteration is gender related. Copyright 2004 Elsevier Inc.

  16. Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure.

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    Balaraman, Sridevi; Idrus, Nirelia M; Miranda, Rajesh C; Thomas, Jennifer D

    2017-05-01

    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 was 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 attenuated 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

  17. Salicylic acid-induced germination, biochemical and developmental alterations in rye (Secale cereale L.)

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    Yanik, Fatma; Aytürk, Özlem; Çetinbaş-Genç, Aslihan; Vardar, Filiz

    2018-01-01

    Salicylic acid (SA) is one of the endogenous plant growth regulators that modulate various metabolic and physiological events. To evaluate the exogenous SA-induced germination, biochemical and developmental alterations, different concentrations (10, 100, 500 and 1000 μM) of SA were applied to rye (Secale cereale L.) seeds in hydroponic culture conditions for 15 days. The observations revealed that seed germination and root elongation were stimulated in 10 μM SA treatment, however they were in...

  18. Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology.

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    Morse, Dennis C; Henck, Judith W; Bailey, Steven A

    2016-04-01

    Pregabalin was administered to pregnant Wistar rats during organogenesis to evaluate potential developmental toxicity. In an embryo-fetal development study, compared with controls, fetuses from pregabalin-treated rats exhibited increased incidence of jugal fused to maxilla (pregabalin 1250 and 2500 mg/kg) and fusion of the nasal sutures (pregabalin 2500 mg/kg). The alterations in skull development occurred in the presence of maternal toxicity (reduced body weight gain) and developmental toxicity (reduced fetal body weight and increased skeletal variations), and were initially classified as malformations. Subsequent investigative studies in pregnant rats treated with pregabalin during organogenesis confirmed the advanced jugal fused to maxilla, and fusion of the nasal sutures at cesarean section (gestation day/postmating day [PMD] 21) in pregabalin-treated groups. In a study designed to evaluate progression of skull development, advanced jugal fused to maxilla and fusion of the nasal sutures was observed on PMD 20-25 and PMD 21-23, respectively (birth occurs approximately on PMD 22). On postnatal day (PND) 21, complete jugal fused to maxilla was observed in the majority of control and 2500 mg/kg offspring. No treatment-related differences in the incidence of skull bone fusions occurred on PND 21, indicating no permanent adverse outcome. Based on the results of the investigative studies, and a review of historical data and scientific literature, the advanced skull bone fusions were reclassified as anatomic variations. Pregabalin was not teratogenic in rats under the conditions of these studies. © 2016 Wiley Periodicals, Inc.

  19. Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring.

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    Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; van den Hove, Daniel L A

    2016-04-01

    A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague-Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect-related behaviors and their underlying molecular mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Trisomy 21 and facial developmental instability.

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    Starbuck, John M; Cole, Theodore M; Reeves, Roger H; Richtsmeier, Joan T

    2013-05-01

    The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the "amplified developmental instability" hypothesis argue that trisomy 21 causes a generalized genetic imbalance that disrupts evolutionarily conserved developmental pathways by decreasing developmental homeostasis and precision throughout development. Based on this model, we test the hypothesis that DS faces exhibit increased developmental instability relative to euploid individuals. Developmental instability was assessed by a statistical analysis of fluctuating asymmetry. We compared the magnitude and patterns of fluctuating asymmetry among siblings using three-dimensional coordinate locations of 20 anatomic landmarks collected from facial surface reconstructions in four age-matched samples ranging from 4 to 12 years: (1) DS individuals (n = 55); (2) biological siblings of DS individuals (n = 55); 3) and 4) two samples of typically developing individuals (n = 55 for each sample), who are euploid siblings and age-matched to the DS individuals and their euploid siblings (samples 1 and 2). Identification in the DS sample of facial prominences exhibiting increased fluctuating asymmetry during facial morphogenesis provides evidence for increased developmental instability in DS faces. We found the highest developmental instability in facial structures derived from the mandibular prominence and lowest in facial regions derived from the frontal prominence. Copyright © 2013 Wiley Periodicals, Inc.

  1. Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis

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    Sadlier Denise M

    2007-02-01

    Full Text Available Abstract Background Osteoporosis, a disease of decreased bone mineral density represents a significant and growing burden in the western world. Aging population structure and therapeutic use of glucocorticoids have contributed in no small way to the increase in the incidence of this disease. Despite substantial investigative efforts over the last number of years the exact molecular mechanism underpinning the initiation and progression of osteoporosis remain to be elucidated. This has meant that no significant advances in therapeutic strategies have emerged, with joint replacement surgery being the mainstay of treatment. Methods In this study we have used an integrated genomics profiling and computational biology based strategy to identify the key osteoblast genes and gene clusters whose expression is altered in response to dexamethasone exposure. Primary human osteoblasts were exposed to dexamethasone in vitro and microarray based transcriptome profiling completed. Results These studies identified approximately 500 osteoblast genes whose expression was altered. Functional characterization of the transcriptome identified developmental networks as being reactivated with 106 development associated genes found to be differentially regulated. Pathway reconstruction revealed coordinate alteration of members of the WNT signaling pathway, including frizzled-2, frizzled-7, DKK1 and WNT5B, whose differential expression in this setting was confirmed by real time PCR. Conclusion The WNT pathway is a key regulator of skeletogenesis as well as differentiation of bone cells. Reactivation of this pathway may lead to altered osteoblast activity resulting in decreased bone mineral density, the pathological hallmark of osteoporosis. The data herein lend weight to the hypothesis that alterations in developmental pathways drive the initiation and progression of osteoporosis.

  2. Developmental programming and transgenerational transmission of obesity.

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    Vickers, M H

    2014-01-01

    The global obesity pandemic is often causally linked to marked changes in diet and lifestyle, namely marked increases in dietary intakes of high-energy diets and concomitant reductions in physical activity levels. However, far less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from environmental perturbations during the early-life period. Human and animal studies have highlighted the link between alterations in the early-life environment and increased susceptibility to obesity and related metabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and maternal obesity, has been shown to lead to transgenerational transmission of metabolic disorders. This association has been conceptualised as the developmental programming hypothesis whereby the impact of environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the physiology of the offspring. Further, evidence to date suggests that this developmental programming is a transgenerational phenomenon, with a number of studies showing transmission of programming effects to subsequent generations, even in the absence of continued environmental stressors, thus perpetuating a cycle of obesity and metabolic disorders. The mechanisms responsible for these transgenerational effects remain poorly understood; evidence to date suggests a number of potential mechanisms underpinning the transgenerational transmission of the developmentally programmed phenotype through both the maternal and paternal lineage. Transgenerational phenotype transmission is often seen as a form of epigenetic inheritance with evidence showing both germline and somatic inheritance of epigenetic modifications leading to phenotype changes across generations. However, there is also evidence for non-genomic components as well as an interaction between the developing fetus with the in utero

  3. Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio)

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    Aluru, Neelakanteswar; Kuo, Elaine; Helfrich, Lily W.; Karchner, Sibel I.; Linney, Elwood A.; Pais, June E.; Franks, Diana G.

    2015-01-01

    DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for 1 h from 4 to 5 h post-fertilization (hpf) and sampled at 12, 24, 48, 72, and 96 hpf to determine dnmt gene expression and DNA methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but the promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2, and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns. - Highlights: • TCDD altered the dnmt expression in a gene and developmental time-specific manner. • TCDD hypermethylated ahrra and hypomethylated c-fos proximal promoter regions. • Functional analysis suggests that ahr2 can regulate dnmt3a1, 3a2, and 3b2 expression. • Dnmt

  4. Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Aluru, Neelakanteswar, E-mail: naluru@whoi.edu [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Kuo, Elaine [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Stanford University, 450 Serra Mall, Stanford, CA 94305 (United States); Helfrich, Lily W. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Northwestern University, 633 Clark St, Evanston, IL 60208 (United States); Karchner, Sibel I. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Linney, Elwood A. [Department of Molecular Genetics and Microbiology, Duke University Medical Center, Box 3020, Durham, NC 27710 (United States); Pais, June E. [New England Biolabs, 240 County Road, Ipswich, MA 01938 (United States); Franks, Diana G. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States)

    2015-04-15

    DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for 1 h from 4 to 5 h post-fertilization (hpf) and sampled at 12, 24, 48, 72, and 96 hpf to determine dnmt gene expression and DNA methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but the promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2, and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns. - Highlights: • TCDD altered the dnmt expression in a gene and developmental time-specific manner. • TCDD hypermethylated ahrra and hypomethylated c-fos proximal promoter regions. • Functional analysis suggests that ahr2 can regulate dnmt3a1, 3a2, and 3b2 expression. • Dnmt

  5. Developmental care does not alter sleep and development of premature infants.

    Science.gov (United States)

    Ariagno, R L; Thoman, E B; Boeddiker, M A; Kugener, B; Constantinou, J C; Mirmiran, M; Baldwin, R B

    1997-12-01

    The Neonatal Individualized Developmental Care Program (NIDCAP) for very low birth weight (VLBW) preterm infants has been suggested by Als et al to improve several medical outcome variables such as time on ventilator, time to nipple feed, the duration of hospital stay, better behavioral performance on Assessment of Preterm Infants' Behavior (APIB), and improved neurodevelopmental outcomes. We have tested the hypothesis of whether the infants who had received NIDCAP would show advanced sleep-wake pattern, behavioral, and neurodevelopmental outcome. Thirty-five VLBW infants were randomly assigned to receive NIDCAP or routine infant care. The goals for NIDCAP intervention were to enhance comfort and stability and to reduce stress and agitation for the preterm infants by: a) altering the environment by decreasing excess light and noise in the neonatal intensive care unit (NICU) and by using covers over the incubators and cribs; b) use of positioning aids such as boundary supports, nests, and buntings to promote a balance of flexion and extension postures; c) modification of direct hands-on caregiving to maximize preparation of infants for, tolerance of, and facilitation of recovery from interventions; d) promotion of self-regulatory behaviors such as holding on, grasping, and sucking; e) attention to the readiness for and the ability to take oral feedings; and f) involving parents in the care of their infants as much as possible. The infants' sleep was recorded at 36 weeks postconceptional age (PCA) and at 3 months corrected age (CA) using the Motility Monitoring System (MMS), an automated, nonintrusive procedure for determining sleep state from movement and respiration patterns. Behavioral and developmental outcome was assessed by the Neurobehavioral Assessment of the Preterm Infant (NAPI) at 36 weeks PCA, the APIB at 42 weeks PCA, and by the Bayley Scales of Infant Development (BSID) at 4, 12, and 24 months CA. Sleep developmental measures at 3 months CA showed a

  6. Facilitating relational framing in children and individuals with developmental delay using the relational completion procedure.

    Science.gov (United States)

    Walsh, Sinead; Horgan, Jennifer; May, Richard J; Dymond, Simon; Whelan, Robert

    2014-01-01

    The Relational Completion Procedure is effective for establishing same, opposite and comparative derived relations in verbally able adults, but to date it has not been used to establish relational frames in young children or those with developmental delay. In Experiment 1, the Relational Completion Procedure was used with the goal of establishing two 3-member sameness networks in nine individuals with Autism Spectrum Disorder (eight with language delay). A multiple exemplar intervention was employed to facilitate derived relational responding when required. Seven of nine participants in Experiment 1 passed tests for derived relations. In Experiment 2, eight participants (all of whom, except one, had a verbal repertoire) were given training with the aim of establishing two 4-member sameness networks. Three of these participants were typically developing young children aged between 5 and 6 years old, all of whom demonstrated derived relations, as did four of the five participants with developmental delay. These data demonstrate that it is possible to reliably establish derived relations in young children and those with developmental delay using an automated procedure. © Society for the Experimental Analysis of Behavior.

  7. Aroclor 1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

    International Nuclear Information System (INIS)

    Kodavanti, Prasada Rao S.; Osorio, Cristina; Royland, Joyce E.; Ramabhadran, Ram; Alzate, Oscar

    2011-01-01

    The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca 2+ -mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit β (ATP5B), creatine kinase, and malate dehydrogenase), calcium signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and intracellular signaling, which might result in developmental neurotoxicity. -- Highlights: ► We performed brain proteomic analysis of rats exposed to the neurotoxicant, Aroclor 1254. ► Cerebellum and

  8. Aroclor 1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, Prasada Rao S., E-mail: kodavanti.prasada@epa.gov [Neurotoxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (United States); Osorio, Cristina [Systems Proteomics Center, University of North Carolina at Chapel Hill, North Carolina (United States); Program on Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, North Carolina (United States); Royland, Joyce E.; Ramabhadran, Ram [Genetic and Cellular Toxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (United States); Alzate, Oscar [Department of Cellular and Developmental Biology, University of North Carolina at Chapel Hill, North Carolina (United States); Systems Proteomics Center, University of North Carolina at Chapel Hill, North Carolina (United States); Program on Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, North Carolina (United States)

    2011-11-15

    The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca{sup 2+}-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit {beta} (ATP5B), creatine kinase, and malate dehydrogenase), calcium signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and intracellular signaling, which might result in developmental neurotoxicity. -- Highlights: Black-Right-Pointing-Pointer We performed brain proteomic analysis of rats exposed to the neurotoxicant

  9. Identification of cytochrome P450 differentiated expression related to developmental stages in bromadiolone resistance in rats (Rattus norvegicus)

    DEFF Research Database (Denmark)

    Markussen, Mette; Heiberg, Ann-Charlotte; Fredholm, Merete

    2008-01-01

    over-express the Cyp2a1 gene. TGhe altered gene expression has been suggested to be involved in the bromadiolone resistance by facilitating enhanced anticoagulant metabolism. To investigate the gene expression of these cytochrome P450 genes in rats of different developmental stages we compared...... expression profiles, from 8-, 12- and 20-week-old resistant rats of the Danish strain to profiles of anticoagulant-susceptible rats of same ages. The three age-groups were selected to represent a group of pre-pubertal, pubertal and adult rats. We found expression profiles of the pre-pubertal and pubertal...... resistant rats to concur with profiles of the adults suggesting that cytochrome P450 enzymes are involved in the Danish bromadiolone resistance regardless of developmental stage. We also investigated the relative importance of the six cytochrome P450s in the different development stages of the resistant...

  10. A relational developmental systems approach to moral development.

    Science.gov (United States)

    Carpendale, Jeremy I M; Hammond, Stuart I; Atwood, Sherrie

    2013-01-01

    Morality and cooperation are central to human life. Psychological explanations for moral development and cooperative behavior will have biological and evolutionary dimensions, but they can differ radically in their approach to biology. In particular, many recent proposals have pursued the view that aspects of morality are innate. We briefly review and critique two of these claims. In contrast to these nativist assumptions about the role of biology in morality, we present an alternative approach based on a relational developmental systems view of moral development. The role for biology in this approach is in setting up the conditions--the developmental system--in which forms of interaction and later forms of thinking emerge.

  11. Developmental Relations Between Reading Comprehension and Reading Strategies

    NARCIS (Netherlands)

    Muijselaar, M.; Swart, N.M.; Steenbeek-Planting, E.G,.; Droop, M.; Verhoeven, L.; de Jong, P.F.

    2017-01-01

    We examined the developmental relations between knowledge of reading strategies and reading comprehension in a longitudinal study of 312 Dutch children from the beginning of fourth grade to the end of fifth grade. Measures for reading comprehension, reading strategies, reading fluency, vocabulary,

  12. A relational framework for understanding bullying: Developmental antecedents and outcomes.

    Science.gov (United States)

    Rodkin, Philip C; Espelage, Dorothy L; Hanish, Laura D

    2015-01-01

    This article reviews current research on the relational processes involved in peer bullying, considering developmental antecedents and long-term consequences. The following themes are highlighted: (a) aggression can be both adaptive and maladaptive, and this distinction has implications for bullies' functioning within peer social ecologies; (b) developmental antecedents and long-term consequences of bullying have not been well-distinguished from the extant research on aggressive behavior; (c) bullying is aggression that operates within relationships of power and abuse. Power asymmetry and repetition elements of traditional bullying definitions have been hard to operationalize, but without these specifications and more dyadic measurement approaches there may be little rationale for a distinct literature on bullying--separate from aggression. Applications of a relational approach to bullying are provided using gender as an example. Implications for future research are drawn from the study of relationships and interpersonal theories of developmental psychopathology. (c) 2015 APA, all rights reserved).

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

    Science.gov (United States)

    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

  14. Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment☆

    Science.gov (United States)

    Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

    2013-01-01

    Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9–10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported. PMID:23890692

  15. The relative age effect in sport: a developmental systems model.

    Science.gov (United States)

    Wattie, Nick; Schorer, Jörg; Baker, Joseph

    2015-01-01

    The policies that dictate the participation structure of many youth sport systems involve the use of a set selection date (e.g. 31 December), which invariably produces relative age differences between those within the selection year (e.g. 1 January to 31 December). Those born early in the selection year (e.g. January) are relatively older—by as much as 12 months minus 1 day—than those born later in the selection year (e.g. December). Research in the area of sport has identified a number of significant developmental effects associated with such relative age differences. However, a theoretical framework that describes the breadth and complexity of relative age effects (RAEs) in sport does not exist in the literature. This paper reviews and summarizes the existing literature on relative age in sport, and proposes a constraints-based developmental systems model for RAEs in sport.

  16. Developmental relations between reading comprehension and reading strategies

    OpenAIRE

    Muijselaar, M.M.L.; Swart, N.M.; Steenbeek-Planting, E.G.; Droop, W.; Verhoeven, L.T.W.; Jong, P.F. de

    2017-01-01

    We examined the developmental relations between knowledge of reading strategies and reading comprehension in a longitudinal study of 312 Dutch children from the beginning of fourth grade to the end of fifth grade. Measures for reading comprehension, reading strategies, reading fluency, vocabulary, and working memory were administered. A structural equation model was constructed to estimate the unique relations between reading strategies and reading comprehension, while controlling for reading...

  17. Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment.

    Science.gov (United States)

    Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

    2013-01-01

    Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9-10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. State-related alterations of gene expression in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Berk, Michael

    2012-01-01

    Munkholm K, Vinberg M, Berk M, Kessing LV. State-related alterations of gene expression in bipolar disorder: a systematic review. Bipolar Disord 2012: 14: 684-696. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective:  Alterations in gene expression in bipolar disorder...... have been found in numerous studies. It is unclear whether such alterations are related to specific mood states. As a biphasic disorder, mood state-related alterations in gene expression have the potential to point to markers of disease activity, and trait-related alterations might indicate...... vulnerability pathways. This review therefore evaluated the evidence for whether gene expression in bipolar disorder is state or trait related. Methods:  A systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline for reporting systematic reviews, based...

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

    Directory of Open Access Journals (Sweden)

    Kathleen M. Gilbert

    2014-01-01

    Full Text Available 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.

  20. Health-Related Physical Fitness in Dutch Children With Developmental Coordination Disorder

    NARCIS (Netherlands)

    van der Hoek, Frouwien D.; Stuive, Ilse; Reinders-Messelink, Heleen A.; Holty, Lian; de Blecourt, Alida C. E.; Maathuis, Carel G. B.; van Weert, Ellen

    2012-01-01

    Objective: To compare components of health-related physical fitness between Dutch children with clinically diagnosed developmental coordination disorder (DCD) and typically developing children (TDC), and to examine associations between motor performance problems and components of health-related

  1. Developmental exposure to terbutaline alters cell signaling in mature rat brain regions and augments the effects of subsequent neonatal exposure to the organophosphorus insecticide chlorpyrifos

    International Nuclear Information System (INIS)

    Meyer, Armando; Seidler, Frederic J.; Aldridge, Justin E.; Slotkin, Theodore A.

    2005-01-01

    Exposure to apparently unrelated neurotoxicants can nevertheless converge on common neurodevelopmental events. We examined the long-term effects of developmental exposure of rats to terbutaline, a β-adrenoceptor agonist used to arrest preterm labor, and the organophosphorus insecticide chlorpyrifos (CPF) separately and together. Treatments mimicked the appropriate neurodevelopmental stages for human exposures: terbutaline on postnatal days (PN) 2-5 and CPF on PN11-14, with assessments conducted on PN45. Although neither treatment affected growth or viability, each elicited alterations in CNS cell signaling mediated by adenylyl cyclase (AC), a transduction pathway shared by numerous neuronal and hormonal signals. Terbutaline altered signaling in the brainstem and cerebellum, with gender differences particularly notable in the cerebellum (enhanced AC in males, suppressed in females). By itself, CPF exposure elicited deficits in AC signaling in the midbrain, brainstem, and striatum. However, sequential exposure to terbutaline followed by CPF produced larger alterations and involved a wider spectrum of brain regions than were obtained with either agent alone. In the cerebral cortex, adverse effects of the combined treatment intensified between PN45 and PN60, suggesting that exposures alter the long-term program for development of synaptic communication, leading to alterations in AC signaling that emerge even after adolescence. These findings indicate that terbutaline, like CPF, is a developmental neurotoxicant, and reinforce the idea that its use in preterm labor may create a subpopulation that is sensitized to long-term CNS effects of organophosphorus insecticides

  2. Developmental and Neurological Implications for Relating Cognition and Affect.

    Science.gov (United States)

    Bart, William M.

    Elements of a theory relating cognition and affect are outlined. The theory is heavily based upon neuroscience research regarding the hemispheric lateralization of various cognitive processes and emotions; specific examples are provided. Developmental research on intelligence as well as theories of intrinsic motivation, are also discussed.…

  3. Altered Developmental Trajectories for Impulsivity and Sensation Seeking among Adolescent Substance Users

    Science.gov (United States)

    Charles, Nora E.; Ryan, Stacy R.; Bray, Bethany C.; Mathias, Charles W.; Acheson, Ashley; Dougherty, Donald M.

    2016-01-01

    A number of studies have associated impulsivity and sensation seeking with level of substance use and risk for developing a substance use disorder. These relationships may be particularly apparent during adolescence, when developmental changes in impulsivity and sensation seeking occur at the same time as increased opportunities for substance use. To examine this, the current study measured impulsivity and sensation seeking from pre-adolescence to mid-adolescence in a sample of youth, the majority of whom were identified as being at risk for developing a substance use disorder based on their family history of substance use disorders. Youth were separated into those who did (n = 117) and did not (n = 269) initiate substance use by mid-adolescence. Results showed that substance users were more impulsive and more sensation seeking during pre-adolescence, prior to any significant substance use, and that greater sensation seeking in pre-adolescence was related to heavier substance use by mid-adolescence. In addition, developmental trajectories for substance-using youth showed a greater increase in sensation seeking but a more modest decrease in impulsivity from pre-adolescence to mid-adolescence. Taken together, these results indicate that increased impulsivity and sensation seeking is apparent in adolescent substance users as early as pre-adolescence, that the difference between substance users and non-users becomes larger across early adolescence as their developmental trajectories diverge, and that greater sensation seeking in pre-adolescence may predict increased substance use by mid-adolescence. PMID:27174219

  4. Developmental trajectories of pitch-related music skills in children with Williams syndrome.

    Science.gov (United States)

    Martínez-Castilla, Pastora; Rodríguez, Manuel; Campos, Ruth

    2016-01-01

    The study of music cognition in Williams syndrome (WS) has resulted in theoretical debates regarding cognitive modularity and development. However, no research has previously investigated the development of music skills in this population. In this study, we used the cross-sectional developmental trajectories approach to assess the development of pitch-related music skills in children with WS compared with typically developing (TD) peers. Thus, we evaluated the role of change over time on pitch-related music skills and the developmental relationships between music skills and different cognitive areas. In the TD children, the pitch-related music skills improved with chronological age and cognitive development. In the children with WS, developmental relationships were only found between several pitch-related music skills and specific cognitive processes. We also found non-systematic relationships between chronological age and the pitch-related music skills, stabilization in the level reached in music when cognitive development was considered, and uneven associations between cognitive and music skills. In addition, the TD and WS groups differed in their patterns of pitch-related music skill development. These results suggest that the development of pitch-related music skills in children with WS is atypical. Our findings stand in contrast with the views that claim innate modularity for music in WS; rather, they are consistent with neuroconstructivist accounts. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Suppressing Farnesyl Diphosphate Synthase Alters Chloroplast Development and Triggers Sterol-Dependent Induction of Jasmonate- and Fe-Related Responses.

    Science.gov (United States)

    Manzano, David; Andrade, Paola; Caudepón, Daniel; Altabella, Teresa; Arró, Montserrat; Ferrer, Albert

    2016-09-01

    Farnesyl diphosphate synthase (FPS) catalyzes the synthesis of farnesyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate. Arabidopsis (Arabidopsis thaliana) contains two genes (FPS1 and FPS2) encoding FPS. Single fps1 and fps2 knockout mutants are phenotypically indistinguishable from wild-type plants, while fps1/fps2 double mutants are embryo lethal. To assess the effect of FPS down-regulation at postembryonic developmental stages, we generated Arabidopsis conditional knockdown mutants expressing artificial microRNAs devised to simultaneously silence both FPS genes. Induction of silencing from germination rapidly caused chlorosis and a strong developmental phenotype that led to seedling lethality. However, silencing of FPS after seed germination resulted in a slight developmental delay only, although leaves and cotyledons continued to show chlorosis and altered chloroplasts. Metabolomic analyses also revealed drastic changes in the profile of sterols, ubiquinones, and plastidial isoprenoids. RNA sequencing and reverse transcription-quantitative polymerase chain reaction transcriptomic analysis showed that a reduction in FPS activity levels triggers the misregulation of genes involved in biotic and abiotic stress responses, the most prominent one being the rapid induction of a set of genes related to the jasmonic acid pathway. Down-regulation of FPS also triggered an iron-deficiency transcriptional response that is consistent with the iron-deficient phenotype observed in FPS-silenced plants. The specific inhibition of the sterol biosynthesis pathway by chemical and genetic blockage mimicked these transcriptional responses, indicating that sterol depletion is the primary cause of the observed alterations. Our results highlight the importance of sterol homeostasis for normal chloroplast development and function and reveal important clues about how isoprenoid and sterol metabolism is integrated within plant physiology and development. © 2016

  6. Developmental and sex-related differences in preschoolers' affective decision making.

    Science.gov (United States)

    Heilman, Renata M; Miu, Andrei C; Benga, Oana

    2009-01-01

    This study investigated developmental and sex-related differences in affective decision making, using a two-deck version of Children's Gambling Task administered to 3- and 4-year-old children. The main findings were that 4-year-old children displayed better decision-making performance than 3-year-olds. This effect was independent of developmental changes in inductive reasoning, language, and working memory. There were also sex differences in decision-making performance, which were apparent only in 3-year-old children and favored girls. Moreover, age predicted awareness of task and the correlation between the latter and decision-making performance was significant, but only in 4-year-old children. This study thus indicates that there is a remarkable developmental leap in affective decision making, whose effects are apparent around the age of 4, which according to our results, also marks the age when the correlation of declarative knowledge and decision-making performance becomes significant.

  7. Sensory retraining: burden in daily life related to altered sensation after orthognathic surgery, a randomized clinical trial.

    Science.gov (United States)

    Phillips, C; Kim, S H; Tucker, M; Turvey, T A

    2010-08-01

    Assess the long-term effect of sensory retraining exercises, age, gender, type of surgery, and pre-surgical psychological distress on patients' perception of the interference related to altered sensation 2 years after orthognathic surgery. A total of 186 subjects with a developmental dentofacial disharmony were enrolled in a multicenter randomized clinical trial: one center was a community-based practice and the other a university-based center. Subjects were randomly allocated to two groups: standard of care mouth opening exercises after BSSO or a progressive series of sensory retraining facial exercises in addition to the opening exercises. At 1, 3, 6, 12, and 24 months after surgery, subjects scored unusual feelings on the face, numbness, and loss of lip sensitivity from 'no problem (1)' to 'serious problem (7)'. A marginal proportional odds model was fit for each of the ordinal outcomes. Up to 2 years after surgery, the opening exercise only group had a higher likelihood of reporting interference in daily activities related to numbness and loss of lip sensitivity than the sensory retraining exercise group. The difference between the two groups was relatively constant. Older subjects and those with elevated psychological distress before surgery reported higher burdens related to unusual facial feelings, numbness, and loss of lip sensitivity (p pre-surgical counseling regarding the impact on daily life of persistent altered sensation following a mandibular osteotomy.

  8. Suppressing Farnesyl Diphosphate Synthase Alters Chloroplast Development and Triggers Sterol-Dependent Induction of Jasmonate- and Fe-Related Responses1[OPEN

    Science.gov (United States)

    Andrade, Paola; Caudepón, Daniel; Arró, Montserrat

    2016-01-01

    Farnesyl diphosphate synthase (FPS) catalyzes the synthesis of farnesyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate. Arabidopsis (Arabidopsis thaliana) contains two genes (FPS1 and FPS2) encoding FPS. Single fps1 and fps2 knockout mutants are phenotypically indistinguishable from wild-type plants, while fps1/fps2 double mutants are embryo lethal. To assess the effect of FPS down-regulation at postembryonic developmental stages, we generated Arabidopsis conditional knockdown mutants expressing artificial microRNAs devised to simultaneously silence both FPS genes. Induction of silencing from germination rapidly caused chlorosis and a strong developmental phenotype that led to seedling lethality. However, silencing of FPS after seed germination resulted in a slight developmental delay only, although leaves and cotyledons continued to show chlorosis and altered chloroplasts. Metabolomic analyses also revealed drastic changes in the profile of sterols, ubiquinones, and plastidial isoprenoids. RNA sequencing and reverse transcription-quantitative polymerase chain reaction transcriptomic analysis showed that a reduction in FPS activity levels triggers the misregulation of genes involved in biotic and abiotic stress responses, the most prominent one being the rapid induction of a set of genes related to the jasmonic acid pathway. Down-regulation of FPS also triggered an iron-deficiency transcriptional response that is consistent with the iron-deficient phenotype observed in FPS-silenced plants. The specific inhibition of the sterol biosynthesis pathway by chemical and genetic blockage mimicked these transcriptional responses, indicating that sterol depletion is the primary cause of the observed alterations. Our results highlight the importance of sterol homeostasis for normal chloroplast development and function and reveal important clues about how isoprenoid and sterol metabolism is integrated within plant physiology and development. PMID

  9. Altered Modulation of Silent Period in Tongue Motor Cortex of Persistent Developmental Stuttering in Relation to Stuttering Severity.

    Science.gov (United States)

    Busan, Pierpaolo; Del Ben, Giovanni; Bernardini, Simona; Natarelli, Giulia; Bencich, Marco; Monti, Fabrizio; Manganotti, Paolo; Battaglini, Piero Paolo

    2016-01-01

    Motor balance in developmental stuttering (DS) was investigated with Transcranial Magnetic Stimulation (TMS), with the aim to define novel neural markers of persistent DS in adulthood. Eleven DS adult males were evaluated with TMS on tongue primary motor cortex, compared to 15 matched fluent speakers, in a "state" condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and silent period thresholds (SPT), recruitment curves, and silent period durations were acquired by recording tongue motor evoked potentials. Tongue silent period duration was increased in DS, especially in the left hemisphere (Pstuttering severity. Pre-TMS electromyography data gave overlapping evidence. Findings suggest the existence of a complex intracortical balance in DS tongue primary motor cortex, with a particular interplay between excitatory and inhibitory mechanisms, also in neural substrates related to silent periods. Findings are discussed with respect to functional and structural impairments in stuttering, and are also proposed as novel neural markers of a stuttering "state" in persistent DS, helping to define more focused treatments (e.g. neuro-modulation).

  10. An Out-of-Math Experience: Einstein, Relativity, and the Developmental Mathematics Student.

    Science.gov (United States)

    Fiore, Greg

    2000-01-01

    Discusses Einstein's special relativity theory and some of the developmental mathematics involved. Presents motivational classroom materials used in discussing relative-motion problems, evaluating a radical expression, graphing with asymptotes, interpreting a graph, studying variation, and solving literal and radical equations. (KHR)

  11. Developmental model of static allometry in holometabolous insects.

    Science.gov (United States)

    Shingleton, Alexander W; Mirth, Christen K; Bates, Peter W

    2008-08-22

    The regulation of static allometry is a fundamental developmental process, yet little is understood of the mechanisms that ensure organs scale correctly across a range of body sizes. Recent studies have revealed the physiological and genetic mechanisms that control nutritional variation in the final body and organ size in holometabolous insects. The implications these mechanisms have for the regulation of static allometry is, however, unknown. Here, we formulate a mathematical description of the nutritional control of body and organ size in Drosophila melanogaster and use it to explore how the developmental regulators of size influence static allometry. The model suggests that the slope of nutritional static allometries, the 'allometric coefficient', is controlled by the relative sensitivity of an organ's growth rate to changes in nutrition, and the relative duration of development when nutrition affects an organ's final size. The model also predicts that, in order to maintain correct scaling, sensitivity to changes in nutrition varies among organs, and within organs through time. We present experimental data that support these predictions. By revealing how specific physiological and genetic regulators of size influence allometry, the model serves to identify developmental processes upon which evolution may act to alter scaling relationships.

  12. Developmental and lactational exposure to dieldrin alters mammary tumorigenesis in Her2/neu transgenic mice.

    Directory of Open Access Journals (Sweden)

    Heather L Cameron

    Full Text Available Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offspring. Sexually mature FVB-MMTV/neu female mice were treated with vehicle (corn oil, or dieldrin (0.45, 2.25, and 4.5 microg/g body weight daily by gavage for 5 days prior to mating and then once weekly throughout gestation and lactation until weaning. Dieldrin concentrations were selected to produce serum levels representative of human background body burdens, occupational exposure, and overt toxicity. Treatment had no effect on litter size, birth weight or the number of pups surviving to weaning. The highest dose of dieldrin significantly increased the total tumor burden and the volume and number of tumors found in the thoracic mammary glands. Increased mRNA and protein expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors from the offspring of dieldrin treated dams. This study indicates that developmental exposure to the environmental contaminant dieldrin causes increased tumor burden in genetically predisposed mice. Dieldrin exposure also altered the expression of BNDF and TrkB, novel modulators of cancer pathogenesis.

  13. Gene expression profiles in the cerebellum and hippocampus following exposure to a neurotoxicant, Aroclor 1254: Developmental effects

    International Nuclear Information System (INIS)

    Royland, Joyce E.; Wu, Jinfang; Zawia, Nasser H.; Kodavanti, Prasada Rao S.

    2008-01-01

    The developmental consequences of exposure to the polychlorinated biphenyls (PCBs) have been widely studied, making PCBs a unique model to understand issues related to environmental mixture of persistent chemicals. PCB exposure in humans adversely affects neurocognitive development, causes psychomotor difficulties, and contributes to attention deficits in children, all of which seem to be associated with altered patterns of neuronal connectivity. In the present study, we examined gene expression profiles in the rat nervous system following PCB developmental exposure. Pregnant rats (Long-Evans) were dosed perinatally with 0 or 6 mg/kg/day of Aroclor 1254 from gestation day 6 through postnatal day (PND) 21. Gene expression in cerebellum and hippocampus from PND7 and PND14 animals was analyzed with an emphasis on developmental aspects. Changes in gene expression (≥ 1.5 fold) in control animals identified normal developmental changes. These basal levels of expression were compared to data from Aroclor 1254-treated animals to determine the impact of gestational PCB exposure on developmental parameters. The results indicate that the expression of a number of developmental genes related to cell cycle, synaptic function, cell maintenance, and neurogenesis is significantly altered from PND7 to PND14. Aroclor 1254 treatment appears to dampen the overall growth-related gene expression levels in both regions with the effect being more pronounced in the cerebellum. Functional analysis suggests that Aroclor 1254 delays maturation of the developing nervous system, with the consequences dependent on the ontological state of the brain area and the functional role of the individual gene. Such changes may underlie learning and memory deficits observed in PCB exposed animals and humans

  14. Developmental improvement and age-related decline in unfamiliar face matching.

    Science.gov (United States)

    Megreya, Ahmed M; Bindemann, Markus

    2015-01-01

    Age-related changes have been documented widely in studies of face recognition and eyewitness identification. However, it is not clear whether these changes arise from general developmental differences in memory or occur specifically during the perceptual processing of faces. We report two experiments to track such perceptual changes using a 1-in- 10 (experiment 1) and 1-in-1 (experiment 2) matching task for unfamiliar faces. Both experiments showed improvements in face matching during childhood and adult-like accuracy levels by adolescence. In addition, face-matching performance declined in adults of the age of 65 years. These findings indicate that developmental improvements and aging-related differences in face processing arise from changes in the perceptual encoding of faces. A clear face inversion effect was also present in all age groups. This indicates that those age-related changes in face matching reflect a quantitative effect, whereby typical face processes are engaged but do not operate at the best-possible level. These data suggest that part of the problem of eyewitness identification in children and elderly persons might reflect impairments in the perceptual processing of unfamiliar faces.

  15. Neural Alterations in Acquired Age-Related Hearing Loss

    Directory of Open Access Journals (Sweden)

    Raksha Anand Mudar

    2016-06-01

    Full Text Available Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional magnetic resonance imaging, diffusion tensor imaging, and event-related electroencephalography. We discuss structural and functional alterations observed in the temporal and frontal cortices and the limbic system. These neural alterations are discussed in the context of common cause, information-degradation, and sensory-deprivation hypotheses, and we suggest possible rehabilitation strategies. Although we are beginning to learn more about changes in neural architecture and functionality related to age-associated hearing loss, much work remains to be done. Understanding the neural alterations will provide objective markers for early identification of neural consequences of age-associated hearing loss and for evaluating benefits of intervention approaches.

  16. The History of Legislation and Regulations Related to Children with Developmental Disabilities: Implications for School Nursing Practice Today

    Science.gov (United States)

    Dang, Michelle T.

    2010-01-01

    A significant number of children in the United States have developmental disabilities. Historically, many children with developmental disabilities were institutionalized and rarely seen in public. Currently, children with developmental disabilities are entitled to education and health-related support services that permit them access to public…

  17. Developmental Neurotoxicity of Traffic-Related Air Pollution: Focus on Autism.

    Science.gov (United States)

    Costa, Lucio G; Chang, Yu-Chi; Cole, Toby B

    2017-06-01

    Epidemiological and animal studies suggest that air pollution may negatively affect the central nervous system (CNS) and contribute to CNS diseases. Traffic-related air pollution is a major contributor to global air pollution, and diesel exhaust (DE) is its most important component. Several studies suggest that young individuals may be particularly susceptible to air pollution-induced neurotoxicity and that perinatal exposure may cause or contribute to developmental disabilities and behavioral abnormalities. In particular, a number of recent studies have found associations between exposures to traffic-related air pollution and autism spectrum disorders (ASD), which are characterized by impairment in socialization and in communication and by the presence of repetitive and unusual behaviors. The cause(s) of ASD are unknown, and while it may have a hereditary component, environmental factors are increasingly suspected as playing a pivotal role in its etiology, particularly in genetically susceptible individuals. Autistic children present higher levels of neuroinflammation and systemic inflammation, which are also hallmarks of exposure to traffic-related air pollution. Gene-environment interactions may play a relevant role in determining individual susceptibility to air pollution developmental neurotoxicity. Given the worldwide presence of elevated air pollution, studies on its effects and mechanisms on the developing brain, genetic susceptibility, role in neurodevelopmental disorders, and possible therapeutic interventions are certainly warranted.

  18. Large scale expression changes of genes related to neuronal signaling and developmental processes found in lateral septum of postpartum outbred mice.

    Directory of Open Access Journals (Sweden)

    Brian E Eisinger

    Full Text Available Coordinated gene expression changes across the CNS are required to produce the mammalian maternal phenotype. Lateral septum (LS is a brain region critically involved with aspects of maternal care, and we recently examined gene expression of whole septum (LS and medial septum in selectively bred maternal mice. Here, we expand on the prior study by 1 conducting microarray analysis solely on LS in virgin and postpartum mice, 2 using outbred mice, and 3 evaluating the role of sensory input on gene expression changes. Large scale changes in genes related to neuronal signaling were identified, including four GABAA receptor subunits. Subunits α4 and δ were downregulated in maternal LS, likely reflecting a reduction in the extrasynaptic, neurosteroid-sensitive α4/δ containing receptor subtype. Conversely, subunits ε and θ were increased in maternal LS. Fifteen K+ channel related genes showed altered expression, as did dopamine receptors Drd1a and Drd2 (both downregulated, hypocretin receptor 1 (Hcrtr1, kappa opioid receptor 1 (Oprk1, and transient receptor potential channel 4 (Trpc4. Expression of a large number of genes linked to developmental processes or cell differentiation were also altered in postpartum LS, including chemokine (C-X-C motif ligand 12 (Cxcl12, fatty acid binding protein 7 (Fabp7, plasma membrane proteolipid (Pllp, and suppressor of cytokine signaling 2 (Socs2. Additional genes that are linked to anxiety, such as glutathione reductase (Gsr, exhibited altered expression. Pathway analysis also identified changes in genes related to cyclic nucleotide metabolism, chromatin structure, and the Ras gene family. The sensory presence of pups was found to contribute to the altered expression of a subset of genes across all categories. This study suggests that both large changes in neuronal signaling and the possible terminal differentiation of neuronal and/or glial cells play important roles in producing the maternal state.

  19. Critical Windows of Cardiovascular Susceptibility to Developmental Hypoxia in Common Snapping Turtle (Chelydra serpentina) Embryos.

    Science.gov (United States)

    Tate, Kevin B; Kohl, Zachary F; Eme, John; Rhen, Turk; Crossley, Dane A

    2015-01-01

    Environmental conditions fluctuate dramatically in some reptilian nests. However, critical windows of environmental sensitivity for cardiovascular development have not been identified. Continuous developmental hypoxia has been shown to alter cardiovascular form and function in embryonic snapping turtles (Chelydra serpentina), and we used this species to identify critical periods during which hypoxia modifies the cardiovascular phenotype. We hypothesized that incubation in 10% O2 during specific developmental periods would have differential effects on the cardiovascular system versus overall somatic growth. Two critical windows were identified with 10% O2 from 50% to 70% of incubation, resulting in relative heart enlargement, either via preservation of or preferential growth of this tissue, while exposure to 10% O2 from 20% to 70% of incubation resulted in a reduction in arterial pressure. The deleterious or advantageous aspects of these embryonic phenotypes in posthatching snapping turtles have yet to be explored. However, identification of these critical windows has provided insight into how the developmental environment alters the phenotype of reptiles and will also be pivotal in understanding its impact on the fitness of egg-laying reptiles.

  20. METHYLMERCURY IMPAIRS NEURONAL DIFFERENTIATION BY ALTERING NEUROTROPHIN SIGNALING.

    Science.gov (United States)

    In previous in vivo studies, we observed that developmental exposure to CH3Hg can alter neocortical morphology and neurotrophin signaling. Using primed PC12 cells as a model system for neuronal differentiation, we examined the hypothesis that the developmental effects of CH3Hg ma...

  1. Binge drinking and family history of alcoholism are associated with an altered developmental trajectory of impulsive choice across adolescence.

    Science.gov (United States)

    Jones, Scott A; Steele, Joel S; Nagel, Bonnie J

    2017-07-01

    To test whether binge drinking, the density of familial alcoholism (FHD) and their interaction are associated with an altered developmental trajectory of impulsive choice across adolescence, and whether more life-time drinks are associated with a greater change in impulsive choice across age. Alcohol-naive adolescents, with varying degrees of FHD, were recruited as part of an ongoing longitudinal study on adolescent development, and were grouped based on whether they remained non-drinkers (n = 83) or initiated binge drinking (n = 33) during follow-up. During all visits, adolescents completed a monetary delay discounting task to measure impulsive choice. The effects of binge-drinking status, FHD and their interaction on impulsive choice across adolescence were tested. Developmental Brain Imaging Laboratory, Oregon Health & Science University, Portland, Oregon, USA. A total of 116 healthy male and female adolescents (ages 10-17 years at baseline) completed two to four visits between July 2008 and May 2016. Discounting rates were obtained based on adolescents' preference for immediate or delayed rewards. FHD was based on parent-reported prevalence of alcohol use disorder in the participant's first- and second-degree relatives. Binge-drinking status was determined based on the number of recent binge-drinking episodes. There was a significant interaction effect of binge-drinking status and FHD on impulsive choice across age (b = 1.090, P alcohol-naive, greater FHD was associated with a steeper decrease in discounting rates across adolescence (b = -0.633, P alcoholism is associated with a steeper decline in impulsive choice across adolescence, but only in those who remain alcohol-naive. Meanwhile, more life-time drinks during adolescence is associated with increases in impulsive choice across age. © 2017 Society for the Study of Addiction.

  2. Relations among motor, social, and cognitive skills in pre-kindergarten children with developmental disabilities.

    Science.gov (United States)

    Kim, Helyn; Carlson, Abby G; Curby, Timothy W; Winsler, Adam

    2016-01-01

    Despite the comorbidity between motor difficulties and certain disabilities, limited research has examined links between early motor, cognitive, and social skills in preschool-aged children with developmental disabilities. The present study examined the relative contributions of gross motor and fine motor skills to the prediction of improvements in children's cognitive and social skills among 2,027 pre-kindergarten children with developmental disabilities, including specific learning disorder, speech/language impairment, intellectual disability, and autism spectrum disorder. Results indicated that for pre-kindergarten children with developmental disabilities, fine motor skills, but not gross motor skills, were predictive of improvements in cognitive and social skills, even after controlling for demographic information and initial skill levels. Moreover, depending on the type of developmental disability, the pattern of prediction of gross motor and fine motor skills to improvements in children's cognitive and social skills differed. Implications are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Perflurooctanoic acid induces developmental cardiotoxicity in chicken embryos and hatchlings

    International Nuclear Information System (INIS)

    Jiang, Qixiao; Lust, Robert M.; Strynar, Mark J.; Dagnino, Sonia; DeWitt, Jamie C.

    2012-01-01

    Highlights: ► PFOA exposure thinned right ventricular wall thickness in D19 chicken embryo hearts. ► PFOA exposure induced left ventricle hypertrophy in hearts of hatchling chickens. ► PFOA exposure induced altered cardiac function in hatchling chickens. -- Abstract: Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that is detectable in serum of the general U.S. population. PFOA is a known developmental toxicant that induces mortality in mammalian embryos and is thought to induce toxicity via interaction with the peroxisome proliferator activated receptor alpha (PPARα). As the cardiovascular system is crucial for embryonic survival, PFOA-induced effects on the heart may partially explain embryonic mortality. To assess impacts of PFOA exposure on the developing heart in an avian model, we used histopathology and immunohistochemical staining for myosin to assess morphological alterations in 19-day-old chicken embryo hearts after PFOA exposure. Additionally, echocardiography and cardiac myofibril ATPase activity assays were used to assess functional alterations in 1-day-old hatchling chickens following developmental PFOA exposure. Overall thinning and thinning of a dense layer of myosin in the right ventricular wall were observed in PFOA-exposed chicken embryo hearts. Alteration of multiple cardiac structural and functional parameters, including left ventricular wall thickness, left ventricular volume, heart rate, stroke volume, and ejection fraction were detected with echocardiography in the exposed hatchling chickens. Assessment of ATPase activity indicated that the ratio of cardiac myofibril calcium-independent ATPase activity to calcium-dependent ATPase activity was not affected, which suggests that developmental PFOA exposure may not affect cardiac energetics. In summary, structural and functional characteristics of the heart appear to be developmental targets of PFOA, possibly at the level of cardiomyocytes. Additional studies will

  4. DSM-V diagnostic criteria for bereavement-related disorders in children and adolescents: developmental considerations.

    Science.gov (United States)

    Kaplow, Julie B; Layne, Christopher M; Pynoos, Robert S; Cohen, Judith A; Lieberman, Alicia

    2012-01-01

    Two bereavement-related disorders are proposed for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V): Adjustment Disorder Related to Bereavement, to be located in the main body of the text as an official diagnostic entity; and Bereavement-Related Disorder, including a Traumatic Death Specifier, to be located in the Appendix as an invitation for further research. These diagnoses currently do not include developmentally informed criteria, despite the importance of developmental processes in the ways children and adolescents grieve. In this article, we draw upon a selective review of the empirical literature and expert clinical knowledge to recommend developmentally informed modifications and specifiers of the proposed criteria for both bereavement disorders and strategies to improve future research. This article is derived from an invited report submitted to the DSM-V Posttraumatic Stress Disorder, Trauma, and Dissociative Disorders Sub-Work Group, and suggested modifications have received preliminary approval to be incorporated into the DSM-V at the time of this writing. Adoption of these proposals will have far-reaching consequences, given that DSM-V criteria will influence both critical treatment choices for bereaved youth and the next generation of research studies.

  5. M-Stream Deficits and Reading-Related Visual Processes in Developmental Dyslexia

    Science.gov (United States)

    Boden, Catherine; Giaschi, Deborah

    2007-01-01

    Some visual processing deficits in developmental dyslexia have been attributed to abnormalities in the subcortical M stream and/or the cortical dorsal stream of the visual pathways. The nature of the relationship between these visual deficits and reading is unknown. The purpose of the present article was to characterize reading-related perceptual…

  6. Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features.

    Science.gov (United States)

    Wehrhan, Falk; Hyckel, Peter; Ries, Jutta; Stockmann, Phillip; Nkenke, Emeka; Schlegel, Karl A; Neukam, Friedrich W; Amann, Kerstin

    2010-10-13

    Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p Msx-1 (p Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue.

  7. Developmental Science: Past, Present, and Future

    Science.gov (United States)

    Lerner, Richard M.

    2012-01-01

    The goal of developmental science is to describe, explain, and optimize intraindividual changes in adaptive developmental regulations and, as well, interindividual differences in such relations, across life. The history of developmental science is reviewed and its current foci, which are framed by relational developmental systems models that…

  8. The Domain of Developmental Psychopathology.

    Science.gov (United States)

    Sroufe, L. Alan; Rutter, Michael

    1984-01-01

    Describes how developmental psychopathology differs from related disciplines, including abnormal psychology, psychiatry, clinical child psychology, and developmental psychology. Points out propositions underlying a developmental perspective and discusses implications for research in developmental psychopathology. (Author/RH)

  9. Epigenetics as a mechanism linking developmental exposures to long-term toxicity

    DEFF Research Database (Denmark)

    Barouki, R; Melén, E; Herceg, Z

    2018-01-01

    A variety of experimental and epidemiological studies lend support to the Developmental Origin of Health and Disease (DOHaD) concept. Yet, the actual mechanisms accounting for mid- and long-term effects of early-life exposures remain unclear. Epigenetic alterations such as changes in DNA methylat......A variety of experimental and epidemiological studies lend support to the Developmental Origin of Health and Disease (DOHaD) concept. Yet, the actual mechanisms accounting for mid- and long-term effects of early-life exposures remain unclear. Epigenetic alterations such as changes in DNA...

  10. Developmental Continuity and Change in Physical, Verbal, and Relational Aggression and Peer Victimization from Childhood to Adolescence

    Science.gov (United States)

    Ettekal, Idean; Ladd, Gary W.

    2017-01-01

    To investigate the developmental course of aggression and peer victimization in childhood and adolescence, distinct subgroups of children were identified based on similarities and differences in their physical, verbal and relational aggression, and victimization. Developmental continuity and change were assessed by examining transitions within and…

  11. Developmental immunotoxicology of lead

    International Nuclear Information System (INIS)

    Dietert, Rodney R.; Lee, Ji-Eun; Hussain, Irshad; Piepenbrink, Michael

    2004-01-01

    The heavy metal, lead, is a known developmental immunotoxicant that has been shown to produce immune alterations in humans as well as other species. Unlike many compounds that exert adverse immune effects, lead exposure at low to moderate levels does not produce widespread loss of immune cells. In contrast, changes resulting from lead exposure are subtle at the immune cell population level but, nevertheless, can be functionally dramatic. A hallmark of lead-induced immunotoxicity is a pronounced shift in the balance in T helper cell function toward T helper 2 responses at the expense of T helper 1 functions. This bias alters the nature and range of immune responses that can be produced thereby influencing host susceptibility to various diseases. Immunotoxic responses to lead appear to differ across life stages not only quantitatively with regard to dose response, but also qualitatively in terms of the spectrum of immune alterations. Experimental studies in several lab animal species suggest the latter stages of gestation are a period of considerable sensitivity for lead-induced immunotoxicity. This review describes the basic characteristics of lead-induced immunotoxicity emphasizing experimental animal results. It also provides a framework for the consideration of toxicant exposure effects across life stages. The existence of and probable basis for developmental windows of immune hyper-susceptibility are presented. Finally, the potential for lead to serve as a perinatal risk factor for childhood asthma as well as other diseases is considered

  12. Examining the Criterion-Related Validity of the Pervasive Developmental Disorder Behavior Inventory

    Science.gov (United States)

    McMorris, Carly A.; Perry, Adrienne

    2015-01-01

    The Pervasive Developmental Disorder Behavior Inventory is a questionnaire designed to aid in the diagnosis of pervasive developmental disorders or autism spectrum disorders. The Pervasive Developmental Disorder Behavior Inventory assesses adaptive and maladaptive behaviors associated with pervasive developmental disorders and provides an…

  13. Cultural Mediation. The Usefulness of Selected Concepts of Developmental Psychology for Coaching and Mentoring Relations

    OpenAIRE

    Smorczewska, Barbara

    2013-01-01

    Some developmental psychological concepts, such as L. S. Vygotsky’s zone of proximal development or H. R. Schaffer’s joint involvement episodes, gave a new perspective in perceiving the process of teaching and development, by providing very detailed characteristics of the situation of acquiring competence in social relations. The mentioned concepts are based on a belief in the developmental potential of humans, and they perceive teaching as future-oriented. These assumptions are also characte...

  14. Developmental programming: the concept, large animal models, and the key role of uteroplacental vascular development.

    Science.gov (United States)

    Reynolds, L P; Borowicz, P P; Caton, J S; Vonnahme, K A; Luther, J S; Hammer, C J; Maddock Carlin, K R; Grazul-Bilska, A T; Redmer, D A

    2010-04-01

    Developmental programming refers to the programming of various bodily systems and processes by a stressor of the maternal system during pregnancy or during the neonatal period. Such stressors include nutritional stress, multiple pregnancy (i.e., increased numbers of fetuses in the gravid uterus), environmental stress (e.g., high environmental temperature, high altitude, prenatal steroid exposure), gynecological immaturity, and maternal or fetal genotype. Programming refers to impaired function of numerous bodily systems or processes, leading to poor growth, altered body composition, metabolic dysfunction, and poor productivity (e.g., poor growth, reproductive dysfunction) of the offspring throughout their lifespan and even across generations. A key component of developmental programming seems to be placental dysfunction, leading to altered fetal growth and development. We discuss various large animal models of developmental programming and how they have and will continue to contribute to our understanding of the mechanisms underlying altered placental function and developmental programming, and, further, how large animal models also will be critical to the identification and application of therapeutic strategies that will alleviate the negative consequences of developmental programming to improve offspring performance in livestock production and human medicine.

  15. Protein expression in the nucleus accumbens of rats exposed to developmental vitamin D deficiency.

    Directory of Open Access Journals (Sweden)

    John McGrath

    Full Text Available INTRODUCTION: Developmental vitamin D (DVD deficiency is a candidate risk factor for schizophrenia. Animal models have confirmed that DVD deficiency is associated with a range of altered genomic, proteomic, structural and behavioural outcomes in the rat. Because the nucleus accumbens has been implicated in neuropsychiatric disorders, in the current study we examined protein expression in this region in adult rats exposed to DVD deficiency METHODS: Female Sprague Dawley rats were maintained on a vitamin D deficient diet for 6 weeks, mated and allowed to give birth, after which a diet containing vitamin D was reintroduced. Male adult offspring (n = 8 were compared to control male (n = 8. 2-D gel electrophoresis-based proteomics and mass spectroscopy were used to investigate differential protein expression. RESULTS: There were 35 spots, mapped to 33 unique proteins, which were significantly different between the two groups. Of these, 22 were down-regulated and 13 up-regulated. The fold changes were uniformly small, with the largest FC being -1.67. Within the significantly different spots, three calcium binding proteins (calbindin1, calbindin2 and hippocalcin were altered. Other proteins associated with DVD deficiency related to mitochondrial function, and the dynamin-like proteins. CONCLUSIONS: Developmental vitamin D deficiency was associated with subtle changes in protein expression in the nucleus accumbens. Disruptions in pathways related to calcium-binding proteins and mitochondrial function may underlie some of the behavioural features associated with animal models of developmental vitamin D deficiency.

  16. Preliminary Validation of a Parent-Child Relational Framework for Teaching Developmental Assessment to Pediatric Residents.

    Science.gov (United States)

    Regalado, Michael; Schneiderman, Janet U; Duan, Lei; Ragusa, Gisele

    A parent-child relational framework was used as a method to train pediatric residents in basic knowledge and observation skills for the assessment of child development. Components of the training framework and its preliminary validation as an alternative to milestone-based approaches are described. Pediatric residents were trained during a 4-week clinical rotation to use a semistructured interview and observe parent-child behavior during health visits using clinical criteria for historical information and observed behavior that reflect developmental change in the parent-child relationship. Clinical impressions of concern versus no concern for developmental delay were derived from parent-child relational criteria and the physical examination. A chart review yielded 330 preterm infants evaluated using this methodology at 4 and 15 months corrected age who also had standardized developmental testing at 6 and 18 months corrected age. Sensitivities and specificities were computed to examine the validity of the clinical assessment compared with standardized testing. A subset of residents who completed 50 or more assessments during the rotation was timed at the end of 4 weeks. Parent-child behavioral markers elicited from the history and/or observed during the health visit correlated highly with standardized developmental assessment. Sensitivities and specificities were 0.72/0.98 and 0.87/0.96 at 4 to 6 and 15 to 18 months, respectively. Residents completed their assessments parent-child relational framework is a potentially efficient and effective approach to training residents in the clinical knowledge and skills of child development assessment. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  17. Intracranial developmental venous anomaly: is it asymptomatic?

    Science.gov (United States)

    Puente, A Bolívar; de Asís Bravo Rodríguez, F; Bravo Rey, I; Romero, E Roldán

    2018-03-16

    Intracranial developmental venous anomalies are the most common vascular malformation. In the immense majority of cases, these anomalies are asymptomatic and discovered incidentally, and they are considered benign. Very exceptionally, however, they can cause neurological symptoms. In this article, we present three cases of patients with developmental venous anomalies that presented with different symptoms owing to complications derived from altered venous drainage. These anomalies were located in the left insula, right temporal lobe, and cerebellum. The exceptionality of the cases presented as well as of the images associated, which show the mechanism through which the symptoms developed, lies in the low incidence of symptomatic developmental venous anomalies reported in the literature. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Developmental evolution: this side of paradise.

    Science.gov (United States)

    Graham, A; McGonnell, I

    1999-09-09

    It has long been appreciated that the evolution of snakes involved the loss of limbs and axis elongation, but their developmental basis has been obscure. It has now been shown that alterations in the deployment of Hox genes and an early block in the formation of hindlimb primordia underpin these modifications.

  19. [Comparison of attachment-related social behaviors in autistic disorder and developmental disability].

    Science.gov (United States)

    Akdemir, Devrim; Pehlivantürk, Berna; Unal, Fatih; Ozusta, Seniz

    2009-01-01

    This study examined social behaviors related to attachment in children with autistic disorder and the differences in these behaviors from those observed in developmentally disabled children. Additionally, we aimed to investigate the relationship between attachment behaviors and clinical variables, such as age, cognitive development, severity of autism, language development, and mothers' attachment styles. The study group consisted of 19 children with autistic disorder (mean age: 37.9 +/- 6.8 months) and the control group consisted of 18 developmentally disabled children without autistic disorder that were matched with respect to age, gender, and cognitive development. The Childhood Autism Rating Scale (CARS) was administered to all the children by two child psychiatrists. Mothers completed the Relationships Scale Questionnaire (RSQ). Cognitive development of the children was assessed with the Stanford-Binet intelligence scale. Attachment behaviors of the children were evaluated with a modified Strange Situation Procedure (SSP). Attachment behaviors in the children with autistic disorder and in the children with developmental disabilities were similar. In contrast to the developmentally disabled group, the children with autistic disorder stayed closer toward their mothers compared with their responses to strangers. In the autistic disorder group, attachment behaviors were not associated with age, intelligence quotient, or mothers' attachment styles; however, a significant relationship between the severity of autism and the presence of speech was observed. Parents' understanding of the attachment needs and the attachment behaviors of their autistic children in the early stages of the disorder may lead to more secure attachment relationships and improved social development.

  20. Developmental plasticity: re-conceiving the genotype.

    Science.gov (United States)

    Sultan, Sonia E

    2017-10-06

    In recent decades, the phenotype of an organism (i.e. its traits and behaviour) has been studied as the outcome of a developmental 'programme' coded in its genotype. This deterministic view is implicit in the Modern Synthesis approach to adaptive evolution as a sorting process among genetic variants. Studies of developmental pathways have revealed that genotypes are in fact differently expressed depending on environmental conditions. Accordingly, the genotype can be understood as a repertoire of potential developmental outcomes or norm of reaction. Reconceiving the genotype as an environmental response repertoire rather than a fixed developmental programme leads to three critical evolutionary insights. First, plastic responses to specific conditions often comprise functionally appropriate trait adjustments, resulting in an individual-level, developmental mode of adaptive variation. Second, because genotypes are differently expressed depending on the environment, the genetic diversity available to natural selection is itself environmentally contingent. Finally, environmental influences on development can extend across multiple generations via cytoplasmic and epigenetic factors transmitted to progeny individuals, altering their responses to their own, immediate environmental conditions and, in some cases, leading to inherited but non-genetic adaptations. Together, these insights suggest a more nuanced understanding of the genotype and its evolutionary role, as well as a shift in research focus to investigating the complex developmental interactions among genotypes, environments and previous environments.

  1. Saccadic Alterations in Severe Developmental Dyslexia

    Directory of Open Access Journals (Sweden)

    Stefano Pensiero

    2013-01-01

    Full Text Available It is not sure if persons with dyslexia have ocular motor deficits in addition to their deficits in rapid visual information processing. A 15-year-old boy afflicted by severe dyslexia was submitted to saccadic eye movement recording. Neurological and ophthalmic examinations were normal apart from the presence of an esophoria for near and slightly longer latencies of pattern visual evoked potentials. Subclinical saccadic alterations were present, which could be at the basis of the reading pathology: (1 low velocities (and larger durations of the adducting saccades of the left eye with undershooting and long-lasting postsaccadic onward drift, typical of the internuclear ophthalmoplegia; (2 saccades interrupted in mid-flight and fixation instability, which are present in cases of brainstem premotor disturbances.

  2. Toward an understanding of late life suicidal behavior: the role of lifespan developmental theory.

    Science.gov (United States)

    Fiske, Amy; O'Riley, Alisa A

    2016-01-01

    Suicidal behavior in late life differs in important ways from suicidal behavior that occurs earlier in the lifespan, suggesting the possibility of developmental differences in the etiology of suicidal behavior. This paper examines late life suicidal behavior within the context of lifespan developmental theory. This paper presents a conceptual framework for using lifespan developmental theory to better understand late life suicidal behavior. We argue that the motivational theory of lifespan development, which focuses on control, is particularly relevant to late life suicide. This theory posits that opportunities to exert control over important aspects of one's life diminish in late life as a result of declines in physical functioning and other factors, and that successful aging is associated with adaptive regulation of this developmental change. Although continued striving to meet goals is normative throughout the lifespan, most individuals also increase the use of compensatory strategies in old age or when faced with a decline in functioning. We propose that individuals who do not adapt to developmental changes by altering their strategies for exerting control will be at risk for suicidal behavior in late life. This paper reviews evidence that supports the importance of control with respect to suicidal outcomes in older adults, as well as findings regarding specific types of control strategies that may be related to suicide risk in older adults with health-related limitations. Although suicidal behavior is not a normal part of aging, the application of lifespan developmental theory may be useful in understanding and potentially preventing suicide among older adults.

  3. Cultural Mediation. The Usefulness of Selected Concepts of Developmental Psychology for Coaching and Mentoring Relations

    Directory of Open Access Journals (Sweden)

    Barbara Smorczewska

    2013-09-01

    Full Text Available Some developmental psychological concepts, such as L. S. Vygotsky’s zone of proximal development or H. R. Schaffer’s joint involvement episodes, gave a new perspective in perceiving the process of teaching and development, by providing very detailed characteristics of the situation of acquiring competence in social relations. The mentioned concepts are based on a belief in the developmental potential of humans, and they perceive teaching as future-oriented. These assumptions are also characteristic for coaching and mentoring which are nowadays becoming more and more popular forms of development in work places; hence an attempt to find some analogy between them. The prepared comparison contributes to extending the theoretical bases of “development cooperation relations,” as coaching and mentoring are jointly referred to.

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

    Science.gov (United States)

    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.

  5. Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse

    Directory of Open Access Journals (Sweden)

    Umezawa Masakazu

    2009-07-01

    Full Text Available Abstract Background Nanotechnology is developing rapidly throughout the world and the production of novel man-made nanoparticles is increasing, it is therefore of concern that nanomaterials have the potential to affect human health. The purpose of this study was to investigate the effects of maternal exposure to nano-sized anatase titanium dioxide (TiO2 on gene expression in the brain during the developmental period using cDNA microarray analysis combined with Gene Ontology (GO and Medical Subject Headings (MeSH terms information. Results Analysis of gene expression using GO terms indicated that expression levels of genes associated with apoptosis were altered in the brain of newborn pups, and those associated with brain development were altered in early age. The genes associated with response to oxidative stress were changed in the brains of 2 and 3 weeks old mice. Changes of the expression of genes associated with neurotransmitters and psychiatric diseases were found using MeSH terms. Conclusion Maternal exposure of mice to TiO2 nanoparticles may affect the expression of genes related to the development and function of the central nervous system.

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

    Science.gov (United States)

    Fenning, Rachel M.; Baker, Jason K.

    2014-01-01

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

  7. The Adolescent and Young Adult with Cancer: A Developmental Life Course Perspective.

    Science.gov (United States)

    Docherty, Sharron L; Kayle, Mariam; Maslow, Gary R; Santacroce, Sheila Judge

    2015-08-01

    Using a Life Course Health Development framework, this article summarizes what is known about the impact of cancer and its treatment on the biopsychosocial world of the adolescent and young adult. Published peer reviewed literature, web-based resources, and cancer-related professional organizations' resources. Adolescents and young adults with cancer, between 15 and 29 years of age, have emerged as a distinct group requiring specialized care. The demands of cancer and its treatment are often directly counter to the developmental needs of this age group and often alter those life course experiences that contribute to resilience, thriving, and flourishing. Providing high-quality care to this age group requires a depth of understanding of the complexity of factors that merge to influence the developmental life course. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Developmental programming: the role of growth hormone.

    Science.gov (United States)

    Oberbauer, Anita M

    2015-01-01

    Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and, more recently, is implicated in the expression of altered phenotypes of future generations. Some phenotypes, such as fertility, bone strength, and adiposity are highly relevant to food animal production and in utero factors that impinge on those traits are vital to understand. A key systemic regulatory hormone is growth hormone (GH), which has a developmental role in virtually all tissues and organs. This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.

  9. Serotonin-related pathways and developmental plasticity: relevance for psychiatric disorders

    Science.gov (United States)

    Dayer, Alexandre

    2014-01-01

    Risk for adult psychiatric disorders is partially determined by early-life alterations occurring during neural circuit formation and maturation. In this perspective, recent data show that the serotonin system regulates key cellular processes involved in the construction of cortical circuits. Translational data for rodents indicate that early-life serotonin dysregulation leads to a wide range of behavioral alterations, ranging from stress-related phenotypes to social deficits. Studies in humans have revealed that serotonin-related genetic variants interact with early-life stress to regulate stress-induced cortisol responsiveness and activate the neural circuits involved in mood and anxiety disorders. Emerging data demonstrate that early-life adversity induces epigenetic modifications in serotonin-related genes. Finally, recent findings reveal that selective serotonin reuptake inhibitors can reinstate juvenile-like forms of neural plasticity, thus allowing the erasure of long-lasting fear memories. These approaches are providing new insights on the biological mechanisms and clinical application of antidepressants. PMID:24733969

  10. The expression of petunia strigolactone pathway genes is altered as part of the endogenous developmental program

    Directory of Open Access Journals (Sweden)

    Revel S M Drummond

    2012-01-01

    Full Text Available Analysis of mutants with increased branching has revealed the strigolactone synthesis/perception pathway which regulates branching in plants. However, whether variation in this well conserved developmental signalling system contributes to the unique plant architectures of different species is yet to be determined. We examined petunia orthologues of the Arabidopsis MAX1 and MAX2 genes to characterise their role in petunia architecture. A single orthologue of MAX1, PhMAX1 which encodes a cytochrome P450, was identified and was able to complement the max1 mutant of Arabidopsis. Petunia has two copies of the MAX2 gene, PhMAX2A and PhMAX2B which encode F-Box proteins. Differences in the transcript levels of these two MAX2-like genes suggest diverging functions. Unlike PhMAX2B, PhMAX2A mRNA levels increase as leaves age. Nonetheless, this gene functionally complements the Arabidopsis max2 mutant indicating that the biochemical activity of the PhMAX2A protein is not significantly different from MAX2. The expression of the petunia strigolactone pathway genes (PhCCD7, PhCCD8, PhMAX1, PhMAX2A, and PhMAX2B was then further investigated throughout the development of wild-type petunia plants. Three of these genes showed changes in mRNA levels over the development series. Alterations to the expression of these genes over time, or in different regions of the plant, may influence the branching growth habit of the plant. Alterations to strigolactone production and/or sensitivity could allow both subtle and dramatic changes to branching within and between species.

  11. Maternal and pregnancy-related factors associated with developmental delay in moderately preterm-born children

    NARCIS (Netherlands)

    Kerstjens, Jorien M; de Winter, Andrea F; Sollie, Krystyna M; Bocca-Tjeertes, Inger F; Potijk, Marieke R; Reijneveld, Sijmen A; Bos, Arend F

    OBJECTIVE: To estimate the association between preexisting maternal and pregnancy-related factors and developmental delay in early childhood in moderately preterm-born children. METHODS: We measured development with the Ages and Stages Questionnaire at age 43-49 months in 834 moderately preterm-born

  12. Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations

    Directory of Open Access Journals (Sweden)

    Elena eCid

    2014-04-01

    Full Text Available Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e. the multiple-hit hypothesis. However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1; including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders.

  13. Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

    Directory of Open Access Journals (Sweden)

    Schlegel Karl A

    2010-10-01

    Full Text Available Abstract Background Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL; however, osteonecrosis of the jaw (ONJ is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP-related and denosumab (anti-RANKL antibody-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL in ONJ-altered and healthy periodontal tissue. Methods Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment. Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Results Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p Conclusions These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to

  14. Developmental Programming, a Pathway to Disease

    Science.gov (United States)

    Cardoso, Rodolfo C.; Puttabyatappa, Muraly

    2016-01-01

    Accumulating evidence suggests that insults occurring during the perinatal period alter the developmental trajectory of the fetus/offspring leading to long-term detrimental outcomes that often culminate in adult pathologies. These perinatal insults include maternal/fetal disease states, nutritional deficits/excess, stress, lifestyle choices, exposure to environmental chemicals, and medical interventions. In addition to reviewing the various insults that contribute to developmental programming and the benefits of animal models in addressing underlying mechanisms, this review focuses on the commonalities in disease outcomes stemming from various insults, the convergence of mechanistic pathways via which various insults can lead to common outcomes, and identifies the knowledge gaps in the field and future directions. PMID:26859334

  15. An Examination of the Relative Age Effect in Developmental Girls' Hockey in Ontario

    Science.gov (United States)

    Smith, Kristy L.; Weir, Patricia L.

    2013-01-01

    The relative age effect (RAE) suggests that athletes may be provided with greater opportunities for success depending on the position of their birthdate in a sport's selection year. While the effect has been well established in men's sports, less is known about women's sports. This study examined the RAE in developmental girls' hockey in Ontario.…

  16. Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment ☆

    OpenAIRE

    Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

    2013-01-01

    Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-...

  17. Dual Systems Competence [Image Omitted] Procedural Processing: A Relational Developmental Systems Approach to Reasoning

    Science.gov (United States)

    Ricco, Robert B.; Overton, Willis F.

    2011-01-01

    Many current psychological models of reasoning minimize the role of deductive processes in human thought. In the present paper, we argue that deduction is an important part of ordinary cognition and we propose that a dual systems Competence [image omitted] Procedural processing model conceptualized within relational developmental systems theory…

  18. The Relative Risk of Divorce in Parents of Children With Developmental Disabilities: Impacts of Lifelong Parenting.

    Science.gov (United States)

    Namkung, Eun Ha; Song, Jieun; Greenberg, Jan S; Mailick, Marsha R; Floyd, Frank J

    2015-11-01

    We prospectively examined the risk of divorce in 190 parents of children with developmental disabilities compared to 7,251 parents of children without disabilities based on a random sample drawn from the community and followed longitudinally for over 50 years. A significant interaction between the parental group status and number of children was found: In the comparison group, having a larger number of children was related to an increased risk of divorce, whereas the number of children did not increase divorce risk among parents of children with developmental disabilities.

  19. The Relative Risk of Divorce in Parents of Children with Developmental Disabilities: Impacts of Lifelong Parenting

    Science.gov (United States)

    Song, Jieun; Greenberg, Jan S.; Mailick, Marsha R.; Floyd, Frank J.

    2015-01-01

    We examined prospectively the risk of divorce in 190 parents of children with developmental disabilities compared to 7,251 parents of children without disabilities based on a random sample drawn from the community and followed longitudinally for over 50 years. A significant interaction between the parental group status and number of children was found: In the comparison group, having a larger number of children was related to an increased risk of divorce, whereas the number of children did not increase divorce risk among parents of children with developmental disabilities. PMID:26505872

  20. ICan: an integrated co-alteration network to identify ovarian cancer-related genes.

    Science.gov (United States)

    Zhou, Yuanshuai; Liu, Yongjing; Li, Kening; Zhang, Rui; Qiu, Fujun; Zhao, Ning; Xu, Yan

    2015-01-01

    Over the last decade, an increasing number of integrative studies on cancer-related genes have been published. Integrative analyses aim to overcome the limitation of a single data type, and provide a more complete view of carcinogenesis. The vast majority of these studies used sample-matched data of gene expression and copy number to investigate the impact of copy number alteration on gene expression, and to predict and prioritize candidate oncogenes and tumor suppressor genes. However, correlations between genes were neglected in these studies. Our work aimed to evaluate the co-alteration of copy number, methylation and expression, allowing us to identify cancer-related genes and essential functional modules in cancer. We built the Integrated Co-alteration network (ICan) based on multi-omics data, and analyzed the network to uncover cancer-related genes. After comparison with random networks, we identified 155 ovarian cancer-related genes, including well-known (TP53, BRCA1, RB1 and PTEN) and also novel cancer-related genes, such as PDPN and EphA2. We compared the results with a conventional method: CNAmet, and obtained a significantly better area under the curve value (ICan: 0.8179, CNAmet: 0.5183). In this paper, we describe a framework to find cancer-related genes based on an Integrated Co-alteration network. Our results proved that ICan could precisely identify candidate cancer genes and provide increased mechanistic understanding of carcinogenesis. This work suggested a new research direction for biological network analyses involving multi-omics data.

  1. Developmental changes in visuo-spatial working memory in normally developing children: event-related potentials study.

    Science.gov (United States)

    Myatchin, Ivan; Lagae, Lieven

    2013-10-01

    Working memory (WM) is very important for normal development. The fronto-parietal neuronal network supporting WM has already been well-studied. Less is known about the cortical activity changes during development of WM. We evaluated the maturation of visual WM network at the electrophysiological level in a group of normally developing children. Multichannel (n=31) event-related potentials (ERP) were measured during a visuo-spatial backmatching task in 69 childrens (6-16 years old). One-backmatching (BM1) and two-backmatching (BM2) tasks were performed. Age-related changes in behavioral parameters (commission and omission errors and reaction times) and ERP parameters (peak amplitudes and latencies) were analyzed between different ages. Clear improvement in performance from young childhood toward adolescence was seen at the behavioral level: decrease of errors and fastening of reaction times. At the electrophysiological level age-related changes were seen in peak latencies and especially in amplitudes. Different peaks have different dynamics in amplitudes and latencies: early peak amplitude decreased and latency shortened with age, which was not always seen in late peaks. This reflects developmental changes in intensity and speed of WM processing. Later peaks were more clearly seen over the right hemisphere in older children, illustrating hemispheric lateralization in visuo-spatial working memory. Our results indicate that not only at the behavioral but also at the electrophysiological level clear age-related dynamics in WM processing can be seen. Furthermore, with ERP we showed that different WM components follow different developmental trajectories. Our work demonstrates that age-related dynamics in intensity and speed of information processing during WM task is reflected in developmental changes in different ERP components. It also states that fronto-parietal visual WM network can be functional even before all its nodes are fully mature. Copyright © 2012 The

  2. Developmental toxicity of engineered nanomaterials in rodents

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-05-15

    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 mortalities 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

  3. Life Span Developmental Approach

    Directory of Open Access Journals (Sweden)

    Ali Eryilmaz

    2011-03-01

    Full Text Available The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of individuals with respect to developmental stages. This developmental approach suggests that scientific disciplines should not explain developmental facts only with age changes. Along with aging, cognitive, biological, and socioemotional development throughout life should also be considered to provide a reasonable and acceptable context, guideposts, and reasonable expectations for the person. There are three important subjects whom life span developmental approach deals with. These are nature vs nurture, continuity vs discontinuity, and change vs stability. Researchers using life span developmental approach gather and produce knowledge on these three most important domains of individual development with their unique scientific methodology.

  4. Developmental trends in adaptive memory.

    Science.gov (United States)

    Otgaar, Henry; Howe, Mark L; Smeets, Tom; Garner, Sarah R

    2014-01-01

    Recent studies have revealed that memory is enhanced when information is processed for fitness-related purposes. The main objective of the current experiments was to test developmental trends in the evolutionary foundation of memory using different types of stimuli and paradigms. In Experiment 1, 11-year-olds and adults were presented with neutral, negative, and survival-related DRM word lists. We found a memory benefit for the survival-related words and showed that false memories were more likely to be elicited for the survival-related word lists than for the other lists. Experiment 2 examined developmental trends in the survival processing paradigm using neutral, negative, and survival-related pictures. A survival processing advantage was found for survival-related pictures in adults, for negative pictures in 11/12-year-olds, and for neutral pictures in 7/8-year-olds. In Experiment 3, 11/12-year-olds and adults had to imagine the standard survival scenario or an adapted survival condition (or pleasantness condition) that was designed to reduce the possibilities for elaborative processing. We found superior memory retention for both survival scenarios in children and adults. Collectively, our results evidently show that the survival processing advantage is developmentally invariant and that certain proximate mechanisms (elaboration and distinctiveness) underlie these developmental trends.

  5. Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis.

    Science.gov (United States)

    Yoshida, Takeichi; Kato, Jun; Maekita, Takao; Yamashita, Satoshi; Enomoto, Shotaro; Ando, Takayuki; Niwa, Tohru; Deguchi, Hisanobu; Ueda, Kazuki; Inoue, Izumi; Iguchi, Mikitaka; Tamai, Hideyuki; Ushijima, Toshikazu; Ichinose, Masao

    2013-10-01

    Chronic inflammation triggered by Helicobacter pylori causes altered DNA methylation in stomach mucosae, which is deeply involved in gastric carcinogenesis. This study aimed to elucidate the correlation between altered mucosal DNA methylation levels and activity of H. pylori-related gastritis, because inflammatory activity shows particular correlations with the development of diffuse-type cancer. Methylation levels in stomach mucosae of 78 healthy volunteers were determined by real-time methylation-specific PCR or bisulfite pyrosequencing. Examined loci were the promoter CpG islands of six genes (FLNc, HAND1, THBD, p41ARC, HRASLS, and LOX) and the CpG sites of non-coding repetitive elements (Alu and Satα) that are reportedly altered by H. pylori infection. Activity of H. pylori-related gastritis was evaluated using two serum markers: H. pylori antibody titer and pepsinogen II. Methylation levels of the six CpG islands were consistently increased, and those of the two repetitive elements were consistently decreased in a stepwise manner with the activity of gastric inflammation as represented by serum marker levels. Each serum marker level was well correlated with the overall DNA methylation status of stomach mucosa, and these two serologic markers were additive in the detection of the mucosa with severely altered DNA methylation. Alteration in mucosal DNA methylation level was closely correlated with activity of H. pylori-related gastritis as evaluated by serum markers. The observed correlation between altered DNA methylation levels and activity of H. pylori-related gastritis appears to be one of the relevant molecular mechanisms underlying the development of diffuse-type cancer.

  6. Molecular marker differences relate to developmental position and subsets of mesodiencephalic dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    Simone M Smits

    Full Text Available The development of mesodiencephalic dopaminergic (mdDA neurons located in the substantia nigra compacta (SNc and ventral tegmental area (VTA follow a number of stages marked by distinct events. After preparation of the region by signals that provide induction and patterning, several transcription factors have been identified, which are involved in specifying the neuronal fate of these cells. The specific vulnerability of SNc neurons is thought to root in these specific developmental programs. The present study examines the positions of young postmitotic mdDA neurons to relate developmental position to mdDA subset specific markers. MdDA neurons were mapped relative to the neuromeric domains (prosomeres 1-3 (P1-3, midbrain, and hindbrain as well as the longitudinal subdivisions (floor plate, basal plate, alar plate, as proposed by the prosomeric model. We found that postmitotic mdDA neurons are located mainly in the floorplate domain and very few in slightly more lateral domains. Moreover, mdDA neurons are present along a large proportion of the anterior/posterior axis extending from the midbrain to P3 in the diencephalon. The specific positions relate to some extent to the presence of specific subset markers as Ahd2. In the adult stage more of such subsets specific expressed genes are present and may represent a molecular map defining molecularly distinct groups of mdDA neurons.

  7. Developmental Exposure to Valproate or Ethanol Alters Locomotor Activity and Retino-Tectal Projection Area in Zebrafish Embryos

    Science.gov (United States)

    Given the minimal developmental neurotoxicity data available for the large number of new and existing chemicals, there is a critical need for alternative methods to identify and prioritize chemicals for further testing. We outline a developmental neurotoxicity screening approach ...

  8. The relation between working memory components and ADHD symptoms from a developmental perspective.

    Science.gov (United States)

    Tillman, Carin; Eninger, Lilianne; Forssman, Linda; Bohlin, Gunilla

    2011-01-01

    The objective was to examine the relations between attention deficit hyperactivity disorder (ADHD) symptoms and four working memory (WM) components (short-term memory and central executive in verbal and visuospatial domains) in 284 6-16-year-old children from the general population. The results showed that verbal and visuospatial short-term memory and verbal central executive uniquely contributed to inattention symptoms. Age interacted with verbal short-term memory in predicting inattention, with the relation being stronger in older children. These findings support the notion of ADHD as a developmental disorder, with changes in associated neuropsychological deficits across time. The results further indicate ADHD-related deficits in several specific WM components.

  9. Developmental programming: gestational bisphenol-A treatment alters trajectory of fetal ovarian gene expression.

    Science.gov (United States)

    Veiga-Lopez, Almudena; Luense, Lacey J; Christenson, Lane K; Padmanabhan, Vasantha

    2013-05-01

    Bisphenol-A (BPA), a ubiquitous environmental endocrine disrupting chemical, is a component of polycarbonate plastic and epoxy resins. Because of its estrogenic properties, there is increasing concern relative to risks from exposures during critical periods of early organ differentiation. Prenatal BPA treatment in sheep results in low birth weight, hypergonadotropism, and ovarian cycle disruptions. This study tested the hypothesis that gestational exposure to bisphenol A, at an environmentally relevant dose, induces early perturbations in the ovarian transcriptome (mRNA and microRNA). Pregnant Suffolk ewes were treated with bisphenol A (0.5 mg/kg, sc, daily, produced ∼2.6 ng/mL of unconjugated BPA in umbilical arterial samples of BPA treated fetuses approaching median levels of BPA measured in maternal circulation) from days 30 to 90 of gestation. Expression of steroidogenic enzymes, steroid/gonadotropin receptors, key ovarian regulators, and microRNA biogenesis components were measured by RT-PCR using RNA derived from fetal ovaries collected on gestational days 65 and 90. An age-dependent effect was evident in most steroidogenic enzymes, steroid receptors, and key ovarian regulators. Prenatal BPA increased Cyp19 and 5α-reductase expression in day 65, but not day 90, ovaries. Fetal ovarian microRNA expression was altered by prenatal BPA with 45 down-regulated (>1.5-fold) at day 65 and 11 down-regulated at day 90 of gestation. These included microRNAs targeting Sry-related high-mobility-group box (SOX) family genes, kit ligand, and insulin-related genes. The results of this study demonstrate that exposure to BPA at an environmentally relevant dose alters fetal ovarian steroidogenic gene and microRNA expression of relevance to gonadal differentiation, folliculogenesis, and insulin homeostasis.

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

    Science.gov (United States)

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

    2016-01-01

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

  11. Epigenetics and the Developmental Origins of Health and ...

    Science.gov (United States)

    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. Developmental exposure to chlorpyrifos alters reactivity to environmental and social cues in adolescent mice

    International Nuclear Information System (INIS)

    Ricceri, Laura; Markina, Nadja; Valanzano, Angela; Fortuna, Stefano; Cometa, Maria Francesca; Meneguz, Annarita; Calamandrei, Gemma

    2003-01-01

    Neonatal mice were treated daily on postnatal days (pnds) 1 through 4 or 11 through 14 with the organophosphate pesticide chlorpyrifos (CPF), at doses (1 or 3 mg/kg) that do not evoke systemic toxicity. Brain acetylcholinesterase (AChE) activity was evaluated within 24 h from termination of treatments. Pups treated on pnds 1-4 underwent ultrasonic vocalization tests (pnds 5, 8, and 11) and a homing test (orientation to home nest material, pnd 10). Pups in both treatment schedules were then assessed for locomotor activity (pnd 25), novelty-seeking response (pnd 35), social interactions with an unfamiliar conspecific (pnd 45), and passive avoidance learning (pnd 60). AChE activity was reduced by 25% after CPF 1-4 but not after CPF 11-14 treatment. CPF selectively affected only the G 4 (tetramer) molecular isoform of AChE. Behavioral analysis showed that early CPF treatment failed to affect neonatal behaviors. Locomotor activity on pnd 25 was increased in 11-14 CPF-treated mice at both doses, and CPF-treated animals in both treatment schedules were more active when exposed to environmental novelty in the novelty-seeking test. All CPF-treated mice displayed more agonistic responses, and such effect was more marked in male mice exposed to the low CPF dose on pnds 11-14. Passive avoidance learning was not affected by CPF. These data indicate that developmental exposure to CPF induces long-term behavioral alterations in the mouse species and support the involvement of neural systems in addition to the cholinergic system in the delayed behavioral toxicity of CPF

  13. Topographic processing in developmental prosopagnosia

    DEFF Research Database (Denmark)

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

    2016-01-01

    deficit in visual processing or visual short-term memory. Interestingly, a classical dissociation could be demonstrated between impaired face memory and preserved topographic memory in two developmental prosopagnosics. We conclude that impairments in topographic memory tend to co-occur with developmental......Anecdotal evidence suggests a relation between impaired spatial (navigational) processing and developmental prosopagnosia. To address this formally, we tested two aspects of topographic processing – that is, perception and memory of mountain landscapes shown from different viewpoints. Participants...

  14. Entrepreneurship in Adolescence: A Relational Developmental Systems Approach

    Science.gov (United States)

    Lerner, Richard M.; Damon, William

    2012-01-01

    Will significant numbers of today's youth become able to succeed in careers that require entrepreneurial capacities? Who among today's youth will have the talent, skills, knowledge, and drive needed to become successful entrepreneurs? To answer these questions, it will be necessary to understand the developmental bases of individual and ecological…

  15. Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally.

    Science.gov (United States)

    Barrett, Catherine E; Hennessey, Thomas M; Gordon, Katelyn M; Ryan, Steve J; McNair, Morgan L; Ressler, Kerry J; Rainnie, Donald G

    2017-01-01

    The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes.

  16. A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes.

    Science.gov (United States)

    Sagvolden, Terje; Johansen, Espen Borgå; Aase, Heidi; Russell, Vivienne Ann

    2005-06-01

    Attention-deficit/hyperactivity disorder (ADHD) is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Inattentiveness, overactivity, and impulsiveness are presently regarded as the main clinical symptoms. The dynamic developmental behavioral theory is based on the hypothesis that altered dopaminergic function plays a pivotal role by failing to modulate nondopaminergic (primarily glutamate and GABA) signal transmission appropriately. A hypofunctioning mesolimbic dopamine branch produces altered reinforcement of behavior and deficient extinction of previously reinforced behavior. This gives rise to delay aversion, development of hyperactivity in novel situations, impulsiveness, deficient sustained attention, increased behavioral variability, and failure to "inhibit" responses ("disinhibition"). A hypofunctioning mesocortical dopamine branch will cause attention response deficiencies (deficient orienting responses, impaired saccadic eye movements, and poorer attention responses toward a target) and poor behavioral planning (poor executive functions). A hypofunctioning nigrostriatal dopamine branch will cause impaired modulation of motor functions and deficient nondeclarative habit learning and memory. These impairments will give rise to apparent developmental delay, clumsiness, neurological "soft signs," and a "failure to inhibit" responses when quick reactions are required. Hypofunctioning dopamine branches represent the main individual predispositions in the present theory. The theory predicts that behavior and symptoms in ADHD result from the interplay between individual predispositions and the surroundings. The exact ADHD symptoms at a particular time in life will vary and be influenced by factors having positive or negative effects on symptom development. Altered or deficient learning and motor functions will produce special needs for optimal parenting and societal styles. Medication will to some degree

  17. Is Season of Birth Related to Developmental Dyslexia?

    Science.gov (United States)

    Donfrancesco, Renato; Iozzino, Roberto; Caruso, Barbara; Ferrante, Laura; Mugnaini, Daniele; Talamo, Alessandra; Miano, Silvia; Dimitri, Andrea; Masi, Gabriele

    2010-01-01

    Different moderators/mediators of risk are involved in developmental dyslexia (DD), but data are inconsistent. We explored the prevalence of season of birth and its association with gender and age of school entry in an Italian sample of dyslexic children compared to an Italian normal control group. The clinical sample included 498 children (345…

  18. Developmental Pathways Are Blueprints for Designing Successful Crops

    Directory of Open Access Journals (Sweden)

    Ben Trevaskis

    2018-06-01

    Full Text Available Genes controlling plant development have been studied in multiple plant systems. This has provided deep insights into conserved genetic pathways controlling core developmental processes including meristem identity, phase transitions, determinacy, stem elongation, and branching. These pathways control plant growth patterns and are fundamentally important to crop biology and agriculture. This review describes the conserved pathways that control plant development, using Arabidopsis as a model. Historical examples of how plant development has been altered through selection to improve crop performance are then presented. These examples, drawn from diverse crops, show how the genetic pathways controlling development have been modified to increase yield or tailor growth patterns to suit local growing environments or specialized crop management practices. Strategies to apply current progress in genomics and developmental biology to future crop improvement are then discussed within the broader context of emerging trends in plant breeding. The ways that knowledge of developmental processes and understanding of gene function can contribute to crop improvement, beyond what can be achieved by selection alone, are emphasized. These include using genome re-sequencing, mutagenesis, and gene editing to identify or generate novel variation in developmental genes. The expanding scope for comparative genomics, the possibility to engineer new developmental traits and new approaches to resolve gene–gene or gene–environment interactions are also discussed. Finally, opportunities to integrate fundamental research and crop breeding are highlighted.

  19. Developmental Systems Theory and the Person-Oriented Approach. Commentary on: "An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics"

    Science.gov (United States)

    Bergman, Lars R.

    2015-01-01

    Molenaar's (2015) article concerns Developmental Systems Theory (DST) in relation to behavior genetics and he presents implications of DST for empirical research, especially the need for subject-specific studies. In this commentary, the article is discussed from a broader developmental science perspective, particularly regarded through the lens of…

  20. Author's Response to Commentaries on: "An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics"

    Science.gov (United States)

    Molenaar, Peter C. M.

    2015-01-01

    In this article, Peter Molenaar responds to three commentaries (this issue) on his article, "An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics." He addresses aspects of relational developmental systems (RDS) mentioned and questions raised in each of the…

  1. Cognitive precursors of the developmental relation between lexical quality and reading comprehension in the intermediate elementary grades

    NARCIS (Netherlands)

    Swart, N.M.; Muijselaar, M.M.L.; Steenbeek-Planting, E.G.; Droop, W.; Jong, P.F. de; Verhoeven, L.T.W.

    2017-01-01

    In a longitudinal study, we investigated how cognitive precursors (short-term memory, working memory, and nonverbal reasoning) influence the developmental relation between lexical quality (decoding and vocabulary) and reading comprehension skill in 282 Dutch students in the intermediate elementary

  2. Cognitive precursors of the developmental relation between lexical quality and reading comprehension in the intermediate elementary grades.

    NARCIS (Netherlands)

    Swart, N.M.; Muijselaar, M.M.L.; Steenbeek-Planting, E.G.; Droop, M.; de Jong, P.F.; Verhoeven, L.

    2017-01-01

    In a longitudinal study, we investigated how cognitive precursors (short-term memory, working memory, and nonverbal reasoning) influence the developmental relation between lexical quality (decoding and vocabulary) and reading comprehension skill in 282 Dutch students in the intermediate elementary

  3. Not all developmental assets are related to positive health outcomes in college students

    Directory of Open Access Journals (Sweden)

    Teoli Daniel A

    2011-07-01

    Full Text Available Abstract Background The purpose of this investigation was to model the relationships between developmental assets, life satisfaction, and health-related quality of life (HRQOL among a stratified, random sample (n = 765, 56% response rate of college students. Methods Structural equation modeling techniques were employed to test the relationships using Mplus v4.21; Model evaluations were based on 1 theoretical salience, 2 global fit indices (chi-square goodness of fit, comparative fit index: CFI and Tucker-Lewis Index: TLI, 3 microfit indices (parameter estimates, root mean squared error of approximation: RMSEA and residuals and 4 parsimony. Results The model fit the data well: χ2(n = 581, 515 = 1252.23, CFI = .94, TLI = .93 and RMSEA = .05. First, participants who reported increased Family Communication also reported higher levels of life satisfaction. Second, as participants reported having more Non-Parental Role Models, life satisfaction decreased and poor mental HRQOL days increased. Finally increased Future Aspirations was related to increased poor mental HRQOL days. Results were variant across gender. Conclusions Preliminary results suggest not all developmental assets are related to positive health outcomes among college students, particularly mental health outcomes. While the findings for Family Communication were expected, the findings for Non-Parental Role Models suggest interactions with potential role models in college settings may be naturally less supportive. Future Aspirations findings suggest college students may harbor a greater temporal urgency for the rigors of an increasingly competitive work world. In both cases, these assets appear associated with increased poor mental HRQOL days.

  4. Major Changes in Growth Rate and Growth Variability of Beech (Fagus sylvatica L.) Related to Soil Alteration and Climate Change in Belgium

    OpenAIRE

    Latte, Nicolas; Perin, Jérôme; Kint, Vincent; Lebourgeois, François; Claessens, Hugues

    2016-01-01

    Global change-particularly climate change, forest management, and atmospheric deposition-has significantly altered forest growing conditions in Europe. The influences of these changes on beech growth (Fagus sylvatica L.) were investigated for the past 80 years in Belgium, using non-linear mixed effects models on ring-width chronologies of 149 mature and dominant beech trees (87-186 years old). The effects of the developmental stage (i.e., increasing tree size) were filtered out in order to fo...

  5. Life Span Developmental Approach

    OpenAIRE

    Ali Eryilmaz

    2011-01-01

    The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of...

  6. Linking Social Change and Developmental Change: Shifting Pathways of Human Development

    Science.gov (United States)

    Greenfield, Patricia M.

    2009-01-01

    P. M. Greenfield's new theory of social change and human development aims to show how changing sociodemographic ecologies alter cultural values and learning environments and thereby shift developmental pathways. Worldwide sociodemographic trends include movement from rural residence, informal education at home, subsistence economy, and…

  7. Endogenous developmental endothelial locus-1 limits ischemia-related angiogenesis by blocking inflammation

    Science.gov (United States)

    Klotzsche - von Ameln, Anne; Cremer, Sebastian; Hoffmann, Jedrzej; Schuster, Peggy; Khedr, Sherif; Korovina, Irina; Troulinaki, Maria; Neuwirth, Ales; Sprott, David; Chatzigeorgiou, Antonios; Economopoulou, Matina; Orlandi, Alessia; Hain, Andreas; Zeiher, Andreas M.; Deussen, Andreas; Hajishengallis, George; Dimmeler, Stefanie; Chavakis, Triantafyllos; Chavakis, Emmanouil

    2017-01-01

    We have recently identified endothelial cell-secreted developmental endothelial locus-1 (Del-1) as an endogenous inhibitor of β2-integrin–dependent leukocyte infiltration. Del-1 was previously also implicated in angiogenesis. Here, we addressed the role of endogenously produced Del-1 in ischemia-related angiogenesis. Intriguingly, Del-1–deficient mice displayed increased neovascularization in two independent ischemic models (retinopathy of prematurity and hind-limb ischemia), as compared to Del-1–proficient mice. On the contrary, angiogenic sprouting in vitro or ex vivo (aortic ring assay) and physiological developmental retina angiogenesis were not affected by Del-1 deficiency. Mechanistically, the enhanced ischemic neovascularization in Del-1-deficiency was linked to higher infiltration of the ischemic tissue by CD45+ hematopoietic and immune cells. Moreover, Del-1-deficiency promoted β2-integrin–dependent adhesion of hematopoietic cells to endothelial cells in vitro, and the homing of hematopoietic progenitor cells and of immune cell populations to ischemic muscles in vivo. Consistently, the increased hind limb ischemia-related angiogenesis in Del-1 deficiency was completely reversed in mice lacking both Del-1 and the β2-integrin LFA-1. Additionally, enhanced retinopathy-associated neovascularization in Del-deficient mice was reversed by LFA-1 blockade. Our data reveal a hitherto unrecognized function of endogenous Del-1 as a local inhibitor of ischemia-induced angiogenesis by restraining LFA-1–dependent homing of pro-angiogenic hematopoietic cells to ischemic tissues. Our findings are relevant for the optimization of therapeutic approaches in the context of ischemic diseases. PMID:28447099

  8. Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Ru-Lan [Department of Physical Medicine and Rehabilitation, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (China); Chen, Wei-Jen; Huang, Shiau-Rung [School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan (China); Lin, Ying-Chin [Department of Family Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan (China); Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Lin, Ming-I; Mu, Shu-Chi [Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Chen, Ray-Jade [Department of Digestive Surgery, Taipei Medical University Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2017-04-15

    Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (As{sup III}), arsenate (As{sup V}), monomethylarsonic acid (MMA{sup V}), and dimethylarsinic acid (DMA{sup V}) were measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G + G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08–2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity. - Highlights: • AS3MT genotypes were found to affect susceptibility to developmental delay. • AS3MT rs3740392 A/G and G/G genotype had a significantly low SMI (DMA

  9. Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan

    International Nuclear Information System (INIS)

    Hsieh, Ru-Lan; Su, Chien-Tien; Shiue, Horng-Sheng; Chen, Wei-Jen; Huang, Shiau-Rung; Lin, Ying-Chin; Lin, Ming-I; Mu, Shu-Chi; Chen, Ray-Jade; Hsueh, Yu-Mei

    2017-01-01

    Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (As III ), arsenate (As V ), monomethylarsonic acid (MMA V ), and dimethylarsinic acid (DMA V ) were measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G + G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08–2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity. - Highlights: • AS3MT genotypes were found to affect susceptibility to developmental delay. • AS3MT rs3740392 A/G and G/G genotype had a significantly low SMI (DMA/MMA) index. • AS3MT

  10. Cellular basis of morphological variation and temperature-related plasticity in Drosophila melanogaster strains with divergent wing shapes.

    Science.gov (United States)

    Torquato, Libéria Souza; Mattos, Daniel; Matta, Bruna Palma; Bitner-Mathé, Blanche Christine

    2014-12-01

    Organ shape evolves through cross-generational changes in developmental patterns at cellular and/or tissue levels that ultimately alter tissue dimensions and final adult proportions. Here, we investigated the cellular basis of an artificially selected divergence in the outline shape of Drosophila melanogaster wings, by comparing flies with elongated or rounded wing shapes but with remarkably similar wing sizes. We also tested whether cellular plasticity in response to developmental temperature was altered by such selection. Results show that variation in cellular traits is associated with wing shape differences, and that cell number may play an important role in wing shape response to selection. Regarding the effects of developmental temperature, a size-related plastic response was observed, in that flies reared at 16 °C developed larger wings with larger and more numerous cells across all intervein regions relative to flies reared at 25 °C. Nevertheless, no conclusive indication of altered phenotypic plasticity was found between selection strains for any wing or cellular trait. We also described how cell area is distributed across different intervein regions. It follows that cell area tends to decrease along the anterior wing compartment and increase along the posterior one. Remarkably, such pattern was observed not only in the selected strains but also in the natural baseline population, suggesting that it might be canalized during development and was not altered by the intense program of artificial selection for divergent wing shapes.

  11. Desiccation stress induces developmental heterochrony in ...

    Indian Academy of Sciences (India)

    Stressful environments are known to perturb developmental patterns in insects. In the purview of desiccation as astressor, relatively little is known about the developmental consequences linked with desiccation tolerance. In thisstudy, we have particularly focused on the exploration of the temporal profile of postembryonic ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Christen, Verena [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132, Muttenz (Switzerland); Rusconi, Manuel; Crettaz, Pierre [Federal Office of Public Health, Division Chemical Products, 3003 Bern (Switzerland); Fent, Karl, E-mail: karl.fent@bluewin.ch [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132, Muttenz (Switzerland); Swiss Federal Institute of Technology Zürich (ETH Zürich), Department of Environmental Systems Sciences, Institute of Biogeochemistry and Pollution Dynamics, CH-8092 Zürich (Switzerland)

    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 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

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

    International Nuclear Information System (INIS)

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

    2017-01-01

    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 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

  14. Mild developmental foreign accent syndrome and psychiatric comorbidity: Altered white matter integrity in speech and emotion regulation networks

    Directory of Open Access Journals (Sweden)

    Marcelo L Berthier

    2016-08-01

    Full Text Available Foreign accent syndrome (FAS is a speech disorder that is defined by the emergence of a peculiar manner of articulation and intonation which is perceived as foreign. In most cases of acquired FAS (AFAS the new accent is secondary to small focal lesions involving components of the bilaterally distributed neural network for speech production. In the past few years FAS has also been described in different psychiatric conditions (conversion disorder, bipolar disorder, schizophrenia as well as in developmental disorders (specific language impairment, apraxia of speech. In the present study, two adult males, one with atypical phonetic production and the other one with cluttering, reported having developmental FAS (DFAS since their adolescence. Perceptual analysis by naïve judges could not confirm the presence of foreign accent, possibly due to the mildness of the speech disorder. However, detailed linguistic analysis provided evidence of prosodic and segmental errors previously reported in AFAS cases. Cognitive testing showed reduced communication in activities of daily living and mild deficits related to psychiatric disorders. Psychiatric evaluation revealed long-lasting internalizing disorders (neuroticism, anxiety, obsessive-compulsive disorder, social phobia, depression, alexithymia, hopelessness, and apathy in both subjects. Diffusion tensor imaging (DTI data from each subject with DFAS were compared with data from a group of 21 age- and gender-matched healthy control subjects. Diffusion parameters (MD, AD, and RD in predefined regions of interest showed changes of white matter microstructure in regions previously related with AFAS and psychiatric disorders. In conclusion, the present findings militate against the possibility that these two subjects have FAS of psychogenic origin. Rather, our findings provide evidence that mild DFAS occurring in the context of subtle, yet persistent, developmental speech disorders may be associated with

  15. Developmental simulation of the adult cranial morphology of Australopithecus sediba

    Directory of Open Access Journals (Sweden)

    Keely B. Carlson

    2016-07-01

    Full Text Available The type specimen of Australopithecus sediba (MH1 is a late juvenile, prompting some commentators to suggest that had it lived to adulthood its morphology would have changed sufficiently so as to render hypotheses regarding its phylogenetic relations suspect. Considering the potentially critical position of this species with regard to the origins of the genus Homo, a deeper understanding of this change is especially vital. As an empirical response to this critique, a developmental simulation of the MH1 cranium was carried out using geometric morphometric techniques to extrapolate adult morphology using extant male and female chimpanzees, gorillas and humans by modelling remaining development. Multivariate comparisons of the simulated adult A. sediba crania with other early hominin taxa indicate that subsequent cranial development primarily reflects development of secondary sexual characteristics and would not likely be substantial enough to alter suggested morphological affinities of A. sediba. This study also illustrates the importance of separating developmental vectors by sex when estimating ontogenetic change. Results of the ontogenetic projections concur with those from mandible morphology, and jointly affirm the taxonomic validity of A. sediba.

  16. Adolescent social defeat induced alterations in anxious behavior and cognitive flexibility in adult mice: effects of developmental stage and social condition

    Directory of Open Access Journals (Sweden)

    Fang Zhang

    2016-07-01

    Full Text Available Negative social experiences during adolescence increase the risk of psychiatric disorders in adulthood. Using resident-intruder stress, the present study aimed to investigate the effects of adolescent social defeat on emotional and cognitive symptoms associated with psychiatric disorders during adulthood and the effects of the developmental stage and social condition on this process. In experiment 1, animals were exposed to social defeat or manipulation for 10 days during early adolescence (EA, PND 28-37, late adolescence (LA, PND 38-47, and adulthood (ADULT, PND 70-79 and then singly housed until the behavioral tests. Behaviors, including social avoidance of the defeat context and cortically mediated cognitive flexibility in an attentional set-shifting task (AST, were assessed during the week following stress or after 6 weeks during adulthood. We determined that social defeat induced significant and continuous social avoidance across age groups at both time points. The mice that experienced social defeat during adulthood exhibited short-term impairments in reversal learning on the AST that dissipated after 6 weeks. In contrast, social defeat during EA but not LA induced a delayed deficit in extra-dimensional set-shifting in adulthood but not during adolescence. In experiment 2, we further examined the effects of social condition (isolation or social housing after stress on the alterations induced by social defeat during EA in adult mice. The adult mice that had experienced stress during EA exhibited social avoidance similar to the avoidance identified in experiment 1 regardless of the isolation or social housing after the stress. However, social housing after the stress ameliorated the cognitive flexibility deficits induced by early adolescent social defeat in the adult mice, and the social condition had no effect on cognitive function. These findings suggest that the effects of social defeat on emotion and cognitive function are differentially

  17. Prevalence and sociodemographic determinants of developmental ...

    African Journals Online (AJOL)

    Birth order and household size also had significant association with delay in various domains. There was no significant association between socioeconomic class and developmental delay in any of the domains. Conclusion: The study showed that developmental delay was relatively common among under-five children in ...

  18. Developmental changes in reading do not alter the development of visual processing skills: An application of explanatory item response models in grades K-2

    Directory of Open Access Journals (Sweden)

    Kristi L Santi

    2015-02-01

    Full Text Available Visual processing has been widely studied in regard to its impact on a students’ ability to read. A less researched area is the role of reading in the development of visual processing skills. A cohort-sequential, accelerated-longitudinal design was utilized with 932 kindergarten, first, and second grade students to examine the impact of reading acquisition on the processing of various types of visual discrimination and visual motor test items. Students were assessed four times per year on a variety of reading measures and reading precursors and two popular measures of visual processing over a three-year period. Explanatory item response models were used to examine the roles of person and item characteristics on changes in visual processing abilities and changes in item difficulties over time. Results showed different developmental patterns for five types of visual processing test items, but most importantly failed to show consistent effects of learning to read on changes in item difficulty. Thus, the present study failed to find support for the hypothesis that learning to read alters performance on measures of visual processing. Rather, visual processing and reading ability improved together over time with no evidence to suggest cross-domain influences from reading to visual processing. Results are discussed in the context of developmental theories of visual processing and brain-based research on the role of visual skills in learning to read.

  19. Developmental biology, the stem cell of biological disciplines.

    Science.gov (United States)

    Gilbert, Scott F

    2017-12-01

    Developmental biology (including embryology) is proposed as "the stem cell of biological disciplines." Genetics, cell biology, oncology, immunology, evolutionary mechanisms, neurobiology, and systems biology each has its ancestry in developmental biology. Moreover, developmental biology continues to roll on, budding off more disciplines, while retaining its own identity. While its descendant disciplines differentiate into sciences with a restricted set of paradigms, examples, and techniques, developmental biology remains vigorous, pluripotent, and relatively undifferentiated. In many disciplines, especially in evolutionary biology and oncology, the developmental perspective is being reasserted as an important research program.

  20. Developmental success, stability, and plasticity in closely related parthenogenetic and sexual lizards (Heteronotia, Gekkonidae).

    Science.gov (United States)

    Kearney, Michael; Shine, Richard

    2004-07-01

    The developmental trajectory of an organism is influenced by the interaction between its genes and the environment in which it develops. For example, the phenotypic traits of a hatchling reptile can be influenced by the organism's genotype, by incubation temperature, and by genetically coded norms of reaction for thermally labile traits. The evolution of parthenogenesis provides a unique opportunity to explore such effects: a hybrid origin of this trait in vertebrates modifies important aspects of the genotype (e.g., heterozygosity, polyploidy) and may thus impact not only on the phenotype generally, but also on the ways in which incubation temperature affects expression of the phenotype. The scarcity of vertebrate parthenogenesis has been attributed to developmental disruptions, but previous work has rarely considered reaction norms of embryogenesis in this respect. We used closely related sexual and asexual races of the Australian gecko Heteronotia binoei, which include those with multiple origins of parthenogenesis, to explore the ways in which reproductive modes (sexual, asexual), incubation temperatures (24, 27, and 30 degrees C), and the interaction between these factors affected hatchling phenotypes. The hatchling traits we considered included incubation period, incidence of deformities, hatchling survivorship, body size and shape, scalation (including fluctuating asymmetry), locomotor performance, and growth rate. Developmental success was slightly reduced (higher proportion of abnormal offspring) in parthenogenetic lineages although there was no major difference in hatching success. Incubation temperature affected a suite of traits including incubation period, tail length, body mass relative to egg mass, labial scale counts, running speed, growth rate, and hatchling survival. Our data also reveal an interaction between reproductive modes and thermal regimes, with the phenotypic traits of parthenogenetic lizards less sensitive to incubation temperature than

  1. Altering endocannabinoid neurotransmission at critical developmental ages: impact on rodent emotionality and cognitive performance

    Directory of Open Access Journals (Sweden)

    Viviana eTrezza

    2012-01-01

    Full Text Available The endocannabinoid system shows functional activity from early stages of brain development: it plays an important role in fundamental developmental processes such as cell proliferation, migration and differentiation, thus shaping brain organization during pre- and postnatal life. Cannabis sativa preparations are among the illicit drugs most commonly used by young people, including pregnant women. The developing brain can be therefore exposed to cannabis preparations during two critical periods: first, in offspring of cannabis-using mothers through perinatal and/or prenatal exposure; second, in adolescent cannabis users during neural maturation. In the last decade, it has become clear that the endocannabinoid system critically modulates memory processing and emotional responses. Therefore, it is well possible that developmental exposure to cannabinoid compounds induces enduring changes in behaviors and neural processes belonging to the cognitive and emotional domains. We address this issue by focusing on rodent studies, in order to provide a framework for understanding the impact of cannabinoid exposure on the developing brain.

  2. Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

    International Nuclear Information System (INIS)

    Tonk, Elisa C.M.; Verhoef, Aart; Gremmer, Eric R.; Loveren, Henk van; Piersma, Aldert H.

    2012-01-01

    The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 at doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the

  3. Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

    Energy Technology Data Exchange (ETDEWEB)

    Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Verhoef, Aart; Gremmer, Eric R. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Loveren, Henk van [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Piersma, Aldert H. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Institute for Risk Assessment Sciences, Veterinary Faculty, Utrecht University, Utrecht (Netherlands)

    2012-04-01

    The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 at doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the

  4. Beyond different levels: embodiment and the developmental system.

    Science.gov (United States)

    Marshall, Peter J

    2014-01-01

    The value of studying a phenomenon at multiple levels of analysis is often emphasized in psychology, but a lack of clarity about the nature of levels and the relations among them remains an impediment to progress. The suggestion here is that an approach combining the tenets of embodiment with the construct of the developmental system provides a way forward. Embodiment opposes the splitting off and elevation of a level of mechanisms that has characterized much of cognitive science. In contrast, a constructivist embodied approach places a level of mechanisms in the context of a formal or systems level of analysis, with developmental process framing the interpenetrating relations between levels. Such an approach stems from a relational worldview that opposes conceptual splits and posits that levels of structure and process comprise an indissociable complementarity. The combination of embodiment and developmental systems within a relational worldview is discussed and elaborated through outlining the integrative approach of relational developmental systems, which has been proposed as a scientific paradigm within which formulations of the interrelations among brain, body, and mind can be advanced.

  5. Developmental vitamin D deficiency alters MK-801-induced behaviours in adult offspring.

    Science.gov (United States)

    Kesby, James P; O'Loan, Jonathan C; Alexander, Suzanne; Deng, Chao; Huang, Xu-Feng; McGrath, John J; Eyles, Darryl W; Burne, Thomas H J

    2012-04-01

    Developmental vitamin D (DVD) deficiency is a candidate risk factor for developing schizophrenia in humans. In rodents DVD deficiency induces subtle changes in the way the brain develops. This early developmental insult leads to select behavioural changes in the adult, such as an enhanced response to amphetamine-induced locomotion in female DVD-deficient rats but not in male DVD-deficient rats and an enhanced locomotor response to the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801, in male DVD-deficient rats. However, the response to MK-801-induced locomotion in female DVD-deficient rats is unknown. Therefore, the aim of the current study was to further examine this behavioural finding in male and female rats and assess NMDA receptor density. DVD-deficient Sprague Dawley rats were assessed for locomotion, ataxia, acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR to multiple doses of MK-801. The NMDA receptor density in relevant brain regions was assessed in a drug-naive cohort. DVD deficiency increased locomotion in response to MK-801 in both sexes. DVD-deficient rats also showed an enhanced ASR compared with control rats, but PPI was normal. Moreover, DVD deficiency decreased NMDA receptor density in the caudate putamen of both sexes. These results suggest that a transient prenatal vitamin D deficiency has a long-lasting effect on NMDA-mediated signalling in the rodent brain and may be a plausible candidate risk factor for schizophrenia and other neuropsychiatric disorders.

  6. Family Life and Developmental Idealism in Yazd, Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Jalal Abbasi-Shavazi

    2012-03-01

    Full Text Available BACKGROUND This paper is motivated by the theory that developmental idealism has been disseminated globally and has become an international force for family and demographic change. Developmental idealism is a set of cultural beliefs and values about development and how development relates to family and demographic behavior. It holds that modern societies are causal forces producing modern families, that modern families help to produce modern societies, and that modern family change is to be expected. OBJECTIVE We examine the extent to which developmental idealism has been disseminated in Iran. We also investigate predictors of the dissemination of developmental idealism. METHODS We use survey data collected in 2007 from a sample of women in Yazd, a city in Iran. We examine the distribution of developmental idealism in the sample and the multivariate predictors of developmental idealism. RESULTS We find considerable support for the expectation that many elements of developmental idealism have been widely disseminated. Statistically significant majorities associate development with particular family attributes, believe that development causes change in families, believe that fertility reductions and age-at-marriage increases help foster development, and perceive family trends in Iran headed toward modernity. As predicted, parental education, respondent education, and income affect adherence to developmental idealism. CONCLUSIONS Developmental idealism has been widely disseminated in Yazd, Iran and is related to social and demographic factors in predicted ways. COMMENTS Although our data come from only one city, we expect that developmental idealism has been widely distributed in Iran, with important implications for family and demographic behavior.

  7. Impact of DNA mismatch repair system alterations on human fertility and related treatments.

    Science.gov (United States)

    Hu, Min-hao; Liu, Shu-yuan; Wang, Ning; Wu, Yan; Jin, Fan

    2016-01-01

    DNA mismatch repair (MMR) is one of the biological pathways, which plays a critical role in DNA homeostasis, primarily by repairing base-pair mismatches and insertion/deletion loops that occur during DNA replication. MMR also takes part in other metabolic pathways and regulates cell cycle arrest. Defects in MMR are associated with genomic instability, predisposition to certain types of cancers and resistance to certain therapeutic drugs. Moreover, genetic and epigenetic alterations in the MMR system demonstrate a significant relationship with human fertility and related treatments, which helps us to understand the etiology and susceptibility of human infertility. Alterations in the MMR system may also influence the health of offspring conceived by assisted reproductive technology in humans. However, further studies are needed to explore the specific mechanisms by which the MMR system may affect human infertility. This review addresses the physiological mechanisms of the MMR system and associations between alterations of the MMR system and human fertility and related treatments, and potential effects on the next generation.

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

    Energy Technology Data Exchange (ETDEWEB)

    Poulsen, Anita H., E-mail: anita.poulsen@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 39 Kessels Rd, Brisbane, Qld 4108 (Australia); Kawaguchi, So, E-mail: so.kawaguchi@aad.gov.au [Australian Antarctic Division, Channel Highway, Kingston, Tas 7050 (Australia); Leppaenen, Matti T., E-mail: matti.t.leppanen@uef.fi [University of Eastern Finland, Joensuu Campus, Department of Biology, FIN-80101 (Finland); Kukkonen, Jussi V.K., E-mail: jussi.kukkonen@uef.fi [University of Eastern Finland, Joensuu Campus, Department of Biology, FIN-80101 (Finland); Bengtson Nash, Susan M., E-mail: s.bengtsonnash@griffith.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 39 Kessels Rd, Brisbane, Qld 4108 (Australia); Griffith University, Atmospheric Environment Research Centre, Brisbane, Qld 4111 (Australia)

    2011-11-15

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

  9. Relative developmental toxicity of short-chain chlorinated paraffins in Zebrafish (Danio rerio) embryos.

    Science.gov (United States)

    Liu, Lihua; Li, Yifan; Coelhan, Mehmet; Chan, Hing Man; Ma, Wanli; Liu, Liyan

    2016-12-01

    Short-chain chlorinated paraffins (SCCPs) are ubiquitous in the environment and might cause adverse environmental and human health effects. Little is known about the relative toxicity of different SCCP compounds especially during development. The objective of this study was to characterize and compare effects of seven SCCP groups at environmentally relevant levels, using a zebrafish (Danio rerio) model. Observations on malformation, survival rates at 96 h post fertilization (hpf), and hatching rates at 72 hpf indicated that the C 10- groups (C 10 H 18 Cl 4 , 1,2,5,6,9,10-C 10 H 16 Cl 6 and C 10 H 15 Cl 7 ) were more toxic than the C 12- groups (C 12 H 22 Cl 4 , C 12 H 19 Cl 7 and 1,1,1,3,10,12,12,12-C 12 H 18 Cl 8 ) and Cereclor 63L. The C 10- groups were also more potent than C 12- groups and Cereclor 63L in decreasing thyroid hormone levels. Among the three compounds within the C 10- group, the compounds with less chlorine content had stronger effects on sub-lethal malformations but less effects on triiodothyronine (T3) and tetraiodothyronine (T4). Only C 10 H 18 Cl 4 significantly decreased the mRNA expression of tyr, ttr, dio2 and dio3 at a dose-dependent manner suggesting that the specific mode of actions differ with different congeners. The mechanisms of disruption of thyroid status by different SCCPs could be different. C 10 H 18 Cl 4 might inhibit T3 production through the inhibition effect on dio2. These results indicate that SCCP exposure could alter gene expression in the hypothalamic-pituitary-thyroid (HPT) axis and thyroid hormone levels. The mechanisms of disruption of thyroid status by different SCCPs could be different. Our results on the relative developmental toxicities of SCCPs will be useful to reach a better understanding of SCCP toxicity supporting environmental risk evaluation and regulation and used as a guidance for environmental monitoring of SCCPs in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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

  11. CDKL5 alterations lead to early epileptic encephalopathy in both genders.

    Science.gov (United States)

    Liang, Jao-Shwann; Shimojima, Keiko; Takayama, Rumiko; Natsume, Jun; Shichiji, Minobu; Hirasawa, Kyoko; Imai, Kaoru; Okanishi, Tohru; Mizuno, Seiji; Okumura, Akihisa; Sugawara, Midori; Ito, Tomoshiro; Ikeda, Hiroko; Takahashi, Yukitoshi; Oguni, Hirokazu; Imai, Katsumi; Osawa, Makiko; Yamamoto, Toshiyuki

    2011-10-01

    Genetic mutations of the cyclin-dependent kinase-like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe-to-profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders. A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG-binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations. One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features. We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  12. GABA FUNCTION IS ALTERED FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM: NEUROANATOMICAL AND NEUROPHYSIOLOGICAL EVIDENCE.

    Science.gov (United States)

    Thyroid hormone deficiency during development produces changes in the structure of neurons and glial cells and alters synaptic function in the hippocampus. GABAergic interneurons comprise the bulk of local inhibitory neuronal circuitry and a subpopulation of these interneurons ...

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

    Science.gov (United States)

    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

  14. Alterations in the proteome of the Euprymna scolopes light organ in response to symbiotic Vibrio fischeri.

    Science.gov (United States)

    Doino Lemus, J; McFall-Ngai, M J

    2000-09-01

    During the onset of the cooperative association between the Hawaiian sepiolid squid Euprymna scolopes and the marine luminous bacterium Vibrio fischeri, the anatomy and morphology of the host's symbiotic organ undergo dramatic changes that require interaction with the bacteria. This morphogenetic process involves an array of tissues, including those in direct contact with, as well as those remote from, the symbiotic bacteria. The bacteria induce the developmental program soon after colonization of the organ, although complete morphogenesis requires 96 h. In this study, to determine critical time points, we examined the biochemistry underlying bacterium-induced host development using two-dimensional polyacrylamide gel electrophoresis. Specifically, V. fischeri-induced changes in the soluble proteome of the symbiotic organ during the first 96 h of symbiosis were identified by comparing the protein profiles of symbiont-colonized and uncolonized organs. Both symbiosis-related changes and age-related changes were analyzed to determine what proportion of the differences in the proteomes was the result of specific responses to interaction with bacteria. Although no differences were detected over the first 24 h, numerous symbiosis-related changes became apparent at 48 and 96 h and were more abundant than age-related changes. In addition, many age-related protein changes occurred 48 h sooner in symbiotic animals, suggesting that the interaction of squid tissue with V. fischeri cells accelerates certain developmental processes of the symbiotic organ. These data suggest that V. fischeri-induced modifications in host tissues that occur in the first 24 h of the symbiosis are independent of marked alterations in the patterns of abundant proteins but that the full 4-day morphogenetic program requires significant alteration of the host soluble proteome.

  15. Planum Temporale Morphology in Children with Developmental Dyslexia

    Science.gov (United States)

    Bloom, Juliana Sanchez; Garcia-Barrera, Mauricio A.; Miller, Carlin J.; Miller, Scott R.; Hynd, George W.

    2013-01-01

    The planum temporale is a highly lateralized cortical region, located within Wernicke’s area, which is thought to be involved in auditory processing, phonological processing, and language. Research has linked abnormal morphology of the planum temporale to developmental dyslexia, although results have varied in large part due to methodological inconsistencies in the literature. This study examined the asymmetry of the planum temporale in 29 children who met criteria for dyslexia and 26 children whose reading was unimpaired. Leftward asymmetry of the planum temporale was found in the total sample and this leftward asymmetry was significantly reduced in children with dyslexia. This reduced leftward asymmetry in children with dyslexia was due to a planum temporale that is larger in the right hemisphere. This study lends support to the idea that planum temporale asymmetry is altered in children with developmental dyslexia. PMID:23707683

  16. Constructivist developmental theory is needed in developmental neuroscience

    Science.gov (United States)

    Arsalidou, Marie; Pascual-Leone, Juan

    2016-12-01

    Neuroscience techniques provide an open window previously unavailable to the origin of thoughts and actions in children. Developmental cognitive neuroscience is booming, and knowledge from human brain mapping is finding its way into education and pediatric practice. Promises of application in developmental cognitive neuroscience rests however on better theory-guided data interpretation. Massive amounts of neuroimaging data from children are being processed, yet published studies often do not frame their work within developmental models—in detriment, we believe, to progress in this field. Here we describe some core challenges in interpreting the data from developmental cognitive neuroscience, and advocate the use of constructivist developmental theories of human cognition with a neuroscience interpretation.

  17. Developmental Defects of Enamel : an increasing reality in the everyday practice

    Directory of Open Access Journals (Sweden)

    Fabrizio Guerra

    2014-09-01

    Full Text Available Developmental defects of enamel (DDE are daily encountered in clinical practice. DDE are alteration in quality and quantity of the enamel, caused by disruption and/or damage to the enamel organ during the amelogenesis process. Several clinical indices have been developed to categorize enamel defects based on their nature, appearance, microscopic features or their cause. The aetiology of DDE is not completely clear. Enamel fluorosis is a hypo-mineralization of enamel characterised by subsurface porosity as a result of excess fluoride intake during the period of enamel formation. Several types of treatment have been reported, related to the degree of enamel defect. Correct diagnosis according to lesion depth and prognosis of the technique are fundamental factors in the treatment decision-making process.

  18. Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia.

    Science.gov (United States)

    Kesby, James P; Burne, Thomas H J; McGrath, John J; Eyles, Darryl W

    2006-09-15

    Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. The behavioral phenotype of adult rats subjected to transient low prenatal vitamin D is characterized by spontaneous hyperlocomotion but normal prepulse inhibition of acoustic startle (PPI). The aim of this study was to examine the impact of selected psychotropic agents and one well-known antipsychotic agent on the behavioral phenotype of DVD deplete rats. Control versus DVD deplete adult rats were assessed on holeboard, open field and PPI. In the open field, animals were given MK-801 and/or haloperidol. For PPI, the animals were given apomorphine or MK-801. DVD deplete rats had increased baseline locomotion on the holeboard task and increased locomotion in response to MK-801 compared to control rats. At low doses, haloperidol antagonized the MK-801 hyperactivity of DVD deplete rats preferentially and, at a high dose, resulted in a more pronounced reduction in spontaneous locomotion in DVD deplete rats. DVD depletion did not affect either baseline or drug-mediated PPI response. These results suggest that DVD deficiency is associated with a persistent alteration in neuronal systems associated with motor function but not those associated with sensory motor gating. In light of the putative association between low prenatal vitamin D and schizophrenia, the discrete behavioral differences associated with the DVD model may help elucidate the neurobiological correlates of schizophrenia.

  19. Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring

    NARCIS (Netherlands)

    Boulle, F.; Pawluski, J.L.; Homberg, J.R.; Machiels, B.; Kroeze, Y.; Kumar, N.; Steinbusch, H.W.; Kenis, G.; Hove, D.L. van den

    2016-01-01

    A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has

  20. Evaluation of the Esthetic Properties of Developmental Defects of Enamel: A Spectrophotometric Clinical Study

    Directory of Open Access Journals (Sweden)

    Fabrizio Guerra

    2015-01-01

    Full Text Available Objectives. Detailed clinical quantification of optical properties of developmental defect of enamel is possible with spectrophotometric evaluation. Developmental defects of enamel (DDE are daily encountered in clinical practice. DDE are an alteration in quality and quantity of the enamel, caused by disruption and/or damage to the enamel organ during amelogenesis. Methods. Several clinical indices have been developed to categorize enamel defects based on their nature, appearance, microscopic features, or cause. A sample of 39 permanent teeth presenting DDE on labial surface was examined using the DDE Modified Index and SpectroShade evaluation. The spectrophotometric approach quantifies L* (luminosity, a* (quantity of green-red, and b* (quantity of blue-yellow of different DDE. Conclusions. SpectroShade evaluation of the optical properties of the enamel defect enhances clinical understanding of severity and extent of the defect and characterizes the enamel alteration in terms of color discrepancy and surface characterization.

  1. Relations between altered stramflow variability and fish assemblages in Eastern USA streams

    Science.gov (United States)

    Meador, Michael R.; Carlisle, Daren M.

    2012-01-01

    Although altered streamflow has been implicated as a major factor affecting fish assemblages, understanding the extent of streamflow alteration has required quantifying attributes of the natural flow regime. We used predictive models to quantify deviation from expected natural streamflow variability for streams in the eastern USA. Sites with >25% change in mean daily streamflow variability compared with what would be expected in a minimally disturbed environment were defined as having altered streamflow variability, based on the 10th and 90th percentiles of the distribution of streamflow variability at 1279 hydrological reference sites. We also used predictive models to assess fish assemblage condition and native species loss based on the proportion of expected native fish species that were observed. Of the 97 sites, 49 (50.5%) were classified as altered with reduced streamflow variability, whereas no sites had increased streamflow variability. Reduced streamflow variability was related to a 35% loss in native fish species, on average, and a >50% loss of species with a preference for riffle habitats. Conditional probability analysis indicated that the probability of fish assemblage impairment increased as the severity of altered streamflow variability increased. Reservoir storage capacity and wastewater discharges were important predictors of reduced streamflow variability as revealed by random forest analysis. Management and conservation of streams will require careful consideration of natural streamflow variation and potential factors contributing to altered streamflow within the entire watershed to limit the loss of critical stream habitats and fish species uniquely adapted to live in those habitats.

  2. Mechanistic insight into neurotoxicity induced by developmental insults

    International Nuclear Information System (INIS)

    Tamm, Christoffer; Ceccatelli, Sandra

    2017-01-01

    Epidemiological and/or experimental studies have shown that unfavorable prenatal environmental factors, such as stress or exposure to certain neurotoxic environmental contaminants, may have adverse consequences for neurodevelopment. Alterations in neurogenesis can have harmful effects not only for the developing nervous system, but also for the adult brain where neurogenesis is believed to play a role in learning, memory, and even in depression. Many recent advances in the understanding of the complex process of nervous system development can be integrated into the field of neurotoxicology. In the past 15 years we have been using cultured neural stem or progenitor cells to investigate the effects of neurotoxic stimuli on cell survival, proliferation and differentiation, with special focus on heritable effects. This is an overview of the work performed by our group in the attempt to elucidate the mechanisms of developmental neurotoxicity and possibly provide relevant information for the understanding of the etiopathogenesis of complex brain disorders. - Highlights: • The developing nervous system is highly sensitive to toxic insults. • Neural stem cells are relevant models for mechanistic studies as well as for identifying heritable effects due to epigenetic changes. • Depending on the dose, the outcome of exposure to neurotoxicants ranges from altered proliferation and differentiation to cell death. • The elucidation of neurotoxicity mechanisms is relevant for understanding the etiopathogenesis of developmental and adult nervous system disorders.

  3. Ground and surface water developmental toxicity at a municipal landfill--Description and weather-related variation

    Science.gov (United States)

    Bruner, M.A.; Rao, M.; Dumont, J.N.; Hull, M.; Jones, T.; Bantle, J.A.

    1998-01-01

    Contaminated groundwater poses a significant health hazard and may also impact wildlife such as amphibians when it surfaces. Using FETAX (Frog Embryo Teratogenesis Assay-Xenopus), the developmental toxicity of ground and surface water samples near a closed municipal landfill at Norman, OK, were evaluated. The groundwater samples were taken from a network of wells in a shallow, unconfined aquifer downgradient from the landfill. Surface water samples were obtained from a pond and small stream adjacent to the landfill. Surface water samples from a reference site in similar habitat were also analyzed. Groundwater samples were highly toxic in the area near the landfill, indicating a plume of toxicants. Surface water samples from the landfill site demonstrated elevated developmental toxicity. This toxicity was temporally variable and was significantly correlated with weather conditions during the 3 days prior to sampling. Mortality was negatively correlated with cumulative rain and relative humidity. Mortality was positively correlated with solar radiation and net radiation. No significant correlations were observed between mortality and weather parameters for days 4–7 preceding sampling.

  4. Development of Mentalizing and Communication: From Viewpoint of Developmental Cybernetics and Developmental Cognitive Neuroscience

    Science.gov (United States)

    Itakura, Shoji

    The ability to mentalize is essential for human socialization. Such ability is strongly related to communication. In this paper, I discuss the development of mentalizing and communication from the perspectives of a new idea, Developmental Cybernetics, and developmental cognitive neuroscience. Children only attributed intention to a robot when they saw it behaving as a human and displaying social signals such as eye gaze. The emergence of powerful new methods and tools, such as neuroimaging, now allows questions about mentalizing to resolved more directly than before.

  5. Are relative depletions altered inside diffuse clouds?

    International Nuclear Information System (INIS)

    Joseph, C.L.

    1988-01-01

    The data of Jenkins, Savage, and Spitzer (1986) were used to analyze interstellar abundances and depletions of Fe, P, Mg, and Mn toward 37 stars, spanning nearly 1.0 (dex) in mean line-of-sight depletion. It was found that the depletions of these elements are linearly correlated and do not show evidence of differences in the rates of depletion or sputtering from one element to another. For a given level of overall depletion, the sightline-to-sightline rms variance in the depletion for each of these elements was less than 0.16 (dex), which is significantly smaller than is the element-to-element variance. The results suggest that, for most diffuse lines of sight, the relative abundances of these elements are set early in the lifetime of the grains and are not altered significantly thereafter. 53 references

  6. Maternal Obesity, Inflammation, and Developmental Programming

    Directory of Open Access Journals (Sweden)

    Stephanie A. Segovia

    2014-01-01

    Full Text Available The prevalence of obesity, especially in women of child-bearing age, is a global health concern. In addition to increasing the immediate risk of gestational complications, there is accumulating evidence that maternal obesity also has long-term consequences for the offspring. The concept of developmental programming describes the process in which an environmental stimulus, including altered nutrition, during critical periods of development can program alterations in organogenesis, tissue development, and metabolism, predisposing offspring to obesity and metabolic and cardiovascular disorders in later life. Although the mechanisms underpinning programming of metabolic disorders remain poorly defined, it has become increasingly clear that low-grade inflammation is associated with obesity and its comorbidities. This review will discuss maternal metainflammation as a mediator of programming in insulin sensitive tissues in offspring. Use of nutritional anti-inflammatories in pregnancy including omega 3 fatty acids, resveratrol, curcumin, and taurine may provide beneficial intervention strategies to ameliorate maternal obesity-induced programming.

  7. Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder.

    Science.gov (United States)

    Coretti, Lorena; Cristiano, Claudia; Florio, Ermanno; Scala, Giovanni; Lama, Adriano; Keller, Simona; Cuomo, Mariella; Russo, Roberto; Pero, Raffaela; Paciello, Orlando; Mattace Raso, Giuseppina; Meli, Rosaria; Cocozza, Sergio; Calignano, Antonio; Chiariotti, Lorenzo; Lembo, Francesca

    2017-03-28

    Alterations of microbiota-gut-brain axis have been invoked in the pathogenesis of autism spectrum disorders (ASD). Mouse models could represent an excellent tool to understand how gut dysbiosis and related alterations may contribute to autistic phenotype. In this study we paralleled gut microbiota (GM) profiles, behavioral characteristics, intestinal integrity and immunological features of colon tissues in BTBR T + tf/J (BTBR) inbred mice, a well established animal model of ASD. Sex differences, up to date poorly investigated in animal models, were specifically addressed. Results showed that BTBR mice of both sexes presented a marked intestinal dysbiosis, alterations of behavior, gut permeability and immunological state with respect to prosocial C57BL/6j (C57) strain. Noticeably, sex-related differences were clearly detected. We identified Bacteroides, Parabacteroides, Sutterella, Dehalobacterium and Oscillospira genera as key drivers of sex-specific gut microbiota profiles associated with selected pathological traits. Taken together, our findings indicate that alteration of GM in BTBR mice shows relevant sex-associated differences and supports the use of BTBR mouse model to dissect autism associated microbiota-gut-brain axis alteration.

  8. Utility of Small Animal Models of Developmental Programming.

    Science.gov (United States)

    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.

  9. Factors Related to the Developmental Experiences of Youth Serving as 4-H Camp Counselors

    Science.gov (United States)

    Carter, David N.; Kotrlik, Joe W.

    2008-01-01

    The purpose of this study was to investigate the developmental experiences of high-school-aged 4-H youth volunteering as counselors at Louisiana 4-H summer camps. A total of 288 counselors from 10 different camping sessions participated in the study. The Youth Experiences Survey 2.0 and the Developmental Experience Survey measured the personal…

  10. Molecular and Chemical Genetic Approaches to Developmental Origins of Aging and Disease in Zebrafish

    Science.gov (United States)

    Sasaki, Tomoyuki; Kishi, Shuji

    2013-01-01

    The incidence of diseases increases rapidly with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but mostly inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states in response to different environmental or genetic perturbations. On the one hand, we hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds of adaptive plasticity by chemical genetic approaches, we have been investigating whether any relationship exists between the regulatory mechanisms that function in early development and in senescence using the zebrafish (Danio rerio), a small freshwater fish and a useful model animal for genetic studies. We have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during embryogenesis (“embryonic senescence”), subsequently showing shortened lifespan in adulthoods. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other hand, unexpected senescence-related genes might also be involved in the early developmental process and regulation. The ease of manipulation using the zebrafish system allows us to conduct an exhaustive exploration of novel genes and small molecular compounds that can be linked to the senescence phenotype, and thereby facilitates searching for the evolutionary and developmental origins

  11. 48 CFR 1019.202-70-13 - Developmental assistance.

    Science.gov (United States)

    2010-10-01

    ... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 1019.202-70-13 Developmental assistance. The forms of developmental assistance a mentor can provide to a protégé include: (a) Management guidance relating to financial management, organizational management, overall business management/planning, business development...

  12. Developmental Programming of Adult Disease: Reprogramming by Melatonin?

    Directory of Open Access Journals (Sweden)

    You-Lin Tain

    2017-02-01

    Full Text Available Adult-onset chronic non-communicable diseases (NCDs can originate from early life through so-called the “developmental origins of health and disease” (DOHaD or “developmental programming”. The DOHaD concept offers the “reprogramming” strategy to shift the treatment from adulthood to early life, before clinical disease is apparent. Melatonin, an endogenous indoleamine produced by the pineal gland, has pleiotropic bioactivities those are beneficial in a variety of human diseases. Emerging evidence support that melatonin is closely inter-related to other proposed mechanisms contributing to the developmental programming of a variety of chronic NCDs. Recent animal studies have begun to unravel the multifunctional roles of melatonin in many experimental models of developmental programming. Even though some progress has been made in research on melatonin as a reprogramming strategy to prevent DOHaD-related NCDs, future human studies should aim at filling the translational gap between animal models and clinical trials. Here, we review several key themes on the reprogramming effects of melatonin in DOHaD research. We have particularly focused on the following areas: mechanisms of developmental programming; the interrelationship between melatonin and mechanisms underlying developmental programming; pathophysiological roles of melatonin in pregnancy and fetal development; and insight provided by animal models to support melatonin as a reprogramming therapy. Rates of NCDs are increasing faster than anticipated all over the world. Hence, there is an urgent need to understand reprogramming mechanisms of melatonin and to translate experimental research into clinical practice for halting a growing list of DOHaD-related NCDs.

  13. Developmental Programming of Adult Disease: Reprogramming by Melatonin?

    Science.gov (United States)

    Tain, You-Lin; Huang, Li-Tung; Hsu, Chien-Ning

    2017-02-16

    Adult-onset chronic non-communicable diseases (NCDs) can originate from early life through so-called the "developmental origins of health and disease" (DOHaD) or "developmental programming". The DOHaD concept offers the "reprogramming" strategy to shift the treatment from adulthood to early life, before clinical disease is apparent. Melatonin, an endogenous indoleamine produced by the pineal gland, has pleiotropic bioactivities those are beneficial in a variety of human diseases. Emerging evidence support that melatonin is closely inter-related to other proposed mechanisms contributing to the developmental programming of a variety of chronic NCDs. Recent animal studies have begun to unravel the multifunctional roles of melatonin in many experimental models of developmental programming. Even though some progress has been made in research on melatonin as a reprogramming strategy to prevent DOHaD-related NCDs, future human studies should aim at filling the translational gap between animal models and clinical trials. Here, we review several key themes on the reprogramming effects of melatonin in DOHaD research. We have particularly focused on the following areas: mechanisms of developmental programming; the interrelationship between melatonin and mechanisms underlying developmental programming; pathophysiological roles of melatonin in pregnancy and fetal development; and insight provided by animal models to support melatonin as a reprogramming therapy. Rates of NCDs are increasing faster than anticipated all over the world. Hence, there is an urgent need to understand reprogramming mechanisms of melatonin and to translate experimental research into clinical practice for halting a growing list of DOHaD-related NCDs.

  14. On the relation between face and object recognition in developmental prosopagnosia

    DEFF Research Database (Denmark)

    Gerlach, Christian; Klargaard, Solja K.; Starrfelt, Randi

    2016-01-01

    There is an ongoing debate about whether face recognition and object recognition constitute separate domains. Clarification of this issue can have important theoretical implications as face recognition is often used as a prime example of domain-specificity in mind and brain. An important source...... of input to this debate comes from studies of individuals with developmental prosopagnosia, suggesting that face recognition can be selectively impaired. We put the selectivity hypothesis to test by assessing the performance of 10 individuals with developmental prosopagnosia on demanding tests of visual...... object processing involving both regular and degraded drawings. None of the individuals exhibited a clear dissociation between face and object recognition, and as a group they were significantly more affected by degradation of objects than control participants. Importantly, we also find positive...

  15. Developmental effects of extremely low frequency electric and magnetic fields

    International Nuclear Information System (INIS)

    Juutilainen, J.

    2003-01-01

    Developmental effects of extremely low frequency (ELF) electric and magnetic fields are briefly reviewed in this paper. The results of animal studies on ELF electric fields are rather consistent, and do not suggest adverse effects on development. The results of studies on ELF magnetic fields suggest effects on bird embryo development, but not consistently in all studies. Results from experiments with other non-mammalian species have also suggested effects on developmental stability. In mammals, pre-natal exposure to ELF magnetic fields does not result in strong adverse effects on development. The only finding that shows some consistency is increase of minor skeleton alterations. Epidemiological studies do not establish an association between human adverse pregnancy outcomes and maternal exposure to ELF fields, although a few studies have reported increased risks associated with some characteristics of magnetic field exposure. Taken as a whole, the results do not show strong adverse effects on development. However, additional studies on the suggested subtle effects on developmental stability might increase our understanding of the sensitivity of organisms to weak ELF fields. (author)

  16. Alterations in theory of mind in patients with schizophrenia and non-psychotic relatives.

    Science.gov (United States)

    Janssen, I; Krabbendam, L; Jolles, J; van Os, Jim

    2003-08-01

    It has been proposed that alterations in theory of mind underlie specific symptoms of psychosis. The present study examined whether alterations in theory of mind reflect a trait that can be detected in non-psychotic relatives of patients with schizophrenia. Participants were 43 patients with schizophrenia or schizoaffective disorder, 41 first-degree non-psychotic relatives and 43 controls from the general population. Theory of mind was assessed using a hinting task and a false-belief task. There was a significant association between schizophrenia risk and failure on the hinting task (OR linear trend = 2.01, 95% CI: 1.22-3.31), with relatives having intermediate values between patients and controls. Adjustment for IQ and neuropsychological factors reduced the association by small amounts. The association between schizophrenia risk and failure on the false-belief tasks was not significant. Changes in theory of mind are associated with schizophrenia liability. General cognitive ability and neuropsychological measures seem to mediate only part of this association.

  17. Receptor tyrosine kinase mutations in developmental syndromes and cancer: two sides of the same coin

    Science.gov (United States)

    McDonell, Laura M.; Kernohan, Kristin D.; Boycott, Kym M.; Sawyer, Sarah L.

    2015-01-01

    Receptor tyrosine kinases (RTKs) are a family of ligand-binding cell surface receptors that regulate a wide range of essential cellular activities, including proliferation, differentiation, cell-cycle progression, survival and apoptosis. As such, these proteins play an important role during development and throughout life; germline mutations in genes encoding RTKs cause several developmental syndromes, while somatic alterations contribute to the pathogenesis of many aggressive cancers. This creates an interesting paradigm in which mutation timing, type and location in a gene leads to different cell signaling and biological responses, and ultimately phenotypic outcomes. In this review, we highlight the roles of RTKs in developmental disorders and cancer. The multifaceted roles of these receptors, their genetic signatures and their signaling during developmental morphogenesis and oncogenesis are discussed. Additionally, we propose that comparative analysis of RTK mutations responsible for developmental syndromes may shed light on those driving tumorigenesis. PMID:26152202

  18. [Contemporary cognitive theories about developmental dyscalculia].

    Science.gov (United States)

    Castro-Cañizares, D; Estévez-Pérez, N; Reigosa-Crespo, V

    To analyze the current theories describing the cognitive mechanisms underlying developmental dyscalculia. The four most researched hypotheses concerning the cognitive deficits related to developmental dyscalculia, as well as experimental evidences supporting or refusing them are presented. The first hypothesis states that developmental dyscalculia is consequence of domain general cognitive deficits. The second hypothesis suggests that it is due to a failure in the development of specialized brain systems dedicated to numerosity processing. The third hypothesis asserts the disorder is caused by a deficit in accessing quantity representation through numerical symbols. The last hypothesis states developmental dyscalculia appears as a consequence of impairments in a generalized magnitude system dedicated to the processing of continuous and discrete magnitudes. None of the hypotheses has been proven more plausible than the rest. Relevant issues rose by them need to be revisited and answered in the light of new experimental designs. In the last years the understanding of cognitive disorders involved in developmental dyscalculia has remarkably increased, but it is nonetheless insufficient. Additional research is required in order to achieve a comprehensive cognitive model of numerical processing development and its disorders. This will improve the diagnostic precision and the effectiveness of developmental dyscalculia intervention strategies.

  19. Developmental toxicity from exposure to various forms of mercury compounds in medaka fish (Oryzias latipes embryos

    Directory of Open Access Journals (Sweden)

    Wu Dong

    2016-08-01

    Full Text Available This study examined developmental toxicity of different mercury compounds, including some used in traditional medicines. Medaka (Oryzias latipes embryos were exposed to 0.001–10 µM concentrations of MeHg, HgCl2, α-HgS (Zhu Sha, and β-HgS (Zuotai from stage 10 (6–7 hpf to 10 days post fertilization (dpf. Of the forms of mercury in this study, the organic form (MeHg proved the most toxic followed by inorganic mercury (HgCl2, both producing embryo developmental toxicity. Altered phenotypes included pericardial edema with elongated or tube heart, reduction of eye pigmentation, and failure of swim bladder inflation. Both α-HgS and β-HgS were less toxic than MeHg and HgCl2. Total RNA was extracted from survivors three days after exposure to MeHg (0.1 µM, HgCl2 (1 µM, α-HgS (10 µM, or β-HgS (10 µM to examine toxicity-related gene expression. MeHg and HgCl2 markedly induced metallothionein (MT and heme oxygenase-1 (Ho-1, while α-HgS and β-HgS failed to induce either gene. Chemical forms of mercury compounds proved to be a major determinant in their developmental toxicity.

  20. Evolutionary and developmental modules.

    Science.gov (United States)

    Lacquaniti, Francesco; Ivanenko, Yuri P; d'Avella, Andrea; Zelik, Karl E; Zago, Myrka

    2013-01-01

    The identification of biological modules at the systems level often follows top-down decomposition of a task goal, or bottom-up decomposition of multidimensional data arrays into basic elements or patterns representing shared features. These approaches traditionally have been applied to mature, fully developed systems. Here we review some results from two other perspectives on modularity, namely the developmental and evolutionary perspective. There is growing evidence that modular units of development were highly preserved and recombined during evolution. We first consider a few examples of modules well identifiable from morphology. Next we consider the more difficult issue of identifying functional developmental modules. We dwell especially on modular control of locomotion to argue that the building blocks used to construct different locomotor behaviors are similar across several animal species, presumably related to ancestral neural networks of command. A recurrent theme from comparative studies is that the developmental addition of new premotor modules underlies the postnatal acquisition and refinement of several different motor behaviors in vertebrates.

  1. Developmental post-natal stress can alter the effects of pre-natal stress on the adult redox balance.

    Science.gov (United States)

    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.

  2. Inhibition of glutathione biosynthesis alters compartmental redox status and the thiol proteome in organogenesis-stage rat conceptuses.

    Science.gov (United States)

    Harris, Craig; Shuster, Daniel Z; Roman Gomez, Rosaicela; Sant, Karilyn E; Reed, Matthew S; Pohl, Jan; Hansen, Jason M

    2013-10-01

    Developmental signals that control growth and differentiation are regulated by environmental factors that generate reactive oxygen species (ROS) and alter steady-state redox environments in tissues and fluids. Protein thiols are selectively oxidized and reduced in distinct spatial and temporal patterns in conjunction with changes in glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (Cys/CySS) redox potentials (E(h)) to regulate developmental signaling. The purpose of this study was to measure compartment-specific thiol redox status in cultured organogenesis-stage rat conceptuses and to evaluate the impact of thiol oxidation on the redox proteome. The visceral yolk sac (VYS) has the highest initial (0 h) total intracellular GSH (GSH+2GSSG) concentration (5.5 mM) and the lowest Eh (-223 mV) as determined by HPLC analysis. Total embryo (EMB) GSH concentrations ranged lower (3.2 mM) and were only slightly more oxidized than the VYS. Total GSH concentrations in yolk sac fluid (YSF) and amniotic fluid (AF) are >500-fold lower than in tissues and are highly oxidized (YSF E(h)=-121 mV and AF E(h)=-49 mV). Steady-state total Cys concentrations (Cys+2CySS) were significantly lower than GSH in tissues but were otherwise equal in VYS and EMB near 0.5 mM. On gestational day 11, total GSH and Cys concentrations in EMB and VYS increase significantly over the 6h time course while E(h) remains relatively constant. The Eh (GSH/GSSG) in YSF and AF become more reduced over time while E(h) (Cys/CySS) become more oxidized. Addition of L-buthionine-S,R-sulfoximine (BS0) to selectively inhibit GSH synthesis and mimic the effects of some GSH-depleting environmental chemicals significantly decreased VYS and EMB GSH and Cys concentrations and increased Eh over the 6h exposure period, showing a greater overall oxidation. In the YSF, BSO caused a significant increase in total Cys concentrations to 1.7 mM but did not significantly change the E(h) for Cys/CySS. A significant net

  3. Developmental pathways of change in fitness and motor competence are related to overweight and obesity status at the end of primary school.

    Science.gov (United States)

    Rodrigues, Luis P; Stodden, David F; Lopes, Vítor P

    2016-01-01

    To test how different developmental pathways of health-related physical fitness and motor competence tests relate to weight status (overweight and obesity) at the end of primary school. Longitudinal study on growth, health-related physical fitness, and motor competence of 472 primary school children assessed yearly throughout 1st to 4th grade, with an average age of 6.3±0.7 years of age at 1st grade. Children's pathways of change on each of the fitness and motor competence tests were determined along the four years of the study. Participants were divided into three groups according to their rate of change in each test over time: Low Rate of Change, Average Rate of Change, and High Rate of Change. A logistic regression was used to predict the odds ratio of becoming overweight or obese, depending on the developmental pathway of change in fitness and motor competence across childhood. Children with a low or average rate of change in their developmental pathways of fitness and motor competence were several times more prone to become overweight or obese at the end of primary school (OR 2.0 to 6.3), independent of sex and body mass index at baseline. Specifically, a negative developmental pathway (Low Rate of Change) in cardiorespiratory fitness demonstrated over a six-fold elevated risk of being overweight or obese, compared to peers with a positive pathway. Not all children improve their motor competence and fitness levels over time and many actually regress over time. Developing positive fitness and motor competence pathways during childhood protects from obesity and overweight. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  4. Low level postnatal methylmercury exposure in vivo alters developmental forms of short-term synaptic plasticity in the visual cortex of rat

    International Nuclear Information System (INIS)

    Dasari, Sameera; Yuan, Yukun

    2009-01-01

    Methylmercury (MeHg) has been previously shown to affect neurotransmitter release. Short-term synaptic plasticity (STP) is primarily related to changes in the probability of neurotransmitter release. To determine if MeHg affects STP development, we examined STP forms in the visual cortex of rat following in vivo MeHg exposure. Neonatal rats received 0 (0.9% NaCl), 0.75 or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which visual cortical slices were prepared for field potential recordings. In slices prepared from rats treated with vehicle, field excitatory postsynaptic potentials (fEPSPs) evoked by paired-pulse stimulation at 20-200 ms inter-stimulus intervals showed a depression (PPD) of the second fEPSP (fEPSP2). PPD was also seen in slices prepared from rats after 15 day treatment with 0.75 or 1.5 mg/kg/day MeHg. However, longer duration treatment (30 days) with either dose of MeHg resulted in paired-pulse facilitation (PPF) of fEPSP2 in the majority of slices examined. PPF remained observable in slices prepared from animals in which MeHg exposure had been terminated for 30 days after completion of the initial 30 day MeHg treatment, whereas slices from control animals still showed PPD. MeHg did not cause any frequency- or region-preferential effect on STP. Manipulations of [Ca 2+ ] e or application of the GABA A receptor antagonist bicuculline could alter the strength and polarity of MeHg-induced changes in STP. Thus, these data suggest that low level postnatal MeHg exposure interferes with the developmental transformation of STP in the visual cortex, which is a long-lasting effect.

  5. Flow paths of water and sediment in a tidal marsh: relations with marsh developmental stage and tidal inundation height

    NARCIS (Netherlands)

    Temmerman, S.; Bouma, T.J.; Govers, G.; Lauwaet, D.

    2005-01-01

    This study provides new insights in the relative role of tidal creeks and the marsh edge in supplying water and sediments to and from tidal marshes for a wide range of tidal inundation cycles with different high water levels and for marsh zones of different developmental stage. Net import or export

  6. Developmental analytic view on narcissism

    Directory of Open Access Journals (Sweden)

    Polona Matjan Štuhec

    2009-07-01

    Full Text Available Narcissistic pathology is connected to the pathology of the self. This article makes an overview of definitions of developmental analytic theories and stops with Kohut, Kernberg, Masterson, Auerbach and Mollon. The self is understood as a separate personality structure and has its own developmental line. Narcissism is a personality disorder that has its roots in preodipal developmental phases, mostly in the practicing and rapprochement subphase and in the oedipal phase as well. Recent research shows that the oedipal phase and the relation between the mother, the child's father (or her partner in general and the child is crucial for the maintenance of the pathological narcissism. Mothers who do not believe in a satisfying relationship with a man in general, keep the child in the dyadic position and do not support the development of the child's own identity.

  7. Prenatal stress alters progestogens to mediate susceptibility to sex-typical, stress-sensitive disorders, such as drug abuse: a review

    Directory of Open Access Journals (Sweden)

    Cheryl A Frye

    2011-10-01

    Full Text Available Maternal-offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well understood. Our hypothesis is that allopregnanolone, during gestation, plays a particularly vital role in mitigating effects of stress on the developing fetus and may mediate, in part, alterations apparent throughout the lifespan. Specifically, altered balance between glucocorticoids and progestogens during critical periods of development (stemming from psychological, immunological, and/or endocrinological stressors during gestation may permanently influence behavior, brain morphology, and/or neuroendocrine-sensitive processes. 5α-reduced progestogens are integral in the developmental programming of sex-typical, stress-sensitive, and/or disorder-relevant phenotypes. Prenatal stress may alter these responses and dysregulate allopregnanolone and its normative effects on stress axis function. As an example of a neurodevelopmental, neuropsychiatric and/or neurodegenerative process, this review focuses on responsiveness to drugs of abuse, which is sensitive to prenatal stress and progestogen milieu. This review explores the notion that allopregnanolone may effect, or be influenced by, prenatal stress, with consequences for neurodevelopmental-, neuropsychiatric- and/or neurodegenerative- relevant processes, such as addiction.

  8. Distribution of linker histone variants during plant cell differentiation in the developmental zones of the maize root, dedifferentiation in callus culture after auxin treatment

    Directory of Open Access Journals (Sweden)

    ANASTASIOS ALATZAS

    2008-01-01

    Full Text Available Although several linker histone variants have been studied in both animal and plant organisms, little is known about their distribution during processes that involve alterations in chromatin function, such as differentiation, dedifferentiation and hormone treatment. In this study, we identified linker histone variants by using specific anti-histone Hl antibodies. Each variant's ratio to total Hl in the three developmental zones of maize (Zea mays L. root and in callus cultures derived from them was estimated in order to define possible alterations either during plant cell differentiation or during their dedifferentiation. We also evaluated linker histone variants' ratios in the developmental zones of maize roots treated with auxin in order to examine the effects of exogenous applied auxin to linker histone variant distribution. Finally, immunohistochemical detection was used to identify the root tissues containing each variant and correlate them with the physiological status of the plant cells. According to the results presented in this study, linker histone variants' ratios are altered in the developmental zones of maize root, while they are similar to the meristematic zone in samples from callus cultures and to the differentiation zone in samples from roots treated with auxin. We propose that the alterations in linker histone variants' ratios are correlated with plant cell differentiation and dedifferentiation.

  9. Developmental alterations in motor coordination and medium spiny neuron markers in mice lacking pgc-1α.

    Directory of Open Access Journals (Sweden)

    Elizabeth K Lucas

    Full Text Available Accumulating evidence implicates the transcriptional coactivator peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α in the pathophysiology of Huntington Disease (HD. Adult PGC-1α (-/- mice exhibit striatal neurodegeneration, and reductions in the expression of PGC-1α have been observed in striatum and muscle of HD patients as well as in animal models of the disease. However, it is unknown whether decreased expression of PGC-1α alone is sufficient to lead to the motor phenotype and striatal pathology characteristic of HD. For the first time, we show that young PGC-1α (-/- mice exhibit severe rotarod deficits, decreased rearing behavior, and increased occurrence of tremor in addition to the previously described hindlimb clasping. Motor impairment and striatal vacuolation are apparent in PGC-1α (-/- mice by four weeks of age and do not improve or decline by twelve weeks of age. The behavioral and pathological phenotype of PGC-1α (-/- mice can be completely recapitulated by conditional nervous system deletion of PGC-1α, indicating that peripheral effects are not responsible for the observed abnormalities. Evaluation of the transcriptional profile of PGC-1α (-/- striatal neuron populations and comparison to striatal neuron profiles of R6/2 HD mice revealed that PGC-1α deficiency alone is not sufficient to cause the transcriptional changes observed in this HD mouse model. In contrast to R6/2 HD mice, PGC-1α (-/- mice show increases in the expression of medium spiny neuron (MSN markers with age, suggesting that the observed behavioral and structural abnormalities are not primarily due to MSN loss, the defining pathological feature of HD. These results indicate that PGC-1α is required for the proper development of motor circuitry and transcriptional homeostasis in MSNs and that developmental disruption of PGC-1α leads to long-term alterations in motor functioning.

  10. Neuroimmune mechanisms of stress: sex differences, developmental plasticity, and implications for pharmacotherapy of stress-related disease.

    Science.gov (United States)

    Deak, Terrence; Quinn, Matt; Cidlowski, John A; Victoria, Nicole C; Murphy, Anne Z; Sheridan, John F

    2015-01-01

    The last decade has witnessed profound growth in studies examining the role of fundamental neuroimmune processes as key mechanisms that might form a natural bridge between normal physiology and pathological outcomes. Rooted in core concepts from psychoneuroimmunology, this review utilizes a succinct, exemplar-driven approach of several model systems that contribute significantly to our knowledge of the mechanisms by which neuroimmune processes interact with stress physiology. Specifically, we review recent evidence showing that (i) stress challenges produce time-dependent and stressor-specific patterns of cytokine/chemokine expression in the CNS; (ii) inflammation-related genes exhibit unique expression profiles in males and females depending upon individual, cooperative or antagonistic interactions between steroid hormone receptors (estrogen and glucocorticoid receptors); (iii) adverse social experiences incurred through repeated social defeat engage a dynamic process of immune cell migration from the bone marrow to brain and prime neuroimmune function and (iv) early developmental exposure to an inflammatory stimulus (carageenin injection into the hindpaw) has a lasting influence on stress reactivity across the lifespan. As such, the present review provides a theoretical framework for understanding the role that neuroimmune mechanisms might play in stress plasticity and pathological outcomes, while at the same time pointing toward features of the individual (sex, developmental experience, stress history) that might ultimately be used for the development of personalized strategies for therapeutic intervention in stress-related pathologies.

  11. Developmental dyscalculia.

    Science.gov (United States)

    Kucian, Karin; von Aster, Michael

    2015-01-01

    Numerical skills are essential in our everyday life, and impairments in the development of number processing and calculation have a negative impact on schooling and professional careers. Approximately 3 to 6 % of children are affected from specific disorders of numerical understanding (developmental dyscalculia (DD)). Impaired development of number processing skills in these children is characterized by problems in various aspects of numeracy as well as alterations of brain activation and brain structure. Moreover, DD is assumed to be a very heterogeneous disorder putting special challenges to define homogeneous diagnostic criteria. Finally, interdisciplinary perspectives from psychology, neuroscience and education can contribute to the design for interventions, and although results are still sparse, they are promising and have shown positive effects on behaviour as well as brain function. In the current review, we are going to give an overview about typical and atypical development of numerical abilities at the behavioural and neuronal level. Furthermore, current status and obstacles in the definition and diagnostics of DD are discussed, and finally, relevant points that should be considered to make an intervention as successful as possible are summarized.

  12. Development and Psychometric Evaluation of a Psychosocial Quality-of-Life Questionnaire for Individuals with Autism and Related Developmental Disorders

    Science.gov (United States)

    Markowitz, Leslie A.; Reyes, Charina; Embacher, Rebecca A.; Speer, Leslie L.; Roizen, Nancy; Frazier, Thomas W.

    2016-01-01

    This study investigated the psychometric properties of the Child and Family Quality of Life scale, a measure of psychosocial quality of life in those with autism and related developmental disorders. Parents of 212 children suspected of autism spectrum disorder completed the Child and Family Quality of Life prior to a diagnostic evaluation. Results…

  13. Social Anxiety in Childhood: Bridging Developmental and Clinical Perspectives

    Science.gov (United States)

    Gazelle, Heidi; Rubin, Kenneth H.

    2010-01-01

    In this introductory chapter, guided by developmental psychopathology and developmental science as overarching integrative theoretical frameworks, the authors define three constructs related to social anxiety in childhood (behavioral inhibition, anxious solitude/withdrawal, and social anxiety disorder) and analyze commonalities and differences in…

  14. Polychlorinated biphenyl-induced alterations of thyroid hormone homeostasis and brain development in the rat

    NARCIS (Netherlands)

    Morse, D.C.

    1995-01-01

    Introduction

    The work described in this thesis was undertaken to gain insight in the processes involved in the developmental neurotoxicity of polychlorinated biphenyls. It has been previously hypothesized that the alteration of thyroid hormone status by PCBs may

  15. Relation between infants'/toddlers' developmental status and their levels of object play

    Directory of Open Access Journals (Sweden)

    Urška Fekonja

    2001-06-01

    Full Text Available The purpose of introduced study was to establish the connection between the highest achieved levels of infant' and toddler's object play and their developmental status. 23 Slovenian infants and toddlers were included in the sample. They were engaged in solitary play with standard toys. Global and partial quotients were established using the early childhood development scale RT-R. The levels of child's solitary play were estimated using assesment scale designed by Belsky and Most. The results showed some statisticaly significant correlations between children's developmental qoutients (global and partial and their highest achieved levels of object play. As the basis for the interpretation of results I used the theories which explain the development of child's language, cognition and play.

  16. Towards Developmental Models of Psychiatric Disorders in Zebrafish

    Directory of Open Access Journals (Sweden)

    William Howard James Norton

    2013-04-01

    Full Text Available Psychiatric disorders are a diverse set of diseases that affect all aspects of mental function including social interaction, thinking, feeling and mood. Although psychiatric disorders place a large economic burden on society, the drugs available to treat them are often palliative with variable efficacy and intolerable side-effects. The development of novel drugs has been hindered by a lack of knowledge about the etiology of these diseases. It is thus necessary to further investigate psychiatric disorders using a combination of human molecular genetics, gene-by-environment studies, in vitro pharmacological and biochemistry experiments, animal models and investigation of the non-biological basis of these diseases, such as environmental effects.Many psychiatric disorders, including autism spectrum disorder, attention-deficit/hyperactivity disorder, mental retardation and schizophrenia can be triggered by alterations to neural development. The zebrafish is a popular model for developmental biology that is increasingly used to study human disease. Recent work has extended this approach to examine psychiatric disorders as well. However, since psychiatric disorders affect complex mental functions that might be human specific, it is not possible to fully model them in fish. In this review, I will propose that the suitability of zebrafish for developmental studies, and the genetic tools available to manipulate them, provide a powerful model to study the roles of genes that are linked to psychiatric disorders during neural development. The relative speed and ease of conducting experiments in zebrafish can be used to address two areas of future research: the contribution of environmental factors to disease onset, and screening for novel therapeutic compounds.

  17. White matter alterations in cocaine users are negatively related to the number of additionally (ab)used substances

    NARCIS (Netherlands)

    Kaag, A.M.; van Wingen, G.A.; Caan, M.W.A.; Homberg, J.R.; van den Brink, W.; Reneman, L.

    Diffusion tensor imaging studies have provided evidence for white matter (WM) alterations in cocaine users. While polysubstance use is a widespread phenomenon among cocaine users, its role in WM alterations in cocaine users is currently unknown. This study examined the relation between the number of

  18. Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

    International Nuclear Information System (INIS)

    Strakovsky, Rita S.; Wang, Huan; Engeseth, Nicki J.; Flaws, Jodi A.; Helferich, William G.; Pan, Yuan-Xiang; Lezmi, Stéphane

    2015-01-01

    Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate the potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague–Dawley rats were dosed with vehicle (oil) or BPA (100 μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG) and free fatty acid (FFA) compositions in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially through the epigenetic regulation of genes, and further alters the response to a HF diet. - Highlights: • Developmental BPA exposure exacerbates HF-diet induced steatosis in adult males. • Gestational BPA exposure increases hepatic lipid accumulation in neonatal males. • BPA decreases Cpt1a and other hepatic β-oxidation genes in neonatal males. • BPA alters neonatal male Cpt1a

  19. Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Strakovsky, Rita S.; Wang, Huan; Engeseth, Nicki J. [Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign (United States); Flaws, Jodi A. [Department of Comparative Biosciences, University of Illinois Urbana-Champaign (United States); Helferich, William G. [Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign (United States); Pan, Yuan-Xiang, E-mail: yxpan@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign (United States); Lezmi, Stéphane, E-mail: slezmi@illinois.edu [Department of Pathobiology, University of Illinois Urbana-Champaign (United States)

    2015-04-15

    Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate the potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague–Dawley rats were dosed with vehicle (oil) or BPA (100 μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG) and free fatty acid (FFA) compositions in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially through the epigenetic regulation of genes, and further alters the response to a HF diet. - Highlights: • Developmental BPA exposure exacerbates HF-diet induced steatosis in adult males. • Gestational BPA exposure increases hepatic lipid accumulation in neonatal males. • BPA decreases Cpt1a and other hepatic β-oxidation genes in neonatal males. • BPA alters neonatal male Cpt1a

  20. Health-related quality of life, developmental milestones, and self-esteem in young adults with bleeding disorders

    NARCIS (Netherlands)

    Limperg, P.F. (P. F.); L. Haverman (Lotte); H. Maurice-Stam (Heleen); M. Coppens; Valk, C. (C.); M.J.H.A. Kruip (Marieke); J.C.J. Eikenboom (Jeroen); M. Peters; M.A. Grootenhuis (Martha)

    2017-01-01

    textabstractBackground: The treatment of bleeding disorders improved in the last decades. However, the effect of growing up with bleeding disorders on developmental, emotional, and social aspects is understudied. Therefore, this study assesses HRQOL, developmental milestones, and self-esteem in

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

    Science.gov (United States)

    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. Health-related quality of life, developmental milestones, and self-esteem in young adults with bleeding disorders

    NARCIS (Netherlands)

    Limperg, P. F.; Haverman, L.; Maurice-Stam, H.; Coppens, M.; Valk, C.; Kruip, M. J. H. A.; Eikenboom, J.; Peters, M.; Grootenhuis, M. A.

    2018-01-01

    The treatment of bleeding disorders improved in the last decades. However, the effect of growing up with bleeding disorders on developmental, emotional, and social aspects is understudied. Therefore, this study assesses HRQOL, developmental milestones, and self-esteem in Dutch young adults (YA) with

  3. I. DEVELOPMENTAL METHODOLOGY AS A CENTRAL SUBDISCIPLINE OF DEVELOPMENTAL SCIENCE.

    Science.gov (United States)

    Card, Noel A

    2017-06-01

    This first chapter introduces the main goals of the monograph and previews the remaining chapters. The goals of this monograph are to provide summaries of our current understanding of advanced developmental methodologies, provide information that can advance our understanding of human development, identify shortcomings in our understanding of developmental methodology, and serve as a flagpost for organizing developmental methodology as a subdiscipline within the broader field of developmental science. The remaining chapters in this monograph address issues in design (sampling and big data), longitudinal data analysis, and issues of replication and research accumulation. The final chapter describes the history of developmental methodology, considers how the previous chapters in this monograph fit within this subdiscipline, and offers recommendations for further advancement. © 2017 The Society for Research in Child Development, Inc.

  4. Replication and robustness in developmental research.

    Science.gov (United States)

    Duncan, Greg J; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J

    2014-11-01

    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key results are robust across estimation methods, data sets, and demographic subgroups. This article makes the case for prioritizing both explicit replications and, especially, within-study robustness checks in developmental psychology. It provides evidence on variation in effect sizes in developmental studies and documents strikingly different replication and robustness-checking practices in a sample of journals in developmental psychology and a sister behavioral science-applied economics. Our goal is not to show that any one behavioral science has a monopoly on best practices, but rather to show how journals from a related discipline address vital concerns of replication and generalizability shared by all social and behavioral sciences. We provide recommendations for promoting graduate training in replication and robustness-checking methods and for editorial policies that encourage these practices. Although some of our recommendations may shift the form and substance of developmental research articles, we argue that they would generate considerable scientific benefits for the field. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2018-07-01

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

  7. Transient developmental Purkinje cell axonal torpedoes in healthy and ataxic mouse cerebellum

    Directory of Open Access Journals (Sweden)

    Lovisa Ljungberg

    2016-11-01

    Full Text Available Information is carried out of the cerebellar cortical microcircuit via action potentials propagated along Purkinje cell axons. In several human neurodegenerative diseases, focal axonal swellings on Purkinje cells – known as torpedoes – have been associated with Purkinje cell loss. Interestingly, torpedoes are also reported to appear transiently during development in rat cerebellum. The function of Purkinje cell axonal torpedoes in health as well as in disease is poorly understood. We investigated the properties of developmental torpedoes in the postnatal mouse cerebellum of wildtype and transgenic mice. We found that Purkinje cell axonal torpedoes transiently appeared on axons of Purkinje neurons, with the largest number of torpedoes observed at postnatal day 11 (P11. This was after peak developmental apoptosis had occurred, when Purkinje cell counts in a lobule were static, suggesting that most developmental torpedoes appear on axons of neurons that persist into adulthood. We found that developmental torpedoes were not associated with a presynaptic GABAergic marker, indicating that they are not synapses. They were seldom found at axonal collateral branch points, and lacked microglia enrichment, suggesting that they are unlikely to be involved in axonal refinement. Interestingly, we found several differences between developmental torpedoes and disease-related torpedoes: developmental torpedoes occured largely on myelinated axons, and were not associated with changes in basket cell innervation on their parent soma. Disease-related torpedoes are typically reported to contain neurofilament; while the majority of developmental torpedoes did as well, a fraction of smaller developmental torpedoes did not. These differences indicate that developmental torpedoes may not be functionally identical to disease-related torpedoes. To study this further, we used a mouse model of spinocerebellar ataxia type 6 (SCA6, and found elevated disease-related

  8. Altered aortic shape in bicuspid aortic valve relatives influences blood flow patterns.

    Science.gov (United States)

    Schnell, Susanne; Smith, Danielle A; Barker, Alex J; Entezari, Pegah; Honarmand, Amir R; Carr, Maria L; Malaisrie, S Chris; McCarthy, Patrick M; Collins, Jeremy; Carr, James C; Markl, Michael

    2016-11-01

    Bicuspid aortic valve (BAV) is known to exhibit familial inheritance and is associated with aortopathy and altered aortic haemodynamics. However, it remains unclear whether BAV-related aortopathy can be inherited independently of valve morphology. Four-dimensional flow magnetic resonance imaging for the in vivo assessment of thoracic aortic 3D blood flow was performed in 24 BAV relatives with trileaflet aortic valves (age = 40 ± 14 years) and 15 healthy controls (age = 37 ± 10 years). Data analysis included aortic dimensions, shape (round/gothic/cubic), and 3D blood flow characteristics (semi-quantitative vortex/helix grading and peak velocities). Cubic and gothic aortic shapes were markedly more prevalent in BAV relatives compared with controls (38 vs. 7%). Ascending aorta (AAo) vortex flow in BAV relatives was significantly increased compared with controls (grading = 1.5 ± 1.0 vs. 0.6 ± 0.9, P = 0.015). Aortic haemodynamics were influenced by aortic shape: peak velocities were reduced for gothic aortas vs. round aortas (P = 0.003); vortex flow was increased for cubic aortas in the AAo (P gothic aortas in the AAo and descending aorta (P = 0.003, P = 0.029). Logistic regression demonstrated significant associations of shape with severity of vortex flow in AAo (P < 0.001) and aortic arch (P = 0.016) in BAV relatives. BAV relatives expressed altered aortic shape and increased vortex flow despite the absence of valvular disease or aortic dilatation. These data suggest a heritable component of BAV-related aortopathy affecting aortic shape and aberrant blood flow, independent of valve morphology. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  9. Developmental transcriptomic analyses for mechanistic insights into critical pathways involved in embryogenesis of pelagic mahi-mahi (Coryphaena hippurus.

    Directory of Open Access Journals (Sweden)

    Elvis Genbo Xu

    Full Text Available Mahi-mahi (Coryphaena hippurus is a commercially and ecologically important species of fish occurring in tropical and temperate waters worldwide. Understanding early life events is crucial for predicting effects of environmental stress, which is largely restricted by a lack of genetic resources regarding expression of early developmental genes and regulation of pathways. The need for anchoring developmental stages to transcriptional activities is highlighted by increasing evidence on the impacts of recurrent worldwide oil spills in this sensitive species during early development. By means of high throughput sequencing, we characterized the developmental transcriptome of mahi-mahi at three critical developmental stages, from pharyngula embryonic stage (24 hpf to 48 hpf yolk-sac larva (transition 1, and to 96 hpf free-swimming larva (transition 2. With comparative analysis by multiple bioinformatic tools, a larger number of significantly altered genes and more diverse gene ontology terms were observed during transition 2 than transition 1. Cellular and tissue development terms were more significantly enriched in transition 1, while metabolism related terms were more enriched in transition 2, indicating a switch progressing from general embryonic development to metabolism during the two transitions. Special focus was given on the most significant common canonical pathways (e.g. calcium signaling, glutamate receptor signaling, cAMP response element-binding protein signaling, cardiac β-adrenergic signaling, etc. and expression of developmental genes (e.g. collagens, myosin, notch, glutamate metabotropic receptor etc., which were associated with morphological changes of nervous, muscular, and cardiovascular system. These data will provide an important basis for understanding embryonic development and identifying molecular mechanisms of abnormal development in fish species.

  10. Developmental Immunotoxicity, Perinatal Programming, and Noncommunicable Diseases: Focus on Human Studies

    Science.gov (United States)

    Dietert, Rodney R.

    2014-01-01

    Developmental immunotoxicity (DIT) is a term given to encompass the environmentally induced disruption of normal immune development resulting in adverse outcomes. A myriad of chemical, physical, and psychological factors can all contribute to DIT. As a core component of the developmental origins of adult disease, DIT is interlinked with three important concepts surrounding health risks across a lifetime: (1) the Barker Hypothesis, which connects prenatal development to later-life diseases, (2) the hygiene hypothesis, which connects newborns and infants to risk of later-life diseases and, (3) fetal programming and epigenetic alterations, which may exert effects both in later life and across future generations. This review of DIT considers: (1) the history and context of DIT research, (2) the fundamental features of DIT, (3) the emerging role of DIT in risk of noncommunicable diseases (NCDs) and (4) the range of risk factors that have been investigated through human research. The emphasis on the human DIT-related literature is significant since most prior reviews of DIT have largely focused on animal research and considerations of specific categories of risk factors (e.g., heavy metals). Risk factors considered in this review include air pollution, aluminum, antibiotics, arsenic, bisphenol A, ethanol, lead (Pb), maternal smoking and environmental tobacco smoke, paracetamol (acetaminophen), pesticides, polychlorinated biphenyls, and polyfluorinated compounds. PMID:26556429

  11. Is the Development of Offenders Related to Crime Scene Behaviors for Burglary? Including Situational Influences in Developmental and Life-Course Theories of Crime.

    Science.gov (United States)

    Fox, Bryanna Hahn; Farrington, David P

    2016-12-01

    Developmental and life-course (DLC) theories of crime aim to identify the causes and correlates of offending over the life span, focusing on the within-individual variations that result in criminal and delinquent behavior. Although there are several notable theories in the field, few contain both developmental and situational factors related to offending, and none explain why individuals commit crimes in different ways. This study aims to address these issues by developing typologies of burglars based on developmental and situational characteristics to help identify the various criminal career paths of the offenders, and how these different criminal careers may relate to the commission of offenses. Results of this study indicate that there are five different criminal career paths among the sampled burglars and four different styles of committing the same offense, and that burglars with certain criminal career features tend to commit a specific style of burglary. Through this research, we aim to extend DLC theories to create a more practical and contextual explanation of the relationship between criminal careers and the commission of offenses, and increase the level of within-individual explained variance in criminal behavior.

  12. Developmental trajectories in primary schoolchildren using n-back task

    Directory of Open Access Journals (Sweden)

    Mónica eLópez-Vicente

    2016-05-01

    Full Text Available Background: Neuropsychological instruments to assess cognitive trajectories during childhood in epidemiological studies are needed. This would improve neurodevelopment characterization in order to identify its potential determinants. We aimed to study whether repeated measures of n-back, a working memory task, detect developmental trajectories in schoolchildren during a one-year follow-up.Methods: We administered the n-back task to 2,897 healthy children aged 7-11 years old from 39 schools in Barcelona (Spain. The task consisted of 2 levels of complexity or loads (2- and 3-back and 2 different stimuli (numbers and words. Participants performed the task four times from January 2012 to March 2013. To study the trajectories during the follow-up, we performed linear mixed-effects models including school, individual and age as random effects.Results: We observed improvements related to age in n-back outcomes d’, HRT and accuracy, as well as reduced cognitive growth at older ages in d’ and HRT. Greater improvements in performance were observed at younger ages, in 2-back, in verbal rather than numerical stimuli and in girls compared to boys. Boys responded faster at baseline, while girls showed increased growth in 2-back numbers. Children with ADHD (Attention Deficit and Hyperactivity Disorder symptoms (15% of boys and 6% of girls had a lower working memory at baseline, but they showed similar cognitive growth trajectories in numbers variants of the task, as compared to children without ADHD symptoms. However, the age-related improvement in response speed was not observed in children with ADHD symptoms. Conclusions: Changes in n-back outcomes reflected developmental trajectories in one-year follow-up. The present results suggest that the repeated administration of this task can be used to study the factors that may alter the cognitive development during childhood.

  13. Temporal abnormalities in children with developmental dyscalculia.

    Science.gov (United States)

    Vicario, Carmelo Mario; Rappo, Gaetano; Pepi, Annamaria; Pavan, Andrea; Martino, Davide

    2012-01-01

    Recent imaging studies have associated Developmental dyscalculia (DD) to structural and functional alterations corresponding Parietal and the Prefrontal cortex (PFC). Since these areas were shown also to be involved in timing abilities, we hypothesized that time processing is abnormal in DD. We compared time processing abilities between 10 children with pure DD (8 years old) and 11 age-matched healthy children. Results show that the DD group underestimated duration of a sub-second scale when asked to perform a time comparison task. The timing abnormality observed in our DD participants is consistent with evidence of a shared fronto-parietal neural network for representing time and quantity.

  14. Use of airborne multispectral scanner data to map alteration related to roll-front uranium migration

    International Nuclear Information System (INIS)

    Peters, D.C.

    1983-01-01

    Computer-enhanced airborne multispectral scanner (MSS) images have been used to detect and map red oxidized alteration related to roll-front uranium migration in the southern Powder River basin, Wyoming. Information in the 0.4- to 1.1-μm spectral region was used to produce a color ratio composite image, upon which the red-altered areas can be differentiated. The red-altered and incipiently altered sandstones result from the migration of a roll-front (or geochemical cell) through the sandstone in the direction of the hydrologic gradient. Most uranium deposits in the Powder River basin occur at the boundary between this oxidized sandstone and reduced sandstone. Therefore, the ability to detect and map this alteration reliably can provide important information about the potential for uranium mineralization down gradient from the altered areas, at the surface in an area of interest. Spectral reflectance studies indicate that a shift in the absorption band edge from 0.52 μm (for goethitic sandstone) to 0.58 μm (for hematitic sandstone) and an intensification of an absorption band at 0.85 μm (for hematitic sandstone) are the bases for identifying the red-altered sandstone as green anomalous areas on the color ratio composite image. Some of the incipiently altered sandstone also appears green, whereas unaltered material and white-altered sandstone appear as blue to cyan colors. Therefore, the composite image is useful in discriminating hematitic sandstone from goethitic sandstone. At high densities (>65%), vegetation masks the sandstones on the color ratio composite image. Artemisia tridentata (sage) and Stipa comata (grass) are the species that have the greatest individual effect on the image

  15. Developmental programming: impact of prenatal testosterone excess on pre- and postnatal gonadotropin regulation in sheep.

    Science.gov (United States)

    Manikkam, Mohan; Thompson, Robert C; Herkimer, Carol; Welch, Kathleen B; Flak, Jonathan; Karsch, Fred J; Padmanabhan, Vasantha

    2008-04-01

    The goal of this study was to explore mechanisms that mediate hypersecretion of LH and progressive loss of cyclicity in female sheep exposed during fetal life to excess testosterone. Our working hypothesis was that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH (but not FSH) secretion and, thus, hypersecretion of LH in adulthood, and that this results from altered developmental gene expression of GnRH and estradiol (E2) receptors, gonadotropin subunits, and paracrine factors that differentially regulate LH and FSH synthesis. We observed that, relative to controls, females exposed during fetal life to excess testosterone, as well as the nor-aromatizable androgen dihydrotestosterone, exhibited enhanced LH but not FSH responses to intermittent delivery of GnRH boluses under conditions in which endogenous LH (GnRH) pulses were suppressed. Luteinizing hormone hypersecretion was more evident in adults than in prepubertal females, and it was associated with development of acyclicity. Measurement of pituitary mRNA concentrations revealed that prenatal testosterone excess induced developmental changes in gene expression of pituitary GnRH and E2 receptors and paracrine modulators of LH and FSH synthesis in a manner consistent with subsequent amplification of LH release. Together, this series of studies suggests that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH response, leading to LH hypersecretion and acyclicity in adulthood, and that this programming involves developmental changes in expression of pituitary genes involved in LH and FSH release.

  16. Developmental immunotoxicity testing of 4-methyl anisole.

    Science.gov (United States)

    Tonk, Elisa C M; Verhoef, Aart; Gremmer, Eric R; van Loveren, Henk; Piersma, Aldert H

    2015-07-01

    The developmental immunotoxicity of 4-methyl anisole (4MA) was investigated in the rat. Four study designs were used, with either premating or post-weaning onset of exposure, continued to postnatal day 50, and with or without additional oral gavage of pups from postnatal day 10 onward. Reduced litter size (benchmark dose lower confidence limit (BMDL) 80mg/kg bw/day) was the most sensitive developmental parameter, with pup relative organ weight effects observed at similar BMDLs, in the absence of maternal toxicity. Eosinophil numbers were reduced at lower doses (BMDL 16mg/kg bw/day). KLH challenge resulted in increased IL-13 and TNF-α responses, and variably reduced IgG production (BMDL 27mg/kg bw/day). T4 levels were reduced by 11% at maximum with a BMDL of 73mg/kg bw/day. Differences between exposure cohorts were limited and were considered to be without biological significance. This study shows that 4MA induces developmental immunotoxicity at doses below those inducing developmental and general toxicity. These observations being independent of the study designs applied suggest that the post-weaning period, included in all designs, is the most relevant sensitive period for inducing 4MA mediated developmental immunotoxicity. Moreover, this study stresses the importance of including developmental immunotoxicity testing by default in regulatory toxicology. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Factors Related to Problem Solving by College Students in Developmental Algebra.

    Science.gov (United States)

    Schonberger, Ann K.

    A study was conducted to contrast the characteristics of three groups of college students who completed a developmental algebra course at the University of Maine at Orono during 1980-81. On the basis of a two-part final examination, involving a multiple-choice test of algebraic concepts and skills and a free-response test of problem-solving…

  18. Developmental toxicology: adequacy of current methods.

    Science.gov (United States)

    Peters, P W

    1998-01-01

    Toxicology embraces several disciplines such as carcinogenicity, mutagenicity and reproductive toxicity. Reproductive toxicology is concerned with possible effects of substances on the reproductive process, i.e. on sexual organs and their functions, endocrine regulation, fertilization, transport of the fertilized ovum, implantation, and embryonic, fetal and postnatal development, until the end-differentiation of the organs is achieved. Reproductive toxicology is divided into areas related to male and female fertility, and developmental toxicology. Developmental toxicology can be further broken down into prenatal and postnatal toxicology. Today, much new information is available about the origins of developmental disorders resulting from chemical exposure. While these findings seem to promise important new developments in methodology and research, there is a danger of losing sight of the precepts and principles established in the light of existing knowledge. There is also a danger that we may fail to correct shortcomings in our existing procedures and practice. The aim of this presentation is to emphasize the importance of testing substances for their impact in advance of their use and to underline that we must use the best existing tools for carrying out risk assessments. Moreover, it needs to be stressed that there are many substances that are never assessed with respect to reproductive and developmental toxicity. Similarly, our programmes for post-marketing surveillance with respect to developmental toxicology are grossly inadequate. Our ability to identify risks to normal development and reproduction would be much improved, first if a number of straightforward precepts were always followed and second, if we had a clearer understanding of what we mean by risk and acceptable levels of risk in the context of development. Other aims of this paper are: to stress the complexity of the different stages of normal prenatal development; to note the principles that are

  19. Are Extremes of Consumption in Eating Disorders Related to an Altered Balance between Reward and Inhibition?

    Science.gov (United States)

    Wierenga, Christina E; Ely, Alice; Bischoff-Grethe, Amanda; Bailer, Ursula F; Simmons, Alan N; Kaye, Walter H

    2014-01-01

    The primary defining characteristic of a diagnosis of an eating disorder (ED) is the "disturbance of eating or eating-related behavior that results in the altered consumption or absorption of food" (DSM V; American Psychiatric Association, 2013). There is a spectrum, ranging from those who severely restrict eating and become emaciated on one end to those who binge and overconsume, usually accompanied by some form of compensatory behaviors, on the other. How can we understand reasons for such extremes of food consummatory behaviors? Recent work on obesity and substance use disorders has identified behaviors and neural pathways that play a powerful role in human consummatory behaviors. That is, corticostriatal limbic and dorsal cognitive neural circuitry can make drugs and food rewarding, but also engage self-control mechanisms that may inhibit their use. Importantly, there is considerable evidence that alterations of these systems also occur in ED. This paper explores the hypothesis that an altered balance of reward and inhibition contributes to altered extremes of response to salient stimuli, such as food. We will review recent studies that show altered sensitivity to reward and punishment in ED, with evidence of altered activity in corticostriatal and insula processes with respect to monetary gains or losses, and tastes of palatable foods. We will also discuss evidence for a spectrum of extremes of inhibition and dysregulation behaviors in ED supported by studies suggesting that this is related to top-down self-control mechanisms. The lack of a mechanistic understanding of ED has thwarted efforts for evidence-based approaches to develop interventions. Understanding how ED behavior is encoded in neural circuits would provide a foundation for developing more specific and effective treatment approaches.

  20. Neural changes associated to procedural learning and automatization process in Developmental Coordination Disorder and/or Developmental Dyslexia.

    Science.gov (United States)

    Biotteau, Maëlle; Péran, Patrice; Vayssière, Nathalie; Tallet, Jessica; Albaret, Jean-Michel; Chaix, Yves

    2017-03-01

    Recent theories hypothesize that procedural learning may support the frequent overlap between neurodevelopmental disorders. The neural circuitry supporting procedural learning includes, among others, cortico-cerebellar and cortico-striatal loops. Alteration of these loops may account for the frequent comorbidity between Developmental Coordination Disorder (DCD) and Developmental Dyslexia (DD). The aim of our study was to investigate cerebral changes due to the learning and automatization of a sequence learning task in children with DD, or DCD, or both disorders. fMRI on 48 children (aged 8-12) with DD, DCD or DD + DCD was used to explore their brain activity during procedural tasks, performed either after two weeks of training or in the early stage of learning. Firstly, our results indicate that all children were able to perform the task with the same level of automaticity, but recruit different brain processes to achieve the same performance. Secondly, our fMRI results do not appear to confirm Nicolson and Fawcett's model. The neural correlates recruited for procedural learning by the DD and the comorbid groups are very close, while the DCD group presents distinct characteristics. This provide a promising direction on the neural mechanisms associated with procedural learning in neurodevelopmental disorders and for understanding comorbidity. Published by Elsevier Ltd.

  1. A single dose of trichloroethylene given during development does not substantially alter markers of neuroinflammation in brains of adult mice.

    Science.gov (United States)

    Meadows, Jacqueline R; Parker, Chevonne; Gilbert, Kathleen M; Blossom, Sarah J; DeWitt, Jamie C

    2017-12-01

    Trichloroethylene (TCE) is a widespread environmental contaminant associated with developmental immunotoxicity and neurotoxicity. Previous studies have shown that MRL +/+ mice exposed to TCE from gestation through early-life demonstrate robust increases in inflammatory markers in peripheral CD4 + T-cells, as well as glutathione depletion and increased oxidative stress in cerebellum-associated with alterations in behavior. Since increased oxidative stress is associated with neuroinflammation, we hypothesized that neuroinflammatory markers could be altered relative to unexposed mice. MRL +/+ mice were given 0.5 mg/ml of TCE in vehicle or vehicle (water with 1% Alkamuls EL-620) from conception through early adulthood via drinking water to dams and then directly to post-weaning offspring. Animals were euthanized at 49 days of age and levels of pro- and anti-inflammatory cytokines, density of T-cell staining, and micro-glial morphology were evaluated in brains to begin to ascertain a neuroinflammatory profile. Levels of IL-6 were decreased in female animals and while not statistically significant, and levels of IL-10 were higher in brains of exposed male and female animals. Supportive of this observation, although not statistically significant, the number of ameboid microglia was higher in exposed relative to unexposed animals. This overall profile suggests the emergence of an anti-inflammatory/neuroprotective phenotype in exposed animals, possibly as a compensatory response to neuroinflammation that is known to be induced by developmental exposure to TCE.

  2. Health-related quality of life and peer relationships in adolescents with developmental coordination disorder and attention-deficit-hyperactivity disorder.

    Science.gov (United States)

    Dewey, Deborah; Volkovinskaia, Anna

    2018-07-01

    Health-related quality of life (HRQoL) and peer relationships were investigated in adolescents with developmental coordination disorder (DCD) and attention-deficit-hyperactivity disorder (ADHD). Adolescents with DCD (n=9), ADHD (n=9), DCD and ADHD (n=10), and typically developing adolescents (n=16) completed the following questionnaires: KIDSCREEN-52 Health-Related Quality of Life Questionnaire and Peer Relations Questionnaire for Children. Twenty-five participants took part in semi-structured interviews. Adolescents with DCD and ADHD had lower HRQoL on the mood and emotions, school environment, and financial resources scales of the KIDSCREEN-52 than adolescents in the DCD and typically developing groups (all p<0.05). On the Peer Relations Questionnaire for Children, the DCD and ADHD group reported significantly higher victimization compared with those in the typically developing (p=0.030) and DCD (p=0.010) groups. Qualitative interviews among young people with DCD and ADHD revealed feelings of marginalization and victimization. Descriptors such as 'misfits', 'oddballs', 'weird', and 'the rejects' were used to describe themselves. HRQoL and peer relationships are negatively affected in adolescents with DCD and ADHD. WHAT THIS PAPER ADDS?: Children with developmental coordination disorder (DCD) do not display poorer overall health-related quality of life (HRQoL) versus typically developing controls. Having DCD and attention-deficit-hyperactivity disorder (ADHD) was associated with poorer HRQoL. Adolescents with DCD and ADHD experience significantly higher levels of peer victimization than typically developing adolescents. HRQoL and peer relationships are significantly associated in adolescent respondents. © 2018 Mac Keith Press.

  3. The Effects of Psychopathology on the Pain Expression of Children and Youth with Intellectual and Developmental Disabilities

    Science.gov (United States)

    Breau, Lynn M.; Camfield, Carol S.

    2011-01-01

    Behavioral pain assessment is possible for children and youth with intellectual and developmental disabilities (IDD). However, pain behavior is often misinterpreted as reflecting psychopathology. We examined whether psychopathology alters pain behavior. Caregivers of 123 children (56 girls ages 40 to 258 months) completed the Non-Communicating…

  4. The two forms of capitalism: developmentalism and economic liberalism

    Directory of Open Access Journals (Sweden)

    LUIZ CARLOS BRESSER-PEREIRA

    Full Text Available ABSTRACT This paper argues that the state and the market are the main institutions regulating capitalism, and, correspondingly, that the form of the economic and political coordination of capitalism will be either developmental or liberal. It defines the developmental state, relates it to the formation of a developmental class coalition, and notes that capitalism was born developmental in its mercantilist phase, turned liberal in the nineteenth century, and, after 1929, became once again developmental, but, now, democratic and progressive. All industrial and capitalist revolutions took place within the framework of developmentalism, whereby the state coordinates the non-competitive sector of the economy and the five macroeconomic prices (which the market is unable to make “right”, while the market coordinates the competitive sector. In the 1970s, a crisis opened the way for a short-lived and reactionary form of capitalism, neoliberalism or rentier-financier capitalism. Since the 2008 Global Financial Crisis, the neoliberal hegemony has come to an end, and we are now experiencing a period of transition.

  5. Characteristics of international websites with information on developmental disabilities.

    Science.gov (United States)

    Reichow, Brian; Gelbar, Nicholas W; Mouradjian, Keri; Shefcyk, Allison; Smith, Isaac C

    2014-10-01

    The Internet often serves as a primary resource for individuals seeking health-related information, and a large and growing number of websites contain information related to developmental disabilities. This paper presents the results of an international evaluation of the characteristics and content of the top 10 ranked results (i.e., not including sponsored results - pay-per-click) returned when one of five terms related to developmental disabilities (i.e., ADHD, autism, down syndrome, learning disability, intellectual disability) was entered into one of six country specific Google online search engines (i.e., Australia (https://www.google.com.au), Canada (https://www.google.ca), Ireland (https://www.google.ie), New Zealand (https://www.google.co.nz), the United Kingdom (https://www.google.co.uk), and the United States (https://www.google.com)) on October 22, 2013. Collectively, we found that international consumers of websites related to developmental disabilities will encounter different websites with differing content and terminology, and should be critical consumers to ensure they locate the information they are seeking. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Oral Supplementation of Melatonin Protects against Fibromyalgia-Related Skeletal Muscle Alterations in Reserpine-Induced Myalgia Rats.

    Science.gov (United States)

    Favero, Gaia; Trapletti, Valentina; Bonomini, Francesca; Stacchiotti, Alessandra; Lavazza, Antonio; Rodella, Luigi Fabrizio; Rezzani, Rita

    2017-06-29

    Fibromyalgia is a chronic syndrome characterized by widespread musculoskeletal pain and an extensive array of other symptoms including disordered sleep, fatigue, depression and anxiety. Important factors involved in the pathogenic process of fibromyalgia are inflammation and oxidative stress, suggesting that ant-inflammatory and/or antioxidant supplementation might be effective in the management and modulation of this syndrome. Recent evidence suggests that melatonin may be suitable for this purpose due to its well known ant-inflammatory, antioxidant and analgesic effects. Thus, in the current study, the effects of the oral supplementation of melatonin against fibromyalgia-related skeletal muscle alterations were evaluated. In detail, 90 Sprague Dawley rats were randomly treated with reserpine, to reproduce the pathogenic process of fibromyalgia and thereafter they received melatonin. The animals treated with reserpine showed moderate alterations at hind limb skeletal muscles level and had difficulty in moving, together with significant morphological and ultrastructural alterations and expression of inflammatory and oxidative stress markers in the gastrocnemius muscle. Interestingly, melatonin, dose and/or time dependently, reduced the difficulties in spontaneous motor activity and the musculoskeletal morphostructural, inflammatory, and oxidative stress alterations. This study suggests that melatonin in vivo may be an effective tool in the management of fibromyalgia-related musculoskeletal morphofunctional damage.

  7. The Zebrafish Models to Explore Genetic and Epigenetic Impacts on Evolutionary Developmental Origins of Aging

    Science.gov (United States)

    Kishi, Shuji

    2014-01-01

    Can we reset, reprogram, rejuvenate or reverse the organismal aging process? Certain genetic manipulations could at least reset and reprogram epigenetic dynamics beyond phenotypic plasticity and elasticity in cells, which can be further manipulated into organisms. However, in a whole complex aging organism, how can we rejuvenate intrinsic resources and infrastructures in an intact/noninvasive manner? The incidence of diseases increases exponentially with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but essentially inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena to rejuvenate over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states based on diverse epigenotypes, in response to intrinsic or extrinsic environmental cues and genetic perturbations. We hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds and windows of plasticity and its robustness by molecular genetic and chemical epigenetic approaches, we have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during their embryonic and/or larval stages (“embryonic/larval senescence”). Subsequently, at least some of these mutant animals were found to show shortened lifespan, while some others would be expected to live longer in adulthoods. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other

  8. Developmental hyperoxia alters CNS mechanisms underlying hypoxic ventilatory depression in neonatal rats.

    Science.gov (United States)

    Hill, Corey B; Grandgeorge, Samuel H; Bavis, Ryan W

    2013-12-01

    Newborn mammals exhibit a biphasic hypoxic ventilatory response (HVR), but the relative contributions of carotid body-initiated CNS mechanisms versus central hypoxia on ventilatory depression during the late phase of the HVR are not well understood. Neonatal rats (P4-5 or P13-15) were treated with a nonselective P2 purinergic receptor antagonist (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, or PPADS; 125mgkg(-1), i.p.) to pharmacologically denervate the peripheral chemoreceptors. At P4-5, rats reared in normoxia showed a progressive decline in ventilation during a 10-min exposure to 12% O2 (21-28% decrease from baseline). No hypoxic ventilatory depression was observed in the older group of neonatal rats (i.e., P13-15), suggesting that the contribution of central hypoxia to hypoxic ventilatory depression diminishes with age. In contrast, rats reared in moderate hyperoxia (60% O2) from birth exhibited no hypoxic ventilatory depression at either age studied. Systemic PPADS had no effect on the ventilatory response to 7% CO2, suggesting that the drug did not cross the blood-brain barrier. These findings indicate that (1) CNS hypoxia depresses ventilation in young, neonatal rats independent of carotid body activation and (2) hyperoxia alters the development of CNS pathways that modulate the late phase of the hypoxic ventilatory response. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Do convergent developmental mechanisms underlie convergent phenotypes?

    Science.gov (United States)

    Wray, Gregory A.

    2002-01-01

    Convergence is a pervasive evolutionary process, affecting many aspects of phenotype and even genotype. Relatively little is known about convergence in developmental processes, however, nor about the degree to which convergence in development underlies convergence in anatomy. A switch in the ecology of sea urchins from feeding to nonfeeding larvae illustrates how convergence in development can be associated with convergence in anatomy. Comparisons to more distantly related taxa, however, suggest that this association may be limited to relatively close phylogenetic comparisons. Similarities in gene expression during development provide another window into the association between convergence in developmental processes and convergence in anatomy. Several well-studied transcription factors exhibit likely cases of convergent gene expression in distantly related animal phyla. Convergence in regulatory gene expression domains is probably more common than generally acknowledged, and can arise for several different reasons. Copyright 2002 S. Karger AG, Basel.

  10. Unilateral implicit motor learning deficit in developmental dyslexia.

    Science.gov (United States)

    Yang, Yang; Hong-Yan, Bi

    2011-02-01

    It has been suggested that developmental dyslexia involves various literacy, sensory, motor skill, and processing speed deficits. Some recent studies have shown that individuals with developmental dyslexia exhibit implicit motor learning deficits, which may be related to cerebellar functioning. However, previous studies on implicit motor learning in developmental dyslexics have produced conflicting results. Findings from cerebellar lesion patients have shown that patients' implicit motor learning performance varied when different hands were used to complete tasks. This suggests that dyslexia may have different effects on implicit motor learning between the two hands if cerebellar dysfunction is involved. To specify this question, we used a one-handed version of a serial reaction time task to compare the performance of 27 Chinese children with developmental dyslexics with another 27 age-matched children without reading difficulties. All the subjects were students from two primary schools, Grades 4 to 6. The results showed that children with developmental dyslexic responded more slowly than nondyslexic children, and exhibited no implicit motor learning in the condition of left-hand response. In contrast, there was no significant difference in reaction time between two groups of children when they used the right hand to respond. This finding indicates that children with developmental dyslexia exhibited normal motor skill and implicit motor learning ability provided the right hand was used. Taken together, these results suggested that Chinese children with developmental dyslexia exhibit unilateral deficits in motor skill and implicit motor learning in the left hand. Our findings lend partial support to the cerebellar deficit theory of developmental dyslexia.

  11. The diversification of developmental biology.

    Science.gov (United States)

    Crowe, Nathan; Dietrich, Michael R; Alomepe, Beverly S; Antrim, Amelia F; ByrneSim, Bay Lauris; He, Yi

    2015-10-01

    In the 1960s, "developmental biology" became the dominant term to describe some of the research that had previously been included under the rubrics of embryology, growth, morphology, and physiology. As scientific societies formed under this new label, a new discipline took shape. Historians, however, have a number of different perspectives on what changes led to this new field of developmental biology and how the field itself was constituted during this period. Using the General Embryological Information Service, a global index of post-World War II development-related research, we have documented and visualized significant changes in the kinds of research that occurred as this new field formed. In particular, our analysis supports the claim that the transition toward developmental biology was marked by a growth in new topics and forms of research. Although many historians privilege the role of molecular biology and/or the molecularization of biology in general during this formative period, we have found that the influence of molecular biology is not sufficient to account for the wide range of new research that constituted developmental biology at the time. Overall, our work creates a robust characterization of the changes that occurred with regard to research on growth and development in the decades following World War II and provides a context for future work on the specific drivers of those changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Are extremes of consumption in eating disorders related to an altered balance between reward and inhibition?

    Directory of Open Access Journals (Sweden)

    Christina E Wierenga

    2014-12-01

    Full Text Available The primary defining characteristic of a diagnosis of an eating disorder (ED is the disturbance of eating or eating-related behavior that results in the altered consumption or absorption of food (DSM V; American Psychiatric Association, 2013. There is a spectrum, ranging from those who severely restrict eating and become emaciated on one end to those who binge and overconsume, usually accompanied by some form of compensatory behaviors, on the other. How can we understand reasons for such extremes of food consummatory behaviors? Recent work on obesity and substance use disorders has identified behaviors and neural pathways that play a powerful role in human consummatory behaviors. That is, corticostriatal limbic and dorsal cognitive neural circuitry can make drugs and food rewarding, but also engage self-control mechanisms that may inhibit their use. Importantly, there is considerable evidence that alterations of these systems also occur in ED. This paper explores the hypothesis that an altered balance of reward and inhibition contributes to altered extremes of response to salient stimuli, such as food. We will review recent studies that show altered sensitivity to reward and punishment in ED, with evidence of altered activity in corticostriatal and insula processes with respect to monetary gains or losses, and tastes of palatable foods. We will also discuss evidence for a spectrum of extremes of inhibition and dysregulation behaviors in ED supported by studies suggesting that this is related to top-down self-control mechanisms. The lack of a mechanistic understanding of ED has thwarted efforts for evidence-based approaches to develop interventions. Understanding how ED behavior is encoded in neural circuits would provide a foundation for developing more specific and effective treatment approaches.

  13. The Significance of Human-Animal Relationships as Modulators of Trauma Effects in Children: A Developmental Neurobiological Perspective

    Science.gov (United States)

    Yorke, Jan

    2010-01-01

    Emotional stress and trauma impacts the neurobiology of children. They are especially vulnerable given the developmental plasticity of the brain. The neural synaptic circular processes between the anterior cingulated cortex, prefrontal cortex, amygdala and the hypothalamus are altered. Trauma results in the release of the peptide glucocortisoid,…

  14. Metabolic Syndrome in Obese Men and Women with Binge Eating Disorder: Developmental Trajectories of Eating and Weight-Related Behaviors

    OpenAIRE

    Blomquist, Kerstin K.; Milsom, Vanessa A.; Barnes, Rachel D.; Boeka, Abbe G.; White, Marney A.; Masheb, Robin M.; Grilo, Carlos M.

    2012-01-01

    The metabolic syndrome (MetSyn), characterized by vascular symptoms, is strongly correlated with obesity, weight-related medical diseases and mortality, and has increased commensurately with secular increases in obesity in the U.S. Little is known about the distribution of MetSynin obese patients with binge eating disorder (BED) or its associations with different developmental trajectories of dieting, binge eating, and obesity problems. Further, inconsistencies in the limited data necessitate...

  15. Analysing growth and development of plants jointly using developmental growth stages.

    Science.gov (United States)

    Dambreville, Anaëlle; Lauri, Pierre-Éric; Normand, Frédéric; Guédon, Yann

    2015-01-01

    Plant growth, the increase of organ dimensions over time, and development, the change in plant structure, are often studied as two separate processes. However, there is structural and functional evidence that these two processes are strongly related. The aim of this study was to investigate the co-ordination between growth and development using mango trees, which have well-defined developmental stages. Developmental stages, determined in an expert way, and organ sizes, determined from objective measurements, were collected during the vegetative growth and flowering phases of two cultivars of mango, Mangifera indica. For a given cultivar and growth unit type (either vegetative or flowering), a multistage model based on absolute growth rate sequences deduced from the measurements was first built, and then growth stages deduced from the model were compared with developmental stages. Strong matches were obtained between growth stages and developmental stages, leading to a consistent definition of integrative developmental growth stages. The growth stages highlighted growth asynchronisms between two topologically connected organs, namely the vegetative axis and its leaves. Integrative developmental growth stages emphasize that developmental stages are closely related to organ growth rates. The results are discussed in terms of the possible physiological processes underlying these stages, including plant hydraulics, biomechanics and carbohydrate partitioning. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Toward a Neuroscience of Adult Cognitive Developmental Theory

    Directory of Open Access Journals (Sweden)

    Fady Girgis

    2018-01-01

    Full Text Available Piaget's genetic epistemology has provided the constructivist approach upon which child developmental theories were founded, in that infants are thought to progress through distinct cognitive stages until they reach maturity in their early 20's. However, it is now well established that cognition continues to develop after early adulthood, and several “neo-Piagetian” theories have emerged in an attempt to better characterize adult cognitive development. For example, Kegan's Constructive Developmental Theory (CDT argues that the thought processes used by adults to construct their reality change over time, and reaching higher stages of cognitive development entails becoming objectively aware of emotions and beliefs that were previously in the realm of the subconscious. In recent years, neuroscience has shown a growing interest in the biological substrates and neural mechanisms encompassing adult cognitive development, because psychological and psychiatric disorders can arise from deficiencies therein. In this article, we will use Kegan's CDT as a framework to discuss adult cognitive development in relation to closely correlated existing constructs underlying social processing, such as the perception of self and others. We will review the functional imaging and electrophysiologic evidence behind two key concepts relating to these posited developmental changes. These include self-related processing, a field that distinguishes between having conscious experiences (“being a self” and being aware of oneself having conscious experiences (“being aware of being a self”; and theory of mind, which is the objective awareness of possessing mental states such as beliefs and desires (i.e., having a “mind” and the understanding that others possess mental states that can be different from one's own. We shall see that cortical midline structures, including the medial prefrontal cortex and cingulate gyrus, as well as the temporal lobe, are associated

  17. Toward a Neuroscience of Adult Cognitive Developmental Theory.

    Science.gov (United States)

    Girgis, Fady; Lee, Darrin J; Goodarzi, Amir; Ditterich, Jochen

    2018-01-01

    Piaget's genetic epistemology has provided the constructivist approach upon which child developmental theories were founded, in that infants are thought to progress through distinct cognitive stages until they reach maturity in their early 20's. However, it is now well established that cognition continues to develop after early adulthood, and several "neo-Piagetian" theories have emerged in an attempt to better characterize adult cognitive development. For example, Kegan's Constructive Developmental Theory (CDT) argues that the thought processes used by adults to construct their reality change over time, and reaching higher stages of cognitive development entails becoming objectively aware of emotions and beliefs that were previously in the realm of the subconscious. In recent years, neuroscience has shown a growing interest in the biological substrates and neural mechanisms encompassing adult cognitive development, because psychological and psychiatric disorders can arise from deficiencies therein. In this article, we will use Kegan's CDT as a framework to discuss adult cognitive development in relation to closely correlated existing constructs underlying social processing, such as the perception of self and others. We will review the functional imaging and electrophysiologic evidence behind two key concepts relating to these posited developmental changes. These include self-related processing, a field that distinguishes between having conscious experiences ("being a self") and being aware of oneself having conscious experiences ("being aware of being a self"); and theory of mind, which is the objective awareness of possessing mental states such as beliefs and desires (i.e., having a "mind") and the understanding that others possess mental states that can be different from one's own. We shall see that cortical midline structures, including the medial prefrontal cortex and cingulate gyrus, as well as the temporal lobe, are associated with psychological tasks that

  18. Cumulative risk and developmental health: an argument for the importance of a family-wide science.

    Science.gov (United States)

    Browne, Dillon T; Plamondon, Andre; Prime, Heather; Puente-Duran, Sofia; Wade, Mark

    2015-01-01

    A substantial body of research links social disadvantage and developmental health via a cascade running from poverty, to cumulative psychosocial risk, to disrupted family dynamics, to child biological regulatory systems and neurocognitive processing, and finally to morbidity across the lifespan. Most research in this area employs single-dyad or between-family methodology. While informative, there are limitations to this approach. Specifically, it is impossible to determine how risk alters psychosocial environments that are similar for all persons within a household, versus processes that are unique to particular children. This is important in light of literature citing the primacy of child-specific environments in driving developmental health. Methodologically speaking, there are both benefits and challenges to family-wide approaches that differentiate between- and within-family environments. This review describes literature linking cumulative risk and developmental health via family process, while articulating the importance of family-wide approaches. Areas of shortcoming and recommendations for a family-wide science are provided. © 2015 John Wiley & Sons, Ltd.

  19. The influence of altered working-side occlusal guidance on masticatory muscles and related jaw movement.

    Science.gov (United States)

    Belser, U C; Hannam, A G

    1985-03-01

    The effect of four different occlusal situations (group function, canine guidance, working side occlusal interference, and hyperbalancing occlusal interference) on EMG activity in jaw elevator muscles and related mandibular movement was investigated on 12 subjects. With a computer-based system, EMG and displacement signals were collected simultaneously during specific functional (unilateral chewing) and parafunctional tasks (mandibular gliding movements and various tooth clenching efforts) and analyzed quantitatively. When a naturally acquired group function was temporarily and artificially changed into a dominant canine guidance, a significant general reduction of elevator muscle activity was observed when subjects exerted full isometric tooth-clenching efforts in a lateral mandibular position. The original muscular coordination pattern (relative contraction from muscle to muscle) remained unaltered during this test. With respect to unilateral chewing, no significant alterations in the activity or coordination of the muscles occurred when an artificial canine guidance was introduced. Introduction of a hyperbalancing occlusal contact caused significant alterations in muscle activity and coordination during maximal tooth clenching in a lateral mandibular position. A marked shift of temporal muscle EMG activity toward the side of the interference and unchanged bilateral activity of the two masseter muscles were observed. The results suggest that canine-protected occlusions do not significantly alter muscle activity during mastication but significantly reduce muscle activity during parafunctional clenching. They also suggest that non-working side contacts dramatically alter the distribution of muscle activity during parafunctional clenching, and that this redistribution may affect the nature of reaction forces at the temporomandibular joints.

  20. Physical activity attenuates age-related biomarker alterations in preclinical AD.

    Science.gov (United States)

    Okonkwo, Ozioma C; Schultz, Stephanie A; Oh, Jennifer M; Larson, Jordan; Edwards, Dorothy; Cook, Dane; Koscik, Rebecca; Gallagher, Catherine L; Dowling, N M; Carlsson, Cynthia M; Bendlin, Barbara B; LaRue, Asenath; Rowley, Howard A; Christian, Brad T; Asthana, Sanjay; Hermann, Bruce P; Johnson, Sterling C; Sager, Mark A

    2014-11-04

    To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent (11)C-Pittsburgh compound B-PET (n = 186) and (18)F-fluorodeoxyglucose-PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group. In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life. © 2014 American Academy of Neurology.

  1. Right cerebral hemisphere and central auditory processing in children with developmental dyslexia

    Directory of Open Access Journals (Sweden)

    Paulina C. Murphy-Ruiz

    2013-11-01

    Full Text Available Objective We hypothesized that if the right hemisphere auditory processing abilities can be altered in children with developmental dyslexia (DD, we can detect dysfunction using specific tests. Method We performed an analytical comparative cross-sectional study. We studied 20 right-handed children with DD and 20 healthy right-handed control subjects (CS. Children in both groups were age, gender, and school-grade matched. Focusing on the right hemisphere’s contribution, we utilized tests to measure alterations in central auditory processing (CAP, such as determination of frequency patterns; sound duration; music pitch recognition; and identification of environmental sounds. We compared results among the two groups. Results Children with DD showed lower performance than CS in all CAP subtests, including those that preferentially engaged the cerebral right hemisphere. Conclusion Our data suggests a significant contribution of the right hemisphere in alterations of CAP in children with DD. Thus, right hemisphere CAP must be considered for examination and rehabilitation of children with DD.

  2. Effect of Developmental Stimulation Program on the Developmental Measures of Toddlers

    Directory of Open Access Journals (Sweden)

    Elahe Ghayebie

    2018-04-01

    Full Text Available Background: The variability in the developmental skills is reduced after the first three years of life; therefore, it is necessary to identify and manage early developmental delays. Aim: The aim of this study was to investigate the effect of developmental stimulation program on the developmental measures of the toddlers. Method: The present randomized controlled clinical trial was conducted on 31 toddlers aged 1-3 years residing at Ali Asghar Foster Care Center within 2016-2017. Developmental interventions were carried out based on the modified guidelines of West Virginia Early Learning Standards Framework for eight weeks (three 2-hour sessions a week. The interventions included a range of age- and developmental-specific activities described in the given guidelines. Child development age was measured based on motor dimensions (i.e., gross and fine and language development (i.e., receptive and expressive before and after the intervention. The data were analyzed in SPSS software (version 11 using independent t-test and Chi-square test. Results: The mean ages of the participants in the control and intervention groups were 19.9±5.5 and 20±6.02, respectively (P=0.62. The mean ages of receptive language development (P=0.003, expressive language development (P

  3. Social-Vocational Skills of Developmentally Disabled and Nonhandicapped Workers in Two Community Employment Sites

    OpenAIRE

    Lignugaris/Kraft, Benjamin; Salzberg, Charles L.; Rule, S.; Stowitschek, J. J.

    1988-01-01

    The social interactions of employees with and without developmental disabilities were observed in two community employment settings during work and breaks. Conversations were frequent and generally concerned work-related topics. Target workers different in how often they interacted with coworkers with and without developmental disabilities. During work, workers with developmental disabilities received commands more often than did their counterparts without developmental disabilities. Work-rel...

  4. Violent Victimization and Perpetration during Adolescence: Developmental Stage Dependent Ecological Models

    Science.gov (United States)

    Matjasko, Jennifer L.; Needham, Belinda L.; Grunden, Leslie N.; Farb, Amy Feldman

    2010-01-01

    Using a variant of the ecological-transactional model and developmental theories of delinquency on a nationally representative sample of adolescents, the current study explored the ecological predictors of violent victimization, perpetration, and both for three different developmental stages during adolescence. We examined the relative influence…

  5. 48 CFR 919.7011 - Developmental assistance.

    Science.gov (United States)

    2010-10-01

    ... limited to: (1) Management guidance relating to: (i) Financial management, (ii) Organizational management, (iii) Overall business management planning, (iv) Business development, and (v) Marketing assistance; (2... PROGRAMS SMALL BUSINESS PROGRAMS The Department of Energy Mentor-Protege Program 919.7011 Developmental...

  6. Field Trip Guide to Serpentinite, Silica-Carbonate Alteration, and Related Hydrothermal Activity in the Clear Lake Region, California

    Energy Technology Data Exchange (ETDEWEB)

    Fraser Goff; George Guthrie

    1999-06-01

    This guide is designed to familiarize scientists with the geology, structure, alteration, and fluids typical of California serpentinites for purposes of carbon dioxide sequestration (Lackner et al., 1995). Goff et al. (1997) and Goff and Lackner (1998) describe the geology and geochemistry of some of the serpentinites from this area. Mechanisms of silica-carbonate alteration were outlined by Barnes et al. (1973). Donnelly-Nolan et al. (1993) most recently reviewed relations between regional hydrothermal alteration and Quarternary volcanic activity. Stanley et al. (1998) summarized geophysical characteristics of the region.

  7. Developmental Ethanol Exposure Causes Reduced Feeding and Reveals a Critical Role for Neuropeptide F in Survival

    Science.gov (United States)

    Guevara, Amanda; Gates, Hillary; Urbina, Brianna; French, Rachael

    2018-01-01

    Food intake is necessary for survival, and natural reward circuitry has evolved to help ensure that animals ingest sufficient food to maintain development, growth, and survival. Drugs of abuse, including alcohol, co-opt the natural reward circuitry in the brain, and this is a major factor in the reinforcement of drug behaviors leading to addiction. At the junction of these two aspects of reward are alterations in feeding behavior due to alcohol consumption. In particular, developmental alcohol exposure (DAE) results in a collection of physical and neurobehavioral disorders collectively referred to as Fetal Alcohol Spectrum Disorder (FASD). The deleterious effects of DAE include intellectual disabilities and other neurobehavioral changes, including altered feeding behaviors. Here we use Drosophila melanogaster as a genetic model organism to study the effects of DAE on feeding behavior and the expression and function of Neuropeptide F. We show that addition of a defined concentration of ethanol to food leads to reduced feeding at all stages of development. Further, genetic conditions that reduce or eliminate NPF signaling combine with ethanol exposure to further reduce feeding, and the distribution of NPF is altered in the brains of ethanol-supplemented larvae. Most strikingly, we find that the vast majority of flies with a null mutation in the NPF receptor die early in larval development when reared in ethanol, and provide evidence that this lethality is due to voluntary starvation. Collectively, we find a critical role for NPF signaling in protecting against altered feeding behavior induced by developmental ethanol exposure. PMID:29623043

  8. The Diagnostic Yield of Array Comparative Genomic Hybridization Is High Regardless of Severity of Intellectual Disability/Developmental Delay in Children.

    Science.gov (United States)

    D'Arrigo, Stefano; Gavazzi, Francesco; Alfei, Enrico; Zuffardi, Orsetta; Montomoli, Cristina; Corso, Barbara; Buzzi, Erika; Sciacca, Francesca L; Bulgheroni, Sara; Riva, Daria; Pantaleoni, Chiara

    2016-05-01

    Microarray-based comparative genomic hybridization is a method of molecular analysis that identifies chromosomal anomalies (or copy number variants) that correlate with clinical phenotypes. The aim of the present study was to apply a clinical score previously designated by de Vries to 329 patients with intellectual disability/developmental disorder (intellectual disability/developmental delay) referred to our tertiary center and to see whether the clinical factors are associated with a positive outcome of aCGH analyses. Another goal was to test the association between a positive microarray-based comparative genomic hybridization result and the severity of intellectual disability/developmental delay. Microarray-based comparative genomic hybridization identified structural chromosomal alterations responsible for the intellectual disability/developmental delay phenotype in 16% of our sample. Our study showed that causative copy number variants are frequently found even in cases of mild intellectual disability (30.77%). We want to emphasize the need to conduct microarray-based comparative genomic hybridization on all individuals with intellectual disability/developmental delay, regardless of the severity, because the degree of intellectual disability/developmental delay does not predict the diagnostic yield of microarray-based comparative genomic hybridization. © The Author(s) 2015.

  9. Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β) Signaling in Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Khin, Sann Sanda [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Pathology Research Unit, Department of Medical Research (Central Myanmar), Naypyitaw, Union of (Myanmar); Kitazawa, Riko [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan); Kondo, Takeshi; Idei, Yuka; Fujimoto, Masayo [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Haraguchi, Ryuma [Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan); Mori, Kiyoshi [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Kitazawa, Sohei, E-mail: kitazawa@m.ehime-u.ac.jp [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan)

    2011-03-03

    Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP) do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β), induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression.

  10. Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β) Signaling in Cancer

    International Nuclear Information System (INIS)

    Khin, Sann Sanda; Kitazawa, Riko; Kondo, Takeshi; Idei, Yuka; Fujimoto, Masayo; Haraguchi, Ryuma; Mori, Kiyoshi; Kitazawa, Sohei

    2011-01-01

    Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP) do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β), induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression

  11. Developmental vitamin D deficiency causes abnormal brain development.

    Science.gov (United States)

    Eyles, D W; Feron, F; Cui, X; Kesby, J P; Harms, L H; Ko, P; McGrath, J J; Burne, T H J

    2009-12-01

    There is now clear evidence that vitamin D is involved in brain development. Our group is interested in environmental factors that shape brain development and how this may be relevant to neuropsychiatric diseases including schizophrenia. The origins of schizophrenia are considered developmental. We hypothesised that developmental vitamin D (DVD) deficiency may be the plausible neurobiological explanation for several important epidemiological correlates of schizophrenia namely: (1) the excess winter/spring birth rate, (2) increased incidence of the disease in 2nd generation Afro-Caribbean migrants and (3) increased urban birth rate. Moreover we have published two pieces of direct epidemiological support for this hypothesis in patients. In order to establish the "Biological Plausibility" of this hypothesis we have developed an animal model to study the effect of DVD deficiency on brain development. We do this by removing vitamin D from the diet of female rats prior to breeding. At birth we return all dams to a vitamin D containing diet. Using this procedure we impose a transient, gestational vitamin D deficiency, while maintaining normal calcium levels throughout. The brains of offspring from DVD-deficient dams are characterised by (1) a mild distortion in brain shape, (2) increased lateral ventricle volumes, (3) reduced differentiation and (4) diminished expression of neurotrophic factors. As adults, the alterations in ventricular volume persist and alterations in brain gene and protein expression emerge. Adult DVD-deficient rats also display behavioural sensitivity to agents that induce psychosis (the NMDA antagonist MK-801) and have impairments in attentional processing. In this review we summarise the literature addressing the function of vitamin D on neuronal and non-neuronal cells as well as in vivo results from DVD-deficient animals. Our conclusions from these data are that vitamin D is a plausible biological risk factor for neuropsychiatric disorders and that

  12. Building a developmental toxicity ontology.

    Science.gov (United States)

    Baker, Nancy; Boobis, Alan; Burgoon, Lyle; Carney, Edward; Currie, Richard; Fritsche, Ellen; Knudsen, Thomas; Laffont, Madeleine; Piersma, Aldert H; Poole, Alan; Schneider, Steffen; Daston, George

    2018-04-03

    As more information is generated about modes of action for developmental toxicity and more data are generated using high-throughput and high-content technologies, it is becoming necessary to organize that information. This report discussed the need for a systematic representation of knowledge about developmental toxicity (i.e., an ontology) and proposes a method to build one based on knowledge of developmental biology and mode of action/ adverse outcome pathways in developmental toxicity. This report is the result of a consensus working group developing a plan to create an ontology for developmental toxicity that spans multiple levels of biological organization. This report provide a description of some of the challenges in building a developmental toxicity ontology and outlines a proposed methodology to meet those challenges. As the ontology is built on currently available web-based resources, a review of these resources is provided. Case studies on one of the most well-understood morphogens and developmental toxicants, retinoic acid, are presented as examples of how such an ontology might be developed. This report outlines an approach to construct a developmental toxicity ontology. Such an ontology will facilitate computer-based prediction of substances likely to induce human developmental toxicity. © 2018 Wiley Periodicals, Inc.

  13. Developmental enamel defects and their impact on child oral health-related quality of life

    Directory of Open Access Journals (Sweden)

    Fabiana Vargas-Ferreira

    2011-12-01

    Full Text Available This cross-sectional study assessed the impact of Developmental Enamel Defects (DED on Child Oral Health-Related Quality of Life (COHRQoL. A sample of 944 11- to 14-year-old Brazilian schoolchildren was examined for the prevalence and severity of DED. The children completed the Child Perceptions Questionnaire (CPQ11-14, and socioeconomic status was also collected using a questionnaire. Poisson regression models were used to assess the association between DED and overall and domain-specific CPQ11-14 scores. The prevalence of DED was 19.7%. In general, children with DED did not indicate any decrease in self-perception. However, this condition was associated with an impact on the functional limitation domain. The presence of DED may cause negative impacts on a child's perception of oral health and on their daily performance.

  14. Transgenerational developmental programming.

    Science.gov (United States)

    Aiken, Catherine E; Ozanne, Susan E

    2014-01-01

    The concept of developmental programming suggests that the early life environment influences offspring characteristics in later life, including the propensity to develop diseases such as the metabolic syndrome. There is now growing evidence that the effects of developmental programming may also manifest in further generations without further suboptimal exposure. This review considers the evidence, primarily from rodent models, for effects persisting to subsequent generations, and evaluates the mechanisms by which developmental programming may be transmitted to further generations. In particular, we focus on the potential role of the intrauterine environment in contributing to a developmentally programmed phenotype in subsequent generations. The literature was systematically searched at http://pubmed.org and http://scholar.google.com to identify published findings regarding transgenerational (F2 and beyond) developmental programming effects in human populations and animal models. Transmission of programming effects is often viewed as a form of epigenetic inheritance, either via the maternal or paternal line. Evidence exists for both germline and somatic inheritance of epigenetic modifications which may be responsible for phenotypic changes in further generations. However, there is increasing evidence for the role of both extra-genomic components of the zygote and the interaction of the developing conceptus with the intrauterine environment in propagating programming effects. The contribution of a suboptimal reproductive tract environment or maternal adaptations to pregnancy may be critical to inheritance of programming effects via the maternal line. As the effects of age exacerbate the programmed metabolic phenotype, advancing maternal age may increase the likelihood of developmental programming effects being transmitted to further generations. We suggest that developmental programming effects could be propagated through the maternal line de novo in generations

  15. Developmental coordination disorder: evaluation and treatment.

    NARCIS (Netherlands)

    Leemrijse, C.

    2003-01-01

    A child's popularity is often related to his or her proficiency in sports and games, and children value physical competence highly. The movement difficulties of children with developmental coordination disorder (DCD) often invite ridicule from their peers. Children with DCD have a poor motor

  16. 48 CFR 819.7110 - Developmental assistance.

    Science.gov (United States)

    2010-10-01

    ... to, the following: (a) Guidance relating to— (1) Financial management; (2) Organizational management; (3) Overall business management/planning; (4) Business development; and (5) Technical assistance. (b... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS VA Mentor-Protégé Program 819.7110 Developmental assistance...

  17. 48 CFR 519.7012 - Developmental assistance.

    Science.gov (United States)

    2010-10-01

    ... guidance relating to— (1) Financial management; (2) Organizational management; (3) Overall business management/planning; and (4) Business development. (b) Engineering and other technical assistance. (c) Loans... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7012 Developmental assistance...

  18. Developmental vitamin D deficiency and schizophrenia: the role of animal models.

    Science.gov (United States)

    Schoenrock, S A; Tarantino, L M

    2016-01-01

    Schizophrenia is a debilitating neuropsychiatric disorder that affects 1% of the US population. Based on twin and genome-wide association studies, it is clear that both genetics and environmental factors increase the risk for developing schizophrenia. Moreover, there is evidence that conditions in utero, either alone or in concert with genetic factors, may alter neurodevelopment and lead to an increased risk for schizophrenia. There has been progress in identifying genetic loci and environmental exposures that increase risk, but there are still considerable gaps in our knowledge. Furthermore, very little is known about the specific neurodevelopmental mechanisms upon which genetics and the environment act to increase disposition to developing schizophrenia in adulthood. Vitamin D deficiency during the perinatal period has been hypothesized to increase risk for schizophrenia in humans. The developmental vitamin D (DVD) deficiency hypothesis of schizophrenia arises from the observation that disease risk is increased in individuals who are born in winter or spring, live further from the equator or live in urban vs. rural settings. These environments result in less exposure to sunlight, thereby reducing the initial steps in the production of vitamin D. Rodent models have been developed to characterize the behavioral and developmental effects of DVD deficiency. This review focuses on these animal models and discusses the current knowledge of the role of DVD deficiency in altering behavior and neurobiology relevant to schizophrenia. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  19. Congenital heart malformations induced by hemodynamic altering surgical interventions

    Directory of Open Access Journals (Sweden)

    Madeline eMidgett

    2014-08-01

    Full Text Available Embryonic heart formation results from a dynamic interplay between genetic and environmental factors. Blood flow during early embryonic stages plays a critical role in heart development, as interactions between flow and cardiac tissues generate biomechanical forces that modulate cardiac growth and remodeling. Normal hemodynamic conditions are essential for proper cardiac development, while altered blood flow induced by surgical manipulations in animal models result in heart defects similar to those seen in humans with congenital heart disease. This review compares the altered hemodynamics, changes in tissue properties, and cardiac defects reported after common surgical interventions that alter hemodynamics in the early chick embryo, and shows that interventions produce a wide spectrum of cardiac defects. Vitelline vein ligation and left atrial ligation decrease blood pressure and flow; and outflow tract banding increases blood pressure and flow velocities. These three surgical interventions result in many of the same cardiac defects, which indicate that the altered hemodynamics interfere with common looping, septation and valve formation processes that occur after intervention and that shape the four-chambered heart. While many similar defects develop after the interventions, the varying degrees of hemodynamic load alteration among the three interventions also result in varying incidence and severity of cardiac defects, indicating that the hemodynamic modulation of cardiac developmental processes is strongly dependent on hemodynamic load.

  20. Developmental Trajectories of Male Physical Violence and Theft

    Science.gov (United States)

    Barker, Edward D.; Séguin, Jean R.; White, Helene Raskin; Bates, Marsha E.; Lacourse, Éric; Carbonneau, René; Tremblay, Richard E.

    2012-01-01

    Context Neurocognitive mechanisms have long been hypothesized to influence developmental trajectories of antisocial behavior. However, studies examining this association tend to aggregate a variety of problem behaviors that may be differently affected by neurocognitive deficits. Objective To describe the developmental trajectories of physical violence and theft from adolescence to adulthood, their associations, and the neurocognitive characteristics of individuals following different patterns of trajectory association. Design Accelerated cohort-sequential, longitudinal design. Setting Rutgers Health and Human Development Project. Participants Six hundred ninety-eight men. Main Outcome Measures Self-reports of physical violence (ages 12–24 years) and theft (ages 12–31 years) were collected across 5 waves. Neurocognitive performance was assessed with executive function and verbal IQ tests between late adolescence and early adulthood. Results The majority (55%) of subjects showed an increased frequency of theft during the study period, while only a minority (13%) evinced an increasing frequency of physical violence. Executive function and verbal IQ performance were negatively related to high frequency of physical violence but positively related to high frequency of theft. Conclusions Developmental trajectories of physical violence and theft during adolescence and early adulthood are different and differently related to neurocognitive functioning. Global indexes of antisocial behavior mask the development of antisocial behavior subtypes and putative causal mechanisms. PMID:17485611

  1. The role of organizational insiders' developmental feedback and proactive personality on newcomers' performance: an interactionist perspective.

    Science.gov (United States)

    Li, Ning; Harris, T Brad; Boswell, Wendy R; Xie, Zhitao

    2011-11-01

    Drawing from an interactionist approach and feedback research, we examine the role of developmental feedback and proactive personality on newcomer task performance and helping behavior. Data were collected from 2 high-tech joint-ventures within the information technology and manufacturing industries located in Shanghai, China. Results based on 151 newcomer-manager dyads showed that supervisor developmental feedback (SDF) positively related to newcomer helping behavior and that SDF and coworker developmental feedback interactively predicted newcomer task performance. We also found differential moderating effects of proactive personality: SDF more strongly related to helping behavior when proactive personality was lower; conversely, coworker developmental feedback more strongly related to helping behavior when proactive personality was higher. (c) 2011 APA, all rights reserved.

  2. Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum

    Directory of Open Access Journals (Sweden)

    Aisa N. Chepkova

    2015-01-01

    Full Text Available Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old to old (18–24 months of age animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers. Field potential recordings from striatal slices revealed age-related alterations in the magnitude and dynamics of electrically induced long-term depression (LTD and significant enhancement of electrically induced long-term potentiation in the middle-aged striatum (6-7 and 12-13 months of age. Corticostriatal NO-dependent LTD induced by pharmacological activation of group I metabotropic glutamate receptors underwent significant reduction with aging and could be restored by inhibition of cGMP hydrolysis indicating that its age-related deficit is caused by an altered NO-cGMP signaling cascade. It is suggested that age-related alterations in corticostriatal synaptic plasticity may result from functional alterations in receptor-activated signaling cascades associated with increasing neuroinflammation and a prooxidant state.

  3. Developmental toxicity in white leghorn chickens following in ovo exposure to perfluorooctane sulfonate (PFOS)

    Science.gov (United States)

    Peden-Adams, M. M.; Stuckey, Joyce E.; Gaworecki, K.M.; Berger-Ritchie, J.; Bryant, K.; Jodice, P.G.; Scott, T.R.; Ferrario, J.B.; Guan, B.; Vigo, C.; Boone, J.S.; McGuinn, W.D.; DeWitt, J.C.; Keil, D.E.

    2009-01-01

    Studies show that perfluorinated compounds cause various toxicological effects; nevertheless, effects on immune function and developmental endpoints have not been addressed at length. This study examined the effects of perfluorooctane sulfonate (PFOS) in white leghorn hatchlings on various developmental, immunological, and clinical health parameters. In addition, serum PFOS concentrations were determined by LC/MS/MS. Embryonic day (ED) 0 eggs were injected with either safflower oil/10% DMSO (control, 0 mg/kg egg wt) or PFOS in safflower oil/10% DMSO at 1, 2.5, or 5 mg/kg egg wt, and the chicks were grown to post-hatch day (PHD) 14. Treatment with PFOS did not affect hatch rate. Following in ovo exposure chicks exhibited increases in spleen mass at all treatment levels, in liver mass at 2.5 and 5 mg/kg egg wt, and in body length (crown-rump length) at the 5 mg/kg treatment. Right wings were shorter in all treatments compared to control. Increases in the frequency of brain asymmetry were evident in all treatment groups. SRBC-specific immunoglobulin (IgM and IgY combined) titers were decreased significantly at all treatment levels, while plasma lysozyme activity was increased at all treatment levels. The PHA skin test response decreased in relation to increasing PFOS dose. Serum concentrations where significant immunological, morphological, and neurological effects were observed at the lowest dose (1 mg/kg egg wt) averaged 154 ng PFOS/g serum. These concentrations fall within environmental ranges reported in blood samples from wild caught avian species; thereby, verifying that the environmental egg concentrations used for the injections do indeed relate to serum levels in hatchlings that are also environmentally relevant. These data indicate that immune alterations and brain asymmetry can occur in birds following in ovo exposure to environmentally relevant concentrations of PFOS and demonstrates the need for further research on the developmental effects of

  4. 29 CFR 1952.221 - Developmental schedule.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Developmental schedule. 1952.221 Section 1952.221 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Management data system operational July 1, 1973. Automated Management data system operational January 1, 1974...

  5. 29 CFR 1952.341 - Developmental schedule.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Developmental schedule. 1952.341 Section 1952.341 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... State Legislature January 1975 and to become effective by May 1, 1975. (d) Management Information System...

  6. Developmental toxicity study in rats exposed dermally to clarified slurry oil for a limited period of gestation

    Energy Technology Data Exchange (ETDEWEB)

    Feuston, M.H.; Mackerer, C.R. [Stonybrook Laboratories, Inc., Princeton, NJ (United States)

    1996-10-11

    Clarified slurry oil (CSO, CAS number 64741-62-4), a refinery stream produced by processing crude oil, is a developmental toxicant when administered dermally throughout gestation to pregnant rats. The manifestations of developmental toxicity observed included embryolethlity and growth retardation; evidence of teratogenicity was limited, and not conclusive. The present study was undertaken to further explore the teratogenic potential of CSO. In an attempt to limit emnbryolethality and thereby promote detection of terata, CSO was administered once daily for a limited period of gestation i[gestation days (GD) 9-12], via dermal application, to pregnant Sprague-Dawley rats at doses of 0, 10, 100, and 1000 mg/kg. All animals were sacrificed on GD 20. Detailed examination of the dams was performed. Due to the screening nature of this investigation, fetal evaluations were limited to body weight measurements, external examinations, and evaluation of select visceral endpoints. In the dams exposed to CSO, significant decreases in body weight [absolute and gain (GD 9-13, GD 0-20)] and in the amount of food consumed were observed at 100 and 1000 mg/kg. Additional evidence of maternal toxicity observed at 1000 mg/kg included decreased absolute and relative thymus weights, increased absolute and relative liver weights, and aberrant serum chemistry. Ingestion of the test material was evident at the high dose. Developmental toxicity was observed at 1000 mg/kg and included increased embryolethality, decreased body weight, and anomalous development (cleft palate, brachydactyly, edema). Although a low incidence of abnormal fetal development was observed at 100 mg/kg, it was not conclusive that the alterations were due to CSO exposure. It is likely that three- to seven-ring polycyclic aromatic compounds present in CSO were responsible for the toxic effects observed. 33 refs., 5 tabs.

  7. Mapping the developmental constraints on working memory span performance.

    Science.gov (United States)

    Bayliss, Donna M; Jarrold, Christopher; Baddeley, Alan D; Gunn, Deborah M; Leigh, Eleanor

    2005-07-01

    This study investigated the constraints underlying developmental improvements in complex working memory span performance among 120 children of between 6 and 10 years of age. Independent measures of processing efficiency, storage capacity, rehearsal speed, and basic speed of processing were assessed to determine their contribution to age-related variance in complex span. Results showed that developmental improvements in complex span were driven by 2 age-related but separable factors: 1 associated with general speed of processing and 1 associated with storage ability. In addition, there was an age-related contribution shared between working memory, processing speed, and storage ability that was important for higher level cognition. These results pose a challenge for models of complex span performance that emphasize the importance of processing speed alone.

  8. Developmental estrogen exposures and disruptions to maternal behavior and brain: Effects of ethinyl estradiol, a common positive control.

    Science.gov (United States)

    Catanese, Mary C; Vandenberg, Laura N

    2017-11-07

    Due of its structural similarity to the endogenous estrogen 17β-estradiol (E2), the synthetic estrogen 17α-ethinyl estradiol (EE2) is widely used to study the effects of estrogenic substances on sensitive organs at multiple stages of development. Here, we investigated the effects of EE2 on maternal behavior and the maternal brain in females exposed during gestation and the perinatal period. We assessed several components of maternal behavior including nesting behavior and pup retrieval; characterized the expression of estrogen receptor (ER)α in the medial preoptic area (MPOA), a brain region critical for the display of maternal behavior; and measured expression of tyrosine hydroxylase, a marker for dopaminergic cells, in the ventral tegmental area (VTA), a brain region important in maternal motivation. We found that developmental exposure to EE2 induces subtle effects on several aspects of maternal behavior including time building the nest and time spent engaged in self-care. Developmental exposure to EE2 also altered ERα expression in the central MPOA during both early and late lactation and led to significantly reduced tyrosine hydroxylase immunoreactivity in the VTA. Our results demonstrate both dose- and postpartum stage-related effects of developmental exposure to EE2 on behavior and brain that manifest later in adulthood, during the maternal period. These findings provide further evidence for effects of exposure to exogenous estrogenic compounds during the critical periods of fetal and perinatal development. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Here, there be dragons: charting autophagy-related alterations in human tumors.

    Science.gov (United States)

    Lebovitz, Chandra B; Bortnik, Svetlana B; Gorski, Sharon M

    2012-03-01

    Macroautophagy (or autophagy) is a catabolic cellular process that is both homeostatic and stress adaptive. Normal cells rely on basal levels of autophagy to maintain cellular integrity (via turnover of long-lived proteins and damaged organelles) and increased levels of autophagy to buoy cell survival during various metabolic stresses (via nutrient and energy provision through lysosomal degradation of cytoplasmic components). Autophagy can function in both tumor suppression and tumor progression, and is under investigation in clinical trials as a novel target for anticancer therapy. However, its role in cancer pathogenesis has yet to be fully explored. In particular, it remains unknown whether in vitro observations will be applicable to human cancer patients. Another outstanding question is whether there exists tumor-specific selection for alterations in autophagy function. In this review, we survey reported mutations in autophagy genes and key autophagy regulators identified in human tumor samples and summarize the literature regarding expression levels of autophagy genes and proteins in various cancer tissues. Although it is too early to draw inferences from this collection of in vivo studies of autophagy-related alterations in human cancers, their results highlight the challenges that must be overcome before we can accurately assess the scope of autophagy's predicted role in tumorigenesis.

  10. Neuroanatomic alterations and social and communication deficits in monozygotic twins discordant for autism disorder.

    Science.gov (United States)

    Mitchell, Shanti R; Reiss, Allan L; Tatusko, Danielle H; Ikuta, Ichiro; Kazmerski, Dana B; Botti, Jo-Anna C; Burnette, Courtney P; Kates, Wendy R

    2009-08-01

    Investigating neuroanatomic differences in monozygotic twins who are discordant for autism can help unravel the relative contributions of genetics and environment to this pervasive developmental disorder. The authors used magnetic resonance imaging (MRI) to investigate several brain regions of interest in monozygotic twins who varied in degree of phenotypic discordance for narrowly defined autism. The subjects were 14 pairs of monozygotic twins between the ages of 5 and 14 years old and 14 singleton age- and gender-matched typically developing comparison subjects. The monozygotic twin group was a cohort of children with narrowly defined autistic deficits and their co-twins who presented with varying levels of autistic deficits. High-resolution MRIs were acquired and volumetric/area measurements obtained for the frontal lobe, amygdala, and hippocampus and subregions of the prefrontal cortex, corpus callosum, and cerebellar vermis. No neurovolumetric/area differences were found between twin pairs. Relative to typically developing comparison subjects, dorsolateral prefrontal cortex volumes and anterior areas of the corpus callosum were significantly altered in autistic twins, and volumes of the posterior vermis were altered in both autistic twins and co-twins. Intraclass correlation analysis of brain volumes between children with autism and their co-twins indicated that the degree of within-pair neuroanatomic concordance varied with brain region. In the group of subjects with narrowly defined autism only, dorsolateral prefrontal cortex, amygdala, and posterior vermis volumes were significantly associated with the severity of autism based on scores from the Autism Diagnostic Observation Schedule-Generic. These findings support previous research demonstrating alterations in the prefrontal cortex, corpus callosum, and posterior vermis in children with autism and further suggest that alterations are associated with the severity of the autism phenotype. Continued research

  11. Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β Signaling in Cancer

    Directory of Open Access Journals (Sweden)

    Kiyoshi Mori

    2011-03-01

    Full Text Available Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β, induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression.

  12. Evidence for developmental programming of cerebral laterality in humans.

    Directory of Open Access Journals (Sweden)

    Alexander Jones

    2011-02-01

    Full Text Available Adverse fetal environments are associated with depression, reduced cognitive ability and increased stress responsiveness in later life, but underlying mechanisms are unknown. Environmental pressures on the fetus, resulting from variations in placental function and maternal nutrition, health and stress might alter neurodevelopment, promoting the development of some brain regions over others. As asymmetry of cerebral activity, with greater right hemisphere activity, has been associated with psychopathology, we hypothesized that regional specialization during fetal life might be reflected persistently in the relative activity of the cerebral hemispheres. We tested this hypothesis in 140 healthy 8-9 year-old children, using tympanic membrane temperature to assess relative blood flow to the cerebral hemispheres at rest and following psychosocial stress (Trier Social Stress Test for Children. Their birth weight and placental weight had already been measured when their mothers took part in a previous study of pregnancy outcomes. We found that children who had a smaller weight at birth had evidence of greater blood flow to the right hemisphere than to the left hemisphere (r = -.09, P = .29 at rest; r = -.18, P = .04 following stress. This finding was strengthened if the children had a relatively low birth weight for their placental weight (r = -.17, P = .05 at rest; r = -.31, P = .0005 following stress. Our findings suggest that lateralization of cerebral activity is influenced persistently by early developmental experiences, with possible consequences for long-term neurocognitive function.

  13. Nonspeech Oral Motor Treatment Issues Related to Children with Developmental Speech Sound Disorders

    Science.gov (United States)

    Ruscello, Dennis M.

    2008-01-01

    Purpose: This article examines nonspeech oral motor treatments (NSOMTs) in the population of clients with developmental speech sound disorders. NSOMTs are a collection of nonspeech methods and procedures that claim to influence tongue, lip, and jaw resting postures; increase strength; improve muscle tone; facilitate range of motion; and develop…

  14. Electrophysiological Assessment of Serotonin and GABA Neuron Function in the Dorsal Raphe during the Third Trimester Equivalent Developmental Period in Mice.

    Science.gov (United States)

    Morton, Russell A; Yanagawa, Yuchio; Valenzuela, C Fernando

    2015-01-01

    Alterations in the development of the serotonin system can have prolonged effects, including depression and anxiety disorders later in life. Serotonin axonal projections from the dorsal raphe undergo extensive refinement during the first 2 weeks of postnatal life in rodents (equivalent to the third trimester of human pregnancy). However, little is known about the functional properties of serotonin and GABA neurons in the dorsal raphe during this critical developmental period. We assessed the functional properties and synaptic connectivity of putative serotoninergic neurons and GABAergic neurons in the dorsal raphe during early [postnatal day (P) P5-P7] and late (P15-P17) stages of the third trimester equivalent period using electrophysiology. Our studies demonstrate that GABAergic neurons are hyperexcitable at P5-P7 relative to P15-P17. Furthermore, putative serotonin neurons exhibit an increase in both excitatory and GABAA receptor-mediated spontaneous postsynaptic currents during this developmental period. Our data suggest that GABAergic neurons and putative serotonin neurons undergo significant electrophysiological changes during neonatal development.

  15. Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.

    Science.gov (United States)

    Martinelli, Simone; Krumbach, Oliver H F; Pantaleoni, Francesca; Coppola, Simona; Amin, Ehsan; Pannone, Luca; Nouri, Kazem; Farina, Luciapia; Dvorsky, Radovan; Lepri, Francesca; Buchholzer, Marcel; Konopatzki, Raphael; Walsh, Laurence; Payne, Katelyn; Pierpont, Mary Ella; Vergano, Samantha Schrier; Langley, Katherine G; Larsen, Douglas; Farwell, Kelly D; Tang, Sha; Mroske, Cameron; Gallotta, Ivan; Di Schiavi, Elia; Della Monica, Matteo; Lugli, Licia; Rossi, Cesare; Seri, Marco; Cocchi, Guido; Henderson, Lindsay; Baskin, Berivan; Alders, Mariëlle; Mendoza-Londono, Roberto; Dupuis, Lucie; Nickerson, Deborah A; Chong, Jessica X; Meeks, Naomi; Brown, Kathleen; Causey, Tahnee; Cho, Megan T; Demuth, Stephanie; Digilio, Maria Cristina; Gelb, Bruce D; Bamshad, Michael J; Zenker, Martin; Ahmadian, Mohammad Reza; Hennekam, Raoul C; Tartaglia, Marco; Mirzaa, Ghayda M

    2018-01-17

    Exome sequencing has markedly enhanced the discovery of genes implicated in Mendelian disorders, particularly for individuals in whom a known clinical entity could not be assigned. This has led to the recognition that phenotypic heterogeneity resulting from allelic mutations occurs more commonly than previously appreciated. Here, we report that missense variants in CDC42, a gene encoding a small GTPase functioning as an intracellular signaling node, underlie a clinically heterogeneous group of phenotypes characterized by variable growth dysregulation, facial dysmorphism, and neurodevelopmental, immunological, and hematological anomalies, including a phenotype resembling Noonan syndrome, a developmental disorder caused by dysregulated RAS signaling. In silico, in vitro, and in vivo analyses demonstrate that mutations variably perturb CDC42 function by altering the switch between the active and inactive states of the GTPase and/or affecting CDC42 interaction with effectors, and differentially disturb cellular and developmental processes. These findings reveal the remarkably variable impact that dominantly acting CDC42 mutations have on cell function and development, creating challenges in syndrome definition, and exemplify the importance of functional profiling for syndrome recognition and delineation. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. A neurocognitive perspective on developmental disregard in children with hemiplegic cerebral palsy

    NARCIS (Netherlands)

    Houwink, A.; Aarts, P.B.M.; Geurts, A.C.H.; Steenbergen, B.

    2011-01-01

    A common problem in children with hemiplegic cerebral palsy (CP) is the asymmetrical development of arm and hand capacity caused by the lack of use of the affected upper limb, or developmental disregard. In this paper, we provide a neuropsychological model that relates developmental disregard to

  17. Applying a Lifespan Developmental Perspective to Chronic Pain: Pediatrics to Geriatrics.

    Science.gov (United States)

    Walco, Gary A; Krane, Elliot J; Schmader, Kenneth E; Weiner, Debra K

    2016-09-01

    An ideal taxonomy of chronic pain would be applicable to people of all ages. Developmental sciences focus on lifespan developmental approaches, and view the trajectory of processes in the life course from birth to death. In this article we provide a review of lifespan developmental models, describe normal developmental processes that affect pain processing, and identify deviations from those processes that lead to stable individual differences of clinical interest, specifically the development of chronic pain syndromes. The goals of this review were 1) to unify what are currently separate purviews of "pediatric pain," "adult pain," and "geriatric pain," and 2) to generate models so that specific elements of the chronic pain taxonomy might include important developmental considerations. A lifespan developmental model is applied to the forthcoming Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks-American Pain Society Pain Taxonomy to ascertain the degree to which general "adult" descriptions apply to pediatric and geriatric populations, or if age- or development-related considerations need to be invoked. Copyright © 2016. Published by Elsevier Inc.

  18. Parental Stress in Families of Children With Autism and Other Developmental Disabilities.

    Science.gov (United States)

    Valicenti-McDermott, Maria; Lawson, Katharine; Hottinger, Kathryn; Seijo, Rosa; Schechtman, Merryl; Shulman, Lisa; Shinnar, Shlomo

    2015-11-01

    The level of parental stress in families of children with autism and other developmental disabilities and its association with child comorbid symptoms was studied in an ethnically diverse population, in a cross-sectional study with structured interview. The sample included 50 families of children with autism and 50 families of children with other developmental disabilities, matched by age/gender. Interview included Parenting Stress Index-Short Form, Gastrointestinal Questionnaire, Child Sleep Habits Questionnaire, and Aberrant Behavior Checklist. In this ethnically diverse sample, parental stress was significantly higher for the autism group and for non-Hispanic and US-born mothers. In both study groups, parental stress was related to child irritability. Parental stress was also related to gastrointestinal problems in the autism group and to sleep difficulties in the developmental disabilities group. Targeting child irritability may be particularly important in reducing parental stress for families of children with autism and other developmental disabilities. © The Author(s) 2015.

  19. Brain Microstructural Abnormalities Are Related to Physiological Alterations in End-Stage Renal Disease.

    Directory of Open Access Journals (Sweden)

    Zhigang Bai

    Full Text Available To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD and examine the relationship between brain microstructure and physiological indictors in the disease.Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18-61 years and 40 age- and gender-matched healthy controls (HCs, 32 men, 22-58 years. A voxel-wise analysis was then used to identify microstructural alterations over the whole brain in the ESRD patients compared with the HCs. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability and dialysis duration were correlated with microstructural integrity for the patients.Compared to the HCs, the ESRD patients exhibited disrupted microstructural integrity in not only white matter (WM but also gray matter (GM regions, as characterized by decreased fractional anisotropy (FA and increased mean diffusivity (MD, axial diffusivity (AD and radial diffusivity (RD. Further correlation analyses revealed that the in MD, AD and RD values showed significantly positive correlations with the blood urea nitrogen in the left superior temporal gyrus and significantly negative correlations with the calcium levels in the left superior frontal gyrus (orbital part in the patients.Our findings suggest that ESRD is associated with widespread diffusion abnormalities in both WM and GM regions in the brain, and microstructural integrity of several GM regions are related to biochemical alterations in the disease.

  20. Fire in the Plio-Pleistocene: the functions of hominin fire use, and the mechanistic, developmental and evolutionary consequences.

    Science.gov (United States)

    Attwell, Laura; Kovarovic, Kris; Kendal, Jeremy

    2015-07-20

    Fire is a powerful natural force that can change landscapes extremely quickly. Hominins have harnessed this resource for their own purposes, with mechanistic and developmental physiological consequences. In addition, the use of fire has niche constructive effects, altering selective environments for genetic and cultural evolution. We review the record for hominin fire use in the Plio-Pleistocene, before considering the various functions for its use, and the resultant mechanistic and developmental consequences. We also adopt the niche construction framework to consider how the use of fire can modify selective environments, and thus have evolutionary consequences at genetic and cultural levels. The light that fire produces may influence photoperiodicity and alter hormonally-controlled bodily rhythms. Fire used for cooking could have extended the range of foods hominins were able to consume, and reduced digestion costs. This may have contributed to the expansion of the hominin brain and facial anatomy, influenced by a higher quality cooked diet. Fire may also have allowed dispersal into northern areas with much cooler climates than the hominin African origin, posing novel problems that affected diet and social behaviour.

  1. Early motor developmental milestones and level of neuroticism in young adulthood

    DEFF Research Database (Denmark)

    Flensborg-Madsen, Trine; Sørensen, Holger Jelling; Revsbech, Rasmus

    2012-01-01

    intelligence. CONCLUSIONS: The findings are the first of their kind and suggest that delays in early motor development may not only characterize psychopathological disorders such as schizophrenia, but may also be associated with the personality dimension of neuroticism in adulthood.......BACKGROUND: Studies investigating early developmental factors in relation to psychopathology have mainly focused on schizophrenia. The personality dimension of neuroticism seems to be a general risk factor for psychopathology, but evidence on associations between early developmental precursors...... and personality traits is almost non-existent. This study is therefore the first to investigate associations between early motor developmental milestones and neuroticism in adulthood. Method Mothers of 9125 children of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the child's first...

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

    Science.gov (United States)

    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.

  3. Fetal functional brain age assessed from universal developmental indices obtained from neuro-vegetative activity patterns.

    Directory of Open Access Journals (Sweden)

    Dirk Hoyer

    Full Text Available Fetal brain development involves the development of the neuro-vegetative (autonomic control that is mediated by the autonomic nervous system (ANS. Disturbances of the fetal brain development have implications for diseases in later postnatal life. In that context, the fetal functional brain age can be altered. Universal principles of developmental biology applied to patterns of autonomic control may allow a functional age assessment. The work aims at the development of a fetal autonomic brain age score (fABAS based on heart rate patterns. We analysed n = 113 recordings in quiet sleep, n = 286 in active sleep, and n = 29 in active awakeness from normals. We estimated fABAS from magnetocardiographic recordings (21.4-40.3 weeks of gestation preclassified in quiet sleep (n = 113, 63 females and active sleep (n = 286, 145 females state by cross-validated multivariate linear regression models in a cross-sectional study. According to universal system developmental principles, we included indices that address increasing fluctuation range, increasing complexity, and pattern formation (skewness, power spectral ratio VLF/LF, pNN5. The resulting models constituted fABAS. fABAS explained 66/63% (coefficient of determination R(2 of training and validation set of the variance by age in quiet, while 51/50% in active sleep. By means of a logistic regression model using fluctuation range and fetal age, quiet and active sleep were automatically reclassified (94.3/93.1% correct classifications. We did not find relevant gender differences. We conclude that functional brain age can be assessed based on universal developmental indices obtained from autonomic control patterns. fABAS reflect normal complex functional brain maturation. The presented normative data are supplemented by an explorative study of 19 fetuses compromised by intrauterine growth restriction. We observed a shift in the state distribution towards active awakeness. The lower WGA

  4. Developmental trajectories of brain maturation and behavior: Relevance to major mental illnesses

    Directory of Open Access Journals (Sweden)

    Sedona Lockhart

    2018-05-01

    Full Text Available Adverse events in childhood and adolescence, such as social neglect or drug abuse, are known to lead to behavioral changes in young adulthood. This is particularly true for the subset of people who are intrinsically more vulnerable to stressful conditions. Yet the underlying mechanisms for such developmental trajectory from early life insult to aberrant adult behavior remains elusive. Adolescence is a period of dynamic physiological, psychological, and behavioral changes, encompassing a distinct neurodevelopmental stage called the ‘critical period’. During adolescence, the brain is uniquely susceptible to stress. Stress mediators may lead to disturbances to biological processes that can cause permanent alterations in the adult stage, even as severe as the onset of mental illness when paired with genetic risk and environmental factors. Understanding the molecular factors governing the critical period and how stress can disturb the maturation processes will allow for better treatment and prevention of late adolescent/young adult onset psychiatric disorders. Keywords: Adolescence, Critical period, Developmental trajectory, Brain maturation, Adult behavior

  5. Selective alterations of neurons and circuits related to early memory loss in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    María eLlorens-Martín

    2014-05-01

    Full Text Available A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer’s disease (AD. The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC. Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII→dentate gyrus→CA3→CA1 and monosynaptic (ECIII→CA1 circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits.

  6. Pharmaceuticals and personal care products alter the holobiome and development of a medically important mosquito

    International Nuclear Information System (INIS)

    Pennington, Marcus J.; Rivas, Nicholas G.; Prager, Sean M.; Walton, William E.; Trumble, John T.

    2015-01-01

    The increasing demand for fresh water has forced many countries to use reclaimed wastewater for agricultural purposes. This water contains pharmaceuticals and personal care products (PPCPs) that remain biologically active following passage through wastewater treatment plants. Run-off from farms and contaminated water from treatment facilities exposes aquatic ecosystems to PPCPs. This study examined the effects of PPCPs on a lower trophic organism. Culex quinquefasciatus larvae were reared in water contaminated with environmentally relevant concentrations of common PPCPs. Acetaminophen alone and a mixture of contaminants were found to increase developmental time of larvae. Susceptibility to Bti increased in larvae exposed to antibiotics, acetaminophen, or a mixture of PPCPs. Antibiotics, hormones, and the mixture altered the mosquito bacterial microbiome. Overall, the results indicate that at environmentally relevant concentrations, PPCPs in reclaimed water can have biologically important effects on an ecologically and medically important lower trophic level insect. - Highlights: • Effects of Pharmaceuticals and Personal Care Products on mosquitoes were examined. • Three PPCP treatments increase susceptibility to a common larvicide (Bti). • Acetaminophen and the mixture of PPCPs caused an increase in developmental time. • The holobiome of mosquitoes treated with PPCPs were sequenced. • Three PPCP regimes changed the holobiome of the mosquitoes. - Pharmaceuticals and personal care products, common to reclaimed wastewater, alter the development of mosquitoes. They also alter the whole-body bacterial microbiome

  7. Validating a Spanish Developmental Spelling Test.

    Science.gov (United States)

    Ferroli, Lou; Krajenta, Marilyn

    The creation and validation of a Spanish version of an English developmental spelling test (DST) is described. An introductory section reviews related literature on the rationale for and construction of DSTs, spelling development in the early grades, and Spanish-English bilingual education. Differences between the English and Spanish test versions…

  8. 29 CFR 1952.151 - Developmental schedule.

    Science.gov (United States)

    2010-07-01

    ... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... developmental plan for a “Management Information System” on the date of Plan approval. This program is to be... years after grant award. (p) A State “Safety and Health” poster will be prepared within ninety (90) days...

  9. Genome Transfer Prevents Fragmentation and Restores Developmental Potential of Developmentally Compromised Postovulatory Aged Mouse Oocytes

    Directory of Open Access Journals (Sweden)

    Mitsutoshi Yamada

    2017-03-01

    Full Text Available Changes in oocyte quality can have great impact on the developmental potential of early embryos. Here we test whether nuclear genome transfer from a developmentally incompetent to a developmentally competent oocyte can restore developmental potential. Using in vitro oocyte aging as a model system we performed nuclear transfer in mouse oocytes at metaphase II or at the first interphase, and observed that development to the blastocyst stage and to term was as efficient as in control embryos. The increased developmental potential is explained primarily by correction of abnormal cytokinesis at anaphase of meiosis and mitosis, by a reduction in chromosome segregation errors, and by normalization of the localization of chromosome passenger complex components survivin and cyclin B1. These observations demonstrate that developmental decline is primarily due to abnormal function of cytoplasmic factors involved in cytokinesis, while the genome remains developmentally fully competent.

  10. Interpersonal Problems and Developmental Trajectories of Binge Eating Disorder

    Science.gov (United States)

    Blomquist, Kerstin K.; Ansell, Emily B.; White, Marney A.; Masheb, Robin M.; Grilo, Carlos M.

    2012-01-01

    Objective To explore associations between specific interpersonal constructs and the developmental progression of behaviors leading to binge eating disorder (BED). Method Eighty-four consecutively evaluated, treatment-seeking obese (BMI ≥ 30) men and women with BED were assessed with structured diagnostic and clinical interviews and completed a battery of established measures to assess the current and developmental eating- and weight-related variables as well as interpersonal functioning. Results Using the interpersonal circumplex structural summary method, amplitude, elevation, the affiliation dimension, and the quadratic coefficient for the dominance dimension were associated with eating and weight-related developmental variables. The amplitude coefficient and more extreme interpersonal problems on the dominance dimension (quadratic)—i.e., problems with being extremely high (domineering) or low in dominance (submissive)—were significantly associated with ayounger age at onset of binge eating, BED, and overweight as well as accounted for significant variance in age at binge eating, BED, and overweight onset. Greater interpersonal problems with having an overly affiliative interpersonal style were significantly associated with, and accounted for significant variance in, ayounger age at diet onset. Discussion Findings provide further support for the importance of interpersonal problems among adults with BED and converge with recent work highlighting the importance of specific types of interpersonal problems for understanding heterogeneity and different developmental trajectories of individuals with BED. PMID:22727087

  11. Change in running kinematics after cycling are related to alterations in running economy in triathletes.

    Science.gov (United States)

    Bonacci, Jason; Green, Daniel; Saunders, Philo U; Blanch, Peter; Franettovich, Melinda; Chapman, Andrew R; Vicenzino, Bill

    2010-07-01

    Emerging evidence suggests that cycling may influence neuromuscular control during subsequent running but the relationship between altered neuromuscular control and run performance in triathletes is not well understood. The aim of this study was to determine if a 45 min high-intensity cycle influences lower limb movement and muscle recruitment during running and whether changes in limb movement or muscle recruitment are associated with changes in running economy (RE) after cycling. RE, muscle activity (surface electromyography) and limb movement (sagittal plane kinematics) were compared between a control run (no preceding cycle) and a run performed after a 45 min high-intensity cycle in 15 moderately trained triathletes. Muscle recruitment and kinematics during running after cycling were altered in 7 of 15 (46%) triathletes. Changes in kinematics at the knee and ankle were significantly associated with the change in VO(2) after cycling (precruitment in some triathletes and that changes in kinematics, especially at the ankle, are closely related to alterations in running economy after cycling. Copyright 2010 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  12. Monoethylhexyl Phthalate Elicits an Inflammatory Response in Adipocytes Characterized by Alterations in Lipid and Cytokine Pathways.

    Science.gov (United States)

    Manteiga, Sara; Lee, Kyongbum

    2017-04-01

    A growing body of evidence links endocrine-disrupting chemicals (EDCs) with obesity-related metabolic diseases. While it has been shown that EDCs can predispose individuals toward adiposity by affecting developmental processes, little is known about the chemicals' effects on adult adipose tissue. Our aim was to study the effects of low, physiologically relevant doses of EDCs on differentiated murine adipocytes. We combined metabolomics, proteomics, and gene expression analysis to characterize the effects of mono-ethylhexyl phthalate (MEHP) in differentiated adipocytes. Repeated exposure to MEHP over several days led to changes in metabolite and enzyme levels indicating elevated lipogenesis and lipid oxidation. The chemical exposure also increased expression of major inflammatory cytokines, including chemotactic factors. Proteomic and gene expression analysis revealed significant alterations in pathways regulated by peroxisome proliferator activated receptor-γ (PPARγ). Inhibiting the nuclear receptor's activity using a chemical antagonist abrogated not only the alterations in PPARγ-regulated metabolic pathways, but also the increases in cytokine expression. Our results show that MEHP can induce a pro-inflammatory state in differentiated adipocytes. This effect is at least partially mediated PPARγ.

  13. Maternal perinatal diet induces developmental programming of bone architecture.

    Science.gov (United States)

    Devlin, M J; Grasemann, C; Cloutier, A M; Louis, L; Alm, C; Palmert, M R; Bouxsein, M L

    2013-04-01

    Maternal high-fat (HF) diet can alter offspring metabolism via perinatal developmental programming. This study tests the hypothesis that maternal HF diet also induces perinatal programming of offspring bone mass and strength. We compared skeletal acquisition in pups from C57Bl/6J mice fed HF or normal diet from preconception through lactation. Three-week-old male and female pups from HF (HF-N) and normal mothers (N-N) were weaned onto normal diet. Outcomes at 14 and 26 weeks of age included body mass, body composition, whole-body bone mineral content (WBBMC) via peripheral dual-energy X-ray absorptiometry, femoral cortical and trabecular architecture via microcomputed tomography, and glucose tolerance. Female HF-N had normal body mass and glucose tolerance, with lower body fat (%) but higher serum leptin at 14 weeks vs. N-N (Pbone volume fraction was 20% higher at 14 weeks in female HF-N vs. N-N (Pbone area was 6% higher at 14 weeks vs. N-N (Pbone, supporting the hypothesis that maternal diet alters postnatal skeletal homeostasis.

  14. Relating stress of mothers of children with developmental disabilities to family-school partnerships.

    Science.gov (United States)

    Burke, Meghan M; Hodapp, Robert M

    2014-02-01

    Although mothers of children with intellectual and developmental disabilities (IDD) experience high levels of stress and schools constitute an important resource, the relation remains unknown between maternal stress and educational services. Responding to a national, web-based survey, 965 mothers of students with disabilities completed a 163-item questionnaire about parent stress. We examined which child, parent, and parent-school characteristics correlated with maternal stress. Mothers with lower stress levels reported better parent-school relationships and low levels of parent advocacy. However, lower stress levels were predominantly shown by mothers with good-to-excellent parent-school relationships (vs. poor-to-fair partnerships) and who engaged in virtually no (vs. any) advocacy activities. Lower maternal stress levels were also noted when children had fewer behavior problems, Down syndrome, and did not have autism. Less stress was also reported by mothers who had not enacted procedural safeguards, were minorities, and rated themselves lower on neuroticism and were more extroverted, dependable, and open to new experiences. This study has important implications for practitioners and researchers.

  15. Quantitative developmental transcriptomes of the Mediterranean sea urchin Paracentrotus lividus.

    Science.gov (United States)

    Gildor, Tsvia; Malik, Assaf; Sher, Noa; Avraham, Linor; Ben-Tabou de-Leon, Smadar

    2016-02-01

    Embryonic development progresses through the timely activation of thousands of differentially activated genes. Quantitative developmental transcriptomes provide the means to relate global patterns of differentially expressed genes to the emerging body plans they generate. The sea urchin is one of the classic model systems for embryogenesis and the models of its developmental gene regulatory networks are of the most comprehensive of their kind. Thus, the sea urchin embryo is an excellent system for studies of its global developmental transcriptional profiles. Here we produced quantitative developmental transcriptomes of the sea urchin Paracentrotus lividus (P. lividus) at seven developmental stages from the fertilized egg to prism stage. We generated de-novo reference transcriptome and identified 29,817 genes that are expressed at this time period. We annotated and quantified gene expression at the different developmental stages and confirmed the reliability of the expression profiles by QPCR measurement of a subset of genes. The progression of embryo development is reflected in the observed global expression patterns and in our principle component analysis. Our study illuminates the rich patterns of gene expression that participate in sea urchin embryogenesis and provide an essential resource for further studies of the dynamic expression of P. lividus genes. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Sleep Deprivation Alters Choice Strategy Without Altering Uncertainty or Loss Aversion Preferences

    Directory of Open Access Journals (Sweden)

    O'Dhaniel A Mullette-Gillman

    2015-10-01

    Full Text Available Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

  17. Sleep deprivation alters choice strategy without altering uncertainty or loss aversion preferences.

    Science.gov (United States)

    Mullette-Gillman, O'Dhaniel A; Kurnianingsih, Yoanna A; Liu, Jean C J

    2015-01-01

    Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD) alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

  18. Developmental Changes in Memory-Related Linguistic Skills and Their Relationship to Episodic Recall in Children.

    Science.gov (United States)

    Uehara, Izumi

    2015-01-01

    This longitudinal study of nine children examined two issues concerning infantile amnesia: the time at which memories for events experienced before the age of 3-4 years disappear from consciousness and whether this timing of memory loss is related to the development of specific aspects of episodic and autobiographical memory. This study followed children from infancy to early childhood and examined the central role of three verbal-cognitive milestones related to autobiographical memory: the age at which children begin to report autobiographical memories using the past tense (Milestone 1); the age at which they begin to verbally acknowledge past events (Milestone 2); and the age at which they begin to spontaneously use memory-related verbs (Milestone 3). As expected, memories of events that occurred before 3-4 years of age were affected by infantile amnesia. Achievement of these milestones followed almost the same developmental progression: Milestone 1 (1 year; 10 months (1;10) to 3 years; 4 months (3;4)) was followed by Milestones 2 (3;1 to 4;0) and 3 (3;5 to 4;4). Milestone 2 was typically related to the onset of infantile amnesia, whereas Milestone 1 occurred during the period for which the children became amnesic as they aged. These data suggest that linguistic meta-cognitive awareness of personal memory is the key feature in infantile amnesia.

  19. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, Jie; Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology and Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-02-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  20. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    International Nuclear Information System (INIS)

    Luo, Hanwen; Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng; Ping, Jie; Xu, Dan; Ma, Lu; Chen, Liaobin; Wang, Hui

    2014-01-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  1. Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

    Science.gov (United States)

    Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

    2013-01-01

    Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

  2. An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics

    Science.gov (United States)

    Molenaar, Peter C. M.

    2015-01-01

    The main theme of this paper concerns the persistent critique of Gilbert Gottlieb on developmental behavior genetics and my reactions to this critique, the latter changing from rejection to complete acceptation. Concise characterizations of developmental behavior genetics, developmental systems theory (to which Gottlieb made essential…

  3. Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour.

    Science.gov (United States)

    Hines, Melissa; Pasterski, Vickie; Spencer, Debra; Neufeld, Sharon; Patalay, Praveetha; Hindmarsh, Peter C; Hughes, Ieuan A; Acerini, Carlo L

    2016-02-19

    Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development. © 2016 The Author(s).

  4. Developmental neurotoxicants in human milk : Comparison of levels and intakes in three European countries

    NARCIS (Netherlands)

    Čechová, Eliška; Scheringer, Martin; Seifertová, Marta; Mikeš, Ondřej; Kroupová, Kristýna; Kuta, Jan; Forns, Joan; Eggesbø, Merete; Quaak, Ilona; de Cock, Marijke; van de Bor, Margot; Patayová, Henrieta; Palkovičová Murínová, Ľubica; Kočan, Anton

    2016-01-01

    Developmental neurotoxicants (DNTs), such as methylmercury (MeHg), polychlorinated biphenyls (PCBs) and selected organochlorine pesticides (OCPs), have gained increasing interest recently due to their possible relation to developmental disorders in children, which are increasing worldwide. We

  5. Prenatal irradiation and developmental disorders of the brain

    International Nuclear Information System (INIS)

    Kameyama, Yoshiro

    1987-01-01

    The radiation sensitivity of the brain of a growing fetus is higher than that of other organs and tissues. Of the various organs in the human body, the brain has the most complicated structure. The major features of developmental disorders of the brain, which are produced rather easily by external causes, are: (a) the sensitive period for developmental disorders is long, (b) undifferentiated nerve cells are sensitive to external causes and (c) such disorders leads to irreversible functional failures after birth. The malformation of the brain and its relations with the sensitivity are briefly described. Experiments with prenatal animals have shown that major developmental disorders of brain tissue include death of undifferentiated cells, lack of constituent neurons and disturbance in structure of the cortex, and that typical developmental abnormalities include dysgenetic hydrocephaly, microcephalia, etc. Teratological features of histogenetic disorders of the brain are then briefly outlined. Various experimental results on these and other disorders caused by radiations are presented and discussed. Data on fetuses exposed to radiations at Hiroshima and Nagasaki are also given and discussed. The last section of the report deals with risk evaluation. (Nogami, K.)

  6. Developmental aspects of the interaction between narcissism, self-esteem and object relations.

    Science.gov (United States)

    Dare, C; Holder, A

    1981-01-01

    This paper reviews the history, within psycho-analysis, of narcissism and shows that it cannot be understood as a unitary concept. This is reflected in much of the extensive literature on the topic. The definition of narcissism solely in terms of the libidinal drive cathexis of the self representation is rejected. Instead, narcissism is defined as the sum of the positively-coloured feeling states attached to the self-representation. By pursuing a developmental investigation of narcissistic and opposing phenomena, the multiple sources which contribute to or detract from the overall level of self-esteem are demonstrated. Such an investigation clarifies the close relationship between the concepts of self-esteem, well-being and narcissism, and differentiating definitions are put forward. The term 'counter-narcissistic' is introduced to denote the negative contributions to self-esteem which detract from the narcissistic input. The interplay between the contributions to the overall quality of self-esteem, deriving on the one hand from somatic and instinctual drive sources, and on the other from object relationships, exemplifies the multiple origins of its qualities at any one time. This interplay is pursued through the sequential developmental phases from infancy to the oedipal level in order to show the complex epigenesis of narcissism, counter-narcissism and self-esteem.

  7. Sex-related differences in cadmium-induced alteration of drug action in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Schnell, R.C.; Pence, D.H.; Prosser, T.D.; Miya, T.S.

    1976-01-01

    Three days after pretreatment of rats of both sexes with cadmium (2 mg/kg, i.p.), the duration of hypnosis induced by hexobarbital (75 mg/kg, i.p.) was potentiated in males but not females. Likewise, similar treatment with cadmium leads to significant inhibition of the metabolism of hexobarbital by hepatic microsomal enzymes obtained from male but not female animals. These data suggest that there is a sex-related difference in the ability of cadmium to alter drug action in rats.

  8. A Neurocognitive Perspective on Developmental Disregard in Children with Hemiplegic Cerebral Palsy

    Science.gov (United States)

    Houwink, Annemieke; Aarts, Pauline B. M.; Geurts, Alexander C. H.; Steenbergen, Bert

    2011-01-01

    A common problem in children with hemiplegic cerebral palsy (CP) is the asymmetrical development of arm and hand capacity caused by the lack of use of the affected upper limb, or developmental disregard. In this paper, we provide a neuropsychological model that relates developmental disregard to attentional processes and motor learning. From this…

  9. Cpt1a gene expression in peripheral blood mononuclear cells as an early biomarker of diet-related metabolic alterations

    Directory of Open Access Journals (Sweden)

    Rubén Díaz-Rúa

    2016-11-01

    Full Text Available Background: Research on biomarkers that provide early information about the development of future metabolic alterations is an emerging discipline. Gene expression analysis in peripheral blood mononuclear cells (PBMC is a promising tool to identify subjects at risk of developing diet-related diseases. Objective: We analysed PBMC expression of key energy homeostasis-related genes in a time-course analysis in order to find out early markers of metabolic alterations due to sustained intake of high-fat (HF and high-protein (HP diets. Design: We administered HF and HP diets (4 months to adult Wistar rats in isocaloric conditions to a control diet, mainly to avoid overweight associated with the intake of hyperlipidic diets and, thus, to be able to characterise markers of metabolically obese normal-weight (MONW syndrome. PBMC samples were collected at different time points of dietary treatment and expression of relevant energy homeostatic genes analysed by real-time reverse transcription-polymerase chain reaction. Serum parameters related with metabolic syndrome, as well as fat deposition in liver, were also analysed. Results: The most outstanding results were those obtained for the expression of the lipolytic gene carnitine palmitoyltransferase 1a (Cpt1a. Cpt1a expression in PBMC increased after only 1 month of exposure to both unbalanced diets, and this increased expression was maintained thereafter. Interestingly, in the case of the HF diet, Cpt1a expression was altered even in the absence of increased body weight but correlated with alterations such as higher insulin resistance, alteration of serum lipid profile and, particularly, increased fat deposition in liver, a feature characteristic of metabolic syndrome, which was even observed in animals fed with HP diet. Conclusions: We propose Cpt1a gene expression analysis in PBMC as an early biomarker of metabolic alterations associated with MONW phenotype due to the intake of isocaloric HF diets, as

  10. Role of epigenetics in developmental biology and transgenerational inheritance.

    Science.gov (United States)

    Skinner, Michael K

    2011-03-01

    The molecular mechanisms involved in developmental biology and cellular differentiation have traditionally been considered to be primarily genetic. Environmental factors that influence early life critical windows of development generally do not have the capacity to modify genome sequence, nor promote permanent genetic modifications. Epigenetics provides a molecular mechanism for environment to influence development, program cellular differentiation, and alter the genetic regulation of development. The current review discusses how epigenetics can cooperate with genetics to regulate development and allow for greater plasticity in response to environmental influences. This impacts area such as cellular differentiation, tissue development, environmental induced disease etiology, epigenetic transgenerational inheritance, and the general systems biology of organisms and evolution. Copyright © 2011 Wiley-Liss, Inc.

  11. Qualitative methodology in developmental psychology

    DEFF Research Database (Denmark)

    Demuth, Carolin; Mey, Günter

    2015-01-01

    Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing rec...... in qualitative research offers a promising avenue to advance the field in this direction.......Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing...

  12. Neurobehavioral impairments caused by developmental imidacloprid exposure in zebrafish.

    Science.gov (United States)

    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.

  13. Parenting Children with Developmental Delays: The Role of Positive Beliefs

    OpenAIRE

    PACZKOWSKI, EMILIE; BAKER, BRUCE L.

    2008-01-01

    Parents of children with developmental delays consistently report higher levels of child behavior problems and also parenting stress than parents of typically developing children. This study examined how mothers' positive beliefs influence the relation between children's behavior problems and mothers' parenting stress among families of children who are developmentally delayed (DD: n = 72) or typically developing (TD: n = 95) and assessed at ages 3, 5, and 7 years. Positive beliefs had a main ...

  14. Attentional networks in developmental dyscalculia

    Directory of Open Access Journals (Sweden)

    Henik Avishai

    2010-01-01

    Full Text Available Abstract Background Very little is known about attention deficits in developmental dyscalculia, hence, this study was designed to provide the missing information. We examined attention abilities of participants suffering from developmental dyscalculia using the attention networks test - interactions. This test was designed to examine three different attention networks--executive function, orienting and alerting--and the interactions between them. Methods Fourteen university students that were diagnosed as suffering from developmental dyscalculia--intelligence and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder--and 14 matched controls were tested using the attention networks test - interactions. All participants were given preliminary tests to measure mathematical abilities, reading, attention and intelligence. Results The results revealed deficits in the alerting network--a larger alerting effect--and in the executive function networks--a larger congruity effect in developmental dyscalculia participants. The interaction between the alerting and executive function networks was also modulated by group. In addition, developmental dyscalculia participants were slower to respond in the non-cued conditions. Conclusions These results imply specific attentional deficits in pure developmental dyscalculia. Namely, those with developmental dyscalculia seem to be deficient in the executive function and alertness networks. They suffer from difficulty in recruiting attention, in addition to the deficits in numerical processing.

  15. Attentional networks in developmental dyscalculia.

    Science.gov (United States)

    Askenazi, Sarit; Henik, Avishai

    2010-01-07

    Very little is known about attention deficits in developmental dyscalculia, hence, this study was designed to provide the missing information. We examined attention abilities of participants suffering from developmental dyscalculia using the attention networks test - interactions. This test was designed to examine three different attention networks--executive function, orienting and alerting--and the interactions between them. Fourteen university students that were diagnosed as suffering from developmental dyscalculia--intelligence and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder--and 14 matched controls were tested using the attention networks test-interactions. All participants were given preliminary tests to measure mathematical abilities, reading, attention and intelligence. The results revealed deficits in the alerting network--a larger alerting effect--and in the executive function networks--a larger congruity effect in developmental dyscalculia participants. The interaction between the alerting and executive function networks was also modulated by group. In addition, developmental dyscalculia participants were slower to respond in the non-cued conditions. These results imply specific attentional deficits in pure developmental dyscalculia. Namely, those with developmental dyscalculia seem to be deficient in the executive function and alertness networks. They suffer from difficulty in recruiting attention, in addition to the deficits in numerical processing.

  16. Differing Developmental Trajectories in Heart Rate Responses to Speech Stimuli in Infants at High and Low Risk for Autism Spectrum Disorder.

    Science.gov (United States)

    Perdue, Katherine L; Edwards, Laura A; Tager-Flusberg, Helen; Nelson, Charles A

    2017-08-01

    We investigated heart rate (HR) in infants at 3, 6, 9, and 12 months of age, at high (HRA) and low (LRC) familial risk for ASD, to identify potential endophenotypes of ASD risk related to attentional responses. HR was extracted from functional near-infrared spectroscopy recordings while infants listened to speech stimuli. Longitudinal analysis revealed that HRA infants and males generally had lower baseline HR than LRC infants and females. HRA infants showed decreased HR responses to early trials over development, while LRC infants showed increased responses. These findings suggest altered developmental trajectories in physiological responses to speech stimuli over the first year of life, with HRA infants showing less social orienting over time.

  17. Developmental Scaffolding

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio

    2015-01-01

    . Within the developmental hierarchy, each module yields an inter-level relationship that makes it possible for the scaffolding to mediate the production of selectable variations. Awide range of genetic, cellular and morphological mechanisms allows the scaffolding to integrate these modular variations...... to the complexity of sign recognition proper of a cellular community. In this semiotic perspective, the apparent goal directness of any developmental strategy should no longer be accounted for by a predetermined genetic program, but by the gradual definition of the relationships selected amongst the ones...

  18. Psychotherapy with people with developmental disabilities

    Directory of Open Access Journals (Sweden)

    Barbara Zafošnik

    2011-08-01

    Full Text Available People with developmental disabilities can experience any psychological abnormalitiy and psychiatric illness as do people without developmental disabilities. Due to different diagnostic criteria, assessment procedures and instruments, we lack definite prevalence rates for people with developmental disabilities, also suffering from mental health problems, eventhough most studies place the rate at 20 to 40%. One of the possible treatment alternatives for augmenting psychological well-being is psychotherapy, but is extremely rarely used for people with severe and profound disabilities, where speech cannot be the main therapeutic medium. So, those that are included in the psychotherapuetic process are predominantly clients with mild developmental disabilities, and they are mostly in cognitive-behavioral therapy. Recently, two models of (psychotherapy for persons with severe and profound developmental disabilities were developed: developmental-dynamic relationship therapy and attachment-based behaviour therapy for children. Conceptually, they both originate form developmental psychoanalytic theories.

  19. The developmental state in Brazil: comparative and historical perspectives

    Directory of Open Access Journals (Sweden)

    BEN ROSS SCHNEIDER

    2015-03-01

    Full Text Available The record of successful developmental states in East Asia and the partial successes of developmental states in Latin America suggest several common preconditions for effective state intervention including a Weberian bureaucracy, monitoring of implementation, reciprocity (subsidies in exchange for performance, and collaborative relations between government and business. Although Brazil failed to develop the high technology manufacturing industry and exports that have fueled sustained growth in East Asia, its developmental state had a number of important, and often neglected, successes, especially in steel, automobiles, mining, ethanol, and aircraft manufacturing. Where Brazil's developmental state was less successful was in promoting sectors like information technology and nuclear energy, as well as overall social and regional equality. In addition, some isolated initiatives by state governments were also effective in promoting particular local segments of industry and agriculture. Comparisons with East Asia, highlight the central role of state enterprises in Brazil that in effect internalized monitoring and reciprocity and bypassed collaboration between business and government (that was overall rarer in Brazil.

  20. Polybrominated diphenyl ethers in relation to autism and developmental delay: a case-control study

    Science.gov (United States)

    2011-01-01

    Background Polybrominated diphenyl ethers (PBDEs) are flame retardants used widely and in increasing amounts in the U.S. over the last few decades. PBDEs and their metabolites cross the placenta and studies in rodents demonstrate neurodevelopmental toxicity from prenatal exposures. PBDE exposures occur both via breastfeeding and hand-to-mouth activities in small children. Methods Participants were 100 children from the CHARGE (CHildhood Autism Risk from Genetics and the Environment) Study, a case-control epidemiologic investigation of children with autism/autism spectrum disorder, with developmental delay and from the general population. Diagnoses of autism were confirmed by the Autism Diagnostic Observation Schedule and Autism Diagnostic Inventory-Revised, and of developmental delay using the Mullen's Scales of Early Learning and the Vineland Adaptive Behavior Scales. Typically developing controls were those with no evidence of delay, autism, or autism spectrum disorder. Eleven PBDE congeners were measured by gas chromatography/mass spectrometry from serum specimens collected after children were assessed. Logistic regression was used to evaluate the association between plasma PBDEs and autism. Results Children with autism/autism spectrum disorder and developmental delay were similar to typically developing controls for all PBDE congeners, but levels were high for all three groups. Conclusions Plasma samples collected post-diagnosis in this study may not represent early life exposures due to changes in diet and introduction of new household products containing PBDEs. Studies with direct measurements of prenatal or infant exposures are needed to assess the possible causal role for these compounds in autism spectrum disorders. PMID:21205326

  1. When words fail us: insights into language processing from developmental and acquired disorders.

    Science.gov (United States)

    Bishop, Dorothy V M; Nation, Kate; Patterson, Karalyn

    2014-01-01

    Acquired disorders of language represent loss of previously acquired skills, usually with relatively specific impairments. In children with developmental disorders of language, we may also see selective impairment in some skills; but in this case, the acquisition of language or literacy is affected from the outset. Because systems for processing spoken and written language change as they develop, we should beware of drawing too close a parallel between developmental and acquired disorders. Nevertheless, comparisons between the two may yield new insights. A key feature of connectionist models simulating acquired disorders is the interaction of components of language processing with each other and with other cognitive domains. This kind of model might help make sense of patterns of comorbidity in developmental disorders. Meanwhile, the study of developmental disorders emphasizes learning and change in underlying representations, allowing us to study how heterogeneity in cognitive profile may relate not just to neurobiology but also to experience. Children with persistent language difficulties pose challenges both to our efforts at intervention and to theories of learning of written and spoken language. Future attention to learning in individuals with developmental and acquired disorders could be of both theoretical and applied value.

  2. A Multidimensional Scaling Approach to Developmental Dimensions in Object Permanence and Tracking Stimuli.

    Science.gov (United States)

    Townes-Rosenwein, Linda

    This paper discusses a longitudinal, exploratory study of developmental dimensions related to object permanence theory and explains how multidimensional scaling techniques can be used to identify developmental dimensions. Eighty infants, randomly assigned to one of four experimental groups and one of four counterbalanced orders of stimuli, were…

  3. PM2.5-bound metal metabolic distribution and coupled lipid abnormality at different developmental windows.

    Science.gov (United States)

    Ku, Tingting; Zhang, Yingying; Ji, Xiaotong; Li, Guangke; Sang, Nan

    2017-09-01

    Atmospheric fine particulate matter (PM 2.5 ) is a serious threat to human health. As a toxicant constituent, metal leads to significant health risks in a population, but exposure to PM 2.5 -bound metals and their biological impacts are not fully understood. In this study, we determined the metal contents of PM 2.5 samples collected from a typical coal-burning city and then investigated the metabolic distributions of six metals (Zn, Pb, Mn, As, Cu, and Cd) following PM 2.5 inhalation in mice in different developmental windows. The results indicate that fine particles were mainly deposited in the lung, but PM 2.5 -bound metals could reach and gather in secondary off-target tissues (the lung, liver, heart and brain) with a developmental window-dependent property. Furthermore, elevations in triglycerides and cholesterol levels in sensitive developmental windows (the young and elderly stages) occurred, and significant associations between metals (Pb, Mn, As and Cd) and cholesterol in the heart, brain, liver and lung were observed. These findings suggest that PM 2.5 inhalation caused selective metal metabolic distribution in tissues with a developmental window-dependent property and that the effects were associated with lipid alterations. This provides a foundation for the underlying systemic toxicity following PM 2.5 exposure based on metal components. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Letter and Colour Matching Tasks: Parametric Measures of Developmental Working Memory Capacity

    Directory of Open Access Journals (Sweden)

    Tamara L. Powell

    2014-01-01

    Full Text Available We investigated the mediating role of interference in developmental assessments of working memory (WM capacity across childhood, adolescence, and young adulthood. One hundred and forty-two participants completed two versions of visuospatial (colour matching task, CMT and verbal (letter matching task, LMT WM tasks, which systematically varied cognitive load in a high and low interference condition. Results showed similar developmental trajectories across high interference contexts (CMT- and LMT-Complex and divergent developmental growth patterns across low interference contexts (CMT- and LMT-Simple. Performance on tasks requiring greater cognitive control was in closer agreement with developmental predictions relative to simple recall guided tasks that rely solely on the storage components of WM. These findings suggest that developmental WM capacity, as measured by the CMT and LMT paradigms, can be better quantified using high interference contexts, in both content domains, and demonstrate steady increases in WM through to mid-adolescence.

  5. A Brief Overview of Adolescent Developmental Problems in Hong Kong

    Science.gov (United States)

    Shek, Daniel T. L.; Keung Ma, Hing; Sun, Rachel C. F.

    2011-01-01

    Several adolescent developmental problems in Hong Kong are briefly reviewed in this paper. First, rising adolescent substance abuse trends are described. Second, Internet use problems and Internet addiction among young people are examined. Third, worrying trends in adolescent sexuality are identified. Fourth, phenomena on bullying among young people are reviewed. Finally, phenomena related to adolescent materialistic orientation are focused upon. With reference to these adolescent developmental problems, possible solutions are briefly discussed particularly with reference to the ecological perspective. It is argued that the related scientific literature provides useful pointers for designing the curriculum in the extension phase of the Project P.A.T.H.S. in Hong Kong. PMID:22194661

  6. Cpt1a gene expression in peripheral blood mononuclear cells as an early biomarker of diet-related metabolic alterations

    KAUST Repository

    Diaz Rua, Ruben; Palou, Andreu; Oliver, Paula

    2016-01-01

    subjects at risk of developing diet-related diseases.Objective: We analysed PBMC expression of key energy homeostasis-related genes in a time-course analysis in order to find out early markers of metabolic alterations due to sustained intake of high-fat (HF) and highprotein (HP) diets.Design: We administered HF and HP diets (4 months) to adult Wistar rats in isocaloric conditions to a control diet, mainly to avoid overweight associated with the intake of hyperlipidic diets and, thus, to be able to characterise markers of metabolically obese normal-weight (MONW) syndrome. PBMC samples were collected at different time points of dietary treatment and expression of relevant energy homeostatic genes analysed by real-time reverse transcription-polymerase chain reaction. Serum parameters related with metabolic syndrome, as well as fat deposition in liver, were also analysed.Results: The most outstanding results were those obtained for the expression of the lipolytic gene carnitine palmitoyltransferase 1a (Cpt1a). Cpt1a expression in PBMC increased after only 1 month of exposure to both unbalanced diets, and this increased expression was maintained thereafter. Interestingly, in the case of the HF diet, Cpt1a expression was altered even in the absence of increased body weight but correlated with alterations such as higher insulin resistance, alteration of serum lipid profile and, particularly, increased fat deposition in liver, a feature characteristic of metabolic syndrome, which was even observed in animals fed with HP diet.Conclusions: We propose Cpt1a gene expression analysis in PBMC as an early biomarker of metabolic alterations associated with MONW phenotype due to the intake of isocaloric HF diets, as well as a marker of increased risk of metabolic diseases

  7. Developmental transcriptome of Aplysia californica'

    KAUST Repository

    Heyland, Andreas

    2010-12-06

    Genome-wide transcriptional changes in development provide important insight into mechanisms underlying growth, differentiation, and patterning. However, such large-scale developmental studies have been limited to a few representatives of Ecdysozoans and Chordates. Here, we characterize transcriptomes of embryonic, larval, and metamorphic development in the marine mollusc Aplysia californica and reveal novel molecular components associated with life history transitions. Specifically, we identify more than 20 signal peptides, putative hormones, and transcription factors in association with early development and metamorphic stages-many of which seem to be evolutionarily conserved elements of signal transduction pathways. We also characterize genes related to biomineralization-a critical process of molluscan development. In summary, our experiment provides the first large-scale survey of gene expression in mollusc development, and complements previous studies on the regulatory mechanisms underlying body plan patterning and the formation of larval and juvenile structures. This study serves as a resource for further functional annotation of transcripts and genes in Aplysia, specifically and molluscs in general. A comparison of the Aplysia developmental transcriptome with similar studies in the zebra fish Danio rerio, the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, and other studies on molluscs suggests an overall highly divergent pattern of gene regulatory mechanisms that are likely a consequence of the different developmental modes of these organisms. © 2010 Wiley-Liss, Inc., A Wiley Company.

  8. ALTERATION RELATED TO HYDROTHERMAL ACTIVITY OF THE NEVADO DEL RUIZ VOLCANO (NRV), COLOMBIA

    OpenAIRE

    Forero, Jhon; Zuluaga, Carlos; Mojica, Jaime

    2011-01-01

    The hydrothermal activity in the NRV generates alteration characterized by mineral associations depending on a number of physic-chemical factors of the hydrothermal system. Petrography of unaltered rocks was used to establish the mineral assemblage prior to rock-fluid interaction. XRD was used in altered rocks, where it was not possible to recognize the alteration products. The observed mineral assemblages indicate advanced and intermediate argillic alterations, this and the observation of ve...

  9. White matter microstructure and developmental improvement of hyperactive/impulsive symptoms in Attention-Deficit/Hyperactivity

    NARCIS (Netherlands)

    Francx, W.; Zwiers, M.P.; Mennes, M.; Oosterlaan, J.; Heslenfeld, D.J.; Hoekstra, P.; Hartman, C.A.; Franke, C.; Faraone, S.V.; O'Dwyer, L.; Buitelaar, J.K.

    2015-01-01

    Background A developmental improvement of symptoms in attention-deficit/hyperactivity disorder (ADHD) is frequently reported, but the underlying neurobiological substrate has not been identified. The aim of this study was to determine whether white matter microstructure is related to developmental

  10. Neurobiological Programming of Early Life Stress: Functional Development of Amygdala-Prefrontal Circuitry and Vulnerability for Stress-Related Psychopathology.

    Science.gov (United States)

    VanTieghem, Michelle R; Tottenham, Nim

    2017-04-25

    Early adverse experiences are associated with heighted vulnerability for stress-related psychopathology across the lifespan. While extensive work has investigated the effects of early adversity on neurobiology in adulthood, developmental approaches can provide further insight on the neurobiological mechanisms that link early experiences and long-term mental health outcomes. In the current review, we discuss the role of emotion regulation circuitry implicated in stress-related psychopathology from a developmental and transdiagnostic perspective. We highlight converging evidence suggesting that multiple forms of early adverse experiences impact the functional development of amygdala-prefrontal circuitry. Next, we discuss how adversity-induced alterations in amygdala-prefrontal development are associated with symptoms of emotion dysregulation and psychopathology. Additionally, we discuss potential mechanisms through which protective factors may buffer the effects of early adversity on amygdala-prefrontal development to confer more adaptive long-term outcomes. Finally, we consider limitations of the existing literature and make suggestions for future longitudinal and translational research that can better elucidate the mechanisms linking early adversity, neurobiology, and emotional phenotypes. Together, these findings may provide further insight into the neuro-developmental mechanisms underlying the emergence of adversity-related emotional disorders and facilitate the development of targeted interventions that can ameliorate risk for psychopathology in youth exposed to early life stress.

  11. Developmental Discourses as a Regime of Truth in Research with Primary School Students

    Science.gov (United States)

    Bartholomaeus, Clare

    2016-01-01

    While developmental discourses have been heavily critiqued in relation to education systems, less attention has been paid to how these impact the data collection process in classroom research. This article utilises Foucault's concept of regime of truth to highlight the pervasiveness of developmental discourses when conducting research in primary…

  12. Alterations of ubiquitin related proteins in the pathology and development of schizophrenia: Evidence from human and animal studies.

    Science.gov (United States)

    Andrews, Jessica L; Goodfellow, Frederic J; Matosin, Natalie; Snelling, Mollie K; Newell, Kelly A; Huang, Xu-Feng; Fernandez-Enright, Francesca

    2017-07-01

    Gene expression analyses in post-mortem schizophrenia brains suggest that a number of ubiquitin proteasome system (UPS) genes are associated with schizophrenia; however the status of UPS proteins in the schizophrenia brain is largely unknown. Ubiquitin related proteins are inherently involved in memory, neuronal survival and morphology, which are processes implicated in neurodevelopmental disorders such as schizophrenia. We examined levels of five UPS proteins (Protein Inhibitor of Activated STAT2 [PIAS2], F-Box and Leucine rich repeat protein 21 [FBXL21], Mouse Double Minute 2 homolog [MDM2], Ubiquitin Carboxyl-Terminal Hydrolase-L1 [UCHL1] and Ubiquitin Conjugating Enzyme E2D1 [UBE2D1]) involved in these neuronal processes, within the dorsolateral prefrontal cortex of post-mortem schizophrenia subjects and matched controls (n = 30/group), in addition to across neurodevelopmental time-points (juvenile, adolescent and adult stages of life), utilizing a well-established neurodevelopmental phencyclidine (PCP) animal model of schizophrenia. We observed significant reductions in PIAS2, FBXL21 and MDM2 in schizophrenia subjects compared to controls (p-values ranging from 0.002 to 0.004). In our developmental PCP model, MDM2 protein was significantly reduced in adult PCP-treated rats compared to controls (p = 0.034). Additionally, FBXL21 (p = 0.022) and UCHL1 (p = 0.022) were significantly decreased, whilst UBE2D1 was increased (p = 0.022), in juvenile phencyclidine-treated rats compared to controls. This is the first study reporting alterations of UPS proteins in post-mortem human schizophrenia subjects and in a neurodevelopmental model of schizophrenia. The findings from this study provide strong support for a role of these UPS proteins in the pathology and development of schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Allostatic load in parents of children with developmental disorders: moderating influence of positive affect.

    Science.gov (United States)

    Song, Jieun; Mailick, Marsha R; Ryff, Carol D; Coe, Christopher L; Greenberg, Jan S; Hong, Jinkuk

    2014-02-01

    This study examines whether parents of children with developmental disorders are at risk of elevated allostatic load relative to control parents and whether positive affect moderates difference in risk. In all, 38 parents of children with developmental disorders and 38 matched comparison parents were analyzed. Regression analyses revealed a significant interaction between parent status and positive affect: parents of children with developmental disorders had lower allostatic load when they had higher positive affect, whereas no such association was evident for comparison parents. The findings suggest that promoting greater positive affect may lower health risks among parents of children with developmental disorders.

  14. Communication-Based Assessment of Developmental Age for Young Children with Developmental Disabilities

    Science.gov (United States)

    DeVeney, Shari L.; Hoffman, Lesa; Cress, Cynthia J.

    2012-01-01

    Purpose: In this study, the authors compared a multiple-domain strategy for assessing developmental age of young children with developmental disabilities who were at risk for long-term reliance on augmentative and alternative communication (AAC) with a communication-based strategy composed of receptive language and communication indices that may…

  15. Action Video Game Experience Related to Altered Large-Scale White Matter Networks.

    Science.gov (United States)

    Gong, Diankun; Ma, Weiyi; Gong, Jinnan; He, Hui; Dong, Li; Zhang, Dan; Li, Jianfu; Luo, Cheng; Yao, Dezhong

    2017-01-01

    With action video games (AVGs) becoming increasingly popular worldwide, the cognitive benefits of AVG experience have attracted continuous research attention over the past two decades. Research has repeatedly shown that AVG experience can causally enhance cognitive ability and is related to neural plasticity in gray matter and functional networks in the brain. However, the relation between AVG experience and the plasticity of white matter (WM) network still remains unclear. WM network modulates the distribution of action potentials, coordinating the communication between brain regions and acting as the framework of neural networks. And various types of cognitive deficits are usually accompanied by impairments of WM networks. Thus, understanding this relation is essential in assessing the influence of AVG experience on neural plasticity and using AVG experience as an interventional tool for impairments of WM networks. Using graph theory, this study analyzed WM networks in AVG experts and amateurs. Results showed that AVG experience is related to altered WM networks in prefrontal networks, limbic system, and sensorimotor networks, which are related to cognitive control and sensorimotor functions. These results shed new light on the influence of AVG experience on the plasticity of WM networks and suggested the clinical applicability of AVG experience.

  16. Action Video Game Experience Related to Altered Large-Scale White Matter Networks

    Directory of Open Access Journals (Sweden)

    Diankun Gong

    2017-01-01

    Full Text Available With action video games (AVGs becoming increasingly popular worldwide, the cognitive benefits of AVG experience have attracted continuous research attention over the past two decades. Research has repeatedly shown that AVG experience can causally enhance cognitive ability and is related to neural plasticity in gray matter and functional networks in the brain. However, the relation between AVG experience and the plasticity of white matter (WM network still remains unclear. WM network modulates the distribution of action potentials, coordinating the communication between brain regions and acting as the framework of neural networks. And various types of cognitive deficits are usually accompanied by impairments of WM networks. Thus, understanding this relation is essential in assessing the influence of AVG experience on neural plasticity and using AVG experience as an interventional tool for impairments of WM networks. Using graph theory, this study analyzed WM networks in AVG experts and amateurs. Results showed that AVG experience is related to altered WM networks in prefrontal networks, limbic system, and sensorimotor networks, which are related to cognitive control and sensorimotor functions. These results shed new light on the influence of AVG experience on the plasticity of WM networks and suggested the clinical applicability of AVG experience.

  17. 5 CFR 9901.345 - Accelerated Compensation for Developmental Positions (ACDP).

    Science.gov (United States)

    2010-01-01

    ... Developmental Positions (ACDP). 9901.345 Section 9901.345 Administrative Personnel DEPARTMENT OF DEFENSE HUMAN RESOURCES MANAGEMENT AND LABOR RELATIONS SYSTEMS (DEPARTMENT OF DEFENSE-OFFICE OF PERSONNEL MANAGEMENT... policy. ACDP recognizes growth and development in the acquisition of job-related competencies combined...

  18. Persistent Effects of Developmental Exposure to 17α-Ethinylestradiol on the Zebrafish (Danio rerio Brain Transcriptome and Behavior

    Directory of Open Access Journals (Sweden)

    Tove Porseryd

    2017-04-01

    Full Text Available The synthetic estrogen 17α-ethinylestradiol (EE2 is an endocrine disrupting compound of concern due to its persistence and widespread presence in the aquatic environment. Effects of developmental exposure to low concentrations of EE2 in fish on reproduction and behavior not only persisted to adulthood, but have also been observed to be transmitted to several generations of unexposed progeny. To investigate the possible biological mechanisms of the persistent anxiogenic phenotype, we exposed zebrafish embryos for 80 days post fertilization to 0, 3, and 10 ng/L EE2 (measured concentrations 2.14 and 7.34 ng/L. After discontinued exposure, the animals were allowed to recover for 120 days in clean water. Adult males and females were later tested for changes in stress response and shoal cohesion, and whole-brain gene expression was analyzed with RNA sequencing. The results show increased anxiety in the novel tank and scototaxis tests, and increased shoal cohesion in fish exposed during development to EE2. RNA sequencing revealed 34 coding genes differentially expressed in male brains and 62 in female brains as a result of EE2 exposure. Several differences were observed between males and females in differential gene expression, with only one gene, sv2b, coding for a synaptic vesicle protein, that was affected by EE2 in both sexes. Functional analyses showed that in female brains, EE2 had significant effects on pathways connected to the circadian rhythm, cytoskeleton and motor proteins and synaptic proteins. A large number of non-coding sequences including 19 novel miRNAs were also differentially expressed in the female brain. The largest treatment effect in male brains was observed in pathways related to cholesterol biosynthesis and synaptic proteins. Circadian rhythm and cholesterol biosynthesis, previously implicated in anxiety behavior, might represent possible candidate pathways connecting the transcriptome changes to the alterations to behavior

  19. Developmental and genetic determinants of leadership role occupancy among women.

    Science.gov (United States)

    Arvey, Richard D; Zhang, Zhen; Avolio, Bruce J; Krueger, Robert F

    2007-05-01

    The genetic and developmental influences on leadership role occupancy were investigated using a sample of 178 fraternal and 214 identical female twins. Two general developmental factors were identified, one involving formal work experiences and the other a family experiences factor hypothesized to influence whether women move into positions of leadership in organizations. Results indicated that 32% of the variance in leadership role occupancy was associated with heritability. The 2 developmental factors also showed significant correlations with leadership role occupancy. However, after genetic factors were partialed out, only the work experience factor was significantly related to leadership role occupancy. Results are discussed in terms of prior life events and experiences that may trigger leadership development and the limitations of this study. 2007 APA, all rights reserved

  20. Remote sensing detection of gold related alteration zones in Um Rus area, Central Eastern Desert of Egypt

    Science.gov (United States)

    Amer, Reda; Kusky, Timothy; El Mezayen, Ahmed

    2012-01-01

    Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and Phased Array L-band Synthetic Aperture Radar (PALSAR) images covering the Um Rus area in the Central Eastern Desert of Egypt were evaluated for mapping geologic structure, lithology, and gold-related alteration zones. The study area is covered by Pan-African basement rocks including gabbro and granodiorite intruded into a variable mixture of metavolcanics and metasediments. The first three principal component analyses (PCA1, PCA2, PCA3) in a Red-Green-Blue (RGB) of the visible through shortwave-infrared (VNIR + SWIR) ASTER bands enabled the discrimination between lithological units. The results show that ASTER band ratios ((2 + 4)/3, (5 + 7)/6, (7 + 9)/8) in RGB identifies the lithological units and discriminates the granodiorite very well from the adjacent rock units.The granodiorites are dissected by gold-bearing quartz veins surrounded by alteration zones. The microscopic examination of samples collected from the alteration zones shows sericitic and argillic alteration zones. The Spectral Angle Mapper (SAM) and Spectral Information Divergence (SID) supervised classification methods were applied using the reference spectra of the USGS spectral library. The results show that these classification methods are capable of mapping the alteration zones as indicated by field verification work. The PALSAR image was enhanced for fracture mapping using the second moment co-occurrence filter. Overlying extracted faults and alteration zone classification images show that the N30E and N-S fractures represent potential zones for gold exploration. It is concluded that the proposed methods can be used as a powerful tool for ore deposit exploration.

  1. Altered Neural Activity during Irony Comprehension in Unaffected First-Degree Relatives of Schizophrenia Patients—An fMRI Study

    Directory of Open Access Journals (Sweden)

    Róbert Herold

    2018-01-01

    Full Text Available Irony is a type of figurative language in which the literal meaning of the expression is the opposite of what the speaker intends to communicate. Even though schizophrenic patients are known as typically impaired in irony comprehension and in the underlying neural functions, to date no one has explored the neural correlates of figurative language comprehension in first-degree relatives of schizophrenic patients. In the present study, we examined the neural correlates of irony understanding in schizophrenic patients and in unaffected first-degree relatives of patients compared to healthy adults with functional MRI. Our aim was to investigate if possible alterations of the neural circuits supporting irony comprehension in first-degree relatives of patients with schizophrenia would fulfill the familiality criterion of an endophenotype. We examined 12 schizophrenic patients, 12 first-degree relatives of schizophrenia patients and 12 healthy controls with functional MRI while they were performing irony and control tasks. Different phases of irony processing were examined, such as context processing and ironic statement comprehension. Patients had significantly more difficulty understanding irony than controls or relatives. Patients also showed markedly different neural activation pattern compared to controls in both stages of irony processing. Although no significant differences were found in the performance of the irony tasks between the control group and the relative group, during the fMRI analysis, the relatives showed stronger brain activity in the left dorsolateral prefrontal cortex during the context processing phase of irony tasks than the control group. However, the controls demonstrated higher activations in the left dorsomedial prefrontal cortex and in the right inferior frontal gyrus during the ironic statement phase of the irony tasks than the relative group. Our results show that despite good task performance, first-degree relatives of

  2. Atypical Sulcal Pattern in Children with Developmental Dyslexia and At-Risk Kindergarteners.

    Science.gov (United States)

    Im, Kiho; Raschle, Nora Maria; Smith, Sara Ashley; Ellen Grant, P; Gaab, Nadine

    2016-03-01

    Developmental dyslexia (DD) is highly heritable and previous studies observed reduced cortical volume, white matter integrity, and functional alterations in left posterior brain regions in individuals with DD. The primary sulcal pattern has been hypothesized to relate to optimal organization and connections of cortical functional areas. It is determined during prenatal development and may reflect early, genetically influenced, brain development. We characterize the sulcal pattern using graph-based pattern analysis and investigate whether sulcal patterns in parieto-temporal and occipito-temporal regions are atypical in elementary school-age children with DD and pre-readers/beginning readers (preschoolers/kindergarteners) with a familial risk (elementary school-age children: n [males/females], age range = 17/11, 84-155 months; preschoolers/kindergarteners: 16/15, 59-84 months). The pattern of sulcal basin area in left parieto-temporal and occipito-temporal regions was significantly atypical (more sulcal basins of smaller size) in children with DD and further correlated with reduced reading performance on single- and nonword reading measures. A significantly atypical sulcal area pattern was also confirmed in younger preschoolers/kindergarteners with a familial risk of DD. Our results provide further support for atypical early brain development in DD and suggest that DD may originate from altered organization or connections of cortical areas in the left posterior regions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. mTORC1 Inhibition Corrects Neurodevelopmental and Synaptic Alterations in a Human Stem Cell Model of Tuberous Sclerosis

    Directory of Open Access Journals (Sweden)

    Veronica Costa

    2016-04-01

    Full Text Available Hyperfunction of the mTORC1 pathway has been associated with idiopathic and syndromic forms of autism spectrum disorder (ASD, including tuberous sclerosis, caused by loss of either TSC1 or TSC2. It remains largely unknown how developmental processes and biochemical signaling affected by mTORC1 dysregulation contribute to human neuronal dysfunction. Here, we have characterized multiple stages of neurogenesis and synapse formation in human neurons derived from TSC2-deleted pluripotent stem cells. Homozygous TSC2 deletion causes severe developmental abnormalities that recapitulate pathological hallmarks of cortical malformations in patients. Both TSC2+/− and TSC2−/− neurons display altered synaptic transmission paralleled by molecular changes in pathways associated with autism, suggesting the convergence of pathological mechanisms in ASD. Pharmacological inhibition of mTORC1 corrects developmental abnormalities and synaptic dysfunction during independent developmental stages. Our results uncouple stage-specific roles of mTORC1 in human neuronal development and contribute to a better understanding of the onset of neuronal pathophysiology in tuberous sclerosis.

  4. A Developmental Neuroscience Perspective on Affect-Biased Attention

    Science.gov (United States)

    Morales, Santiago; Fu, Xiaoxue; Pérez-Edgar, Koraly E.

    2016-01-01

    There is growing interest regarding the impact of affect-biased attention on psychopathology. However, most of the research to date lacks a developmental approach. In the present review, we examine the role affect-biased attention plays in shaping socioemotional trajectories within a developmental neuroscience framework. We propose that affect-biased attention, particularly if stable and entrenched, acts as a developmental tether that helps sustain early socioemotional and behavioral profiles over time, placing some individuals on maladaptive developmental trajectories. Although most of the evidence is found in the anxiety literature, we suggest that these relations may operate across multiple domains of interest, including positive affect, externalizing behaviors, drug use, and eating behaviors. We also review the general mechanisms and neural correlates of affect-biased attention, as well as the current evidence for the co-development of attention and affect. Based on the reviewed literature, we propose a model that may help us better understand the nuances of affect-biased attention across development. The model may serve as a strong foundation for ongoing attempts to identify neurocognitive mechanisms and intervene with individuals at risk. Finally, we discuss open issues for future research that may help bridge existing gaps in the literature. PMID:27606972

  5. Developmental origins of brain disorders: roles for dopamine

    Directory of Open Access Journals (Sweden)

    Kelli M Money

    2013-12-01

    Full Text Available Neurotransmitters and neuromodulators, such as dopamine, participate in a wide range of behavioral and cognitive functions in the adult brain, including movement, cognition, and reward. Dopamine-mediated signaling plays a fundamental neurodevelopmental role in forebrain differentiation and circuit formation. These developmental effects, such as modulation of neuronal migration and dendritic growth, occur before synaptogenesis and demonstrate novel roles for dopaminergic signaling beyond neuromodulation at the synapse. Pharmacologic and genetic disruptions demonstrate that these effects are brain region- and receptor subtype-specific. For example, the striatum and frontal cortex exhibit abnormal neuronal structure and function following prenatal disruption of dopamine receptor signaling. Alterations in these processes are implicated in the pathophysiology of neuropsychiatric disorders, and emerging studies of neurodevelopmental disruptions may shed light on the pathophysiology of abnormal neuronal circuitry in neuropsychiatric disorders.

  6. A developmental metatheory of psychopathology.

    Science.gov (United States)

    Karasu, T B

    1994-01-01

    The author proposes an integrative model of psychopathology in light of the contemporary need to bridge diverse ideological frameworks. This model has its major foundations in drive, ego, object relations, and self psychoanalytic perspectives as they impact upon interactional patterns of infancy. The chronology of these theoretical orientations is presented as parallel to a changing focus upon different successive stages in the course of individual development. The longstanding controversy between conflict and deficit theories, which undergirds the various schools of thought, is addressed: a developmental orientation is offered as the overriding conceptual connection between them. Conflict and deficit phenomena are regarded as intertwined and not incompatible: Unconscious drives, desires and wishes, ego defenses, and compromise formations as well as object relationship deficiencies and structural voids and defects in the self are combined to encompass a broad spectrum of psychopathology and its sources: the above intrapsychic and interpersonal factors are interfaced with significant reciprocal dyadic (mother/child) and triadic (father/mother/child) influences upon ongoing maturational processes. For heuristic purposes, a fourfold matrix--dyadic deficit, dyadic conflict, triadic deficit, and triadic conflict--is delineated. Clinical characteristics and developmental precursors of each of the four prototypes, especially with regard to early relational events, are examined.

  7. Developmental plasticity: Friend or foe?

    Science.gov (United States)

    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.

  8. Altered Amygdala Development and Fear Processing in Prematurely Born Infants

    Science.gov (United States)

    Cismaru, Anca Liliana; Gui, Laura; Vasung, Lana; Lejeune, Fleur; Barisnikov, Koviljka; Truttmann, Anita; Borradori Tolsa, Cristina; Hüppi, Petra S.

    2016-01-01

    Context: Prematurely born children have a high risk of developmental and behavioral disabilities. Cerebral abnormalities at term age have been clearly linked with later behavior alterations, but existing studies did not focus on the amygdala. Moreover, studies of early amygdala development after premature birth in humans are scarce. Objective: To compare amygdala volumes in very preterm infants at term equivalent age (TEA) and term born infants, and to relate premature infants’ amygdala volumes with their performance on the Laboratory Temperament Assessment Battery (Lab-TAB) fear episode at 12 months. Participants: Eighty one infants born between 2008 and 2014 at the University Hospitals of Geneva and Lausanne, taking part in longitudinal and functional imaging studies, who had undergone a magnetic resonance imaging (MRI) scan at TEA enabling manual amygdala delineation. Outcomes: Amygdala volumes assessed by manual segmentation of MRI scans; volumes of cortical and subcortical gray matter, white matter and cerebrospinal fluid (CSF) automatically segmented in 66 infants; scores for the Lab-TAB fear episode for 42 premature infants at 12 months. Results: Amygdala volumes were smaller in preterm infants at TEA than term infants (mean difference 138.03 mm3, p amygdala volumes were larger than left amygdala volumes (mean difference 36.88 mm3, p Amygdala volumes showed significant correlation with the intensity of the escape response to a fearsome toy (rs = 0.38, p = 0.013), and were larger in infants showing an escape response compared to the infants showing no escape response (mean difference 120.97 mm3, p = 0.005). Amygdala volumes were not significantly correlated with the intensity of facial fear, distress vocalizations, bodily fear and positive motor activity in the fear episode. Conclusion: Our results indicate that premature birth is associated with a reduction in amygdala volumes and white matter volumes at TEA, suggesting that altered amygdala development

  9. Evolution of developmental sequences in lepidosaurs

    Directory of Open Access Journals (Sweden)

    Tomasz Skawiński

    2017-04-01

    Full Text Available Background Lepidosaurs, a group including rhynchocephalians and squamates, are one of the major clades of extant vertebrates. Although there has been extensive phylogenetic work on this clade, its interrelationships are a matter of debate. Morphological and molecular data suggest very different relationships within squamates. Despite this, relatively few studies have assessed the utility of other types of data for inferring squamate phylogeny. Methods We used developmental sequences of 20 events in 29 species of lepidosaurs. These sequences were analysed using event-pairing and continuous analysis. They were transformed into cladistic characters and analysed in TNT. Ancestral state reconstructions were performed on two main phylogenetic hypotheses of squamates (morphological and molecular. Results Cladistic analyses conducted using characters generated by these methods do not resemble any previously published phylogeny. Ancestral state reconstructions are equally consistent with both morphological and molecular hypotheses of squamate phylogeny. Only several inferred heterochronic events are common to all methods and phylogenies. Discussion Results of the cladistic analyses, and the fact that reconstructions of heterochronic events show more similarities between certain methods rather than phylogenetic hypotheses, suggest that phylogenetic signal is at best weak in the studied developmental events. Possibly the developmental sequences analysed here evolve too quickly to recover deep divergences within Squamata.

  10. Intestinal permeability and nutritional status in developmental disorders.

    Science.gov (United States)

    Souza, Nilian Carla Silva; Mendonca, Jacqueline Nakau; Portari, Guilherme Vannucchi; Jordao Junior, Alceu Afonso; Marchini, Julio Sergio; Chiarello, Paula Garcia

    2012-01-01

    Autism is a developmental disorder with a possible connection between dietary components and triggering or worsening of symptoms. An altered intestinal permeability might allow absorption of incompletely digested peptides (gluten and casein) that could produce opioid-like activity on the brain, causing significant changes in behavior. To assess the intestinal permeability and nutritional status of participants with developmental disorders to determine if changes in the intestinal mucosal barrier and/or injury to the intercellular junctions have occurred that might justify application of further dietary modifications. To assess intestinal permeability, the research team analyzed participants urine under fasting conditions, using gas chromatography to determine chromatographic peaks. To assess nutritional status, the team determined participants heights and weights and performed a bioelectric bioimpedance examination at least 4 hours after their most recent meal. In addition, the team determined food intake using three diet diaries. They asked participants and caregivers to register each food consumed during 2 nonconsecutive weekdays and 1 weekend day. The study occurred at the Ribeirao Preto School of Medicine, Sao Paulo University. Seven participants aged 9 to 23 years with developmental disorders (the developmental group, DG) completed the study. The research team recruited them through the Association of Friends of the Autistic Persons of Ribeirao Preto in Ribeirao Preto, Brazil. The control group (CG) consisted of nonsmoking healthy volunteers in the general population who were similar in age to the experimental group and did not suffer from diseases that potentially could influence nutritional status and intestinal function. To assess intestinal permeability, participants ingested 150 mL of an isosmolar solution of the sugars mannitol (2 g) and lactulose (7.5 g) under fasting conditions and the researchers collected all voided urine over a period of 5 hours

  11. Brief Report: Developmental Change in Theory of Mind Abilities in Children with Autism.

    Science.gov (United States)

    Steele, Shelly; Joseph, Robert M.; Tager-Flusberg, Helen

    2003-01-01

    A longitudinal study investigated developmental change in theory of mind among 57 children (ages 4-14) with autism. Theory of mind tests were administered on an initial visit and one year later. Data indicated significant developmental improvement in theory of mind ability, which was primarily related to the children's language ability. (Contains…

  12. Stress-related behavioral alterations accompanying cocaine toxicity: the effects of mixed opioid drugs.

    Science.gov (United States)

    Hayase, T; Yamamoto, Y; Yamamoto, K

    2000-12-01

    The present study evaluated the effects of mixed opioid drugs on the severity of cocaine (COCA) toxicity by examining stress-related behavioral alterations in mice. In order to ascertain the strength of the stress, the continuous observation of the behavioral symptoms in the cage and the forced swimming test (Porsolt test) were performed in the COCA (75 mg/kg, i.p.)-treated groups, with or without the mixed mu-kappa receptor-related opioid drugs, buprenorphine (BUP) and pentazocine (PEN). Using the high-sensitivity activity measuring instrument Supermex, both the spontaneous behaviors in the cage and the forced swimming behaviors in the water were assessed as activity counts. The behavioral alterations in the COCA-treated groups were compared with a group of mice given a 10 min immobilization stress (IM group). In the COCA-only group, a prolonged increase in the spontaneous behaviors accompanied by convulsive seizures was observed even in the surviving mice, unlike in the IM group. However, an acceleration of behavioral despair in the Porsolt test similar to that observed in the IM group was observed in the COCA group after the disappearance of the acute toxic symptoms (5 hours after the COCA treatment). Among the opioid-treated groups, the mortality rate was attenuated only in the COCA-BUP (0.25 mg/kg, i.p.) group. In the COCA-BUP group, a prolonged suppression of the morbid hyperactivity in the cage except for the convulsive seizures, and a normalization of the swimming behavior in the Porsolt test were observed in the survivors. On the other hand, in the COCA-PEN (5 mg/kg, i.p.) group, the swimming behavior in the Porsolt test was abnormally increased in addition to the prolonged morbid hyperactivity in the cage. Therefore, the COCA-induced stress-related behaviors were normalized in the group of mice treated with BUP, a group with a good prognosis.

  13. Taxonomic and developmental aspects of radiosensitivity

    International Nuclear Information System (INIS)

    Harrison, F.L.; Anderson, S.L.

    1996-11-01

    Considerable information is available on the effects of radioactivity on adult and early life stages of organisms. The preponderance of data is on mortality after a single irradiation with relatively high doses. Unfortunately, because experiments were carried out under different conditions and for different time periods, the validity of comparing the results from different laxonomic groups is questionable. In general, the conclusions are that there is a relationship (1) between radioresistance to high doses of acute radiation and taxonomy of the organism, primitive forms being more radioresistant than complex vertebrates and (2) between radiosensitivity and developmental stage, early life stages being more sensitive than later stages. The first conclusion may be related to the capability of the organism to repopulate cells and to differentiate and redifferentiate them; the second to the rate of cellular division and to the degree of differentiation. In question, however, is the relevance of the responses from high levels of acute radiation to that of the responses to long-term exposure to low levels of radiation, which are ecologically of more interest. Data from studies of the effects of acute and chronic exposure on development of gametes and zygotes indicate that, for some fishes and invertebrates, responses at the cellular and molecular levels show effect levels comparable to those observed in some mammals. Acute doses between 0,05 and 0.5Cy and dose rates between 0.02 to 0.2mCy/h appear to define critical ranges in which detrimental effects on fertility are first observed in a variety of radiosensitive organisms. To better understand inherent radiosensitivity, we need more information on the ability of cells to repopulate and differentiate and to prevent or repair damage to biological critical molecules, such as DNA, because these factors may alter significantly organisms'' responses to radiation

  14. Taxonomic and developmental aspects of radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, F.L. [Lawrence Livermore National Lab., CA (United States); Anderson, S.L. [Lawrence Berkeley National Lab., CA (United States)

    1996-11-01

    Considerable information is available on the effects of radioactivity on adult and early life stages of organisms. The preponderance of data is on mortality after a single irradiation with relatively high doses. Unfortunately, because experiments were carried out under different conditions and for different time periods, the validity of comparing the results from different laxonomic groups is questionable. In general, the conclusions are that there is a relationship (1) between radioresistance to high doses of acute radiation and taxonomy of the organism, primitive forms being more radioresistant than complex vertebrates and (2) between radiosensitivity and developmental stage, early life stages being more sensitive than later stages. The first conclusion may be related to the capability of the organism to repopulate cells and to differentiate and redifferentiate them; the second to the rate of cellular division and to the degree of differentiation. In question, however, is the relevance of the responses from high levels of acute radiation to that of the responses to long-term exposure to low levels of radiation, which are ecologically of more interest. Data from studies of the effects of acute and chronic exposure on development of gametes and zygotes indicate that, for some fishes and invertebrates, responses at the cellular and molecular levels show effect levels comparable to those observed in some mammals. Acute doses between 0,05 and 0.5Cy and dose rates between 0.02 to 0.2mCy/h appear to define critical ranges in which detrimental effects on fertility are first observed in a variety of radiosensitive organisms. To better understand inherent radiosensitivity, we need more information on the ability of cells to repopulate and differentiate and to prevent or repair damage to biological critical molecules, such as DNA, because these factors may alter significantly organisms` responses to radiation.

  15. Developmental exposure to terbutaline and chlorpyrifos: pharmacotherapy of preterm labor and an environmental neurotoxicant converge on serotonergic systems in neonatal rat brain regions

    International Nuclear Information System (INIS)

    Aldridge, Justin E.; Meyer, Armando; Seidler, Frederic J.; Slotkin, Theodore A.

    2005-01-01

    Developmental exposure to unrelated neurotoxicants can nevertheless produce similar neurobehavioral outcomes. We examined the effects of developmental exposure to terbutaline, a tocolytic β 2 -adrenoceptor agonist used to arrest preterm labor, and chlorpyrifos (CPF), a widely used organophosphate pesticide, on serotonin (5HT) systems. Treatments were chosen to parallel periods typical of human developmental exposures, terbutaline (10 mg/kg) on postnatal days (PN) 2-5 and CPF (5 mg/kg) on PN11-14, with assessments conducted on PN45, comparing each agent alone as well as sequential administration of both. Although neither treatment affected growth or viability, each elicited similar alterations in factors that are critical to the function of the 5HT synapse: 5HT 1A receptors, 5HT 2 receptors, and the presynaptic 5HT transporter (5HTT). Either agent elicited global increases in 5HT receptors and the 5HTT in brain regions possessing 5HT cell bodies (midbrain, brainstem) as well as in the hippocampus, which contains 5HT projections. For both terbutaline and CPF, males were affected more than females, although there were some regional disparities in the sex selectivity between the two agents. Both altered 5HT receptor-mediated cell signaling, suppressing stimulatory effects on adenylyl cyclase and enhancing inhibitory effects. When animals were exposed sequentially to both agents, the outcomes were no more than additive and, for many effects, less than additive, suggesting convergence of the two agents on a common set of developmental mechanisms. Our results indicate that 5HT systems represent a target for otherwise unrelated neuroteratogens

  16. Triphenyl phosphate-induced developmental toxicity in zebrafish: Potential role of the retinoic acid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Isales, Gregory M.; Hipszer, Rachel A.; Raftery, Tara D. [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States); Chen, Albert; Stapleton, Heather M. [Division of Environmental Sciences and Policy, Nicholas School of the Environment, Duke University, Durham, NC (United States); Volz, David C., E-mail: volz@mailbox.sc.edu [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States)

    2015-04-15

    Highlights: • Triphenyl phosphate-induced toxicity in zebrafish embryos is enhanced in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate uptake or metabolism within zebrafish embryos is not altered in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate decreases expression of cytochrome P450 26a1 in zebrafish embryos. • Triphenyl phosphate inhibits retinoic acid-induced activation of human retinoic acid receptors. - Abstract: Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) – a high-production volume organophosphate-based flame retardant – results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) – a nuclear receptor that regulates vertebrate heart morphogenesis – in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5–72 h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) – a primary TPP metabolite – were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) – a major target gene for RA-induced RAR activation in zebrafish – and found that RA and TPP exposure resulted in a ∼5-fold increase and decrease in cyp26a1 expression, respectively, relative to vehicle-exposed embryos. To address whether TPP may

  17. Developmental toxicity assessment of common excipients using a stem cell-based in vitro morphogenesis model.

    Science.gov (United States)

    Yuan, Chloe J; Marikawa, Yusuke

    2017-11-01

    Various chemical compounds can inflict developmental toxicity when sufficiently high concentrations are exposed to embryos at the critical stages of development. Excipients, such as coloring agents and preservatives, are pharmacologically inactive ingredients that are included in various medications, foods, and cosmetics. However, concentrations that may adversely affect embryo development are largely unknown for most excipients. Here, the lowest observed adverse effect level (LOAEL) to inflict developmental toxicity was assessed for three coloring agents (allura red, brilliant blue, and tartrazine) and three preservatives (butylated hydroxyanisole, metabisulfite, and methylparaben). Adverse impact of a compound exposure was determined using the stem cell-based in vitro morphogenesis model, in which three-dimensional cell aggregates, or embryoid bodies (EBs), recapitulate embryonic processes of body axis elongation and patterning. LOAEL to impair EB morphogenesis was 200 μM for methylparaben, 400 μM for butylated hydroxyanisole, 600 μM for allura red and brilliant blue, and 1000 μM for metabisulfite. Gene expression analyses of excipient-treated EBs revealed that butylated hydroxyanisole and methylparaben significantly altered profiles of developmental regulators involved in axial elongation and patterning of the body. The present study may provide a novel in vitro approach to investigate potential developmental toxicity of common excipients with mechanistic insights. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Computers in Education of Children with Intellectual and Related Developmental Disorders

    Directory of Open Access Journals (Sweden)

    Valentina Kirinic

    2010-03-01

    Full Text Available Children suffering from intellectual deficiency and disorders arising from such a condition tend to be provided with a specific form of education, depending on the deficiency type and degree. Apart from the disorder itself, the acquisition of knowledge, skills and learning habits depends on the children’s motivation for learning, as well as the accessibility of the computer. When used in conformance with pedagogical, didactic and clinical standards, the computer as an educational aid may prove helpful for education and training of children with developmental disorders. Using computers also enables communication and fosters communication skills resulting in the development of self-confidence.

  19. Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Gazdzinski, Lisa M.; Cormier, Kyle; Lu, Fred G.; Lerch, Jason P.; Wong, C. Shun; Nieman, Brian J.

    2012-01-01

    Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.

  20. Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gazdzinski, Lisa M.; Cormier, Kyle [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Lu, Fred G. [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Lerch, Jason P. [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Wong, C. Shun [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Department of Radiation Oncology, University of Toronto, Toronto (Canada); Nieman, Brian J., E-mail: bjnieman@phenogenomics.ca [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

    2012-12-01

    Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.

  1. Developmental neurotoxicity of pyrethroid insecticides in zebrafish embryos.

    Science.gov (United States)

    DeMicco, Amy; Cooper, Keith R; Richardson, Jason R; White, Lori A

    2010-01-01

    Pyrethroid insecticides are one of the most commonly used residential and agricultural insecticides. Based on the increased use of pyrethroids and recent studies showing that pregnant women and children are exposed to pyrethroids, there are concerns over the potential for developmental neurotoxicity. However, there have been relatively few studies on the developmental neurotoxicity of pyrethroids. In this study, we sought to investigate the developmental toxicity of six common pyrethroids, three type I compounds (permethrin, resmethrin, and bifenthrin) and three type II compounds (deltamethrin, cypermethrin, and lambda-cyhalothrin), and to determine whether zebrafish embryos may be an appropriate model for studying the developmental neurotoxicity of pyrethroids. Exposure of zebrafish embryos to pyrethroids caused a dose-dependent increase in mortality and pericardial edema, with type II compounds being the most potent. At doses approaching the LC(50), permethrin and deltamethrin caused craniofacial abnormalities. These findings are consistent with mammalian studies demonstrating that pyrethroids are mildly teratogenic at very high doses. However, at lower doses, body axis curvature and spasms were observed, which were reminiscent of the classic syndromes observed with pyrethroid toxicity. Treatment with diazepam ameliorated the spasms, while treatment with the sodium channel antagonist MS-222 ameliorated both spasms and body curvature, suggesting that pyrethroid-induced neurotoxicity is similar in zebrafish and mammals. Taken in concert, these data suggest that zebrafish may be an appropriate alternative model to study the mechanism(s) responsible for the developmental neurotoxicity of pyrethroid insecticides and aid in identification of compounds that should be further tested in mammalian systems.

  2. [Environmental and genetic variables related with alterations in language acquisition in early childhood].

    Science.gov (United States)

    Moriano-Gutierrez, A; Colomer-Revuelta, J; Sanjuan, J; Carot-Sierra, J M

    2017-01-01

    A great deal of research has addressed problems in the correct acquisition of language, but with few overall conclusions. The reasons for this lie in the individual variability, the existence of different measures for assessing language and the fact that a complex network of genetic and environmental factors are involved in its development. To review the environmental and genetic variables that have been studied to date, in order to gain a better under-standing of the causes of specific language impairment and create new evidence that can help in the development of screening systems for the early detection of these disorders. The environmental variables related with poorer early child language development include male gender, low level of education of the mother, familial history of problems with language or psychiatric problems, perinatal problems and health problems in early childhood. Bilingualism seems to be a protective factor. Temperament and language are related. Within the genetic factors there are several specific genes associated with language, two of which have a greater influence on its physiological acquisition: FOXP2 and CNTNAP2. The other genes that are most related with specific language disorders are ATP2C2, CMIP, ROBO2, ZNF277 and NOP9. The key to comprehending the development of specific language disorders lies in reaching an understanding of the true role played by genes in the ontogenesis, in the regulation of the different developmental processes, and how this role is modulated by the environment.

  3. Alteration of gene expression by alcohol exposure at early neurulation.

    Science.gov (United States)

    Zhou, Feng C; Zhao, Qianqian; Liu, Yunlong; Goodlett, Charles R; Liang, Tiebing; McClintick, Jeanette N; Edenberg, Howard J; Li, Lang

    2011-02-21

    We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos. This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube

  4. Comparative developmental neurotoxicity of flame-retardants, polybrominated flame-retardants and organophosphorous compounds, in mice

    Energy Technology Data Exchange (ETDEWEB)

    Eriksson, P.; Johansson, N.; Viberg, H.; Fischer, C.; Fredriksson, A. [Dept. of Environmental Toxicology, Uppsala Univ. (Sweden)

    2004-09-15

    Recently we have reported that certain PBDEs, such as 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47), 2,2',4,4',5- pentabromodiphenyl ether (PBDE 99), 2,2',4,4',5,5'-hexabromodiphenyl ether (PBDE153) and 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (PBDE 209) can cause developmental neurotoxic effects when given to neonatal mice. The developmental neurotoxic effects after neonatal exposure to PBDE 209 are suggested to be caused by a metabolite (possible de-brominated one). Neonatal exposure HBCDD has also been shown to cause developmental neurotoxic effects. Neonatal exposure to PBDE 99, PBDE 153 and HBCDD was also found to affect learning and memory in the adult animal. The induction of permanent aberration in spontaneous behaviour was induced during limited period of the neonatal brain development. The altered spontaneous behaviour was also seen to worsen with age. In these studies we have also found that the cholinergic system is one target that is affected, observed as changes in the response of the cholinergic system and a decrease in cholinergic receptors, and is one of the mechanisms underlying the observed behavioural changes. BFRs so far studied TBBPA appears not to cause developmental neurotoxic effects when administered at the same dose levels to neonatal mice. In the present studies we have investigated whether neonatal exposure to three highly brominated dipehenyl ethers, 2,2',3,4,4',5',6'-heptabromodiphenyl ether (PBDE183), 2,2',3'4'4',5,5',6- octabromodiphenyl ether (PBDE 203) and 2,2',3,3',4,4',5',6'-nonabromodiphenyl ether (PBDE 206) can induce developmental neurotoxic effects, such as aberrations in spontaneous behaviour and in learning and memory. Furthermore, neonatal developmental neurotoxicity effects were also studied for two OPs used as FR, triphenyl phosphate and tris(2-chloro-ethyl)phosphate.

  5. Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: A developmental study

    Science.gov (United States)

    Xavier-Neto, Jose; Carvalho, Murilo; Pascoalino, Bruno dos Santos; Cardoso, Alisson Campos; Costa, Ângela Maria Sousa; Pereira, Ana Helena Macedo; Santos, Luana Nunes; Saito, Ângela; Marques, Rafael Elias; Smetana, Juliana Helena Costa; Consonni, Silvio Roberto; Bandeira, Carla; Costa, Vivian Vasconcelos; Bajgelman, Marcio Chaim; de Oliveira, Paulo Sérgio Lopes; Cordeiro, Marli Tenorio; Gonzales Gil, Laura Helena Vega; Pauletti, Bianca Alves; Granato, Daniela Campos; Paes Leme, Adriana Franco; Freitas-Junior, Lucio; Holanda de Freitas, Carolina Borsoi Moraes; Teixeira, Mauro Martins; Bevilacqua, Estela; Franchini, Kleber

    2017-01-01

    The teratogenic mechanisms triggered by ZIKV are still obscure due to the lack of a suitable animal model. Here we present a mouse model of developmental disruption induced by ZIKV hematogenic infection. The model utilizes immunocompetent animals from wild-type FVB/NJ and C57BL/6J strains, providing a better analogy to the human condition than approaches involving immunodeficient, genetically modified animals, or direct ZIKV injection into the brain. When injected via the jugular vein into the blood of pregnant females harboring conceptuses from early gastrulation to organogenesis stages, akin to the human second and fifth week of pregnancy, ZIKV infects maternal tissues, placentas and embryos/fetuses. Early exposure to ZIKV at developmental day 5 (second week in humans) produced complex manifestations of anterior and posterior dysraphia and hydrocephalus, as well as severe malformations and delayed development in 10.5 days post-coitum (dpc) embryos. Exposure to the virus at 7.5–9.5 dpc induces intra-amniotic hemorrhage, widespread edema, and vascular rarefaction, often prominent in the cephalic region. At these stages, most affected embryos/fetuses displayed gross malformations and/or intrauterine growth restriction (IUGR), rather than isolated microcephaly. Disrupted conceptuses failed to achieve normal developmental landmarks and died in utero. Importantly, this is the only model so far to display dysraphia and hydrocephalus, the harbinger of microcephaly in humans, as well as arthrogryposis, a set of abnormal joint postures observed in the human setting. Late exposure to ZIKV at 12.5 dpc failed to produce noticeable malformations. We have thus characterized a developmental window of opportunity for ZIKV-induced teratogenesis encompassing early gastrulation, neurulation and early organogenesis stages. This should not, however, be interpreted as evidence for any safe developmental windows for ZIKV exposure. Late developmental abnormalities correlated with

  6. Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: A developmental study.

    Directory of Open Access Journals (Sweden)

    Jose Xavier-Neto

    2017-02-01

    Full Text Available The teratogenic mechanisms triggered by ZIKV are still obscure due to the lack of a suitable animal model. Here we present a mouse model of developmental disruption induced by ZIKV hematogenic infection. The model utilizes immunocompetent animals from wild-type FVB/NJ and C57BL/6J strains, providing a better analogy to the human condition than approaches involving immunodeficient, genetically modified animals, or direct ZIKV injection into the brain. When injected via the jugular vein into the blood of pregnant females harboring conceptuses from early gastrulation to organogenesis stages, akin to the human second and fifth week of pregnancy, ZIKV infects maternal tissues, placentas and embryos/fetuses. Early exposure to ZIKV at developmental day 5 (second week in humans produced complex manifestations of anterior and posterior dysraphia and hydrocephalus, as well as severe malformations and delayed development in 10.5 days post-coitum (dpc embryos. Exposure to the virus at 7.5-9.5 dpc induces intra-amniotic hemorrhage, widespread edema, and vascular rarefaction, often prominent in the cephalic region. At these stages, most affected embryos/fetuses displayed gross malformations and/or intrauterine growth restriction (IUGR, rather than isolated microcephaly. Disrupted conceptuses failed to achieve normal developmental landmarks and died in utero. Importantly, this is the only model so far to display dysraphia and hydrocephalus, the harbinger of microcephaly in humans, as well as arthrogryposis, a set of abnormal joint postures observed in the human setting. Late exposure to ZIKV at 12.5 dpc failed to produce noticeable malformations. We have thus characterized a developmental window of opportunity for ZIKV-induced teratogenesis encompassing early gastrulation, neurulation and early organogenesis stages. This should not, however, be interpreted as evidence for any safe developmental windows for ZIKV exposure. Late developmental abnormalities

  7. Sex and disease-related alterations of anterior insula functional connectivity in chronic abdominal pain.

    Science.gov (United States)

    Hong, Jui-Yang; Kilpatrick, Lisa A; Labus, Jennifer S; Gupta, Arpana; Katibian, David; Ashe-McNalley, Cody; Stains, Jean; Heendeniya, Nuwanthi; Smith, Suzanne R; Tillisch, Kirsten; Naliboff, Bruce; Mayer, Emeran A

    2014-10-22

    Resting-state functional magnetic resonance imaging has been used to investigate intrinsic brain connectivity in healthy subjects and patients with chronic pain. Sex-related differences in the frequency power distribution within the human insula (INS), a brain region involved in the integration of interoceptive, affective, and cognitive influences, have been reported. Here we aimed to test sex and disease-related alterations in the intrinsic functional connectivity of the dorsal anterior INS. The anterior INS is engaged during goal-directed tasks and modulates the default mode and executive control networks. By comparing functional connectivity of the dorsal anterior INS in age-matched female and male healthy subjects and patients with irritable bowel syndrome (IBS), a common chronic abdominal pain condition, we show evidence for sex and disease-related alterations in the functional connectivity of this region: (1) male patients compared with female patients had increased positive connectivity of the dorsal anterior INS bilaterally with the medial prefrontal cortex (PFC) and dorsal posterior INS; (2) female patients compared with male patients had greater negative connectivity of the left dorsal anterior INS with the left precuneus; (3) disease-related differences in the connectivity between the bilateral dorsal anterior INS and the dorsal medial PFC were observed in female subjects; and (4) clinical characteristics were significantly correlated to the insular connectivity with the dorsal medial PFC in male IBS subjects and with the precuneus in female IBS subjects. These findings are consistent with the INS playing an important role in modulating the intrinsic functional connectivity of major networks in the resting brain and show that this role is influenced by sex and diagnosis. Copyright © 2014 the authors 0270-6474/14/3414252-08$15.00/0.

  8. Developmental inter-relations between early maternal depression, contextual risks, and interpersonal stress, and their effect on later child cognitive functioning.

    Science.gov (United States)

    Jensen, Sarah K G; Dumontheil, Iroise; Barker, Edward D

    2014-07-01

    Maternal depression and contextual risks (e.g. poverty) are known to impact children's cognitive and social functioning. However, few published studies have examined how stress in the social environment (i.e. interpersonal stress) might developmentally inter-relate with maternal depression and contextual risks to negatively affect a child in these domains. This was the purpose of the current study. Mother-child pairs (n = 6979) from the Avon Longitudinal Study of Parents were the study participants. Mothers reported on depression, contextual risks, and interpersonal stress between pregnancy and 33 months child age. At age 8, the children underwent cognitive assessments and the mothers reported on the children's social cognitive skills. Maternal depression, contextual risks, and interpersonal stress showed strong continuity and developmental inter-relatedness. Maternal depression and contextual risks directly predicted a range of child outcomes, including executive functions and social cognitive skills. Interpersonal stress worked indirectly via maternal depression and contextual risks to negatively affect child outcomes. Maternal depression and contextual risks each increased interpersonal stress in the household, which, in turn, contributed to reduced child cognitive and social functioning. © 2013 Wiley Periodicals, Inc.

  9. Behavioral effects of developmental methylmercury drinking water exposure in rodents.

    Science.gov (United States)

    Bisen-Hersh, Emily B; Farina, Marcelo; Barbosa, Fernando; Rocha, Joao B T; Aschner, Michael

    2014-04-01

    Early methylmercury (MeHg) exposure can have long-lasting consequences likely arising from impaired developmental processes, the outcome of which has been exposed in several longitudinal studies of affected populations. Given the large number of newborns at an increased risk of learning disabilities associated with in utero MeHg exposure, it is important to study neurobehavioral alterations using ecologically valid and physiologically relevant models. This review highlights the benefits of using the MeHg drinking water exposure paradigm and outlines behavioral outcomes arising from this procedure in rodents. Combination treatments that exacerbate or ameliorate MeHg-induced effects, and possible molecular mechanisms underlying behavioral impairment are also discussed. Copyright © 2013 Elsevier GmbH. All rights reserved.

  10. Role of the pre- and post-natal environment in developmental programming of health and productivity.

    Science.gov (United States)

    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.

  11. White matter microstructure and developmental improvement of hyperactive/impulsive symptoms in Attention-Deficit/Hyperactivity Disorder

    NARCIS (Netherlands)

    Francx, W.C.L.; Zwiers, M.P.; Mennes, M.J.J.; Oosterlaan, J.; Heslenfeld, D.J.; Hoekstra, P.J.; Hartman, C.A.; Franke, B.; Faraone, S.V; O'Dwyer, L.G.; Buitelaar, J.K.

    2015-01-01

    Background A developmental improvement of symptoms in Attention-Deficit/Hyperactivity Disorder (ADHD) is frequently reported, but the underlying neurobiological substrate has not been identified. The aim of this study was to determine whether white matter microstructure is related to developmental

  12. White matter microstructure and developmental improvement of hyperactive/impulsive symptoms in attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Francx, Winke; Zwiers, Marcel P.; Mennes, Maarten; Oosterlaan, Jaap; Heslenfeld, Dirk; Hoekstra, Pieter J.; Hartman, Catharina A.; Franke, Barbara; Faraone, Stephen V.; O'Dwyer, Laurence; Buitelaar, Jan K.

    2015-01-01

    Background: A developmental improvement of symptoms in attention-deficit/hyperactivity disorder (ADHD) is frequently reported, but the underlying neurobiological substrate has not been identified. The aim of this study was to determine whether white matter microstructure is related to developmental

  13. Developmental pathways of change in health-related fitness and motor competence are related to obesity development in childhood

    OpenAIRE

    Rodrigues, Luis Paulo; Lopes, Vítor P.

    2013-01-01

    The epidemic obesity in chi1dhood is well acknowledged worldwide. Althongh researchers agree that explaining models for childhood obesity can include several risk factors, the question remains as to which speci fic predictors can be the touchstone to solving the probIem. In recent years, a modeI of developmental mechanisms influencing the physical activity and weight pathways of children has been presented by Stodden and colleagnes (2008). In this model it is predicted that children ...

  14. HDAC4: a key factor underlying brain developmental alterations in CDKL5 disorder.

    Science.gov (United States)

    Trazzi, Stefania; Fuchs, Claudia; Viggiano, Rocchina; De Franceschi, Marianna; Valli, Emanuele; Jedynak, Paulina; Hansen, Finn K; Perini, Giovanni; Rimondini, Roberto; Kurz, Thomas; Bartesaghi, Renata; Ciani, Elisabetta

    2016-09-15

    Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase predominantly expressed in the brain. Mutations of the CDKL5 gene lead to CDKL5 disorder, a neurodevelopmental pathology that shares several features with Rett Syndrome and is characterized by severe intellectual disability. The phosphorylation targets of CDKL5 are largely unknown, which hampers the discovery of therapeutic strategies for improving the neurological phenotype due to CDKL5 mutations. Here, we show that the histone deacetylase 4 (HDAC4) is a direct phosphorylation target of CDKL5 and that CDKL5-dependent phosphorylation promotes HDAC4 cytoplasmic retention. Nuclear HDAC4 binds to chromatin as well as to MEF2A transcription factor, leading to histone deacetylation and altered neuronal gene expression. By using a Cdkl5 knockout (Cdkl5 -/Y) mouse model, we found that hypophosphorylated HDAC4 translocates to the nucleus of neural precursor cells, thereby reducing histone 3 acetylation. This effect was reverted by re-expression of CDKL5 or by inhibition of HDAC4 activity through the HDAC4 inhibitor LMK235. In Cdkl5 -/Y mice treated with LMK235, defective survival and maturation of neuronal precursor cells and hippocampus-dependent memory were fully normalized. These results demonstrate a critical role of HDAC4 in the neurodevelopmental alterations due to CDKL5 mutations and suggest the possibility of HDAC4-targeted pharmacological interventions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. NCT and Developmental Psychology: A Welcome Rapprochement

    Science.gov (United States)

    Gauvain, Mary

    2013-01-01

    For over 50 years, developmental psychologists have conducted research around the world to understand the relation between culture and cognition. In fact, psychologists have been interested in this topic for over a century. In the late 1800s, Wundt introduced "Elements of Folk Psychology," the study of how culture becomes part of higher…

  16. Development of the uncinate fasciculus: Implications for theory and developmental disorders.

    Science.gov (United States)

    Olson, Ingrid R; Von Der Heide, Rebecca J; Alm, Kylie H; Vyas, Govinda

    2015-08-01

    The uncinate fasciculus (UF) is a long-range white matter tract that connects limbic regions in the temporal lobe to the frontal lobe. The UF is one of the latest developing tracts, and continues maturing into the third decade of life. As such, individual differences in the maturational profile of the UF may serve to explain differences in behavior. Indeed, atypical macrostructure and microstructure of the UF have been reported in numerous studies of individuals with developmental and psychiatric disorders such as social deprivation and maltreatment, autism spectrum disorders, conduct disorder, risk taking, and substance abuse. The present review evaluates what we currently know about the UF's developmental trajectory and reviews the literature relating UF abnormalities to specific disorders. Additionally, we take a dimensional approach and critically examine symptoms and behavioral impairments that have been demonstrated to cluster with UF aberrations, in an effort to relate these impairments to our speculations regarding the functionality of the UF. We suggest that developmental disorders with core problems relating to memory retrieval, reward and valuation computation, and impulsive decision making may be linked to aberrations in uncinate microstructure. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Development of the uncinate fasciculus: Implications for theory and developmental disorders

    Directory of Open Access Journals (Sweden)

    Ingrid R. Olson

    2015-08-01

    Full Text Available The uncinate fasciculus (UF is a long-range white matter tract that connects limbic regions in the temporal lobe to the frontal lobe. The UF is one of the latest developing tracts, and continues maturing into the third decade of life. As such, individual differences in the maturational profile of the UF may serve to explain differences in behavior. Indeed, atypical macrostructure and microstructure of the UF have been reported in numerous studies of individuals with developmental and psychiatric disorders such as social deprivation and maltreatment, autism spectrum disorders, conduct disorder, risk taking, and substance abuse. The present review evaluates what we currently know about the UF's developmental trajectory and reviews the literature relating UF abnormalities to specific disorders. Additionally, we take a dimensional approach and critically examine symptoms and behavioral impairments that have been demonstrated to cluster with UF aberrations, in an effort to relate these impairments to our speculations regarding the functionality of the UF. We suggest that developmental disorders with core problems relating to memory retrieval, reward and valuation computation, and impulsive decision making may be linked to aberrations in uncinate microstructure.

  18. Transcranial magnetic stimulation in developmental stuttering: Relations with previous neurophysiological research and future perspectives.

    Science.gov (United States)

    Busan, P; Battaglini, P P; Sommer, M

    2017-06-01

    Developmental stuttering (DS) is a disruption of the rhythm of speech, and affected people may be unable to execute fluent voluntary speech. There are still questions about the exact causes of DS. Evidence suggests there are differences in the structure and functioning of motor systems used for preparing, executing, and controlling motor acts, especially when they are speech related. Much research has been obtained using neuroimaging methods, ranging from functional magnetic resonance to diffusion tensor imaging and electroencephalography/magnetoencephalography. Studies using transcranial magnetic stimulation (TMS) in DS have been uncommon until recently. This is surprising considering the relationship between the functionality of the motor system and DS, and the wide use of TMS in motor-related disturbances such as Parkinson's Disease, Tourette's Syndrome, and dystonia. Consequently, TMS could shed further light on motor aspects of DS. The present work aims to investigate the use of TMS for understanding DS neural mechanisms by reviewing TMS papers in the DS field. Until now, TMS has contributed to the understanding of the excitatory/inhibitory ratio of DS motor functioning, also helping to better understand and critically review evidence about stuttering mechanisms obtained from different techniques, which allowed the investigation of cortico-basal-thalamo-cortical and white matter/connection dysfunctions. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  19. Interleukin-6 Contributes to Age-Related Alteration of Cytokine Production by Macrophages

    Science.gov (United States)

    Gomez, Christian R.; Karavitis, John; Palmer, Jessica L.; Faunce, Douglas E.; Ramirez, Luis; Nomellini, Vanessa; Kovacs, Elizabeth J.

    2010-01-01

    Here, we studied in vitro cytokine production by splenic macrophages obtained from young and aged BALB/c wild type (WT) and IL-6 knockout (IL-6 KO) mice. Relative to macrophages obtained from young WT mice given lipopolysaccharide (LPS), those from aged WT mice had decreased production of proinflammatory cytokines. In contrast, when compared to macrophages from young IL-6 KO mice, LPS stimulation yielded higher levels of these cytokines by cells from aged IL-6 KO mice. Aging or IL-6 deficiency did not affected the percentage of F4/80+ macrophages, or the surface expression of Toll-like receptor 4 (TLR4) and components of the IL-6 receptor. Overall, our results indicate that IL-6 plays a role in regulating the age-related defects in macrophages through alteration of proinflammatory cytokines, adding to the complexity of IL-6-mediated impairment of immune cell function with increasing age. PMID:20671912

  20. Developmental trajectory of time perspective: From children to older adults.

    Science.gov (United States)

    Chen, Tao; Liu, Lu-Lu; Cui, Ji-Fang; Chen, Xing-Jie; Wang, Ya

    2016-12-01

    Time perspective is a fundamental dimension of the psychological time construct, with a pervasive and powerful influence on human behavior. However, the developmental trajectory of time perspective across a human lifespan remains unclear. The current study aimed to portray the developmental trajectory of all dimensions of time perspectives from children to older adults in a large sample. A total of 1,901 individuals (aged 9-84 years) completed measures of time perspective. They were then divided into five age groups: children, teenagers, young adults, middle-aged adults, and older adults. Results suggested that each time perspective showed a unique developmental pattern across the lifespan. Moreover, perceived economic situation and education were related to some dimensions of time perspective. © 2016 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  1. DEVELOPMENTAL TAXONOMY OF CONDUCT DISORDER

    OpenAIRE

    Jelena Kostić; Milkica Nešić; Jasminka Marković; Miodrag Stanković

    2015-01-01

    Conduct disorder is a heterogeneous disorder in terms of etiology, course and prognosis, and currently, there is no singular model that would describe the development of the disorder. The results of empirical research on males confirm this heterogeneity, as they point out to two possible developmental pathways: childhood-onset and adolescentonset type. This paper presents the basic elements of developmental taxonomic theory which argues that there are two different developmental pathways to c...

  2. Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies.

    Science.gov (United States)

    Guerrini, Renzo; Parrini, Elena

    2012-12-01

    Rett syndrome is an X-linked neurodevelopmental disorder that manifests in early childhood with developmental stagnation, and loss of spoken language and hand use, with the development of distinctive hand stereotypies, severe cognitive impairment, and autistic features. About 60% of patients have epilepsy. Seizure onset before the age of 3 years is unlikely, and onset after age 20 is rare. Diagnosis of Rett syndrome is based on key clinical elements that identify "typical" Rett syndrome but also "variant" or "atypical" forms. Diagnostic criteria have been modified only slightly over time, even after discovering that MECP2 gene alterations are present in >90% of patients with typical Rett syndrome but only in 50-70% of atypical cases. Over the last several years, intragenic or genomic alterations of the CDKL5 and FOXG1 genes have been associated with severe cognitive impairment, early onset epilepsy and, often, dyskinetic movement disorders, which have variably been defined as Rett variants. It is now clearly emerging that epilepsy has distinctive characteristics in typical Rett syndrome and in the different syndromes caused by CDKL5 and FOXG1 gene alterations. The progressive parting of CDKL5- and FOXG1-gene-related encephalopathies from the core Rett syndrome is reflected by the effort to produce clearer diagnostic criteria for typical and atypical Rett syndrome. Efforts to characterize the molecular pathology underlying these developmental encephalopathies are pointing to abnormalities of telencephalic development, neuronal morphogenesis, maturation and maintenance, and dendritic arborization. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  3. Developmental block and programmed cell death in Bos indicus embryos: effects of protein supplementation source and developmental kinetics.

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    Sheila Merlo Garcia

    Full Text Available The aims of this study were to determine if the protein source of the medium influences zebu embryo development and if developmental kinetics, developmental block and programmed cell death are related. The culture medium was supplemented with either fetal calf serum or bovine serum albumin. The embryos were classified as Fast (n = 1,235 or Slow (n = 485 based on the time required to reach the fourth cell cycle (48 h and 90 h post insemination - hpi -, respectively. The Slow group was further separated into two groups: those presenting exactly 4 cells at 48 hpi (Slow/4 cells and those that reached the fourth cell cycle at 90 hpi (Slow. Blastocyst quality, DNA fragmentation, mitochondrial membrane potential and signs of apoptosis or necrosis were evaluated. The Slow group had higher incidence of developmental block than the Fast group. The embryos supplemented with fetal calf serum had lower quality. DNA fragmentation and mitochondrial membrane potential were absent in embryos at 48 hpi but present at 90 hpi. Early signs of apoptosis were more frequent in the Slow and Slow/4 cell groups than in the Fast group. We concluded that fetal calf serum reduces blastocyst development and quality, but the mechanism appears to be independent of DNA fragmentation. The apoptotic cells detected at 48 hpi reveal a possible mechanism of programmed cell death activation prior to genome activation. The apoptotic cells observed in the slow-developing embryos suggested a relationship between programmed cell death and embryonic developmental kinetics in zebu in vitro-produced embryos.

  4. Developmental Foreign Accent Syndrome: report of a new case

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    Stefanie eKeulen

    2016-03-01

    Full Text Available This paper presents the case of a 17-year-old right-handed Belgian boy with developmental FAS and comorbid developmental apraxia of speech (DAS. Extensive neuropsychological and neurolinguistic investigations demonstrated a normal IQ but impaired planning (visuo-constructional dyspraxia. A Tc-99m-ECD SPECT revealed a significant hypoperfusion in the prefrontal and medial frontal regions, as well as in the lateral temporal regions. Hypoperfusion in the right cerebellum almost reached significance. It is hypothesized that these clinical findings support the view that FAS and DAS are related phenomena following impairment of the cerebro-cerebellar network.

  5. Glycomics and glycoproteomics focused on aging and age-related diseases--Glycans as a potential biomarker for physiological alterations.

    Science.gov (United States)

    Miura, Yuri; Endo, Tamao

    2016-08-01

    Since glycosylation depends on glycosyltransferases, glycosidases, and sugar nucleotide donors, it is susceptible to the changes associated with physiological and pathological conditions. Therefore, alterations in glycan structures may be good targets and biomarkers for monitoring health conditions. Since human aging and longevity are affected by genetic and environmental factors such as diseases, lifestyle, and social factors, a scale that reflects various environmental factors is required in the study of human aging and longevity. We herein focus on glycosylation changes elucidated by glycomic and glycoproteomic studies on aging, longevity, and age-related diseases including cognitive impairment, diabetes mellitus, and frailty. We also consider the potential of glycan structures as biomarkers and/or targets for monitoring physiological and pathophysiological changes. Glycan structures are altered in age-related diseases. These glycans and glycoproteins may be involved in the pathophysiology of these diseases and, thus, be useful diagnostic markers. Age-dependent changes in N-glycans have been reported previously in cohort studies, and characteristic N-glycans in extreme longevity have been proposed. These findings may lead to a deeper understanding of the mechanisms underlying aging as well as the factors influencing longevity. Alterations in glycosylation may be good targets and biomarkers for monitoring health conditions, and be applicable to studies on age-related diseases and healthy aging. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Population genetic structure of a centipede species with high levels of developmental instability.

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    Giuseppe Fusco

    Full Text Available European populations of the geophilomorph centipede Haplophilus subterraneus show a high proportion of individuals with morphological anomalies, suggesting high levels of developmental instability. The broad geographic distribution of this phenomenon seems to exclude local environmental causes, but the source of instability is still to be identified. The goal of the present study was to collect quantitative data on the occurrence of phenodeviants in different populations, along with data on the patterns of genetic variation within and between populations, in order to investigate possible association between developmental instability and genetic features. In a sample of 11 populations of H. subterraneus, distributed in western and central Europe, we looked for phenodeviants, in particular with respect to trunk morphology, and studied genetic variation through the genotyping of microsatellite loci. Overall, no support was found to the idea that developmental instability in H. subterraneus is related to a specific patterns of genetic variation, including inbreeding estimates. We identified a major genetic partition that subdivides French populations from the others, and a low divergence among northwestern areas, which are possibly related to the post-glacial recolonization from southern refugia and/or to recent anthropogenic soil displacements. A weak correlation between individual number of leg bearing segments and the occurrence of trunk anomalies seems to support a trade-off between these two developmental traits. These results, complemented by preliminary data on developmental stability in two related species, suggest that the phenomenon has not a simple taxonomic distribution, while it exhibits an apparent localization in central and eastern Europe.

  7. Motor activity changes induced by sub-encephalopathic lead exposure during different developmental phases in rats

    International Nuclear Information System (INIS)

    Van Rooyen, J.M.; Offermeier, J.; Brand, L.; Botha, F.; Rossouw, J.; Lategan, A.J.; Botes, M.S.

    1988-01-01

    Two groups of rats were exposed to lead (0,2% lead acetate in drinking water) for periods of 21 days during different developmental phases. Lead exposure was initiated on day 1 and day 22 after birth, for rats in groups 1 and 2, respectively. Measurements of locomotor activity (LA) and [ 3 H]spiperone binding assays were performed on day 50 after birth. Lead exposure resulted in the potentiation of the LA effects of 5 mg/kg apomorphine without altering the LA effects of 50 mg/kg piribedil in group 1. Lead exposure resulted in an attenuation of the LA effects of apomorphine and piribedil in group 2. Lead exposure did not alter the K D and B max values of [ 3 H]spiperone in membranes prepared from the rat striatum or nucleus accumbens

  8. Major Changes in Growth Rate and Growth Variability of Beech (Fagus sylvatica L. Related to Soil Alteration and Climate Change in Belgium

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    Nicolas Latte

    2016-08-01

    Full Text Available Global change—particularly climate change, forest management, and atmospheric deposition—has significantly altered forest growing conditions in Europe. The influences of these changes on beech growth (Fagus sylvatica L. were investigated for the past 80 years in Belgium, using non-linear mixed effects models on ring-width chronologies of 149 mature and dominant beech trees (87–186 years old. The effects of the developmental stage (i.e., increasing tree size were filtered out in order to focus on time-dependent growth changes. Beech radial growth was divided into a low-frequency signal (=growth rate, mainly influenced by forest management and atmospheric deposition, and into a high-frequency variability (≈mean sensitivity, mainly influenced by climate change. Between 1930 and 2008, major long-term and time-dependent changes were highlighted. The beech growth rate has decreased by about 38% since the 1950–1960s, and growth variability has increased by about 45% since the 1970–1980s. Our results indicate that (1 before the 1980s, beech growth rate was not predominantly impacted by climate change but rather by soil alteration (i.e., soil compaction and/or nitrogen deposition; and (2 since the 1980s, climate change induced more frequent and intense yearly growth reductions that amplified the growth rate decrease. The highlighted changes were similar in the two ecoregions of Belgium, although more pronounced in the lowlands than in the uplands.

  9. Why developmental psychology is incomplete without comparative and cross-cultural perspectives

    Science.gov (United States)

    Nielsen, Mark; Haun, Daniel

    2016-01-01

    As a discipline, developmental psychology has a long history of relying on animal models and data collected among distinct cultural groups to enrich and inform theories of the ways social and cognitive processes unfold through the lifespan. However, approaches that draw together developmental, cross-cultural and comparative perspectives remain rare. The need for such an approach is reflected in the papers by Heyes (2015 Phil. Trans. R. Soc. B 371, 20150069. (doi:10.1098/rstb.2015.0069)), Schmelz & Call (2015 Phil. Trans. R. Soc. B 371, 20150067. (doi:10.1098/rstb.2015.0067)) and Keller (2015 Phil. Trans. R. Soc. B 371, 20150070. (doi:10.1098/rstb.2015.0070)) in this theme issue. Here, we incorporate these papers into a review of recent research endeavours covering a range of core aspects of social cognition, including social learning, cooperation and collaboration, prosociality, and theory of mind. In so doing, we aim to highlight how input from comparative and cross-cultural empiricism has altered our perspectives of human development and, in particular, led to a deeper understanding of the evolution of the human cultural mind. PMID:26644590

  10. Why developmental psychology is incomplete without comparative and cross-cultural perspectives.

    Science.gov (United States)

    Nielsen, Mark; Haun, Daniel

    2016-01-19

    As a discipline, developmental psychology has a long history of relying on animal models and data collected among distinct cultural groups to enrich and inform theories of the ways social and cognitive processes unfold through the lifespan. However, approaches that draw together developmental, cross-cultural and comparative perspectives remain rare. The need for such an approach is reflected in the papers by Heyes (2015 Phil. Trans. R. Soc. B 371, 20150069. (doi:10.1098/rstb.2015.0069)), Schmelz & Call (2015 Phil. Trans. R. Soc. B 371, 20150067. (doi:10.1098/rstb.2015.0067)) and Keller (2015 Phil. Trans. R. Soc. B 371, 20150070. (doi:10.1098/rstb.2015.0070)) in this theme issue. Here, we incorporate these papers into a review of recent research endeavours covering a range of core aspects of social cognition, including social learning, cooperation and collaboration, prosociality, and theory of mind. In so doing, we aim to highlight how input from comparative and cross-cultural empiricism has altered our perspectives of human development and, in particular, led to a deeper understanding of the evolution of the human cultural mind. © 2015 The Author(s).

  11. Hot and cool executive function in children and adolescents with autism spectrum disorder: Cross-sectional developmental trajectories.

    Science.gov (United States)

    Kouklari, Evangelia-Chrysanthi; Tsermentseli, Stella; Monks, Claire P

    2017-10-20

    The development of executive function (EF) in autism spectrum disorder (ASD) has only been investigated using "cool"-cognitive-EF tasks. Little is known about the development of "hot"-affective-EF and whether it follows a similar developmental pathway. This study employed a cross-sectional developmental trajectories approach to examine the developmental changes in cool (working memory, inhibition, and planning) and hot EF (delay discounting and affective decision-making) of ASD participants (n = 79) and controls (n = 91) relative to age and IQ, shedding more light on the hot-cool EF organization. The developmental trajectories of some aspects of cool EF (working memory and planning) differed significantly as a function of age in ASD participants relative to controls. For both hot EFs, no significant age-related changes were found in either group. These findings extend our understanding regarding the maturation of EF from childhood through adolescence in ASD.

  12. A categorical structure-activity relationship analysis of the developmental toxicity of antithyroid drugs.

    Science.gov (United States)

    Cunningham, Albert R; Carrasquer, C Alex; Mattison, Donald R

    2009-01-01

    The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR) model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

  13. Maternal effects and the evolution of brain size in birds: overlooked developmental constraints.

    Science.gov (United States)

    Garamszegi, L Z; Biard, C; Eens, M; Møller, A P; Saino, N; Surai, P

    2007-01-01

    A central dogma for the evolution of brain size posits that the maintenance of large brains incurs developmental costs, because they need prolonged periods to grow during the early ontogeny. Such constraints are supported by the interspecific relationship between ontological differences and relative brain size in birds and mammals. Given that mothers can strongly influence the development of the offspring via maternal effects that potentially involve substances essential for growing brains, we argue that such effects may represent an important but overlooked component of developmental constraints on brain size. To demonstrate the importance of maternal effect on the evolution of brains, we investigated the interspecific relationship between relative brain size and maternal effects, as reflected by yolk testosterone, carotenoids, and vitamins A and E in a phylogenetic study of birds. Females of species with relatively large brains invested more in eggs in terms of testosterone and vitamin E than females of species with small brains. The effects of carotenoid and vitamin A levels on the evolution of relative brain size were weaker and non-significant. The association between relative brain size and yolk testosterone was curvilinear, suggesting that very high testosterone levels can be suppressive. However, at least in moderate physiological ranges, the positive relationship between components of maternal effects and relative brain size may imply one aspect of developmental costs of large brains. The relationship between vitamin E and relative brain size was weakened when we controlled for developmental mode, and thus the effect of this antioxidant may be indirect. Testosterone-enhanced neurogenesis and vitamin E-mediated defence against oxidative stress may have key functions when the brain of the embryo develops, with evolutionary consequences for relative brain size.

  14. Developmental stages of developmental screening: steps to implementation of a successful program.

    Science.gov (United States)

    Pinto-Martin, Jennifer A; Dunkle, Margaret; Earls, Marian; Fliedner, Dane; Landes, Cynthia

    2005-11-01

    Through the use of 2-stage screening strategies, research studies have shown that autism spectrum disorders and other developmental disabilities can now be detected reliably and with greater validity and in children as young as 18 months of age. Screening and diagnostic practices in the medical and educational arena lag far behind clinical research, however, with the average patient age at time of diagnosis being 3 to 6 years.We discuss the challenges of instituting universal developmental screening as part of pediatric care and present 2 models of existing or planned programs of early screening for autism spectrum disorder and developmental disability (1 in a community-based setting and 1 in a pediatric setting), and discuss the pros and cons of the different strategies.

  15. Gene expression in developing fibres of Upland cotton (Gossypium hirsutum L.) was massively altered by domestication.

    Science.gov (United States)

    Rapp, Ryan A; Haigler, Candace H; Flagel, Lex; Hovav, Ran H; Udall, Joshua A; Wendel, Jonathan F

    2010-11-15

    Understanding the evolutionary genetics of modern crop phenotypes has a dual relevance to evolutionary biology and crop improvement. Modern upland cotton (Gossypium hirsutum L.) was developed following thousands of years of artificial selection from a wild form, G. hirsutum var. yucatanense, which bears a shorter, sparser, layer of single-celled, ovular trichomes ('fibre'). In order to gain an insight into the nature of the developmental genetic transformations that accompanied domestication and crop improvement, we studied the transcriptomes of cotton fibres from wild and domesticated accessions over a developmental time course. Fibre cells were harvested between 2 and 25 days post-anthesis and encompassed the primary and secondary wall synthesis stages. Using amplified messenger RNA and a custom microarray platform designed to interrogate expression for 40,430 genes, we determined global patterns of expression during fibre development. The fibre transcriptome of domesticated cotton is far more dynamic than that of wild cotton, with over twice as many genes being differentially expressed during development (12,626 versus 5273). Remarkably, a total of 9465 genes were diagnosed as differentially expressed between wild and domesticated fibres when summed across five key developmental time points. Human selection during the initial domestication and subsequent crop improvement has resulted in a biased upregulation of components of the transcriptional network that are important for agronomically advanced fibre, especially in the early stages of development. About 15% of the differentially expressed genes in wild versus domesticated cotton fibre have no homology to the genes in databases. We show that artificial selection during crop domestication can radically alter the transcriptional developmental network of even a single-celled structure, affecting nearly a quarter of the genes in the genome. Gene expression during fibre development within accessions and expression

  16. Developmental Delay’ Reconsidered: The Critical Role of Age-Dependent, Co-variant Development

    Directory of Open Access Journals (Sweden)

    Yonata Levy

    2018-04-01

    Full Text Available In memory of Annette Karmiloff-Smith.This paper reviews recent neurobiological research reporting structural co-variance and temporal dependencies in age-dependent gene expression, parameters of cortical maturation, long range connectivity and interaction of the biological network with the environment. This research suggests that age by size trajectories of brain structures relate to functional properties more than absolute sizes. In line with these findings, recent behavioral studies of typically developing children whose language development was delayed reported long term consequences of such delays. As for neurodevelopmental disorders, disrupted developmental timing and slow acquisitional pace are hallmarks of these populations. It is argued that these behavioral and neuro-biological results highlight the need to commit to a developmental model which will reflect the fact that temporal dependencies overseeing structural co-variance among developmental components are major regulatory factors of typical development of the brain/mind network. Consequently, the concept of ‘developmental delay’ in developmental theorizing needs to be reconsidered.

  17. Developmental and Individual Differences in Understanding of Fractions

    Science.gov (United States)

    Siegler, Robert S.; Pyke, Aryn A.

    2013-01-01

    We examined developmental and individual differences in 6th and 8th graders' fraction arithmetic and overall mathematics achievement and related them to differences in understanding of fraction magnitudes, whole number division, executive functioning, and metacognitive judgments within a crosssectional design. Results indicated that the difference…

  18. Emotion and Cognition: An Intricately Bound Developmental Process

    Science.gov (United States)

    Bell, Martha Ann; Wolfe, Christy D.

    2004-01-01

    Regulatory aspects of development can best be understood by research that conceptualizes relations between cognition and emotion. The neural mechanisms associated with regulatory processes may be the same as those associated with higher order cognitive processes. Thus, from a developmental cognitive neuroscience perspective, emotion and cognition…

  19. Developmental Trajectories of Hand Movements in Typical Infants and Those at Risk of Developmental Disorders: An Observational Study of Kinematics during the First Year of Life

    Directory of Open Access Journals (Sweden)

    Lisa Ouss

    2018-02-01

    are significantly associated with age in cohorts of typical and at-risk infantsdiffer significantly at 5–6 months of age, depending on the context: relating either with an object or a person.Environmental and developmental factors shape the developmental trajectories of hand movements in different cohorts: environment for infants with VIMs; stage of development for premature infants and those with West syndrome; and both factors for infants with orality disorders.The curvature of hand movements specifically reflects atypical development in infants with West syndrome when developmental age is considered.We aimed to discriminate between typical and atypical developmental trajectory patterns of at-risk infants in an interactive setting in this observational and longitudinal study, with the assumption that hand movements (HM reflect preverbal communication and its disorders. We examined the developmental trajectories of HM in five cohorts of at-risk infants and one control cohort, followed from ages 2 to 10 months: 25 West syndrome (WS, 13 preterm birth (PB, 16 orality disorder (OD, 14 with visually impaired mothers (VIM, 7 early hospitalization (EH, and 19 typically developing infants (TD. Video-recorded data were collected in three different structured interactive contexts. Descriptors of the hand motion were used to examine the extent to which HM were associated with age and cohort. We obtained four principal results: (i the kinematics of HM (spatial use, curvature, acceleration, and velocity were significantly associated with age in all cohorts; (ii HM significantly differed at 5–6 months of age in TD infants, depending on the context; (iii environmental and developmental factors shaped the developmental trajectories of HM in different cohorts: environment for VIM, development for PB and WS, and both factors for OD and; (iv the curvatures of HM showed atypical development in WS infants when developmental age was considered. These findings support the importance

  20. Developmental Education: A Proposed Model For Guidance and Counseling

    Science.gov (United States)

    Gazda, George M.

    1978-01-01

    Coins a new term for counselors--"developmental education"--which the author defines as developing specific life-coping skills. The article also examines some ethical questions which are related to this intentional manipulation of the human condition. (Author/HMV)

  1. 4D Flow Analysis of BAV-Related Fluid-Dynamic Alterations: Evidences of Wall Shear Stress Alterations in Absence of Clinically-Relevant Aortic Anatomical Remodeling

    Directory of Open Access Journals (Sweden)

    Filippo Piatti

    2017-06-01

    Full Text Available Bicuspid aortic valve (BAV is the most common congenital cardiac disease and is a foremost risk factor for aortopathies. Despite the genetic basis of BAV and of the associated aortopathies, BAV-related alterations in aortic fluid-dynamics, and particularly in wall shear stresses (WSSs, likely play a role in the progression of aortopathy, and may contribute to its pathogenesis. To test whether WSS may trigger aortopathy, in this study we used 4D Flow sequences of phase-contrast cardiac magnetic resonance imaging (CMR to quantitatively compare the in vivo fluid dynamics in the thoracic aorta of two groups of subjects: (i five prospectively enrolled young patients with normo-functional BAV and with no aortic dilation and (ii ten age-matched healthy volunteers. Through the semi-automated processing of 4D Flow data, the aortic bulk flow at peak systole was quantified, and WSSs acting on the endothelium of the ascending aorta were characterized throughout the systolic phase in terms of magnitude and time-dependency through a method recently developed by our group. Variables computed for each BAV patient were compared vs. the corresponding distribution of values obtained for healthy controls. In BAV patients, ascending aorta diameter was measured on cine-CMR images at baseline and at 3-year follow-up. As compared to controls, normo-functional BAV patients were characterized by minor bulk flow disturbances at peak systole. However, they were characterized by evident alterations of WSS distribution and peak values in the ascending aorta. In particular, in four BAV patients, who were characterized by right-left leaflet fusion, WSS peak values exceeded by 27–46% the 90th percentile of the distribution obtained for healthy volunteers. Only in the BAV patient with right-non-coronary leaflet fusion the same threshold was exceeded by 132%. Also, evident alterations in the time-dependency of WSS magnitude and direction were observed. Despite, these fluid

  2. Floral Developmental Pattern Changes on Neoregelia‘Flandria’(BROMELIACEAE Analysed by Markov Chain methodologyADRIANA

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    Adriana Pico

    2003-01-01

    Full Text Available Neoregelia 'Flandria'and N. 'Van Durme'are ornamental cultivars of Bromelia.Propagation by seeds is not viable and prunes constitutes the only way to propagateavoiding alterations. In this article the developmental floral pattern of 72 Bromeliastreated with ANA 190 ppm (T1, Ethrel: ANA + ETHREL,(T2 y ETHREL, (T3 anddivided into two age groups: E1 y E2 are shown. The treatments studied generated moreelongated plants and six new patterns. Using the Markov chain methodology theprobability to evolve to any pattern and the percentage of each were studied.

  3. Parental divorce and developmental progression: an inquiry into their relationship.

    Science.gov (United States)

    Wallerstein, J; Resnikoff, D

    1997-02-01

    The authors argue that the patterning of conscious and unconscious needs, wishes, and expectations that parents and children bring to each other is often profoundly altered under the impact of divorce and the parents' subsequent adult relationships. These changes, which are inherent in the divorce experience, have the power to modify significantly or derail the young child's developmental course. Clinical observations from an ongoing longitudinal research project show striking changes in the child's image of his parents, as portrayed here in the vivid play and fantasy of a psychologically sturdy child, concurrent with psychological changes in both parents and in their parenting. A follow-up, twelve years later, is reported. The authors suggest that the stable parenting of this child's first three years represented an internalised template of good relationships, which enabled him, despite the father's subsequent abandonment, the mother's grave acting out and the stepfather's rejection, to turn away from his disappointment in his parents, to wrest what was available from school, friends and others, and to propel himself forward at each point to the next developmental stage, moving increasingly away from his family towards independence and competence. The consistency of the child's inner life and integrity is contrasted with the depression of his parents and the instability of their parenting.

  4. Time related alterations in digestibility and faecal characteristics as affected by dietary composition in the Nile tilapia (Oreochromis niloticus L.)

    NARCIS (Netherlands)

    Amirkolaie, A.K.; Schrama, J.W.

    2015-01-01

    After being shifted to a new diet, time related alterations in digestibility, faecal waste production and faeces recovery in Nile tilapia were assessed in relation with dietary ingredient composition. Four experimental diets were formulated according to a 2 by 2 factorial design: two starch

  5. Sampling in Developmental Science: Situations, Shortcomings, Solutions, and Standards.

    Science.gov (United States)

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

    2013-12-01

    Sampling is a key feature of every study in developmental science. Although sampling has far-reaching implications, too little attention is paid to sampling. Here, we describe, discuss, and evaluate four prominent sampling strategies in developmental science: population-based probability sampling, convenience sampling, quota sampling, and homogeneous sampling. We then judge these sampling strategies by five criteria: whether they yield representative and generalizable estimates of a study's target population, whether they yield representative and generalizable estimates of subsamples within a study's target population, the recruitment efforts and costs they entail, whether they yield sufficient power to detect subsample differences, and whether they introduce "noise" related to variation in subsamples and whether that "noise" can be accounted for statistically. We use sample composition of gender, ethnicity, and socioeconomic status to illustrate and assess the four sampling strategies. Finally, we tally the use of the four sampling strategies in five prominent developmental science journals and make recommendations about best practices for sample selection and reporting.

  6. Possible Link Between Stress-related Factors and Altered Body Composition in Women with Polycystic Ovarian Syndrome.

    Science.gov (United States)

    Basu, Barnali Ray; Chowdhury, Olivia; Saha, Sudip Kumar

    2018-01-01

    Stress is an invisible factor affecting modern day living and is strongly associated with many disease pathogenesis including polycystic ovarian syndrome (PCOS) in women. PCOS is the most frequent endocrinological disorder that affects women of reproductive age, leading to metabolic dysfunction and body composition alterations. Salivary amylase and cortisol are major stress mediators that have been implicated in PCOS. However, their role in altering body composition in PCOS is yet to be deciphered. The present study aimed at understanding the relation between stress-associated factors and alterations in body composition among PCOS patients. This study enrolled a total of 100 patients (PCOS) and 60 age-matched controls. The female patients were of ages between 13 and 30 years. Standard assay kits were used to evaluate the α-amylase activity and cortisol level in saliva. The participants were chosen on the basis of the Rotterdam American Society for Reproductive Medicine/European Society of Human Reproduction criteria. Saliva was collected from each participant as per the protocol of Salimetrics, USA. Statistical analysis was performed using SPSS version 20 for Windows. The quantitative variables are described as mean ± standard deviation. P stress scenario in their system. Moreover, overweight PCOS participants reflected higher amylase activity than the lean patients participants. Pulse rate, body mass index (BMI), visceral adiposity, and waist-hip ratio (WHR) was considerably higher in the PCOS patients participants compared to controls. A significant correlation could be drawn between the α-amylase activity and BMI or WHR, respectively, among PCOS patients. These observations indicate a strong link between the stress marker and alterations in the body composition parameters of PCOS patients participants. Higher prevalence of stress in PCOS patients participants has a critical role in their altered body composition.

  7. Adaptive developmental delay in Chagas disease vectors: an evolutionary ecology approach.

    Directory of Open Access Journals (Sweden)

    Frédéric Menu

    2010-05-01

    Full Text Available The developmental time of vector insects is important in population dynamics, evolutionary biology, epidemiology and in their responses to global climatic change. In the triatomines (Triatominae, Reduviidae, vectors of Chagas disease, evolutionary ecology concepts, which may allow for a better understanding of their biology, have not been applied. Despite delay in the molting in some individuals observed in triatomines, no effort was made to explain this variability.We applied four methods: (1 an e-mail survey sent to 30 researchers with experience in triatomines, (2 a statistical description of the developmental time of eleven triatomine species, (3 a relationship between development time pattern and climatic inter-annual variability, (4 a mathematical optimization model of evolution of developmental delay (diapause.85.6% of responses informed on prolonged developmental times in 5(th instar nymphs, with 20 species identified with remarkable developmental delays. The developmental time analysis showed some degree of bi-modal pattern of the development time of the 5(th instars in nine out of eleven species but no trend between development time pattern and climatic inter-annual variability was observed. Our optimization model predicts that the developmental delays could be due to an adaptive risk-spreading diapause strategy, only if survival throughout the diapause period and the probability of random occurrence of "bad" environmental conditions are sufficiently high.Developmental delay may not be a simple non-adaptive phenotypic plasticity in development time, and could be a form of adaptive diapause associated to a physiological mechanism related to the postponement of the initiation of reproduction, as an adaptation to environmental stochasticity through a spreading of risk (bet-hedging strategy. We identify a series of parameters that can be measured in the field and laboratory to test this hypothesis. The importance of these findings is

  8. Developmental Database for Phenology Models: Related Insect and Mite Species Have Similar Thermal Requirements

    Czech Academy of Sciences Publication Activity Database

    Jarošík, Vojtěch; Honěk, A.; Magarey, R. D.; Skuhrovec, J.

    2011-01-01

    Roč. 104, č. 6 (2011), s. 1870-1876 ISSN 0022-0493 R&D Projects: GA MŠk LC06073; GA ČR GA206/09/0563 Grant - others:European Comission(XE) 212459 Program:FP7 Institutional support: RVO:67985939 Keywords : lower developmental threshold * base temperature * rate of development Subject RIV: EH - Ecology, Behaviour OBOR OECD: Ecology Impact factor: 1.699, year: 2011

  9. A cohort study of developmental polychlorinated biphenyl (PCB) exposure in relation to post-vaccination antibody response at 6-months of age

    International Nuclear Information System (INIS)

    Jusko, Todd A.; De Roos, Anneclaire J.; Schwartz, Stephen M.; Paige Lawrence, B.; Palkovicova, Lubica; Nemessanyi, Tomas; Drobna, Beata; Fabisikova, Anna; Kocan, Anton; Sonneborn, Dean; Jahnova, Eva; Kavanagh, Terrance J.; Trnovec, Tomas; Hertz-Picciotto, Irva

    2010-01-01

    Background: Extensive experimental data in animals indicate that exposure to polychlorinated biphenyls (PCBs) during pregnancy leads to changes in offspring immune function during the postnatal period. Whether developmental PCB exposure influences immunologic development in humans has received little study. Methods: The study population was 384 mother-infant pairs recruited from two districts of eastern Slovakia for whom prospectively collected maternal, cord, and 6-month infant blood specimens were available. Several PCB congeners were measured in maternal, cord, and 6-month infant sera by high-resolution gas chromatography with electron capture detection. Concentrations of IgG-specific anti-haemophilus influenzae type b, tetanus toxoid, and diphtheria toxoid were assayed in 6-month infant sera using ELISA methods. Multiple linear regression was used to estimate the relation between maternal, cord, and 6-month infant PCB concentrations and the antibody concentrations evaluated at 6-months of age. Results: Overall, there was little evidence of an association between infant antibody concentrations and PCB measures during the pre- and early postnatal period. In addition, our results did not show specificity in terms of associations limited to a particular developmental period (e.g. pre- vs. postnatal), a particular antibody, or a particular PCB congener. Conclusions: At the PCB concentrations measured in this cohort, which are high relative to most human populations today, we did not detect an association between maternal or early postnatal PCB exposure and specific antibody responses at 6-months of age.

  10. A cohort study of developmental polychlorinated biphenyl (PCB) exposure in relation to post-vaccination antibody response at 6-months of age

    Energy Technology Data Exchange (ETDEWEB)

    Jusko, Todd A., E-mail: juskota@niehs.nih.gov [Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, MD A3-05, 111 T.W. Alexander Dr, Rall Bldg 101, Rm A361, Research Triangle Park, NC 27709-2233 (United States); Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); De Roos, Anneclaire J.; Schwartz, Stephen M. [Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Paige Lawrence, B. [Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (United States); Palkovicova, Lubica [Department of Environmental Medicine, Slovak Medical University, Bratislava (Slovakia); Nemessanyi, Tomas [Department of Immunology and Immunotoxicology, Slovak Medical University, Bratislava (Slovakia); Drobna, Beata; Fabisikova, Anna; Kocan, Anton [Department of Toxic Organic Pollutants, Slovak Medical University, Bratislava (Slovakia); Sonneborn, Dean [Department of Public Health Sciences, University of California, Davis, CA (United States); Jahnova, Eva [Department of Immunology and Immunotoxicology, Slovak Medical University, Bratislava (Slovakia); Kavanagh, Terrance J. [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA (United States); Trnovec, Tomas [Department of Toxic Organic Pollutants, Slovak Medical University, Bratislava (Slovakia); Hertz-Picciotto, Irva [Department of Public Health Sciences, University of California, Davis, CA (United States)

    2010-05-15

    Background: Extensive experimental data in animals indicate that exposure to polychlorinated biphenyls (PCBs) during pregnancy leads to changes in offspring immune function during the postnatal period. Whether developmental PCB exposure influences immunologic development in humans has received little study. Methods: The study population was 384 mother-infant pairs recruited from two districts of eastern Slovakia for whom prospectively collected maternal, cord, and 6-month infant blood specimens were available. Several PCB congeners were measured in maternal, cord, and 6-month infant sera by high-resolution gas chromatography with electron capture detection. Concentrations of IgG-specific anti-haemophilus influenzae type b, tetanus toxoid, and diphtheria toxoid were assayed in 6-month infant sera using ELISA methods. Multiple linear regression was used to estimate the relation between maternal, cord, and 6-month infant PCB concentrations and the antibody concentrations evaluated at 6-months of age. Results: Overall, there was little evidence of an association between infant antibody concentrations and PCB measures during the pre- and early postnatal period. In addition, our results did not show specificity in terms of associations limited to a particular developmental period (e.g. pre- vs. postnatal), a particular antibody, or a particular PCB congener. Conclusions: At the PCB concentrations measured in this cohort, which are high relative to most human populations today, we did not detect an association between maternal or early postnatal PCB exposure and specific antibody responses at 6-months of age.

  11. Developmental changes in the metabolic network of snapdragon flowers.

    Directory of Open Access Journals (Sweden)

    Joëlle K Muhlemann

    Full Text Available Evolutionary and reproductive success of angiosperms, the most diverse group of land plants, relies on visual and olfactory cues for pollinator attraction. Previous work has focused on elucidating the developmental regulation of pathways leading to the formation of pollinator-attracting secondary metabolites such as scent compounds and flower pigments. However, to date little is known about how flowers control their entire metabolic network to achieve the highly regulated production of metabolites attracting pollinators. Integrative analysis of transcripts and metabolites in snapdragon sepals and petals over flower development performed in this study revealed a profound developmental remodeling of gene expression and metabolite profiles in petals, but not in sepals. Genes up-regulated during petal development were enriched in functions related to secondary metabolism, fatty acid catabolism, and amino acid transport, whereas down-regulated genes were enriched in processes involved in cell growth, cell wall formation, and fatty acid biosynthesis. The levels of transcripts and metabolites in pathways leading to scent formation were coordinately up-regulated during petal development, implying transcriptional induction of metabolic pathways preceding scent formation. Developmental gene expression patterns in the pathways involved in scent production were different from those of glycolysis and the pentose phosphate pathway, highlighting distinct developmental regulation of secondary metabolism and primary metabolic pathways feeding into it.

  12. Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective.

    Science.gov (United States)

    Zirra, Alexandra; Wiethoff, Sarah; Patani, Rickie

    2016-01-01

    Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs) became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover fundamental mechanisms of disease, it is imperative to first understand the developmental neurobiology underpinning their lineage restriction choices in order to predictably manipulate cell fate to desired derivatives. Significant progress in developmental biology provides an invaluable resource for rationalising directed differentiation of hiPSCs to cellular derivatives of the nervous system. In this paper we begin by reviewing core developmental concepts underlying neural induction in order to provide context for how such insights have guided reductionist in vitro models of neural conversion from hiPSCs. We then discuss early factors relevant in neural patterning, again drawing upon crucial knowledge gained from developmental neurobiological studies. We conclude by discussing open questions relating to these concepts and how their resolution might serve to strengthen the promise of pluripotent stem cells in regenerative medicine.

  13. Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective

    Directory of Open Access Journals (Sweden)

    Alexandra Zirra

    2016-01-01

    Full Text Available Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover fundamental mechanisms of disease, it is imperative to first understand the developmental neurobiology underpinning their lineage restriction choices in order to predictably manipulate cell fate to desired derivatives. Significant progress in developmental biology provides an invaluable resource for rationalising directed differentiation of hiPSCs to cellular derivatives of the nervous system. In this paper we begin by reviewing core developmental concepts underlying neural induction in order to provide context for how such insights have guided reductionist in vitro models of neural conversion from hiPSCs. We then discuss early factors relevant in neural patterning, again drawing upon crucial knowledge gained from developmental neurobiological studies. We conclude by discussing open questions relating to these concepts and how their resolution might serve to strengthen the promise of pluripotent stem cells in regenerative medicine.

  14. Alterations in brain structures related to taste reward circuitry in ill and recovered anorexia nervosa and in bulimia nervosa.

    Science.gov (United States)

    Frank, Guido K; Shott, Megan E; Hagman, Jennifer O; Mittal, Vijay A

    2013-10-01

    The pathophysiology of anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. The authors assessed taste pleasantness and reward sensitivity in relation to brain structure, which may be related to food avoidance commonly seen in eating disorders. The authors used structural MR imaging to study gray and white matter volumes in women with current restricting-type anorexia nervosa (N=19), women recovered from restricting-type anorexia nervosa (N=24), women with bulimia nervosa (N=19), and healthy comparison women (N=24). All eating disorder groups exhibited increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manual tracing confirmed larger gyrus rectus volume, and volume predicted taste pleasantness ratings across all groups. Analyses also indicated other morphological differences between diagnostic categories. Antero-ventral insula gray matter volumes were increased on the right side in the anorexia nervosa and recovered anorexia nervosa groups and on the left side in the bulimia nervosa group relative to the healthy comparison group. Dorsal striatum volumes were reduced in the recovered anorexia nervosa and bulimia nervosa groups and predicted sensitivity to reward in all three eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas relative to the healthy comparison group. The results held when a range of covariates, such as age, depression, anxiety, and medications, were controlled for. Brain structure in the medial orbitofrontal cortex, insula, and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value.

  15. Altering the trajectory of early postnatal cortical development can lead to structural and behavioural features of autism

    Directory of Open Access Journals (Sweden)

    Chomiak Taylor

    2010-08-01

    Full Text Available Abstract Background Autism is a behaviourally defined neurodevelopmental disorder with unknown etiology. Recent studies in autistic children consistently point to neuropathological and functional abnormalities in the temporal association cortex (TeA and its associated structures. It has been proposed that the trajectory of postnatal development in these regions may undergo accelerated maturational alterations that predominantly affect sensory recognition and social interaction. Indeed, the temporal association regions that are important for sensory recognition and social interaction are one of the last regions to mature suggesting a potential vulnerability to early maturation. However, direct evaluation of the emerging hypothesis that an altered time course of early postnatal development can lead to an ASD phenotype remains lacking. Results We used electrophysiological, histological, and behavioural techniques to investigate if the known neuronal maturational promoter valproate, similar to that in culture systems, can influence the normal developmental trajectory of TeA in vivo. Brain sections obtained from postnatal rat pups treated with VPA in vivo revealed that almost 40% of cortical cells in TeA prematurely exhibited adult-like intrinsic electrophysiological properties and that this was often associated with gross cortical hypertrophy and a reduced predisposition for social play behaviour. Conclusions The co-manifestation of these functional, structural and behavioural features suggests that alteration of the developmental time course in certain high-order cortical networks may play an important role in the neurophysiological basis of autism.

  16. A Categorical Structure-Activity Relationship Analysis of the Developmental Toxicity of Antithyroid Drugs

    Directory of Open Access Journals (Sweden)

    Cunningham AlbertR

    2009-11-01

    Full Text Available The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

  17. A Categorical Structure-Activity Relationship Analysis of the Developmental Toxicity of Antithyroid Drugs

    Directory of Open Access Journals (Sweden)

    Albert R. Cunningham

    2009-01-01

    Full Text Available The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

  18. Pragmatic Language Skills of Children with Developmental Disabilities: A Descriptive and Relational Study in Turkey

    Science.gov (United States)

    Diken, Özlem

    2014-01-01

    Problem Statement: Because communication skills, particularly pragmatic skills, are fundamental for living an independent life in society, these skills are vital to the quality of life of individuals with developmental disabilities (DD) and their families. Studies of the pragmatic skills of individuals with DD can provide important insights into…

  19. BDE-47 causes developmental retardation with down-regulated expression profiles of ecdysteroid signaling pathway-involved nuclear receptor (NR) genes in the copepod Tigriopus japonicus.

    Science.gov (United States)

    Hwang, Dae-Sik; Han, Jeonghoon; Won, Eun-Ji; Kim, Duck-Hyun; Jeong, Chang-Bum; Hwang, Un-Ki; Zhou, Bingsheng; Choe, Joonho; Lee, Jae-Seong

    2016-08-01

    2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is a persistent organic pollutant (POP) in marine environments. Despite its adverse effects (e.g. developmental retardation) in ecdysozoa, the effects of BDE-47 on transcription of ecdysteroid signaling pathway-involved-nuclear receptor (NR) genes and metamorphosis-related genes have not been examined in copepods. To examine the deleterious effect of BDE-47 on copepod molting and metamorphosis, BDE-47 was exposed to the harpacticoid copepod Tigriopus japonicus, followed by monitoring developmental retardation and transcriptional alteration of NR genes. The developmental rate was significantly inhibited (P<0.05) in response to BDE-47 and the agricultural insecticide gamma-hexachlorocyclohexane. Conversely, the ecdysteroid agonist ponasterone A (PoA) led to decreased molting and metamorphosis time (P<0.05) from the nauplius stage to the adult stage. In particular, expression profiles of all NR genes were the highest at naupliar stages 5-6 except for SVP, FTZ-F1, and HR96 genes. Nuclear receptor USP, HR96, and FTZ-F1 genes also showed significant sex differences (P<0.05) in gene expression levels over different developmental stages, indicating that these genes may be involved in vitellogenesis. NR gene expression patterns showed significant decreases (P<0.05) in response to BDE-47 exposure, implying that molting and metamorphosis retardation is likely associated with NR gene expression. In summary, BDE-47 leads to molting and metamorphosis retardation and suppresses transcription of NR genes. This information will be helpful in understanding the molting and metamorphosis delay mechanism in response to BDE-47 exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Mitochondrial Dysfunction, Disruption of F-Actin Polymerization, and Transcriptomic Alterations in Zebrafish Larvae Exposed to Trichloroethylene.

    Science.gov (United States)

    Wirbisky, Sara E; Damayanti, Nur P; Mahapatra, Cecon T; Sepúlveda, Maria S; Irudayaraj, Joseph; Freeman, Jennifer L

    2016-02-15

    Trichloroethylene (TCE) is primarily used as an industrial degreasing agent and has been in use since the 1940s. TCE is released into the soil, surface, and groundwater. From an environmental and regulatory standpoint, more than half of Superfund hazardous waste sites on the National Priority List are contaminated with TCE. Occupational exposure to TCE occurs primarily via inhalation, while environmental TCE exposure also occurs through ingestion of contaminated drinking water. Current literature links TCE exposure to various adverse health effects including cardiovascular toxicity. Current studies aiming to address developmental cardiovascular toxicity utilized rodent and avian models, with the majority of studies using relatively higher parts per million (mg/L) doses. In this study, to further investigate developmental cardiotoxicity of TCE, zebrafish embryos were treated with 0, 10, 100, or 500 parts per billion (ppb; μg/L) TCE during embryogenesis and/or through early larval stages. After the appropriate exposure period, angiogenesis, F-actin, and mitochondrial function were assessed. A significant dose-response decrease in angiogenesis, F-actin, and mitochondrial function was observed. To further complement this data, a transcriptomic profile of zebrafish larvae was completed to identify gene alterations associated with the 10 ppb TCE exposure. Results from the transcriptomic data revealed that embryonic TCE exposure caused significant changes in genes associated with cardiovascular disease, cancer, and organismal injury and abnormalities with a number of targets in the FAK signaling pathway. Overall, results from our study support TCE as a developmental cardiovascular toxicant, provide molecular targets and pathways for investigation in future studies, and indicate a need for continued priority for environmental regulation.

  1. HC-Pro silencing suppressor significantly alters the gene expression profile in tobacco leaves and flowers

    Directory of Open Access Journals (Sweden)

    Lehto Kirsi

    2011-04-01

    Full Text Available Abstract Background RNA silencing is used in plants as a major defence mechanism against invasive nucleic acids, such as viruses. Accordingly, plant viruses have evolved to produce counter defensive RNA-silencing suppressors (RSSs. These factors interfere in various ways with the RNA silencing machinery in cells, and thereby disturb the microRNA (miRNA mediated endogene regulation and induce developmental and morphological changes in plants. In this study we have explored these effects using previously characterized transgenic tobacco plants which constitutively express (under CaMV 35S promoter the helper component-proteinase (HC-Pro derived from a potyviral genome. The transcript levels of leaves and flowers of these plants were analysed using microarray techniques (Tobacco 4 × 44 k, Agilent. Results Over expression of HC-Pro RSS induced clear phenotypic changes both in growth rate and in leaf and flower morphology of the tobacco plants. The expression of 748 and 332 genes was significantly changed in the leaves and flowers, respectively, in the HC-Pro expressing transgenic plants. Interestingly, these transcriptome alterations in the HC-Pro expressing tobacco plants were similar as those previously detected in plants infected with ssRNA-viruses. Particularly, many defense-related and hormone-responsive genes (e.g. ethylene responsive transcription factor 1, ERF1 were differentially regulated in these plants. Also the expression of several stress-related genes, and genes related to cell wall modifications, protein processing, transcriptional regulation and photosynthesis were strongly altered. Moreover, genes regulating circadian cycle and flowering time were significantly altered, which may have induced a late flowering phenotype in HC-Pro expressing plants. The results also suggest that photosynthetic oxygen evolution, sugar metabolism and energy levels were significantly changed in these transgenic plants. Transcript levels of S

  2. Reading in developmental prosopagnosia

    DEFF Research Database (Denmark)

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

    2018-01-01

    exposure durations (targeting the word superiority effect), and d) text reading. RESULTS: Participants with developmental prosopagnosia performed strikingly similar to controls across the four reading tasks. Formal analysis revealed a significant dissociation between word and face recognition......, that is, impaired reading in developmental prosopagnosia. METHOD: We tested 10 adults with developmental prosopagnosia and 20 matched controls. All participants completed the Cambridge Face Memory Test, the Cambridge Face Perception test and a Face recognition questionnaire used to quantify everyday face...... recognition experience. Reading was measured in four experimental tasks, testing different levels of letter, word, and text reading: (a) single word reading with words of varying length,(b) vocal response times in single letter and short word naming, (c) recognition of single letters and short words at brief...

  3. Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations.

    Science.gov (United States)

    Ozturk, Nihal; Olgar, Yusuf; Er, Hakan; Kucuk, Murathan; Ozdemir, Semir

    2017-01-01

    The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.

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

    Science.gov (United States)

    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 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.

  5. Alteration of consciousness in focal epilepsy: the global workspace alteration theory.

    Science.gov (United States)

    Bartolomei, Fabrice; McGonigal, Aileen; Naccache, Lionel

    2014-01-01

    Alteration of consciousness (AOC) is an important clinical manifestation of partial seizures that greatly impacts the quality of life of patients with epilepsy. Several theories have been proposed in the last fifty years. An emerging concept in neurology is the global workspace (GW) theory that postulates that access to consciousness (from several sensorial modalities) requires transient coordinated activity from associative cortices, in particular the prefrontal cortex and the posterior parietal associative cortex. Several lines of evidence support the view that partial seizures alter consciousness through disturbance of the GW. In particular, a nonlinear relation has been shown between excess of synchronization in the GW regions and the degree of AOC. Changes in thalamocortical synchrony occurring during the spreading of the ictal activity seem particularly involved in the mechanism of altered consciousness. This link between abnormal synchrony and AOC offers new perspectives in the treatment of the AOC since means of decreasing consciousness alteration in seizures could improve patients' quality of life. © 2013.

  6. Altered Adipogenesis in Zebrafish Larvae Following High Fat Diet and Chemical Exposure Is Visualised by Stimulated Raman Scattering Microscopy

    Directory of Open Access Journals (Sweden)

    Marjo J. den Broeder

    2017-04-01

    Full Text Available Early life stage exposure to environmental chemicals may play a role in obesity by altering adipogenesis; however, robust in vivo methods to quantify these effects are lacking. The goal of this study was to analyze the effects of developmental exposure to chemicals on adipogenesis in the zebrafish (Danio rerio. We used label-free Stimulated Raman Scattering (SRS microscopy for the first time to image zebrafish adipogenesis at 15 days post fertilization (dpf and compared standard feed conditions (StF to a high fat diet (HFD or high glucose diet (HGD. We also exposed zebrafish embryos to a non-toxic concentration of tributyltin (TBT, 1 nM or Tris(1,3-dichloroisopropylphosphate (TDCiPP, 0.5 µM from 0–6 dpf and reared larvae to 15 dpf under StF. Potential molecular mechanisms of altered adipogenesis were examined by qPCR. Diet-dependent modulation of adipogenesis was observed, with HFD resulting in a threefold increase in larvae with adipocytes, compared to StF and HGD. Developmental exposure to TBT but not TDCiPP significantly increased adipocyte differentiation. The expression of adipogenic genes such as pparda, lxr and lepa was altered in response to HFD or chemicals. This study shows that SRS microscopy can be successfully applied to zebrafish to visualize and quantify adipogenesis, and is a powerful approach for identifying obesogenic chemicals in vivo.

  7. Altered Adipogenesis in Zebrafish Larvae Following High Fat Diet and Chemical Exposure Is Visualised by Stimulated Raman Scattering Microscopy

    Science.gov (United States)

    den Broeder, Marjo J.; Moester, Miriam J. B.; Kamstra, Jorke H.; Cenijn, Peter H.; Davidoiu, Valentina; Kamminga, Leonie M.; Ariese, Freek; de Boer, Johannes F.; Legler, Juliette

    2017-01-01

    Early life stage exposure to environmental chemicals may play a role in obesity by altering adipogenesis; however, robust in vivo methods to quantify these effects are lacking. The goal of this study was to analyze the effects of developmental exposure to chemicals on adipogenesis in the zebrafish (Danio rerio). We used label-free Stimulated Raman Scattering (SRS) microscopy for the first time to image zebrafish adipogenesis at 15 days post fertilization (dpf) and compared standard feed conditions (StF) to a high fat diet (HFD) or high glucose diet (HGD). We also exposed zebrafish embryos to a non-toxic concentration of tributyltin (TBT, 1 nM) or Tris(1,3-dichloroisopropyl)phosphate (TDCiPP, 0.5 µM) from 0–6 dpf and reared larvae to 15 dpf under StF. Potential molecular mechanisms of altered adipogenesis were examined by qPCR. Diet-dependent modulation of adipogenesis was observed, with HFD resulting in a threefold increase in larvae with adipocytes, compared to StF and HGD. Developmental exposure to TBT but not TDCiPP significantly increased adipocyte differentiation. The expression of adipogenic genes such as pparda, lxr and lepa was altered in response to HFD or chemicals. This study shows that SRS microscopy can be successfully applied to zebrafish to visualize and quantify adipogenesis, and is a powerful approach for identifying obesogenic chemicals in vivo. PMID:28441764

  8. Associations of early developmental milestones with adult intelligence

    DEFF Research Database (Denmark)

    Flensborg-Madsen, Trine; Mortensen, Erik Lykke

    2018-01-01

    developmental milestones at a 3-year examination, and all children were administered the Wechsler Adult Intelligence Scale when they were 20–34 years old. Later attainment of a number of milestones was associated with lower adult IQ with the strongest associations found for those related to language and social......The study investigated whether age at attainment of 20 developmental milestones within the areas of language, walking, eating, dressing, social interaction, and toilet training was associated with adult intelligence. Mothers of 821 children of the Copenhagen Perinatal Cohort recorded 20...... interaction. The adjusted full-scale IQ means were 107.0, 101.8, and 100.6 for being able to form a sentence at less than 24 months, at 24 months, and later than 24 months....

  9. Root developmental programs shape the Medicago truncatula nodule meristem

    NARCIS (Netherlands)

    Franssen, H.; Xiao, T.T.; Kulikova, O.; Wan, X.; Bisseling, T.; Scheres, B.; Heidstra, R.

    2015-01-01

    Nodules on the roots of legume plants host nitrogen-fixing Rhizobium bacteria. Several lines of evidence indicate that nodules are evolutionarily related to roots. We determined whether developmental control of the Medicago truncatula nodule meristem bears resemblance to that in root meristems

  10. Motor activity changes induced by sub-encephalopathic lead exposure during different developmental phases in rats

    Energy Technology Data Exchange (ETDEWEB)

    Van Rooyen, J M; Offermeier, J; Brand, L; Botha, F; Rossouw, J; Lategan, A J; Botes, M S

    1988-05-01

    Two groups of rats were exposed to lead (0,2% lead acetate in drinking water) for periods of 21 days during different developmental phases. Lead exposure was initiated on day 1 and day 22 after birth, for rats in groups 1 and 2, respectively. Measurements of locomotor activity (LA) and (/sup 3/H)spiperone binding assays were performed on day 50 after birth. Lead exposure resulted in the potentiation of the LA effects of 5 mg/kg apomorphine without altering the LA effects of 50 mg/kg piribedil in group 1. Lead exposure resulted in an attenuation of the LA effects of apomorphine and piribedil in group 2. Lead exposure did not alter the K/sub D/ and B/sub max/ values of (/sup 3/H)spiperone in membranes prepared from the rat striatum or nucleus accumbens.

  11. Altered modular organization of structural cortical networks in children with autism.

    Directory of Open Access Journals (Sweden)

    Feng Shi

    Full Text Available Autism is a complex developmental disability that characterized by deficits in social interaction, language skills, repetitive stereotyped behaviors and restricted interests. Although great heterogeneity exists, previous findings suggest that autism has atypical brain connectivity patterns and disrupted small-world network properties. However, the organizational alterations in the autistic brain network are still poorly understood. We explored possible organizational alterations of 49 autistic children and 51 typically developing controls, by investigating their brain network metrics that are constructed upon cortical thickness correlations. Three modules were identified in controls, including cortical regions associated with brain functions of executive strategic, spatial/auditory/visual, and self-reference/episodic memory. There are also three modules found in autistic children with similar patterns. Compared with controls, autism demonstrates significantly reduced gross network modularity, and a larger number of inter-module connections. However, the autistic brain network demonstrates increased intra- and inter-module connectivity in brain regions including middle frontal gyrus, inferior parietal gyrus, and cingulate, suggesting one underlying compensatory mechanism associated with brain functions of self-reference and episodic memory. Results also show that there is increased correlation strength between regions inside frontal lobe, as well as impaired correlation strength between frontotemporal and frontoparietal regions. This alteration of correlation strength may contribute to the organization alteration of network structures in autistic brains.

  12. Cross-fostering alters advertisement vocalizations of grasshopper mice (Onychomys): Evidence for the developmental stress hypothesis.

    Science.gov (United States)

    Pasch, Bret; Abbasi, Mustafa Z; Wilson, Macey; Zhao, Daniel; Searle, Jeremy B; Webster, Michael S; Rice, Aaron N

    2016-04-01

    Nutritional stress can have lasting impacts on the development of traits involved in vocal production. Cross-fostering experiments are often used to examine the propensity for vocal learning in a variety of taxa, but few studies assess the influence of malnourishment that can occur as a byproduct of this technique. In this study, we reciprocally cross-fostered sister taxa of voluble grasshopper mice (genus Onychomys) to explore their propensity for vocal learning. Vocalizations of Onychomys leucogaster did not differ between control and cross-fostered animals, but cross-fostered Onychomys arenicola produced vocalizations that were higher in frequency in a direction away from tutors. These same animals exhibited a transient reduction in body mass early in development, indicative of malnutrition. Our findings simultaneously refute vocal learning and support the developmental stress hypothesis to highlight the importance of early ontogeny on the production of vocalizations later in life. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

    Science.gov (United States)

    Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

    2016-08-01

    Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  14. A Developmental-Contextual Model of Depressive Symptoms in Mexican-Origin Female Adolescents

    Science.gov (United States)

    Bámaca-Colbert, Mayra Y.; Umaña-Taylor, Adriana J.; Gayles, Jochebed G.

    2011-01-01

    The current study tested a developmental-contextual model of depressive symptomatology among early and middle adolescent Mexican-origin females and their mothers. The final sample was comprised of 271 dyads. We examined the interrelations among cultural (i.e., acculturation dissonance), developmental (i.e., pubertal development and autonomy expectation discrepancies), and interpersonal (i.e., mother-daughter conflict and maternal supportive parenting) factors in predicting adolescents’ depressive symptoms. For both early and middle adolescents, maternal support was negatively associated with mother-daughter conflict and depressive symptoms. Importantly, mother-daughter autonomy expectation discrepancies were positively associated with mother-daughter conflict, but this association was found only among early adolescents. Further, mother-daughter acculturation dissonance was positively associated with mother-daughter conflict, but only among middle adolescents. Findings call for concurrently examining the interface of developmental, relational, and cultural factors in predicting female adolescents’ depressive symptomatology and the potential differences by developmental stage (e.g., early vs. middle adolescence) PMID:21967564

  15. Effects of developmental bisphenol A exposure on reproductive-related behaviors in California mice (Peromyscus californicus: a monogamous animal model.

    Directory of Open Access Journals (Sweden)

    Scott A Williams

    Full Text Available Bisphenol A (BPA, a pervasive, endocrine disrupting compound (EDC, acts as a mixed agonist-antagonist with respect to estrogens and other steroid hormones. We hypothesized that sexually selected traits would be particularly sensitive to EDC. Consistent with this concept, developmental exposure of males from the polygynous deer mouse, Peromyscus maniculatus, to BPA resulted in compromised spatial navigational ability and exploratory behaviors, while there was little effect on females. Here, we have examined a related, monogamous species, the California mouse (Peromyscus californicus, where we predicted that males would be less sensitive to BPA in terms of navigational and exploratory behaviors, while displaying other traits related to interactions with females and territorial marking that might be vulnerable to disruption. As in the deer mouse experiments, females were fed either a phytoestrogen-free CTL diet through pregnancy and lactation or the same diet supplemented with BPA (50 mg/kg feed weight or ethinyl estradiol (EE (0.1 part per billion to provide a "pure" estrogen control. After weaning, pups were maintained on CTL diet until they had reached sexual maturity, at which time behaviors were evaluated. In addition, territorial marking was assessed in BPA-exposed males housed alone and when a control male was visible in the testing arena. In contrast to deer mice, BPA and EE exposure had no effect on spatial navigational skills in either male or female California mice. While CTL females exhibited greater exploratory behavior than CTL males, BPA exposure abolished this sex difference. BPA-exposed males, however, engaged in less territorial marking when CTL males were present. These studies demonstrate that developmental BPA exposure can disrupt adult behaviors in a sex- and species-dependent manner and are consistent with the hypothesis that sexually selected traits are particularly vulnerable to endocrine disruption and should be a

  16. Developmental psychopathology: a paradigm shift or just a relabeling?

    Science.gov (United States)

    Rutter, Michael

    2013-11-01

    Developmental psychopathology is described as a conceptual approach that involves a set of research methods that capitalize on developmental and psychopathological variations to ask questions about mechanisms and processes. Achievements are described in relation to attachment and attachment disorders, autism, schizophrenia, childhood antecedents of adult psychopathology, testing for environmental mediation of risk effects, gene-environment interplay, intellectual and language functioning, effects of mentally ill parents on the children, stress and vulnerability to depression, ethnicity and schizophrenia, and drug response. Continuities and discontinuities over the course of development are discussed in relation to attention-deficit/hyperactivity disorder, antisocial behavior, eating disorders, substance abuse and dependency, pharmacological and behavioral addictions, and a range of other disorders. Research challenges are considered in relation to spectrum concepts, the adolescent development of a female preponderance for depression, the mechanisms involved in age differences in response to drugs and to lateralized brain injury, the processing of experiences, the biological embedding of experiences, individual differences in response to environmental hazards, nature-nurture integration, and brain plasticity.

  17. The phenotypic plasticity of developmental modules

    Directory of Open Access Journals (Sweden)

    Aabha I. Sharma

    2016-08-01

    Full Text Available Abstract Background Organisms develop and evolve in a modular fashion, but how individual modules interact with the environment remains poorly understood. Phenotypically plastic traits are often under selection, and studies are needed to address how traits respond to the environment in a modular fashion. In this study, tissue-specific plasticity of melanic spots was examined in the large milkweed bug, Oncopeltus fasciatus. Results Although the size of the abdominal melanic bands varied according to rearing temperatures, wing melanic bands were more robust. To explore the regulation of abdominal pigmentation plasticity, candidate genes involved in abdominal melanic spot patterning and biosynthesis of melanin were analyzed. While the knockdown of dopa decarboxylase (Ddc led to lighter pigmentation in both the wings and the abdomen, the shape of the melanic elements remained unaffected. Although the knockdown of Abdominal-B (Abd-B partially phenocopied the low-temperature phenotype, the abdominal bands were still sensitive to temperature shifts. These observations suggest that regulators downstream of Abd-B but upstream of DDC are responsible for the temperature response of the abdomen. Ablation of wings led to the regeneration of a smaller wing with reduced melanic bands that were shifted proximally. In addition, the knockdown of the Wnt signaling nuclear effector genes, armadillo 1 and armadillo 2, altered both the melanic bands and the wing shape. Thus, the pleiotropic effects of Wnt signaling may constrain the amount of plasticity in wing melanic bands. Conclusions We propose that when traits are regulated by distinct pre-patterning mechanisms, they can respond to the environment in a modular fashion, whereas when the environment impacts developmental regulators that are shared between different modules, phenotypic plasticity can manifest as a developmentally integrated system.

  18. Developmental changes of beta-adrenergic receptor-linked adenylate cyclase of rat liver

    International Nuclear Information System (INIS)

    Katz, M.S.; Boland, S.R.; Schmidt, S.J.

    1985-01-01

    beta-Adrenergic agonist-sensitive adenylate cyclase activity and binding of the beta-adrenergic antagonist(-)-[ 125 I]iodopindolol were studied in rat liver during development of male Fischer 344 rats ages 6-60 days. In liver homogenates maximum adenylate cyclase response to beta-adrenergic agonist (10(-5) M isoproterenol or epinephrine) decreased by 73% (P less than 0.01) between 6 and 60 days, with most of the decrease (56%; P less than 0.01) occurring by 20 days. beta-adrenergic receptor density (Bmax) showed a corresponding decrease of 66% (P less than 0.01) by 20 days without subsequent change. Binding characteristics of stereospecificity, pharmacological specificity, saturability with time, and reversibility were unchanged with age. GTP-, fluoride-, forskolin-, and Mn2+-stimulated adenylate cyclase activities also decreased during development, suggesting a decrease of activity of the catalytic component and/or guanine nucleotide regulatory component of adenylate cyclase. These results indicate that the developmental decrease of beta-adrenergic agonist-sensitive adenylate cyclase activity may result from decreased numbers of beta-adrenergic receptors. Developmental alterations of nonreceptor components of the enzyme may also contribute to changes of catecholamine-sensitive adenylate cyclase

  19. Importance of investing in adolescence from a developmental science perspective.

    Science.gov (United States)

    Dahl, Ronald E; Allen, Nicholas B; Wilbrecht, Linda; Suleiman, Ahna Ballonoff

    2018-02-21

    This review summarizes the case for investing in adolescence as a period of rapid growth, learning, adaptation, and formational neurobiological development. Adolescence is a dynamic maturational period during which young lives can pivot rapidly-in both negative and positive directions. Scientific progress in understanding adolescent development provides actionable insights into windows of opportunity during which policies can have a positive impact on developmental trajectories relating to health, education, and social and economic success. Given current global changes and challenges that affect adolescents, there is a compelling need to leverage these advances in developmental science to inform strategic investments in adolescent health.

  20. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

    Directory of Open Access Journals (Sweden)

    Zhu Zhu

    2016-01-01

    Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  1. Early Intervention in Children with Developmental Disabilities

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2016-01-01

    Full Text Available Developmental disabilities consist of conditions that delay or impair the physical, cognitive, and/or psychological development of children. If not intervened at the earliest, these disabilities will cause significant negative impact on multiple domains of functioning such as learning, language, self-care and capacity for independent living. Common developmental disabilities include autism spectrum disorders, intellectual disabilities, developmental delay and cerebral palsy. About one fourth of young children in developing countries are at risk for or have developmental delay or disabilities. Inadequate stimulation has significant negative impact on physical, socioemotional and cognitive development of children. Hence early scientific intervention programs are necessary in the management of children at risk for developmental delay.

  2. Developmental venous anomalies: appearance on whole-brain CT digital subtraction angiography and CT perfusion

    International Nuclear Information System (INIS)

    Hanson, Eric H.; Roach, Cayce J.; Ringdahl, Erik N.; Wynn, Brad L.; DeChancie, Sean M.; Mann, Nathan D.; Diamond, Alan S.; Orrison, William W.

    2011-01-01

    Developmental venous anomalies (DVA) consist of dilated intramedullary veins that converge into a large collecting vein. The appearance of these anomalies was evaluated on whole-brain computed tomography (CT) digital subtraction angiography (DSA) and CT perfusion (CTP) studies. CT data sets of ten anonymized patients were retrospectively analyzed. Five patients had evidence of DVA and five age- and sex-matched controls were without known neurovascular abnormalities. CT angiograms, CT arterial-venous views, 4-D CT DSA and CTP maps were acquired on a dynamic volume imaging protocol on a 320-detector row CT scanner. Whole-brain CTP parameters were evaluated for cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT), and delay. DSA was utilized to visualize DVA anatomy. Radiation dose was recorded from the scanner console. Increased CTP values were present in the DVA relative to the unaffected contralateral hemisphere of 48%, 32%, and 26%; and for the control group with matched hemispheric comparisons of 2%, -10%, and 9% for CBF, CBV, and MTT, respectively. Average effective radiation dose was 4.4 mSv. Whole-brain DSA and CTP imaging can demonstrate a characteristic appearance of altered DVA hemodynamic parameters and capture the anomalies in superior cortices of the cerebrum and the cerebellum. Future research may identify the rare subsets of patients at increased risk of adverse outcomes secondary to the altered hemodynamics to facilitate tailored imaging surveillance and application of appropriate preventive therapeutic measures. (orig.)

  3. Developmental venous anomalies: appearance on whole-brain CT digital subtraction angiography and CT perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Eric H. [Advanced Medical Imaging and Genetics (Amigenics), Las Vegas, NV (United States); Touro University Nevada College of Osteopathic Medicine, Henderson, NV (United States); University of Nevada Las Vegas, Department of Health Physics and Diagnostic Sciences, 4505 Maryland Parkway, Box 453037, Las Vegas, NV (United States); Amigenics, Inc, Las Vegas, NV (United States); Roach, Cayce J. [Advanced Medical Imaging and Genetics (Amigenics), Las Vegas, NV (United States); University of Nevada Las Vegas, School of Life Sciences, Las Vegas, NV (United States); Ringdahl, Erik N. [University of Nevada Las Vegas, Department of Psychology, Las Vegas, NV (United States); Wynn, Brad L. [Family Medicine Spokane, Spokane, WA (United States); DeChancie, Sean M.; Mann, Nathan D. [Touro University Nevada College of Osteopathic Medicine, Henderson, NV (United States); Diamond, Alan S. [CHW Nevada Imaging Company, Nevada Imaging Centers, Spring Valley, Las Vegas, NV (United States); Orrison, William W. [Touro University Nevada College of Osteopathic Medicine, Henderson, NV (United States); University of Nevada Las Vegas, Department of Health Physics and Diagnostic Sciences, 4505 Maryland Parkway, Box 453037, Las Vegas, NV (United States); CHW Nevada Imaging Company, Nevada Imaging Centers, Spring Valley, Las Vegas, NV (United States); University of Nevada School of Medicine, Department of Medical Education, Reno, NV (United States)

    2011-05-15

    Developmental venous anomalies (DVA) consist of dilated intramedullary veins that converge into a large collecting vein. The appearance of these anomalies was evaluated on whole-brain computed tomography (CT) digital subtraction angiography (DSA) and CT perfusion (CTP) studies. CT data sets of ten anonymized patients were retrospectively analyzed. Five patients had evidence of DVA and five age- and sex-matched controls were without known neurovascular abnormalities. CT angiograms, CT arterial-venous views, 4-D CT DSA and CTP maps were acquired on a dynamic volume imaging protocol on a 320-detector row CT scanner. Whole-brain CTP parameters were evaluated for cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT), and delay. DSA was utilized to visualize DVA anatomy. Radiation dose was recorded from the scanner console. Increased CTP values were present in the DVA relative to the unaffected contralateral hemisphere of 48%, 32%, and 26%; and for the control group with matched hemispheric comparisons of 2%, -10%, and 9% for CBF, CBV, and MTT, respectively. Average effective radiation dose was 4.4 mSv. Whole-brain DSA and CTP imaging can demonstrate a characteristic appearance of altered DVA hemodynamic parameters and capture the anomalies in superior cortices of the cerebrum and the cerebellum. Future research may identify the rare subsets of patients at increased risk of adverse outcomes secondary to the altered hemodynamics to facilitate tailored imaging surveillance and application of appropriate preventive therapeutic measures. (orig.)

  4. Alterations of parenchymal microstructure, neuronal connectivity and cerebrovascular resistance at adolescence following mild to moderate traumatic brain injury in early development.

    Science.gov (United States)

    Parent, Maxime; Li, Ying; Santhakumar, Vijayalakshmi; Hyder, Fahmeed; Sanganahalli, Basavaraju G; Kannurpatti, Sridhar

    2018-06-01

    TBI is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence. 1 Based on the non-localized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity and neurovascular function are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2-months after injury, using functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). fMRI based resting state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus and thalamus accompanied by decrease in the spatial extent of their corresponding RSFC networks and inter-hemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus and motor cortex. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), reporting on axonal and microstructural integrity of the brain, indicated similar inter-hemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in inter-hemispheric structural connectivity. Hippocampus, thalamus and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance and parenchymal microstructure in the adolescent brain

  5. The emergence of psychopathy: implications for the neuropsychological approach to developmental disorders.

    Science.gov (United States)

    Blair, R J R

    2006-09-01

    In this paper, I am going to examine the disorder of psychopathy and consider how genetic anomalies could give rise to the relatively specific neuro-cognitive impairments seen in individuals with this disorder. I will argue that genetic anomalies in psychopathy reduce the salience of punishment information (perhaps as a function of noradrenergic disturbance). I will argue that the ability of the amygdala to form the stimulus-punishment associations necessary for successful socialization is disrupted and that because of this, individuals with psychopathy do not learn to avoid actions that will harm others. It is noted that this model follows the neuropsychological approach to the study of developmental disorders, an approach that has been recently criticized. I will argue that these criticisms are less applicable to psychopathy. Indeed, animal work on the development of the neural systems necessary for emotion, does not support a constructivist approach with respect to affect. Importantly, such work indicates that while environmental effects can alter the responsiveness of the basic neural architecture mediating emotion, environmental effects do not construct this architecture. However, caveats to the neuropsychological approach with reference to this disorder are noted.

  6. The developmental spectrum of proximal radioulnar synostosis

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, Alison M. [University of Manitoba, Winnipeg Regional Health Association Program of Genetics and Metabolism, Winnipeg, MB (Canada); University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, WRHA Program of Genetics and Metabolism, Departments of Paediatrics and Child Health, Biochemistry and Medical Genetics, Winnipeg, MB (Canada); Kibria, Lisa [University of Manitoba, Department of School of Medical Rehabilitation, Winnipeg, MB (Canada); Reed, Martin H. [University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, Department of Diagnostic Imaging, Winnipeg, MB (Canada)

    2010-01-15

    can occur in the same patient. Furthermore, both anomalies can be seen in different patients with the same genetic diagnosis, further supporting the notion that these defects are developmentally related. Posterior dislocation of the radial head and radioulnar fusion are considered to be related primary developmental anomalies of radioulnar differentiation/segmentation. We speculate that the eventual specific defect of this spectrum is influenced by very subtle differences in developmental timing. This is in contrast to patients with transverse forearm defects who can also display radial head dislocation but in an anterior or lateral direction. This direction of dislocation is seen when an abnormal force is exerted on a normally formed radial head later in development or postnatally in disorders such as multiple osteochondromatosis and various mesomelic dysplasias, or as a result of trauma. (orig.)

  7. An alter-centric perspective on employee innovation: The importance of alters' creative self-efficacy and network structure.

    Science.gov (United States)

    Grosser, Travis J; Venkataramani, Vijaya; Labianca, Giuseppe Joe

    2017-09-01

    While most social network studies of employee innovation behavior examine the focal employees' ("egos'") network structure, we employ an alter-centric perspective to study the personal characteristics of employees' network contacts-their "alters"-to better understand employee innovation. Specifically, we examine how the creative self-efficacy (CSE) and innovation behavior of employees' social network contacts affects their ability to generate and implement novel ideas. Hypotheses were tested using a sample of 144 employees in a U.S.-based product development organization. We find that the average CSE of alters in an employee's problem solving network is positively related to that employee's innovation behavior, with this relationship being mediated by these alters' average innovation behavior. The relationship between the alters' average innovation behavior and the employee's own innovation behavior is strengthened when these alters have less dense social networks. Post hoc results suggest that having network contacts with high levels of CSE also leads to an increase in ego's personal CSE 1 year later in cases where the employee's initial level of CSE was relatively low. Implications for theory and practice are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Developmental and familial predictors of adult cognitive traits in the European starling

    Science.gov (United States)

    Nettle, Daniel; Andrews, Clare P.; Monaghan, Pat; Brilot, Ben O.; Bedford, Thomas; Gillespie, Robert; Bateson, Melissa

    2015-01-01

    In birds, there is evidence that adult cognitive traits can both run in families and be affected by early developmental influences. However, different studies use different cognitive tasks, which may not be measuring the same traits, and also focus on different developmental factors. We report results from a study in which we administered multiple cognitive tasks (autoshaping, discrimination learning, reversal learning, progressive ratio schedule, extinction learning and impulsivity) to a cohort of 34 European starlings, Sturnus vulgaris, for which several early developmental measures were available. The cohort consisted of siblings raised either apart or together, whose position in the size hierarchy of the rearing brood had been experimentally manipulated. We examined how the different cognitive measures covaried, the extent to which they ran in families, and which of the developmental factors predicted which of the cognitive outcomes. We found that discrimination and reversal learning speeds were positively correlated, as were breakpoint on the progressive ratio schedule and resistance to extinction. Otherwise, the cognitive measures were uncorrelated, suggesting that they reflected different underlying traits. All traits except discrimination and reversal learning speed ran in families to a substantial extent. Using a model selection approach, we found evidence that natal brood size and developmental telomere attrition (the extent to which the birds' erythrocyte telomeres shortened in early life, an integrative measure of developmental stress) were related to several adult cognitive measures. Results are discussed with respect to the best way of measuring avian cognitive abilities, and the utility of developmental telomere attrition as a predictor of adult outcomes. PMID:26405302

  10. The Influence of Pathologies upon Sensory Perception and Sensory Coordination in Children with Developmental Dyslexia and Learning Disorders: A Unified Theory of Developmental Dyslexia.

    Science.gov (United States)

    Ewing, Graham Wilfred; Parvez, Syed Hasan

    2012-03-01

    This case is presented to explain that developmental dyslexia and related autistic spectrum disorders have solely pathological origins. There is a general consensus of opinion which supports the phonological theory. However, this largely ignores the biological basis for all aspects of the brain's development and function, and hence, for its dysfunction. A unified explanation must take into account all salient features including cognitive dysfunction, encephalograph (EEG) frequencies, neural networks, physiological systems, autonomic nervous system and the function of the cerebellum. It must explain the significance of the brain waves and neurons and their normally synchronized or coherent function. This article builds upon an earlier article by the authors, which incorporates a review and discussion of the prevailing theories or models for developmental dyslexia. It looks at the issues from a top-down 'systems biology' perspective. It concludes that it may be only the body's biochemistry and, in particular, the onset of pathologies that explain the phenomena which we recognize as developmental dyslexia. Pathologies experienced in the early prepubescent years influence neural development. They influence the speed and coherent transmission of data between the senses and neural centers. It is proposed that this explains the nature and occurrence of what we recognize as developmental dyslexia.

  11. [Non-autistic pervasive developmental disorders: Rett syndrome, disintegrative disorder and pervasive developmental disorder not otherwise specified

    NARCIS (Netherlands)

    Mercadante, M.T.; Gaag, R.J. van der; Schwartzman, J.S.

    2006-01-01

    The category "Pervasive Developmental Disorders" includes autistic disorder, Asperger's syndrome, Rett's syndrome, childhood disintegrative disorder, and a residual category, named pervasive developmental disorder not otherwise specified. In this review, Rett's syndrome and childhood disintegrative

  12. Fertility in The Netherlands as an expected value process and developmental readiness.

    Science.gov (United States)

    Taris, T W

    1998-01-01

    In this 2-wave panel study, the decision to have children was examined in the context of Feather's (1982) expectancy-value model among a representative sample of 288 childless Dutch adults aged 18-30 years. The effects of 2 indicators of developmental readiness (age and duration of relationship) were also explored. It was expected that (a) the likelihood of having a baby would increase as a function of intentions, evaluations of being childless, and expected rewards of having children and (b) developmental readiness would be positively related to whether respondents had children at the 2nd wave of the study. Structural equation modeling was used. The results largely supported expectations. Developmental readiness affected fertility both directly and indirectly via the expected rewards of having children.

  13. Neglect-like characteristics of developmental disregard in children with cerebral palsy revealed by event related potentials

    NARCIS (Netherlands)

    Zielinski, I.M.; Steenbergen, B.; Baas, C.M.; Aarts, P.B.M.; Jongsma, M.L.A.

    2014-01-01

    Background Children with unilateral Cerebral Palsy (CP) often show diminished awareness of the remaining capacity of their affected upper limb. This phenomenon is known as Developmental Disregard (DD). DD has been explained by operant conditioning. Alternatively, DD can be described as a

  14. What Is a Developmental-Behavioral Pediatrician?

    Science.gov (United States)

    ... social worker. Developmental-behavioral pediatricians work closely with parents, families, and schools. Developmental-behavioral pediatricians understand that children’s development and behavior happen first and foremost in the ...

  15. Postnatal Developmental Trajectories of Neural Circuits in the Primate Prefrontal Cortex: Identifying Sensitive Periods for Vulnerability to Schizophrenia

    Science.gov (United States)

    Hoftman, Gil D.; Lewis, David A.

    2011-01-01

    Schizophrenia is a disorder of cognitive neurodevelopment with characteristic abnormalities in working memory attributed, at least in part, to alterations in the circuitry of the dorsolateral prefrontal cortex. Various environmental exposures from conception through adolescence increase risk for the illness, possibly by altering the developmental trajectories of prefrontal cortical circuits. Macaque monkeys provide an excellent model system for studying the maturation of prefrontal cortical circuits. Here, we review the development of glutamatergic and γ-aminobutyric acid (GABA)-ergic circuits in macaque monkey prefrontal cortex and discuss how these trajectories may help to identify sensitive periods during which environmental exposures, such as those associated with increased risk for schizophrenia, might lead to the types of abnormalities in prefrontal cortical function present in schizophrenia. PMID:21505116

  16. Developmental Deltamethrin Exposure Causes Persistent Changes in Dopaminergic Gene Expression, Neurochemistry, and Locomotor Activity in Zebrafish.

    Science.gov (United States)

    Kung, Tiffany S; Richardson, Jason R; Cooper, Keith R; White, Lori A

    2015-08-01

    Pyrethroids are commonly used insecticides that are considered to pose little risk to human health. However, there is an increasing concern that children are more susceptible to the adverse effects of pesticides. We used the zebrafish model to test the hypothesis that developmental exposure to low doses of the pyrethroid deltamethrin results in persistent alterations in dopaminergic gene expression, neurochemistry, and locomotor activity. Zebrafish embryos were treated with deltamethrin (0.25-0.50 μg/l), at concentrations below the LOAEL, during the embryonic period [3-72 h postfertilization (hpf)], after which transferred to fresh water until the larval stage (2-weeks postfertilization). Deltamethrin exposure resulted in decreased transcript levels of the D1 dopamine (DA) receptor (drd1) and increased levels of tyrosine hydroxylase at 72 hpf. The reduction in drd1 transcripts persisted to the larval stage and was associated with decreased D2 dopamine receptor transcripts. Larval fish, exposed developmentally to deltamethrin, had increased levels of homovanillic acid, a DA metabolite. Since the DA system is involved in locomotor activity, we measured the swim activity of larval fish following a transition to darkness. Developmental exposure to deltamethrin significantly increased larval swim activity which was attenuated by concomitant knockdown of the DA transporter. Acute exposure to methylphenidate, a DA transporter inhibitor, increased swim activity in control larva, while reducing swim activity in larva developmentally exposed to deltamethrin. Developmental exposure to deltamethrin causes locomotor deficits in larval zebrafish, which is likely mediated by dopaminergic dysfunction. This highlights the need to understand the persistent effects of low-dose neurotoxicant exposure during development. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Sampling in Developmental Science: Situations, Shortcomings, Solutions, and Standards

    Science.gov (United States)

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

    2014-01-01

    Sampling is a key feature of every study in developmental science. Although sampling has far-reaching implications, too little attention is paid to sampling. Here, we describe, discuss, and evaluate four prominent sampling strategies in developmental science: population-based probability sampling, convenience sampling, quota sampling, and homogeneous sampling. We then judge these sampling strategies by five criteria: whether they yield representative and generalizable estimates of a study’s target population, whether they yield representative and generalizable estimates of subsamples within a study’s target population, the recruitment efforts and costs they entail, whether they yield sufficient power to detect subsample differences, and whether they introduce “noise” related to variation in subsamples and whether that “noise” can be accounted for statistically. We use sample composition of gender, ethnicity, and socioeconomic status to illustrate and assess the four sampling strategies. Finally, we tally the use of the four sampling strategies in five prominent developmental science journals and make recommendations about best practices for sample selection and reporting. PMID:25580049

  18. Working-memory training improves developmental dyslexia in Chinese children

    Institute of Scientific and Technical Information of China (English)

    Yan Luo; Jing Wang; Hanrong Wu; Dongmei Zhu; Yu Zhang

    2013-01-01

    Although plasticity in the neural system underlies working memory, and working memory can be improved by training, there is thus far no evidence that children with developmental dyslexia can were recruited from an elementary school in Wuhan, China. They received working-memory training, including training in visuospatial memory, verbal memory, and central executive tasks. The difficulty of the tasks was adjusted based on the performance of each subject, and the training sessions lasted 40 minutes per day, for 5 weeks. The results showed that working-memory training significantly enhanced performance on the nontrained working memory tasks such as the visuospatial, the verbal domains, and central executive tasks in children with developmental dyslexia. More importantly, the visual rhyming task and reading fluency task were also significantly improved by training. Progress on working memory measures was related to changes in reading skills. These experimental findings indicate that working memory is a pivotal factor in reading development among children with developmental dyslexia, and interventions to improve working memory may help dyslexic children to become more proficient in reading.

  19. Developmental reversals in recognition memory in children and adults.

    Science.gov (United States)

    Gross, Julien; Gardiner, Beatrix; Hayne, Harlene

    2016-01-01

    Older members of a given species typically exhibit superior learning and memory abilities relative to younger members, however, the developmental difference does not always occur in this younger-to-older direction. Developmental reversals are thought to reflect adaptive responses to the unique challenges imposed by the infant's niche. In humans, identification of developmental reversals has largely been precluded because infants, children, and adults are rarely tested using the same experimental procedures. Here, we adapted the visual recognition memory task and tested 3-year-olds and adults using one set of child-oriented stimuli and one set of adult-orientated stimuli. When tested immediately, children and adults exhibited recognition memory for both stimuli. When tested after a 1-week delay, children exhibited recognition memory for the child-oriented stimuli, but not for the adult-oriented stimuli and adults exhibited recognition memory for the adult-oriented stimuli, but not for the child-oriented stimuli. These data have important implications for current theories of memory development. © 2015 Wiley Periodicals, Inc.

  20. Music cognition: a developmental perspective.

    Science.gov (United States)

    Stalinski, Stephanie M; Schellenberg, E Glenn

    2012-10-01

    Although music is universal, there is a great deal of cultural variability in music structures. Nevertheless, some aspects of music processing generalize across cultures, whereas others rely heavily on the listening environment. Here, we discuss the development of musical knowledge, focusing on four themes: (a) capabilities that are present early in development; (b) culture-general and culture-specific aspects of pitch and rhythm processing; (c) age-related changes in pitch perception; and (d) developmental changes in how listeners perceive emotion in music. Copyright © 2012 Cognitive Science Society, Inc.

  1. Developmental Kindergarten Program Evaluation Report.

    Science.gov (United States)

    Blois, George T.; Cushing, Katherine S.

    The evaluation of the Developmental Kindergarten (DK) Program at the Harrison School District #2, Colorado Springs, Colorado, involved pre- and post-testing of student academic gains and interviewing of principals and teachers. The program aimed to provide developmentally appropriate activities for students believed to be "at risk" of…

  2. Developmentally Appropriate Peace Education Curricula

    Science.gov (United States)

    Lewsader, Joellen; Myers-Walls, Judith A.

    2017-01-01

    Peace education has been offered to children for decades, but those curricula have been only minimally guided by children's developmental stages and needs. In this article, the authors apply their research on children's developmental understanding of peace along with peace education principles and Vygotsky's sociocultural theory to present…

  3. Differentiating human NT2/D1 neurospheres as a versatile in vitro 3D model system for developmental neurotoxicity testing

    International Nuclear Information System (INIS)

    Hill, E.J.; Woehrling, E.K.; Prince, M.; Coleman, M.D.

    2008-01-01

    Developmental neurotoxicity is a major issue in human health and may have lasting neurological implications. In this preliminary study we exposed differentiating Ntera2/clone D1 (NT2/D1) cell neurospheres to known human teratogens classed as non-embryotoxic (acrylamide), weakly embryotoxic (lithium, valproic acid) and strongly embryotoxic (hydroxyurea) as listed by European Centre for the Validation of Alternative Methods (ECVAM) and examined endpoints of cell viability and neuronal protein marker expression specific to the central nervous system, to identify developmental neurotoxins. Following induction of neuronal differentiation, valproic acid had the most significant effect on neurogenesis, in terms of reduced viability and decreased neuronal markers. Lithium had least effect on viability and did not significantly alter the expression of neuronal markers. Hydroxyurea significantly reduced cell viability but did not affect neuronal protein marker expression. Acrylamide reduced neurosphere viability but did not affect neuronal protein marker expression. Overall, this NT2/D1-based neurosphere model of neurogenesis, may provide the basis for a model of developmental neurotoxicity in vitro

  4. A Developmental Investigation of Processing Costs in Implicature Production

    Science.gov (United States)

    Pouscoulous, Nausicaa; Noveck, Ira A.; Politzer, Guy; Bastide, Anne

    2007-01-01

    Much developmental work has been devoted to "scalar implicatures." These are implicitly communicated propositions linked to relatively weak terms (consider how "Some" pragmatically implies "Not all") that are more likely to be carried out by adults than by children. Children tend to retain the linguistically encoded…

  5. Developmental rates and morphological properties of fibres in two ...

    African Journals Online (AJOL)

    It was found, however, that dry sites, where trees are experiencing comparatively high levels of environmental stress, can be expected to experience greater extremes in developmental processes between seasons, or over relatively short periods, generally, than wetter sites. These sorts of fluctuations will also translate into ...

  6. Developmental constraints on behavioural flexibility.

    Science.gov (United States)

    Holekamp, Kay E; Swanson, Eli M; Van Meter, Page E

    2013-05-19

    We suggest that variation in mammalian behavioural flexibility not accounted for by current socioecological models may be explained in part by developmental constraints. From our own work, we provide examples of constraints affecting variation in behavioural flexibility, not only among individuals, but also among species and higher taxonomic units. We first implicate organizational maternal effects of androgens in shaping individual differences in aggressive behaviour emitted by female spotted hyaenas throughout the lifespan. We then compare carnivores and primates with respect to their locomotor and craniofacial adaptations. We inquire whether antagonistic selection pressures on the skull might impose differential functional constraints on evolvability of skulls and brains in these two orders, thus ultimately affecting behavioural flexibility in each group. We suggest that, even when carnivores and primates would theoretically benefit from the same adaptations with respect to behavioural flexibility, carnivores may nevertheless exhibit less behavioural flexibility than primates because of constraints imposed by past adaptations in the morphology of the limbs and skull. Phylogenetic analysis consistent with this idea suggests greater evolutionary lability in relative brain size within families of primates than carnivores. Thus, consideration of developmental constraints may help elucidate variation in mammalian behavioural flexibility.

  7. Delayed processing of global shape information in developmental prosopagnosia

    DEFF Research Database (Denmark)

    Gerlach, Christian; Klargaard, Solja K.; Petersen, Anders

    2017-01-01

    individuals with DP in Navon’s paradigm we find evidence of a reduced global precedence effect: The DPs are slower than controls to process global but not local shape information. Importantly, and in contrast to previous studies, we demonstrate that the DPs perform normally in a comprehensive test of visual......There is accumulating evidence suggesting that a central deficit in developmental prosopagnosia (DP), a disorder characterized by profound and lifelong difficulties with face recognition, concerns impaired holistic processing. Some of this evidence comes from studies using Navon’s paradigm where...... individuals with DP show a greater local or reduced global bias compared with controls. However, it has not been established what gives rise to this altered processing bias. Is it a reduced global precedence effect, changes in susceptibility to interference effects or both? By analyzing the performance of 10...

  8. Inversion effects for faces and objects in developmental prosopagnosia

    DEFF Research Database (Denmark)

    Klargaard, Solja K; Starrfelt, Randi; Gerlach, Christian

    2018-01-01

    The disproportionate face inversion effect (dFIE) concerns the finding that face recognition is more affected by inversion than recognition of non-face objects; an effect assumed to reflect that face recognition relies on special operations. Support for this notion comes from studies showing...... that face processing in developmental prosopagnosia (DP) is less affected by inversion than it is in normal subjects, and that DPs may even display face inversion superiority effects, i.e. better processing of inverted compared to upright faces. To date, however, there are no reports of direct comparisons...... between inversion effects for faces and objects, investigating whether the altered inversion effect in DP is specific to faces. We examined this question by comparing inversion effects for faces and cars in two otherwise identical recognition tasks in a group of DPs (N = 16) and a matched control group...

  9. Possible link between stress-related factors and altered body composition in women with polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Barnali Ray Basu

    2018-01-01

    Full Text Available Background: Stress is an invisible factor affecting modern day living and is strongly associated with many disease pathogenesis including polycystic ovarian syndrome (PCOS in women. PCOS is the most frequent endocrinological disorder that affects women of reproductive age, leading to metabolic dysfunction and body composition alterations. Salivary amylase and cortisol are major stress mediators that have been implicated in PCOS. However, their role in altering body composition in PCOS is yet to be deciphered. Aim: The present study aimed at understanding the relation between stress-associated factors and alterations in body composition among PCOS patients. Design: This study enrolled a total of 100 patients (PCOS and 60 age-matched controls. The female patients were of ages between 13 and 30 years. Materials and Methods: Standard assay kits were used to evaluate the α-amylase activity and cortisol level in saliva. The participants were chosen on the basis of the Rotterdam American Society for Reproductive Medicine/European Society of Human Reproduction criteria. Saliva was collected from each participant as per the protocol of Salimetrics, USA. Statistical Analysis: Statistical analysis was performed using SPSS version 20 for Windows. The quantitative variables are described as mean ± standard deviation. P < 0.05 was considered significant. Results: Increased salivary cortisol level and α-amylase activity were seen in the PCOS population as compared to age-matched controls suggesting patients a sustained stress scenario in their system. Moreover, overweight PCOS participants reflected higher amylase activity than the lean patients participants. Pulse rate, body mass index (BMI, visceral adiposity, and waist-hip ratio (WHR was considerably higher in the PCOS patients participants compared to controls. A significant correlation could be drawn between the α-amylase activity and BMI or WHR, respectively, among PCOS patients. These observations

  10. CEREBELLUM: LINKS BETWEEN DEVELOPMENT, DEVELOPMENTAL DISORDERS AND MOTOR LEARNING

    Directory of Open Access Journals (Sweden)

    Mario U Manto

    2012-01-01

    Full Text Available The study of the links and interactions between development and motor learning has noticeable implications for the understanding and management of neurodevelopmental disorders. This is particularly relevant for the cerebellum which is critical for sensorimotor learning. The olivocerebellar pathway is a key pathway contributing to learning of motor skills. Its developmental maturation and remodelling are being unravelled. Advances in genetics have led to major improvements in our appraisal of the genes involved in cerebellar development, especially studies in mutant mice. Cerebellar neurogenesis is compartmentalized in relationship with neurotransmitter fate. The Engrailed-2 gene is a major actor of the specification of cerebellar cell types and late embryogenic morphogenesis. Math1, expressed by the rhombic lip (RL, is required for the genesis of glutamatergic neurons. Mutants deficient for the transcription factor Ptf1a display a lack of Purkinje cells and gabaergic interneurons. Rora gene contributes to the developmental signalling between granule cells and Purkinje neurons. The expression profile of SHH (Sonic hedgehog in postnatal stages determines the final size/shape of the cerebellum. Genes affecting the development impact upon the physiological properties of the cerebellar circuits. For instance, receptors are developmentally regulated and their action interferes directly with developmental processes. Another field of research which is expanding relates to very preterm neonates. They are at risk for cerebellar lesions, which may themselves impair the developmental events. Very preterm neonates often show sensori-motor deficits, highlighting another major link between impaired development and learning deficiencies. Pathways playing a critical role in cerebellar development are likely to become therapeutical targets for several neurodevelopmental disorders.

  11. Syntactic Complexity Effects of Russian Relative Clause Sentences in Children with and without Developmental Language Disorder.

    Science.gov (United States)

    Rakhlin, Natalia; Kornilov, Sergey A; Kornilova, Tatiana V; Grigorenko, Elena L

    2016-01-01

    We investigated relative clause (RC) comprehension in 44 Russian-speaking children with typical language (TD) and developmental language disorder (DLD); M age = 10.67, SD = 2.84, and 22 adults. Flexible word order and morphological case in Russian allowed us to isolate factors that are obscured in English, helping us to identify sources of syntactic complexity and evaluate their roles in RC comprehension by children with typical language and their peers with DLD. We administered a working memory and an RC comprehension (picture-choice) task, which contained subject- and object-gap center-embedded and right branching RCs. The TD group, but not adults, demonstrated the effects of gap, embedding, and case. Their lower accuracy relative to adults was not fully attributable to differences in working memory. The DLD group displayed lower than TD children overall accuracy, accounted for by their lower working memory scores. While the effect of gap and embedding on their performance was not different from what was found for the TD group, children with DLD exhibited a diminished effect of case, suggesting reduced sensitivity to morphological case markers as processing cues. The implications of these results to theories of syntactic complexity and core deficits in DLD are discussed.

  12. Eating disorders in adolescence: attachment issues from a developmental perspective

    Directory of Open Access Journals (Sweden)

    Manuela eGander

    2015-08-01

    Full Text Available In the present article we review findings from an emerging body of research on attachment issues in adolescents with eating disorders from a developmental perspective. First, we will outline the crucial developmental changes in the attachment system and discuss how they might be related to the early onset of the disease. Then we will report on the major results from attachment studies using self-report and narrative instruments in that age group. Studies with a developmental approach on attachment will be analyzed in more detail. The high incidence of the unresolved attachment pattern in eating disorder samples is striking, especially for patients with anorexia nervosa. Interestingly, this predominance of the unresolved category was also found in their mothers. To date, these transgenerational aspects are still poorly understood and therefore represent an exciting research frontier. Future studies that include larger adolescent samples and provide a more detailed description including symptom severity and comorbidity would contribute to a better understanding of this complex and painful condition.

  13. The Developing, Aging Neocortex: How genetics and epigenetics influence early developmental patterning and age-related change.

    Directory of Open Access Journals (Sweden)

    Kelly J. Huffman

    2012-10-01

    Full Text Available A hallmark of mammalian development is the generation of functional subdivisions within the nervous system. In humans, this regionalization creates a complex system that regulates behavior, cognition, memory and emotion. During development, specification of neocortical tissue that leads to functional sensory and motor regions results from an interplay between cortically intrinsic, molecular processes, such as gene expression, and extrinsic processes regulated by sensory input. Cortical specification in mice occurs pre- and perinatally, when gene expression is robust and various anatomical distinctions are observed alongside an emergence of physiological function. After patterning, gene expression continues to shift and axonal connections mature into an adult form. The function of adult cortical gene expression may be to maintain neocortical subdivisions that were established during early patterning. As some changes in neocortical gene expression have been observed past early development into late adulthood, gene expression may also play a role in the altered neocortical function observed in age-related cognitive decline and brain dysfunction. This review provides a discussion of how neocortical gene expression and specific patterns of neocortical sensori-motor axonal connections develop and change throughout the lifespan of the animal. We posit that a role of neocortical gene expression in neocortex is to regulate plasticity mechanisms that impact critical periods for sensory and motor plasticity in aging. We describe results from several studies in aging brain that detail changes in gene expression that may relate to microstructural changes observed in brain anatomy. We discuss the role of altered glucocorticoid signaling in age-related cognitive and functional decline, as well as how aging in the brain may result from immune system activation. We describe how caloric restriction or reduction of oxidative stress may ameliorate effects of aging

  14. Peer victimization (and harsh parenting) as developmental correlates of cognitive reactivity, a diathesis for depression.

    Science.gov (United States)

    Cole, David A; Martin, Nina C; Sterba, Sonya K; Sinclair-McBride, Keneisha; Roeder, Kathryn M; Zelkowitz, Rachel; Bilsky, Sarah A

    2014-05-01

    Prior research has shown cognitive reactivity to be a diathesis for depression. Seeking evidence for the developmental origins of such diatheses, the current study examined peer victimization and harsh parenting as developmental correlates of cognitive reactivity in 571 children and adolescents (ages 8-13 years). Four major findings emerged. First, a new method for assessing cognitive reactivity in children and adolescents showed significant reliability and demonstrated construct validity vis-à-vis its relation to depression. Second, history of more severe peer victimization was significantly related to cognitive reactivity, with verbal victimization being more strongly tied to cognitive reactivity than other subtypes of peer victimization. Third, harsh parenting was also significantly related to cognitive reactivity. Fourth, both peer victimization and harsh parenting made unique statistical contributions to cognitive reactivity, after controlling for the effects of the other. Taken together, these findings provide preliminary support for a developmental model pertaining to origins of cognitive reactivity in children and adolescents.

  15. The relationship of undernutrition/psychosocial factors and developmental outcomes of children in extreme poverty in Ethiopia.

    Science.gov (United States)

    Worku, Berhanu Nigussie; Abessa, Teklu Gemechu; Wondafrash, Mekitie; Vanvuchelen, Marleen; Bruckers, Liesbeth; Kolsteren, Patrick; Granitzer, Marita

    2018-02-09

    , limited child-to-child interactions and mother-child relationships were negatively related mainly to gross motor and language performances of children in extreme poverty. Undernutrition and psychosocial factors were negatively related to the developmental outcomes, independently, of children living in extreme poverty. Intervention, for these children, should integrate home-based play-assisted developmental stimulation and nutritional rehabilitation.

  16. doublesex alters aggressiveness as a function of social context and sex in the polyphenic beetle Onthophagus taurus.

    Science.gov (United States)

    Beckers, Oliver M; Kijimoto, Teiya; Moczek, Armin P

    2017-10-01

    Despite sharing nearly the same genome, individuals within the same species can vary drastically in both morphology and behaviour as a function of developmental stage, sex or developmental plasticity. Thus, regulatory processes must exist that enable the stage-, sex- or environment-specific expression of traits and their integration during ontogeny, yet exactly how trait complexes are co-regulated and integrated is poorly understood. In this study, we explore the developmental genetic basis of the regulation and integration of environment-dependent sexual dimorphism in behaviour and morphology in the horn-polyphenic dung beetle Onthophagus taurus through the experimental manipulation of the transcription factor doublesex (dsx). The gene dsx plays a profound role in the developmental regulation of morphological differences between sexes as well as alternative male morphs by inhibiting horn formation in females but enabling nutrition-responsive horn growth in males. Specifically, we investigated whether experimental downregulation of dsx expression affects male and female aggressive and courtship behaviours in two social contexts: interactions between individuals of the same sex and interactions between males and females. We find that dsx downregulation significantly alters aggressiveness in both males and females, yet does so differently for both sexes as a function of social context: dsx RNAi males exhibited elevated aggression towards males but showed reduced aggression towards females, whereas dsx RNAi females became more aggressive towards males, while their aggressiveness towards other females was unaffected. Moreover, we document unexpectedly high levels of female aggression independent of dsx treatment in both wild-type and control-injected individuals. Lastly, we found no effects of dsx RNAi on courtship and mating behaviours. We discuss the role of dsx in the regulation of sex-specific and plastic behaviours, the unexpectedly high levels of aggression of

  17. Parenchymal abnormalities associated with developmental venous anomalies

    Energy Technology Data Exchange (ETDEWEB)

    San Millan Ruiz, Diego; Gailloud, Philippe [Johns Hopkins Hospital, Division of Interventional Neuroradiology, Baltimore, MD (United States); Delavelle, Jacqueline [Geneva University Hospital, Neuroradiology Section, Department of Radiology and Medical Informatics, Geneva (Switzerland); Yilmaz, Hasan; Ruefenacht, Daniel A. [Geneva University Hospital, Section of Interventional Neuroradiology, Department of Clinical Neurosciences, Geneva (Switzerland); Piovan, Enrico; Bertramello, Alberto; Pizzini, Francesca [Verona City Hospital, Service of Neuroradiology, Verona (Italy)

    2007-12-15

    To report a retrospective series of 84 cerebral developmental venous anomalies (DVAs), focusing on associated parenchymal abnormalities within the drainage territory of the DVA. DVAs were identified during routine diagnostic radiological work-up based on magnetic resonance imaging (MRI) (60 cases), computed tomography (CT) (62 cases) or both (36 cases). Regional parenchymal modifications within the drainage territory of the DVA, such as cortical or subcortical atrophy, white matter density or signal alterations, dystrophic calcifications, presence of haemorrhage or a cavernous-like vascular malformation (CVM), were noted. A stenosis of the collecting vein of the DVA was also sought for. Brain abnormalities within the drainage territory of a DVA were encountered in 65.4% of the cases. Locoregional brain atrophy occurred in 29.7% of the cases, followed by white matter lesions in 28.3% of MRI investigations and 19.3% of CT investigations, CVMs in 13.3% of MRI investigations and dystrophic calcification in 9.6% of CT investigations. An intracranial haemorrhage possibly related to a DVA occurred in 2.4% cases, and a stenosis on the collecting vein was documented in 13.1% of cases. Parenchymal abnormalities were identified for all DVA sizes. Brain parenchymal abnormalities were associated with DVAs in close to two thirds of the cases evaluated. These abnormalities are thought to occur secondarily, likely during post-natal life, as a result of chronic venous hypertension. Outflow obstruction, progressive thickening of the walls of the DVA and their morphological organization into a venous convergence zone are thought to contribute to the development of venous hypertension in DVA. (orig.)

  18. Cpt1a gene expression in peripheral blood mononuclear cells as an early biomarker of diet-related metabolic alterations

    KAUST Repository

    Diaz-Rua, Ruben

    2016-11-23

    Background: Research on biomarkers that provide early information about the development of future metabolic alterations is an emerging discipline. Gene expression analysis in peripheral blood mononuclear cells (PBMC) is a promising tool to identify subjects at risk of developing diet-related diseases.

  19. Developmentalism: An Obscure but Pervasive Restriction

    Directory of Open Access Journals (Sweden)

    J. E. Stone

    1996-04-01

    Full Text Available Despite continuing criticism of public education, experimentally demonstrated and field tested teaching methods have been ignored, rejected, and abandoned. Instead of a stable consensus regarding best teaching practices, there seems only an unending succession of innovations. A longstanding educational doctrine appears to underlie this anomalous state of affairs. Termed developmentalism, it presumes "natural" ontogenesis to be optimal and it requires experimentally demonstrated teaching practices to overcome a presumption that they interfere with an optimal developmental trajectory. It also discourages teachers and parents from asserting themselves with children. Instead of effective interventions, it seeks the preservation of a postulated natural perfection. Developmentalism's rich history is expressed in a literature extending over 400 years. Its notable exponents include Jean Jacques Rousseau, John Dewey, and Jean Piaget; and its most recent expressions include "developmentally appropriate practice" and "constructivism." In the years during which it gained ascendance, developmentalism served as a basis for rejecting harsh and inhumane teaching methods. Today it impedes efforts to hold schools accountable for student academic achievement.

  20. Developmental retardation, reduced fecundity, and modulated expression of the defensome in the intertidal copepod Tigriopus japonicus exposed to BDE-47 and PFOS.

    Science.gov (United States)

    Han, Jeonghoon; Won, Eun-Ji; Lee, Min-Chul; Seo, Jung Soo; Lee, Su-Jae; Lee, Jae-Seong

    2015-08-01

    2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and perfluorooctane sulfonate (PFOS) are widely dispersed persistent organic pollutants (POPs) in the marine ecosystem. However, their toxic effects on marine organisms are still poorly understood. In this study, we investigated the effects of BDE-47 and PFOS on development and reproduction at the organismal level and reactive oxygen species (ROS) production and gene expression patterns of the defensome at the cellular level in the intertidal copepod Tigriopus japonicus. In copepods exposed to BDE-47 and PFOS, we observed developmental retardation and reduced fecundity, suggesting repercussions on in vivo endpoints through alterations to the normal molting and reproduction system of T. japonicus. BDE-47 and PFOS increased levels of ROS in T. japonicus in a concentration-dependent manner, indicating that POPs can induce oxidative stress through the generation of ROS. Additionally, transcript profiles of genes related to detoxification (e.g., CYPs), antioxidant functions (e.g., GST- sigma, catalase, MnSOD), apoptosis (e.g., p53, Rb), and cellular proliferation (e.g., PCNA) were modulated over 72h in response to BDE-47 (120μg/L) and PFOS (1000μg/L). These findings indicate that BDE-47 and PFOS can induce oxidative stress-mediated DNA damage repair systems with transcriptional regulation of detoxification, antioxidant, and apoptosis-related genes, resulting in developmental retardation and reduced fecundity in the copepod T. japonicus. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Contribution of G protein-coupled estrogen receptor 1 (GPER) to 17β-estradiol-induced developmental toxicity in zebrafish.

    Science.gov (United States)

    Diamante, Graciel; Menjivar-Cervantes, Norma; Leung, Man Sin; Volz, David C; Schlenk, Daniel

    2017-05-01

    Exposure to 17β-estradiol (E2) influences the regulation of multiple signaling pathways, and E2-mediated disruption of signaling events during early development can lead to malformations such as cardiac defects. In this study, we investigated the potential role of the G-protein estrogen receptor 1 (GPER) in E2-induced developmental toxicity. Zebrafish embryos were exposed to E2 from 2h post fertilization (hpf) to 76 hpf with subsequent transcriptional measurements of heart and neural crest derivatives expressed 2 (hand2), leucine rich repeat containing 10 (lrrc10), and gper at 12, 28 and 76 hpf. Alteration in the expression of lrrc10, hand2 and gper was observed at 12 hpf and 76 hpf, but not at 28 hpf. Expression of these genes was also altered after exposure to G1 (a GPER agonist) at 76 hpf. Expression of lrrc10, hand2 and gper all coincided with the formation of cardiac edema at 76 hpf as well as other developmental abnormalities. While co-exposure of G1 with G36 (a GPER antagonist) rescued G1-induced abnormalities and altered gene expression, co-exposure of E2 with G36, or ICI 182,780 (an estrogen receptor antagonist) did not rescue E2-induced cardiac deformities or gene expression. In addition, no effects on the concentrations of downstream ER and GPER signaling molecules (cAMP or calcium) were observed in embryo homogenates after E2 treatment. These data suggest that the impacts of E2 on embryonic development at this stage are complex and may involve multiple receptor and/or signaling pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Cheating by exploitation of developmental prestalk patterning in Dictyostelium discoideum.

    Directory of Open Access Journals (Sweden)

    Anupama Khare

    2010-02-01

    Full Text Available The cooperative developmental system of the social amoeba Dictyostelium discoideum is susceptible to exploitation by cheaters-strains that make more than their fair share of spores in chimerae. Laboratory screens in Dictyostelium have shown that the genetic potential for facultative cheating is high, and field surveys have shown that cheaters are abundant in nature, but the cheating mechanisms are largely unknown. Here we describe cheater C (chtC, a strong facultative cheater mutant that cheats by affecting prestalk differentiation. The chtC gene is developmentally regulated and its mRNA becomes stalk-enriched at the end of development. chtC mutants are defective in maintaining the prestalk cell fate as some of their prestalk cells transdifferentiate into prespore cells, but that defect does not affect gross developmental morphology or sporulation efficiency. In chimerae between wild-type and chtC mutant cells, the wild-type cells preferentially give rise to prestalk cells, and the chtC mutants increase their representation in the spore mass. Mixing chtC mutants with other cell-type proportioning mutants revealed that the cheating is directly related to the prestalk-differentiation propensity of the victim. These findings illustrate that a cheater can victimize cooperative strains by exploiting an established developmental pathway.

  3. Cheating by Exploitation of Developmental Prestalk Patterning in Dictyostelium discoideum

    Science.gov (United States)

    Khare, Anupama; Shaulsky, Gad

    2010-01-01

    The cooperative developmental system of the social amoeba Dictyostelium discoideum is susceptible to exploitation by cheaters—strains that make more than their fair share of spores in chimerae. Laboratory screens in Dictyostelium have shown that the genetic potential for facultative cheating is high, and field surveys have shown that cheaters are abundant in nature, but the cheating mechanisms are largely unknown. Here we describe cheater C (chtC), a strong facultative cheater mutant that cheats by affecting prestalk differentiation. The chtC gene is developmentally regulated and its mRNA becomes stalk-enriched at the end of development. chtC mutants are defective in maintaining the prestalk cell fate as some of their prestalk cells transdifferentiate into prespore cells, but that defect does not affect gross developmental morphology or sporulation efficiency. In chimerae between wild-type and chtC mutant cells, the wild-type cells preferentially give rise to prestalk cells, and the chtC mutants increase their representation in the spore mass. Mixing chtC mutants with other cell-type proportioning mutants revealed that the cheating is directly related to the prestalk-differentiation propensity of the victim. These findings illustrate that a cheater can victimize cooperative strains by exploiting an established developmental pathway. PMID:20195510

  4. Embryo-larval exposure to atrazine reduces viability and alters oxidative stress parameters in Drosophila melanogaster.

    Science.gov (United States)

    Figueira, Fernanda Hernandes; Aguiar, Lais Mattos de; Rosa, Carlos Eduardo da

    2017-01-01

    The herbicide atrazine has been used worldwide with subsequent residual contamination of water and food, which may cause adverse effects on non-target organisms. Animal exposure to this herbicide may affect development, reproduction and energy metabolism. Here, the effects of atrazine regarding survival and redox metabolism were assessed in the fruit fly D. melanogaster exposed during embryonic and larval development. The embryos (newly fertilized eggs) were exposed to different atrazine concentrations (10μM and 100μM) in the diet until the adult fly emerged. Pupation and emergence rates, developmental time and sex ratio were determined as well as oxidative stress parameters and gene expression of the antioxidant defence system were evaluated in newly emerged male and female flies. Atrazine exposure reduced pupation and emergence rates in fruit flies without alterations to developmental time and sex ratio. Different redox imbalance patterns were observed between males and females exposed to atrazine. Atrazine caused an increase in oxidative damage, reactive oxygen species generation and antioxidant capacity and decreased thiol-containing molecules. Further, atrazine exposure altered the mRNA expression of antioxidant genes (keap1, sod, sod2, cat, irc, gss, gclm, gclc, trxt, trxr-1 and trxr-2). Reductions in fruit fly larval and pupal viability observed here are likely consequences of the oxidative stress induced by atrazine exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Research on structure-alteration zone related to uranium mineralization and its exploration significance

    International Nuclear Information System (INIS)

    Huang Xianfang; Liu Dechang; Ye Fawang; Dong Xiuzhen; Yang Xu Zhang Hongguang

    2008-01-01

    The paper is focused on recommending geological characteristics of structure-alteration zone which is found from image interpretation in Bashibulake District, north of Tarim Basin, expounding remote sensing information enhancement and extraction technique, analyzing image feature, genetic mechanism and discussing the relationship between uranium mineralization and structure-alteration zone. A new discovery is raised through applying remote sensing information analysis and geologic analysis, that is, the uranium deposits in Bashibulake District are controlled by structure-alteration zone. The new understanding provides a new view point for reconsidering main controlling factors and uranium mineralization distribution in the area. It is helpful for further reconnaissance and exploration in the area. (authors)

  6. Altered patterns of directed connectivity within the reading network of dyslexic children and their relation to reading dysfluency

    Directory of Open Access Journals (Sweden)

    Gojko Žarić

    2017-02-01

    Full Text Available Reading is a complex cognitive skill subserved by a distributed network of visual and language-related regions. Disruptions of connectivity within this network have been associated with developmental dyslexia but their relation to individual differences in the severity of reading problems remains unclear. Here we investigate whether dysfunctional connectivity scales with the level of reading dysfluency by examining EEG recordings during visual word and false font processing in 9-year-old typically reading children (TR and two groups of dyslexic children: severely dysfluent (SDD and moderately dysfluent (MDD dyslexics. Results indicated weaker occipital to inferior-temporal connectivity for words in both dyslexic groups relative to TRs. Furthermore, SDDs exhibited stronger connectivity from left central to right inferior-temporal and occipital sites for words relative to TRs, and for false fonts relative to both MDDs and TRs. Importantly, reading fluency was positively related with forward and negatively with backward connectivity. Our results suggest disrupted visual processing of words in both dyslexic groups, together with a compensatory recruitment of right posterior brain regions especially in the SDDs during word and false font processing. Functional connectivity in the brain’s reading network may thus depend on the level of reading dysfluency beyond group differences between dyslexic and typical readers.

  7. Roadside Judgments in Children with Developmental Co-ordination Disorder

    Science.gov (United States)

    Purcell, Catherine; Wann, John P.; Wilmut, Kate; Poulter, Damian

    2011-01-01

    As pedestrians, the perceptual ability to accurately judge the relative rate of approaching vehicles and select a suitable crossing gap requires sensitivity to looming. It also requires that crossing judgments are synchronized with motoric capabilities. Previous research has suggested that children with Developmental Co-ordination Disorder (DCD)…

  8. 29 CFR 1902.33 - Developmental period.

    Science.gov (United States)

    2010-07-01

    ... consideration of developmental changes by OSHA. Generally, whenever a State completes a developmental step, it must submit the resulting plan change as a supplement to its plan to OSHA for approval. OSHA's approval...

  9. Altered structural connectivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography.

    Science.gov (United States)

    Wada, Akihiko; Shizukuishi, Takashi; Kikuta, Junko; Yamada, Haruyasu; Watanabe, Yusuke; Imamura, Yoshiki; Shinozaki, Takahiro; Dezawa, Ko; Haradome, Hiroki; Abe, Osamu

    2017-05-01

    Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

  10. BDE-47 causes developmental retardation with down-regulated expression profiles of ecdysteroid signaling pathway-involved nuclear receptor (NR) genes in the copepod Tigriopus japonicus

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Dae-Sik; Han, Jeonghoon; Won, Eun-Ji; Kim, Duck-Hyun; Jeong, Chang-Bum [Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 16419 (Korea, Republic of); Hwang, Un-Ki [Marine Ecological Risk Assessment Center, West Sea Fisheries Research Institute, National Fisheries Research & Development Institute, Incheon 46083 (Korea, Republic of); Zhou, Bingsheng [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Choe, Joonho [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141 (Korea, Republic of); Lee, Jae-Seong, E-mail: jslee2@skku.edu [Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 16419 (Korea, Republic of)

    2016-08-15

    Highlights: • The developmental rate was significantly inhibited (P < 0.05) in response to BDE-47. • Expression profiles of nearly all NR genes were the highest at naupliar stages 5–6. • USP, HR96, and FTZ-F1 genes showed significant sex differences (P < 0.05) over different developmental stages. • NR gene expression patterns showed significant decreases (P<0.05) in response to BDE-47. • BDE-47 leads to molting and metamorphosis retardation and suppresses transcription of NR genes. - Abstract: 2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47) is a persistent organic pollutant (POP) in marine environments. Despite its adverse effects (e.g. developmental retardation) in ecdysozoa, the effects of BDE-47 on transcription of ecdysteroid signaling pathway-involved-nuclear receptor (NR) genes and metamorphosis-related genes have not been examined in copepods. To examine the deleterious effect of BDE-47 on copepod molting and metamorphosis, BDE-47 was exposed to the harpacticoid copepod Tigriopus japonicus, followed by monitoring developmental retardation and transcriptional alteration of NR genes. The developmental rate was significantly inhibited (P < 0.05) in response to BDE-47 and the agricultural insecticide gamma-hexachlorocyclohexane. Conversely, the ecdysteroid agonist ponasterone A (PoA) led to decreased molting and metamorphosis time (P < 0.05) from the nauplius stage to the adult stage. In particular, expression profiles of all NR genes were the highest at naupliar stages 5–6 except for SVP, FTZ-F1, and HR96 genes. Nuclear receptor USP, HR96, and FTZ-F1 genes also showed significant sex differences (P < 0.05) in gene expression levels over different developmental stages, indicating that these genes may be involved in vitellogenesis. NR gene expression patterns showed significant decreases (P < 0.05) in response to BDE-47 exposure, implying that molting and metamorphosis retardation is likely associated with NR gene expression. In summary, BDE-47

  11. BDE-47 causes developmental retardation with down-regulated expression profiles of ecdysteroid signaling pathway-involved nuclear receptor (NR) genes in the copepod Tigriopus japonicus

    International Nuclear Information System (INIS)

    Hwang, Dae-Sik; Han, Jeonghoon; Won, Eun-Ji; Kim, Duck-Hyun; Jeong, Chang-Bum; Hwang, Un-Ki; Zhou, Bingsheng; Choe, Joonho; Lee, Jae-Seong

    2016-01-01

    Highlights: • The developmental rate was significantly inhibited (P < 0.05) in response to BDE-47. • Expression profiles of nearly all NR genes were the highest at naupliar stages 5–6. • USP, HR96, and FTZ-F1 genes showed significant sex differences (P < 0.05) over different developmental stages. • NR gene expression patterns showed significant decreases (P<0.05) in response to BDE-47. • BDE-47 leads to molting and metamorphosis retardation and suppresses transcription of NR genes. - Abstract: 2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47) is a persistent organic pollutant (POP) in marine environments. Despite its adverse effects (e.g. developmental retardation) in ecdysozoa, the effects of BDE-47 on transcription of ecdysteroid signaling pathway-involved-nuclear receptor (NR) genes and metamorphosis-related genes have not been examined in copepods. To examine the deleterious effect of BDE-47 on copepod molting and metamorphosis, BDE-47 was exposed to the harpacticoid copepod Tigriopus japonicus, followed by monitoring developmental retardation and transcriptional alteration of NR genes. The developmental rate was significantly inhibited (P < 0.05) in response to BDE-47 and the agricultural insecticide gamma-hexachlorocyclohexane. Conversely, the ecdysteroid agonist ponasterone A (PoA) led to decreased molting and metamorphosis time (P < 0.05) from the nauplius stage to the adult stage. In particular, expression profiles of all NR genes were the highest at naupliar stages 5–6 except for SVP, FTZ-F1, and HR96 genes. Nuclear receptor USP, HR96, and FTZ-F1 genes also showed significant sex differences (P < 0.05) in gene expression levels over different developmental stages, indicating that these genes may be involved in vitellogenesis. NR gene expression patterns showed significant decreases (P < 0.05) in response to BDE-47 exposure, implying that molting and metamorphosis retardation is likely associated with NR gene expression. In summary, BDE-47

  12. Associations Between Maternal-Foetal Attachment and Infant Developmental Outcomes: A Systematic Review.

    Science.gov (United States)

    Branjerdporn, Grace; Meredith, Pamela; Strong, Jenny; Garcia, Jenniffer

    2017-03-01

    Objectives Infant developmental outcomes may be influenced by a range of prenatal maternal characteristics. While there is some evidence to suggest that maternal-foetal attachment may be associated with infant developmental outcomes, there is a need to systematically review this evidence to guide future research and clinical practice. Methods Five electronic databases were systematically scanned. Key journals and reference lists were hand-searched. Papers were included if: (1) pregnant women were assessed for maternal-foetal attachment; (2) the infants were later assessed, under 2 years old, for any developmental outcome (e.g., social-emotional, cognition, motor, language, adaptive behaviour); and (3) they were published in English. Two independent reviewers used the STROBE checklist to appraise the quality of each paper. Results Of the 968 papers identified, eight were included in the review, and four of these were of low quality (infant temperament (n = 5), adaptive behaviour (e.g., colic, sleep) (n = 2), and milestone attainment (n = 1). There is some evidence to suggest that lower maternal-foetal attachment is related to suboptimal developmental outcomes. However, these results should be interpreted with caution due to the limited and low quality studies available. Conclusions Although maternal-foetal attachment may be associated with infant developmental outcomes, future research is required which: (1) considers a range of developmental outcomes, (2) has increased scientific rigour, (3) assesses mother-infant dyads at different prenatal and postnatal time points, and (4) examines different target populations.

  13. Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects.

    Directory of Open Access Journals (Sweden)

    Tiziano Pramparo

    2011-03-01

    Full Text Available Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3ε that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3ε, and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can

  14. Research Review: Evaluating and reformulating the developmental taxonomic theory of antisocial behaviour

    Science.gov (United States)

    Fairchild, Graeme; Goozen, Stephanie HM; Calder, Andrew J; Goodyer, Ian M

    2013-01-01

    BackgroundThe developmental taxonomic theory proposes that there are two subtypes of antisocial behaviour. The first is a neurodevelopmental disorder which emerges in early childhood and follows a life-course persistent course, whereas the second emerges in adolescence, remits in early adulthood and reflects peer processes such as mimicry of antisocial peers. The aim of this review was to evaluate the developmental taxonomic theory in the light of recent empirical research. MethodsWe conducted a comprehensive literature review comparing these subtypes of antisocial behaviour based on searches on PubMed and other scientific databases covering the period from 1993 to 2013. We focused on research encompassing psychiatric epidemiology, personality assessment, neuropsychology, neuroendocrinology, genetics, and structural and functional neuroimaging. Sixty one empirical studies were identified that investigated one of these forms of antisocial behaviour separately or explicitly compared childhood-onset and adolescence-onset forms of antisocial behaviour. ResultsEmpirical research provides support for the hypothesis that life-course persistent antisocial behaviour is a neurodevelopmental disorder which emerges in the transactions between individual vulnerabilities and environmental adversity. In contrast to the developmental taxonomic theory, however, empirical findings suggest that severe antisocial behaviour that emerges in adolescence frequently has a negative prognosis and is rarely limited to the adolescent period. In addition, both forms of antisocial behaviour are associated with emotion processing deficits, changes in brain structure and function, alterations in cortisol secretion, and atypical personality traits (such as increased callous-unemotional traits). ConclusionsWe conclude that the developmental taxonomic theory is in need of revision, as differences between life-course persistent and adolescence-onset forms of antisocial behaviour appear to be

  15. Developmental principles: fact or fiction.

    Science.gov (United States)

    Durston, A J

    2012-01-01

    While still at school, most of us are deeply impressed by the underlying principles that so beautifully explain why the chemical elements are ordered as they are in the periodic table, and may wonder, with the theoretician Brian Goodwin, "whether there might be equally powerful principles that account for the awe-inspiring diversity of body forms in the living realm". We have considered the arguments for developmental principles, conclude that they do exist and have specifically identified features that may generate principles associated with Hox patterning of the main body axis in bilaterian metazoa in general and in the vertebrates in particular. We wonder whether this exercise serves any purpose. The features we discuss were already known to us as parts of developmental mechanisms and defining developmental principles (how, and at which level?) adds no insight. We also see little profit in the proposal by Goodwin that there are principles outside the emerging genetic mechanisms that need to be taken into account. The emerging developmental genetic hierarchies already reveal a wealth of interesting phenomena, whatever we choose to call them.

  16. The Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge

    2001-01-01

    AbstractIn the nineties, the concept of the developmental work (DW) has become a significant point of orientation for the actors on Danish labour market. The DW has moved the focus of the labour market from wages and working time towards work and production. For employees, the DW promises...... developmental possibilities, influence and responsibility, but also greater social responsibility for the firm. For firms, the DW promises increased competitiveness and better products. In this paper we present the concept of the DW as one which encourages the development of work, production and organisation...... of the firm and show that the DW is different from mainstream management concepts, as the DW...

  17. Future Directions in Sleep and Developmental Psychopathology.

    Science.gov (United States)

    Meltzer, Lisa J

    2017-01-01

    It is critical for psychologists to gain a better understanding about the intersection between sleep and developmental psychopathology. However, while many strive to answer the question of whether sleep causes developmental psychopathology, or vice versa, ultimately the relationship between sleep and developmental psychopathology is complex and dynamic. This article considers future directions in the field of clinical child and adolescent psychology that go beyond this mechanistic question, highlighting areas important to address for clinicians and researchers who strive to better understand how best to serve children and adolescents with developmental psychopathology. Questions are presented about what is normal in terms of sleep across development, the role of individual variability in terms of sleep needs and vulnerability to sleep loss, and how sleep may serve as a risk or resilience factor for developmental psychopathology, concluding with considerations for interventions.

  18. Developmental programming: effect of prenatal steroid excess on intraovarian components of insulin signaling pathway and related proteins in sheep.

    Science.gov (United States)

    Ortega, Hugo H; Rey, Florencia; Velazquez, Melisa M L; Padmanabhan, Vasantha

    2010-06-01

    Prenatal testosterone (T) excess increases ovarian follicular recruitment, follicular persistence, insulin resistance, and compensatory hyperinsulinemia. Considering the importance of insulin in ovarian physiology, in this study, using prenatal T- and dihydrotestosterone (DHT, a nonaromatizable androgen)-treated female sheep, we tested the hypothesis that prenatal androgen excess alters the intraovarian insulin signaling cascade and metabolic mediators that have an impact on insulin signaling. Changes in ovarian insulin receptor (INSRB), insulin receptor substrate 1 (IRS1), mammalian target of rapamycin (MTOR), phosphatidylinositol 3-kinase (PIK3), peroxisome proliferator-activated receptor-gamma (PPARG), and adiponectin proteins were determined at fetal (Days 90 and 140), postpubertal (10 mo), and adult (21 mo) ages by immunohistochemistry. Results indicated that these proteins were expressed in granulosa, theca, and stromal compartments, with INSRB, IRS1, PPARG, and adiponectin increasing in parallel with advanced follicular differentiation. Importantly, prenatal T excess induced age-specific changes in PPARG and adiponectin expression, with increased PPARG expression evident during fetal life and decreased antral follicular adiponectin expression during adult life. Comparison of developmental changes in prenatal T and DHT-treated females found that the effects on PPARG were programmed by androgenic actions of T, whereas the effects on adiponectin were likely by its estrogenic action. These results suggest a role for PPARG in the programming of ovarian disruptions by prenatal T excess, including a decrease in antral follicular adiponectin expression and a contributory role for adiponectin in follicular persistence and ovulatory failure.

  19. DEVELOPMENTAL TAXONOMY OF CONDUCT DISORDER

    Directory of Open Access Journals (Sweden)

    Jelena Kostić

    2015-12-01

    Full Text Available Conduct disorder is a heterogeneous disorder in terms of etiology, course and prognosis, and currently, there is no singular model that would describe the development of the disorder. The results of empirical research on males confirm this heterogeneity, as they point out to two possible developmental pathways: childhood-onset and adolescentonset type. This paper presents the basic elements of developmental taxonomic theory which argues that there are two different developmental pathways to conduct disorder which have different causes and serve as the basis for the current typology of conduct disorders in the classification systems. Such a typology of conduct disorders in the diagnostic classification allows better understanding, prognosis and choice of treatment.

  20. Berberine exposure triggers developmental effects on planarian regeneration.

    Science.gov (United States)

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

    2014-05-09

    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.