Critical developmental windows for morphology and hematology revealed by intermittent and continuous hypoxic incubation in embryos of quail (Coturnix coturnix)

PubMed Central

Elmonoufy, Nourhan A.

2017-01-01

Hypoxia during embryonic growth in embryos is frequently a powerful determinant of development, but at least in avian embryos the effects appear to show considerable intra- and inter-specific variation. We hypothesized that some of this variation may arise from different protocols that may or may not result in exposure during the embryo’s critical window for hypoxic effects. To test this hypothesis, quail embryos (Coturnix coturnix) in the intact egg were exposed to hypoxia (~15% O2) during “early” (Day 0 through Day 5, abbreviated as D0-D5), “middle” (D6-D10) or “late” (D11-D15) incubation or for their entire 16–18 day incubation (“continuous hypoxia”) to determine critical windows for viability and growth. Viability, body mass, beak and toe length, heart mass, and hematology (hematocrit and hemoglobin concentration) were measured on D5, D10, D15 and at hatching typically between D16 and D18 Viability rate was ~50–70% immediately following the exposure period in the early, middle and late hypoxic groups, but viability improved in the early and late groups once normoxia was restored. Middle hypoxia groups showed continuing low viability, suggesting a critical period from D6-D10 for embryo viability. The continuous hypoxia group experienced viability reaching <10% after D15. Hypoxia, especially during late and continuous hypoxia, also inhibited growth of body, beak and toe when measured at D15. Full recovery to normal body mass upon hatching occurred in all other groups except for continuous hypoxia. Contrary to previous avian studies, heart mass, hematocrit and hemoglobin concentration were not altered by any hypoxic incubation pattern. Although hypoxia can inhibit embryo viability and organ growth during most incubation periods, the greatest effects result from continuous or middle incubation hypoxic exposure. Hypoxic inhibition of growth can subsequently be “repaired” by catch-up growth if a final period of normoxic development is available. Collectively, these data indicate a critical developmental window for hypoxia susceptibility during the mid-embryonic period of development. PMID:28926567

Critical developmental windows for morphology and hematology revealed by intermittent and continuous hypoxic incubation in embryos of quail (Coturnix coturnix).

PubMed

Burggren, Warren W; Elmonoufy, Nourhan A

2017-01-01

Hypoxia during embryonic growth in embryos is frequently a powerful determinant of development, but at least in avian embryos the effects appear to show considerable intra- and inter-specific variation. We hypothesized that some of this variation may arise from different protocols that may or may not result in exposure during the embryo's critical window for hypoxic effects. To test this hypothesis, quail embryos (Coturnix coturnix) in the intact egg were exposed to hypoxia (~15% O2) during "early" (Day 0 through Day 5, abbreviated as D0-D5), "middle" (D6-D10) or "late" (D11-D15) incubation or for their entire 16-18 day incubation ("continuous hypoxia") to determine critical windows for viability and growth. Viability, body mass, beak and toe length, heart mass, and hematology (hematocrit and hemoglobin concentration) were measured on D5, D10, D15 and at hatching typically between D16 and D18 Viability rate was ~50-70% immediately following the exposure period in the early, middle and late hypoxic groups, but viability improved in the early and late groups once normoxia was restored. Middle hypoxia groups showed continuing low viability, suggesting a critical period from D6-D10 for embryo viability. The continuous hypoxia group experienced viability reaching <10% after D15. Hypoxia, especially during late and continuous hypoxia, also inhibited growth of body, beak and toe when measured at D15. Full recovery to normal body mass upon hatching occurred in all other groups except for continuous hypoxia. Contrary to previous avian studies, heart mass, hematocrit and hemoglobin concentration were not altered by any hypoxic incubation pattern. Although hypoxia can inhibit embryo viability and organ growth during most incubation periods, the greatest effects result from continuous or middle incubation hypoxic exposure. Hypoxic inhibition of growth can subsequently be "repaired" by catch-up growth if a final period of normoxic development is available. Collectively, these data indicate a critical developmental window for hypoxia susceptibility during the mid-embryonic period of development.

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia

PubMed Central

Do, Kim Q.; Cuenod, Michel; Hensch, Takao K.

2015-01-01

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry. PMID:26032508

Worldwide variability in growth and its association with health: Incorporating body composition, developmental plasticity, and intergenerational effects.

PubMed

Wells, Jonathan C K

2017-03-01

In their seminal book "Worldwide variation in human growth," published in 1976, Eveleth and Tanner highlighted substantial variability within and between populations in the magnitude and schedule of human growth. In the four decades since then, research has clarified why growth variability is so closely associated with human health. First, growth patterns are strongly associated with body composition, both in the short- and long-term. Poor growth in early life constrains the acquisition of lean tissue, while compensatory "catch-up" growth may elevate body fatness. Second, these data are examples of the fundamental link between growth and developmental plasticity. Growth is highly sensitive to ecological stresses and stimuli during early "critical windows," but loses much of this sensitivity as it undergoes canalization during early childhood. Crucially, the primary source of stimuli during early "critical windows" is not the external environment itself, but rather maternal phenotype, which transduces the impact of ecological conditions. Maternal phenotype, representing many dimensions of "capital," thus generates a powerful impact on the developmental trajectory of the offspring. There is increasing evidence that low levels of maternal capital impact the offspring's size at birth, schedule of maturation, and body composition and physiological function in adulthood. While evidence has accrued of substantial heritability in adult height, it is clear that the pathway through which it is attained has major implications for metabolic phenotype. Integrating these perspectives is important for understanding how developmental plasticity may on the one hand contribute to adaptation, while on the other shape susceptibility to non-communicable disease. © 2017 Wiley Periodicals, Inc.

Lagged kernel machine regression for identifying time windows of susceptibility to exposures of complex mixtures.

PubMed

Liu, Shelley H; Bobb, Jennifer F; Lee, Kyu Ha; Gennings, Chris; Claus Henn, Birgit; Bellinger, David; Austin, Christine; Schnaas, Lourdes; Tellez-Rojo, Martha M; Hu, Howard; Wright, Robert O; Arora, Manish; Coull, Brent A

2018-07-01

The impact of neurotoxic chemical mixtures on children's health is a critical public health concern. It is well known that during early life, toxic exposures may impact cognitive function during critical time intervals of increased vulnerability, known as windows of susceptibility. Knowledge on time windows of susceptibility can help inform treatment and prevention strategies, as chemical mixtures may affect a developmental process that is operating at a specific life phase. There are several statistical challenges in estimating the health effects of time-varying exposures to multi-pollutant mixtures, such as: multi-collinearity among the exposures both within time points and across time points, and complex exposure-response relationships. To address these concerns, we develop a flexible statistical method, called lagged kernel machine regression (LKMR). LKMR identifies critical exposure windows of chemical mixtures, and accounts for complex non-linear and non-additive effects of the mixture at any given exposure window. Specifically, LKMR estimates how the effects of a mixture of exposures change with the exposure time window using a Bayesian formulation of a grouped, fused lasso penalty within a kernel machine regression (KMR) framework. A simulation study demonstrates the performance of LKMR under realistic exposure-response scenarios, and demonstrates large gains over approaches that consider each time window separately, particularly when serial correlation among the time-varying exposures is high. Furthermore, LKMR demonstrates gains over another approach that inputs all time-specific chemical concentrations together into a single KMR. We apply LKMR to estimate associations between neurodevelopment and metal mixtures in Early Life Exposures in Mexico and Neurotoxicology, a prospective cohort study of child health in Mexico City.

Periods of cardiovascular susceptibility to hypoxia in embryonic american alligators (Alligator mississippiensis)

PubMed Central

Tate, Kevin B.; Rhen, Turk; Eme, John; Kohl, Zachary F.; Crossley, Janna; Elsey, Ruth M.

2016-01-01

During embryonic development, environmental perturbations can affect organisms' developing phenotype, a process known as developmental plasticity. Resulting phenotypic changes can occur during discrete, critical windows of development. Critical windows are periods when developing embryos are most susceptible to these perturbations. We have previously documented that hypoxia reduces embryo size and increases relative heart mass in American alligator, and this study identified critical windows when hypoxia altered morphological, cardiovascular function and cardiac gene expression of alligator embryos. We hypothesized that incubation in hypoxia (10% O2) would increase relative cardiac size due to cardiac enlargement rather than suppression of somatic growth. We exposed alligator embryos to hypoxia during discrete incubation periods to target windows where the embryonic phenotype is altered. Hypoxia affected heart growth between 20 and 40% of embryonic incubation, whereas somatic growth was affected between 70 and 90% of incubation. Arterial pressure was depressed by hypoxic exposure during 50–70% of incubation, whereas heart rate was depressed in embryos exposed to hypoxia during a period spanning 70–90% of incubation. Expression of Vegf and PdgfB was increased in certain hypoxia-exposed embryo treatment groups, and hypoxia toward the end of incubation altered β-adrenergic tone for arterial pressure and heart rate. It is well known that hypoxia exposure can alter embryonic development, and in the present study, we have identified brief, discrete windows that alter the morphology, cardiovascular physiology, and gene expression in embryonic American alligator. PMID:27101296

The Moving Window Technique: A Window into Developmental Changes in Attention during Facial Emotion Recognition

ERIC Educational Resources Information Center

Birmingham, Elina; Meixner, Tamara; Iarocci, Grace; Kanan, Christopher; Smilek, Daniel; Tanaka, James W.

2013-01-01

The strategies children employ to selectively attend to different parts of the face may reflect important developmental changes in facial emotion recognition. Using the Moving Window Technique (MWT), children aged 5-12 years and adults ("N" = 129) explored faces with a mouse-controlled window in an emotion recognition task. An…

Is There a Critical Period for the Developmental Neurotoxicity of Low-Level Tobacco Smoke Exposure?

PubMed

Slotkin, Theodore A; Stadler, Ashley; Skavicus, Samantha; Card, Jennifer; Ruff, Jonathan; Levin, Edward D; Seidler, Frederic J

2017-01-01

Secondhand tobacco smoke exposure in pregnancy increases the risk of neurodevelopmental disorders. We evaluated in rats whether there is a critical period during which tobacco smoke extract (TSE) affects the development of acetylcholine and serotonin systems, prominent targets for adverse effects of nicotine and tobacco smoke. We simulated secondhand smoke exposure by administering TSE so as to produce nicotine concentrations one-tenth those in active smoking, with 3 distinct, 10-day windows: premating, early gestation or late gestation. We conducted longitudinal evaluations in multiple brain regions, starting in early adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure in any of the 3 windows impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although the adverse effects were seen for all 3 treatment windows, there was a distinct progression, with lowest sensitivity for premating exposure and higher sensitivity for gestational exposures. Serotonin receptors were also reduced by TSE exposure with the same profile: little effect with premating exposure, intermediate effect with early gestational exposure and large effect with late gestational exposure. As serotonergic circuits can offset the neurobehavioral impact of cholinergic deficits, these receptor changes were maladaptive. Thus, there is no single 'critical period' for effects of low-level tobacco smoke but there is differential sensitivity dependent upon the developmental stage at the time of exposure. Our findings reinforce the need to avoid secondhand smoke exposure not only during pregnancy, but also in the period prior to conception, or generally for women of childbearing age. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

How flexible is phenotypic plasticity? Developmental windows for trait induction and reversal.

PubMed

Hoverman, Jason T; Relyea, Rick A

2007-03-01

Inducible defenses allow prey to modulate their phenotypic responses to the level of predation risk in the environment and reduce the cost of constitutive defenses. Inherent in this statement is that prey must alter their phenotypes during development in order to form these defenses. This has lead many ecologists and evolutionary biologists to call for studies that examine developmental plasticity to provide insights into the importance of development in controlling the trajectories of trait formation, the integration of phenotypes over ontogeny, and the establishment of developmental windows for trait formation and reversal. By moving away from studies that focus on a single point in development, we can obtain a more complete understanding of the phenotypic decisions and limitations of prey. We exposed freshwater snails (Helisoma trivolvis) to environments in which predatory water bugs (Belostoma flumineum) were always absent, always present, or added and removed at different points in development. We discovered that snails formed morphological defenses against water bugs. Importantly, after the initial induction of defenses, snails showed similar developmental trajectories as snails reared without predators. Further, the snails possessed wide developmental windows for inducible defenses that extended past sexual maturity. However, being induced later in development appeared to have an associated cost (i.e., decreased shell thickness) that was not found when water bugs were always present. This epiphenotype (i.e., new shell formation as an extension of the current shell) suggests that resource limitation plays an important role in responses to temporal variation in predation risk and may have critical ecological costs that limit the benefits of the inducible defense. Lastly, the ability of snails to completely reverse their defenses was limited to early in ontogeny due to the constraints associated with modular growth of shell material. In sum, we demonstrate that taking a developmental perspective is extremely valuable for understanding the ecology of inducible defenses.

Neuroendocrine models of social anxiety disorder

PubMed Central

van Honk, Jack; Bos, Peter A.; Terburg, David; Heany, Sarah; Stein, Dan J.

2015-01-01

Social anxiety disorder (SAD) is a highly prevalent and disabling disorder with key behavioral traits of social fearfulness, social avoidance, and submissiveness. Here we argue that hormonal systems play a key role in mediating social anxiety, and so may be important in SAD. Hormonal alterations, often established early in development through the interaction between biological and psychological factors (eg, genetic predisposition x early trauma), predispose to socially fearful, avoidant, and submissive behavior. However, whereas gene variants and histories of trauma persist, hormonal systems can be remodeled over the course of life. Hormones play a key role during the periods of all sensitive developmental windows (ie, prenatal, neonatal, puberty, aging), and are capable of opening up new developmental windows in adulthood. Indeed, the developmental plasticity of our social brain, and thus of social behavior in adulthood, critically depends on steroid hormones such as testosterone and peptide hormones such as oxytocin. These steroid and peptide hormones in interaction with social experiences may have potential for reprogramming the socially anxious brain. Certainly, single administrations of oxytocin and testosterone in humans reduce socially fearful, avoidant, and submissive behavior. Such work may ultimately lead to new approaches to the treatment of SAD. PMID:26487809

Differential Immunotoxicity Induced by Two Different Windows of Developmental Trichloroethylene Exposure

PubMed Central

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

2014-01-01

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

Assessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model

PubMed Central

Sant, Karilyn E.; Jacobs, Haydee M.; Xu, Jiali; Borofski, Katrina A.; Moss, Larry G.; Moss, Jennifer B.; Timme-Laragy, Alicia R.

2016-01-01

The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio). Using endogenously expressed fluorescent protein markers for developing zebrafish beta cells and exocrine pancreas tissue, we documented differences in islet area and incidence rates of islet morphological variants in zebrafish embryos between 48 and 96 h post fertilization (hpf), raised under control conditions commonly used in embryotoxicity assays. We identified critical windows for chemical exposures during which increased incidences of endocrine pancreas abnormalities were observed following exposure to cyclopamine (2–12 hpf), Mono-2-ethylhexyl phthalate (MEHP) (3–48 hpf), and Perfluorooctanesulfonic acid (PFOS) (3–48 hpf). Both islet area and length of the exocrine pancreas were sensitive to oxidative stress from exposure to the oxidant tert-butyl hydroperoxide during a highly proliferative critical window (72 hpf). Finally, pancreatic dysmorphogenesis following developmental exposures is discussed with respect to human disease. PMID:28393070

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

PubMed

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.

From Mice to Men: research models of developmental programming

PubMed Central

Rabadán-Diehl, C.; Nathanielsz, P.

2012-01-01

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

Bayesian distributed lag interaction models to identify perinatal windows of vulnerability in children's health.

PubMed

Wilson, Ander; Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Wright, Robert O; Wright, Rosalind J; Coull, Brent A

2017-07-01

Epidemiological research supports an association between maternal exposure to air pollution during pregnancy and adverse children's health outcomes. Advances in exposure assessment and statistics allow for estimation of both critical windows of vulnerability and exposure effect heterogeneity. Simultaneous estimation of windows of vulnerability and effect heterogeneity can be accomplished by fitting a distributed lag model (DLM) stratified by subgroup. However, this can provide an incomplete picture of how effects vary across subgroups because it does not allow for subgroups to have the same window but different within-window effects or to have different windows but the same within-window effect. Because the timing of some developmental processes are common across subpopulations of infants while for others the timing differs across subgroups, both scenarios are important to consider when evaluating health risks of prenatal exposures. We propose a new approach that partitions the DLM into a constrained functional predictor that estimates windows of vulnerability and a scalar effect representing the within-window effect directly. The proposed method allows for heterogeneity in only the window, only the within-window effect, or both. In a simulation study we show that a model assuming a shared component across groups results in lower bias and mean squared error for the estimated windows and effects when that component is in fact constant across groups. We apply the proposed method to estimate windows of vulnerability in the association between prenatal exposures to fine particulate matter and each of birth weight and asthma incidence, and estimate how these associations vary by sex and maternal obesity status in a Boston-area prospective pre-birth cohort study. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum

PubMed Central

Maltese, Marta; Stanic, Jennifer; Tassone, Annalisa; Sciamanna, Giuseppe; Ponterio, Giulia; Vanni, Valentina; Martella, Giuseppina; Imbriani, Paola; Bonsi, Paola; Mercuri, Nicola Biagio

2018-01-01

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a+/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a+/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a+/Δgag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers. PMID:29504938

DPOAEs in infants developmentally exposed to PCBs show two differently time spaced exposure sensitive windows.

PubMed

Koštiaková, Vladimíra; Moleti, Arturo; Wimmerová, Soňa; Jusko, Todd A; Palkovičová Murínová, Ľubica; Sisto, Renata; Richterová, Denisa; Kováč, Ján; Čonka, Kamil; Patayová, Henrieta; Tihányi, Juraj; Trnovec, Tomáš

2016-10-01

The study aim was to identify the timing of sensitive windows for ototoxicity related to perinatal exposure to PCBs. A total of 351 and 214 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 and 72 months, respectively, and distortion product otoacoustic emissions (DPOAEs) at 11 frequencies were recorded. Cord and child 6-, 16-, 45-, and 72- month blood samples were analyzed for PCB 153 concentration. The PCB 153 concentration-time profiles were approximated with a system model to calculate area under the PCB*time curves (AUCs) for specific time intervals (3 and 6 months for 45 and 72 months data, respectively). DPOAE amplitudes were correlated (Spearman) with cord serum PCB and AUCs, markers of prenatal and postnatal exposure, respectively. Two exposure critical windows were identified in infants, the first related to prenatal and early postnatal and the second to postnatal exposure to PCBs. Our data have shown tonotopicity, sexual dimorphism, and asymmetry in ototoxicity of PCBs. Copyright © 2016. Published by Elsevier Ltd.

RELAP5-3D developmental assessment: Comparison of version 4.2.1i on Linux and Windows

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

Bayless, Paul D.

2014-06-01

Figures have been generated comparing the parameters used in the developmental assessment of the RELAP5-3D code, version 4.2i, compiled on Linux and Windows platforms. The figures, which are the same as those used in Volume III of the RELAP5-3D code manual, compare calculations using the semi-implicit solution scheme with available experiment data. These figures provide a quick, visual indication of how the code predictions differ between the Linux and Windows versions.

RELAP5-3D Developmental Assessment. Comparison of Version 4.3.4i on Linux and Windows

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

Bayless, Paul David

2015-10-01

Figures have been generated comparing the parameters used in the developmental assessment of the RELAP5-3D code, version 4.3i, compiled on Linux and Windows platforms. The figures, which are the same as those used in Volume III of the RELAP5-3D code manual, compare calculations using the semi-implicit solution scheme with available experiment data. These figures provide a quick, visual indication of how the code predictions differ between the Linux and Windows versions.

Biochemical basis for pharmacological intervention as a reprogramming strategy against hypertension and kidney disease of developmental origin.

PubMed

Tain, You-Lin; Chan, Samuel H H; Chan, Julie Y H

2018-07-01

The concept of "developmental origins of health and disease" (DOHaD) stipulates that both hypertension and kidney disease may take origin from early-life insults. The DOHaD concept also offers reprogramming strategies aiming at shifting therapeutic interventions from adulthood to early life, even before clinical symptoms are evident. Based on those two concepts, this review will present the evidence for the existence of, and the programming mechanisms in, kidney developmental programming that may lead to hypertension and kidney disease. This will be followed by potential pharmacological interventions that may serve as a reprogramming strategy to counter the rising epidemic of hypertension and kidney disease. We point out that before patients could benefit from this strategy, the most pressing issue is for the growing body of evidence from animal studies in support of pharmacological intervention as a reprogramming strategy to long-term protect against hypertension and kidney disease of developmental origins to be validated clinically and the critical window, drug dose, dosing regimen, and therapeutic duration identified. Copyright © 2018 Elsevier Inc. All rights reserved.

Windows of susceptibility and consequences of early life exposures to 17β–estradiol on medaka (Oryzias latipes) reproductive success

USGS Publications Warehouse

Lee Pow, Crystal S. D.; Tilahun, Kedamawit; Creech, Kari; Law, J. Mac; Cope, W. Gregory; Kwak, Thomas J.; Rice, James A.; Aday, D. Derek; Kullman, Seth W.

2017-01-01

Estrogens and estrogen mimics are commonly found in surface waters and are associated with deleterious effects in fish populations. Impaired fertility and fecundity in fish following chronic exposures to estrogens and estrogen mimics during critical windows in development are well documented. However, information regarding differential reproductive effects of exposure within defined developmental stages remains sparse. In this study, reproductive capacity was assessed in Japanese medaka (Oryzias latipes) after exposure to two concentrations of 17β–estradiol (E2β; 2 ng/L and 50 ng/L) during four distinct stages of development: gonad development, gonad differentiation, development of secondary sex characteristics (SSC) and gametogenesis. Exposure to E2β did not adversely impact survival, hatch success, growth, or genotypic ratios. In contrast, exposure to 50 ng/L E2β during SSC development altered phenotypic ratios and SSC. Exposure to both E2β treatments reduced reproductive capacity (fertility, fecundity) by 7.3–57.4% in adult medaka breeding pairs, with hindrance of SSC development resulting in the largest disruption in breeding capacity (51.6–57.4% decrease) in the high concentration. This study documents differential effects among four critical stages of development and provides insight into factors (window of exposure, exposure concentration and duration of exposure period) contributing to reproductive disruption in fish.

Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum.

PubMed

Maltese, Marta; Stanic, Jennifer; Tassone, Annalisa; Sciamanna, Giuseppe; Ponterio, Giulia; Vanni, Valentina; Martella, Giuseppina; Imbriani, Paola; Bonsi, Paola; Mercuri, Nicola Biagio; Gardoni, Fabrizio; Pisani, Antonio

2018-03-05

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a +/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a +/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a +/Δgag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers. © 2018, Maltese et al.

The study on achievement of motor milestones and associated factors among children in rural North India

PubMed Central

Gupta, Arti; Kalaivani, Mani; Gupta, Sanjeev Kumar; Rai, Sanjay K.; Nongkynrih, Baridalyne

2016-01-01

Background: Nearly 14% of children worldwide do not reach their developmental potential in early childhood. The early identification of delays in achieving milestones is critical. The World Health Organization (WHO) has developed normal age ranges for the achievement of motor milestones by healthy children. This study aimed to assess the gross motor developmental achievements and associated factors among children in rural India. Materials and Methods: A cross-sectional study was conducted with rural children in North India. A pretested questionnaire was used to collect the data. The median age at the time of the highest observed milestone was calculated and compared with the WHO windows of achievement. Results: Overall, 221 children aged 4–18 months were included in the study. The median age of motor development exhibited a 0.1–2.1-month delay compared to the WHO median age of motor milestone achievement. The prevalence of the gross motor milestone achievements for each of the six milestones ranged from 91.6% to 98.4%. Developmental delay was observed in 6.3% of the children. After adjusting for different variables, children with birth order of second or more were found to be significantly associated with the timely achievement of gross motor milestones. Conclusion: The apparently healthy children of the rural area of Haryana achieved gross motor milestones with some delay with respect to the WHO windows of achievement. Although the median value of this delay was low, awareness campaigns should be implemented to promote timely identification of children with development delays. PMID:27843845

Embryonic critical windows: changes in incubation temperature alter survival, hatchling phenotype, and cost of development in lake whitefish (Coregonus clupeaformis).

PubMed

Mueller, Casey A; Eme, John; Manzon, Richard G; Somers, Christopher M; Boreham, Douglas R; Wilson, Joanna Y

2015-04-01

The timing, success and energetics of fish embryonic development are strongly influenced by temperature. However, it is unclear if there are developmental periods, or critical windows, when oxygen use, survival and hatchling phenotypic characteristics are particularly influenced by changes in the thermal environment. Therefore, we examined the effects of constant incubation temperature and thermal shifts on survival, hatchling phenotype, and cost of development in lake whitefish (Coregonus clupeaformis) embryos. We incubated whitefish embryos at control temperatures of 2, 5, or 8 °C, and shifted embryos across these three temperatures at the end of gastrulation or organogenesis. We assessed hatch timing, mass at hatch, and yolk conversion efficiency (YCE). We determined cost of development, the amount of oxygen required to build a unit of mass, for the periods from fertilization-organogenesis, organogenesis-fin flutter, fin flutter-hatch, and for total development. An increase in incubation temperature decreased time to 50 % hatch (164 days at 2 °C, 104 days at 5 °C, and 63 days at 8 °C), survival decreased from 55 % at 2 °C, to 38 % at 5 °C, and 17 % at 8 °C, and hatchling yolk-free dry mass decreased from 1.27 mg at 2 °C to 0.61 mg at 8 °C. Thermal shifts altered time to 50 % hatch and hatchling yolk-free dry mass and revealed a critical window during gastrulation in which a temperature change reduced survival. YCE decreased and cost of development increased with increased incubation temperature, but embryos that hatched at 8 °C and were incubated at colder temperatures during fertilization-organogenesis had reduced cost. The relationship between cost of development and temperature was altered during fin flutter-hatch, indicating it may be a critical window during which temperature has the greatest impact on energetic processes. The increase in cost of development with an increase in temperature has not been documented in other fishes and suggests whitefish embryos are more energy efficient at colder temperatures.

Critical windows in embryonic development: Shifting incubation temperatures alter heart rate and oxygen consumption of Lake Whitefish (Coregonus clupeaformis) embryos and hatchlings.

PubMed

Eme, J; Mueller, C A; Manzon, R G; Somers, C M; Boreham, D R; Wilson, J Y

2015-01-01

Critical windows are periods of developmental susceptibility when the phenotype of an embryonic, juvenile or adult animal may be vulnerable to environmental fluctuations. Temperature has pervasive effects on poikilotherm physiology, and embryos are especially vulnerable to temperature shifts. To identify critical windows, we incubated whitefish embryos at control temperatures of 2°C, 5°C, or 8°C, and shifted treatments among temperatures at the end of gastrulation or organogenesis. Heart rate (fH) and oxygen consumption ( [Formula: see text] ) were measured across embryonic development, and [Formula: see text] was measured in 1-day old hatchlings. Thermal shifts, up or down, from initial incubation temperatures caused persistent changes in fH and [Formula: see text] compared to control embryos measured at the same temperature (2°C, 5°C, or 8°C). Most prominently, when embryos were measured at organogenesis, shifting incubation temperature after gastrulation significantly lowered [Formula: see text] or fH. Incubation at 2°C or 5°C through gastrulation significantly lowered [Formula: see text] (42% decrease) and fH (20% decrease) at 8°C, incubation at 2°C significantly lowered [Formula: see text] (40% decrease) and fH (30% decrease) at 5°C, and incubation at 5°C and 8°C significantly lowered [Formula: see text] at 2°C (27% decrease). Through the latter half of development, [Formula: see text] and fH in embryos were not different from control values for thermally shifted treatments. However, in hatchlings measured at 2°C, [Formula: see text] was higher in groups incubated at 5°C or 8°C through organogenesis, compared to 2°C controls (43 or 65% increase, respectively). Collectively, these data suggest that embryonic development through organogenesis represents a critical window of embryonic and hatchling phenotypic plasticity. This study presents an experimental design that identified thermally sensitive periods for fish embryos. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Epigenetic impacts of endocrine disruptors in the brain☆

PubMed Central

Walker, Deena M.; Gore, Andrea C.

2017-01-01

The acquisition of reproductive competence is organized and activated by steroid hormones acting upon the hypothalamus during critical windows of development. This review describes the potential role of epigenetic processes, particularly DNA methylation, in the regulation of sexual differentiation of the hypothalamus by hormones. We examine disruption of these processes by endocrine-disrupting chemicals (EDCs) in an age-, sex-, and region-specific manner, focusing on how perinatal EDCs act through epigenetic mechanisms to reprogram DNA methylation and sex steroid hormone receptor expression throughout life. These receptors are necessary for brain sexual differentiation and their altered expression may underlie disrupted reproductive physiology and behavior. Finally, we review the literature on histone modifications and non-coding RNA involvement in brain sexual differentiation and their perturbation by EDCs. By putting these data into a sex and developmental context we conclude that perinatal EDC exposure alters the developmental trajectory of reproductive neuroendocrine systems in a sex-specific manner. PMID:27663243

Developmental Audits with Challenging Youth

ERIC Educational Resources Information Center

Brendtro, Larry K.; du Toit, Lesley; Bath, Howard; Van Bockern, Steve

2006-01-01

The Developmental Audit[R] is a new strength-based assessment model for youth who are in conflict in home, school, or community. Developmental Audits involve collaboration with young persons who are seen as experts on themselves. Discussing challenging life events provides a window to the young person's private logic and goals. The audit scans…

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

PubMed

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

2014-12-23

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

Organizational effects of the antiandrogen, Vinclozolin, on penis development in the mouse.

PubMed

Amato, Ciro M; Boyd, Morgan; Yang, Joshua; McCoy, Krista A

2018-04-14

Endocrine disrupting chemicals (EDCs) are pollutants found throughout the environment that disrupt normal endocrine processes. In mice, penis development is thought to be most susceptible to EDCs during a critical developmental window occurring on embryonic days (E) 15.5-17.5. However, androgen signaling begins on E13.5 when Androgen Receptor (AR) protein is found in the genitalia and testosterone is circulating. We hypothesize that disrupting androgen signaling prior to the established critical window sensitizes the penis to future androgen disruption. To test this hypothesis, CD1 dams were exposed to Vinclozolin or a corn oil solvent control on E13.5 and E14.5 and AR levels were measured with immunohistochemistry on E14.5. Early antiandrogen exposure reduced AR within nuclei and decreased intensity of AR expression within E14.5 genitalia. To evaluate the influence of antiandrogen exposure before the known critical window of penis development, two groups of pregnant dams (n = 3) were exposed to Vinclozolin starting at either E13.5 or E14.5 and continued exposure through E16.5. Histology and M.O.U.S.E. scoring were used to quantify penis abnormalities. To account for differences in total doses mice experienced due to differences in length of dosing time, we compared animals that received the same total doses. Exposure to antiandrogens on E13.5 exacerbated malformations when exposure was continued through sexually dimorphic development. Both exposure time and Vinclozolin dose are important for severity of Vinclozolin-induced penis abnormalities in mice. This work shows, antiandrogen exposure prior to sensitive periods can exacerbate the effects of later antiandrogen exposure on reproductive development.

Evaluation of an Out-of-the-Window Air Traffic Control Tower Simulation for Controller Training

DOT National Transportation Integrated Search

1996-09-01

This study gathered evidence concerning the potential usefulness of out-of-the-window air traffic control tower : simulation for training tower controllers. Data were collected from all ten developmental controllers who completed : simulation trainin...

Developmental pathways in infants from 4 to 24 months.

PubMed

Valla, L; Birkeland, M S; Hofoss, D; Slinning, K

2017-07-01

There has been limited epidemiological research describing population-based samples regarding developmental pathways throughout infancy, and the research that exists has revealed substantial diversity. Identifying predictors for developmental pathways can inform early intervention services. The Ages and Stages Questionnaire was used to measure communication, gross motor, fine motor, problem-solving and personal-social skills longitudinally in a large, population-based sample of 1555 infants recruited from well-baby clinics in five municipalities in southeast Norway. We conducted latent class analyses to identify common pathways within the five developmental areas. Our results indicated that most classes of infants showed generally positive and stable normative developmental pathways. However, for communication and gross motor areas, more heterogeneity was found. For gross motor development, a class of 10% followed a U-shaped curve. A class of 8% had a declining communication pathway and did not reach the level of the high stable communication class at 24 months. Low gestational age, low Apgar score, male sex, maternal depression symptoms, non-Scandinavian maternal ethnicity and high maternal education significantly predict less beneficial communication pathways. The results suggest that infants with low gestational age, low Apgar score, male sex and a mother with depression symptoms or non-Scandinavian ethnicity may be at risk of developing less beneficial developmental pathways, especially within the communication area. Targeting these infants for surveillance and support might be protective against delayed development in several areas during a critical window of development. © 2017 John Wiley & Sons Ltd.

Trematode infection causes malformations and population effects in a declining New Zealand fish.

PubMed

Kelly, David W; Thomas, Harriet; Thieltges, David W; Poulin, Robert; Tompkins, Daniel M

2010-03-01

1. Animal malformations engender wide public and scientific concern because of associated environmental health risks. This is highlighted by increased incidence of limb malformations in amphibians associated with trematode infections and disturbance. Malformations may signal new emerging disease threats, but whether the phenomenon is broadly applicable across taxa, or has population-scale impacts, is unknown. 2. Malformations are widely reported in fish and, until now, have been attributed mainly to contaminants. We tested whether the trematode Telogaster opisthorchis caused severe malformations, leading to population effects, in Galaxias anomalus, a threatened New Zealand freshwater fish. 3. Experimental infection of larval fish caused increasing spinal malformation and mortality with infection intensity that closely matched field patterns. Field malformation frequency peaked in January (65%), before declining sharply in February (25%) and remaining low thereafter. 4. The peak occurred during a 'critical window' of larval development, with the decline coincident with a population crash, indicating that malformation was causing mortality in the field. 5. The occurrence of such critical developmental windows may explain why this mechanism of population impact has been overlooked. With global environmental stressors predicted to enhance trematode infections, our results show that parasite-induced malformation, and its population-scale impacts, could be more widespread than previously considered.

Letter-sound processing deficits in children with developmental dyslexia: An ERP study.

PubMed

Moll, Kristina; Hasko, Sandra; Groth, Katharina; Bartling, Jürgen; Schulte-Körne, Gerd

2016-04-01

The time course during letter-sound processing was investigated in children with developmental dyslexia (DD) and typically developing (TD) children using electroencephalography. Thirty-eight children with DD and 25 TD children participated in a visual-auditory oddball paradigm. Event-related potentials (ERPs) elicited by standard and deviant stimuli in an early (100-190 ms) and late (560-750 ms) time window were analysed. In the early time window, ERPs elicited by the deviant stimulus were delayed and less left lateralized over fronto-temporal electrodes for children with DD compared to TD children. In the late time window, children with DD showed higher amplitudes extending more over right frontal electrodes. Longer latencies in the early time window and stronger right hemispheric activation in the late time window were associated with slower reading and naming speed. Additionally, stronger right hemispheric activation in the late time window correlated with poorer phonological awareness skills. Deficits in early stages of letter-sound processing influence later more explicit cognitive processes during letter-sound processing. Identifying the neurophysiological correlates of letter-sound processing and their relation to reading related skills provides insight into the degree of automaticity during letter-sound processing beyond behavioural measures of letter-sound-knowledge. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Neurogenesis and Developmental Anesthetic Neurotoxicity

PubMed Central

Kang, Eunchai; Berg, Daniel A.; Furmanski, Orion; Jackson, William M.; Ryu, Yun Kyoung; Gray, Christy D.; Mintz, C. David

2017-01-01

The mechanism by which anesthetics might act on the developing brain in order to cause long term deficits remains incompletely understood. The hippocampus has been identified as a structure that is likely to be involved, as rodent models show numerous deficits in behavioral tasks of learning that are hippocampal-dependent. The hippocampus is an unusual structure in that it is the site of large amounts of neurogenesis postnatally, particularly in the first year of life in humans, and these newly generated neurons are critical to the function of this structure. Intriguingly, neurogenesis is a major developmental event that occurs during postulated windows of vulnerability to developmental anesthetic neurotoxicity across the different species in which it has been studied. In this review, we examine the evidence for anesthetic effects on neurogenesis in the early postnatal period and ask whether neurogenesis should be studied further as a putative mechanism of injury. Multiple anesthetics are considered, and both in vivo and in vitro work is presented. While there is abundant evidence that anesthetics act to suppress neurogenesis at several different phases, evidence of a causal link between these effects and any change in learning behavior remains elusive. PMID:27751818

Neurogenesis and developmental anesthetic neurotoxicity.

PubMed

Kang, Eunchai; Berg, Daniel A; Furmanski, Orion; Jackson, William M; Ryu, Yun Kyoung; Gray, Christy D; Mintz, C David

The mechanism by which anesthetics might act on the developing brain in order to cause long term deficits remains incompletely understood. The hippocampus has been identified as a structure that is likely to be involved, as rodent models show numerous deficits in behavioral tasks of learning that are hippocampal-dependent. The hippocampus is an unusual structure in that it is the site of large amounts of neurogenesis postnatally, particularly in the first year of life in humans, and these newly generated neurons are critical to the function of this structure. Intriguingly, neurogenesis is a major developmental event that occurs during postulated windows of vulnerability to developmental anesthetic neurotoxicity across the different species in which it has been studied. In this review, we examine the evidence for anesthetic effects on neurogenesis in the early postnatal period and ask whether neurogenesis should be studied further as a putative mechanism of injury. Multiple anesthetics are considered, and both in vivo and in vitro work is presented. While there is abundant evidence that anesthetics act to suppress neurogenesis at several different phases, evidence of a causal link between these effects and any change in learning behavior remains elusive. Copyright © 2016. Published by Elsevier Inc.

Kinase-activating and kinase-impaired cardio-facio-cutaneous syndrome alleles have activity during zebrafish development and are sensitive to small molecule inhibitors.

PubMed

Anastasaki, Corina; Estep, Anne L; Marais, Richard; Rauen, Katherine A; Patton, E Elizabeth

2009-07-15

The Ras/MAPK pathway is critical for human development and plays a central role in the formation and progression of most cancers. Children born with germ-line mutations in BRAF, MEK1 or MEK2 develop cardio-facio-cutaneous (CFC) syndrome, an autosomal dominant syndrome characterized by a distinctive facial appearance, heart defects, skin and hair abnormalities and mental retardation. CFC syndrome mutations in BRAF promote both kinase-activating and kinase-impaired variants. CFC syndrome has a progressive phenotype, and the availability of clinically active inhibitors of the MAPK pathway prompts the important question as to whether such inhibitors might be therapeutically effective in the treatment of CFC syndrome. To study the developmental effects of CFC mutant alleles in vivo, we have expressed a panel of 28 BRAF and MEK alleles in zebrafish embryos to assess the function of human disease alleles and available chemical inhibitors of this pathway. We find that both kinase-activating and kinase-impaired CFC mutant alleles promote the equivalent developmental outcome when expressed during early development and that treatment of CFC-zebrafish embryos with inhibitors of the FGF-MAPK pathway can restore normal early development. Importantly, we find a developmental window in which treatment with a MEK inhibitor can restore the normal early development of the embryo, without the additional, unwanted developmental effects of the drug.

Constructivist developmental theory is needed in developmental neuroscience

NASA Astrophysics Data System (ADS)

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.

Do mitochondria play a role in remodelling lace plant leaves during programmed cell death?

PubMed

Lord, Christina E N; Wertman, Jaime N; Lane, Stephanie; Gunawardena, Arunika H L A N

2011-06-06

Programmed cell death (PCD) is the regulated death of cells within an organism. The lace plant (Aponogeton madagascariensis) produces perforations in its leaves through PCD. The leaves of the plant consist of a latticework of longitudinal and transverse veins enclosing areoles. PCD occurs in the cells at the center of these areoles and progresses outwards, stopping approximately five cells from the vasculature. The role of mitochondria during PCD has been recognized in animals; however, it has been less studied during PCD in plants. The following paper elucidates the role of mitochondrial dynamics during developmentally regulated PCD in vivo in A. madagascariensis. A single areole within a window stage leaf (PCD is occurring) was divided into three areas based on the progression of PCD; cells that will not undergo PCD (NPCD), cells in early stages of PCD (EPCD), and cells in late stages of PCD (LPCD). Window stage leaves were stained with the mitochondrial dye MitoTracker Red CMXRos and examined. Mitochondrial dynamics were delineated into four categories (M1-M4) based on characteristics including distribution, motility, and membrane potential (ΔΨm). A TUNEL assay showed fragmented nDNA in a gradient over these mitochondrial stages. Chloroplasts and transvacuolar strands were also examined using live cell imaging. The possible importance of mitochondrial permeability transition pore (PTP) formation during PCD was indirectly examined via in vivo cyclosporine A (CsA) treatment. This treatment resulted in lace plant leaves with a significantly lower number of perforations compared to controls, and that displayed mitochondrial dynamics similar to that of non-PCD cells. Results depicted mitochondrial dynamics in vivo as PCD progresses within the lace plant, and highlight the correlation of this organelle with other organelles during developmental PCD. To the best of our knowledge, this is the first report of mitochondria and chloroplasts moving on transvacuolar strands to form a ring structure surrounding the nucleus during developmental PCD. Also, for the first time, we have shown the feasibility for the use of CsA in a whole plant system. Overall, our findings implicate the mitochondria as playing a critical and early role in developmentally regulated PCD in the lace plant.

Ocean acidification has little effect on developmental thermal windows of echinoderms from Antarctica to the tropics.

PubMed

Karelitz, Sam E; Uthicke, Sven; Foo, Shawna A; Barker, Mike F; Byrne, Maria; Pecorino, Danilo; Lamare, Miles D

2017-02-01

As the ocean warms, thermal tolerance of developmental stages may be a key driver of changes in the geographical distributions and abundance of marine invertebrates. Additional stressors such as ocean acidification may influence developmental thermal windows and are therefore important considerations for predicting distributions of species under climate change scenarios. The effects of reduced seawater pH on the thermal windows of fertilization, embryology and larval morphology were examined using five echinoderm species: two polar (Sterechinus neumayeri and Odontaster validus), two temperate (Fellaster zelandiae and Patiriella regularis) and one tropical (Arachnoides placenta). Responses were examined across 12-13 temperatures ranging from -1.1 °C to 5.7 °C (S. neumayeri), -0.5 °C to 10.7 °C (O. validus), 5.8 °C to 27 °C (F. zelandiae), 6.0 °C to 27.1 °C (P. regularis) and 13.9 °C to 34.8 °C (A. placenta) under present-day and near-future (2100+) ocean acidification conditions (-0.3 pH units) and for three important early developmental stages 1) fertilization, 2) embryo (prehatching) and 3) larval development. Thermal windows for fertilization were broad and were not influenced by a pH decrease. Embryological development was less thermotolerant. For O. validus, P. regularis and A. placenta, low pH reduced normal development, albeit with no effect on thermal windows. Larval development in all five species was affected by both temperature and pH; however, thermal tolerance was not reduced by pH. Results of this study suggest that in terms of fertilization and development, temperature will remain as the most important factor influencing species' latitudinal distributions as the ocean continues to warm and decrease in pH, and that there is little evidence of a synergistic effect of temperature and ocean acidification on the thermal control of species ranges. © 2016 John Wiley & Sons Ltd.

Difference of auditory brainstem responses by stimulating to round and oval window in animal experiments.

PubMed

Lee, Jyung Hyun; Park, Hyo Soon; Wei, Qun; Kim, Myoung Nam; Cho, Jin-Ho

2017-01-02

ABSTACT To ensure the safety and efficacy of implantable hearing aids, animal experiments are an essential developmental procedure, in particular, auditory brainstem responses (ABRs) can be used to verify the objective effectiveness of implantable hearing aids. This study measured and compared the ABRs generated when applying the same vibration stimuli to an oval window and round window. The ABRs were measured using a TDT system 3 (TDT, USA), while the vibration stimuli were applied to a round window and oval window in 4 guinea pigs using a piezo-electric transducer with a proper contact tip. A paired t-test was used to determine any differences between the ABR amplitudes when applying the stimulation to an oval window and round window. The paired t-test revealed a significant difference between the ABR amplitudes generated by the round and oval window stimulation (t = 10.079, α < .0001). Therefore, the results confirmed that the biological response to round window stimulation was not the same as that to oval window stimulation.

Through Shared Windows: Outreach Project for Infants, Toddlers, and Children with Developmental Disabilities. Final Report.

ERIC Educational Resources Information Center

Harrison, Holly

This final report describes activities and accomplishments of the Through Shared Windows (TSW) Outreach Project, a 4-year project at the University of New Mexico designed to improve services to young children with disabilities and their families. Three major outcomes were accomplished. First, a Web site was developed that focuses on observational…

Advances in asthma and allergy genetics in 2007.

PubMed

Vercelli, Donata

2008-08-01

This review discusses the main advances in the genetics of asthma and allergy published in the Journal in 2007. The association studies discussed herein addressed 3 main topics: the effect of the environment and gene-environment interactions on asthma/allergy susceptibility, the contribution of T(H)2 immunity gene variants to allergic inflammation, and the role of filaggrin mutations in atopic dermatitis and associated phenotypes. Other articles revealed novel, potentially important candidate genes or confirmed known ones. Collectively, the works published in 2007 reiterate that allergy and asthma are typical complex diseases; that is, they are disorders in which intricate interactions among environmental and genetic factors modify disease susceptibility by altering the fundamental structural and functional properties of target organs at critical developmental windows.

Gene x Environment Interactions in Reading Disability and Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Pennington, Bruce F.; McGrath, Lauren M.; Rosenberg, Jenni; Barnard, Holly; Smith, Shelley D.; Willcutt, Erik G.; Friend, Angela; DeFries, John C.; Olson, Richard K.

2009-01-01

This article examines Gene x Environment (G x E) interactions in two comorbid developmental disorders--reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD)--as a window on broader issues on G x E interactions in developmental psychology. The authors first briefly review types of G x E interactions, methods for detecting…

Mindfulness and Compassion Training in Adolescence: A Developmental Contemplative Science Perspective

ERIC Educational Resources Information Center

Roeser, Robert W.; Pinela, Cristi

2014-01-01

Adolescence is a developmental period of risk, as well as a window of opportunity for cultivating positive development and thriving. It is characterized by simultaneous changes in the brain, body, mind, and social domains that offer a platform for building new skills and habits. This chapter discusses the role that secular forms of mindfulness and…

Influence of Conduct Problems and Depressive Symptomatology on Adolescent Substance Use: Developmentally Proximal versus Distal Effects

ERIC Educational Resources Information Center

Maslowsky, Julie; Schulenberg, John E.; Zucker, Robert A.

2014-01-01

The identification of developmentally specific windows at which key predictors of adolescent substance use are most influential is a crucial task for informing the design of appropriately targeted substance use prevention and intervention programs. The current study examined effects of conduct problems and depressive symptomatology on changes in…

Drosophila Fragile X Mental Retardation Protein Developmentally Regulates Activity-Dependent Axon Pruning

PubMed Central

Tessier, Charles R.; Broadie, Kendal

2014-01-01

Summary Fragile X Syndrome (FraX) is a broad-spectrum neurological disorder with symptoms ranging from hyperexcitability to mental retardation and autism. Loss of the fragile X mental retardation 1 (fmr1) gene product, the mRNA-binding translational regulator FMRP, causes structural over-elaboration of dendritic and axonal processes as well as functional alterations in synaptic plasticity at maturity. It is unclear, however, whether FraX is primarily a disease of development, a disease of plasticity or both; a distinction vital for engineering intervention strategies. To address this critical issue, we have used the Drosophila FraX model to investigate the developmental roles of Drosophila FMRP (dFMRP). dFMRP expression and regulation of chickadee/profilin coincides with a transient window of late brain development. During this time, dFMRP is positively regulated by sensory input activity, and required to limit axon growth and for efficient activity-dependent pruning of axon branches in the Mushroom Body learning/memory center. These results demonstrate that dFMRP has a primary role in activity-dependent neural circuit refinement in late brain development. PMID:18321984

The Role of Maternal Nutrition During the Periconceptional Period and Its Effect on Offspring Phenotype.

PubMed

Fleming, Tom P; Eckert, Judith J; Denisenko, Oleg

2017-01-01

The early preimplantation embryo has been rigorously studied for decades to understand inherent reproductive and developmental mechanisms driving its morphogenesis from before fertilisation through to and beyond implantation. Recent research has demonstrated that this short developmental window is also critical for the embryo's interaction with external, maternal factors, particularly nutritional status. Here, maternal dietary quality has been shown to alter the pattern of development in an enduring way that can influence health throughout the lifetime. Thus, using mouse models, maternal protein restriction exclusively during the preimplantation period with normal nutrition thereafter is sufficient to cause adverse cardiometabolic and neurological outcomes in adult offspring. Evidence for similar effects whereby environmental factors during the periconceptional window can programme postnatal disease risk can be found in human and large animal models and also in response to in vitro conditions such as assisted conception and related infertility treatments. In this review, using mouse malnutrition models, we evaluate the step-by-step mechanisms that lead from maternal poor diet consumption though to offspring disease. We consider how adverse programming within the embryo may be induced, what nutrient factors and signalling pathways may be involved, and how these cues act to change the embryo in distinct ways across placental and foetal lineage paths, leading especially to changes in the growth trajectory which in turn associate with later disease risk. These mechanisms straddle epigenetic, molecular, cellular and physiological levels of biology and suggest, for health outcomes, preimplantation development to be the most important time in our lives.

Maternal obesity and prenatal programming.

PubMed

Elshenawy, Summer; Simmons, Rebecca

2016-11-05

Obesity is a significant and increasing public health concern in the United States and worldwide. Clinical and epidemiological evidence clearly shows that genetic and environmental factors contribute to the increased susceptibility of humans to obesity and its associated comorbidities; the interplay of these factors is explained by the concept of epigenetics. The impact of maternal obesity goes beyond the newborn period; fetal programming during the critical window of pregnancy, can have long term detrimental effects on the offspring as well as future generations. Emerging evidence is uncovering a link between the clinical and molecular findings in the offspring with epigenetic changes in the setting of maternal obesity. Research targeted towards reducing the transgenerational propagation and developmental programming of obesity is vital in reducing the increasing rates of disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Manipulation of BDNF signaling modifies the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex.

PubMed

Anomal, Renata; de Villers-Sidani, Etienne; Merzenich, Michael M; Panizzutti, Rogerio

2013-01-01

Sensory experience powerfully shapes cortical sensory representations during an early developmental "critical period" of plasticity. In the rat primary auditory cortex (A1), the experience-dependent plasticity is exemplified by significant, long-lasting distortions in frequency representation after mere exposure to repetitive frequencies during the second week of life. In the visual system, the normal unfolding of critical period plasticity is strongly dependent on the elaboration of brain-derived neurotrophic factor (BDNF), which promotes the establishment of inhibition. Here, we tested the hypothesis that BDNF signaling plays a role in the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex. Elvax resin implants filled with either a blocking antibody against BDNF or the BDNF protein were placed on the A1 of rat pups throughout the critical period window. These pups were then exposed to 7 kHz pure tone for 7 consecutive days and their frequency representations were mapped. BDNF blockade completely prevented the shaping of cortical tuning by experience and resulted in poor overall frequency tuning in A1. By contrast, BDNF infusion on the developing A1 amplified the effect of 7 kHz tone exposure compared to control. These results indicate that BDNF signaling participates in the experience-dependent plasticity induced by pure tone exposure during the critical period in A1.

Tuning the chemosensory window

PubMed Central

Zhou, Shanshan; Mackay, Trudy FC

2010-01-01

Accurate perception of chemical signals from the environment is critical for the fitness of most animals. Drosophila melanogaster experiences its chemical environment through families of chemoreceptors that include olfactory receptors, gustatory receptors and odorant binding proteins. Its chemical environment, however, changes during its life cycle and the interpretation of chemical signals is dependent on dynamic social and physical surroundings. Phenotypic plasticity of gene expression of the chemoreceptor repertoire allows flies to adjust the chemosensory window through which they “view” their world and to modify the ensemble of expressed chemoreceptor proteins in line with their developmental and physiological state and according to their needs to locate food and oviposition sites under different social and physical environmental conditions. Furthermore, males and females differ in their expression profiles of chemoreceptor genes. Thus, each sex experiences its chemical environment via combinatorial activation of distinct chemoreceptor ensembles. The remarkable phenotypic plasticity of the chemoreceptor repertoire raises several fundamental questions. What are the mechanisms that translate environmental cues into regulation of chemoreceptor gene expression? How are gustatory and olfactory cues integrated perceptually? What is the relationship between ensembles of odorant binding proteins and odorant receptors? And, what is the significance of co-regulated chemoreceptor transcriptional networks? PMID:20305396

Transient activation of dopaminergic neurons during development modulates visual responsiveness, locomotion and brain activity in a dopamine ontogeny model of schizophrenia.

PubMed

Calcagno, B; Eyles, D; van Alphen, B; van Swinderen, B

2013-01-08

It has been observed that certain developmental environmental risk factors for schizophrenia when modeled in rodents alter the trajectory of dopaminergic development, leading to persistent behavioural changes in adults. This has recently been articulated as the "dopamine ontogeny hypothesis of schizophrenia". To test one aspect of this hypothesis, namely that transient dopaminergic effects during development modulate attention-like behavior and arousal in adults, we turned to a small-brain model, Drosophila melanogaster. By applying genetic tools allowing transient activation or silencing of dopaminergic neurons in the fly brain, we investigated whether a critical window exists during development when altered dopamine (DA) activity levels could lead to impairments in arousal states in adult animals. We found that increased activity in dopaminergic neurons in later stages of development significantly increased visual responsiveness and locomotion, especially in adult males. This misallocation of visual salience and hyperactivity mimicked the effect of acute methamphetamine feeding to adult flies, suggesting up-regulated DA signaling could result from developmental manipulations. Finally, brain recordings revealed significantly reduced gamma-band activity in adult animals exposed to the transient developmental insult. Together, these data support the idea that transient alterations in DA signaling during development can permanently alter behavior in adults, and that a reductionist model such as Drosophila can be used to investigate potential mechanisms underlying complex cognitive disorders such as schizophrenia.

Investigating the Impact of Maternal Residential Mobility on Identifying Critical Windows of Susceptibility to Ambient Air Pollution During Pregnancy.

PubMed

Warren, Joshua L; Son, Ji-Young; Pereira, Gavin; Leaderer, Brian P; Bell, Michelle L

2018-05-01

Identifying periods of increased vulnerability to air pollution during pregnancy with respect to the development of adverse birth outcomes can improve understanding of possible mechanisms of disease development and provide guidelines for protection of the child. Exposure to air pollution during pregnancy is typically based on the mother's residence at delivery, potentially resulting in exposure misclassification and biasing the estimation of critical windows of pregnancy. In this study, we determined the impact of maternal residential mobility during pregnancy on defining weekly exposure to particulate matter less than or equal to 10 μm in aerodynamic diameter (PM10) and estimating windows of susceptibility to term low birth weight. We utilized data sets from 4 Connecticut birth cohorts (1988-2008) that included information on all residential addresses between conception and delivery for each woman. We designed a simulation study to investigate the impact of increasing levels of mobility on identification of critical windows. Increased PM10 exposure during pregnancy weeks 16-18 was associated with an increased probability of term low birth weight. Ignoring residential mobility when defining weekly exposure had only a minor impact on the identification of critical windows for PM10 and term low birth weight in the data application and simulation study. Identification of critical pregnancy windows was robust to exposure misclassification caused by ignoring residential mobility in these Connecticut birth cohorts.

Developmental time windows for axon growth influence neuronal network topology.

PubMed

Lim, Sol; Kaiser, Marcus

2015-04-01

Early brain connectivity development consists of multiple stages: birth of neurons, their migration and the subsequent growth of axons and dendrites. Each stage occurs within a certain period of time depending on types of neurons and cortical layers. Forming synapses between neurons either by growing axons starting at similar times for all neurons (much-overlapped time windows) or at different time points (less-overlapped) may affect the topological and spatial properties of neuronal networks. Here, we explore the extreme cases of axon formation during early development, either starting at the same time for all neurons (parallel, i.e., maximally overlapped time windows) or occurring for each neuron separately one neuron after another (serial, i.e., no overlaps in time windows). For both cases, the number of potential and established synapses remained comparable. Topological and spatial properties, however, differed: Neurons that started axon growth early on in serial growth achieved higher out-degrees, higher local efficiency and longer axon lengths while neurons demonstrated more homogeneous connectivity patterns for parallel growth. Second, connection probability decreased more rapidly with distance between neurons for parallel growth than for serial growth. Third, bidirectional connections were more numerous for parallel growth. Finally, we tested our predictions with C. elegans data. Together, this indicates that time windows for axon growth influence the topological and spatial properties of neuronal networks opening up the possibility to a posteriori estimate developmental mechanisms based on network properties of a developed network.

Independent Orbiter Assessment (IOA): Analysis of the purge, vent and drain subsystem

NASA Technical Reports Server (NTRS)

Bynum, M. C., III

1987-01-01

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results corresponding to the Orbiter PV and D (Purge, Vent and Drain) Subsystem hardware. The PV and D Subsystem controls the environment of unpressurized compartments and window cavities, senses hazardous gases, and purges Orbiter/ET Disconnect. The subsystem is divided into six systems: Purge System (controls the environment of unpressurized structural compartments); Vent System (controls the pressure of unpressurized compartments); Drain System (removes water from unpressurized compartments); Hazardous Gas Detection System (HGDS) (monitors hazardous gas concentrations); Window Cavity Conditioning System (WCCS) (maintains clear windows and provides pressure control of the window cavities); and External Tank/Orbiter Disconnect Purge System (prevents cryo-pumping/icing of disconnect hardware). Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. Four of the sixty-two failure modes analyzed were determined as single failures which could result in the loss of crew or vehicle. A possible loss of mission could result if any of twelve single failures occurred. Two of the criticality 1/1 failures are in the Window Cavity Conditioning System (WCCS) outer window cavity, where leakage and/or restricted flow will cause failure to depressurize/repressurize the window cavity. Two criticality 1/1 failures represent leakage and/or restricted flow in the Orbiter/ET disconnect purge network which prevent cryopumping/icing of disconnect hardware. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode.

Piaget's Structural Developmental Psychology. v. Ideology-Critique and the Possibility of a Critical Developmental Theory.

ERIC Educational Resources Information Center

Broughton, John M.

1981-01-01

This final essay in a five-part series examining Piaget's structural developmental psychology suggests that a psychological theory which integrates aspects of developmental structuralism within a critical social framework can be developed. (Author/RH)

Do mitochondria play a role in remodelling lace plant leaves during programmed cell death?

PubMed Central

2011-01-01

Background Programmed cell death (PCD) is the regulated death of cells within an organism. The lace plant (Aponogeton madagascariensis) produces perforations in its leaves through PCD. The leaves of the plant consist of a latticework of longitudinal and transverse veins enclosing areoles. PCD occurs in the cells at the center of these areoles and progresses outwards, stopping approximately five cells from the vasculature. The role of mitochondria during PCD has been recognized in animals; however, it has been less studied during PCD in plants. Results The following paper elucidates the role of mitochondrial dynamics during developmentally regulated PCD in vivo in A. madagascariensis. A single areole within a window stage leaf (PCD is occurring) was divided into three areas based on the progression of PCD; cells that will not undergo PCD (NPCD), cells in early stages of PCD (EPCD), and cells in late stages of PCD (LPCD). Window stage leaves were stained with the mitochondrial dye MitoTracker Red CMXRos and examined. Mitochondrial dynamics were delineated into four categories (M1-M4) based on characteristics including distribution, motility, and membrane potential (ΔΨm). A TUNEL assay showed fragmented nDNA in a gradient over these mitochondrial stages. Chloroplasts and transvacuolar strands were also examined using live cell imaging. The possible importance of mitochondrial permeability transition pore (PTP) formation during PCD was indirectly examined via in vivo cyclosporine A (CsA) treatment. This treatment resulted in lace plant leaves with a significantly lower number of perforations compared to controls, and that displayed mitochondrial dynamics similar to that of non-PCD cells. Conclusions Results depicted mitochondrial dynamics in vivo as PCD progresses within the lace plant, and highlight the correlation of this organelle with other organelles during developmental PCD. To the best of our knowledge, this is the first report of mitochondria and chloroplasts moving on transvacuolar strands to form a ring structure surrounding the nucleus during developmental PCD. Also, for the first time, we have shown the feasibility for the use of CsA in a whole plant system. Overall, our findings implicate the mitochondria as playing a critical and early role in developmentally regulated PCD in the lace plant. PMID:21645374

In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse

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

Wang, Wei, E-mail: weiwang2@illinois.edu; Hafner, Katlyn S., E-mail: katlynhafner@gmail.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the effects of in utero BPA exposure on early ovarian development and the consequences of such exposure on female reproduction in later reproductive life are unclear. Thus, we determined the effects of in utero BPA exposure during a critical developmental window on germ cell nest breakdown, a process required for establishment of the finite primordial follicle pool, and on female reproduction. Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil (vehicle), diethylstilbestrol (DES; 0.05 μg/kg, positive control), or BPA (0.5, 20, and 50 μg/kg) from gestationalmore » day 11 until birth. Ovarian morphology and gene expression profiles then were examined in F1 female offspring on postnatal day (PND) 4 and estrous cyclicity was examined daily after weaning for 30 days. F1 females were also subjected to breeding studies with untreated males at three to nine months. The results indicate that BPA inhibits germ cell nest breakdown via altering expression of selected apoptotic factors. BPA also significantly advances the age of first estrus, shortens the time that the females remain in estrus, and increases the time that the females remain in metestrus and diestrus compared to controls. Further, F1 females exposed to low doses of BPA exhibit various fertility problems and have a significantly higher percentage of dead pups compared to controls. These results indicate that in utero exposure to low doses of BPA during a critical ovarian developmental window interferes with early ovarian development and reduces fertility with age. - Highlights: • In utero BPA exposure inhibits germ cell nest breakdown in female mouse offspring. • In utero BPA exposure alters expression of apoptosis regulators in the ovaries of mouse offspring. • In utero BPA exposure advances first estrus age and alters cyclicity in mouse offspring. • In utero BPA exposure causes various fertility problems in female mouse offspring.« less

CRITICAL WINDOWS FOR REPRODUCTIVE HEALTH IN CHILDREN AND ADOLESCENTS

EPA Science Inventory

This workgroup report addresses the central question: what are the critical windows during development (pre-conception through puberty) when exposure to xenobiotics may have the greatest adverse impact on subsequent reproductive health. The reproductive system develops in stages...

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

PubMed

Barouki, R; Melén, E; Herceg, Z; Beckers, J; Chen, J; Karagas, M; Puga, A; Xia, Y; Chadwick, L; Yan, W; Audouze, K; Slama, R; Heindel, J; Grandjean, P; Kawamoto, T; Nohara, K

2018-05-01

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 methylation, histone modifications and the expression of certain RNAs have been suggested as possible mediators of long-term health effects of environmental stressors. This report captures discussions and conclusions debated during the last Prenatal Programming and Toxicity meeting held in Japan. Its first aim is to propose a number of criteria that are critical to support the primary contribution of epigenetics in DOHaD and intergenerational transmission of environmental stressors effects. The main criteria are the full characterization of the stressors, the actual window of exposure, the target tissue and function, the specificity of the epigenetic changes and the biological plausibility of the linkage between those changes and health outcomes. The second aim is to discuss long-term effects of a number of stressors such as smoking, air pollution and endocrine disruptors in order to identify the arguments supporting the involvement of an epigenetic mechanism. Based on the developed criteria, missing evidence and suggestions for future research will be identified. The third aim is to critically analyze the evidence supporting the involvement of epigenetic mechanisms in intergenerational and transgenerational effects of environmental exposure and to particularly discuss the role of placenta and sperm. While the article is not a systematic review and is not meant to be exhaustive, it critically assesses the contribution of epigenetics in the long-term effects of environmental exposures as well as provides insight for future research. Copyright © 2018 Elsevier Ltd. All rights reserved.

A steroid-controlled global switch in sensitivity to apoptosis during Drosophila development.

PubMed

Kang, Yunsik; Bashirullah, Arash

2014-02-01

Precise control over activation of the apoptotic machinery is critical for development, tissue homeostasis and disease. In Drosophila, the decision to trigger apoptosis--whether in response to developmental cues or to DNA damage--converges on transcription of inhibitor of apoptosis protein (IAP) antagonists reaper, hid and grim. Here we describe a parallel process that regulates the sensitivity to, rather than the execution of, apoptosis. This process establishes developmental windows that are permissive or restrictive for triggering apoptosis, where the status of cells determines their capacity to die. We characterize one switch in the sensitivity to apoptotic triggers, from restrictive to permissive, that occurs during third-instar larval (L3) development. Early L3 animals are highly resistant to induction of apoptosis by expression of IAP-antagonists, DNA-damaging agents and even knockdown of the IAP diap1. This resistance to apoptosis, however, is lost in wandering L3 animals after acquiring a heightened sensitivity to apoptotic triggers. This switch in sensitivity to death activators is mediated by a change in mechanisms available for activating endogenous caspases, from an apoptosome-independent to an apoptosome-dependent pathway. This switch in apoptotic pathways is regulated in a cell-autonomous manner by the steroid hormone ecdysone, through changes in expression of critical pro-, but not anti-, apoptotic genes. This steroid-controlled switch defines a novel, physiologically-regulated, mechanism for controlling sensitivity to apoptosis and provides new insights into the control of apoptosis during development. © 2013 Published by Elsevier Inc.

Mechanisms linking energy balance and reproduction: impact of prenatal environment.

PubMed

Rhinehart, Erin M

2016-01-01

The burgeoning field of metabolic reproduction regulation has been gaining momentum due to highly frequent discoveries of new neuroendocrine factors regulating both energy balance and reproduction. Universally throughout the animal kingdom, energy deficits inhibit the reproductive axis, which demonstrates that reproduction is acutely sensitive to fuel availability. Entrainment of reproductive efforts with energy availability is especially critical for females because they expend large amounts of energy on gestation and lactation. Research has identified an assortment of both central and peripheral factors involved in the metabolic regulation of reproduction. From an evolutionary perspective, these mechanisms likely evolved to optimize reproductive fitness in an environment with an unpredictable food supply and regular bouts of famine. To be effective, however, the mechanisms responsible for the metabolic regulation of reproduction must also retain developmental plasticity to allow organisms to adapt their reproductive strategies to their particular niche. In particular, the prenatal environment has emerged as a critical developmental window for programming the mechanisms responsible for the metabolic control of reproduction. This review will discuss the current knowledge about hormonal and molecular mechanisms that entrain reproduction with prevailing energy availability. In addition, it will provide an evolutionary, human life-history framework to assist in the interpretation of findings on gestational programming of the female reproductive function, with a focus on pubertal timing as an example. Future research should aim to shed light on mechanisms underlying the prenatal modulation of the adaptation to an environment with unstable resources in a way that optimizes reproductive fitness.

Decreasing-Rate Pruning Optimizes the Construction of Efficient and Robust Distributed Networks.

PubMed

Navlakha, Saket; Barth, Alison L; Bar-Joseph, Ziv

2015-07-01

Robust, efficient, and low-cost networks are advantageous in both biological and engineered systems. During neural network development in the brain, synapses are massively over-produced and then pruned-back over time. This strategy is not commonly used when designing engineered networks, since adding connections that will soon be removed is considered wasteful. Here, we show that for large distributed routing networks, network function is markedly enhanced by hyper-connectivity followed by aggressive pruning and that the global rate of pruning, a developmental parameter not previously studied by experimentalists, plays a critical role in optimizing network structure. We first used high-throughput image analysis techniques to quantify the rate of pruning in the mammalian neocortex across a broad developmental time window and found that the rate is decreasing over time. Based on these results, we analyzed a model of computational routing networks and show using both theoretical analysis and simulations that decreasing rates lead to more robust and efficient networks compared to other rates. We also present an application of this strategy to improve the distributed design of airline networks. Thus, inspiration from neural network formation suggests effective ways to design distributed networks across several domains.

Decreasing-Rate Pruning Optimizes the Construction of Efficient and Robust Distributed Networks

PubMed Central

Navlakha, Saket; Barth, Alison L.; Bar-Joseph, Ziv

2015-01-01

Robust, efficient, and low-cost networks are advantageous in both biological and engineered systems. During neural network development in the brain, synapses are massively over-produced and then pruned-back over time. This strategy is not commonly used when designing engineered networks, since adding connections that will soon be removed is considered wasteful. Here, we show that for large distributed routing networks, network function is markedly enhanced by hyper-connectivity followed by aggressive pruning and that the global rate of pruning, a developmental parameter not previously studied by experimentalists, plays a critical role in optimizing network structure. We first used high-throughput image analysis techniques to quantify the rate of pruning in the mammalian neocortex across a broad developmental time window and found that the rate is decreasing over time. Based on these results, we analyzed a model of computational routing networks and show using both theoretical analysis and simulations that decreasing rates lead to more robust and efficient networks compared to other rates. We also present an application of this strategy to improve the distributed design of airline networks. Thus, inspiration from neural network formation suggests effective ways to design distributed networks across several domains. PMID:26217933

Maternal Diet Modulates Placenta Growth and Gene Expression in a Mouse Model of Diabetic Pregnancy

PubMed Central

Kappen, Claudia; Kruger, Claudia; MacGowan, Jacalyn; Salbaum, J. Michael

2012-01-01

Unfavorable maternal diet during pregnancy can predispose the offspring to diseases later in life, such as hypertension, metabolic syndrome, and obesity. However, the molecular basis for this phenomenon of “developmental programming” is poorly understood. We have recently shown that a diet nutritionally optimized for pregnancy can nevertheless be harmful in the context of diabetic pregnancy in the mouse, associated with a high incidence of neural tube defects and intrauterine growth restriction. We hypothesized that placental abnormalities may contribute to impaired fetal growth in these pregnancies, and therefore investigated the role of maternal diet in the placenta. LabDiet 5015 diet was associated with reduced placental growth, commencing at midgestation, when compared to pregnancies in which the diabetic dam was fed LabDiet 5001 maintenance chow. Furthermore, by quantitative RT-PCR we identify 34 genes whose expression in placenta at midgestation is modulated by diet, diabetes, or both, establishing biomarkers for gene-environment interactions in the placenta. These results implicate maternal diet as an important factor in pregnancy complications and suggest that the early phases of placenta development could be a critical time window for developmental origins of adult disease. PMID:22701643

[Endocrine disruptors, reproduction and hormone-dependent cancers].

PubMed

Fenichel, Patrick; Brucker-Davis, Françoise; Chevalier, Nicolas

2016-01-01

Endocrine disruptors are natural or synthetic chemical compounds which are present in the environment and which are able to interfere with hormonal regulation pathways and to induce human health deleterious effects. While their precise implication in human health and diseases is still matter of debates, it becomes likely that they have to be considered as risk factors in numerous chronic diseases: developmental and reproductive defects and hormone dependent cancers (present review), metabolic diseases (obesity and type 2 diabetes), neurodevelopmental or neurodegenerative diseases. Low doses exposure during critical windows of exposure such as foetal, perinatal and peri-pubertal periods, or chronic exposure with bioaccumulation in the adipose tissue, and possible synergic effects of several compounds ("cocktail effect") may participate to the genetic/environment interface suspected to participate to the pathophysiology of many diseases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

In utero undernourishment perturbs the adult sperm methylome and is linked to metabolic disease transmission

PubMed Central

Radford, Elizabeth J.; Corish, Jennifer A.; Seisenberger, Stefanie; Hore, Timothy A.; Reik, Wolf; Erkek, Serap; Peters, Antoine H. F. M.; Patti, Mary-Elizabeth; Ferguson-Smith, Anne C.

2015-01-01

Adverse prenatal environments can promote metabolic disease in offspring and subsequent generations. Animal models and epidemiological data implicate epigenetic inheritance but mechanisms remain unknown. In an intergenerational developmental programming model affecting F2 metabolism, we demonstrate that the in utero nutritional environment of F1 embryos alters the germline DNA methylome of F1 adult males in a locus-specific manner. Differentially methylated regions are hypomethylated and enriched in nucleosome-retaining regions. A substantial fraction is resistant to early embryo methylation reprogramming, potentially impacting F2 development. Importantly, differential methylation is not maintained in F2 tissues, yet locus-specific expression is perturbed. Thus, in utero nutritional exposures during critical windows of germ cell development can impact the male germline methylome, associated with metabolic disease in offspring. PMID:25011554

Alterations in audiovisual simultaneity perception in amblyopia

PubMed Central

2017-01-01

Amblyopia is a developmental visual impairment that is increasingly recognized to affect higher-level perceptual and multisensory processes. To further investigate the audiovisual (AV) perceptual impairments associated with this condition, we characterized the temporal interval in which asynchronous auditory and visual stimuli are perceived as simultaneous 50% of the time (i.e., the AV simultaneity window). Adults with unilateral amblyopia (n = 17) and visually normal controls (n = 17) judged the simultaneity of a flash and a click presented with both eyes viewing. The signal onset asynchrony (SOA) varied from 0 ms to 450 ms for auditory-lead and visual-lead conditions. A subset of participants with amblyopia (n = 6) was tested monocularly. Compared to the control group, the auditory-lead side of the AV simultaneity window was widened by 48 ms (36%; p = 0.002), whereas that of the visual-lead side was widened by 86 ms (37%; p = 0.02). The overall mean window width was 500 ms, compared to 366 ms among controls (37% wider; p = 0.002). Among participants with amblyopia, the simultaneity window parameters were unchanged by viewing condition, but subgroup analysis revealed differential effects on the parameters by amblyopia severity, etiology, and foveal suppression status. Possible mechanisms to explain these findings include visual temporal uncertainty, interocular perceptual latency asymmetry, and disruption of normal developmental tuning of sensitivity to audiovisual asynchrony. PMID:28598996

Alterations in audiovisual simultaneity perception in amblyopia.

PubMed

Richards, Michael D; Goltz, Herbert C; Wong, Agnes M F

2017-01-01

Amblyopia is a developmental visual impairment that is increasingly recognized to affect higher-level perceptual and multisensory processes. To further investigate the audiovisual (AV) perceptual impairments associated with this condition, we characterized the temporal interval in which asynchronous auditory and visual stimuli are perceived as simultaneous 50% of the time (i.e., the AV simultaneity window). Adults with unilateral amblyopia (n = 17) and visually normal controls (n = 17) judged the simultaneity of a flash and a click presented with both eyes viewing. The signal onset asynchrony (SOA) varied from 0 ms to 450 ms for auditory-lead and visual-lead conditions. A subset of participants with amblyopia (n = 6) was tested monocularly. Compared to the control group, the auditory-lead side of the AV simultaneity window was widened by 48 ms (36%; p = 0.002), whereas that of the visual-lead side was widened by 86 ms (37%; p = 0.02). The overall mean window width was 500 ms, compared to 366 ms among controls (37% wider; p = 0.002). Among participants with amblyopia, the simultaneity window parameters were unchanged by viewing condition, but subgroup analysis revealed differential effects on the parameters by amblyopia severity, etiology, and foveal suppression status. Possible mechanisms to explain these findings include visual temporal uncertainty, interocular perceptual latency asymmetry, and disruption of normal developmental tuning of sensitivity to audiovisual asynchrony.

Long-term effects of nutritional programming of the embryo and fetus: mechanisms and critical windows.

PubMed

Symonds, Michael E; Stephenson, Terence; Gardner, David S; Budge, Helen

2007-01-01

The maternal nutritional and metabolic environment is critical in determining not only reproduction, but also long-term health and viability. In the present review, the effects of maternal nutritional manipulation at defined stages of gestation coinciding with embryogenesis, maximal placental or fetal growth will be discussed. Long-term outcomes from these three developmental windows appear to be very different, with brain and cardiovascular function being most sensitive to influences in the embryonic period, the kidney during placental development and adipose tissue in the fetal phase. In view of the similarities in fetal development, number and maturity at birth, there are close similarities in these outcomes between findings from epidemiological studies in historical human cohorts and nutritional manipulation of large animals, such as sheep. One key nutrient that may modulate the long-term metabolic effects is the supply of glucose from the mother to the fetus, because this is sensitive to both global changes in food intake, maternal glucocorticoid status and an increase in the carbohydrate content of the diet. The extent to which these dietary-induced changes may reflect epigenetic changes remains to be established, especially when considering the very artificial diets used to induce these types of effects. In summary, the maintenance of a balanced and appropriate supply of glucose from the mother to the fetus may be pivotal in ensuring optimal embryonic, placental and fetal growth. Increased or decreased maternal plasma glucose alone, or in conjunction with other macro- or micronutrients, may result in offspring at increased risk of adult diseases.

Translational toxicology: a developmental focus for integrated research strategies.

PubMed

Hughes, Claude; Waters, Michael; Allen, David; Obasanjo, Iyabo

2013-09-30

Given that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean? Our assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures.The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows: 1) Assessing human exposures in critical windows across the lifespan; 2) Defining modes of action and relevance of data from animal models; 3) Use of mathematical models to develop plausible predictions as the basis for: 4) Protective and restorative human health interventions. The discussion focuses on the critical window of in-utero development. Exposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics.

Thermoelastic Analysis of Hyper-X Camera Windows Suddenly Exposed to Mach 7 Stagnation Aerothermal Shock

NASA Technical Reports Server (NTRS)

Ko, William L.; Gong, Leslie

2000-01-01

To visually record the initial free flight event of the Hyper-X research flight vehicle immediately after separation from the Pegasus(registered) booster rocket, a video camera was mounted on the bulkhead of the adapter through which Hyper-X rides on Pegasus. The video camera was shielded by a protecting camera window made of heat-resistant quartz material. When Hyper-X separates from Pegasus, this camera window will be suddenly exposed to Mach 7 stagnation thermal shock and dynamic pressure loading (aerothermal loading). To examine the structural integrity, thermoelastic analysis was performed, and the stress distributions in the camera windows were calculated. The critical stress point where the tensile stress reaches a maximum value for each camera window was identified, and the maximum tensile stress level at that critical point was found to be considerably lower than the tensile failure stress of the camera window material.

Optogenetic Examination of Prefrontal-Amygdala Synaptic Development.

PubMed

Arruda-Carvalho, Maithe; Wu, Wan-Chen; Cummings, Kirstie A; Clem, Roger L

2017-03-15

A brain network comprising the medial prefrontal cortex (mPFC) and amygdala plays important roles in developmentally regulated cognitive and emotional processes. However, very little is known about the maturation of mPFC-amygdala circuitry. We conducted anatomical tracing of mPFC projections and optogenetic interrogation of their synaptic connections with neurons in the basolateral amygdala (BLA) at neonatal to adult developmental stages in mice. Results indicate that mPFC-BLA projections exhibit delayed emergence relative to other mPFC pathways and establish synaptic transmission with BLA excitatory and inhibitory neurons in late infancy, events that coincide with a massive increase in overall synaptic drive. During subsequent adolescence, mPFC-BLA circuits are further modified by excitatory synaptic strengthening as well as a transient surge in feedforward inhibition. The latter was correlated with increased spontaneous inhibitory currents in excitatory neurons, suggesting that mPFC-BLA circuit maturation culminates in a period of exuberant GABAergic transmission. These findings establish a time course for the onset and refinement of mPFC-BLA transmission and point to potential sensitive periods in the development of this critical network. SIGNIFICANCE STATEMENT Human mPFC-amygdala functional connectivity is developmentally regulated and figures prominently in numerous psychiatric disorders with a high incidence of adolescent onset. However, it remains unclear when synaptic connections between these structures emerge or how their properties change with age. Our work establishes developmental windows and cellular substrates for synapse maturation in this pathway involving both excitatory and inhibitory circuits. The engagement of these substrates by early life experience may support the ontogeny of fundamental behaviors but could also lead to inappropriate circuit refinement and psychopathology in adverse situations. Copyright © 2017 the authors 0270-6474/17/372976-10$15.00/0.

WORKSHOP TO IDENTIFY CRITICAL WINDOWS OF EXPOSURE FOR CHILDREN'S HEALTH: REPRODUCTIVE HEALTH IN CHILDREN AND ADOLESCENTS WORK GROUP SUMMARY

EPA Science Inventory

This workgroup report addresses the central question: what are the critical windows during development (pre-conception through puberty) when exposure to xenobiotics may have the greatest adverse impact on subsequent reproductive health. The reproductive system develops in stages...

Potential for Bias When Estimating Critical Windows for Air Pollution in Children's Health.

PubMed

Wilson, Ander; Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Wright, Robert O; Wright, Rosalind J; Coull, Brent A

2017-12-01

Evidence supports an association between maternal exposure to air pollution during pregnancy and children's health outcomes. Recent interest has focused on identifying critical windows of vulnerability. An analysis based on a distributed lag model (DLM) can yield estimates of a critical window that are different from those from an analysis that regresses the outcome on each of the 3 trimester-average exposures (TAEs). Using a simulation study, we assessed bias in estimates of critical windows obtained using 3 regression approaches: 1) 3 separate models to estimate the association with each of the 3 TAEs; 2) a single model to jointly estimate the association between the outcome and all 3 TAEs; and 3) a DLM. We used weekly fine-particulate-matter exposure data for 238 births in a birth cohort in and around Boston, Massachusetts, and a simulated outcome and time-varying exposure effect. Estimates using separate models for each TAE were biased and identified incorrect windows. This bias arose from seasonal trends in particulate matter that induced correlation between TAEs. Including all TAEs in a single model reduced bias. DLM produced unbiased estimates and added flexibility to identify windows. Analysis of body mass index z score and fat mass in the same cohort highlighted inconsistent estimates from the 3 methods. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: A developmental study

PubMed Central

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 damage to the placenta, particularly to the labyrinthine layer, suggesting that circulatory changes are integral to the altered phenotypes. PMID:28231241

Assisted reproductive technologies and children's neurodevelopmental outcomes.

PubMed

Hediger, Mary L; Bell, Erin M; Druschel, Charlotte M; Buck Louis, Germaine M

2013-02-01

Initial reports suggested that children conceived with assisted reproductive technologies (ART) may be at increased risk for a spectrum of developmental disabilities. Evolving evidence suggests that some of the early risks may have been overstated when not taking plurality of birth or gestational age at delivery into consideration, as both are independent risk factors for neurodevelopmental disabilities arising from alterations in structure and function or limitations in activities. Continued research is needed to overcome lingering data gaps in light of the equivocal literature for many neurodevelopmental disabilities relative to ART, increasing utilization of services, and changes in the clinical management of infecund couples such as the adoption of natural cycles or in vitro maturation treatment options. Population-based cohorts with longitudinal assessment of the multifaceted nature of neurodevelopment across critical and sensitive windows is paramount for the development of empirically based guidance for clinical and population health. Copyright © 2013 American Society for Reproductive Medicine. All rights reserved.

Manganese Exposure and Cognition Across the Lifespan: Contemporary Review and Argument for Biphasic Dose-Response Health Effects

PubMed Central

Vollet, Kaitlin; Dietrich, Kim N.

2016-01-01

Manganese (Mn) is both an essential micronutrient and potential neurotoxicant. This dual role underlies a growing body of literature demonstrating that Mn exhibits a biphasic dose-response relationship with neurocognitive outcomes. We reviewed recent epidemiologic studies from 2007–2016 that investigated the relationship between Mn exposure and cognitive outcomes across the lifespan: early life, school-aged children, and adulthood. In total, 27 research articles were included in this review: 12 pediatric and 15 adult studies (10 occupational and five environmental exposures). The majority of these studies provided evidence of the negative effects of Mn exposure on cognition. The pediatric literature provides evidence that both high and low levels of Mn are negatively associated with intellectual development. Future Mn research should include examination of non-linear relationships and multiple neurotoxicants across the lifespan, and particularly during critical developmental windows. PMID:27722879

In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism.

PubMed

Radford, Elizabeth J; Ito, Mitsuteru; Shi, Hui; Corish, Jennifer A; Yamazawa, Kazuki; Isganaitis, Elvira; Seisenberger, Stefanie; Hore, Timothy A; Reik, Wolf; Erkek, Serap; Peters, Antoine H F M; Patti, Mary-Elizabeth; Ferguson-Smith, Anne C

2014-08-15

Adverse prenatal environments can promote metabolic disease in offspring and subsequent generations. Animal models and epidemiological data implicate epigenetic inheritance, but the mechanisms remain unknown. In an intergenerational developmental programming model affecting F2 mouse metabolism, we demonstrate that the in utero nutritional environment of F1 embryos alters the germline DNA methylome of F1 adult males in a locus-specific manner. Differentially methylated regions are hypomethylated and enriched in nucleosome-retaining regions. A substantial fraction is resistant to early embryo methylation reprogramming, which may have an impact on F2 development. Differential methylation is not maintained in F2 tissues, yet locus-specific expression is perturbed. Thus, in utero nutritional exposures during critical windows of germ cell development can impact the male germline methylome, associated with metabolic disease in offspring. Copyright © 2014, American Association for the Advancement of Science.

Endocrine disruptors and prostate cancer risk

PubMed Central

Prins, Gail S

2010-01-01

There is increasing evidence both from epidemiology studies and animal models that specific endocrine-disrupting compounds may influence the development or progression of prostate cancer. In large part, these effects appear to be linked to interference with estrogen signaling, either through interacting with ERs or by influencing steroid metabolism and altering estrogen levels within the body. In humans, epidemiologic evidence links specific pesticides, PCBs and inorganic arsenic exposures to elevated prostate cancer risk. Studies in animal models also show augmentation of prostate carcinogenesis with several other environmental estrogenic compounds including cadmium, UV filters and BPA. Importantly, there appears to be heightened sensitivity of the prostate to these endocrine disruptors during the critical developmental windows including in utero and neonatal time points as well as during puberty. Thus infants and children may be considered a highly susceptible population for ED exposures and increased risk of prostate cancers with aging. PMID:18524946

Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision.

PubMed

Lu, Catherine P; Polak, Lisa; Keyes, Brice E; Fuchs, Elaine

2016-12-23

The gain of eccrine sweat glands in hairy body skin has empowered humans to run marathons and tolerate temperature extremes. Epithelial-mesenchymal cross-talk is integral to the diverse patterning of skin appendages, but the molecular events underlying their specification remain largely unknown. Using genome-wide analyses and functional studies, we show that sweat glands are specified by mesenchymal-derived bone morphogenetic proteins (BMPs) and fibroblast growth factors that signal to epithelial buds and suppress epithelial-derived sonic hedgehog (SHH) production. Conversely, hair follicles are specified when mesenchymal BMP signaling is blocked, permitting SHH production. Fate determination is confined to a critical developmental window and is regionally specified in mice. In contrast, a shift from hair to gland fates is achieved in humans when a spike in BMP silences SHH during the final embryonic wave(s) of bud morphogenesis. Copyright © 2016, American Association for the Advancement of Science.

Regulating Critical Period Plasticity: Insight from the Visual System to Fear Circuitry for Therapeutic Interventions

PubMed Central

Nabel, Elisa M.; Morishita, Hirofumi

2013-01-01

Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development – the preeminent model of experience-dependent critical period plasticity-actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins – endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions. PMID:24273519

Spatial-temporal modeling of the association between air pollution exposure and preterm birth: identifying critical windows of exposure.

PubMed

Warren, Joshua; Fuentes, Montserrat; Herring, Amy; Langlois, Peter

2012-12-01

Exposure to high levels of air pollution during the pregnancy is associated with increased probability of preterm birth (PTB), a major cause of infant morbidity and mortality. New statistical methodology is required to specifically determine when a particular pollutant impacts the PTB outcome, to determine the role of different pollutants, and to characterize the spatial variability in these results. We develop a new Bayesian spatial model for PTB which identifies susceptible windows throughout the pregnancy jointly for multiple pollutants (PM(2.5) , ozone) while allowing these windows to vary continuously across space and time. We geo-code vital record birth data from Texas (2002-2004) and link them with standard pollution monitoring data and a newly introduced EPA product of calibrated air pollution model output. We apply the fully spatial model to a region of 13 counties in eastern Texas consisting of highly urban as well as rural areas. Our results indicate significant signal in the first two trimesters of pregnancy with different pollutants leading to different critical windows. Introducing the spatial aspect uncovers critical windows previously unidentified when space is ignored. A proper inference procedure is introduced to correctly analyze these windows. © 2012, The International Biometric Society.

Design and Verification of Critical Pressurised Windows for Manned Spaceflight

NASA Astrophysics Data System (ADS)

Lamoure, Richard; Busto, Lara; Novo, Francisco; Sinnema, Gerben; Leal, Mendes M.

2014-06-01

The Window Design for Manned Spaceflight (WDMS) project was tasked with establishing the state-of-art and explore possible improvements to the current structural integrity verification and fracture control methodologies for manned spacecraft windows.A critical review of the state-of-art in spacecraft window design, materials and verification practice was conducted. Shortcomings of the methodology in terms of analysis, inspection and testing were identified. Schemes for improving verification practices and reducing conservatism whilst maintaining the required safety levels were then proposed.An experimental materials characterisation programme was defined and carried out with the support of the 'Glass and Façade Technology Research Group', at the University of Cambridge. Results of the sample testing campaign were analysed, post-processed and subsequently applied to the design of a breadboard window demonstrator.Two Fused Silica glass window panes were procured and subjected to dedicated analyses, inspection and testing comprising both qualification and acceptance programmes specifically tailored to the objectives of the activity.Finally, main outcomes have been compiled into a Structural Verification Guide for Pressurised Windows in manned spacecraft, incorporating best practices and lessons learned throughout this project.

Overview of Fabrication Techniques and Lessons Learned with Accelerator Vacuum Windows

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

Ader, C. R.; McGee, M. W.; Nobrega, L. E.

Vacuum thin windows have been used in Fermilab's accelerators for decades and typically have been overlooked in terms of their criticality and fragility. Vacuum windows allow beam to pass through while creating a boundary between vacuum and air or high vacuum and low vacuum areas. The design of vacuum windows, including Titanium and Beryllium windows, will be discussed as well as fabrication, testing, and operational concerns. Failure of windows will be reviewed as well as safety approaches to mitigating failures and extending the lifetimes of vacuum windows. Various methods of calculating the strengths of vacuum windows will be explored, includingmore » FEA.« less

Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development--the LIFE Study.

PubMed

Buck Louis, Germaine M; Schisterman, Enrique F; Sweeney, Anne M; Wilcosky, Timothy C; Gore-Langton, Robert E; Lynch, Courtney D; Boyd Barr, Dana; Schrader, Steven M; Kim, Sungduk; Chen, Zhen; Sundaram, Rajeshwari

2011-09-01

The relationship between the environment and human fecundity and fertility remains virtually unstudied from a couple-based perspective in which longitudinal exposure data and biospecimens are captured across sensitive windows. In response, we completed the LIFE Study with methodology that intended to empirically evaluate a priori purported methodological challenges: implementation of population-based sampling frameworks suitable for recruiting couples planning pregnancy; obtaining environmental data across sensitive windows of reproduction and development; home-based biospecimen collection; and development of a data management system for hierarchical exposome data. We used two sampling frameworks (i.e., fish/wildlife licence registry and a direct marketing database) for 16 targeted counties with presumed environmental exposures to persistent organochlorine chemicals to recruit 501 couples planning pregnancies for prospective longitudinal follow-up while trying to conceive and throughout pregnancy. Enrolment rates varied from <1% of the targeted population (n = 424,423) to 42% of eligible couples who were successfully screened; 84% of the targeted population could not be reached, while 36% refused screening. Among enrolled couples, ∼ 85% completed daily journals while trying; 82% of pregnant women completed daily early pregnancy journals, and 80% completed monthly pregnancy journals. All couples provided baseline blood/urine samples; 94% of men provided one or more semen samples and 98% of women provided one or more saliva samples. Women successfully used urinary fertility monitors for identifying ovulation and home pregnancy test kits. Couples can be recruited for preconception cohorts and will comply with intensive data collection across sensitive windows. However, appropriately sized sampling frameworks are critical, given the small percentage of couples contacted found eligible and reportedly planning pregnancy at any point in time. © Published 2011. This article is a US Government work and is in the public domain in the USA.

Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia.

PubMed

Khulan, Batbayar; Cooper, Wendy N; Skinner, Benjamin M; Bauer, Julien; Owens, Stephen; Prentice, Andrew M; Belteki, Gusztav; Constancia, Miguel; Dunger, David; Affara, Nabeel A

2012-05-01

In addition to the genetic constitution inherited by an organism, the developmental trajectory and resulting mature phenotype are also determined by mechanisms acting during critical windows in early life that influence and establish stable patterns of gene expression. This is the crux of the developmental origins of health and disease hypothesis that suggests undernutrition during gestation and infancy predisposes to ill health in later life. The hypothesis that periconceptional maternal micronutrient supplementation might affect fetal genome-wide methylation within gene promoters was explored in cord blood samples from offspring of Gambian women enrolled into a unique randomized, double blind controlled trial. Significant changes in the epigenome in cord blood DNA samples were further explored in a subset of offspring at 9 months. Gender-specific changes related to periconceptional nutritional supplementation were identified in cord blood DNA samples, some of which showed persistent changes in infant blood DNA samples. Significant effects of periconceptional micronutrient supplementation were also observed in postnatal samples which were not evident in cord blood. In this Gambian population, the increased death rate of individuals born in nutritionally poor seasons has been related to infection and it is of interest that we identified differential methylation at genes associated with defence against infection and immune response. Although the sample size was relatively small, these pilot data suggest that periconceptional nutrition in humans is an important determinant of newborn whole genome methylation patterns but may also influence postnatal developmental patterns of gene promoter methylation linking early with disease risk.

Exposure to a PBDE/OH-BDE mixture alters juvenile zebrafish (Danio rerio) development

PubMed Central

Macaulay, Laura J.; Chernick, Melissa; Chen, Albert; Hinton, David E.; Bailey, Jordan M.; Kullman, Seth W.; Levin, Edward D.; Stapleton, Heather M.

2017-01-01

Polybrominated diphenyl ethers (PBDEs) and halogenated phenolic compounds (e.g., hydroxylated BDEs (OH-BDEs)) arecontaminants detected together frequently in human tissues, and are structurally similar to thyroid hormones (TH). THs partially mediate metamorphic transitions between life stages in zebrafish, making this a critical developmental window which may be uniquely vulnerable to chemicals disrupting thyroid signaling. In this study, zebrafish were exposed to 6-OH-BDE-47 (30 nM) alone or to a low (30 μg/L) or high dose (600 μg/L) mixture of PentaBDEs, 6-OH-BDE-47 (0.5–6 μg/L), & 2,4,6 tribromophenol (TBP) (5–100 μg/L) during juvenile development (9–23 days post fertilization; dpf) and evaluated for developmental endpoints mediated by TH signaling. Fish were sampled at three time points and examined for developmental and skeletal morphology, apical thyroid and skeletal gene markers, and modifications in swimming behavior (as adults). Exposure to the high mixture resulted in > 85% mortality within one week of exposure, despite being below reported acute toxicity thresholds for individual congeners. The low mixture and 6-OH-BDE-47 groups exhibited reductions in body length and delayed maturation, specifically relating to swim bladder,?, fin, and pigmentation development. Reduced skeletal ossification was also observed in 6-OH-BDE-47 treated fish. Assessment of thyroid and osteochondral gene regulatory networks demonstrated significantly increased expression of genes that regulate skeletal development and THs. Overall, these results indicate that exposures to PBDEs/OH-BDEs mixtures adversely impact zebrafish maturation during metamorphosis. PMID:27329031

MYSTERIES OF THE HUMAN FETUS REVEALED

PubMed Central

SANDMAN, CURT A

2015-01-01

The impressive program of research from the DiPietro laboratory succeeds in its aim to document the ontogeny of human fetal neurobehavioral development. From studies of great depth and breadth, and wielding creative methods of assessment, DiPietro et al open a window into the largely inaccessible developing human fetal brain. This commentary, with reference to the seminal cardiovascular studies of the Lacey's, supports the measures of the fetal heart to index fetal well-being and to provide evidence of stimulus processing. A separate case is made that the DiPietro program provides unique and invaluable information for assessing the influential Developmental Origins of Health and Disease or Fetal Programming Models. The goal of these models, to predict or understand the influences of early experience or response patterns on later postnatal life, is identical to the ultimate goal of the DiPietro program. Because human fetal behavior is uncontaminated by socialization or parenting or peers, it may be the best reflection of fetal exposures. The remarkable neurobehavioral profiles generated by the DiPietro program can make a critical contribution to the Fetal Programming Model in terms of sensitive and critical periods of nervous system vulnerability and to specify gestational periods of neurobehavioral risk.. PMID:26303720

[Guidelines for complementary feeding in healthy infants].

PubMed

Romero-Velarde, Enrique; Villalpando-Carrión, Salvador; Pérez-Lizaur, Ana Berta; Iracheta-Gerez, Ma de la Luz; Alonso-Rivera, Carlos Gilberto; López-Navarrete, Gloria Elena; García-Contreras, Andrea; Ochoa-Ortiz, Erika; Zarate-Mondragón, Flora; López-Pérez, Gerardo Tiburcio; Chávez-Palencia, Clío; Guajardo-Jáquez, Manuel; Vázquez-Ortiz, Salvador; Pinzón-Navarro, Beatriz Adriana; Torres-Duarte, Karely Noemy; Vidal-Guzmán, José Domingo; Michel-Gómez, Pedro Luis; López-Contreras, Iris Nallely; Arroyo-Cruz, Liliana Verenice; Almada-Velasco, Pamela; Saltigeral-Simental, Patricia; Ríos-Aguirre, Alejandro; Domínguez-Pineda, Lorena; Rodríguez-González, Perla; Crabtree-Ramírez, Úrsula; Hernández-Rosiles, Vanessa; Pinacho-Velázquez, José Luis

A proper nutrition during the first two years of life is critical to reach the full potential of every human being; now, this period is recognized as a critical window for promoting optimal growth, development, and good health. Therefore, adequate feeding at this stage of life has an impact on health, nutritional status, growth and development of children; not only in the short term, but in the medium and long term. This paper provides recommendations on complementary feeding (CF) presented as questions or statements that are important for those who take care for children during this stage of life. For example: When to start complementary feedings: 4 or 6 months of age?; Exposure to potentially allergenic foods; Introduction of sweetened beverages; Use of artificial sweeteners and light products; Food introduction sequence; Food consistency changes according to neurological maturation; Number of days to test acceptance and tolerance to new foods; Amounts for each meal; Inadequate complementary feeding practices; Myths and realities of complementary feeding; Developmental milestones; Practice of "Baby Led Weaning" and practice of vegetarianism. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Framework for sex differences in adolescent neurobiology: A focus on cannabinoids

PubMed Central

Viveros, Maria-Paz; Marco-López, Eva María; López-Gallardo, Meritxell; Garcia-Segura, Luis Miguel; Wagner, Edward J.

2017-01-01

This review highlights the salient findings that have furthered our understanding of how sex differences are initiated during development and maintained throughout life. First we discuss how gonadal steroid hormones organize the framework for sex differences within critical periods of development—namely, during those exposures which occur in utero and post-partum, as well as those which occur during puberty. Given the extensive precedence of sex differences in cannabinoid-regulated biology, we then focus on the disparities within the endogenous cannabinoid system, as well as those observed with exogenously administered cannabinoids. We start with how the expression of cannabinoid CB1 receptors is regulated throughout development. This is followed by a discussion of differential vulnerability to the pathological sequelae stemming from cannabinoid exposure during adolescence. Next we talk about sex differences in the interactions between cannabinoids and other drugs of abuse, followed by the organizational and activational roles of gonadal steroids in establishing and maintaining the sex dependence in the biological actions of cannabinoids. Finally, we discuss ways to utilize this knowledge to strategically target critical developmental windows of vulnerability/susceptibility and thereby implement more effective therapeutic interventions for afflictions that may be more prevalent in one sex vs. the other. PMID:20869396

Fragile X Mental Retardation Protein Regulates Activity-Dependent Membrane Trafficking and Trans-Synaptic Signaling Mediating Synaptic Remodeling

PubMed Central

Sears, James C.; Broadie, Kendal

2018-01-01

Fragile X syndrome (FXS) is the leading monogenic cause of autism and intellectual disability. The disease arises through loss of fragile X mental retardation protein (FMRP), which normally exhibits peak expression levels in early-use critical periods, and is required for activity-dependent synaptic remodeling during this transient developmental window. FMRP canonically binds mRNA to repress protein translation, with targets that regulate cytoskeleton dynamics, membrane trafficking, and trans-synaptic signaling. We focus here on recent advances emerging in these three areas from the Drosophila disease model. In the well-characterized central brain mushroom body (MB) olfactory learning/memory circuit, FMRP is required for activity-dependent synaptic remodeling of projection neurons innervating the MB calyx, with function tightly restricted to an early-use critical period. FMRP loss is phenocopied by conditional removal of FMRP only during this critical period, and rescued by FMRP conditional expression only during this critical period. Consistent with FXS hyperexcitation, FMRP loss defects are phenocopied by heightened sensory experience and targeted optogenetic hyperexcitation during this critical period. FMRP binds mRNA encoding Drosophila ESCRTIII core component Shrub (human CHMP4 homolog) to restrict Shrub translation in an activity-dependent mechanism only during this same critical period. Shrub mediates endosomal membrane trafficking, and perturbing Shrub expression is known to interfere with neuronal process pruning. Consistently, FMRP loss and Shrub overexpression targeted to projection neurons similarly causes endosomal membrane trafficking defects within synaptic boutons, and genetic reduction of Shrub strikingly rescues Drosophila FXS model defects. In parallel work on the well-characterized giant fiber (GF) circuit, FMRP limits iontophoretic dye loading into central interneurons, demonstrating an FMRP role controlling core neuronal properties through the activity-dependent repression of translation. In the well-characterized Drosophila neuromuscular junction (NMJ) model, developmental synaptogenesis and activity-dependent synaptic remodeling both require extracellular matrix metalloproteinase (MMP) enzymes interacting with the heparan sulfate proteoglycan (HSPG) glypican dally-like protein (Dlp) to restrict trans-synaptic Wnt signaling, with FXS synaptogenic defects alleviated by both MMP and HSPG reduction. This new mechanistic axis spanning from activity to FMRP to HSPG-dependent MMP regulation modulates activity-dependent synaptogenesis. We discuss future directions for these mechanisms, and intersecting research priorities for FMRP in glial and signaling interactions. PMID:29375303

Developmental milestones among Aboriginal children in Canada

PubMed Central

Findlay, Leanne; Kohen, Dafna; Miller, Anton

2014-01-01

BACKGROUND: Windows of achievement provide age ranges for the attainment of early developmental skills. Group-specific research is warranted given that development may be influenced by social or cultural factors. OBJECTIVES: To examine developmental milestones for Inuit, Métis and off-reserve First Nation children in Canada, based on developmental domains collected from the 2006 Aboriginal Children’s Survey. Sociodemographic and health predictors of risk for developmental delay were also examined. RESULTS: The ranges in which children achieve certain developmental milestones are presented. Gross motor and self-help skills were found to be achieved earlier (across the three Aboriginal groups), whereas language skills were achieved slightly later than in Canadian children in general. Furthermore, health factors (eg, low birth weight, chronic health conditions) were associated with late achievement of developmental outcomes even when sociodemographic characteristics were considered. CONCLUSIONS: Findings suggest that the timing of milestone achievement may differ for Aboriginal children, highlighting the importance of establishing culturally specific norms and standards rather than relying on those derived from general populations. This information may be useful for practitioners and parents interested in identifying the age ranges for development, as well as age ranges indicating potential for developmental risk and opportunities for early intervention among Aboriginal children. PMID:24855426

Detection with Enhanced Energy Windowing Phase I Report

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

Bass, David A.; Enders, Alexander L.

2016-12-01

This document reviews the progress of Phase I of the Detection with Enhanced Energy Windowing (DEEW) project. The DEEW project is the implementation of software incorporating an algorithm which reviews data generated by radiation portal monitors and utilizes advanced and novel techniques for detecting radiological and fissile material while not alarming on Naturally Occurring Radioactive Material. Independent testing indicated that the Enhanced Energy Windowing algorithm showed promise at reducing the probability of alarm in the stream of commerce compared to existing algorithms and other developmental algorithms, while still maintaining adequate sensitivity to threats. This document contains a brief description ofmore » the project, instructions for setting up and running the applications, and guidance to help make reviewing the output files and source code easier.« less

Varying Susceptibility of the Female Mammary Gland to In Utero Windows of BPA Exposure.

PubMed

Hindman, Andrea R; Mo, Xiaokui Molly; Helber, Hannah L; Kovalchin, Claire E; Ravichandran, Nanditha; Murphy, Alina R; Fagan, Abigail M; St John, Pamela M; Burd, Craig J

2017-10-01

In utero exposure to the endocrine disrupting compound bisphenol A (BPA) is known to disrupt mammary gland development and increase tumor susceptibility in rodents. It is unclear whether different periods of in utero development might be more susceptible to BPA exposure. We exposed pregnant CD-1 mice to BPA at different times during gestation that correspond to specific milestones of in utero mammary gland development. The mammary glands of early-life and adult female mice, exposed in utero to BPA, were morphologically and molecularly (estrogen receptor-α and Ki67) evaluated for developmental abnormalities. We found that BPA treatment occurring before mammary bud invasion into the mesenchyme [embryonic day (E)12.5] incompletely resulted in the measured phenotypes of mammary gland defects. Exposing mice up to the point at which the epithelium extends into the precursor fat pad (E16.5) resulted in a nearly complete BPA phenotype and exposure during epithelial extension (E15.5 to E18.5) resulted in a partial phenotype. Furthermore, the relative differences in phenotypes between exposure windows highlight the substantial correlations between early-life molecular changes (estrogen receptor-α and Ki67) in the stroma and the epithelial elongation defects in mammary development. These data further implicate BPA action in the stroma as a critical mediator of epithelial phenotypes. Copyright © 2017 Endocrine Society.

Multimodal lexical processing in auditory cortex is literacy skill dependent.

PubMed

McNorgan, Chris; Awati, Neha; Desroches, Amy S; Booth, James R

2014-09-01

Literacy is a uniquely human cross-modal cognitive process wherein visual orthographic representations become associated with auditory phonological representations through experience. Developmental studies provide insight into how experience-dependent changes in brain organization influence phonological processing as a function of literacy. Previous investigations show a synchrony-dependent influence of letter presentation on individual phoneme processing in superior temporal sulcus; others demonstrate recruitment of primary and associative auditory cortex during cross-modal processing. We sought to determine whether brain regions supporting phonological processing of larger lexical units (monosyllabic words) over larger time windows is sensitive to cross-modal information, and whether such effects are literacy dependent. Twenty-two children (age 8-14 years) made rhyming judgments for sequentially presented word and pseudoword pairs presented either unimodally (auditory- or visual-only) or cross-modally (audiovisual). Regression analyses examined the relationship between literacy and congruency effects (overlapping orthography and phonology vs. overlapping phonology-only). We extend previous findings by showing that higher literacy is correlated with greater congruency effects in auditory cortex (i.e., planum temporale) only for cross-modal processing. These skill effects were specific to known words and occurred over a large time window, suggesting that multimodal integration in posterior auditory cortex is critical for fluent reading. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Early life stress-induced alterations in rat brain structures measured with high resolution MRI.

PubMed

Sarabdjitsingh, R Angela; Loi, Manila; Joëls, Marian; Dijkhuizen, Rick M; van der Toorn, Annette

2017-01-01

Adverse experiences early in life impair cognitive function both in rodents and humans. In humans this increases the vulnerability to develop mental illnesses while in the rodent brain early life stress (ELS) abnormalities are associated with changes in synaptic plasticity, excitability and microstructure. Detailed information on the effects of ELS on rodent brain structural integrity at large and connectivity within the brain is currently lacking; this information is highly relevant for understanding the mechanism by which early life stress predisposes to mental illnesses. Here, we exposed rats to 24 hours of maternal deprivation (MD) at postnatal day 3, a paradigm known to increase corticosterone levels and thereby activate glucocorticoid receptors in the brain. Using structural magnetic resonance imaging we examined: i) volumetric changes and white/grey matter properties of the whole cerebrum and of specific brain areas; and ii) whether potential alterations could be normalized by blocking glucocorticoid receptors with mifepristone during the critical developmental window of early adolescence, i.e. between postnatal days 26 and 28. The results show that MD caused a volumetric reduction of the prefrontal cortex, particularly the ventromedial part, and the orbitofrontal cortex. Within the whole cerebrum, white (relative to grey) matter volume was decreased and region-specifically in prefrontal cortex and dorsomedial striatum following MD. A trend was found for the hippocampus. Grey matter fractions were not affected. Treatment with mifepristone did not normalize these changes. This study indicates that early life stress in rodents has long lasting consequences for the volume and structural integrity of the brain. However, changes were relatively modest and-unlike behavior- not mitigated by blockade of glucocorticoid receptors during a critical developmental period.

Supporting Optimal Neurodevelopmental Outcomes in Infants and Children With Congenital Heart Disease.

PubMed

Peterson, Jennifer K

2018-06-01

Improved survival has led to increased recognition of developmental delays in infants and children with congenital heart disease. Risk factors for developmental delays in congenital heart disease survivors may not be modifiable; therefore, it is important that lifesaving, high-technology critical care interventions be combined with nursing interventions that are also developmentally supportive. Implementing developmental care in a pediatric cardiac intensive care unit requires change implementation strategies and widespread support from all levels of health care professionals. This manuscript reviews developmentally supportive interventions such as massage, developmentally supportive positioning, kangaroo care, cue-based feeding, effective pain/anxiety management, and procedural preparation and identifies strategies to implement developmentally supportive interventions in the care of infants and children with congenital heart disease. Improving developmental support for these infants and children at high risk for developmental delay may improve their outcomes and help promote family-centered care. ©2018 American Association of Critical-Care Nurses.

Developmental windows of breast cancer risk provide opportunities for targeted chemoprevention

PubMed Central

Martinson, Holly A.; Lyons, Traci R.; Giles, Erin D.; Borges, Virginia F.; Schedin, Pepper

2014-01-01

The magnitude of the breast cancer problem implores researchers to aggressively investigate prevention strategies. However, several barriers currently reduce the feasibility of breast cancer prevention. These barriers include the inability to accurately predict future breast cancer diagnosis at the individual level, the need for improved understanding of when to implement interventions, uncertainty with respect to optimal duration of treatment, and negative side effects associated with currently approved chemoprevention therapies. None-the-less, the unique biology of the mammary gland, with its postnatal development and conditional terminal differentiation, may permit the resolution of many of these barriers. Specifically, lifecycle-specific windows of breast cancer risk have been identified that may be amenable to risk-reducing strategies. Here, we argue for prevention research focused on two of these lifecycle windows of risk: postpartum mammary gland involution and peri-menopause. We provide evidence that these windows are highly amenable to targeted, limited duration treatments. Such approaches could result in the prevention of postpartum and postmenopausal breast cancers, correspondingly. PMID:23664839

UTILIZATION OF A PBPK MODEL TO PREDICT THE DISTRIBUTION OF 2, 3, 7-8 TETRACHLORODIBENZO-P-DIOXIN (TCDD) IN HUMANS DURING CRITICAL WINDOWS OF DEVELOPMENT

EPA Science Inventory

Utilization of A PBPK model to predict the distribution of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in humans during critical windows of development.
C Emond1, MJ DeVito2 and LS Birnbaum2
1National Research Council, US EPA, ORD, NHEERL, (ETD, PK), RTP, NC, 27711, USA 2 US...

Abscisic acid (ABA) sensitivity regulates desiccation tolerance in germinated Arabidopsis seeds.

PubMed

Maia, Julio; Dekkers, Bas J W; Dolle, Miranda J; Ligterink, Wilco; Hilhorst, Henk W M

2014-07-01

During germination, orthodox seeds lose their desiccation tolerance (DT) and become sensitive to extreme drying. Yet, DT can be rescued, in a well-defined developmental window, by the application of a mild osmotic stress before dehydration. A role for abscisic acid (ABA) has been implicated in this stress response and in DT re-establishment. However, the path from the sensing of an osmotic cue and its signaling to DT re-establishment is still largely unknown. Analyses of DT, ABA sensitivity, ABA content and gene expression were performed in desiccation-sensitive (DS) and desiccation-tolerant Arabidopsis thaliana seeds. Furthermore, loss and re-establishment of DT in germinated Arabidopsis seeds was studied in ABA-deficient and ABA-insensitive mutants. We demonstrate that the developmental window in which DT can be re-established correlates strongly with the window in which ABA sensitivity is still present. Using ABA biosynthesis and signaling mutants, we show that this hormone plays a key role in DT re-establishment. Surprisingly, re-establishment of DT depends on the modulation of ABA sensitivity rather than enhanced ABA content. In addition, the evaluation of several ABA-insensitive mutants, which can still produce normal desiccation-tolerant seeds, but are impaired in the re-establishment of DT, shows that the acquisition of DT during seed development is genetically different from its re-establishment during germination. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Critical evaluation of round window membrane sealing in the treatment of idiopathic sudden unilateral hearing loss.

PubMed

Hoch, Stephan; Vomhof, Thomas; Teymoortash, Afshin

2015-03-01

Rupture of the round window membrane with consecutive development of a perilymphatic fistula (PLF) is still a matter of controversial debate in the pathogenesis of idiopathic sudden sensorineural hearing loss (SSHL). Until now no consensus exists about whether these patients benefit from performing an exploratory tympanotomy with sealing of the round window. The aim of the present study was to analyze critically the effectiveness of sealing the round window membrane in patients with SSHL. The clinical data of 51 patients with SSHL and a mean hearing decline of at least 60 dB over 5 frequencies who were treated with tympanotomy and sealing of the round window membrane were retrospectively analyzed. The results have been compared to the current state of the literature. Intraoperatively a round window membrane rupture or fluid leak was observed in none of the patients. After performing tympanotomy the mean improvement of hearing level was 32.7 dB. Twenty of 51 examined patients (39.2%) showed a mean improvement of the hearing level of more than 30 dB and a complete remission could be detected in 12 patients (23.5%). Reviewing the literature revealed no standard guidelines for definition or treatment of SSHL as well as for evaluation of hearing loss and its recovery. The results of the present study and the literature should be discussed critically. It is unclear whether tympanotomy and sealing of the round window membrane may be a meaningful treatment for SSHL. Therefore this procedure should be discussed as a therapeutic option only in selected patients with sudden deafness or profound hearing loss in which PLF is strongly suspicious or conservative treatment failed.

T cell developmental arrest in former premature infants increases risk of respiratory morbidity later in infancy

PubMed Central

Scheible, Kristin M.; Emo, Jason; Laniewski, Nathan; Baran, Andrea M.; Peterson, Derick R.; Bandyopadhyay, Sanjukta; Straw, Andrew G.; Huyck, Heidie; Ashton, John M.; Tripi, Kelly Schooping; Arul, Karan; Werner, Elizabeth; Scalise, Tanya; Maffett, Deanna; Caserta, Mary; Ryan, Rita M.; Reynolds, Anne Marie; Ren, Clement L.; Topham, David J.; Mariani, Thomas J.; Pryhuber, Gloria S.

2018-01-01

The inverse relationship between gestational age at birth and postviral respiratory morbidity suggests that infants born preterm (PT) may miss a critical developmental window of T cell maturation. Despite a continued increase in younger PT survivors with respiratory complications, we have limited understanding of normal human fetal T cell maturation, how ex utero development in premature infants may interrupt normal T cell development, and whether T cell development has an effect on infant outcomes. In our longitudinal cohort of 157 infants born between 23 and 42 weeks of gestation, we identified differences in T cells present at birth that were dependent on gestational age and differences in postnatal T cell development that predicted respiratory outcome at 1 year of age. We show that naive CD4+ T cells shift from a CD31–TNF-α+ bias in mid gestation to a CD31+IL-8+ predominance by term gestation. Former PT infants discharged with CD31+IL8+CD4+ T cells below a range similar to that of full-term born infants were at an over 3.5-fold higher risk for respiratory complications after NICU discharge. This study is the first to our knowledge to identify a pattern of normal functional T cell development in later gestation and to associate abnormal T cell development with health outcomes in infants. PMID:29467329

Studying action representation in children via motor imagery.

PubMed

Gabbard, Carl

2009-12-01

The use of motor imagery is a widely used experimental paradigm for the study of cognitive aspects of action planning and control in adults. Furthermore, there are indications that motor imagery provides a window into the process of action representation. These notions complement internal model theory suggesting that such representations allow predictions (estimates) about the mapping of the self to parameters of the external world; processes that enable successful planning and execution of action. The ability to mentally represent action is important to the development of motor control. This paper presents a critical review of motor imagery research conducted with children (typically developing and special populations) with focus on its merits and possible shortcomings in studying action representation. Included in the review are age-related findings, possible brain structures involved, experimental paradigms, and recommendations for future work. The merits of this review are associated with the apparent increasing attraction for using and studying motor imagery to understand the developmental aspects of action processing in children.

The Utility of Stage-specific Mid-to-late Drosophila Follicle Isolation

PubMed Central

Spracklen, Andrew J.; Tootle, Tina L.

2013-01-01

Drosophila oogenesis or follicle development has been widely used to advance the understanding of complex developmental and cell biologic processes. This methods paper describes how to isolate mid-to-late stage follicles (Stage 10B-14) and utilize them to provide new insights into the molecular and morphologic events occurring during tight windows of developmental time. Isolated follicles can be used for a variety of experimental techniques, including in vitro development assays, live imaging, mRNA expression analysis and western blot analysis of proteins. Follicles at Stage 10B (S10B) or later will complete development in culture; this allows one to combine genetic or pharmacologic perturbations with in vitro development to define the effects of such manipulations on the processes occurring during specific periods of development. Additionally, because these follicles develop in culture, they are ideally suited for live imaging studies, which often reveal new mechanisms that mediate morphological events. Isolated follicles can also be used for molecular analyses. For example, changes in gene expression that result from genetic perturbations can be defined for specific developmental windows. Additionally, protein level, stability, and/or posttranslational modification state during a particular stage of follicle development can be examined through western blot analyses. Thus, stage-specific isolation of Drosophila follicles provides a rich source of information into widely conserved processes of development and morphogenesis. PMID:24326735

Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

PubMed Central

Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W.; Marschalek, Rolf; Menéndez, Pablo

2015-01-01

Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a “multiple-and-sequential-hit” model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one “big-hit” might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

Constructing Sexuality and Identity in an Online Teen Chat Room

ERIC Educational Resources Information Center

Subrahmanyam, K.; Greenfield, P. M.; Tynes, B.

2004-01-01

In this article, we propose that adolescents' online interactions are both a literal and a metaphoric screen for representing major adolescent developmental issues, such as sexuality and identity. Because of the public nature of Internet chat rooms, they provide an open window into the expression of adolescent concerns. Our study utilizes this…

Neuroimaging: A Window to the Neurological Foundations of Learning and Behavior in Children.

ERIC Educational Resources Information Center

Lyon, G. Reid, Ed.; Rumsey, Judith M., Ed.

This book presents 11 papers on the use of neuroimaging technology in brain-related disorders. The text contains full-color neuroimaging scans and provides both theoretical and methodological explanations of the various neuroimaging techniques and their application to developmental disorders in children. The papers are grouped into three sections,…

HIGH-CONTENT ANALYSIS OF PRIMARY RAT NEURAL CORTICALCULTURES FOR DEVELOPMENTAL NEUROTOXICITY SCREENING

EPA Science Inventory

Development of the vertebrate nervous system proceeds through a number of critical processes, ultimately concluding with the extension of neurites and establishment of synaptic networks. Early-life exposure to toxicants that perturb these critical developmental processes can po...

Lateral Root Initiation in Arabidopsis: Developmental Window, Spatial Patterning, Density and Predictability

PubMed Central

DUBROVSKY, J. G.; GAMBETTA, G. A.; HERNÁNDEZ-BARRERA, A.; SHISHKOVA, S.; GONZÁLEZ, I.

2006-01-01

• Background and Aims The basic regulatory mechanisms that control lateral root (LR) initiation are still poorly understood. An attempt is made to characterize the pattern and timing of LR initiation, to define a developmental window in which LR initiation takes place and to address the question of whether LR initiation is predictable. • Methods The spatial patterning of LRs and LR primordia (LRPs) on cleared root preparations were characterized. New measures of LR and LRP densities (number of LRs and/or LRPs divided by the length of the root portions where they are present) were introduced and illustrate the shortcomings of the more customarily used measure through a comparative analysis of the mutant aux1-7. The enhancer trap line J0121 was used to monitor LR initiation in time-lapse experiments and a plasmolysis-based method was developed to determine the number of pericycle cells between successive LRPs. • Key Results LRP initiation occurred strictly acropetally and no de novo initiation events were found between already developed LRs or LRPs. However, LRPs did not become LRs in a similar pattern. The longitudinal spacing of lateral organs was variable and the distance between lateral organs was proportional to the number of cells and the time between initiations of successive LRPs. There was a strong tendency towards alternation in LR initiation between the two pericycle cell files adjacent to the protoxylem poles. LR density increased with time due to the emergence of slowly developing LRPs and appears to be unique for individual Arabidopsis accessions. • Conclusions. In Arabidopsis there is a narrow developmental window for LR initiation, and no specific cell-count or distance-measuring mechanisms have been found that determine the site of successive initiation events. Nevertheless, the branching density and lateral organ density (density of LRs and LRPs) are accession-specific, and based on the latter density the average distance between successive LRs can be predicted. PMID:16390845

Ontogeny and Regulation of the Serotonin Transporter: Providing Insights into Human Disorders

PubMed Central

Daws, Lynette C.; Gould, Georgianna G.

2011-01-01

Serotonin (5-hydroxytryptamine, 5-HT) was one of the first neurotransmitters for which a role in development was identified. Pharmacological and gene knockout studies have revealed a critical role for 5-HT in numerous processes, including cell division, neuronal migration, differentiation and synaptogenesis. An excess in brain 5-HT appears to be mechanistically linked to abnormal brain development, which in turn is associated with neurological disorders. Ambient levels of 5-HT are controlled by a vast orchestra of proteins, including a multiplicity of pre- and post-synaptic 5-HT receptors, heteroreceptors, enzymes and transporters. The 5-HT transporter (SERT, 5-HTT) is arguably the most powerful regulator of ambient extracellular 5-HT. SERT is the high-affinity uptake mechanism for 5-HT and exerts tight control over the strength and duration of serotonergic neurotransmission. Perturbation of its expression level or function has been implicated in many diseases, prominent among them are psychiatric disorders. This review synthesizes existing information on the ontogeny of SERT during embryonic and early postnatal development though adolescence, along with factors that influence its expression and function during these critical developmental windows. We integrate this knowledge to emphasize how inappropriate SERT expression or its dysregulation may be linked to the pathophysiology of psychiatric, cardiovascular and gastrointestinal diseases. PMID:21447358

Approaches and considerations for the assessment of immunotoxicity for environmental chemicals: a workshop summary.

PubMed

Boverhof, Darrell R; Ladics, Greg; Luebke, Bob; Botham, Jane; Corsini, Emanuela; Evans, Ellen; Germolec, Dori; Holsapple, Michael; Loveless, Scott E; Lu, Haitian; van der Laan, Jan Willem; White, Kimber L; Yang, Yung

2014-02-01

As experience is gained with toxicology testing and as new assays and technologies are developed, it is critical for stakeholders to discuss opportunities to advance our overall testing strategies. To facilitate these discussions, a workshop on practices for assessing immunotoxicity for environmental chemicals was held with the goal of sharing perspectives on immunotoxicity testing strategies and experiences, developmental immunotoxicity (DIT), and integrated and alternative approaches to immunotoxicity testing. Experiences across the chemical and pharmaceutical industries suggested that standard toxicity studies, combined with triggered-based testing approaches, represent an effective and efficient approach to evaluate immunotoxic potential. Additionally, discussions on study design, critical windows, and new guideline approaches and experiences identified important factors to consider before initiating DIT evaluations including assay choice and timing and the impact of existing adult data. Participants agreed that integrating endpoints into standard repeat-dose studies should be considered for fulfilling any immunotoxicity testing requirements, while also maximizing information and reducing animal use. Participants also acknowledged that in vitro evaluation of immunosuppression is complex and may require the use of multiple assays that are still being developed. These workshop discussions should contribute to developing an effective but more resource and animal efficient approach for evaluating chemical immunotoxicity. Copyright © 2013 Elsevier Inc. All rights reserved.

MYSTERIES OF THE HUMAN FETUS REVEALED.

PubMed

Sandman, Curt A

2015-09-01

The impressive program of research from the DiPietro laboratory succeeds in its aim to document the ontogeny of human fetal neurobehavioral development. From studies of great depth and breadth, and wielding creative methods of assessment, DiPietro et al. open a window into the largely inaccessible developing human fetal brain. This commentary, with reference to the seminal cardiovascular studies of the Laceys, supports the measures of the fetal heart to index fetal well-being and to provide evidence of stimulus processing. A separate case is made that the DiPietro program provides unique and invaluable information for assessing the influential Developmental Origins of Health and Disease or Fetal Programming Models. The goal of these models, to predict or understand the influences of early experience or response patterns on later postnatal life, is identical to the ultimate goal of the DiPietro program. Because human fetal behavior is uncontaminated by socialization or parenting or peers, it may be the best reflection of fetal exposures. The remarkable neurobehavioral profiles generated by the DiPietro program can make a critical contribution to the Fetal Programming Model in terms of sensitive and critical periods of nervous system vulnerability and to specify gestational periods of neurobehavioral risk. © 2015 The Society for Research in Child Development, Inc.

Sleep Is Overrated: The Developmental Education Innovative Research Imperative

ERIC Educational Resources Information Center

Burley, Hansel

2008-01-01

Developmental education sits at the nexus of all things educational, yet developmental education research seems asleep, unaware of the valuable and critical perspectives the field can provide. In that light, this article addresses the developmental education identity crisis addressed by Arendale (2005) in "Terms of Endearment,"…

A Motor-Skills Programme to Enhance Visual Motor Integration of Selected Pre-School Learners

ERIC Educational Resources Information Center

Africa, Eileen K.; van Deventer, Karel J.

2017-01-01

Pre-schoolers are in a window period for motor skill development. Visual-motor integration (VMI) is the foundation for academic and sport skills. Therefore, it must develop before formal schooling. This study attempted to improve VMI skills. VMI skills were measured with the "Beery-Buktenica developmental test of visual-motor integration 6th…

The use of computational inspection to identify process window limiting hotspots and predict sub-15nm defects with high capture rate

NASA Astrophysics Data System (ADS)

Ham, Boo-Hyun; Kim, Il-Hwan; Park, Sung-Sik; Yeo, Sun-Young; Kim, Sang-Jin; Park, Dong-Woon; Park, Joon-Soo; Ryu, Chang-Hoon; Son, Bo-Kyeong; Hwang, Kyung-Bae; Shin, Jae-Min; Shin, Jangho; Park, Ki-Yeop; Park, Sean; Liu, Lei; Tien, Ming-Chun; Nachtwein, Angelique; Jochemsen, Marinus; Yan, Philip; Hu, Vincent; Jones, Christopher

2017-03-01

As critical dimensions for advanced two dimensional (2D) DUV patterning continue to shrink, the exact process window becomes increasingly difficult to determine. The defect size criteria shrink with the patterning critical dimensions and are well below the resolution of current optical inspection tools. As a result, it is more challenging for traditional bright field inspection tools to accurately discover the hotspots that define the process window. In this study, we use a novel computational inspection method to identify the depth-of-focus limiting features of a 10 nm node mask with 2D metal structures (single exposure) and compare the results to those obtained with a traditional process windows qualification (PWQ) method based on utilizing a focus modulated wafer and bright field inspection (BFI) to detect hotspot defects. The method is extended to litho-etch litho-etch (LELE) on a different test vehicle to show that overlay related bridging hotspots also can be identified.

Comparing rat and rabbit embryo-fetal developmental toxicity studies for 379 pharmaceuticals: On systemic dose and developmental effects (Critical Reviews in Toxicology)

EPA Science Inventory

A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental adverse ef...

The mammalian respiratory system and critical windows of exposure for children's health.

PubMed Central

Pinkerton, K E; Joad, J P

2000-01-01

The respiratory system is a complex organ system composed of multiple cell types involved in a variety of functions. The development of the respiratory system occurs from embryogenesis to adult life, passing through several distinct stages of maturation and growth. We review embryonic, fetal, and postnatal phases of lung development. We also discuss branching morphogenesis and cellular differentiation of the respiratory system, as well as the postnatal development of xenobiotic metabolizing systems within the lungs. Exposure of the respiratory system to a wide range of chemicals and environmental toxicants during perinatal life has the potential to significantly affect the maturation, growth, and function of this organ system. Although the potential targets for exposure to toxic factors are currently not known, they are likely to affect critical molecular signals expressed during distinct stages of lung development. The effects of exposure to environmental tobacco smoke during critical windows of perinatal growth are provided as an example leading to altered cellular and physiological function of the lungs. An understanding of critical windows of exposure of the respiratory system on children's health requires consideration that lung development is a multistep process and cannot be based on studies in adults. Images Figure 1 Figure 4 PMID:10852845

Bird-Window Collisions at a West-Coast Urban Park Museum: Analyses of Bird Biology and Window Attributes from Golden Gate Park, San Francisco.

PubMed

Kahle, Logan Q; Flannery, Maureen E; Dumbacher, John P

2016-01-01

Bird-window collisions are a major and poorly-understood generator of bird mortality. In North America, studies of this topic tend to be focused east of the Mississippi River, resulting in a paucity of data from the Western flyways. Additionally, few available data can critically evaluate factors such as time of day, sex and age bias, and effect of window pane size on collisions. We collected and analyzed 5 years of window strike data from a 3-story building in a large urban park in San Francisco, California. To evaluate our window collision data in context, we collected weekly data on local bird abundance in the adjacent parkland. Our study asks two overarching questions: first-what aspects of a bird's biology might make them more likely to fatally strike windows; and second, what characteristics of a building's design contribute to bird-window collisions. We used a dataset of 308 fatal bird strikes to examine the relationships of strikes relative to age, sex, time of day, time of year, and a variety of other factors, including mitigation efforts. We found that actively migrating birds may not be major contributors to collisions as has been found elsewhere. We found that males and young birds were both significantly overrepresented relative to their abundance in the habitat surrounding the building. We also analyzed the effect of external window shades as mitigation, finding that an overall reduction in large panes, whether covered or in some way broken up with mullions, effectively reduced window collisions. We conclude that effective mitigation or design will be required in all seasons, but that breeding seasons and migratory seasons are most critical, especially for low-rise buildings and other sites away from urban migrant traps. Finally, strikes occur throughout the day, but mitigation may be most effective in the morning and midday.

Bird-Window Collisions at a West-Coast Urban Park Museum: Analyses of Bird Biology and Window Attributes from Golden Gate Park, San Francisco

PubMed Central

Kahle, Logan Q.; Flannery, Maureen E.; Dumbacher, John P.

2016-01-01

Bird-window collisions are a major and poorly-understood generator of bird mortality. In North America, studies of this topic tend to be focused east of the Mississippi River, resulting in a paucity of data from the Western flyways. Additionally, few available data can critically evaluate factors such as time of day, sex and age bias, and effect of window pane size on collisions. We collected and analyzed 5 years of window strike data from a 3-story building in a large urban park in San Francisco, California. To evaluate our window collision data in context, we collected weekly data on local bird abundance in the adjacent parkland. Our study asks two overarching questions: first–what aspects of a bird’s biology might make them more likely to fatally strike windows; and second, what characteristics of a building’s design contribute to bird-window collisions. We used a dataset of 308 fatal bird strikes to examine the relationships of strikes relative to age, sex, time of day, time of year, and a variety of other factors, including mitigation efforts. We found that actively migrating birds may not be major contributors to collisions as has been found elsewhere. We found that males and young birds were both significantly overrepresented relative to their abundance in the habitat surrounding the building. We also analyzed the effect of external window shades as mitigation, finding that an overall reduction in large panes, whether covered or in some way broken up with mullions, effectively reduced window collisions. We conclude that effective mitigation or design will be required in all seasons, but that breeding seasons and migratory seasons are most critical, especially for low-rise buildings and other sites away from urban migrant traps. Finally, strikes occur throughout the day, but mitigation may be most effective in the morning and midday. PMID:26731417

Exploring Shop Window Displays

ERIC Educational Resources Information Center

Christopoulou, Martha

2011-01-01

Using visual resources from everyday life in art lessons can enrich students' knowledge about the creation of visual images, artifacts, and sites, and develop their critical understanding about the cultural impact of these images and their effects on people's lives. Through examining an exhibition in the windows of Selfridges department store in…

Cortical Development, Plasticity and Re-Organization in Children with Cochlear Implants

ERIC Educational Resources Information Center

Sharma, Anu; Nash, Amy A.; Dorman, Michael

2009-01-01

A basic tenet of developmental neurobiology is that certain areas of the cortex will re-organize, if appropriate stimulation is withheld for long periods. Stimulation must be delivered to a sensory system within a narrow window of time (a sensitive period) if that system is to develop normally. In this article, we will describe age cut-offs for a…

Active two-phase cooling of an IR window for a hypersonic interceptor

NASA Astrophysics Data System (ADS)

Burzlaff, B. H.; Chivian, Jay S.; Cotten, W. D.; Hemphill, R. B.; Huhlein, Michael A.

1993-06-01

A novel actively cooled window for an IR sensor on a hypersonic interceptor is envisioned which achieves an IR window with high transmittance, low emittance, and low image distortion under high aerodynamic heat flux. The cooling concept employs two-phase convective boiling of liquid ammonia. Coolant is confined to narrow, parallel channels within the window to minimize obscuration of the aperture. The high latent heat of vaporization of ammonia minimizes coolant mass-flow requirements. Low boiling temperatures at projected operating pressures promote high thermal conductivity and low emissivity in the window. The concept was tested with thermal measurements on sub-mm width coolant channels in Si. High values for heat transfer coefficient and critical heat flux were obtained. Thermal gradients within the window can be controlled by the coolant channel configuration. Design options are investigated by predicting the effect of aerodynamic heat flux on the image produced by an IR sensor with a cooled window. Ammonia-cooled IR windows will function in the anticipated aerothermal environment.

Developmental issues in underage drinking research.

PubMed

To better understand underage drinking and how it can be prevented, research is being conducted in a wide variety of disciplines--focusing on aspects such as risk and protective factors, biological processes underlying human development, and the impact of socioenvironmental and pharmacologic influences on these mechanisms. This article examines underage drinking from a developmental perspective, which seeks to identify critical developmental periods during which interventions may be especially useful. These critical periods can provide key opportunities to redirect the course of development and alter the life course trajectory of the individual.

A developmental perspective on congenital muscular torticollis: a critical appraisal of the evidence.

PubMed

Tessmer, Angela; Mooney, Paula; Pelland, Lucie

2010-01-01

The aims of this review were to (1) identify and evaluate research evidence regarding the developmental outcomes of infants with congenital muscular torticollis (CMT) and (2) critically appraise and compare the outcomes of interventions targeting neck muscle extensibility and strength with those considering neck muscle function within the broader context of global infant development. An association between CMT and early developmental delay is supported by levels 3B, 4, and 5 evidence; no evidence was found of longer-term influences of CMT on the development of perceptual, cognitive, and motor skills. The effectiveness of passive manual stretching is supported by levels 2A, 3B, 4, and 5 evidence; no clear evidence was found of the effectiveness of developmentally supportive interventions. Controlled studies are needed to clarify the developmental consequences of CMT.

Research Review: A Critical Review of Studies on the Developmental Trajectories of Antisocial Behavior in Females

ERIC Educational Resources Information Center

Fontaine, Nathalie; Carbonneau, Rene; Vitaro, Frank; Barker, Edward D.; Tremblay, Richard E.

2009-01-01

Background: Knowledge on the onset and the development of antisocial behavior in females is limited, because most of the research in this domain is based on males. Methods: We critically reviewed 46 empirical studies that examined developmental trajectories of antisocial behavior in females, notably to help determine whether or not an…

Deep Processing Strategies and Critical Thinking: Developmental Trajectories Using Latent Growth Analyses

ERIC Educational Resources Information Center

Phan, Huy P.

2011-01-01

The author explored the developmental courses of deep learning approach and critical thinking over a 2-year period. Latent growth curve modeling (LGM) procedures were used to test and trace the trajectories of both theoretical frameworks over time. Participants were 264 (119 women, 145 men) university undergraduates. The Deep Learning subscale of…

The Impact of Chess Instruction on the Critical Thinking Ability and Mathematical Achievement of Developmental Mathematics Students

ERIC Educational Resources Information Center

Berkley, Darrin K.

2012-01-01

This sequential explanatory mixed-methods study determined whether the game of chess can be used as an educational tool to improve critical thinking skills of developmental mathematics students and improve mathematics achievement for these students. Five research questions were investigated. These questions were as follows: (a) Is there a…

Do convergent developmental mechanisms underlie convergent phenotypes?

NASA Technical Reports Server (NTRS)

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.

Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study

PubMed Central

Longhi, M. Paula; Hoti, Mimoza; Patel, Minal B.; O’Dwyer, Michael; Nourshargh, Sussan; Barnes, Michael R.; Brohi, Karim

2017-01-01

Background Severe trauma induces a widespread response of the immune system. This “genomic storm” can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways. We postulated that the hyperacute window after trauma may hold the key to understanding how the genomic storm is initiated and may lead to a new understanding of the pathogenesis of MODS. Methods and findings We performed whole blood transcriptome and flow cytometry analyses on a total of 70 critically injured patients (Injury Severity Score [ISS] ≥ 25) at The Royal London Hospital in the hyperacute time period within 2 hours of injury. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS ≤ 4). We then performed flow cytometry analyses in 34 critically injured patients and compared findings with those of 9 healthy volunteers. Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21%) were differentially expressed compared to the hyperacute window. Only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury. Pathway analysis showed principally up-regulation of pattern recognition and innate inflammatory pathways, with down-regulation of adaptive responses. Immune deconvolution, flow cytometry, and modular analysis suggested a central role for neutrophils and Natural Killer (NK) cells, with underexpression of T- and B cell responses. In the transcriptome cohort, 20 critically injured patients later developed MODS. Compared with the 16 patients who did not develop MODS (NoMODS), maximal differential expression was seen within the hyperacute window. In MODS versus NoMODS, 363 genes were differentially expressed on admission, compared to only 33 at 24 hours postinjury. MODS transcripts differentially expressed in the hyperacute window showed enrichment among diseases and biological functions associated with cell survival and organismal death rather than inflammatory pathways. There was differential up-regulation of NK cell signalling pathways and markers in patients who would later develop MODS, with down-regulation of neutrophil deconvolution markers. This study is limited by its sample size, precluding more detailed analyses of drivers of the hyperacute response and different MODS phenotypes, and requires validation in other critically injured cohorts. Conclusions In this study, we showed how the hyperacute postinjury time window contained a focused, specific signature of the response to critical injury that led to widespread genomic activation. A transcriptomic signature for later development of MODS was present in this hyperacute window; it showed a strong signal for cell death and survival pathways and implicated NK cells and neutrophil populations in this differential response. PMID:28715416

Modulation of Perineuronal Nets and Parvalbumin with Developmental Song Learning

PubMed Central

Balmer, Timothy S.; Carels, Vanessa M.; Frisch, Jillian L.; Nick, Teresa A.

2009-01-01

Neural circuits and behavior are shaped during developmental phases of maximal plasticity known as sensitive or critical periods. Neural correlates of sensory critical periods have been identified, but their roles remain unclear. Factors that define critical periods in sensorimotor circuits and behavior are not known. Birdsong learning in the zebra finch occurs during a sensitive period similar to that for human speech. We now show that perineuronal nets, which correlate with sensory critical periods, surround parvalbumin-positive neurons in brain areas that are dedicated to singing. The percentage of both total and parvalbumin-positive neurons with perineuronal nets increased with development. In HVC (this acronym is the proper name), a song area important for sensorimotor integration, the percentage of parvalbumin neurons with perineuronal nets correlated with song maturity. Shifting the vocal critical period with tutor song deprivation decreased the percentage of neurons that were parvalbumin positive and the relative staining intensity of both parvalbumin and a component of perineuronal nets. Developmental song learning shares key characteristics with sensory critical periods, suggesting shared underlying mechanisms. PMID:19828802

Sleep Deprivation During Early-Adult Development Results in Long-Lasting Learning Deficits in Adult Drosophila

PubMed Central

Seugnet, Laurent; Suzuki, Yasuko; Donlea, Jeff M.; Gottschalk, Laura; Shaw, Paul J.

2011-01-01

Study Objectives: Multiple lines of evidence indicate that sleep is important for the developing brain, although little is known about which cellular and molecular pathways are affected. Thus, the aim of this study was to determine whether the early adult life of Drosophila, which is associated with high amounts of sleep and critical periods of brain plasticity, could be used as a model to identify developmental processes that require sleep. Subjects: Wild type Canton-S Drosophila melanogaster. Design; Intervention: Flies were sleep deprived on their first full day of adult life and allowed to recover undisturbed for at least 3 days. The animals were then tested for short-term memory and response-inhibition using aversive phototaxis suppression (APS). Components of dopamine signaling were further evaluated using mRNA profiling, immunohistochemistry, and pharmacological treatments. Measurements and Results: Flies exposed to acute sleep deprivation on their first day of life showed impairments in short-term memory and response inhibition that persisted for at least 6 days. These impairments in adult performance were reversed by dopamine agonists, suggesting that the deficits were a consequence of reduced dopamine signaling. However, sleep deprivation did not impact dopaminergic neurons as measured by their number or by the levels of dopamine, pale (tyrosine hydroxylase), dopadecarboxylase, and the Dopamine transporter. However, dopamine pathways were impacted as measured by increased transcript levels of the dopamine receptors D2R and dDA1. Importantly, blocking signaling through the dDA1 receptor in animals that were sleep deprived during their critical developmental window prevented subsequent adult learning impairments. Conclusions: These data indicate that sleep plays an important and phylogenetically conserved role in the developing brain. Citation: Seugnet L; Suzuki Y; Donlea JM; Gottschalk L; Shaw PJ. Sleep deprivation during early-adult development results in long-lasting learning deficits in adult drosophila. SLEEP 2011;34(2):137-146. PMID:21286249

Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.

PubMed

Doll, Caleb A; Broadie, Kendal

2016-05-01

Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early-use critical period. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation Theory for Developmental Mathematics Practitioners

ERIC Educational Resources Information Center

Duranczyk, Irene Mary

2007-01-01

This article is designed to present an overview of critical theory, research, and evaluation for the developmental mathematics educator. Students caught in the gap between high school mathematics preparation and entry-level college mathematics expectations--developmental mathematics education students--need to have their personal narratives told…

Transient Overexposure of Neuregulin 3 during Early Postnatal Development Impacts Selective Behaviors in Adulthood

PubMed Central

Paterson, Clare; Law, Amanda J.

2014-01-01

Neuregulin 3 (NRG3), a specific ligand for ErbB4 and a neuronal-enriched neurotrophin is implicated in the genetic predisposition to a broad spectrum of neurodevelopmental, neurocognitive and neuropsychiatric disorders, including Alzheimer's disease, autism and schizophrenia. Genetic studies in schizophrenia demonstrate that risk variants in NRG3 are associated with cognitive and psychotic symptom severity, accompanied by increased expression of prefrontal cortical NRG3. Despite our expanding knowledge of genetic involvement of NRG3 in neurological disorders, little is known about the neurodevelopmental mechanisms of risk. Here we exploited the fact that a paralog of NRG3, NRG1, readily penetrates the murine blood brain barrier (BBB). In this study we synthesized the bioactive epidermal growth factor (EGF) domain of NRG3, and using previously validated in-vivo peripheral injection methodologies in neonatal mice, demonstrate that NRG3 successfully crosses the BBB, where it activates its receptor ErbB4 and downstream Akt signaling at levels of bioactivity comparable to NRG1. To determine the impact of NRG3 overexpression during one critical developmental window, C57BL/6 male mice were subcutaneously injected daily with NRG1-EGF, NRG3-EGF or vehicle from postnatal days 2–10. Mice were tested in adulthood using a comprehensive battery of behavioral tasks relevant to neurocognitive and psychiatric disorders. In agreement with previous studies, developmental overexposure to NRG1 induced multiple non-CNS mediated peripheral effects as well as severely disrupting performance of prepulse inhibition of the startle response. In contrast, NRG3 had no effect on any peripheral measures investigated or sensorimotor gating. Specifically, developmental NRG3 overexposure produced an anxiogenic-like phenotype and deficits in social behavior in adulthood. These results provide primary data to support a role for NRG3 in brain development and function, which appears to be distinct from its paralog NRG1. Furthermore we demonstrate how perturbations in NRG3 expression at distinct developmental stages may contribute to the neurological deficits observed in brain disorders such as schizophrenia and autism. PMID:25093331

Peripartum Antibiotics Promote Gut Dysbiosis, Loss of Immune Tolerance, and Inflammatory Bowel Disease in Genetically Prone Offspring.

PubMed

Miyoshi, Jun; Bobe, Alexandria M; Miyoshi, Sawako; Huang, Yong; Hubert, Nathaniel; Delmont, Tom O; Eren, A Murat; Leone, Vanessa; Chang, Eugene B

2017-07-11

Factors affecting the developing neonatal gut microbiome and immune networks may increase the risk of developing complex immune disorders such as inflammatory bowel diseases (IBD). In particular, peripartum antibiotics have been suggested as risk factors for human IBD, although direct evidence is lacking. Therefore, we examined the temporal impact of the commonly used antibiotic cefoperazone on both maternal and offspring microbiota when administered to dams during the peripartum period in the IL-10-deficient murine colitis model. By rigorously controlling for cage, gender, generational, and murine pathobiont confounders, we observed that offspring from cefoperazone-exposed dams develop a persistent gut dysbiosis into adulthood associated with skewing of the host immune system and increased susceptibility to spontaneous and chemically dextran sodium sulfate (DSS)-induced colitis. Thus, early life exposure to antibiotic-induced maternal dysbiosis during a critical developmental window for gut microbial assemblage and immune programming elicits a lasting impact of increased IBD risk on genetically susceptible offspring. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Prenatal stress in birds: pathways, effects, function and perspectives.

PubMed

Henriksen, Rie; Rettenbacher, Sophie; Groothuis, Ton G G

2011-06-01

Although most work on prenatal stress has been conducted on mammalian species, birds provide useful alternative models since avian embryos develop outside the mother's body in a concealed environment, the egg, which is produced during a short time window of 4-14 days. This facilitates measurement of maternal substances provided for and manipulation of the embryo without interfering with the mother's physiology. We critically review prenatal corticosterone mediated effects in birds by reviewing both studies were females had elevated levels of plasma corticosterone during egg formation and studies applying corticosterone injections directly into the egg. A selected review of the mammalian literature is used as background. The results suggest that besides prenatal exposure to corticosterone itself, maternal corticosterone affects offspring's behaviour and physiology via alteration of other egg components. However, results are inconsistent, perhaps due to the interaction with variation in the post-natal environment, sex, age, developmental mode and details of treatment. The potential role of adaptive maternal programming has not been tested adequately and suggestions for future research are discussed. Copyright © 2011. Published by Elsevier Ltd.

Maternal di-(2-ethylhexyl) phthalate exposure during pregnancy causes fetal growth restriction in a stage-specific but gender-independent manner.

PubMed

Shen, Ru; Zhao, Ling-Li; Yu, Zhen; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Zhang, Zhi-Hui; Xu, De-Xiang

2017-01-01

Di (2-ethylhexyl) phthalate (DEHP) is male developmental toxicant that impairs testis development with reduced anogenital distance. The present study aimed to investigate whether maternal DEHP exposure during pregnancy causes intrauterine growth restriction (IUGR) in a gender-specific manner and to identify the critical window of DEHP-induced fetal IUGR. Pregnant mice were administered with DEHP (0, 50 or 200mg/kg) by gavage. Fetal IUGR was observed not only in males but also in females when litters were exposed to DEHP on gestational day (GD)0-GD17. Interestingly, fetal weight and crown-rump length were reduced, markedly in dams with DEHP on GD13-GD17, slightly in dams with on GD7-GD12, but not in dams with on GD0-GD6. Further analysis showed that maternal DEHP exposure on GD7-GD12 inhibited cell proliferation, lowered placental weight, and reduced blood sinusoid area in placental labyrinth layer. These results suggest that maternal DEHP exposure induces IUGR in a stage-specific but gender-independent manner. Copyright © 2016 Elsevier Inc. All rights reserved.

A developmental-psychobiological approach to developmental neuropsychology.

PubMed

Michel, G F

2001-01-01

Although both developmental psychobiology and developmental neuropsychology examine the interface between biological and psychological processes, they differ in conceptual framework. This article argues for the incorporation into developmental neuropsychology of certain aspects of the conceptual framework of developmental psychobiology. Three principles of dynamic psychobiological interaction are described and applied to four issues in neuropsychology (handedness, sex differences in behavior, critical periods, and modularity of structure-function relations). Then, it is proposed that developmental psychobiology can make four direct contributions to developmental neuropsychology. Finally, it is argued that the value of the conceptual framework provided by developmental psychobiology depends, in part, on how well it translates into procedures that can be applied in the clinical settings of the developmental neuropsychologist.

Proper Installation of Replacement Windows | Efficient Windows

Science.gov Websites

. Quality installation is critical for an airtight fit and a continuous water barrier to prevent drafts , water damage and condensation. The complexity of the installation depends on whether you are considering and specifications. Install level, plumb, and square. Install water tight: water must be prevented

Using multimedia technology to help combat the negative effects of protective isolation on patients: the Open Window project--an engineering challenge.

PubMed

Hegarty, F; Roche, D; McCabe, C; McCann, S

2009-01-01

The Open Window project was established with the aim of creating a "virtual window" for each patient who is confined to protective isolation due to treatment for illness. This virtual window as developed provides a range of media or experiences. This paper describes the approach taken to the system design and discusses initial experiences with implementing such a system in a critical care setting. The system design was predicated on two guiding principles. Firstly it should be intuitive to use and the technology used to create the virtual window hidden from patient view. Secondly the system must be able to be installed at the point of care in a way that delivers the experience under the patient's control, without compromising the function or safety of the clinical environment. Patient acceptance of the system is being measured as part of an on-going trial and at this interim phase of data analysis 100% (n=55) of participants in the intervention group have reported that the technology was easy to use. We conclude that the system as designed and installed is an effective, robust and reliable system upon which to base a multimedia interventions in a critical care room.

Environmental factors associated with a spectrum of neurodevelopmental deficits.

PubMed

Mendola, Pauline; Selevan, Sherry G; Gutter, Suzanne; Rice, Deborah

2002-01-01

A number of environmental agents have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. Critical windows of vulnerability to the effects of these agents occur both pre- and postnatally. The nervous system is relatively unique in that different parts are responsible for different functional domains, and these develop at different times (e.g., motor control, sensory, intelligence and attention). In addition, the many cell types in the brain have different windows of vulnerability with varying sensitivities to environmental agents. This review focuses on two environmental agents, lead and methylmercury, to illustrate the neurobehavioral and cognitive effects that can result from early life exposures. Special attention is paid to distinguishing between the effects detected following episodes of poisoning and those detected following lower dose exposures. Perinatal and childhood exposure to high doses of lead results in encephalopathy and convulsions. Lower-dose lead exposures have been associated with impairment in intellectual function and attention. At high levels of prenatal exposure, methylmercury produces mental retardation, cerebral palsy and visual and auditory deficits in children of exposed mothers. At lower levels of methylmercury exposure, the effects in children have been more subtle. Other environmental neurotoxicants that have been shown to produce developmental neurotoxicity include polychlorinated biphenyls (PCBs), dioxins, pesticides, ionizing radiation, environmental tobacco smoke, and maternal use of alcohol, tobacco, marijuana and cocaine. Exposure to environmental agents with neurotoxic effects can result in a spectrum of adverse outcomes from severe mental retardation and disability to more subtle changes in function depending on the timing and dose of the chemical agent. Copyright 2002 Wiley-Liss, Inc.

Laser-induced damage and fracture in fused silica vacuum windows

NASA Astrophysics Data System (ADS)

Campbell, John H.; Hurst, Patricia A.; Heggins, Dwight D.; Steele, William A.; Bumpas, Stanley E.

1997-05-01

Laser induced damage, that initiates catastrophic fracture, has been observed in large, fused silica lenses that also serve as vacuum barriers in high-fluence positions on the Nova and Beamlet lasers. In nearly all cases damage occurs on the vacuum side of the lens. The damage can lead to catastrophic crack growth if the flaw size exceeds the critical flaw size for SiO2. If the elastic stored energy in the lens in high enough, the lens will fracture into many pieces resulting in an implosion. The consequences of such an implosion can be severe, particularly for large vacuum systems. Three parameters control the degree of fracture in the vacuum barrier window: (1) the elastic stored energy, (2) the ratio of the window thickness to flaw depth and (3) secondary crack propagation. Fracture experiments have ben carried our on 15-cm diameter fused silica windows that contain surface flaws caused by laser damage. The results of these experiments, combined with data from window failures on Beamlet and Nova have been sued to develop design criteria for a 'fail-safe' lens. Specifically the window must be made thick enough such that the peak tensile stress is less than 500 psi and the corresponding ratio of the thickness to critical flaw size is less than 6. Under these conditions a properly mounted window, upon failure, will break into only tow pieces and will not implode. One caveat to these design criteria is that the air leak through the window before secondary crack growth occurs. Finite element stress calculations of a window before and immediately following fracture into two pieces show that the elastic stored energy is redistributed if the fragments 'lock' in place and thereby bridge the opening. In such cases, the peak stresses at the flaw site can increase leading to further crack growth.

Adolescent Sex and Mass Media: A Developmental Approach.

ERIC Educational Resources Information Center

Chapin, John R.

2000-01-01

Media critics point to adolescents' exposure to "sexy" television and popular music. Developmental transitions lead to increased information seeking, and developmental tasks force adolescents to find information sources other than their parents, implying a link between sexy media and adolescent development. Media research informed by knowledge of…

Neuropsychological basic deficits in preschoolers at risk for ADHD: a meta-analysis.

PubMed

Pauli-Pott, Ursula; Becker, Katja

2011-06-01

Widely accepted neuropsychological theories on attention deficit hyperactivity disorder (ADHD) assume that the complex symptoms of the disease arise from developmentally preceding neuropsychological basic deficits. These deficits in executive functions and delay aversion are presumed to emerge in the preschool period. The corresponding normative developmental processes include phases of relative stability and rapid change. These non-linear developmental processes might have implications for concurrent and predictive associations between basic deficits and ADHD symptoms. To derive a description of the nature and strength of these associations, a meta-analysis was conducted. It is assumed that weighted mean effect sizes differ between basic deficits and depend on age. The meta-analysis included 25 articles (n=3005 children) in which associations between assessments of basic deficits (i.e. response inhibition, interference control, delay aversion, working memory, flexibility, and vigilance/arousal) in the preschool period and concurrent or subsequent ADHD symptoms or diagnosis of ADHD had been analyzed. For response inhibition and delay aversion, mean effect sizes were of medium to large magnitude while the mean effect size for working memory was small. Meta-regression analyses revealed that effect sizes of delay aversion tasks significantly decreased with increasing age while effect sizes of interference control tasks and Continuous Performance Tests (CPTs) significantly increased. Depending on the normative maturational course of each skill, time windows might exist that allow for a more or less valid assessment of a specific deficit. In future research these time windows might help to describe early developing forms of ADHD and to identify children at risk. Copyright © 2011 Elsevier Ltd. All rights reserved.

Age Differences in Prenatal Testosterone's Protective Effects on Disordered Eating Symptoms: Developmental Windows of Expression?

PubMed Central

Culbert, Kristen M.; Breedlove, S. Marc; Sisk, Cheryl L.; Keel, Pamela K.; Neale, Michael C.; Boker, Steven M.; Burt, S. Alexandra; Klump, Kelly L.

2015-01-01

Prenatal testosterone exposure may be protective against disordered eating. However, prior studies have produced mixed results. Developmental differences in prenatal testosterone's protective effects on disordered eating may explain these discrepancies. Indeed, studies have differed in the age of participants assessed, with data supporting prenatal testosterone effects on disordered eating in early adolescent and young adult samples but not in late adolescence. The present series of studies are the first to investigate age differences in prenatal testosterone's protective effects on disordered eating. Two indirect markers of higher prenatal testosterone were examined: 1) lower finger-length ratios [index (2D)/ring (4D) finger] (Study 1), and 2) lower disordered eating in females from opposite-sex twin pairs (who are thought to be exposed to higher prenatal testosterone from their male co-twin) relative to female controls (Study 2). Participants were twins from the Michigan State University Twin Registry (Study 1: n = 409; Study 2: n = 1,538) in early adolescence, late adolescence, or young adulthood. Disordered eating was assessed with well-validated questionnaires. Finger-length ratios were measured from hand scans, using electronic computer calipers. Findings were consistent across both studies. Higher prenatal testosterone (lower 2D:4D; females from opposite-sex twin pairs vs. controls) predicted lower disordered eating in early adolescence and young adulthood only. Prenatal testosterone-disordered eating associations were not observed during late adolescence. Results point to the possibility of developmental windows of expression for prenatal testosterone's protective effects on disordered eating and suggest that prior discrepant results may reflect age differences across samples. PMID:25621790

A Teacher's Window into the Child's Mind and Papers from the Institute for Neuro-Physiological Psychology. A Non-Invasive Approach to Solving Learning and Behavior Problems.

ERIC Educational Resources Information Center

Goddard, Sally

This book describes a neuro-developmental approach to learning difficulty assessment and remediation through assessment of a student's reception of information through the sensory channels, processing of sensory information in the brain, and repertoire of responses for expression. Chapter 1, "Reflexes: Their Impact on Success or Failure in…

Children Who Desperately Want To Read, But Are Not Working at Grade Level: Use Movement Patterns as "Windows" To Discover Why.

ERIC Educational Resources Information Center

Corso, Marjorie

A qualitative longitudinal study, first of four parts, compared developmental movement levels and academic learning levels in young children. Subjects were 28 children of various ages who were not working up to grade level but who did not qualify for learning disability services. Parents completed a detailed demographic survey and a neurological…

Optimizing the performance of bandpass photon detectors for inverse photoemission: Transmission of alkaline earth fluoride window crystals

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

Thiede, Christian, E-mail: christian.thiede@uni-muenster.de; Schmidt, Anke B.; Donath, Markus

2015-08-15

Bandpass photon detectors are widely used in inverse photoemission in the isochromat mode at energies in the vacuum-ultraviolet spectral range. The energy bandpass of gas-filled counters is usually formed by the ionization threshold of the counting gas as high-pass filter and the transmission cutoff of an alkaline earth fluoride window as low-pass filter. The transmission characteristics of the window have, therefore, a crucial impact on the detector performance. We present transmission measurements in the vacuum-ultraviolet spectral range for alkaline earth fluoride window crystals in the vicinity of the transmission cutoff as a function of crystal purity, surface finish, surface contamination,more » temperature, and thickness. Our findings reveal that the transmission characteristics of the window crystal and, thus, the detector performance depend critically on these window parameters.« less

USB Storage Device Forensics for Windows 10.

PubMed

Arshad, Ayesha; Iqbal, Waseem; Abbas, Haider

2018-05-01

Significantly increased use of USB devices due to their user-friendliness and large storage capacities poses various threats for many users/companies in terms of data theft that becomes easier due to their efficient mobility. Investigations for such data theft activities would require gathering critical digital information capable of recovering digital forensics artifacts like date, time, and device information. This research gathers three sets of registry and logs data: first, before insertion; second, during insertion; and the third, after removal of a USB device. These sets are analyzed to gather evidentiary information from Registry and Windows Event log that helps in tracking a USB device. This research furthers the prior research on earlier versions of Microsoft Windows and compares it with latest Windows 10 system. Comparison of Windows 8 and Windows 10 does not show much difference except for new subkey under USB Key in registry. However, comparison of Windows 7 with latest version indicates significant variances. © 2017 American Academy of Forensic Sciences.

40 CFR Appendix L to Subpart A of... - Approved Critical Uses and Limiting Critical Conditions for Those Uses for the 2013 Control Period

Code of Federal Regulations, 2014 CFR

2014-07-01

... growers Moderate to severe black root rot or crown rot.Moderate to severe yellow or purple nutsedge... meet a critical market window, such as during the holiday season. Dry Cured Pork Products Members of...

Developmental Thyroid Hormone Insufficiency Reduces Expression of Brain-Derived Neurotrophic Factor (BDNF) in Adults But Not in Neonates

EPA Science Inventory

Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for many developmental and physiological aspects of CNS function. Severe hypothyroidism in the early neonatal period results in developmental and cognitive impairments and reductions in mRNA and protein expressio...

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

EPA Science Inventory

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 ...

Multivariate Longitudinal Methods for Studying Developmental Relationships between Depression and Academic Achievement

ERIC Educational Resources Information Center

Grimm, Kevin J.

2007-01-01

Recent advances in methods and computer software for longitudinal data analysis have pushed researchers to more critically examine developmental theories. In turn, researchers have also begun to push longitudinal methods by asking more complex developmental questions. One such question involves the relationships between two developmental…

Censored Glauber Dynamics for the Mean Field Ising Model

NASA Astrophysics Data System (ADS)

Ding, Jian; Lubetzky, Eyal; Peres, Yuval

2009-11-01

We study Glauber dynamics for the Ising model on the complete graph on n vertices, known as the Curie-Weiss Model. It is well known that at high temperature ( β<1) the mixing time is Θ( nlog n), whereas at low temperature ( β>1) it is exp ( Θ( n)). Recently, Levin, Luczak and Peres considered a censored version of this dynamics, which is restricted to non-negative magnetization. They proved that for fixed β>1, the mixing-time of this model is Θ( nlog n), analogous to the high-temperature regime of the original dynamics. Furthermore, they showed cutoff for the original dynamics for fixed β<1. The question whether the censored dynamics also exhibits cutoff remained unsettled. In a companion paper, we extended the results of Levin et al. into a complete characterization of the mixing-time for the Curie-Weiss model. Namely, we found a scaling window of order 1/sqrt{n} around the critical temperature β c =1, beyond which there is cutoff at high temperature. However, determining the behavior of the censored dynamics outside this critical window seemed significantly more challenging. In this work we answer the above question in the affirmative, and establish the cutoff point and its window for the censored dynamics beyond the critical window, thus completing its analogy to the original dynamics at high temperature. Namely, if β=1+ δ for some δ>0 with δ 2 n→∞, then the mixing-time has order ( n/ δ)log ( δ 2 n). The cutoff constant is (1/2+[2(ζ2 β/ δ-1)]-1), where ζ is the unique positive root of g( x)=tanh ( β x)- x, and the cutoff window has order n/ δ.

The uncrowded window of object recognition

PubMed Central

Pelli, Denis G; Tillman, Katharine A

2009-01-01

It is now emerging that vision is usually limited by object spacing rather than size. The visual system recognizes an object by detecting and then combining its features. ‘Crowding’ occurs when objects are too close together and features from several objects are combined into a jumbled percept. Here, we review the explosion of studies on crowding—in grating discrimination, letter and face recognition, visual search, selective attention, and reading—and find a universal principle, the Bouma law. The critical spacing required to prevent crowding is equal for all objects, although the effect is weaker between dissimilar objects. Furthermore, critical spacing at the cortex is independent of object position, and critical spacing at the visual field is proportional to object distance from fixation. The region where object spacing exceeds critical spacing is the ‘uncrowded window’. Observers cannot recognize objects outside of this window and its size limits the speed of reading and search. PMID:18828191

Using WebCT as a Supplemental Tool to Enhance Critical Thinking and Engagement among Developmental Reading Students

ERIC Educational Resources Information Center

Burgess, Melissa L.

2009-01-01

The purpose of this research was to examine possible outcomes of developmental students' critical thinking and motivation to read when the online learning community, WebCT, was implemented. My role, in addition to instructor, was that of participant-observer. I implemented WebCT tools, such as discussion board and chat, over a four-month period…

Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs

PubMed Central

Peck, Sun H.; O'Donnell, Philip J.M.; Kang, Jennifer L.; Malhotra, Neil R.; Dodge, George R.; Pacifici, Maurizio; Shore, Eileen M.; Haskins, Mark E.; Smith, Lachlan J.

2015-01-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein may contribute to this cellular dysfunction. These results also highlight the importance of early diagnosis and therapeutic intervention to prevent the progression of debilitating skeletal disease in MPS patients. PMID:26422116

Developmental neurotoxic effects of two pesticides: Behavior and biomolecular studies on chlorpyrifos and carbaryl

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

Lee, Iwa; Eriksson, Per; Fredriksson, Anders

In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brainmore » growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5 mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0 mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8–12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development. - Highlights: • A single neonatal exposure to chlorpyrifos or carbaryl induced developmental neurotoxic effects. • The neurotoxic effects were not caused by acute AChE inhibition. • The neurotoxic effects manifested as altered levels of neuroproteins in the developing brain. • The neurotoxic effects manifested as adult persistent aberrant behavior and cognitive function. • The neurotoxic effects are suggested to be caused by disrupted brain development.« less

Effects of mixing eggs of different initial incubation time on the hatching pattern, chick embryonic development and post-hatch performance.

PubMed

Zhong, Zhentao; Yu, Yue; Jin, Shufang; Pan, Jinming

2018-01-01

The hatch window that varies from 24 to 48 h is known to influence post-hatch performance of chicks. A narrow hatch window is needed for commercial poultry industry to acquire a high level of uniformity of chick quality. Hatching synchronization observed in avian species presents possibilities in altering hatch window in artificial incubation. Layer eggs which were laid on the same day by a single breeder flock and stored for no more than two days started incubation 12 h apart to obtain developmental distinction. The eggs of different initial incubation time were mixed as rows adjacent to rows on day 12 of incubation. During the hatching period (since day 18), hatching time of individual eggs and hatch window were obtained by video recordings. Embryonic development (day 18 and 20) and post-hatch performance up to day 7 were measured. The manipulation of mixing eggs of different initial incubation time shortened the hatch window of late incubated eggs in the manipulated group by delaying the onset of hatching process, and improved the hatchability. Compared to the control groups, chick embryos or chicks in the egg redistribution group showed no significant difference in embryonic development and post-hatch performance up to day 7. We have demonstrated that eggs that were incubated with advanced eggs performed a narrow spread of hatch with higher hatchability, normal embryonic development as well as unaffected chick quality. This specific manipulation is applicable in industrial poultry production to shorten hatch window and improve the uniformity of chick quality.

Beyond Mirrors and Windows: A Critical Content Analysis of Latinx Children's Books

ERIC Educational Resources Information Center

Braden, Eliza G.; Rodriguez, Sanjuana C.

2016-01-01

This critical content analysis examines the representation of Latinx characters in 15 picture books published in 2013 and identified by Children's Cooperative Book Center (CCBC) as having significant Latinx content. The theoretical framework undergirding this study is Critical Race Theory (Ladson-Billings, 1998; Solórzano & Yosso, 2002;…

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

EPA Science Inventory

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

Toilet Training Individuals with Autism and Other Developmental Disabilities: A Critical Review

ERIC Educational Resources Information Center

Kroeger, K. A.; Sorensen-Burnworth, Rena

2009-01-01

The following article reviews the current literature addressing toilet training individuals with autism and other developmental disabilities. The review addresses programs typical to toilet training the developmental disability population, most of which are modeled after the original Foxx and Azrin [Azrin, N. H., & Foxx, R. M. (1971). A rapid…

Developmental Education: The Cost Literature and What We Can Learn from It

ERIC Educational Resources Information Center

Saxon, D. Patrick

2017-01-01

Developmental education is often criticized for its expense. Some believe that it represents a failure of secondary education and is, therefore, a redundant expense. Others believe that developmental education serves a vital role in preparing students for college and is, therefore, a necessary expense. This article provides a review of the…

Children Who Desperately Want To Read, But Are Not Working at Grade Level: Use Movement Patterns As "Windows" To Discover Why. Part II: The Transverse Midline.

ERIC Educational Resources Information Center

Corso, Marjorie

This paper discusses a multi-part longitudinal study which compared the developmental movement levels and the academic learning level in young children, noting that the relationship between movement education and academic education is based on the assumption that both realms of learning are dependent on the adequate development of the brain. The…

Cognitive Biases in Children and Adolescents With Chronic Pain: A Review of Findings and a Call for Developmental Research.

PubMed

Lau, Jennifer Y F; Heathcote, Lauren C; Beale, Sarah; Gray, Suzy; Jacobs, Konrad; Wilkinson, Nick; Crombez, Geert

2018-06-01

Cognitive biases that emphasize bodily harm, injury, and illness could play a role in the maintenance of chronic pain by facilitating fear and avoidance. Whereas extensive research has established attention, interpretation, and memory biases in adults with chronic pain, far less is known about these same biases in children and adolescents with pain. Studying cognitive biases in attention, interpretation, and memory in relation to pain occurring in youth is important because youth is a time when pain can first become chronic, and when relationships between cognitive biases and pain outcomes emerge and stabilize. Thus, youth potentially offers a time window for the prevention of chronic pain problems. In this article, we summarize the growing corpus of data that have measured cognitive biases in relation to pediatric pain. We conclude that although biases in attention, interpretation, and memory characterize children and adolescents with varying pain experiences, questions regarding the direction, magnitude, nature, and role of these biases remain. We call for independent extension of cognitive bias research in children and adolescents, using well powered longitudinal studies with wide age ranges and psychometrically sound experimental measures to clarify these findings and any developmental trends in the links between cognitive biases and pain outcomes. This article provides a rationale for the theoretical and practical importance of studying the role of cognitive biases in children and adolescents with chronic pain, which has to date, been relatively understudied. Existing findings are reviewed critically, and recommendations for future research are offered. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Titanium dioxide nanoparticles: some aspects of toxicity/focus on the development.

PubMed

Rollerova, E; Tulinska, J; Liskova, A; Kuricova, M; Kovriznych, J; Mlynarcikova, A; Kiss, A; Scsukova, S

2015-04-01

Nanosized titanium dioxide (TiO2) particles belong to the most widely manufactured nanoparticles (NPs) on a global scale because of their photocatalytic properties and the related surface effects. TiO2 NPs are in the top five NPs used in consumer products. Ultrafine TiO2 is widely used in the number of applications, including white pigment in paint, ceramics, food additive, food packaging material, sunscreens, cosmetic creams, and, component of surgical implants. Data evidencing rapid distribution, slow or ineffective elimination, and potential long-time tissue accumulation are especially important for the human risk assessment of ultrafine TiO2 and represent new challenges to more responsibly investigate potential adverse effects by the action of TiO2 NPs considering their ubiquitous exposure in various doses. Transport of ultrafine TiO2 particles in systemic circulation and further transition through barriers, especially the placental and blood-brain ones, are well documented. Therefore, from the developmental point of view, there is a raising concern in the exposure to TiO2 NPs during critical windows, in the pregnancy or the lactation period, and the fact that human mothers, women and men in fertile age and last but not least children may be exposed to high cumulative doses. In this review, toxicokinetics and particularly toxicity of TiO2 NPs in relation to the developing processes, oriented mainly on the development of the central nervous system, are discussed Keywords: nanoparticles, nanotoxicity, nanomaterials, titanium dioxide, reproductive toxicity, developmental toxicity, blood brain barrier, placental barrier.

Conjugation and deconjugation reactions within the fetoplacental compartment in a sheep model: a key factor determining bisphenol A fetal exposure.

PubMed

Corbel, Tanguy; Perdu, Elisabeth; Gayrard, Véronique; Puel, Sylvie; Lacroix, Marlène Z; Viguié, Catherine; Toutain, Pierre-Louis; Zalko, Daniel; Picard-Hagen, Nicole

2015-04-01

The widespread human exposure to bisphenol A (BPA), an endocrine disruptor targeting developmental processes, underlines the need to better understand the mechanisms of fetal exposure. Animal studies have shown that at a late stage of pregnancy BPA is efficiently conjugated by the fetoplacental unit, mainly into BPA-glucuronide (BPA-G), which remains trapped within the fetoplacental unit. Fetal exposure to BPA-G might in turn contribute to in situ exposure to bioactive BPA, following its deconjugation into parent BPA at the level of fetal sensitive tissues. The objectives of our study were 1) to characterize the BPA glucurono- and sulfoconjugation capabilities of the ovine fetal liver at different developmental stages, 2) to compare hepatic conjugation activities in human and sheep, and 3) to evaluate the extent of BPA conjugation and deconjugation processes in placenta and fetal gonads. At an early stage of pregnancy, and despite functional sulfoconjugation activity, ovine fetuses expressed low hepatic BPA conjugation capabilities, suggesting that this stage of development represents a critical window in terms of BPA exposure. Conversely, the late ovine fetus expressed an efficient detoxification system that metabolized BPA into BPA-G. Hepatic glucuronidation activities were quantitatively similar in adult sheep and humans. In placenta, BPA conjugation and BPA-G deconjugation activities were relatively balanced, whereas BPA-G hydrolysis was systematically higher than BPA conjugation in gonads. The possible reactivation of BPA-G into BPA could contribute to an increased exposure of fetal sensitive tissues to bioactive BPA in situ. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Developmental changes in organization of structural brain networks.

PubMed

Khundrakpam, Budhachandra S; Reid, Andrew; Brauer, Jens; Carbonell, Felix; Lewis, John; Ameis, Stephanie; Karama, Sherif; Lee, Junki; Chen, Zhang; Das, Samir; Evans, Alan C

2013-09-01

Recent findings from developmental neuroimaging studies suggest that the enhancement of cognitive processes during development may be the result of a fine-tuning of the structural and functional organization of brain with maturation. However, the details regarding the developmental trajectory of large-scale structural brain networks are not yet understood. Here, we used graph theory to examine developmental changes in the organization of structural brain networks in 203 normally growing children and adolescents. Structural brain networks were constructed using interregional correlations in cortical thickness for 4 age groups (early childhood: 4.8-8.4 year; late childhood: 8.5-11.3 year; early adolescence: 11.4-14.7 year; late adolescence: 14.8-18.3 year). Late childhood showed prominent changes in topological properties, specifically a significant reduction in local efficiency, modularity, and increased global efficiency, suggesting a shift of topological organization toward a more random configuration. An increase in number and span of distribution of connector hubs was found in this age group. Finally, inter-regional connectivity analysis and graph-theoretic measures indicated early maturation of primary sensorimotor regions and protracted development of higher order association and paralimbic regions. Our finding reveals a time window of plasticity occurring during late childhood which may accommodate crucial changes during puberty and the new developmental tasks that an adolescent faces.

Dynamic CRM occupancy reflects a temporal map of developmental progression.

PubMed

Wilczyński, Bartek; Furlong, Eileen E M

2010-06-22

Development is driven by tightly coordinated spatio-temporal patterns of gene expression, which are initiated through the action of transcription factors (TFs) binding to cis-regulatory modules (CRMs). Although many studies have investigated how spatial patterns arise, precise temporal control of gene expression is less well understood. Here, we show that dynamic changes in the timing of CRM occupancy is a prevalent feature common to all TFs examined in a developmental ChIP time course to date. CRMs exhibit complex binding patterns that cannot be explained by the sequence motifs or expression of the TFs themselves. The temporal changes in TF binding are highly correlated with dynamic patterns of target gene expression, which in turn reflect transitions in cellular function during different stages of development. Thus, it is not only the timing of a TF's expression, but also its temporal occupancy in refined time windows, which determines temporal gene expression. Systematic measurement of dynamic CRM occupancy may therefore serve as a powerful method to decode dynamic changes in gene expression driving developmental progression.

Gender-Fair and Gender-Congruent Practices for Young Children's Naturalist Intelligence: From the Perspective of Developmentally and Culturally Appropriate Practice (DCAP).

ERIC Educational Resources Information Center

Hyun, Eunsook

Developmentally and Culturally Appropriate Practice (DCAP) is a culturally congruent and critical pedagogy that serves as a framework for early childhood education for all individuals. This paper examines young children's gender differences in learning and their gender-oriented culture and promotes developmentally and culturally appropriate…

Comparison of rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on the nature and severity of developmental effects (Critical Reviews in Toxicology)

EPA Science Inventory

Regulatory non-clinical safety testing of human pharmaceutical compounds typically requires embryo fetal developmental toxicity (EFDT) testing in two species, (one rodent and one non-rodent, usually the rat and the rabbit). The question has been raised whether under some conditio...

Method of identifying features in indexed data

DOEpatents

Jarman, Kristin H [Richland, WA; Daly, Don Simone [Richland, WA; Anderson, Kevin K [Richland, WA; Wahl, Karen L [Richland, WA

2001-06-26

The present invention is a method of identifying features in indexed data, especially useful for distinguishing signal from noise in data provided as a plurality of ordered pairs. Each of the plurality of ordered pairs has an index and a response. The method has the steps of: (a) providing an index window having a first window end located on a first index and extending across a plurality of indices to a second window end; (b) selecting responses corresponding to the plurality of indices within the index window and computing a measure of dispersion of the responses; and (c) comparing the measure of dispersion to a dispersion critical value. Advantages of the present invention include minimizing signal to noise ratio, signal drift, varying baseline signal and combinations thereof.

Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.

PubMed Central

Rice, D; Barone, S

2000-01-01

Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 8 Figure 9 Figure 12 Figure 14 Figure 16 Figure 17 PMID:10852851

Interferometer for Space Station Windows

NASA Technical Reports Server (NTRS)

Hall, Gregory

2003-01-01

Inspection of space station windows for micrometeorite damage would be a difficult task insitu using current inspection techniques. Commercially available optical profilometers and inspection systems are relatively large, about the size of a desktop computer tower, and require a stable platform to inspect the test object. Also, many devices currently available are designed for a laboratory or controlled environments requiring external computer control. This paper presents an approach using a highly developed optical interferometer to inspect the windows from inside the space station itself using a self- contained hand held device. The interferometer would be capable as a minimum of detecting damage as small as one ten thousands of an inch in diameter and depth while interrogating a relatively large area. The current developmental state of this device is still in the proof of concept stage. The background section of this paper will discuss the current state of the art of profilometers as well as the desired configuration of the self-contained, hand held device. Then, a discussion of the developments and findings that will allow the configuration change with suggested approaches appearing in the proof of concept section.

Palaeoenvironment and Its Control on the Formation of Miocene Marine Source Rocks in the Qiongdongnan Basin, Northern South China Sea

PubMed Central

Li, Wenhao; Zhang, Zhihuan; Wang, Weiming; Lu, Shuangfang; Li, Youchuan; Fu, Ning

2014-01-01

The main factors of the developmental environment of marine source rocks in continental margin basins have their specificality. This realization, in return, has led to the recognition that the developmental environment and pattern of marine source rocks, especially for the source rocks in continental margin basins, are still controversial or poorly understood. Through the analysis of the trace elements and maceral data, the developmental environment of Miocene marine source rocks in the Qiongdongnan Basin is reconstructed, and the developmental patterns of the Miocene marine source rocks are established. This paper attempts to reveal the hydrocarbon potential of the Miocene marine source rocks in different environment and speculate the quality of source rocks in bathyal region of the continental slope without exploratory well. Our results highlight the palaeoenvironment and its control on the formation of Miocene marine source rocks in the Qiongdongnan Basin of the northern South China Sea and speculate the hydrocarbon potential of the source rocks in the bathyal region. This study provides a window for better understanding the main factors influencing the marine source rocks in the continental margin basins, including productivity, preservation conditions, and the input of terrestrial organic matter. PMID:25401132

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

PubMed Central

Tain, You-Lin; Hsu, Chien-Ning

2017-01-01

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

Child Health, Developmental Plasticity, and Epigenetic Programming

PubMed Central

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

2011-01-01

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

Alteration of infant attention and activity by polychlorinated biphenyls: unravelling critical windows of susceptibility using physiologically based pharmacokinetic modeling.

PubMed

Verner, M-A; Plusquellec, P; Muckle, G; Ayotte, P; Dewailly, E; Jacobson, S W; Jacobson, J L; Charbonneau, M; Haddad, S

2010-09-01

Pre- and postnatal exposure to polychlorinated biphenyls (PCBs) can impair behavioural function in animal models at doses within the range at which humans are commonly exposed. Yet, epidemiologic studies conducted in the US and Europe are inconsistent with regard to the developmental effects of lactational exposure to these chemicals. This inconsistency may be due to limitations in the current methodological approaches for assessing postnatal exposure to PCBs. Our study used a physiologically based pharmacokinetic (PBPK) model to simulate blood PCB levels during specific pre- and postnatal periods and to evaluate the relation of those levels to infant behaviour. A previously validated PBPK model was used to simulate infant blood PCB-153 levels at delivery and on a month-by-month basis during the first year of life for Inuit infants enrolled in a longitudinal birth cohort. Infant behaviour was assessed using the Behaviour Rating Scales (BRS) of the Bayley Scales of Infant Development (BSID-II) at 11 months of age and video coding of inattention and activity measured during the administration of the mental development subscale of the BSID-II. The estimated pre- and postnatal PCB exposure measures predicted significant increases in inattention and activity at 11 months. Whereas inattention was related to prenatal exposure, activity level, measured by non-elicited activity, was best predicted by postnatal exposure, with the strongest association obtained for simulated PCB levels during the 4th month of life. These findings are consistent with previous reports indicating PCB-induced behavioural alteration in attention and activity level. Simulated infant toxicokinetic profiles for the first year of life revealed windows of susceptibility during which PCBs may impair infant attention and activity. Copyright © 2010 Elsevier Inc. All rights reserved.

Parental verbal abuse and the mediating role of self-criticism in adult internalizing disorders.

PubMed

Sachs-Ericsson, Natalie; Verona, Edelyn; Joiner, Thomas; Preacher, Kristopher J

2006-07-01

Researchers (e.g., [Gibb, B.E., 2002. Childhood maltreatment and negative cognitive styles. A quantitative and qualitative review. Clinical Psychology Review, 22 (2), 223-246]; [Rose, D.T., Abramson, L.Y., 1992. Developmental predictors of depressive cognitive styles: developmental perspectives on depression. In Cicchetti, D., Toth, S.L. (Eds.), Developmental Perspectives on Depression. Rochester symposium on developmental psychopathology, vol. 4, pp. 323-349]) have proposed that when childhood abuse is verbal (rather than sexual or physical), the child is more likely to develop a negative self-schema because the negative self-cognitions are directly supplied to the child by the abuser (e.g., "you are stupid"). In a test of this theory in adult participants, and drawing on the National Comorbidity Survey (NCS) (N=5877), we investigate the mediating role of current levels of self-criticism on the relationship between retrospective reports of parental verbal abuse, as well as sexual and physical abuse, and adult internalizing symptoms. We found self-criticism, but not dependency traits, to fully mediate the relationship between childhood verbal abuse perpetrated by parents and internalizing (depression, anxiety) symptoms. On the other hand, self-criticism was only a partial mediator of the relationship between the other types of abuse and internalizing symptoms. The NCS data is cross-sectional, which limits any firm conclusions regarding causality. While these results are suggestive that self-criticism is a mediator of the relationship between abuse and internalizing symptoms, longitudinal data are necessary to help rule out alternative explanations. Results of this study suggest that childhood abuse experiences, and in particular verbal abuse, may confer risk for internalizing disorders in part because verbal abuse influences the development of a self-critical style.

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

PubMed Central

Suri, Deepika; Teixeira, Cátia M; Cagliostro, Martha K Caffrey; Mahadevia, Darshini; Ansorge, Mark S

2015-01-01

Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system development, such sensitive periods shape the formation of neurocircuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint as well as the environmental context. While allowing for adaptation, such sensitive periods are also vulnerability windows during which external and internal factors can confer risk to disorders by derailing otherwise resilient developmental programs. Here we review developmental periods that are sensitive to monoamine signaling and impact adult behaviors of relevance to psychiatry. Specifically, we review (1) a serotonin-sensitive period that impacts sensory system development, (2) a serotonin-sensitive period that impacts cognition, anxiety- and depression-related behaviors, and (3) a dopamine- and serotonin-sensitive period affecting aggression, impulsivity and behavioral response to psychostimulants. We discuss preclinical data to provide mechanistic insight, as well as epidemiological and clinical data to point out translational relevance. The field of translational developmental neuroscience has progressed exponentially providing solid conceptual advances and unprecedented mechanistic insight. With such knowledge at hand and important methodological innovation ongoing, the field is poised for breakthroughs elucidating the developmental origins of neuropsychiatric disorders, and thus understanding pathophysiology. Such knowledge of sensitive periods that determine the developmental trajectory of complex behaviors is a necessary step towards improving prevention and treatment approaches for neuropsychiatric disorders. PMID:25178408

Milestones of critical thinking: a developmental model for medicine and nursing.

PubMed

Papp, Klara K; Huang, Grace C; Lauzon Clabo, Laurie M; Delva, Dianne; Fischer, Melissa; Konopasek, Lyuba; Schwartzstein, Richard M; Gusic, Maryellen

2014-05-01

Critical thinking is essential to a health professional's competence to assess, diagnose, and care for patients. Defined as the ability to apply higher-order cognitive skills (conceptualization, analysis, evaluation) and the disposition to be deliberate about thinking (being open-minded or intellectually honest) that lead to action that is logical and appropriate, critical thinking represents a "meta-competency" that transcends other knowledge, skills, abilities, and behaviors required in health care professions. Despite its importance, the developmental stages of critical thinking have not been delineated for nurses and physicians. As part of a task force of educators who considered different developmental stage theories, the authors have iteratively refined and proposed milestones in critical thinking. The attributes associated with unreflective, beginning, practicing, advanced, accomplished, and challenged critical thinkers are conceived as independent of an individual's level of training. Depending on circumstances and environmental factors, even the most experienced clinician may demonstrate attributes associated with a challenged thinker. The authors use the illustrative case of a patient with abdominal pain to demonstrate how critical thinking may manifest in learners at different stages of development, analyzing how the learner at each stage applies information obtained in the patient interaction to arrive at a differential diagnosis and plan for evaluation. The authors share important considerations and provide this work as a foundation for the development of effective approaches to teaching and promoting critical thinking and to establishing expectations for learners in this essential meta-competency.

Application study of filamentary composites in a commercial jet aircraft fuselage

NASA Technical Reports Server (NTRS)

Johnson, R. W.; June, R. R.

1972-01-01

A study of applications of filamentary composite materials to aircraft fuselage structure was performed. General design criteria were established and material studies conducted using the 727-200 forebody as the primary structural component. Three design approaches to the use of composites were investigated: uniaxial reinforcement of metal structure, uniaxial and biaxial reinforcement of metal structure, and an all-composite design. Materials application studies for all three concepts were conducted on fuselage shell panels, keel beam, floor beams, floor panels, body frames, fail-safe straps, and window frames. Cost benefit studies were conducted and developmental program costs estimated. On the basis of weight savings, cost effectiveness, developmental program costs, and potential for early application on commercial aircraft, the unaxial design is recommended for a 5-year flight service evaluation program.

Parent-reported Temperament Trajectories among Infant Siblings of Children with Autism

PubMed Central

del Rosario, Mithi; Gillespie-Lynch, Kristen; Johnson, Scott; Sigman, Marian; Hutman, Ted

2013-01-01

Temperament atypicalities have been documented in infancy and early development in children who develop autism spectrum disorders (ASD). The current study investigates whether there are differences in developmental trajectories of temperament between infants and toddlers with and without ASD. Parents of infant siblings of children with autism completed the Carey Temperament Scales about their child at 6, 12, 18, 24, and 36 months of age. Temperament trajectories of children with ASD reflected increases over time in activity level, and decreasing adaptability and approach behaviors relative to high-risk typically developing children. This study is the first to compare temperament trajectories between high-risk typically developing infants and infants subsequently diagnosed with ASD in the developmental window when overt symptoms of ASD first emerge. PMID:23820765

Prenatal Testosterone Programming of Insulin Resistance in the Female Sheep.

PubMed

Puttabyatappa, Muraly; Padmanabhan, Vasantha

2017-01-01

Insulin resistance, a common feature of metabolic disorders such as obesity, nonalcoholic fatty liver disease, metabolic syndrome, and polycystic ovary syndrome, is a risk factor for development of diabetes. Because sex hormones orchestrate the establishment of sex-specific behavioral, reproductive, and metabolic differences, a role for them in the developmental origin of insulin resistance is also to be expected. Female sheep exposed to male levels of testosterone during fetal life serve as an excellent translational model for delineating programming of insulin resistance. This chapter summarizes the ontogeny of insulin resistance, the tissue-specific changes in insulin sensitivity, and the various factors that are involved in the programming and maintenance of the insulin resistance in adult female sheep that were developmentally exposed to fetal male levels of testosterone during the sexual-differentiation window.

Early continuous white noise exposure alters l-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit glutamate receptor 2 and gamma-aminobutyric acid type a receptor subunit beta3 protein expression in rat auditory cortex.

PubMed

Xu, Jinghong; Yu, Liping; Zhang, Jiping; Cai, Rui; Sun, Xinde

2010-02-15

Auditory experience during the postnatal critical period is essential for the normal maturation of auditory function. Previous studies have shown that rearing infant rat pups under conditions of continuous moderate-level noise delayed the emergence of adult-like topographic representational order and the refinement of response selectivity in the primary auditory cortex (A1) beyond normal developmental benchmarks and indefinitely blocked the closure of a brief, critical-period window. To gain insight into the molecular mechanisms of these physiological changes after noise rearing, we studied expression of the AMPA receptor subunit GluR2 and GABA(A) receptor subunit beta3 in the auditory cortex after noise rearing. Our results show that continuous moderate-level noise rearing during the early stages of development decreases the expression levels of GluR2 and GABA(A)beta3. Furthermore, noise rearing also induced a significant decrease in the level of GABA(A) receptors relative to AMPA receptors. However, in adult rats, noise rearing did not have significant effects on GluR2 and GABA(A)beta3 expression or the ratio between the two units. These changes could have a role in the cellular mechanisms involved in the delayed maturation of auditory receptive field structure and topographic organization of A1 after noise rearing. Copyright 2009 Wiley-Liss, Inc.

REPRODUCTIVE AND DEVELOPMENTAL EFFECTS IN MAMMALIAN AND AVIAN SPECIES FROM EXPOSURE TO ELF (EXTREMELY LOW FREQUENCY) FIELDS

EPA Science Inventory

This paper critically reviews the Extremely Low Frequency (ELF) Electromagnetic Fields literature from 1978 to the present in regard to research dealing with the reproductive and developmental effects of exposure.

CUMULATIVE DEVELOPMENTAL EFFECTS OF ENDOCRINE DISRUPTERS: SYNERGY OR ADDITIVITY?

EPA Science Inventory

Exposure to chemicals with hormonal activity during critical developmental periods can disrupt reproductive function and development. Within the last decade, several classes of pesticides and toxic substances have been shown to disrupt differentiation of the male rat reproductive...

Accreditation of Developmental Disabilities Programs.

ERIC Educational Resources Information Center

Hemp, Richard; Braddock, David

1988-01-01

Data gathered from 296 agency accreditation surveys, conducted by the Accreditation Council on Services for People with Developmental Disabilities, were analyzed, focusing on ownership, services provided, size of residential units, critical standards, characteristics of individuals served, and accreditation outcome. Redundancies between private…

Automated Critical Test Findings Identification and Online Notification System Using Artificial Intelligence in Imaging.

PubMed

Prevedello, Luciano M; Erdal, Barbaros S; Ryu, John L; Little, Kevin J; Demirer, Mutlu; Qian, Songyue; White, Richard D

2017-12-01

Purpose To evaluate the performance of an artificial intelligence (AI) tool using a deep learning algorithm for detecting hemorrhage, mass effect, or hydrocephalus (HMH) at non-contrast material-enhanced head computed tomographic (CT) examinations and to determine algorithm performance for detection of suspected acute infarct (SAI). Materials and Methods This HIPAA-compliant retrospective study was completed after institutional review board approval. A training and validation dataset of noncontrast-enhanced head CT examinations that comprised 100 examinations of HMH, 22 of SAI, and 124 of noncritical findings was obtained resulting in 2583 representative images. Examinations were processed by using a convolutional neural network (deep learning) using two different window and level configurations (brain window and stroke window). AI algorithm performance was tested on a separate dataset containing 50 examinations with HMH findings, 15 with SAI findings, and 35 with noncritical findings. Results Final algorithm performance for HMH showed 90% (45 of 50) sensitivity (95% confidence interval [CI]: 78%, 97%) and 85% (68 of 80) specificity (95% CI: 76%, 92%), with area under the receiver operating characteristic curve (AUC) of 0.91 with the brain window. For SAI, the best performance was achieved with the stroke window showing 62% (13 of 21) sensitivity (95% CI: 38%, 82%) and 96% (27 of 28) specificity (95% CI: 82%, 100%), with AUC of 0.81. Conclusion AI using deep learning demonstrates promise for detecting critical findings at noncontrast-enhanced head CT. A dedicated algorithm was required to detect SAI. Detection of SAI showed lower sensitivity in comparison to detection of HMH, but showed reasonable performance. Findings support further investigation of the algorithm in a controlled and prospective clinical setting to determine whether it can independently screen noncontrast-enhanced head CT examinations and notify the interpreting radiologist of critical findings. © RSNA, 2017 Online supplemental material is available for this article.

Seasonal heterogeneity of ocean warming: a mortality sink for ectotherm colonizers.

PubMed

Maffucci, Fulvio; Corrado, Raffaele; Palatella, Luigi; Borra, Marco; Marullo, Salvatore; Hochscheid, Sandra; Lacorata, Guglielmo; Iudicone, Daniele

2016-04-05

Distribution shifts are a common adaptive response of marine ectotherms to climate change but the pace of redistribution depends on species-specific traits that may promote or hamper expansion to northern habitats. Here we show that recently, the loggerhead turtle (Caretta caretta) has begun to nest steadily beyond the northern edge of the species' range in the Mediterranean basin. This range expansion is associated with a significant warming of spring and summer sea surface temperature (SST) that offers a wider thermal window suitable for nesting. However, we found that post-hatchlings departing from this location experience low winter SST that may affect their survival and thus hamper the stabilization of the site by self-recruitment. The inspection of the Intergovernmental Panel on Climate Change model projections and observational data on SST trends shows that, despite the annual warming for this century, winter SST show little or no trends. Therefore, thermal constraints during the early developmental phase may limit the chance of population growth at this location also in the near future, despite increasingly favourable conditions at the nesting sites. Quantifying and understanding the interplay between dispersal and environmental changes at all life stages is critical for predicting ectotherm range expansion with climate warming.

Seasonal heterogeneity of ocean warming: a mortality sink for ectotherm colonizers

NASA Astrophysics Data System (ADS)

Maffucci, Fulvio; Corrado, Raffaele; Palatella, Luigi; Borra, Marco; Marullo, Salvatore; Hochscheid, Sandra; Lacorata, Guglielmo; Iudicone, Daniele

2016-04-01

Distribution shifts are a common adaptive response of marine ectotherms to climate change but the pace of redistribution depends on species-specific traits that may promote or hamper expansion to northern habitats. Here we show that recently, the loggerhead turtle (Caretta caretta) has begun to nest steadily beyond the northern edge of the species’ range in the Mediterranean basin. This range expansion is associated with a significant warming of spring and summer sea surface temperature (SST) that offers a wider thermal window suitable for nesting. However, we found that post-hatchlings departing from this location experience low winter SST that may affect their survival and thus hamper the stabilization of the site by self-recruitment. The inspection of the Intergovernmental Panel on Climate Change model projections and observational data on SST trends shows that, despite the annual warming for this century, winter SST show little or no trends. Therefore, thermal constraints during the early developmental phase may limit the chance of population growth at this location also in the near future, despite increasingly favourable conditions at the nesting sites. Quantifying and understanding the interplay between dispersal and environmental changes at all life stages is critical for predicting ectotherm range expansion with climate warming.

The Programming of the Social Brain by Stress During Childhood and Adolescence: From Rodents to Humans.

PubMed

Tzanoulinou, Stamatina; Sandi, Carmen

2017-01-01

The quality and quantity of social experience is fundamental to an individual's health and well-being. Early life stress is known to be an important factor in the programming of the social brain that exerts detrimental effects on social behaviors. The peri-adolescent period, comprising late childhood and adolescence, represents a critical developmental window with regard to the programming effects of stress on the social brain. Here, we discuss social behavior and the physiological and neurobiological consequences of stress during peri-adolescence in the context of rodent paradigms that model human adversity, including social neglect and isolation, social abuse, and exposure to fearful experiences. Furthermore, we discuss peri-adolescent stress as a potent component that influences the social behaviors of individuals in close contact with stressed individuals and that can also influence future generations. We also discuss the temporal dynamics programmed by stress on the social brain and debate whether social behavior alterations are adaptive or maladaptive. By revising the existing literature and defining open questions, we aim to expand the framework in which interactions among peri-adolescent stress, the social brain, and behavior can be better conceptualized.

Delayed Accumulation of H3K27me3 on Nascent DNA Is Essential for Recruitment of Transcription Factors at Early Stages of Stem Cell Differentiation.

PubMed

Petruk, Svetlana; Cai, Jingli; Sussman, Robyn; Sun, Guizhi; Kovermann, Sina K; Mariani, Samanta A; Calabretta, Bruno; McMahon, Steven B; Brock, Hugh W; Iacovitti, Lorraine; Mazo, Alexander

2017-04-20

Recruitment of transcription factors (TFs) to repressed genes in euchromatin is essential to activate new transcriptional programs during cell differentiation. However, recruitment of all TFs, including pioneer factors, is impeded by condensed H3K27me3-containing chromatin. Single-cell and gene-specific analyses revealed that, during the first hours of induction of differentiation of mammalian embryonic stem cells (ESCs), accumulation of the repressive histone mark H3K27me3 is delayed after DNA replication, indicative of a decondensed chromatin structure in all regions of the replicating genome. This delay provides a critical "window of opportunity" for recruitment of lineage-specific TFs to DNA. Increasing the levels of post-replicative H3K27me3 or preventing S phase entry inhibited recruitment of new TFs to DNA and significantly blocked cell differentiation. These findings suggest that recruitment of lineage-specifying TFs occurs soon after replication and is facilitated by a decondensed chromatin structure. This insight may explain the developmental plasticity of stem cells and facilitate their exploitation for therapeutic purposes. Copyright © 2017 Elsevier Inc. All rights reserved.

Maternal Obesity and Developmental Programming of Metabolic Disorders in Offspring: Evidence from Animal Models

PubMed Central

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

2011-01-01

The incidence of obesity and overweight has reached epidemic proportions in the developed world as well as in those countries transitioning to first world economies, and this represents a major global health problem. Concern is rising over the rapid increases in childhood obesity and metabolic disease that will translate into later adult obesity. Although an obesogenic nutritional environment and increasingly sedentary lifestyle contribute to our risk of developing obesity, a growing body of evidence links early life nutritional adversity to the development of long-term metabolic disorders. In particular, the increasing prevalence of maternal obesity and excess maternal weight gain has been associated with a heightened risk of obesity development in offspring in addition to an increased risk of pregnancy-related complications. The mechanisms that link maternal obesity to obesity in offspring and the level of gene-environment interactions are not well understood, but the early life environment may represent a critical window for which intervention strategies could be developed to curb the current obesity epidemic. This paper will discuss the various animal models of maternal overnutrition and their importance in our understanding of the mechanisms underlying altered obesity risk in offspring. PMID:21969822

[Nutritionnal epigenomics: consequences of unbalanced diets on epigenetics processes of programming during lifespan and between generations].

PubMed

Junien, C; Gallou-Kabani, C; Vigé, A; Gross, M-S

2005-04-01

Epigenetic changes associated with DNA methylation and histone modifications leading to chromatin remodeling and regulation of gene expression underlie the developmental programming of obesity, type 2 diabetes, cardiovascular diseases and metabolic syndrome. This review focuses on converging data supporting the hypothesis that, in addition to "thrifty genotype" inheritance, individuals with obesity, type 2 diabetes, and metabolic syndrome (MetS) with an increased risk of cardiovascular diseases have suffered improper "epigenetic programming" during their fetal/postnatal development due to maternal inadequate nutrition and metabolic disturbances and also during their lifetime, that could even be transmitted to the next generation(s). We highlight the susceptibility of epigenetic mechanisms controlling gene expression to environmental influences due to their inherent malleability, emphasizing the participation of transposable elements and the potential role of imprinted genes during critical time windows in epigenetic programming, from the very beginning of development, throughout life. Increasing our understanding on epigenetic patterns significance and their role in development, evolution and adaptation and on small molecules (nutrients, drugs) that reverse epigenetic (in)activation should provide us with the means to "unlock" silenced (enhanced) genes, and to "convert" the obsolete human thrifty genotype into a "squandering" phenotype.

Sex, Glia, and Development: interactions in health and disease

PubMed Central

Schwarz, Jaclyn M.; Bilbo, Staci D.

2012-01-01

Microglia and astrocytes are the primary immune cells within the central nervous system. Microglia influence processes including neural development, synaptic plasticity and cognition; while their activation and production of immune molecules can induce stereotyped sickness behaviors or pathologies including cognitive dysfunction. Given their role in health and disease, we propose that glia may be also be a critical link in understanding the etiology of many neuropsychiatric disorders that present with a strong sex-bias in their symptoms or prevalence. Specifically, males are more likely to be diagnosed with disorders that have distinct developmental origins such as autism or schizophrenia. In contrast, females are more likely to be diagnosed with disorders that present later in life, after the onset of adolescence, such as depression and anxiety disorders. In this review we will summarize the evidence suggesting that sex differences in the colonization and function of glia within the normal developing brain may contribute to distinct windows of vulnerability between males and females. We will also highlight the current gaps in our knowledge as well as the future directions and considerations of research aimed at understanding the link between neuroimmune function and sex differences in mental health disorders. PMID:22387107

Developmental Changes in Organization of Structural Brain Networks

PubMed Central

Khundrakpam, Budhachandra S.; Reid, Andrew; Brauer, Jens; Carbonell, Felix; Lewis, John; Ameis, Stephanie; Karama, Sherif; Lee, Junki; Chen, Zhang; Das, Samir; Evans, Alan C.; Ball, William S.; Byars, Anna Weber; Schapiro, Mark; Bommer, Wendy; Carr, April; German, April; Dunn, Scott; Rivkin, Michael J.; Waber, Deborah; Mulkern, Robert; Vajapeyam, Sridhar; Chiverton, Abigail; Davis, Peter; Koo, Julie; Marmor, Jacki; Mrakotsky, Christine; Robertson, Richard; McAnulty, Gloria; Brandt, Michael E.; Fletcher, Jack M.; Kramer, Larry A.; Yang, Grace; McCormack, Cara; Hebert, Kathleen M.; Volero, Hilda; Botteron, Kelly; McKinstry, Robert C.; Warren, William; Nishino, Tomoyuki; Robert Almli, C.; Todd, Richard; Constantino, John; McCracken, James T.; Levitt, Jennifer; Alger, Jeffrey; O'Neil, Joseph; Toga, Arthur; Asarnow, Robert; Fadale, David; Heinichen, Laura; Ireland, Cedric; Wang, Dah-Jyuu; Moss, Edward; Zimmerman, Robert A.; Bintliff, Brooke; Bradford, Ruth; Newman, Janice; Evans, Alan C.; Arnaoutelis, Rozalia; Bruce Pike, G.; Louis Collins, D.; Leonard, Gabriel; Paus, Tomas; Zijdenbos, Alex; Das, Samir; Fonov, Vladimir; Fu, Luke; Harlap, Jonathan; Leppert, Ilana; Milovan, Denise; Vins, Dario; Zeffiro, Thomas; Van Meter, John; Lange, Nicholas; Froimowitz, Michael P.; Botteron, Kelly; Robert Almli, C.; Rainey, Cheryl; Henderson, Stan; Nishino, Tomoyuki; Warren, William; Edwards, Jennifer L.; Dubois, Diane; Smith, Karla; Singer, Tish; Wilber, Aaron A.; Pierpaoli, Carlo; Basser, Peter J.; Chang, Lin-Ching; Koay, Chen Guan; Walker, Lindsay; Freund, Lisa; Rumsey, Judith; Baskir, Lauren; Stanford, Laurence; Sirocco, Karen; Gwinn-Hardy, Katrina; Spinella, Giovanna; McCracken, James T.; Alger, Jeffry R.; Levitt, Jennifer; O'Neill, Joseph

2013-01-01

Recent findings from developmental neuroimaging studies suggest that the enhancement of cognitive processes during development may be the result of a fine-tuning of the structural and functional organization of brain with maturation. However, the details regarding the developmental trajectory of large-scale structural brain networks are not yet understood. Here, we used graph theory to examine developmental changes in the organization of structural brain networks in 203 normally growing children and adolescents. Structural brain networks were constructed using interregional correlations in cortical thickness for 4 age groups (early childhood: 4.8–8.4 year; late childhood: 8.5–11.3 year; early adolescence: 11.4–14.7 year; late adolescence: 14.8–18.3 year). Late childhood showed prominent changes in topological properties, specifically a significant reduction in local efficiency, modularity, and increased global efficiency, suggesting a shift of topological organization toward a more random configuration. An increase in number and span of distribution of connector hubs was found in this age group. Finally, inter-regional connectivity analysis and graph-theoretic measures indicated early maturation of primary sensorimotor regions and protracted development of higher order association and paralimbic regions. Our finding reveals a time window of plasticity occurring during late childhood which may accommodate crucial changes during puberty and the new developmental tasks that an adolescent faces. PMID:22784607

Bird-Window Collisions: A Critical Animal Welfare and Conservation Issue.

PubMed

Klem, Daniel

2015-01-01

Sheet glass and plastic in the form of clear and reflective windows are universally lethal to birds. Reasonable interpretation of available scientific evidence describes windows as a principal human-associated avian mortality factor that is an indiscriminant killer of common species as well as species of conservation concern. A conservative toll estimates 1 billion or more annual fatalities in the United States alone. The injury and death from birds striking windows are foreseeable and preventable, but the most promising legal measures and commercial products are not being applied or made available to protect defenseless victims. Avian window casualties are important for birds and people, and they have nonhuman animal welfare, biodiversity, sustainability, legal, and ethical and moral value justifying responsible human action. Preventing this unintended and unwanted lethal hazard for free-flying birds should be an obligation. Short-term solutions include retrofitting existing panes with a variety of proven measures that among others include applying various materials to cover the outside surface of windows. Long-term solutions include current and proposed bird-safe sheet glass and plastic for remodeling and new construction that have patterns that transform windows into barriers that birds see and avoid.

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

ERIC Educational Resources Information Center

Humphreys, Betsy P.

2013-01-01

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

A Response to Edwin Fenton. An Exchange of Views between Edwin Fenton and Jack R. Fraenkel, the Cognitive-Developmental Approach to Moral Education

ERIC Educational Resources Information Center

Fraenkel, Jack R.

1977-01-01

Restatement of the author's criticisms of Fenton's article about Kohlberg's cognitive-developmental approach to moral education in the April 1976 issue of "Social Education." Emphasis is made that (1) Fenton's definitive summations of Kohlberg's works should be more tentative and cautious, because (2) some parts of moral developmental research are…

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

EPA Science Inventory

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

Developmental Thyroid Hormone Disruption: Prevalence, Environmental Contaminants and Neurodevelopmental Consequences

EPA Science Inventory

Thyroid hormones (TH) are critical for growth and development and particularly brain development. There are numerous environmental agents that lead to marginal reductions of circulating TH. Although it is clear that severe developmental hypothyroidism is profoundly detrimental to...

Neurodevelopmental Consequences of Low-Level Thyroid Hormone Disruption Induced by Environmental Contaminants

EPA Science Inventory

Inadequate levels of thyroid hormone during critical developmental periods lead to stunted growth, mental retardation, and neurological 'cretinism'. Animal models of developmental thyroid hormone deficiency mirror well the impact of severe insults to the thyroid system. However, ...

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

EPA Science Inventory

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

Perinatal Bisphenol A Exposure and Adult Glucose Homeostasis: Identifying Critical Windows of Exposure

PubMed Central

Liu, Jingli; Yu, Pan; Qian, Wenyi; Li, Yan; Zhao, Jingjing; Huan, Fei; Wang, Jun; Xiao, Hang

2013-01-01

Bisphenol A (BPA) is a widespread endocrine-disrupting chemical used as the building block for polycarbonate plastics. Epidemiological evidence has correlated BPA exposure with higher risk of heart disease and type 2 diabetes. However, it remains unknown whether there are critical windows of susceptibility to BPA exposure on the development of dysglycemia. This study was an attempt to investigate the critical windows and the long-term consequences of perinatal exposure to BPA on glucose homeostasis. Pregnant mice were given either vehicle or BPA (100 µg/kg/day) at different time of perinatal stage: 1) on days 1–6 of pregnancy (P1–P6, preimplantation exposure); 2) from day 6 of pregnancy until postnatal day (PND) 0 (P6–PND0, fetal exposure); 3) from lactation until weaning (PND0–PND21, neonatal exposure); and 4) from day 6 of gestation until weaning (P6–PND21, fetal and neonatal exposure). At 3, 6 and 8 months of age, offspring in each group were challenged with glucose and insulin tolerance tests. Then islet morphometry and β-cell function were measured. The glucose homeostasis was impaired in P6-PND0 mice from 3 to 6 months of age, and this continued to 8 months in males, but not females. While in PND0-PND21 and P6-PND21 BPA-treated groups, only the 3-month-old male offspring developed glucose intolerance. Moreover, at the age of 3 months, perinatal exposure to BPA resulted in the increase of β-cell mass mainly due to the coordinate changes in cell replication, neogenesis, and apoptosis. The alterations of insulin secretion and insulin sensitivity, rather than β-cell mass, were consistent with the development of glucose intolerance. Our findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and the effects of BPA were dose, sex, and time-dependent. Fetal development stage may be the critical window of susceptibility to BPA exposure. PMID:23675523

Teaching Understanding and Developing Critical Thinking.

ERIC Educational Resources Information Center

Eulie, Joseph

1988-01-01

Examines the relationship between teaching content or knowledge, and teaching the skills of critical thinking and problem solving. Presents key strategies to help students understand and develop critical thinking skills. Recommends use of the developmental lesson and provides several model lessons. (LS)

Developmental age strengthens barriers to ethanol accumulation in zebrafish.

PubMed

Lovely, C Ben; Nobles, Regina D; Eberhart, Johann K

2014-09-01

Fetal Alcohol Spectrum Disorders (FASD) describes a wide range of phenotypic defects affecting facial and neurological development associated with ethanol teratogenicity. It affects approximately 1 in 100 children born in the United States each year. Genetic predisposition along with timing and dosage of ethanol exposure are critical in understanding the prevalence and variability of FASD. The zebrafish attributes of external fertilization, genetic tractability, and high fecundity make it a powerful tool for FASD studies. However, a lack of consensus of ethanol treatment paradigms has limited the interpretation of these various studies. Here we address this concern by examining ethanol tissue concentrations across timing and genetic background. We utilize headspace gas chromatography to determine ethanol concentration in the AB, fli1:EGFP, and Tu backgrounds. In addition, we treated these embryos with ethanol over two different developmental time windows, 6-24 h post fertilization (hpf) and 24-48 hpf. Our analysis demonstrates that embryos rapidly equilibrate to a sub-media level of ethanol. Embryos then maintain this level of ethanol for the duration of exposure. The ethanol tissue concentration level is independent of genetic background, but is timing-dependent. Embryos exposed from 6 to 24 hpf were 2.7-4.2-fold lower than media levels, while embryos were 5.7-6.2-fold lower at 48 hpf. This suggests that embryos strengthen one or more barriers to ethanol as they develop. In addition, both the embryo and, to a lesser extent, the chorion, surrounding the embryo are barriers to ethanol. Overall, this work will help tighten ethanol treatment regimens and strengthen zebrafish as a model of FASD. Copyright © 2014 Elsevier Inc. All rights reserved.

A novel mode-of-action mediated by the fetal muscle nicotinic acetylcholine receptor resulting in developmental toxicity in rats.

PubMed

Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Terry, Claire; Millar, Neil S; Zablotny, Carol L; Gibb, Alasdair; Marshall, Valerie; Collins, Toby; Carney, Edward W; Billington, Richard

2012-06-01

Sulfoxaflor (X11422208), a novel agricultural molecule, induced fetal effects (forelimb flexure, hindlimb rotation, and bent clavicle) and neonatal death in rats at high doses (≥ 400 ppm in diet); however, no such effects occurred in rabbit dietary studies despite achieving similar maternal and fetal plasma exposure levels. Mode-of-action (MoA) studies were conducted to test the hypothesis that the effects in rats had a single MoA induced by sulfoxaflor agonism on the fetal rat muscle nicotinic acetylcholine receptor (nAChR). The studies included cross-fostering and critical windows of exposure studies in rats, fetal ((α1)(2)β1γδ) and adult ((α1)(2)β1δε) rat and human muscle nAChR in vitro agonism experiments, and neonatal rat phrenic nerve-hemidiaphragm contracture studies. The weight of evidence from these studies supported a novel MoA where sulfoxaflor is an agonist to the fetal, but not adult, rat muscle nAChR and that prolonged agonism on this receptor in fetal/neonatal rats causes sustained striated muscle contracture resulting in concomitant reduction in muscle responsiveness to physiological nerve stimulation. Fetal effects were inducible with as little as 1 day of exposure at the end of gestation, but were rapidly reversible after birth, consistent with a pharmacological MoA. With respect to human relevance, sulfoxaflor was shown to have no agonism on human fetal or adult muscle nAChRs. Taken together, the data support the hypothesis that the developmental effects of sulfoxaflor in rats are mediated via sustained agonism on the fetal muscle nAChR during late fetal development and are considered not relevant to humans.

Embryonic exposure to environmentally relevant concentrations of a brominated flame retardant reduces the size of song-control nuclei in a songbird.

PubMed

Eng, Margaret L; Winter, Viktoria; Elliott, John E; MacDougall-Shackleton, Scott A; Williams, Tony D

2018-05-22

Environmental contaminants have the potential to act as developmental stressors and impair development of song and the brain of songbirds, but they have been largely unstudied in this context. 2,2',4,4',5-Pentabromodiphenyl ether (BDE-99) is a brominated flame retardant congener that has demonstrated endocrine disrupting effects, and has pervaded the global environment. We assessed the effects of in ovo exposure to environmentally relevant levels of BDE-99 on the neuroanatomy of the song-control system in a model songbird species, the zebra finch (Taeniopygia guttata). Embryos were exposed via egg injection to a vehicle control (DMSO), 10, 100 or 1000 ng BDE-99/g egg on the day the egg was laid. Chicks were raised to sexual maturity to investigate long-term effects of BDE-99 on the adult male brain. Three key song-control nuclei (Area X, HVC, RA) all showed a dose-dependent trend toward decreasing volume as BDE-99 concentration increased, and birds exposed to 1000 ng/g in ovo BDE-99 had significantly smaller song-control nuclei volume compared to control birds. High environmental concentrations of BDE-99 in avian tissues can be within that range and thus could affect development of the song-control system in birds, and potentially other processes. We previously found that BDE-99 exposure during the nestling period had no effect of on the song-control system, although it did have significant effects on some behavioural endpoints. Taken together, these results suggest that exposure to PBDEs during critical developmental windows can significantly alter neurological development. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio) development

PubMed Central

Truong, Lisa; Barton, Carrie L.; Chase, Tyler T.; Gonnerman, Greg D.; Wong, Carmen P.; Tanguay, Robert L.; Ho, Emily

2017-01-01

Zinc deficiency and chronic low level exposures to inorganic arsenic in drinking water are both significant public health concerns that affect millions of people including pregnant women. These two conditions can co-exist in the human population but little is known about their interaction, and in particular, whether zinc deficiency sensitizes individuals to arsenic exposure and toxicity, especially during critical windows of development. To address this, we utilized the Danio rerio (zebrafish) model to test the hypothesis that parental zinc deficiency sensitizes the developing embryo to low-concentration arsenic toxicity, leading to altered developmental outcomes. Adult zebrafish were fed defined zinc deficient and zinc adequate diets and were spawned resulting in zinc adequate and zinc deficient embryos. The embryos were treated with environmentally relevant concentrations of 0, 50, and 500 ppb arsenic. Arsenic exposure significantly reduced the amount of zinc in the developing embryo by ~7%. The combination of zinc deficiency and low-level arsenic exposures did not sensitize the developing embryo to increased developmental malformations or mortality. The combination did cause a 40% decline in physical activity of the embryos, and this decline was significantly greater than what was observed with zinc deficiency or arsenic exposure alone. Significant changes in RNA expression of genes that regulate zinc homeostasis, response to oxidative stress and insulin production (including zip1, znt7, nrf2, ogg1, pax4, and insa) were found in zinc deficient, or zinc deficiency and arsenic exposed embryos. Overall, the data suggests that the combination of zinc deficiency and arsenic exposure has harmful effects on the developing embryo and may increase the risk for developing chronic diseases like diabetes. PMID:28837703

Neural Correlates of Belief- and Desire-Reasoning

ERIC Educational Resources Information Center

Liu, David; Meltzoff, Andrew N.; Wellman, Henry M.

2009-01-01

Theory of mind requires an understanding of both desires and beliefs. Moreover, children understand desires before beliefs. Little is known about the mechanisms underlying this developmental lag. Additionally, previous neuroimaging and neurophysiological studies have neglected the direct comparison of these developmentally critical mental-state…

Ozone and hypertensive disorders of pregnancy in Florida: Identifying critical windows of exposure.

PubMed

Hu, Hui; Ha, Sandie; Xu, Xiaohui

2017-02-01

Ozone (O 3 ) has been linked to hypertensive disorders of pregnancy (HDP). However, inconsistent results have been reported, and no study has examined the critical exposure windows during pregnancy. We used Florida birth vital statistics records to investigate the association between HDP and O 3 exposure among 655,529 pregnancies with conception dates between 2005 and 2007. Individual O 3 exposure was assessed at mothers' home address at the time of delivery using the Hierarchical Bayesian space-time statistical model. We examined the association during three predefined exposure windows including trimester 1, trimester 2, and trimesters 1&2, as well as in each week of the first two trimesters using distributed lag models. Pregnancies with HDP had a higher mean exposure to O 3 (39.07 in trimester 1, 39.02 in trimester 2, and 39.06 in trimesters 1&2, unit: ppb) than those without HDP (38.65 in trimester 1, 38.57 in trimester 2, and 38.61 in trimesters 1&2, unit: ppb). In the adjusted logistic regression model, increased odds of HDP were observed for each 5 ppb increase in O 3 (OR Trimester1 =1.04, 95% CI: 1.03, 1.06; OR Trimester2 =1.03, 95% CI: 1.02, 1.04; OR Trimester1&2 =1.07, 95% CI: 1.05, 1.08). In the distributed lag models, elevated odds of HDP were observed with increased O 3 exposure during the 1st to 24th weeks of gestation, with higher odds during early pregnancy. O 3 exposure during pregnancy is related to increased odds of HDP, and early pregnancy appears to be a potentially critical window of exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

A developmental perspective on the link between parents' employment and children's obesity.

PubMed

Crosnoe, Robert; Dunifon, Rachel

2017-01-01

Despite public concerns about the negative implications of the increased labor force participation of mothers for child development, decades of research have revealed few risks and some benefits. One potential risk-a consistently observed association between maternal employment and childhood obesity-offers a window into how some dimensions of family health may be undermined by work in an economic and policy context that is not family friendly. The purpose of this article is to identify ways that a developmental perspective can enrich the literature on how children's weight may be related to the work experiences of both mothers and fathers across diverse populations, a literature that heretofore has been dominated by economic and demographic perspectives, focused almost solely on women, and largely ignored racial/ethnic variation. After reviewing the extant literature, we put forward a conceptual model that uses ecological and developmental insights to identify the mechanisms by which parents' employment might matter to children's weight and discuss this model in the context of the contemporary landscape of family policy. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

DEVELOPMENTAL DIVERSITY OF AMPHIBIANS

PubMed Central

Elinson, Richard P.; del Pino, Eugenia M.

2011-01-01

The current model amphibian, Xenopus laevis, develops rapidly in water to a tadpole which metamorphoses into a frog. Many amphibians deviate from the X. laevis developmental pattern. Among other adaptations, their embryos develop in foam nests on land or in pouches on their mother’s back or on a leaf guarded by a parent. The diversity of developmental patterns includes multinucleated oogenesis, lack of RNA localization, huge non-pigmented eggs, and asynchronous, irregular early cleavages. Variations in patterns of gastrulation highlight the modularity of this critical developmental period. Many species have eliminated the larva or tadpole and directly develop to the adult. The wealth of developmental diversity among amphibians coupled with the wealth of mechanistic information from X. laevis permit comparisons that provide deeper insights into developmental processes. PMID:22662314

The Teachable Moment and the Handicapped Infant.

ERIC Educational Resources Information Center

Langley, M. Beth

The report examines, from a cognitive developmental view, research on the teachable moment or critical learning period in handicapped infants. The author explains that developmental gaps are produced by a mismatch between the infant's readiness and opportunity to learn. Characteristics and educational implications of specific handicapping…

EXTRAPOLATION FROM IN VITRO MECHANISMS TO IN VIVO EFFECTS FOR DEVELOPMENTAL NEUROTOXICOLOGY.

EPA Science Inventory

Processes that are critical to development of the nervous system can be altered by both genetic and epigenetic factors. Developmental exposure to neurotoxicants can alter these processes and lead to perturbation of normal neural development. As numerous processes occur in tande...

Towards Building an AOP-based Prenatal Developmental Toxicity Ontology (CEFIC LRI Workshop - Brussels)

EPA Science Inventory

Ontologies are a way to formalize domain-specific scientific knowledge. A developmental ontology would help researchers describe the pathways and processes critical to embryonic development and provide a way to link their chemical disruption to adverse outcomes. Designing one for...

The Dynamic Lift of Developmental Process

ERIC Educational Resources Information Center

Smith, Linda B.; Breazeal, Cynthia

2007-01-01

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

REPRODUCTIVE AND DEVELOPMENTAL EFFECTS OF CONTAMINANTS IN OVIPAROUS VEREBRATES: WORKSHOP INTRODUCTION

EPA Science Inventory

The purpose of this book is to disseminate the critical discussions on reproductive and developmental effects in oviparous vertebrates that occurred during the SETAC Pellston Workshop in Fairmont, Montana in July 1997. The workshop brought together experts from fields of reprodu...

The Costs of Remedial and Developmental Education in Postsecondary Education

ERIC Educational Resources Information Center

Martinez, Maria Emilia; Bain, Steve Frank

2014-01-01

Current research and policy literature indicate an increase in remediation courses nationwide (Tierney & Garcia, 2011; Parsad & Lewis, 2003). However, the most critical theme in research suggests variability and possible inaccuracies in remedial and developmental education data (Kirst, 2007; Venezia, Kirst & Antonio, 2004). In…

Nicotine-induced plasticity during development: modulation of the cholinergic system and long-term consequences for circuits involved in attention and sensory processing.

PubMed

Heath, Christopher J; Picciotto, Marina R

2009-01-01

Despite a great deal of progress, more than 10% of pregnant women in the USA smoke. Epidemiological studies have demonstrated correlations between developmental tobacco smoke exposure and sensory processing deficits, as well as a number of neuropsychiatric conditions, including attention deficit hyperactivity disorder. Significantly, data from animal models of developmental nicotine exposure have suggested that the nicotine in tobacco contributes significantly to the effects of developmental smoke exposure. Consequently, we hypothesize that nicotinic acetylcholine receptors (nAChRs) are important for setting and refining the strength of corticothalamic-thalamocortical loops during critical periods of development and that disruption of this process by developmental nicotine exposure can result in long-lasting dysregulation of sensory processing. The ability of nAChR activation to modulate synaptic plasticity is likely to underlie the effects of both endogenous cholinergic signaling and pharmacologically administered nicotine to alter cellular, physiological and behavioral processes during critical periods of development.

Understanding the Complex Relationship between Critical Thinking and Science Reasoning among Undergraduate Thesis Writers

ERIC Educational Resources Information Center

Dowd, Jason E.; Thompson, Robert J., Jr.; Schif, Leslie A.; Reynolds, Julie A.

2018-01-01

Developing critical-thinking and scientific reasoning skills are core learning objectives of science education, but little empirical evidence exists regarding the interrelationships between these constructs. Writing effectively fosters students' development of these constructs, and it offers a unique window into studying how they relate. In this…

An approach to emotion recognition in single-channel EEG signals: a mother child interaction

NASA Astrophysics Data System (ADS)

Gómez, A.; Quintero, L.; López, N.; Castro, J.

2016-04-01

In this work, we perform a first approach to emotion recognition from EEG single channel signals extracted in four (4) mother-child dyads experiment in developmental psychology. Single channel EEG signals are analyzed and processed using several window sizes by performing a statistical analysis over features in the time and frequency domains. Finally, a neural network obtained an average accuracy rate of 99% of classification in two emotional states such as happiness and sadness.

Developmental Origins of Common Disease: Epigenetic Contributions to Obesity.

PubMed

Kappil, Maya; Wright, Robert O; Sanders, Alison P

2016-08-31

The perinatal period is a window of susceptibility for later life disease. Recent epigenetic findings are beginning to increase our understanding of the molecular mechanisms that may contribute to the programming of obesity. This review summarizes recent evidence that supports the role of epigenetically mediated early life programming in the later onset of obesity. Establishing such links between environmental exposures and modifiable molecular changes ultimately holds promise to inform interventional efforts toward alleviating the environmentally mediated onset of obesity.

Developmental Origins of Common Disease: Epigenetic Contributions to Obesity

PubMed Central

Kappil, Maya; Wright, Robert O.; Sanders, Alison P.

2016-01-01

The perinatal period is a window of susceptibility for later life disease. Recent epigenetic findings are beginning to increase our understanding of the molecular mechanisms that may contribute to the programming of obesity. This review summarizes recent evidence that supports the role of epigenetically mediated early life programming in the later onset of obesity. Establishing such links between environmental exposures and modifiable molecular changes ultimately holds promise to inform interventional efforts toward alleviating the environmentally mediated onset of obesity. PMID:27216778

Influence of gravity and light on the developmental polarity of Ceratopteris richardii fern spores

NASA Technical Reports Server (NTRS)

Edwards, E. S.; Roux, S. J.

1998-01-01

The polarity of germinating single-celled spores of the fern Ceratopteris richardii Brogn. is influenced by gravity during a time period prior to the first cellular division designated a "polarity-determination window". After this window closes, control of polarity is seen in the downward (with respect to gravity) migration of the nucleus along the proximal face of the spore and the subsequent downward growth of the primary rhizoid. When spores are germinated on a clinostat the direction of nuclear migration and subsequent primary rhizoid growth is random. However, in each case the direction of nuclear migration predicts the direction of rhizoid elongation. Although it is the most obvious movement, the downward migration is not the first movement of the nucleus. During the polarity-determination window, the nucleus moves randomly within a region centered behind the trilete marking. While the polarity of many fern spores has been reported to be controlled by light, spores of C. richardii are the first documented to have their polarity influenced by gravity. Directional white light also affects the polarity of these spores, but this influence is slight and is secondary to that of gravity.

The round window region and contiguous areas: endoscopic anatomy and surgical implications.

PubMed

Marchioni, Daniele; Alicandri-Ciufelli, Matteo; Pothier, David D; Rubini, Alessia; Presutti, Livio

2015-05-01

The round window region is a critical area of the middle ear; the aim of this paper is to describe its anatomy from an endoscopic perspective, emphasizing some structures, the knowledge of which could have important implications during surgery, as well as to evaluate what involvement cholesteatoma may have with these structures. Retrospective review of video recordings of endoscopic ear surgeries and retrospective database review were conducted in Tertiary university referral center. Videos from endoscopic middle ear procedures carried out between June 2010 and September 2012 and stored in a shared database were reviewed retrospectively. Surgeries in which an endoscopic magnification of the round window region and the inferior retrotympanum area was performed intraoperatively were included in the study. Involvement by cholesteatoma of those regions was also documented based on information obtained from the surgical database. Conformation of the tegmen of the round window niche may influence the surgical view of round window membrane. A structure connecting the round window area to the petrous apex, named the subcochlear canaliculus, is described. Cholesteatoma can invade the round window areas in some patients. Endoscopic approaches can guarantee a very detailed view and allow the exploration of the round window region. Exact anatomical knowledge of this region can have important advantages during surgery, since some pathology can invade inside cavities or tunnels otherwise not seen by instrumentation that produces a straight-line view (e.g. microscope).

Round window chamber and fustis: endoscopic anatomy and surgical implications.

PubMed

Marchioni, Daniele; Soloperto, Davide; Colleselli, Elena; Tatti, Maria Fatima; Patel, Nirmal; Jufas, Nicholas

2016-11-01

The round window region is of critical importance in the anatomy of the middle ear. The aim of this paper is to describe its anatomy from an endoscopic point of view, emphasizing structures that have important surgical implications, in particular the fustis and the subcochlear canaliculus. The fustis, a smooth bony structure that forms the floor of the round window region, is a constant and important structure. It seems to indicate the round window membrane and the correct position of scala tympani. A structure connecting the round window region to the petrous apex, named the subcochlear canaliculus, is also described. A retrospective review of video recordings of endoscopic dissection and surgical procedures, carried out between June 2014 and February 2015, was conducted across two Tertiary university referral centers. A total of 42 dissections were analyzed in the study. We observed the fustis in all the cases and we identify two different anatomical conformations. The subcochlear canaliculus was found in 81.0 %, with a pneumatization direct to the petrous apex in 47.7 %. Conformation and limits of the round window niche may influence the surgical view of the round window membrane. Endoscopic approaches allow a very detailed view, which enables a comprehensive exploration of the round window region. Accurate knowledge of the anatomical relationships of this region has important advantages during middle ear surgery.

Environmental Toxicants and Developmental Disabilities: A Challenge for Psychologists

ERIC Educational Resources Information Center

Koger, Susan M.; Schettler, Ted; Weiss, Bernard

2005-01-01

Developmental, learning, and behavioral disabilities are a significant public health problem. Environmental chemicals can interfere with brain development during critical periods, thereby impacting sensory, motor, and cognitive function. Because regulation in the United States is based on limited testing protocols and essentially requires proof of…

Language-Universal Sensory Deficits in Developmental Dyslexia: English, Spanish, and Chinese

ERIC Educational Resources Information Center

Goswami, Usha; Wang, H.-L. Sharon; Cruz, Alicia; Fosker, Tim; Mead, Natasha; Huss, Martina

2011-01-01

Studies in sensory neuroscience reveal the critical importance of accurate sensory perception for cognitive development. There is considerable debate concerning the possible sensory correlates of "phonological processing", the primary cognitive risk factor for developmental dyslexia. Across languages, children with dyslexia have a specific…

Mentor Texts Squared: Helping Students Explore Voice through Readings That Promote Critical Consciousness

ERIC Educational Resources Information Center

Molina, Sarina Chugani; Manasse, Mark

2015-01-01

Much research has been conducted documenting the reading and writing challenges students in pre-college courses face (Crosby, 2007; Masterson, 2007). Some colleges label these courses "developmental," "remedial," or "basic skills" courses. These "developmental" students comprise both US-born and immigrant…

Autism Spectrum Disorders: A Natural Fit with DDD.

ERIC Educational Resources Information Center

Myles, Brenda Smith; Simpson, Richard L.; Babkie, Andrea M.

2003-01-01

This position statement from the Critical Issues Committee of the Developmental Disabilities Division of the Council for Exceptional Children focuses on clarifying the place of autism spectrum disorders within the field of developmental disabilities. The representation of concerns relating to autism spectrum disorders by the Developmental…

Refocusing Developmental Education

ERIC Educational Resources Information Center

Brothen, Thomas; Wambach, Cathrine A.

2012-01-01

Dissatisfaction with student success has caused a crisis in developmental education. Critics from both inside and outside the field question whether remedial courses really prepare students for future college work or even if they are properly part of the college mission. In this article, we review research and present information that suggests…

QUANTITATIVE IN VITRO MEASUREMENT OF CELLULAR PROCESSES CRITICAL TO THE DEVELOPMENT OF NEURAL CONNECTIVITY USING HCA.

EPA Science Inventory

New methods are needed to screen thousands of environmental chemicals for toxicity, including developmental neurotoxicity. In vitro, cell-based assays that model key cellular events have been proposed for high throughput screening of chemicals for developmental neurotoxicity. Whi...

Considering Development in Developmental Disorders

ERIC Educational Resources Information Center

Paterson, Sarah J.; Parish-Morris, Julia; Hirsh-Pasek, Kathryn; Golinkoff, Roberta Michnick

2016-01-01

Various theorists have argued for the importance of a developmental approach to studying typical development (Karmiloff-Smith, 1998; Lerner, 1996; Lerner & Hood, 1986; Masten & Cicchetti, 2010; Overton, 2014; Overton & Lerner, 2012, 2014), and there are reasons to believe that this issue is even more critical to the study of…

Annual Research Review: The role of the environment in the developmental psychopathology of autism spectrum condition.

PubMed

Mandy, William; Lai, Meng-Chuan

2016-03-01

Although autism spectrum condition (ASC) is strongly genetic in origin, accumulating evidence points to the critical roles of various environmental influences on its emergence and subsequent developmental course. A developmental psychopathology framework was used to synthesise literature on environmental factors associated with the onset and course of ASC (based on a systematic search of the literature using PubMed, PsychInfo and Google Scholar databases). Particular emphasis was placed on gene-environment interplay, including gene-environment interaction (G × E) and gene-environment correlation (rGE). Before conception, advanced paternal and maternal ages may independently enhance offspring risk for ASC. Exogenous prenatal risks are evident (e.g. valproate and toxic chemicals) or possible (e.g. selective serotonin reuptake inhibitors), and processes endogenous to the materno-foeto-placental unit (e.g. maternal diabetes, enhanced steroidogenic activities and maternal immune activation) likely heighten offspring vulnerability to ASC. Folate intake is a prenatal protective factor, with a particular window of action around 4 weeks preconception and during the first trimester. These prenatal risks and protective mechanisms appear to involve G × E and potentially rGE. A variety of perinatal risks are related to offspring ASC risk, possibly reflecting rGE. Postnatal social factors (e.g. caregiver-infant interaction, severe early deprivation) during the first years of life may operate through rGE to influence the likelihood of manifesting a full ASC phenotype from a 'prodromal' phase (a proposal distinct to the discredited and harmful 'refrigerator mother hypothesis'); and later postnatal risks, after the full manifestation of ASC, shape life span development through transactions mediated by rGE. There is no evidence that vaccination is a postnatal risk for ASC. Future investigations should consider the specificity of risks for ASC versus other atypical neurodevelopmental trajectories, timing of risk and protective mechanisms, animal model systems to study mechanisms underlying gene-environment interplay, large-sample genome-envirome designs to address G × E and longitudinal studies to elucidate how rGE plays out over time. Clinical and public health implications are discussed. © 2016 Association for Child and Adolescent Mental Health.

Model Analyst’s Toolkit User Guide, Version 7.1.0

DTIC Science & Technology

2015-08-01

Help > About)  Environment details ( operating system )  metronome.log file, located in your MAT 7.1.0 installation folder  Any log file that...requirements to run the Model Analyst’s Toolkit:  Windows XP operating system (or higher) with Service Pack 2 and all critical Windows updates installed...application icon on your desktop  Create a Quick Launch icon – Creates a MAT application icon on the taskbar for operating systems released

Updating appetitive memory during reconsolidation window: critical role of cue-directed behavior and amygdala central nucleus.

PubMed

Olshavsky, Megan E; Song, Bryan J; Powell, Daniel J; Jones, Carolyn E; Monfils, Marie-H; Lee, Hongjoo J

2013-01-01

When presented with a light cue followed by food, some rats simply approach the foodcup (Nonorienters), while others first orient to the light in addition to displaying the food-cup approach behavior (Orienters). Cue-directed orienting may reflect enhanced attentional and/or emotional processing of the cue, suggesting divergent natures of cue-information processing in Orienters and Nonorienters. The current studies investigate how differences in cue processing might manifest in appetitive memory retrieval and updating using a paradigm developed to persistently attenuate fear responses (Retrieval-extinction paradigm; Monfils et al., 2009). First, we examined whether the retrieval-extinction paradigm could attenuate appetitive responses in Orienters and Nonorienters. Next, we investigated if the appetitive memory could be updated using reversal learning (fear conditioning) during the reconsolidation window (as opposed to repeated unreinforced trials, i.e., extinction). Both extinction and new fear learning given within the reconsolidation window were effective at persistently updating the initial appetitive memory in the Orienters, but not the Nonorienters. Since conditioned orienting is mediated by the amygdala central nucleus (CeA), our final experiment examined the CeA's role in the retrieval-extinction process. Bilateral CeA lesions interfered with the retrieval-extinction paradigm-did not prevent spontaneous recovery of food-cup approach. Together, our studies demonstrate the critical role of conditioned orienting behavior and the CeA in updating appetitive memory during the reconsolidation window.

Theoretical life history responses of juvenile Oncorhynchus mykiss to changes in food availability using a dynamic state-dependent approach

USGS Publications Warehouse

Romine, Jason G.; Benjamin, Joseph R.; Perry, Russell W.; Casal, Lynne; Connolly, Patrick J.; Sauter, Sally S.

2013-01-01

Marine subsidies can play an important role in the growth, survival, and migratory behavior of rearing juvenile salmonids. Availability of high-energy, marine-derived food sources during critical decision windows may influence the timing of emigration or the decision to forego emigration completely and remain in the freshwater environment. Increasing growth and growth rate during these decision windows may result in an altered juvenile population structure, which will ultimately affect the adult population age-structure. We used a state dependent model to understand how the juvenile Oncorhynchus mykiss population structure may respond to increased availability of salmon eggs in their diet during critical decision windows. Our models predicted an increase in smolt production until coho salmon eggs comprised more than 50 percent of juvenile O. mykiss diet at the peak of the spawning run. At higher-than intermediate levels of egg consumption, smolt production decreased owing to increasing numbers of fish adopting a resident life-history strategy. Additionally, greater growth rates decreased the number of age-3 smolts and increased the number of age-2 smolts. Increased growth rates with higher egg consumption also decreased the age at which fish adopted the resident pathway. Our models suggest that the introduction of a high-energy food source during critical periods of the year could be sufficient to increase smolt production.

IGF-1 deficiency in a critical period early in life influences the vascular aging phenotype in mice by altering miRNA-mediated post-transcriptional gene regulation: implications for the developmental origins of health and disease hypothesis.

PubMed

Tarantini, Stefano; Giles, Cory B; Wren, Jonathan D; Ashpole, Nicole M; Valcarcel-Ares, M Noa; Wei, Jeanne Y; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

2016-08-01

Epidemiological findings support the concept of Developmental Origins of Health and Disease, suggesting that early-life hormonal influences during a sensitive period of development have a fundamental impact on vascular health later in life. The endocrine changes that occur during development are highly conserved across mammalian species and include dramatic increases in circulating IGF-1 levels during adolescence. The present study was designed to characterize the effect of developmental IGF-1 deficiency on the vascular aging phenotype. To achieve that goal, early-onset endocrine IGF-1 deficiency was induced in mice by knockdown of IGF-1 in the liver using Cre-lox technology (Igf1 f/f mice crossed with mice expressing albumin-driven Cre recombinase). This model exhibits low-circulating IGF-1 levels during the peripubertal phase of development, which is critical for the biology of aging. Due to the emergence of miRNAs as important regulators of the vascular aging phenotype, the effect of early-life IGF-1 deficiency on miRNA expression profile in the aorta was examined in animals at 27 months of age. We found that developmental IGF-1 deficiency elicits persisting late-life changes in miRNA expression in the vasculature, which significantly differed from those in mice with adult-onset IGF-1 deficiency (TBG-Cre-AAV8-mediated knockdown of IGF-1 at 5 month of age in Igf1 f/f mice). Using a novel computational approach, we identified miRNA target genes that are co-expressed with IGF-1 and associate with aging and vascular pathophysiology. We found that among the predicted targets, the expression of multiple extracellular matrix-related genes, including collagen-encoding genes, were downregulated in mice with developmental IGF-1 deficiency. Collectively, IGF-1 deficiency during a critical period during early in life results in persistent changes in post-transcriptional miRNA-mediated control of genes critical targets for vascular health, which likely contribute to the deleterious late-life cardiovascular effects known to occur with developmental IGF-1 deficiency.

Design and RF measurements of a 5 GHz 500 kW window for the ITER LHCD system

NASA Astrophysics Data System (ADS)

Hillairet, J.; Achard, J.; Bae, Y. S.; Bernard, J. M.; Dechambre, N.; Delpech, L.; Ekedahl, A.; Faure, N.; Goniche, M.; Kim, J.; Larroque, S.; Magne, R.; Marfisi, L.; Namkung, W.; Park, H.; Park, S.; Poli, S.; Vulliez, K.

2014-02-01

CEA/IRFM is conducting R&D efforts in order to validate the critical RF components of the 5 GHz ITER LHCD system, which is expected to transmit 20 MW of RF power to the plasma. Two 5 GHz 500 kW BeO pill-box type window prototypes have been manufactured in 2012 by the PMB Company, in close collaboration with CEA/IRFM. Both windows have been validated at low power, showing good agreement between measured and modeling, with a return loss better than 32 dB and an insertion loss below 0.05 dB. This paper reports on the window RF design and the low power measurements. The high power tests up to 500kW have been carried out in March 2013 in collaboration with NFRI. Results of these tests are also reported.

Investigations on the carbon contaminations on the alkali cells of DPAL with hydrocarbon buffer gas

NASA Astrophysics Data System (ADS)

Li, Zhiyong; Tan, Rongqing; Wang, Yujie; Ye, Qing; Bian, Jintian; Huang, Wei; Li, Hui; Han, Gaoce

2017-10-01

Diode pumped alkali laser (DPAL) with hydrocarbon buffer gases has the features of low threshold and high efficiency. The chemical reaction between alkali and hydrocarbon gases affects the life time of DPAL. In this paper, a method based on Fourier transform infrared spectroscopy and Lambert-Beer law is adopted to find a safe temperature at which DPAL runs for a long term. A theoretical model is established to figure out ways to reduce the peak temperature in the cell window. The results indicates that 170 °C is a safe temperature. Although the absorbance of the cell window to the pump light and alkali laser is lower, there is temperature increase. Small light-transmitting area and air blowing on the windows can reduce the peak temperature effectively. Cooling the cell window is essential and critical in a long-term running DPAL.

Low-E Storm Windows Gain Acceptance as a Home Weatherization Measure

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

Gilbride, Theresa L.; Cort, Katherine A.

This article for Home Energy Magazine describes work by the U.S. Department of Energy to develop low-emissivity storm windows as an energy efficiency-retrofit option for existing homes. The article describes the low-emissivity invisible silver metal coatings on the glass, which reflect heat back into the home in winter or back outside in summer and the benefits of low-e storm windows including insulation, air sealing, noise blocking, protection of antique windows, etc. The article also describes Pacific Northwest National Laboratory's efforts on behalf of DOE to overcome market barriers to adoption of the technology, including performance validation studies in the PNNLmore » Lab Homes, cost effectiveness analysis, production of reports, brochures, how-to guides on low-e storm window installation for the Building America Solution Center, and a video posted on YouTube. PNNL's efforts were reviewed by the Pacific Northwest Regional Technical Forum (RTF), which serves as the advisory board to the Pacific Northwest Electric Power Planning Council and Bonneville Power Administration. In late July 2015, the RTF approved the low-e storm window measure’s savings and specifications, a critical step in integrating low-e storm windows into energy-efficiency planning and utility weatherization and incentive programs. PNNL estimates that more than 90 million homes in the United States with single-pane or low-performing double-pane windows would benefit from the technology. Low-e storm windows are suitable not only for private residences but also for small commercial buildings, historic properties, and facilities that house residents, such as nursing homes, dormitories, and in-patient facilities. To further assist in the market transformation of low-e storm windows and other high-efficiency window attachments, DOE helped found the window Attachment Energy Rating Council (AERC) in 2015. AERC is an independent, public interest, non-profit organization whose mission is to rate, label, and certify the performance of window attachments.« less

Statistically Characterizing Intra- and Inter-Individual Variability in Children with Developmental Coordination Disorder

ERIC Educational Resources Information Center

King, Bradley R.; Harring, Jeffrey R.; Oliveira, Marcio A.; Clark, Jane E.

2011-01-01

Previous research investigating children with Developmental Coordination Disorder (DCD) has consistently reported increased intra- and inter-individual variability during motor skill performance. Statistically characterizing this variability is not only critical for the analysis and interpretation of behavioral data, but also may facilitate our…

Psychotropic Medication Adherence among Community-Based Individuals with Developmental Disabilities and Mental Illness

ERIC Educational Resources Information Center

Tan, Xi; Marshall, Vincent D.; Balkrishnan, Rajesh; Patel, Isha; Chang, Jongwha; Erickson, Steven R.

2015-01-01

Psychotropic medications are a common treatment for mental illness in people with developmental disabilities. Medication adherence is a critical determinant of the effectiveness of psychotropic drugs, but psychotropic medication adherence research specific to this population remains limited. This retrospective study analyzed Marketscan®…

Crystallizing Conditions, Developmental Advance and Education. First Annual Report.

ERIC Educational Resources Information Center

Feldman, David

This research report outlines progress made in the development of a conceptual framework (called "crystallization") which is intended to explain the conditions found to be critical to the child's potential for developmental change. The research completed and proposed on crystallization has centered around four main areas of activity: (1)…

The (Be)Comings and Goings of "Developmental Disabilities": The Cultural Politics of "Impairment"

ERIC Educational Resources Information Center

Goodley, Dan; Roets, Griet

2008-01-01

Disability should be a concern for those interested in analysing and subverting the cultural politics of education. In this paper we address this concern through connecting critical analyses of "developmental disabilities" (formerly "mental retardation"), disability studies and poststructuralism. We target normative constructions of "developmental…

IN VITRO SCREENING OF DEVELOPMENTAL NEUROTOXICANTS IN RAT PRIMARY CORTICAL NEURONS USING HIGH CONTENT IMAGE

EPA Science Inventory

There is a need for more efficient and cost-effective methods for identifying, characterizing and prioritizing chemicals which may result in developmental neurotoxicity. One approach is to utilize in vitro test systems which recapitulate the critical processes of nervous system d...

Applying a Constructivist-Developmental Practice-Based Learning Framework to the Recreation Internship Experience

ERIC Educational Resources Information Center

Craig, Patricia J.; Sable, Janet R.

2011-01-01

The recreation internship is one of the most critical components of professional preparation education, yet educators have done little to explore the experience from a constructivist-developmental growth perspective. This article presents a practice-based learning framework that shows promise for fostering moral development among recreation…

Meanings of Sisterhood and Developmental Disability: Narratives from White Nondisabled Sisters

ERIC Educational Resources Information Center

McGraw, Lori A.; Walker, Alexis J.

2007-01-01

Integrating thought from critical feminist and disability theorists via a strategic social constructionist perspective, the authors analyzed 10 in-depth qualitative interviews to begin to understand the dialogue between (a) how nondisabled sisters understand themselves and their siblings with developmental disabilities and (b) wider systems of…

Recommendations for Developing Alternative Test Methods for Screening and Prioritization of Chemicals for Developmental Neurotoxicity

EPA Science Inventory

Developmental neurotoxicity testing (DNT) is perceived by many stakeholders to be an area in critical need of alternative methods to current animal testing protocols and gUidelines. An immediate goal is to develop test methods that are capable of screening large numbers of chemic...

Developing Critical Thinking for the Internet

ERIC Educational Resources Information Center

Pachtman, Andrew B.

2012-01-01

The internet is the defining technology for an entire generation. It requires the student to be able to critically evaluate information. It also requires the student to think critically about what information is contained in the information retrieved. How do we prepare developmental education students for these tasks? This article discusses the…

A Critical Analysis of IQ Studies of Adopted Children

ERIC Educational Resources Information Center

Richardson, Ken; Norgate, Sarah H.

2006-01-01

The pattern of parent-child correlations in adoption studies has long been interpreted to suggest substantial additive genetic variance underlying variance in IQ. The studies have frequently been criticized on methodological grounds, but those criticisms have not reflected recent perspectives in genetics and developmental theory. Here we apply…

The effect of deworming on early childhood development in Peru: A randomized controlled trial.

PubMed

Joseph, Serene A; Casapía, Martín; Lazarte, Fabiola; Rahme, Elham; Pezo, Lidsky; Blouin, Brittany; Gyorkos, Theresa W

2015-12-01

There is a knowledge gap on the effect of early childhood deworming on development in low- and middle-income countries. This evidence is important in the critical window of growth and development before two years of age. A randomized controlled trial of the benefit, and optimal timing and frequency, of deworming on development was conducted in Iquitos, Peru. Children were enrolled during routine 12-month growth and development visits and randomly allocated to: (1) deworming at the 12-month visit and placebo at the 18-month visit; (2) placebo at the 12-month visit and deworming at the 18-month visit; (3) deworming at the 12 and 18-month visits; or (4) placebo at the 12 and 18-month visits. The Bayley Scales of Infant Development III was used to assess cognitive, language and motor skills at the 12 and 24-month visits. One-way ANOVA analyses used an intention-to-treat approach. Between September 2011 and June 2012, 1760 children were enrolled. Attendance at the 24-month visit was 88.8% ( n =1563). Raw scores on all subtests increased over 12 months; however, cognitive and expressive language scaled scores decreased. There was no statistically significant benefit of deworming, or effect of timing or frequency, on any of the development scores. Baseline height and weight and maternal education were associated with development scores at 24 months. After 12 months of follow-up, an overall benefit of deworming on cognition, language or fine motor development was not detected. Additional integrated child and maternal interventions should be considered to prevent developmental deficits in this critical period.

Social Origins of Developmental Risk for Mental and Physical Illness.

PubMed

Cameron, Judy L; Eagleson, Kathie L; Fox, Nathan A; Hensch, Takao K; Levitt, Pat

2017-11-08

Adversity in early childhood exerts an enduring impact on mental and physical health, academic achievement, lifetime productivity, and the probability of interfacing with the criminal justice system. More science is needed to understand how the brain is affected by early life stress (ELS), which produces excessive activation of stress response systems broadly throughout the child's body (toxic stress). Our research examines the importance of sex, timing and type of stress exposure, and critical periods for intervention in various brain systems across species. Neglect (the absence of sensitive and responsive caregiving) or disrupted interaction with offspring induces robust, lasting consequences in mice, monkeys, and humans. Complementary assessment of internalizing disorders and brain imaging in children suggests that early adversity can interfere with white matter development in key brain regions, which may increase risk for emotional difficulties in the long term. Neural circuits that are most plastic during ELS exposure in monkeys sustain the greatest change in gene expression, offering a mechanism whereby stress timing might lead to markedly different long-term behaviors. Rodent models reveal that disrupted maternal-infant interactions yield metabolic and behavioral outcomes often differing by sex. Moreover, ELS may further accelerate or delay critical periods of development, which reflect GABA circuit maturation, BDNF, and circadian Clock genes. Such factors are associated with several mental disorders and may contribute to a premature closure of plastic windows for intervention following ELS. Together, complementary cross-species studies are elucidating principles of adaptation to adversity in early childhood with molecular, cellular, and whole organism resolution. Copyright © 2017 the authors 0270-6474/17/3710783-09$15.00/0.

Toddler Developmental Delays After Extensive Hospitalization: Primary Care Practitioner Guidelines.

PubMed

Lehner, Dana C; Sadler, Lois S

2015-01-01

This review investigated developmental delays toddlers may encounter after a lengthy pediatric hospitalization (30 days or greater). Physical, motor, cognitive, and psychosocial development of children aged 1 to 3 years was reviewed to raise awareness of factors associated with developmental delay after extensive hospitalization. Findings from the literature suggest that neonatal and pediatric intensive care unit (NICU/PICU) graduates are most at risk for developmental delays, but even non-critical hospital stays interrupt development to some extent. Primary care practitioners (PCPs) may be able to minimize risk for delays through the use of formal developmental screening tests and parent report surveys. References and resources are described for developmental assessment to help clinicians recognize delays and to educate families about optimal toddler development interventions. Pediatric PCPs play a leading role in coordinating health and developmental services for the young child following an extensive hospital stay.

Study of Mechanical and Thermal Impact of a Plasma Focus Discharge on Diagnostic Elements of PFM-72M Installation

NASA Astrophysics Data System (ADS)

Bashutin, O. A.; Savelov, A. S.; Sidorov, P. P.

2017-12-01

Mechanical and thermal impact of the plasma focus discharge on structural elements of diagnostic windows of the PFM-72m discharge installation are calculated. The absence of critical impact at early discharge stages and during the first 300 ns after the "plasma focus" formation is shown. The possibility of shock impact on the surface of diagnostic windows at later times, which may result in their substantial deformation and destruction, is demonstrated.

The inability to mentally represent action may be associated with performance deficits in children with developmental coordination disorder.

PubMed

Gabbard, Carl; Bobbio, Tatiana

2011-03-01

Several research studies indicate that children with developmental coordination disorder (DCD) show delays with an array of perceptual-motor skills. One of the explanations, based on limited research, is that these children have problems generating and/or monitoring a mental (action) representation of intended actions, termed the "internal modeling deficit" (IMD) hypothesis. According to the hypothesis, children with DCD have significant limitations in their ability to accurately generate and utilize internal models of motor planning and control. The focus of this review is on one of the methods used to examine action representation-motor imagery, which theorists argue provides a window into the process of action representation (e.g., Jeannerod, 2001 . Neural simulation of action: A unifying mechanism for motor cognition. Neuroimage, 14, 103-109.). Included in the review are performance studies of typically developing and DCD children, and possible brain structures involved.

Childhood Stuttering – Where are we and Where are we going?

PubMed Central

Smith, Anne; Weber, Christine

2017-01-01

Remarkable progress has been made over the past two decades in expanding our understanding of the behavioral, peripheral physiological, and central neurophysiological bases of stuttering in early childhood. It is clear that stuttering is a neurodevelopmental disorder characterized by atypical development of speech motor planning and execution networks. The speech motor system must interact in complex ways with neural systems mediating language, other cognitive, and emotional processes. During the time window when stuttering typically appears and follows its path to either recovery or persistence, all of these neurobehavioral systems are undergoing rapid and dramatic developmental changes. We summarize our current understanding of the various developmental trajectories relevant for the understanding of stuttering in early childhood. We also present theoretical and experimental approaches that we believe will be optimal for even more rapid progress toward developing better and more targeted treatment for stuttering in the preschool children who are more likely to persist in stuttering. PMID:27701705

Development of Problem-Based Learning Oriented Teaching Learning Materials to Facilitate Students’ Mastery of Concept and Critical Thinking Skill

NASA Astrophysics Data System (ADS)

Reza, M.; Ibrahim, M.; Rahayu, Y. S.

2018-01-01

This research aims to develop problem-based learning oriented teaching materials to improve students’ mastery of concept and critical thinking skill. Its procedure was divided into two phases; developmental phase and experimental phase. This developmental research used Four-D Model. However, within this research, the process of development would not involve the last stages, which is disseminate. The teaching learning materials which were developed consist of lesson plan, student handbook, student worksheet, achievement test and critical thinking skill test. The experimental phase employs a research design called one group pretest-posttest design. Results show that the validity of the teaching materials which were developed was good and revealed the enhancement of students’ activities with positive response to the teaching learning process. Furthermore, the learning materials improve the students’ mastery of concept and critical thinking skill.

Gender considerations in ventilatory and metabolic development in rats: special emphasis on the critical period

PubMed Central

LIU, QIULI; WONG-RILEY, MARGARET T.T

2013-01-01

In rats, a critical period exists around postnatal day (P) 12-13, when an imbalance between heightened inhibition and suppressed excitation led to a weakened ventilatory and metabolic response to acute hypoxia. An open question was whether the two genders follow the same or different developmental trends throughout the first 3 postnatal weeks and whether the critical period exists in one or both genders. The present large-scale, in-depth ventilatory and metabolic study was undertaken to address this question. Our data indicated that: 1) the ventilatory and metabolic rates in both normoxia and acute hypoxia were comparable between the two genders from P0 to P21; thus, gender was never significant as a main effect; and 2) the age effect was highly significant in all parameters studies for both genders, and both genders exhibited a significantly weakened response to acute hypoxia during the critical period. Thus, the two genders have comparable developmental trends, and the critical period exists in both genders in rats. PMID:23797186

Macroevolutionary developmental biology: Embryos, fossils, and phylogenies.

PubMed

Organ, Chris L; Cooper, Lisa Noelle; Hieronymus, Tobin L

2015-10-01

The field of evolutionary developmental biology is broadly focused on identifying the genetic and developmental mechanisms underlying morphological diversity. Connecting the genotype with the phenotype means that evo-devo research often considers a wide range of evidence, from genetics and morphology to fossils. In this commentary, we provide an overview and framework for integrating fossil ontogenetic data with developmental data using phylogenetic comparative methods to test macroevolutionary hypotheses. We survey the vertebrate fossil record of preserved embryos and discuss how phylogenetic comparative methods can integrate data from developmental genetics and paleontology. Fossil embryos provide limited, yet critical, developmental data from deep time. They help constrain when developmental innovations first appeared during the history of life and also reveal the order in which related morphologies evolved. Phylogenetic comparative methods provide a powerful statistical approach that allows evo-devo researchers to infer the presence of nonpreserved developmental traits in fossil species and to detect discordant evolutionary patterns and processes across levels of biological organization. © 2015 Wiley Periodicals, Inc.

Role of the pre- and post-natal environment in developmental programming of health and productivity.

PubMed

Reynolds, Lawrence P; Caton, Joel S

2012-05-06

The concept that developmental insults (for example, poor pre- or postnatal nutrition) can have long-term consequences on health and well-being of the offspring has been termed developmental programming. In livestock, developmental programming affects production traits, including growth, body composition, and reproduction. Although low birth weight was used as a proxy for compromised fetal development in the initial epidemiological studies, based on controlled studies using livestock and other animal models in the last two decades we now know that developmental programming can occur independently of any effects on birth weight. Studies in humans, rodents, and livestock also have confirmed the critical role of the placenta in developmental programming. In addition, the central role of epigenetic regulation in developmental programming has been confirmed. Lastly, relatively simple therapeutic/management strategies designed to 'rescue' placental development and function are being developed to minimize the effects of developmental programming on health and productivity of humans, livestock, and other mammals. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Neural systems underlying reward and approach behaviors in childhood and adolescence.

PubMed

Galván, Adriana

2014-01-01

Transitions into and out of adolescence are critical developmental periods of reward-seeking and approach behaviors. Converging evidence suggests that intriguing reward-related behavioral shifts are mediated by developmental changes in frontostriatal circuitry. This chapter explores how the conceptual frameworks and empirical studies in the field of developmental cognitive neuroscience have contributed to understanding reward-related behavior across development.The chapter concludes with some implications for adaptive and maladaptive behaviors that arise from these behaviors as children transition from childhood to adolescence.

Spiritual Formation as Social: Toward a Vygotskyan Developmental Perspective

ERIC Educational Resources Information Center

Estep, James Riley, Jr.

2002-01-01

Spiritual formation is a critical concern for any Christian religious educator. While Scripture provides a depiction of spiritual growth, we have often turned to the developmental theorists to better understand the ecology of spiritual formation. One neglected voice in this instance is the late Russian developmentalist Lev S. Vygotsky. His unique…

Application of Targeted Functional Assays to Assess a Putative Vascular Disruption Developmental Toxicity Pathway Informed By ToxCast High-Throughput Screening Data

EPA Science Inventory

Chemical perturbation of vascular development is a putative toxicity pathway which may result in developmental toxicity. EPA’s high-throughput screening (HTS) ToxCast program contains assays which measure cellular signals and biological processes critical for blood vessel develop...

Meeting Developmental Challenges during Emerging Adulthood: The Role of Personality and Social Resources

ERIC Educational Resources Information Center

Shulman, Shmuel; Kalnitzki, Esther; Shahar, Golan

2009-01-01

A one-year follow-up study examined the role of developmental challenges, personality (dependency, self-criticism, and personal efficacy), and support systems in adaptation among Israeli emerging adults (N = 236) participating in a preparatory academic program. Participants were assessed during their enrollment in the preparatory academic program…

Developmental and Social Determinants of Religious Social Categorization

ERIC Educational Resources Information Center

van der Straten Waillet, Nastasya; Roskam, Isabelle

2012-01-01

The purpose of this study was to assess developmental and social determinants of the age at which children become aware that the social environment can be marked by categorization into religious groups and that those groups are associated with different religious beliefs. The results show that middle childhood is a critical period for this…

Families of Individuals with Intellectual and Developmental Disabilities: Policy, Funding, Services, and Experiences

ERIC Educational Resources Information Center

Hewitt, Amy; Agosta, John; Heller, Tamar; Williams, Ann Cameron; Reinke, Jennifer

2013-01-01

Families are critical in the provision of lifelong support to individuals with intellectual and developmental disabilities (IDD). Today, more people with IDD receive long-term services and supports while living with their families. Thus, it is important that researchers, practitioners, and policy makers understand how to best support families who…

The Uptake of Secondary Prevention by Adults with Intellectual and Developmental Disabilities

ERIC Educational Resources Information Center

Ouellette-Kuntz, H.; Cobigo, V.; Balogh, R.; Wilton, A.; Lunsky, Y.

2015-01-01

Background: Secondary prevention involves the early detection of disease while it is asymptomatic to prevent its progression. For adults with intellectual and developmental disabilities, secondary prevention is critical as they may not have the ability to recognize the early signs and symptoms of disease or lack accessible information about these.…

Technical Elements, Demonstration Projects, and Fiscal Models in Medicaid Managed Care for People with Developmental Disabilities.

ERIC Educational Resources Information Center

Kastner, Theodore A.; Walsh, Kevin K.; Criscione, Teri

1997-01-01

Presents a general model of the structure and functioning of managed care and describes elements (provider networks, fiscal elements, risk estimation, case-mix, management information systems, practice parameters, and quality improvement) critical to people with developmental disabilities. Managed care demonstration projects and a hypothetical…

Developmental Tasks of Women Entering Higher Education at Mid-Life. Final Report.

ERIC Educational Resources Information Center

Richardson, Virginia; Sands, Roberta G.

Women who enrolled in college during their middle-aged years (between ages 30 and 49) were studied. Attention was directed to: the relationship between returning to school and critical developmental issues; the influence of educational experience on understanding such issues; and the stress factors experienced by mid-life university women.…

Perceptions of Early Intervention Services: Adolescent and Adult Mothers in Two States

ERIC Educational Resources Information Center

Thompson, Stacy D.; Bruns, Deborah A.

2013-01-01

Early intervention (EI) provides critical services to families with young children who have diagnosed disabilities, developmental delays, or who are at-risk for developmental delays. Very little is known about the experiences of adolescent mothers who have children who qualify for EI services. The authors investigated the perceptions of adolescent…

Latinas/os in Community College Developmental Education: Increasing Moments of Academic and Interpersonal Validation

ERIC Educational Resources Information Center

Acevedo-Gil, Nancy; Solorzano, Daniel G.; Santos, Ryan E.

2014-01-01

This qualitative study examines the experiences of Latinas/os in community college English and math developmental education courses. Critical race theory in education and the theory of validation serve as guiding frameworks. The authors find that institutional agents provide academic validation by emphasizing high expectations, focusing on social…

Using Administrative Health Data to Identify Individuals with Intellectual and Developmental Disabilities: A Comparison of Algorithms

ERIC Educational Resources Information Center

Lin, E.; Balogh, R.; Cobigo, V.; Ouellette-Kuntz, H.; Wilton, A. S.; Lunsky, Y.

2013-01-01

Background: Individuals with intellectual and developmental disabilities (IDD) experience high rates of physical and mental health problems; yet their health care is often inadequate. Information about their characteristics and health services needs is critical for planning efficient and equitable services. A logical source of such information is…

Latinas/os in Community College Developmental Education: Increasing Moments of Academic and Interpersonal Validation

ERIC Educational Resources Information Center

Acevedo-Gil, Nancy; Santos, Ryan E.; Alonso, LLuliana; Solorzano, Daniel G.

2015-01-01

This qualitative study examines the experiences of Latinas/os in community college English and math developmental education courses. Critical race theory in education and the theory of validation serve as guiding frameworks. The authors find that institutional agents provide academic validation by emphasizing high expectations, focusing on social…

A Comprehensive Guide to Intellectual and Developmental Disabilities. Second Edition

ERIC Educational Resources Information Center

Wehmeyer, Michael L.. Ed.; Brown, Ivan, Ed.; Percy, Maire, Ed.; Fung, W. L. Alan, Ed.; Shogren, Karrie A., Ed.

2017-01-01

The trusted core disability textbook gets a comprehensive update in this second edition, now thoroughly revised to include all the critical topics today's professionals need to know about as they work with people who have intellectual and developmental disabilities. Brought to you by a new team of world-renowned experts and contributors, this…

Future Directions in Sleep and Developmental Psychopathology.

PubMed

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.

Scaffolding Critical Thinking in the Zone of Proximal Development

ERIC Educational Resources Information Center

Wass, Rob; Harland, Tony; Mercer, Alison

2011-01-01

This paper explores student experiences of learning to think critically. Twenty-six zoology undergraduates took part in the study for three years of their degree at the University of Otago, New Zealand. Vygotsky's developmental model of the Zone of Proximal Development (ZPD) provided a framework as we examined how critical thinking was developed.…

PERSONALITY PREDISPOSITIONS IN CHINESE ADOLESCENTS: THE RELATION BETWEEN SELF-CRITICISM, DEPENDENCY, AND PROSPECTIVE INTERNALIZING SYMPTOMS

PubMed Central

Cohen, Joseph R.; Young, Jami F.; Hankin, Benjamin L.; Yao, Shuqiao; Zhu, Xiong Zhao; Abela, John R.Z.

2015-01-01

The present study examined the prospective relation between two personality predispositions, self-criticism and dependency, and internalizing symptoms. Specifically, it was examined whether self-criticism and dependency predicted symptoms of depression and social anxiety, and if a moderation (e.g. diathesis-stress) or mediation model best explained the relation between the personality predispositions and emotional distress in Chinese adolescents. Participants included 1,150 adolescents (597 females and 553 males) from mainland China. Participants completed self-report measures of self-criticism, dependency, and neuroticism at baseline, and self-report measures of negative events, depressive symptoms, and social anxiety symptoms once a month for six months. Findings showed that self-criticism predicted depressive symptoms, while dependency predicted social anxiety symptoms. In addition, support was found for a mediation model, as opposed to a moderation model, with achievement stressors mediating the relation between self-criticism and depressive symptoms. Overall, these findings highlight new developmental pathways for the development of depression and social anxiety symptoms in mainland Chinese adolescents. Implications for cross-cultural developmental psychopathology research are discussed. PMID:25798026

Seasonal heterogeneity of ocean warming: a mortality sink for ectotherm colonizers

PubMed Central

Maffucci, Fulvio; Corrado, Raffaele; Palatella, Luigi; Borra, Marco; Marullo, Salvatore; Hochscheid, Sandra; Lacorata, Guglielmo; Iudicone, Daniele

2016-01-01

Distribution shifts are a common adaptive response of marine ectotherms to climate change but the pace of redistribution depends on species-specific traits that may promote or hamper expansion to northern habitats. Here we show that recently, the loggerhead turtle (Caretta caretta) has begun to nest steadily beyond the northern edge of the species’ range in the Mediterranean basin. This range expansion is associated with a significant warming of spring and summer sea surface temperature (SST) that offers a wider thermal window suitable for nesting. However, we found that post-hatchlings departing from this location experience low winter SST that may affect their survival and thus hamper the stabilization of the site by self-recruitment. The inspection of the Intergovernmental Panel on Climate Change model projections and observational data on SST trends shows that, despite the annual warming for this century, winter SST show little or no trends. Therefore, thermal constraints during the early developmental phase may limit the chance of population growth at this location also in the near future, despite increasingly favourable conditions at the nesting sites. Quantifying and understanding the interplay between dispersal and environmental changes at all life stages is critical for predicting ectotherm range expansion with climate warming. PMID:27044321

Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

PubMed

Greco, Tiffany; Hovda, David A; Prins, Mayumi L

2015-02-01

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc.

Changes in gene expression associated with reproductive maturation in wild female baboons.

PubMed

Babbitt, Courtney C; Tung, Jenny; Wray, Gregory A; Alberts, Susan C

2012-01-01

Changes in gene expression during development play an important role in shaping morphological and behavioral differences, including between humans and nonhuman primates. Although many of the most striking developmental changes occur during early development, reproductive maturation represents another critical window in primate life history. However, this process is difficult to study at the molecular level in natural primate populations. Here, we took advantage of ovarian samples made available through an unusual episode of human-wildlife conflict to identify genes that are important in this process. Specifically, we used RNA sequencing (RNA-Seq) to compare genome-wide gene expression patterns in the ovarian tissue of juvenile and adult female baboons from Amboseli National Park, Kenya. We combined this information with prior evidence of selection occurring on two primate lineages (human and chimpanzee). We found that in cases in which genes were both differentially expressed over the course of ovarian maturation and also linked to lineage-specific selection this selective signature was much more likely to occur in regulatory regions than in coding regions. These results suggest that adaptive change in the development of the primate ovary may be largely driven at the mechanistic level by selection on gene regulation, potentially in relationship to the physiology or timing of female reproductive maturation.

SWATH label-free proteomics analyses revealed the roles of oxidative stress and antioxidant defensing system in sclerotia formation of Polyporus umbellatus

NASA Astrophysics Data System (ADS)

Li, Bing; Tian, Xiaofang; Wang, Chunlan; Zeng, Xu; Xing, Yongmei; Ling, Hong; Yin, Wanqiang; Tian, Lixia; Meng, Zhixia; Zhang, Jihui; Guo, Shunxing

2017-01-01

Understanding the initiation and maturing mechanisms is important for rational manipulating sclerotia differentiation and growth from hypha of Polyporus umbellatus. Proteomes in P. umbellatus sclerotia and hyphae at initial, developmental and mature phases were studied. 1391 proteins were identified by nano-liquid chromatograph-mass spectrometry (LC-MS) in Data Dependant Acquisition mode, and 1234 proteins were quantified successfully by Sequential Window Acquisition of all THeoretical fragment ion spectra-MS (SWATH-MS) technology. There were 347 differentially expressed proteins (DEPs) in sclerotia at initial phase compared with those in hypha, and the DEP profiles were dynamically changing with sclerotia growth. Oxidative stress (OS) in sclerotia at initial phase was indicated by the repressed proteins of respiratory chain, tricarboxylic acid cycle and the activation of glycolysis/gluconeogenesis pathways were determined based on DEPs. The impact of glycolysis/gluconeogenesis on sclerotium induction was further verified by glycerol addition assays, in which 5% glycerol significantly increased sclerotial differentiation rate and biomass. It can be speculated that OS played essential roles in triggering sclerotia differentiation from hypha of P. umbellatus, whereas antioxidant activity associated with glycolysis is critical for sclerotia growth. These findings reveal a mechanism for sclerotial differentiation in P. umbellatus, which may also be applicable for other fungi.

Changes in Gene Expression Associated with Reproductive Maturation in Wild Female Baboons

PubMed Central

Babbitt, Courtney C.; Tung, Jenny; Wray, Gregory A.; Alberts, Susan C.

2012-01-01

Changes in gene expression during development play an important role in shaping morphological and behavioral differences, including between humans and nonhuman primates. Although many of the most striking developmental changes occur during early development, reproductive maturation represents another critical window in primate life history. However, this process is difficult to study at the molecular level in natural primate populations. Here, we took advantage of ovarian samples made available through an unusual episode of human–wildlife conflict to identify genes that are important in this process. Specifically, we used RNA sequencing (RNA-Seq) to compare genome-wide gene expression patterns in the ovarian tissue of juvenile and adult female baboons from Amboseli National Park, Kenya. We combined this information with prior evidence of selection occurring on two primate lineages (human and chimpanzee). We found that in cases in which genes were both differentially expressed over the course of ovarian maturation and also linked to lineage-specific selection this selective signature was much more likely to occur in regulatory regions than in coding regions. These results suggest that adaptive change in the development of the primate ovary may be largely driven at the mechanistic level by selection on gene regulation, potentially in relationship to the physiology or timing of female reproductive maturation. PMID:22155733

Role of the immune modulator programmed cell death-1 during development and apoptosis of mouse retinal ganglion cells

PubMed Central

Chen, Ling; Sham, Caroline W.; Chan, Ann M.; Francisco, Loise M.; Wu, Yin; Mareninov, Sergey; Sharpe, Arlene H.; Freeman, Gordon J.; Yang, Xian-Jie; Braun, Jonathan; Gordon, Lynn K.

2011-01-01

PURPOSE Mammalian programmed cell death-1 (PD-1) is a membrane-associated receptor regulating the balance between T cell activation, tolerance and immunopathology, however its role in neurons has not yet been defined. We investigate the hypothesis that PD-1 signaling actively promotes retinal ganglion cell (RGC) death within the developing mouse retina. METHODS Mature retinal cell types expressing PD-1 were identified by immunofluorescence staining of vertical retina sections; developmental expression was localized by immunostaining and quantified by Western analysis. PD-1 involvement in developmental RGC survival was assessed in vitro using retina explants and in vivo using PD-1 knockout mice. PD-1 ligand gene expression was detected by RT-PCR. RESULTS PD-1 is expressed in most adult RGCs, and undergoes dynamic upregulation during the early postnatal window of retinal cell maturation and physiological programmed cell death (PCD). In vitro blockade of PD-1 signaling during this time selectively increases survival of RGCs. Furthermore, PD-1 deficient mice show a selective increase in RGC number in the neonatal retina at the peak of developmental RGC death. Lastly, throughout postnatal retina maturation, we find gene expression of both immune PD-1 ligand genes, PD-L1 and PD-L2. CONCLUSIONS These findings collectively support a novel role for a PD-1-mediated signaling pathway in developmental PCD during postnatal RGC maturation. PMID:19420345

Window of visibility - A psychophysical theory of fidelity in time-sampled visual motion displays

NASA Technical Reports Server (NTRS)

Watson, A. B.; Ahumada, A. J., Jr.; Farrell, J. E.

1986-01-01

A film of an object in motion presents on the screen a sequence of static views, while the human observer sees the object moving smoothly across the screen. Questions related to the perceptual identity of continuous and stroboscopic displays are examined. Time-sampled moving images are considered along with the contrast distribution of continuous motion, the contrast distribution of stroboscopic motion, the frequency spectrum of continuous motion, the frequency spectrum of stroboscopic motion, the approximation of the limits of human visual sensitivity to spatial and temporal frequencies by a window of visibility, the critical sampling frequency, the contrast distribution of staircase motion and the frequency spectrum of this motion, and the spatial dependence of the critical sampling frequency. Attention is given to apparent motion, models of motion, image recording, and computer-generated imagery.

Age at adoption from institutional care as a window into the lasting effects of early experiences

PubMed Central

Julian, Megan M.

2013-01-01

One of the major questions of human development is how early experience impacts the course of development years later. Children adopted from institutional care experience varying levels of deprivation in their early life followed by qualitatively better care in an adoptive home, providing a unique opportunity to study the lasting effects of early deprivation and its timing. The effects of age at adoption from institutional care are discussed for multiple domains of social and behavioral development within the context of several prominent developmental hypotheses about the effects of early deprivation (cumulative effects, experience-expectant developmental programming, and experience-adaptive developmental programming). Age at adoption effects are detected in a majority of studies, particularly when children experienced global deprivation and were assessed in adolescence. For most outcomes, institutionalization beyond a certain age is associated with a step-like increase in risk for lasting social and behavioral problems, with the step occurring at an earlier age for children who experienced more severe levels of deprivation. Findings are discussed in terms of their concordance and discordance with our current hypotheses, and speculative explanations for the findings are offered. PMID:23576122

Commonly dysregulated genes in murine APL cells

PubMed Central

Yuan, Wenlin; Payton, Jacqueline E.; Holt, Matthew S.; Link, Daniel C.; Watson, Mark A.; DiPersio, John F.; Ley, Timothy J.

2007-01-01

To identify genes that are commonly dysregulated in a murine model of acute promyelocytic leukemia (APL), we first defined gene expression patterns during normal murine myeloid development; serial gene expression profiling studies were performed with primary murine hematopoietic progenitors that were induced to undergo myeloid maturation in vitro with G-CSF. Many genes were reproducibly expressed in restricted developmental “windows,” suggesting a structured hierarchy of expression that is relevant for the induction of developmental fates and/or differentiated cell functions. We compared the normal myeloid developmental transcriptome with that of APL cells derived from mice expressing PML-RARα under control of the murine cathepsin G locus. While many promyelocyte-specific genes were highly expressed in all APL samples, 116 genes were reproducibly dysregulated in many independent APL samples, including Fos, Jun, Egr1, Tnf, and Vcam1. However, this set of commonly dysregulated genes was expressed normally in preleukemic, early myeloid cells from the same mouse model, suggesting that dysregulation occurs as a “downstream” event during disease progression. These studies suggest that the genetic events that lead to APL progression may converge on common pathways that are important for leukemia pathogenesis. PMID:17008535

Present and future of developmental neuropsychopharmacology.

PubMed

Arango, Celso

2015-05-01

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

The Construct of the Multisensory Temporal Binding Window and its Dysregulation in Developmental Disabilities

PubMed Central

Wallace, Mark T.; Stevenson, Ryan A.

2014-01-01

Behavior, perception and cognition are strongly shaped by the synthesis of information across the different sensory modalities. Such multisensory integration often results in performance and perceptual benefits that reflect the additional information conferred by having cues from multiple senses providing redundant or complementary information. The spatial and temporal relationships of these cues provide powerful statistical information about how these cues should be integrated or “bound” in order to create a unified perceptual representation. Much recent work has examined the temporal factors that are integral in multisensory processing, with many focused on the construct of the multisensory temporal binding window – the epoch of time within which stimuli from different modalities is likely to be integrated and perceptually bound. Emerging evidence suggests that this temporal window is altered in a series of neurodevelopmental disorders, including autism, dyslexia and schizophrenia. In addition to their role in sensory processing, these deficits in multisensory temporal function may play an important role in the perceptual and cognitive weaknesses that characterize these clinical disorders. Within this context, focus on improving the acuity of multisensory temporal function may have important implications for the amelioration of the “higher-order” deficits that serve as the defining features of these disorders. PMID:25128432

Integrating genetic and toxicogenomic information for determining underlying susceptibility to developmental disorders.

PubMed

Robinson, Joshua F; Port, Jesse A; Yu, Xiaozhong; Faustman, Elaine M

2010-10-01

To understand the complex etiology of developmental disorders, an understanding of both genetic and environmental risk factors is needed. Human and rodent genetic studies have identified a multitude of gene candidates for specific developmental disorders such as neural tube defects (NTDs). With the emergence of toxicogenomic-based assessments, scientists now also have the ability to compare and understand the expression of thousands of genes simultaneously across strain, time, and exposure in developmental models. Using a systems-based approach in which we are able to evaluate information from various parts and levels of the developing organism, we propose a framework for integrating genetic information with toxicogenomic-based studies to better understand gene-environmental interactions critical for developmental disorders. This approach has allowed us to characterize candidate genes in the context of variables critical for determining susceptibility such as strain, time, and exposure. Using a combination of toxicogenomic studies and complementary bioinformatic tools, we characterize NTD candidate genes during normal development by function (gene ontology), linked phenotype (disease outcome), location, and expression (temporally and strain-dependent). In addition, we show how environmental exposures (cadmium, methylmercury) can influence expression of these genes in a strain-dependent manner. Using NTDs as an example of developmental disorder, we show how simple integration of genetic information from previous studies into the standard microarray design can enhance analysis of gene-environment interactions to better define environmental exposure-disease pathways in sensitive and resistant mouse strains. © Wiley-Liss, Inc.

ISSUES IN ENDOCRINE DISRUPTION: COMPARING CRITICAL PERIODS OF HORMONE SENSITIVITY

EPA Science Inventory

Japanese medaka (Oryzias latipes) have been developed as a model species to compare the effects of endocrine active chemicals at critical life-stage periods of hormonal sensitivity, specifically as reproductively active adults, during the developmental period of differentiation, ...

ASSESSMENT OF THE REPRODUCTIVE AXIS: COMPARING CRITICAL PERIODS OF HORMONE SENSITIVITY.

EPA Science Inventory

Japanese medaka (Oryzias latipes) have been developed as a model species to compare the effects of endocrine active chemicals at critical life-stage periods of hormonal sensitivity, specifically as reproductively active adults, during the developmental period of differentiation, ...

Infants Show a Facilitation Effect for Native Language Phonetic Perception between 6 and 12 Months

ERIC Educational Resources Information Center

Kuhl, Patricia K.; Stevens, Erica; Hayashi, Akiko; Deguchi, Toshisada; Kiritani, Shigeru; Iverson, Paul

2006-01-01

Patterns of developmental change in phonetic perception are critical to theory development. Many previous studies document a decline in nonnative phonetic perception between 6 and 12 months of age. However, much less experimental attention has been paid to developmental change in native-language phonetic perception over the same time period. We…

Verbal Interaction and Development in Families with Adolescents. Advances in Applied Developmental Psychology, Volume 15.

ERIC Educational Resources Information Center

Hofer, Manfred, Ed.; Youniss, James, Ed.; Noack, Peter, Ed.

Individuation theory is rooted in the belief that it is a major developmental task for adolescents to establish their identity while simultaneously maintaining a relationship with their parents. Building on the individuation paradigm, the researchers contributing to this edited volume zeroed in on discourse as a critical mechanism through which…

Research on Children & Adolescents with Mental, Behavioral & Developmental Disorders. Mobilizing a National Initiative. Report of a Study.

ERIC Educational Resources Information Center

Institute of Medicine (NAS), Washington, DC. Div. of Mental Health and Behavioral Medicine.

This report focuses on the 7.5 million children in the United States with diagnosable mental illnesses, examining developmental, behavioral and emotional disorders in this group. Progress being made toward understanding, preventing, and treating these disorders is documented, future directions for research are put forth, and critical resource…

My House Is Covered with Papers! Reflections on a Generation of Active Citizenship. Community Supported Living Series.

ERIC Educational Resources Information Center

O'Brien, Connie Lyle; O'Brien, John

This booklet highlights some of the insights that five mothers of children with developmental disabilities have gained after a generation of working together to improve the lives of people with developmental disabilities in Wisconsin. It discusses civic activism, the critical importance of organized parent support, difficulties in collaborating…

Lasting Effects on Body Weight and Mammary Gland Gene Expression in Female Mice upon Early Life Exposure to n-3 but Not n-6 High-Fat Diets

EPA Science Inventory

Exposure to an imbalance of nutrients prior to conception and during critical developmental periods can have lasting consequences on physiological processes resulting in chronic diseases later in life. Developmental programming has been shown to involve structural and functional ...

Neurocognitive Approaches to Developmental Disorders of Numerical and Mathematical Cognition: The Perils of Neglecting the Role of Development

ERIC Educational Resources Information Center

Ansari, Daniel

2010-01-01

The present paper provides a critical overview of how adult neuropsychological models have been applied to the study of the atypical development of numerical cognition. Specifically, the following three assumptions are challenged: 1. Profiles of strength and weaknesses do not change over developmental time. 2. Similar neuronal structures are…

Motor Skill Interventions to Improve Fundamental Movement Skills of Preschoolers with Developmental Delay

ERIC Educational Resources Information Center

Kirk, Megan A.; Rhodes, Ryan E.

2011-01-01

Preschoolers with developmental delay (DD) are at risk for poor fundamental movement skills (FMS), but a paucity of early FMS interventions exist. The purpose of this review was to critically appraise the existing interventions to establish direction for future trials targeting preschoolers with DD. A total of 11 studies met the inclusion…

Cross-Cultural Adaptation of a Pre-School Screening Instrument: Comparison of Korean and US Populations

ERIC Educational Resources Information Center

Heo, K. H.; Squires, J.; Yovanoff, P.

2008-01-01

Background: Accurate and efficient developmental screening measures are critical for early identification of developmental problems; however, few reliable and valid tests are available in Korea as well as other countries outside the USA. The Ages and Stages Questionnaires (ASQ) was chosen for study with young children in Korea. Methods: The ASQ…

Multidimensional Family Therapy for Young Adolescent Substance Abuse: Twelve-Month Outcomes of a Randomized Controlled Trial

ERIC Educational Resources Information Center

Liddle, Howard A.; Rowe, Cynthia L.; Dakof, Gayle A.; Henderson, Craig E.; Greenbaum, Paul E.

2009-01-01

Research has established the dangers of early onset substance use for young adolescents and its links to a host of developmental problems. Because critical developmental detours can begin or be exacerbated during early adolescence, specialized interventions that target known risk and protective factors in this period are needed. This controlled…

The Psychological Development of Low-Birthweight Children. Annual Advances in Applied Developmental Psychology, Volume 6.

ERIC Educational Resources Information Center

Friedman, Sarah L., Ed.; Sigman, Marian D., Ed.

This book addresses the critical issues, as well as contemporary approaches, used to deal with the developmental, social, intellectual, and coping problems of low-birthweight infants and their families. Following an introduction by I. E. Sigel, the chapters are: (1) "Past, Present, and Future Directions in Research on the Development of…

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

ERIC Educational Resources Information Center

Barbarin, Oscar A.

2015-01-01

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

A Home-Based Media Approach for Developing Critical Skills in Young Visually Impaired Children. Final Report.

ERIC Educational Resources Information Center

Moore, Sheri Bortner

The final report summarizes beginnings as well as accomplishments of a program designed to develop materials for parents and teachers working with visually impaired children at the birth-24 month developmental level. The focus of the materials was to help parents and teachers prevent and remediate developmental lags associated with visual…

Effects of Inter-Alpha Inhibitor Proteins on Neonatal Brain Injury: Age, Task and Treatment Dependent Neurobehavioral Outcomes

PubMed Central

Threlkeld, Steven W.; Gaudet, Cynthia M.; La Rue, Molly E.; Dugas, Ethan; Hill, Courtney A.; Lim, Yow-Pin; Stonestreet, Barbara S.

2014-01-01

Hypoxic-ischemic (HI) brain injury is frequently associated with premature and/or full term birth related complications. HI injury often results in learning and processing deficits that reflect widespread damage to an extensive range of cortical and sub-cortical brain structures. Further, inflammation has been implicated in the long-term progression and severity of HI injury. Recently, Inter-alpha Inhibitor Proteins (IAIPs) have been shown to attenuate inflammation in models of systemic infection. Importantly, preclinical studies of neonatal HI injury and neuroprotection often focus on single time windows of assessment or single behavioral domains. This approach limits translational validity, given evidence for a diverse spectrum of neurobehavioral deficits that may change across developmental windows following neonatal brain injury. Therefore, the aims of this research were to assess the effects of human IAIPs on early neocortical cell death (72 hours post insult), adult regional brain volume measurements (cerebral cortex, hippocampus, striatum, corpus callosum) and long-term behavioral outcomes in juvenile (P38-50) and adult (P80+) periods across two independent learning domains (spatial and non-spatial learning), after postnatal day 7 HI injury in rats. Here, for the first time, we show that IAIPs reduce acute neocortical neuronal cell death and improve brain weight outcome 72 hours following HI injury in the neonatal rat. Further, these longitudinal studies are the first to show age, task and treatment dependent improvements in behavioral outcome for both spatial and non-spatial learning following systemic administration of IAIPs in neonatal HI injured rats. Finally, results also show sparing of brain regions critical for spatial and non-spatial learning in adult animals treated with IAIPs at the time of injury onset. These data support the proposal that Inter-alpha Inhibitor Proteins may serve as novel therapeutics for brain injury associated with premature birth and/or neonatal brain injury and highlight the importance of assessing multiple ages, brain regions and behavioral domains when investigating experimental treatment efficacy. PMID:25084519

Optical Studies of Pure Fluids about Their Critical Points

NASA Astrophysics Data System (ADS)

Pang, Kian Tiong

Three optical experiments were performed on pure fluids near their critical points. In the first two setups, CH_3F and H_2C:CF _2 were each tested in a temperature -controlled, prism-shaped cell and a thin parallel-windows cell. In the prism cell, a laser beam was additionally deflected by the fluid present. From the deflection data, the refractive index was related to the density to find the Lorentz-Lorenz function. Critical temperature (T _{c}), density, refractive index and electronic polarizability were found. In the second experiment, a critically-filled, thin parallel-windows cell was placed in one arm of a Mach-Zehnder interoferometer. Fluid density was monitored by changes in the fringe pattern with changing cell temperature. The aim was to improve on the precision of T_{c}: T_{c}{rm (CH}_3 F) = (44cdot9087 +/- 0cdot0002)C; T _{c}{rm(H}_2C:CF _2) = (29cdot7419 +/- 0cdot0001)C; and, to study the coexistence curve and diameter as close to T_{c} as possible. The critical behaviour was compared to the theoretical renormalization group calculations. The derived coefficients were tested against a proposed three-body interaction to explain the field-mixing term in the diameter near the critical point. It was found that H_2C:CF_2 behaved as predicted by such an interaction; CH _3F (and CHF_3) did not. The third experiment was a feasibility study to find out if (critical) isotherms could be measured optically in a setup which combined the prism and parallel-windows cells. The aim was to map isotherms in as wide a range of pressure and density as possible and to probe the critical region directly. Pressure was monitored by a precise digital pressure gauge. CH_3F and CHF _3 were tested in this system. It was found that at low densities, the calculated second and third virial coefficients agreed with reference values. However, the data around the critical point were not accurate enough for use to calculate the critical exponent, delta . The calculated value was consistently smaller than the expected value. It was believed that the present setup had thermal isolation problems. Suggestions were made as to the improvements of this isotherm cell setup. Lastly, a joint project with the Department of Ophthalmology, UBC to assemble a vitreous fluorophotometer is discussed in Appendix F. The upgrading of the instrument took up the initial two years of this PhD programme.

Effect of the time window on the heat-conduction information filtering model

NASA Astrophysics Data System (ADS)

Guo, Qiang; Song, Wen-Jun; Hou, Lei; Zhang, Yi-Lu; Liu, Jian-Guo

2014-05-01

Recommendation systems have been proposed to filter out the potential tastes and preferences of the normal users online, however, the physics of the time window effect on the performance is missing, which is critical for saving the memory and decreasing the computation complexity. In this paper, by gradually expanding the time window, we investigate the impact of the time window on the heat-conduction information filtering model with ten similarity measures. The experimental results on the benchmark dataset Netflix indicate that by only using approximately 11.11% recent rating records, the accuracy could be improved by an average of 33.16% and the diversity could be improved by 30.62%. In addition, the recommendation performance on the dataset MovieLens could be preserved by only considering approximately 10.91% recent records. Under the circumstance of improving the recommendation performance, our discoveries possess significant practical value by largely reducing the computational time and shortening the data storage space.

Defining the therapeutic time window for suppressing the inflammatory prostaglandin E2 signaling after status epilepticus

PubMed Central

Du, Yifeng; Kemper, Timothy; Qiu, Jiange; Jiang, Jianxiong

2016-01-01

Neuroinflammation is a common feature in nearly all neurological and some psychiatric disorders. Resembling its extraneural counterpart, neuroinflammation can be both beneficial and detrimental depending on the responding molecules. The overall effect of inflammation on disease progression is highly dependent on the extent of inflammatory mediator production and the duration of inflammatory induction. The time-dependent aspect of inflammatory responses suggests that the therapeutic time window for quelling neuroinflammation might vary with molecular targets and injury types. Therefore, it is important to define the therapeutic time window for anti-inflammatory therapeutics, as contradicting or negative results might arise when different treatment regimens are utilized even in similar animal models. Herein, we discuss a few critical factors that can help define the therapeutic time window and optimize treatment paradigm for suppressing the cyclooxygenase-2/prostaglandin-mediated inflammation after status epilepticus. These determinants should also be relevant to other anti-inflammatory therapeutic strategies for the CNS diseases. PMID:26689339

Microeconomics of process control in semiconductor manufacturing

NASA Astrophysics Data System (ADS)

Monahan, Kevin M.

2003-06-01

Process window control enables accelerated design-rule shrinks for both logic and memory manufacturers, but simple microeconomic models that directly link the effects of process window control to maximum profitability are rare. In this work, we derive these links using a simplified model for the maximum rate of profit generated by the semiconductor manufacturing process. We show that the ability of process window control to achieve these economic objectives may be limited by variability in the larger manufacturing context, including measurement delays and process variation at the lot, wafer, x-wafer, x-field, and x-chip levels. We conclude that x-wafer and x-field CD control strategies will be critical enablers of density, performance and optimum profitability at the 90 and 65nm technology nodes. These analyses correlate well with actual factory data and often identify millions of dollars in potential incremental revenue and cost savings. As an example, we show that a scatterometry-based CD Process Window Monitor is an economically justified, enabling technology for the 65nm node.

Borromean Windows for Three-Particle Systems under Screened Coulomb Interactions

NASA Astrophysics Data System (ADS)

Jiang, Zi-Shi; Song, Xiu-Dan; Zhou, Lin; Kar, Sabyasachi

2017-05-01

We have carried out calculations to search Borromean windows (BWs) for 11 different three-body systems interacting with screened Coulomb (Yukawa-type) potentials using Hylleraas-type wave functions within the framework of a variational approach. The critical values of the screening parameters for the ground states of the systems under consideration are reported for which the three-body systems are stable, while all the possible fragments are unbound; that is, it shows windows for Borromean binding. Supported by the National Natural Science Foundation of China under Grant No. 11304086, the University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province of China under Grant No. UNPYSCT-2015019, and the Natural Science Foundation for Distinguished Young Scholars in Heilongjiang University under Grant No. JCL201503

Broadband laser ranging precision and accuracy experiments with PDV benchmarking

NASA Astrophysics Data System (ADS)

Catenacci, Jared; Daykin, Ed; Howard, Marylesa; Lalone, Brandon; Miller, Kirk

2017-06-01

Broadband laser ranging (BLR) is a developmental diagnostic designed to measure the precise position of surfaces and particle clouds moving at velocities of several kilometers per second. Recent single stage gas gun experiments were conducted to quantify the precision and accuracy possible with a typical BLR system. For these experiments, the position of a mirrored projectile is measured relative to the location of a stationary optical flat (uncoated window) mounted within the gun catch tank. Projectile velocity is constrained to one-dimensional motion within the gun barrel. A collimating probe is aligned to be orthogonal to both the target window and the mirrored impactor surface. The probe is used to simultaneously measure the position and velocity with a BLR and conventional Photonic Doppler Velocimetry (PDV) system. Since there is a negligible lateral component to the target velocity, coupled with strong signal returns from a mirrored surface, integrating the PDV measurement provides a high fidelity distance measurement reference to which the BLR measurement may be compared.

Optimized ex-ovo culturing of chick embryos to advanced stages of development.

PubMed

Cloney, Kellie; Franz-Odendaal, Tamara Anne

2015-01-24

Research in anatomy, embryology, and developmental biology has largely relied on the use of model organisms. In order to study development in live embryos model organisms, such as the chicken, are often used. The chicken is an excellent model organism due to its low cost and minimal maintenance, however they present observational challenges because they are enclosed in an opaque eggshell. In order to properly view the embryo as it develops, the shell must be windowed or removed. Both windowing and ex ovo techniques have been developed to assist researchers in the study of embryonic development. However, each of the methods has limitations and challenges. Here, we present a simple, optimized ex ovo culture technique for chicken embryos that enables the observation of embryonic development from stage HH 19 into late stages of development (HH 40), when many organs have developed. This technique is easy to adopt in both undergraduate classes and more advanced research laboratories where embryo manipulations are conducted.

War's enduring effects on the development of egalitarian motivations and in-group biases.

PubMed

Bauer, Michal; Cassar, Alessandra; Chytilová, Julie; Henrich, Joseph

2014-01-01

In suggesting that new nations often coalesce in the decades following war, historians have posed an important psychological question: Does the experience of war generate an enduring elevation in people's egalitarian motivations toward their in-group? We administered social-choice tasks to more than 1,000 children and adults differentially affected by wars in the Republic of Georgia and Sierra Leone. We found that greater exposure to war created a lasting increase in people's egalitarian motivations toward their in-group, but not their out-groups, during a developmental window starting in middle childhood (around 7 years of age) and ending in early adulthood (around 20 years of age). Outside this window, war had no measurable impact on social motivations in young children and had only muted effects on the motivations of older adults. These "war effects" are broadly consistent with predictions from evolutionary approaches that emphasize the importance of group cooperation in defending against external threats, though they also highlight key areas in need of greater theoretical development.

Developmental Origins of Perfectionism Among African American Youth

PubMed Central

Herman, Keith C.; Trotter, Reid; Reinke, Wendy M.; Ialongo, Nicholas

2013-01-01

The present study used a person-centered latent variable approach to classify types of perfectionism among 6th-grade African American children living in an urban setting. In particular, the authors were interested in determining whether an adaptive subtype could be found and validated against external criteria. The authors also attempted to identify any developmental precursors that could reliably differentiate the perfectionist subtypes. A social learning and competence framework was used to select potential 1st-grade risk and protective factors for future perfectionism profiles. Four classes best described the children’s perfectionism scores in 6th grade. Three of these classes resembled the profiles most commonly seen in prior perfectionism research (Non-Critical/Adaptive, Critical/Maladaptive, and Non-Perfectionist). The fourth class, Non-Striving, was characterized by extremely low levels of reported personal standards. Sixth-grade correlates confirmed the distinctiveness of these classes. In particular, the Critical/Maladaptive and Non-Striving classes had higher rates of internalizing symptoms and disorders. Additionally, several 1st-grade predictors suggested unique developmental origins of these classes. The Critical/Maladaptive class was characterized by lower academic skills and elevated teacher-rated attention problems, hyperactivity, shyness, and peer rejection. The Non-Striving class had higher rates of family alcohol problems and lower levels of parent praise. Implications regarding the universal and culture-specific origins and effects of perfectionism are discussed. PMID:21574697

Norms for developmental milestones using VABS-II and association with anthropometric measures among apparently healthy urban Indian preschool children.

PubMed

Selvam, Sumithra; Thomas, Tinku; Shetty, Priya; Zhu, Jianjun; Raman, Vijaya; Khanna, Deepti; Mehra, Ruchika; Kurpad, Anura V; Srinivasan, Krishnamachari

2016-12-01

Assessment of developmental milestones based on locally developed norms is critical for accurate estimate of overall development of a child's cognitive, behavioral, social, and emotional development. A cross-sectional study was done to develop age specific norms for developmental milestones using Vineland Adaptive Behavior Scales (VABS-II) (Sparrow, Cicchetti, & Balla, 2005) for apparently healthy children from 2 to 5 years from urban Bangalore, India, and to examine its association with anthropometric measures. Mothers (or caregivers) of 412 children participated in the study. Age-specific norms using inferential norming method and adaptive levels for all domains and subdomains were derived. Low adaptive level, also called delayed developmental milestone, was observed in 2.3% of the children, specifically 2.7% in motor and daily living skills and 2.4% in communication skills. When these children were assessed on the existing U.S. norms, there was a significant overestimation of delayed development in socialization and motor skills, whereas delay in communication and daily living skills were underestimated (all p < .01). Multiple linear regression revealed that stunted and underweight children had significantly lower developmental scores for communication and motor skills compared with normal children (β coefficient ranges from 2.6-5.3; all p < .01). In the absence of Indian normative data for VABS-II in preschool children, the prevalence of developmental delay could either be under- or overestimated using Western norms. Thus, locally referenced norms are critical for reliable assessments of development in children. Stunted and underweight children are more likely to have poorer developmental scores compared with healthy children. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

How one might miss early warning signals of critical transitions in time series data: A systematic study of two major currency pairs

PubMed Central

Ciamarra, Massimo Pica; Cheong, Siew Ann

2018-01-01

There is growing interest in the use of critical slowing down and critical fluctuations as early warning signals for critical transitions in different complex systems. However, while some studies found them effective, others found the opposite. In this paper, we investigated why this might be so, by testing three commonly used indicators: lag-1 autocorrelation, variance, and low-frequency power spectrum at anticipating critical transitions in the very-high-frequency time series data of the Australian Dollar-Japanese Yen and Swiss Franc-Japanese Yen exchange rates. Besides testing rising trends in these indicators at a strict level of confidence using the Kendall-tau test, we also required statistically significant early warning signals to be concurrent in the three indicators, which must rise to appreciable values. We then found for our data set the optimum parameters for discovering critical transitions, and showed that the set of critical transitions found is generally insensitive to variations in the parameters. Suspecting that negative results in the literature are the results of low data frequencies, we created time series with time intervals over three orders of magnitude from the raw data, and tested them for early warning signals. Early warning signals can be reliably found only if the time interval of the data is shorter than the time scale of critical transitions in our complex system of interest. Finally, we compared the set of time windows with statistically significant early warning signals with the set of time windows followed by large movements, to conclude that the early warning signals indeed provide reliable information on impending critical transitions. This reliability becomes more compelling statistically the more events we test. PMID:29538373

How one might miss early warning signals of critical transitions in time series data: A systematic study of two major currency pairs.

PubMed

Wen, Haoyu; Ciamarra, Massimo Pica; Cheong, Siew Ann

2018-01-01

There is growing interest in the use of critical slowing down and critical fluctuations as early warning signals for critical transitions in different complex systems. However, while some studies found them effective, others found the opposite. In this paper, we investigated why this might be so, by testing three commonly used indicators: lag-1 autocorrelation, variance, and low-frequency power spectrum at anticipating critical transitions in the very-high-frequency time series data of the Australian Dollar-Japanese Yen and Swiss Franc-Japanese Yen exchange rates. Besides testing rising trends in these indicators at a strict level of confidence using the Kendall-tau test, we also required statistically significant early warning signals to be concurrent in the three indicators, which must rise to appreciable values. We then found for our data set the optimum parameters for discovering critical transitions, and showed that the set of critical transitions found is generally insensitive to variations in the parameters. Suspecting that negative results in the literature are the results of low data frequencies, we created time series with time intervals over three orders of magnitude from the raw data, and tested them for early warning signals. Early warning signals can be reliably found only if the time interval of the data is shorter than the time scale of critical transitions in our complex system of interest. Finally, we compared the set of time windows with statistically significant early warning signals with the set of time windows followed by large movements, to conclude that the early warning signals indeed provide reliable information on impending critical transitions. This reliability becomes more compelling statistically the more events we test.

PARK2-dependent mitophagy induced by acidic postconditioning protects against focal cerebral ischemia and extends the reperfusion window.

PubMed

Shen, Zhe; Zheng, Yanrong; Wu, Jiaying; Chen, Ying; Wu, Xiaoli; Zhou, Yiting; Yuan, Yang; Lu, Shousheng; Jiang, Lei; Qin, Zhenghong; Chen, Zhong; Hu, Weiwei; Zhang, Xiangnan

2017-03-04

Prompt reperfusion after cerebral ischemia is critical for neuronal survival. Any strategies that extend the limited reperfusion window will be of great importance. Acidic postconditioning (APC) is a mild acidosis treatment that involves inhaling CO 2 during reperfusion following ischemia. APC attenuates ischemic brain injury although the underlying mechanisms have not been elucidated. Here we report that APC reinforces ischemia-reperfusion-induced mitophagy in middle cortical artery occlusion (MCAO)-treated mice, and in oxygen-glucose deprivation (OGD)-treated brain slices and neurons. Inhibition of mitophagy compromises neuroprotection conferred by APC. Furthermore, mitophagy and neuroprotection are abolished in Park2 knockout mice, indicating that APC-induced mitophagy is facilitated by the recruitment of PARK2 to mitochondria. Importantly, in MCAO mice, APC treatment extended the effective reperfusion window from 2 to 4 h, and this window was further extended to 6 h by exogenously expressing PARK2. Taken together, we found that PARK2-dependent APC-induced mitophagy renders the brain resistant to ischemic injury. APC treatment could be a favorable strategy to extend the thrombolytic time window for stroke therapy.

The dynamic lift of developmental process.

PubMed

Smith, Linda B; Breazeal, Cynthia

2007-01-01

What are the essential properties of human intelligence, currently unparalleled in its power relative to other biological forms and relative to artificial forms of intelligence? We suggest that answering this question depends critically on understanding developmental process. This paper considers three principles potentially essential to building human-like intelligence: the heterogeneity of the component processes, the embedding of development in a social world, and developmental processes that change the cognitive system as a function of the history of soft-assemblies of these heterogeneous processes in specific tasks. The paper uses examples from human development and from developmental robotics to show how these processes also may underlie biological intelligence and enable us to generate more advanced forms of artificial intelligence.

Teaching critical thinking in a developmental biology course at an American liberal arts college.

PubMed

Adams, Dany S

2003-01-01

We all expect our students to learn facts and concepts, but more importantly, we want them to learn how to evaluate new information from an educated and skeptical perspective; that is, we want them to become critical thinkers. For many of us who are scientists and teachers, critical thought is either intuitive or we learned it so long ago that it is not at all obvious how to pass on the skills to our students. Explicitly discussing the logic that underlies the experimental basis of developmental biology is an easy and very successful way to teach critical thinking skills. Here, I describe some simple changes to a lecture course that turn the practice of critical thinking into the centerpiece of the learning process. My starting point is the "Evidence and Antibodies" sidelight in Gilbert's Developmental Biology (2000), which I use as an introduction to the ideas of correlation, necessity and sufficiency, and to the kinds of experiments required to gather each type of evidence: observation ("show it"), loss of function ("block it") and gain of function ("move it"). Thereafter, every experiment can be understood quickly by the class and discussed intelligently with a common vocabulary. Both verbal and written reinforcement of these ideas dramatically improve the students' ability to evaluate new information. In particular, they are able to evaluate claims about cause and effect; they become experts at distinguishing between correlation and causation. Because the intellectual techniques are so powerful and the logic so satisfying, the students come to view the critical assessment of knowledge as a fun puzzle and the rigorous thinking behind formulating a question as an exciting challenge.

Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and pubertal development in girls.

PubMed

Watkins, Deborah J; Sánchez, Brisa N; Téllez-Rojo, Martha Maria; Lee, Joyce M; Mercado-García, Adriana; Blank-Goldenberg, Clara; Peterson, Karen E; Meeker, John D

2017-11-01

Over the past several decades, the age of pubertal onset in girls has shifted downward worldwide. As early pubertal onset is associated with increased risky behavior and psychological issues during adolescence and cardiometabolic disease and cancer in adulthood, this is an important public health concern. Exposure to endocrine disrupting chemicals during critical windows of in utero development may play a role in this trend. Our objective was to investigate trimester-specific phthalate and BPA exposure in relation to pubertal development among girls in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. We measured maternal urinary phthalate metabolites and BPA in samples collected during the first, second, and third trimesters of pregnancy. To assess reproductive development among their female children, we measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation, including Tanner staging for breast and pubic hair development and menarche status, at age 8-13 years (n = 120). We used linear and logistic regression to examine measures of trimester-specific in utero exposure as predictors of peripubertal hormone levels and pubertal onset, respectively. In secondary analyses, we evaluated estimated exposure at the midpoint of the first trimester and rates of change in exposure across pregnancy in relation to outcomes. Several phthalate metabolites measured throughout in utero development were associated with higher serum testosterone concentrations, while a number of metabolites measured in the third trimester were associated with higher DHEA-S. For example, an interquartile range (IQR) increase in mean monoethyl phthalate (MEP) levels across pregnancy was associated with 44% higher peripubertal testosterone (95% CI: 13-83%), while an IQR increase in di-2-ethylhexyl phthalate metabolites (ΣDEHP) specifically in the third trimester was associated with 25% higher DHEA-S (95%CI: 4.7-47%). In IQR increase in mean mono-2-ethylhexyl phthalate (MEHP) levels across pregnancy was associated with lower odds of having a Tanner Stage >1 for breast development (OR = 0.32, 95%CI: 0.11-0.95), while MEHP in the third trimester was associated with higher odds of having a Tanner Stage >1 for pubic hair development (OR = 3.76, 95%CI: 1.1-12.8). Results from secondary analyses were consistent with findings from our main analysis. These findings suggest that female reproductive development may be more vulnerable to the effects of phthalate or BPA exposure during specific critical periods of in utero development. This highlights the need for comprehensive characterizations of in utero exposure and consideration of windows of susceptibility in developmental epidemiological studies. Future research should consider repeated measures of in utero phthalate and BPA exposure within each trimester and across pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

NEURODEVELOPMENTAL EFFECTS OF ENVIRONMENTAL EXPOSURES

EPA Science Inventory

Neurodevelopmental Effects of Environmental Exposures
Sherry G. Selevan, Pauline Mendola, Deborah C. Rice (US EPA, Washington,
DC)

The nervous system starts development early in gestation and continues to develop through adolescence. Thus, critical windows of vuln...

Critical Analysis of a Population Mental Health Strategy: Effects on Stigma for People with Intellectual and Developmental Disabilities

ERIC Educational Resources Information Center

Hamdani, Yani; Ary, Ayelet; Lunsky, Yona

2017-01-01

Introduction: Stigma is widely identified as an issue affecting the health and well-being of people with intellectual and developmental disabilities (IDD), and those with mental illnesses. To address this issue, a population mental health strategy, which includes a focus on reducing stigma and discrimination, was developed by the government of…

A Focus on Upper Elementary Teacher Preparation: Developmentally Appropriate Practice and Standards Shaping Our Programs

ERIC Educational Resources Information Center

Finnan, Christine

2010-01-01

This article is a call to action for elementary teacher educators. Our early childhood and middle grades colleagues made a clear case for the importance of focusing on specific developmental characteristics and family and community influences on development during the critical years they represent. A similar case has not been made for the upper…

Technologies for Self-Determination for Youth with Developmental Disabilities. Technologies for Voice: A Critical Issues Brief

ERIC Educational Resources Information Center

Skouge, James R.; Kelly, Mary L.; Roberts, Kelly D.; Leake, David W.; Stodden, Robert A.

2007-01-01

This paper focuses on "technologies for voice" that are related to the self-determination of youth with developmental disabilities. The authors describe a self-determination model that values family-focused, community-referenced pedagogies employing "new media" to give voice to youth and their families. In line with the adage that a picture is…

Financial Well-Being of US Parents Caring for Coresident Children and Adults with Developmental Disabilities: An Age Cohort Analysis

ERIC Educational Resources Information Center

Parish, Susan L.; Rose, Roderick A.; Swaine, Jamie G.

2010-01-01

Background: Understanding how financial well-being changes through the life course of caregiving parents of children with developmental disabilities is critically important. Methods: We analyse SIPP (U.S. Census Bureau) data to describe income poverty, asset poverty, income, net worth, and liquid assets of US parents (N = 753) of children with…

Not a Stage! A Critical Re-Conception of Young Adolescent Education. Adolescent Cultures, School and Society. Volume 60

ERIC Educational Resources Information Center

Vagle, Mark D., Ed.

2012-01-01

"Not a Stage!" is written for teachers, students, and scholars interested in the academic, social, and emotional needs of young adolescents. It is unique because it actively resists basing the practice, research, and theory of young adolescent education on developmentalism and the developmental stage of young adolescence. The purpose of…

Catching Fish and Avoiding Sharks: Investigating Factors That Influence Developmentally Appropriate Measurement of Preschoolers' Inhibitory Control

ERIC Educational Resources Information Center

Howard, Steven J.; Okely, Anthony D.

2015-01-01

Although researchers agree that the first 5 years of life are critical for children's developing executive functions (EFs), further advances are hindered by a lack of consensus on the design and selection of developmentally appropriate EF tasks for young children. Given this debate, well-established adult measures of EF routinely have been adapted…

Education for Critical Moral Consciousness

ERIC Educational Resources Information Center

Mustakova-Possardt, Elena

2004-01-01

This paper proposes a lifespan developmental model of critical moral consciousness and examines its implications for education in childhood, adolescence and adulthood. Mature moral consciousness, central to negotiating the challenges of the 21st century, is characterized by a deepening lifelong integration of moral motivation, agency and critical…

Evaluation of SNS Beamline Shielding Configurations using MCNPX Accelerated by ADVANTG

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

Risner, Joel M; Johnson, Seth R.; Remec, Igor

2015-01-01

Shielding analyses for the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory pose significant computational challenges, including highly anisotropic high-energy sources, a combination of deep penetration shielding and an unshielded beamline, and a desire to obtain well-converged nearly global solutions for mapping of predicted radiation fields. The majority of these analyses have been performed using MCNPX with manually generated variance reduction parameters (source biasing and cell-based splitting and Russian roulette) that were largely based on the analyst's insight into the problem specifics. Development of the variance reduction parameters required extensive analyst time, and was often tailored to specific portionsmore » of the model phase space. We previously applied a developmental version of the ADVANTG code to an SNS beamline study to perform a hybrid deterministic/Monte Carlo analysis and showed that we could obtain nearly global Monte Carlo solutions with essentially uniform relative errors for mesh tallies that cover extensive portions of the model with typical voxel spacing of a few centimeters. The use of weight window maps and consistent biased sources produced using the FW-CADIS methodology in ADVANTG allowed us to obtain these solutions using substantially less computer time than the previous cell-based splitting approach. While those results were promising, the process of using the developmental version of ADVANTG was somewhat laborious, requiring user-developed Python scripts to drive much of the analysis sequence. In addition, limitations imposed by the size of weight-window files in MCNPX necessitated the use of relatively coarse spatial and energy discretization for the deterministic Denovo calculations that we used to generate the variance reduction parameters. We recently applied the production version of ADVANTG to this beamline analysis, which substantially streamlined the analysis process. We also tested importance function collapsing (in space and energy) capabilities in ADVANTG. These changes, along with the support for parallel Denovo calculations using the current version of ADVANTG, give us the capability to improve the fidelity of the deterministic portion of the hybrid analysis sequence, obtain improved weight-window maps, and reduce both the analyst and computational time required for the analysis process.« less

Cyclopamine-induced synophthalmia in sheep: defining a critical window and toxicokinetic evaluation.

PubMed

Welch, K D; Panter, K E; Lee, S T; Gardner, D R; Stegelmeier, B L; Cook, D

2009-07-01

Cyclopamine, a steroidal alkaloid, from the plant Veratrum californicum is teratogenic, causing a range of different birth defects. The critical window for cyclopamine-induced synophthalmia formation has been reported to be gestational day (GD) 14. The objectives of this study were to better describe cyclopamine-induced craniofacial deformities, to better define the window of susceptibility to synophthalmia formation, and to characterize cyclopamine toxicokinetics in sheep. Ewes were dosed i.v. with purified cyclopamine for toxicokinetic analysis. Another four groups of ewes were dosed orally twice daily with 0.88 g/kg of V. californicum on GD 13, 14 or 15 or consecutively on GD days 13-15. Pregnancy and pre-partum fetal malformations were determined by ultrasound imaging on GD 60. At parturition lambs were assessed for gross malformations. The elimination half-life of cyclopamine in ewes was determined to be 1.1 +/- 0.1 h. The rapid clearance of cyclopamine indicates that ingestion of V. californicum must occur during a very narrow window for synophthalmia formation to occur. Ewes dosed with V. californicum on GD 13 or 14 had lambs with various craniofacial malformations including cyclopia, maxillary dysplasia and mandibular micrognathia. Ewes dosed on GD 15 delivered normal lambs. Ewes dosed consecutively on GD 13-15 were not pregnant at GD 60 and Veratrum-induced embryonic death was assumed to be the cause. Interestingly, lambs with cyclopia were smaller, under-developed and appeared premature even though their twin appeared fully developed. Initial evaluations suggest this was due to placental dysplasia. 2009 by John Wiley & Sons, Ltd.

Dynamic proteomics emphasizes the importance of selective mRNA translation and protein turnover during Arabidopsis seed germination.

PubMed

Galland, Marc; Huguet, Romain; Arc, Erwann; Cueff, Gwendal; Job, Dominique; Rajjou, Loïc

2014-01-01

During seed germination, the transition from a quiescent metabolic state in a dry mature seed to a proliferative metabolic state in a vigorous seedling is crucial for plant propagation as well as for optimizing crop yield. This work provides a detailed description of the dynamics of protein synthesis during the time course of germination, demonstrating that mRNA translation is both sequential and selective during this process. The complete inhibition of the germination process in the presence of the translation inhibitor cycloheximide established that mRNA translation is critical for Arabidopsis seed germination. However, the dynamics of protein turnover and the selectivity of protein synthesis (mRNA translation) during Arabidopsis seed germination have not been addressed yet. Based on our detailed knowledge of the Arabidopsis seed proteome, we have deepened our understanding of seed mRNA translation during germination by combining two-dimensional gel-based proteomics with dynamic radiolabeled proteomics using a radiolabeled amino acid precursor, namely [(35)S]-methionine, in order to highlight de novo protein synthesis, stability, and turnover. Our data confirm that during early imbibition, the Arabidopsis translatome keeps reflecting an embryonic maturation program until a certain developmental checkpoint. Furthermore, by dividing the seed germination time lapse into discrete time windows, we highlight precise and specific patterns of protein synthesis. These data refine and deepen our knowledge of the three classical phases of seed germination based on seed water uptake during imbibition and reveal that selective mRNA translation is a key feature of seed germination. Beyond the quantitative control of translational activity, both the selectivity of mRNA translation and protein turnover appear as specific regulatory systems, critical for timing the molecular events leading to successful germination and seedling establishment.

Dynamic Proteomics Emphasizes the Importance of Selective mRNA Translation and Protein Turnover during Arabidopsis Seed Germination*

PubMed Central

Galland, Marc; Huguet, Romain; Arc, Erwann; Cueff, Gwendal; Job, Dominique; Rajjou, Loïc

2014-01-01

During seed germination, the transition from a quiescent metabolic state in a dry mature seed to a proliferative metabolic state in a vigorous seedling is crucial for plant propagation as well as for optimizing crop yield. This work provides a detailed description of the dynamics of protein synthesis during the time course of germination, demonstrating that mRNA translation is both sequential and selective during this process. The complete inhibition of the germination process in the presence of the translation inhibitor cycloheximide established that mRNA translation is critical for Arabidopsis seed germination. However, the dynamics of protein turnover and the selectivity of protein synthesis (mRNA translation) during Arabidopsis seed germination have not been addressed yet. Based on our detailed knowledge of the Arabidopsis seed proteome, we have deepened our understanding of seed mRNA translation during germination by combining two-dimensional gel-based proteomics with dynamic radiolabeled proteomics using a radiolabeled amino acid precursor, namely [35S]-methionine, in order to highlight de novo protein synthesis, stability, and turnover. Our data confirm that during early imbibition, the Arabidopsis translatome keeps reflecting an embryonic maturation program until a certain developmental checkpoint. Furthermore, by dividing the seed germination time lapse into discrete time windows, we highlight precise and specific patterns of protein synthesis. These data refine and deepen our knowledge of the three classical phases of seed germination based on seed water uptake during imbibition and reveal that selective mRNA translation is a key feature of seed germination. Beyond the quantitative control of translational activity, both the selectivity of mRNA translation and protein turnover appear as specific regulatory systems, critical for timing the molecular events leading to successful germination and seedling establishment. PMID:24198433

Cerebellum: links between development, developmental disorders and motor learning

PubMed Central

Manto, Mario U.; Jissendi, Patrice

2012-01-01

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 remodeling are being unraveled. 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, 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 signaling between granule cells and Purkinje neurons. The expression profile of 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 developments and learning deficiencies. Pathways playing a critical role in cerebellar development are likely to become therapeutical targets for several neurodevelopmental disorders. PMID:22291620

Doppler Imaging in Aortic Stenosis: The Importance of the Nonapical Imaging Windows to Determine Severity in a Contemporary Cohort.

PubMed

Thaden, Jeremy J; Nkomo, Vuyisile T; Lee, Kwang Je; Oh, Jae K

2015-07-01

Although the highest aortic valve velocity was thought to be obtained from imaging windows other than the apex in about 20% of patients with severe aortic stenosis (AS), its occurrence appears to be increasing as the age of patients has increased with the application of transcatheter aortic valve replacement. The aim of this study was to determine the frequency with which the highest peak jet velocity (Vmax) is found at each imaging window, the degree to which neglecting nonapical imaging windows underestimates AS severity, and factors influencing the location of the optimal imaging window in contemporary patients. Echocardiograms obtained in 100 consecutive patients with severe AS from January 3 to May 23, 2012, in which all imaging windows were interrogated, were retrospectively analyzed. AS severity (aortic valve area and mean gradient) was calculated on the basis of the apical imaging window alone and the imaging window with the highest peak jet velocity. The left ventricular-aortic root angle measured in the parasternal long-axis view as well as clinical variables were correlated with the location of highest peak jet velocity. Vmax was most frequently obtained in the right parasternal window (50%), followed by the apex (39%). Subjects with acute angulation more commonly had Vmax at the right parasternal window (65% vs 43%, P = .05) and less commonly had Vmax at the apical window (19% vs 48%, P = .005), but Vmax was still located outside the apical imaging window in 52% of patients with obtuse aortic root angles. If nonapical windows were neglected, 8% of patients (eight of 100) were misclassified from high-gradient severe AS to low-gradient severe AS, and another 15% (15 of 100) with severe AS (aortic valve area < 1.0 cm(2)) were misclassified as having moderate AS (aortic valve area > 1.0 cm(2)). In this contemporary cohort, Vmax was located outside the apical imaging window in 61% of patients, and neglecting the nonapical imaging windows resulted in the misclassification of AS severity in 23% of patients. Aortic root angulation as measured by two-dimensional echocardiography influences the location of Vmax modestly. Despite increasing time constraints on many echocardiography laboratories, these data confirm that routine Doppler interrogation from multiple imaging windows is critical to accurately determine the severity of AS in contemporary clinical practice. Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Opening the Windows of Wonder: A Critical Investigation into the Teaching and Learning of Poetry at Key Stage Four in Northern Ireland

ERIC Educational Resources Information Center

Hanratty, Brian

2008-01-01

This article, which investigates the teaching of poetry at Key Stage Four in Northern Ireland, argues that poetry has a radical, and even subversive, role to play in an increasingly examination-driven educational culture. By focusing partly on the views of a number of poets and critics, the article evaluates the, at times, contested nature of…

Cell segmentation in histopathological images with deep learning algorithms by utilizing spatial relationships.

PubMed

Hatipoglu, Nuh; Bilgin, Gokhan

2017-10-01

In many computerized methods for cell detection, segmentation, and classification in digital histopathology that have recently emerged, the task of cell segmentation remains a chief problem for image processing in designing computer-aided diagnosis (CAD) systems. In research and diagnostic studies on cancer, pathologists can use CAD systems as second readers to analyze high-resolution histopathological images. Since cell detection and segmentation are critical for cancer grade assessments, cellular and extracellular structures should primarily be extracted from histopathological images. In response, we sought to identify a useful cell segmentation approach with histopathological images that uses not only prominent deep learning algorithms (i.e., convolutional neural networks, stacked autoencoders, and deep belief networks), but also spatial relationships, information of which is critical for achieving better cell segmentation results. To that end, we collected cellular and extracellular samples from histopathological images by windowing in small patches with various sizes. In experiments, the segmentation accuracies of the methods used improved as the window sizes increased due to the addition of local spatial and contextual information. Once we compared the effects of training sample size and influence of window size, results revealed that the deep learning algorithms, especially convolutional neural networks and partly stacked autoencoders, performed better than conventional methods in cell segmentation.

GOCE Re-Entry Predictions for the Italian Civil Protection Authorities

NASA Astrophysics Data System (ADS)

Pardini, Carmen; Anselmo, Luciano

2015-03-01

The uncommon nature of the GOCE reentry campaign, sharing an uncontrolled orbital decay with a finely controlled attitude along the atmospheric drag direction, made the reentry predictions for this satellite an interesting case study, especially because nobody was able to say a priori if and when the attitude control would have failed, leading to an unrestrained tumbling and a sudden variation of the orbital decay rate. As in previous cases, ISTI/CNR was in charge of reentry predictions for the Italian civil protection authorities, monitoring also the satellite decay in the frame of an international reentry campaign promoted by the Inter-Agency Space Debris Coordination Committee (IADC). Due to the peculiar nature of the GOCE reentry, the definition of reliable uncertainty windows was not easy, especially considering the critical use of this information for civil protection evaluations. However, after an initial period of test and analysis, reasonable and conservative criteria were elaborated and applied, with good and consistent results through the end of the reentry campaign. In the last three days of flight, reentries were simulated over Italy to obtain quite accurate ground tracks, debris swaths and air space crossing time windows associated with the critical passes over the national territory still included in the global uncertainty windows.

The improvement of a simple theoretical model for the prediction of the sound insulation of double leaf walls.

PubMed

Davy, John L

2010-02-01

This paper presents a revised theory for predicting the sound insulation of double leaf cavity walls that removes an approximation, which is usually made when deriving the sound insulation of a double leaf cavity wall above the critical frequencies of the wall leaves due to the airborne transmission across the wall cavity. This revised theory is also used as a correction below the critical frequencies of the wall leaves instead of a correction due to Sewell [(1970). J. Sound Vib. 12, 21-32]. It is found necessary to include the "stud" borne transmission of the window frames when modeling wide air gap double glazed windows. A minimum value of stud transmission is introduced for use with resilient connections such as steel studs. Empirical equations are derived for predicting the effective sound absorption coefficient of wall cavities without sound absorbing material. The theory is compared with experimental results for double glazed windows and gypsum plasterboard cavity walls with and without sound absorbing material in their cavities. The overall mean, standard deviation, maximum, and minimum of the differences between experiment and theory are -0.6 dB, 3.1 dB, 10.9 dB at 1250 Hz, and -14.9 dB at 160 Hz, respectively.

Transmittance of semitransparent windows with absorbing cap-shaped droplets condensed on their backside

NASA Astrophysics Data System (ADS)

Zhu, Keyong; Pilon, Laurent

2017-11-01

This study aims to investigate systematically light transfer through semitransparent windows with absorbing cap-shaped droplets condensed on their backside as encountered in greenhouses, solar desalination plants, photobioreactors and covered raceway ponds. The Monte Carlo ray-tracing method was used to predict the normal-hemispherical transmittance, reflectance, and normal absorptance accounting for reflection and refraction at the air/droplet, droplet/window, and window/air interfaces and absorption in both the droplets and the window. The droplets were monodisperse or polydisperse and arranged either in an ordered hexagonal pattern or randomly distributed on the backside with droplet contact angle θc ranging between 0 and 180° The normal-hemispherical transmittance was found to be independent of the spatial distribution of droplets. However, it decreased with increasing droplet diameter and polydispersity. The normal-hemispherical transmittance featured four distinct optical regimes for semitransparent window supporting nonabsorbing droplets. These optical regimes were defined based on contact angle and critical angle for internal reflection at the droplet/air interface. However, for strongly absorbing droplets, the normal-hemispherical transmittance (i) decreased monotonously with increasing contact angle for θc <90° and (ii) remained constant and independent of droplet absorption index kd, droplet mean diameter dm, and contact angle θc for θc ≥ 90° Analytical expressions for the normal-hemispherical transmittance were provided in the asymptotic cases when (1) the window was absorbing but the droplets were nonabsorbing with any contact angles θc, and (2) the droplets were strongly absorbing with contact angle θc >90° Finally, the spectral normal-hemispherical transmittance of a 3 mm-thick glass window supporting condensed water droplets for wavelength between 0.4 and 5 μm was predicted and discussed in light of the earlier parametric study and asymptotic behavior.

The impact of windows and daylight on acute-care nurses' physiological, psychological, and behavioral health.

PubMed

Zadeh, Rana Sagha; Shepley, Mardelle McCuskey; Williams, Gary; Chung, Susan Sung Eun

2014-01-01

To investigate the physiological and psychological effects of windows and daylight on registered nurses. To date, evidence has indicated that appropriate environmental lighting with characteristics similar to natural light can improve mood, alertness, and performance. The restorative effects of windows also have been documented. Hospital workspaces generally lack windows and daylight, and the impact of the lack of windows and daylight on healthcare employees' well being has not been thoroughly investigated. Data were collected using multiple methods with a quasi-experimental approach (i.e., biological measurements, behavioral mapping, and analysis of archival data) in an acute-care nursing unit with two wards that have similar environmental and organizational conditions, and similar patient populations and acuity, but different availability of windows in the nursing stations. Findings indicated that blood pressure (p < 0.0001) decreased and body temperature increased (p = 0.03). Blood oxygen saturation increased (p = 0.02), but the difference was clinically insignificant. Communication (p < 0.0001) and laughter (p = 0.03) both increased, and the subsidiary behavior indicators of sleepiness and deteriorated mood (p = 0.02) decreased. Heart rate (p = 0.07), caffeine intake (p = 0.3), self-reported sleepiness (p = 0.09), and the frequency of medication errors (p = 0.14) also decreased, but insignificantly. The findings support evidence from laboratory and field settings of the benefits of windows and daylight. A possible micro-restorative effect of windows and daylight may result in lowered blood pressure and increased oxygen saturation and a positive effect on circadian rhythms (as suggested by body temperature) and morning sleepiness. Critical care/intensive care, lighting, nursing, quality care, work environment.

Transmittance of transparent windows with non-absorbing cap-shaped droplets condensed on their backside

NASA Astrophysics Data System (ADS)

Zhu, Keyong; Huang, Yong; Pruvost, Jeremy; Legrand, Jack; Pilon, Laurent

2017-06-01

This study aims to quantify systematically the effect of non-absorbing cap-shaped droplets condensed on the backside of transparent windows on their directional-hemispherical transmittance and reflectance. Condensed water droplets have been blamed to reduce light transfer through windows in greenhouses, solar desalination plants, and photobioreactors. Here, the directional-hemispherical transmittance was predicted by Monte Carlo ray-tracing method. For the first time, both monodisperse and polydisperse droplets were considered, with contact angle between 0 and 180°, arranged either in an ordered hexagonal pattern or randomly distributed on the window backside with projected surface area coverage between 0 and 90%. The directional-hemispherical transmittance was found to be independent of the size and spatial distributions of the droplets. Instead, it depended on (i) the incident angle, (ii) the optical properties of the window and droplets, and on (iii) the droplet contact angle and (iv) projected surface area coverage. In fact, the directional-hemispherical transmittance decreased with increasing incident angle. Four optical regimes were identified in the normal-hemispherical transmittance. It was nearly constant for droplet contact angles either smaller than the critical angle θcr (predicted by Snell's law) for total internal reflection at the droplet/air interface or larger than 180°-θcr. However, between these critical contact angles, the normal-hemispherical transmittance decreased rapidly to reach a minimum at 90° and increased rapidly with increasing contact angles up to 180°-θcr. This was attributed to total internal reflection at the droplet/air interface which led to increasing reflectance. In addition, the normal-hemispherical transmittance increased slightly with increasing projected surface area coverage for contact angle was smaller than θcr. However, it decreased monotonously with increasing droplet projected surface area coverage for contact angle larger than θcr. These results can be used to select the material or surface coating with advantageous surface properties for applications when dropwise condensation may otherwise have a negative effect on light transmittance.

Kant on the history of nature: the ambiguous heritage of the critical philosophy for natural history.

PubMed

Sloan, Phillip R

2006-12-01

This paper seeks to show Kant's importance for the formal distinction between descriptive natural history and a developmental history of nature that entered natural history discussions in the late eighteenth century. It is argued that he developed this distinction initially upon Buffon's distinctions of 'abstract' and 'physical' truths, and applied these initially in his distinction of 'varieties' from 'races' in anthropology. In the 1770s, Kant appears to have given theoretical preference to the 'history' of nature [Naturgeschichte] over 'description' of nature [Naturbeschreibung]. Following Kant's confrontations with Johann Herder and Georg Forster in the late 1780s, Kant weakened the epistemic status of the 'history of nature' and gave theoretical preference to 'description of nature'. As a result, Kant's successors, such as Goethe, could draw from Kant either a justification for a developmental history of nature, or, as this paper argues, a warrant from the critical philosophy for denying the validity of the developmental history of nature as anything more than a 'regulative' idea of reason.

Developmental Neurocircuitry of Motivation in Adolescence: A Critical Period of Addiction Vulnerability

PubMed Central

Chambers, R. Andrew; Taylor, Jane R.; Potenza, Marc N.

2010-01-01

Objective Epidemiological studies indicate that experimentation with addictive drugs and onset of addictive disorders is primarily concentrated in adolescence and young adulthood. The authors describe basic and clinical data supporting adolescent neurodevelopment as a biologically critical period of greater vulnerability for experimentation with substances and acquisition of substance use disorders. Method The authors reviewed recent literature regarding neurocircuitry underlying motivation, impulsivity, and addiction, with a focus on studies investigating adolescent neurodevelopment. Results Adolescent neurodevelopment occurs in brain regions associated with motivation, impulsivity, and addiction. Adolescent impulsivity and/or novelty seeking as a transitional trait behavior can be explained in part by maturational changes in frontal cortical and subcortical monoaminergic systems. These developmental processes may advantageously promote learning drives for adaptation to adult roles but may also confer greater vulnerability to the addictive actions of drugs. Conclusions An exploration of developmental changes in neurocircuitry involved in impulse control has significant implications for understanding adolescent behavior, addiction vulnerability, and the prevention of addiction in adolescence and adulthood. PMID:12777258

Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity

PubMed Central

Smith, Milo R.; Burman, Poromendro

2016-01-01

Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders, such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate plasticity signatures. We tested the hypothesis that inflammation disrupts developmental cortical plasticity in vivo using the mouse ocular dominance model of experience-dependent plasticity in primary visual cortex. We found that the administration of systemic lipopolysaccharide suppressed plasticity during juvenile critical period with accompanying transcriptional changes in a particular set of molecular regulators within primary visual cortex. These findings suggest that inflammation may have unrecognized adverse consequences on the postnatal developmental trajectory and indicate that treating inflammation may reduce the burden of neurodevelopmental disorders. PMID:28101530

Psychosocially influenced cancer: diverse early-life stress experiences and links to breast cancer.

PubMed

Schuler, Linda A; Auger, Anthony P

2010-11-01

This perspective on Boyd et al. (beginning on page 1398 in this issue of the journal) discusses recent published research examining the interplay between social stress and breast cancer. Cross-disciplinary studies using genetically defined mouse models and established neonatal and peripubertal paradigms of social stress are illuminating biological programming by diverse early-life experiences for the risk of breast cancer. Understanding the mechanisms underlying this programming can lead to the identification of risk factors and sensitive developmental windows, enabling improved prevention and treatment strategies for this devastating disease. ©2010 AACR.

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

PubMed

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

2016-10-01

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

Why Do Anxious Children Become Depressed Teenagers?: The Role of Social Evaluative Threat and Reward Processing

PubMed Central

Silk, Jennifer S.; Davis, Stephanie; McMakin, Dana L.; Dahl, Ronald E.; Forbes, Erika E.

2012-01-01

Background Depression is a leading cause of worldwide disability. Adolescence represents a key developmental window in which rates of this disorder increase markedly. Children with an anxiety disorder show a particular risk of developing depression during adolescence. Method We present and review evidence for a developmental model that considers the intersection of two vulnerabilities relevant to the trajectory from anxiety to depression: difficulties in response to potential social evaluation and changes in reward processing at puberty. Results Evidence suggests that these vulnerabilities (a) have been associated with depression, (b) are likely to be problematic in many but not all anxious youth, and (c) may be exacerbated by maturational processes that occur around pubertal development in ways that can create a negative spiral into a depressive disorder. Conclusions We discuss the possibility that early intervention strategies targeting key aspects of these vulnerabilities could alter the trajectory away from depression for many anxious youth. PMID:22340187

Sensitive periods in fear learning and memory.

PubMed

King, Elizabeth C; Pattwell, Siobhan S; Glatt, Charles E; Lee, Francis S

2014-01-01

Adolescence represents a uniquely sensitive developmental stage in the transition from childhood to adulthood. During this transition, neuronal circuits are particularly susceptible to modification by experience. In addition, adolescence is a stage in which the incidence of anxiety disorders peaks in humans and over 75% of adults with fear-related disorders met diagnostic criteria as children and adolescents. While postnatal critical periods of plasticity for primary sensory processes, such as in the visual system are well established, less is known about potential critical or sensitive periods for fear learning and memory. Here, we review the non-linear developmental aspects of fear learning and memory during a transition period into and out of adolescence. We also review the literature on the non-linear development of GABAergic neurotransmission, a key regulator of critical period plasticity. We provide a model that may inform improved treatment strategies for children and adolescents with fear-related disorders.

Sensitive periods in fear learning and memory

PubMed Central

King, Elizabeth C.; Pattwell, Siobhan S.; Glatt, Charles E.; Lee, Francis S.

2015-01-01

Adolescence represents a uniquely sensitive developmental stage in the transition from childhood to adulthood. During this transition, neuronal circuits are particularly susceptible to modification by experience. In addition, adolescence is a stage in which the incidence of anxiety disorders peaks in humans and over 75% of adults with fear-related disorders met diagnostic criteria as children and adolescents. While postnatal critical periods of plasticity for primary sensory processes, such as in the visual system are well established, less is known about potential critical or sensitive periods for fear learning and memory. Here, we review the nonlinear developmental aspects of fear learning and memory during a transition period into and out of adolescence. We also review the literature on the non-linear development of GABAergic neurotransmission, a key regulator of critical period plasticity. We provide a model that may inform improved treatment strategies for children and adolescents with fear-related disorders. PMID:23611461

Long-term care for people with developmental disabilities: a critical analysis.

PubMed

Palley, H A; Van Hollen, V

2000-08-01

This article explores how the trends toward long-term community care affecting people with developmental disabilities developed. Appropriateness of care and quality of life issues are discussed. The article also reviews the development of long-term care for frail and disabled elderly people and explores the arguments for a continuum of care that have developed in this area. The authors conclude that future policies with respect to meeting long-term care needs for people with developmental disabilities must be addressed flexibly on an individual basis, related to individual needs, and must provide a continuum of care services.

Prescribing family criticism as a paradoxical intervention.

PubMed

Bergman, J S

1983-12-01

Two case studies are presented in which parental criticism of children was prescribed in two fused families, who in part were fused because of the mutual and intense criticism between the parents and children. In both cases, prescribing the criticism resulted in blocking the parental criticism, thus forcing the family members to interact in new and different ways. Blocking the criticism permitted the individuals and the family to evolve to the next developmental stages in the family life cycle. Discussion is detailed as to why the prescription of family criticism led to shifts in the family system.

Stage-Specific Plasticity in Ovary Size Is Regulated by Insulin/Insulin-Like Growth Factor and Ecdysone Signaling in Drosophila

PubMed Central

Mendes, Cláudia C.; Mirth, Christen K.

2016-01-01

Animals from flies to humans adjust their development in response to environmental conditions through a series of developmental checkpoints, which alter the sensitivity of organs to environmental perturbation. Despite their importance, we know little about the molecular mechanisms through which this change in sensitivity occurs. Here we identify two phases of sensitivity to larval nutrition that contribute to plasticity in ovariole number, an important determinant of fecundity, in Drosophila melanogaster. These two phases of sensitivity are separated by the developmental checkpoint called “critical weight”; poor nutrition has greater effects on ovariole number in larvae before critical weight than after. We find that this switch in sensitivity results from distinct developmental processes. In precritical weight larvae, poor nutrition delays the onset of terminal filament cell differentiation, the starting point for ovariole development, and strongly suppresses the rate of terminal filament addition and the rate of increase in ovary volume. Conversely, in postcritical weight larvae, poor nutrition affects only the rate of increase in ovary volume. Our results further indicate that two hormonal pathways, the insulin/insulin-like growth factor and the ecdysone-signaling pathways, modulate the timing and rates of all three developmental processes. The change in sensitivity in the ovary results from changes in the relative contribution of each pathway to the rates of terminal filament addition and increase in ovary volume before and after critical weight. Our work deepens our understanding of how hormones act to modify the sensitivity of organs to environmental conditions, thereby affecting their plasticity. PMID:26715667

Building Critical Capacities for Leadership Learning.

PubMed

Torrez, Mark Anthony; Rocco, Melissa L

2015-01-01

Cognitive elements of transformational learning, particularly metacognition and critical self-reflection, are discussed as essential considerations for leadership development in the 21st century. The importance of developmentally sequencing leadership-learning experiences and addressing evolving complexities of leadership identity are also explored. © 2015 Wiley Periodicals, Inc., A Wiley Company.

Generation of interior cavity noise due to window vibration excited by turbulent flows past a generic side-view mirror

NASA Astrophysics Data System (ADS)

Yao, Hua-Dong; Davidson, Lars

2018-03-01

We investigate the interior noise caused by turbulent flows past a generic side-view mirror. A rectangular glass window is placed downstream of the mirror. The window vibration is excited by the surface pressure fluctuations and emits the interior noise in a cuboid cavity. The turbulent flows are simulated using a compressible large eddy simulation method. The window vibration and interior noise are predicted with a finite element method. The wavenumber-frequency spectra of the surface pressure fluctuations are analyzed. The spectra are identified with some new features that cannot be explained by the Chase model for turbulent boundary layers. The spectra contain a minor hydrodynamic domain in addition to the hydrodynamic domain caused by the main convection of the turbulent boundary layer. The minor domain results from the local convection of the recirculating flow. These domains are formed in bent elliptic shapes. The spanwise expansion of the wake is found causing the bending. Based on the wavenumber-frequency relationships in the spectra, the surface pressure fluctuations are decomposed into hydrodynamic and acoustic components. The acoustic component is more efficient in the generation of the interior noise than the hydrodynamic component. However, the hydrodynamic component is still dominant at low frequencies below approximately 250 Hz since it has low transmission losses near the hydrodynamic critical frequency of the window. The structural modes of the window determine the low-frequency interior tonal noise. The combination of the mode shapes of the window and cavity greatly affects the magnitude distribution of the interior noise.

Developmental mechanisms underlying variation in craniofacial disease and evolution.

PubMed

Fish, Jennifer L

2016-07-15

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

Maturation of the P3 and concurrent oscillatory processes during adolescence.

PubMed

Mathes, Birgit; Khalaidovski, Ksenia; Wienke, Annika S; Schmiedt-Fehr, Christina; Basar-Eroglu, Canan

2016-07-01

During adolescence event-related modulations of the neural response may increase. For slow event-related components, such as the P3, this developmental change may be masked due to increased amplitude levels of ongoing delta and theta oscillations in adolescents. In a cross-sectional study design, EEG was measured in 51 participants between 13 and 24years. A visual oddball paradigm was used to elicit the P3. Our analysis focused on fronto-parietal activations within the P3 time-window and the concurrent time-frequency characteristics in the delta (∼0.5-4Hz) and theta (∼4-7Hz) band. The parietal P3 amplitude was similar across the investigated age range, while the amplitude at frontal regions increased with age. The pre-stimulus amplitudes of delta and theta oscillations declined with age, while post-stimulus amplitude enhancement and inter-trial phase coherence increased. These changes affected fronto-parietal electrode sites. The parietal P3 maximum seemed comparable for adolescents and young adults. Detailed analysis revealed that within the P3 time-window brain maturation during adolescence may lead to reduced spontaneous slow-wave oscillations, increased amplitude modulation and time precision of event-related oscillations, and altered P3 scalp topography. Time-frequency analyses may help to distinguish selective neurodevelopmental changes within the P3 time window. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model

PubMed Central

Silva-Santos, Sara; van Woerden, Geeske M.; Bruinsma, Caroline F.; Mientjes, Edwin; Jolfaei, Mehrnoush Aghadavoud; Distel, Ben; Kushner, Steven A.; Elgersma, Ype

2015-01-01

Angelman syndrome (AS) is a severe neurodevelopmental disorder that results from loss of function of the maternal ubiquitin protein ligase E3A (UBE3A) allele. Due to neuron-specific imprinting, the paternal UBE3A copy is silenced. Previous studies in murine models have demonstrated that strategies to activate the paternal Ube3a allele are feasible; however, a recent study showed that pharmacological Ube3a gene reactivation in adulthood failed to rescue the majority of neurocognitive phenotypes in a murine AS model. Here, we performed a systematic study to investigate the possibility that neurocognitive rescue can be achieved by reinstating Ube3a during earlier neurodevelopmental windows. We developed an AS model that allows for temporally controlled Cre-dependent induction of the maternal Ube3a allele and determined that there are distinct neurodevelopmental windows during which Ube3a restoration can rescue AS-relevant phenotypes. Motor deficits were rescued by Ube3a reinstatement in adolescent mice, whereas anxiety, repetitive behavior, and epilepsy were only rescued when Ube3a was reinstated during early development. In contrast, hippocampal synaptic plasticity could be restored at any age. Together, these findings suggest that Ube3a reinstatement early in development may be necessary to prevent or rescue most AS-associated phenotypes and should be considered in future clinical trial design. PMID:25866966

Resource quality affects weapon and testis size and the ability of these traits to respond to selection in the leaf-footed cactus bug, Narnia femorata.

PubMed

Sasson, Daniel A; Munoz, Patricio R; Gezan, Salvador A; Miller, Christine W

2016-04-01

The size of weapons and testes can be central to male reproductive success. Yet, the expression of these traits is often extremely variable. Studies are needed that take a more complete organism perspective, investigating the sources of variation in both traits simultaneously and using developmental conditions that mimic those in nature. In this study, we investigated the components of variation in weapon and testis sizes using the leaf-footed cactus bug, Narnia femorata (Hemiptera: Coreidae) on three natural developmental diets. We show that the developmental diet has profound effects on both weapon and testis expression and scaling. Intriguingly, males in the medium-quality diet express large weapons but have relatively tiny testes, suggesting complex allocation decisions. We also find that heritability, evolvability, and additive genetic variation are highest in the high-quality diet for testis and body mass. This result suggests that these traits may have an enhanced ability to respond to selection during a small window of time each year when this diet is available. Taken together, these results illustrate that normal, seasonal fluctuations in the nutritional environment may play a large role in the expression of sexually selected traits and the ability of these traits to respond to selection.

Evaluation of the developmental toxicity of lead in the Danio rerio body.

PubMed

Roy, Nicole M; DeWolf, Sarah; Carneiro, Bruno

2015-01-01

Lead has been utilized throughout history and is widely distributed and mobilized globally. Although lead in the environment has been somewhat mitigated, the nature of lead and its extensive uses in the past prohibit it from being completely absent from our environment and exposure to lead is still a public health concern. Most studies regarding lead toxicity have focused on the brain. However, little is found in the literature on the effects of lead in other tissues. Here, we utilize the zebrafish model system to investigate effects of lead exposure during early developmental time windows at 24, 48 and 72 h post fertilization in the body. We analyze whole body, notochord and somatic muscle changes, vascular changes of the body, as well as motor neuron alterations. We find lead exposure induces a curved body phenotype with concomitant changes in somite length, decreased notochord staining and abnormal muscle staining using live and in situ approaches. Furthermore, altered vasculature within the somatic regions, loss and/or alternations of motor neuron extension both dorsally and ventrally from the spinal cord, loss of Rohon-Beard sensory neurons, and increased areas of apoptosis were found. We conclude that lead is developmentally toxic to other areas of the developing embryo, not just the brain. Copyright © 2014 Elsevier B.V. All rights reserved.

When can parents most influence their child's development? Expert knowledge and perceived local realities.

PubMed

Worthman, Carol M; Tomlinson, Mark; Rotheram-Borus, Mary Jane

2016-04-01

Compelling evidence for the long-term impact of conditions in gestation and early childhood on both physical and psychosocial functioning and productivity has stimulated a focus in global health policy and social services on the "first 1000 days". Consequently, related initiatives may assume that rationale for this orientation and the agency of parents during this period is self-evident and widely shared among parents and communities. In 2012, we tested this assumption among a sample of 38 township-dwelling caregivers in Cape Town, by asking a question identified during a study of cultural models of parenting, namely: At what age or stage can a parent or caregiver have the most influence on a child's development? Formal cultural consensus analysis of responses met criteria for strong agreement that the period for greatest impact of parenting on a child's development occurs at adolescence, at a median age of 12 years. In follow-up focus groups and structured interviews, caregivers articulated clear ecological and developmental reasons for this view, related to protection both of developmental potential and against powerful, context-specific ecological risks (early pregnancy, substance ab/use, violence and gangs) that emerge during adolescence. Such risks threaten educational attainment, reproductive health, and social derailment with enduring consequences for lifetime well-being that caregivers are highly motivated to prevent. Developmental needs in pregnancy and early childhood, by contrast, were considered more manageable. These findings resonate with emerging evidence for multiple sensitive periods with corresponding developmental needs, and urge the value of complementing efforts to optimize early development with those to sustain and enhance it during later windows of developmental opportunity such as adolescence. Our results also indicate the need to consult local views of developmental risk and parenting practice in communicating with caregivers and planning interventions, and the value of using available methodological tools to do so. Copyright © 2016 Elsevier Ltd. All rights reserved.

When can parents most influence their child’s development? Expert knowledge and perceived local realities

PubMed Central

Worthman, Carol M.; Tomlinson, Mark; Rotheram-Borus, Mary Jane

2016-01-01

Compelling evidence for the long-term impact of conditions in gestation and early childhood on both physical and psychosocial functioning and productivity has stimulated a focus in global health policy and social services on the “first 1000 days”. Consequently, related initiatives may assume that rationale for this orientation and the agency of parents during this period is self-evident and widely shared among parents and communities. We tested this assumption in 2012 among a sample of 38 township-dwelling caregivers in Cape Town, by asking a question identified during a study of cultural models of parenting, namely: At what age or stage can a parent or caregiver have the most influence on a child’s development? Formal cultural consensus analysis of responses met criteria for strong agreement that the period for greatest impact of parenting on a child’s development occurs at adolescence, at a median age of 12 years. In follow-up focus groups and structured interviews, caregivers articulated clear ecological and developmental reasons for this view, related to protection both of developmental potential and against powerful, context-specific ecological risks (early pregnancy, substance ab/use, violence and gangs) that emerge during adolescence. Such risks threaten educational attainment, reproductive health, and social derailment with enduring consequences for lifetime well-being that caregivers are highly motivated to prevent. Developmental needs in pregnancy and early childhood, by contrast, were considered more manageable. These findings resonate with emerging evidence for multiple sensitive periods with corresponding developmental needs, and urge the value of complementing efforts to optimize early development with those to sustain and enhance it during later windows of developmental opportunity such as adolescence. Our results also indicate the need to consult local views of developmental risk and parenting practice in communicating with caregivers and planning interventions, and the value of using available methodological tools to do so. PMID:26945544

Comparative developmental psychology: how is human cognitive development unique?

PubMed

Rosati, Alexandra G; Wobber, Victoria; Hughes, Kelly; Santos, Laurie R

2014-04-29

The fields of developmental and comparative psychology both seek to illuminate the roots of adult cognitive systems. Developmental studies target the emergence of adult cognitive systems over ontogenetic time, whereas comparative studies investigate the origins of human cognition in our evolutionary history. Despite the long tradition of research in both of these areas, little work has examined the intersection of the two: the study of cognitive development in a comparative perspective. In the current article, we review recent work using this comparative developmental approach to study non-human primate cognition. We argue that comparative data on the pace and pattern of cognitive development across species can address major theoretical questions in both psychology and biology. In particular, such integrative research will allow stronger biological inferences about the function of developmental change, and will be critical in addressing how humans come to acquire species-unique cognitive abilities.

Perspective Imagery in Synthetic Scenes used to Control and Guide Aircraft during Landing and Taxi: Some Issues and Concerns

NASA Technical Reports Server (NTRS)

Johnson, Walter W.; Kaiser, Mary K.

2003-01-01

Perspective synthetic displays that supplement, or supplant, the optical windows traditionally used for guidance and control of aircraft are accompanied by potentially significant human factors problems related to the optical geometric conformality of the display. Such geometric conformality is broken when optical features are not in the location they would be if directly viewed through a window. This often occurs when the scene is relayed or generated from a location different from the pilot s eyepoint. However, assuming no large visual/vestibular effects, a pilot cad often learn to use such a display very effectively. Important problems may arise, however, when display accuracy or consistency is compromised, and this can usually be related to geometrical discrepancies between how the synthetic visual scene behaves and how the visual scene through a window behaves. In addition to these issues, this paper examines the potentially critical problem of the disorientation that can arise when both a synthetic display and a real window are present in a flight deck, and no consistent visual interpretation is available.

Modelling the regulatory system for diabetes mellitus with a threshold window

NASA Astrophysics Data System (ADS)

Yang, Jin; Tang, Sanyi; Cheke, Robert A.

2015-05-01

Piecewise (or non-smooth) glucose-insulin models with threshold windows for type 1 and type 2 diabetes mellitus are proposed and analyzed with a view to improving understanding of the glucose-insulin regulatory system. For glucose-insulin models with a single threshold, the existence and stability of regular, virtual, pseudo-equilibria and tangent points are addressed. Then the relations between regular equilibria and a pseudo-equilibrium are studied. Furthermore, the sufficient and necessary conditions for the global stability of regular equilibria and the pseudo-equilibrium are provided by using qualitative analysis techniques of non-smooth Filippov dynamic systems. Sliding bifurcations related to boundary node bifurcations were investigated with theoretical and numerical techniques, and insulin clinical therapies are discussed. For glucose-insulin models with a threshold window, the effects of glucose thresholds or the widths of threshold windows on the durations of insulin therapy and glucose infusion were addressed. The duration of the effects of an insulin injection is sensitive to the variation of thresholds. Our results indicate that blood glucose level can be maintained within a normal range using piecewise glucose-insulin models with a single threshold or a threshold window. Moreover, our findings suggest that it is critical to individualise insulin therapy for each patient separately, based on initial blood glucose levels.

Quality of statistical reporting in developmental disability journals.

PubMed

Namasivayam, Aravind K; Yan, Tina; Wong, Wing Yiu Stephanie; van Lieshout, Pascal

2015-12-01

Null hypothesis significance testing (NHST) dominates quantitative data analysis, but its use is controversial and has been heavily criticized. The American Psychological Association has advocated the reporting of effect sizes (ES), confidence intervals (CIs), and statistical power analysis to complement NHST results to provide a more comprehensive understanding of research findings. The aim of this paper is to carry out a sample survey of statistical reporting practices in two journals with the highest h5-index scores in the areas of developmental disability and rehabilitation. Using a checklist that includes critical recommendations by American Psychological Association, we examined 100 randomly selected articles out of 456 articles reporting inferential statistics in the year 2013 in the Journal of Autism and Developmental Disorders (JADD) and Research in Developmental Disabilities (RDD). The results showed that for both journals, ES were reported only half the time (JADD 59.3%; RDD 55.87%). These findings are similar to psychology journals, but are in stark contrast to ES reporting in educational journals (73%). Furthermore, a priori power and sample size determination (JADD 10%; RDD 6%), along with reporting and interpreting precision measures (CI: JADD 13.33%; RDD 16.67%), were the least reported metrics in these journals, but not dissimilar to journals in other disciplines. To advance the science in developmental disability and rehabilitation and to bridge the research-to-practice divide, reforms in statistical reporting, such as providing supplemental measures to NHST, are clearly needed.

Multisensory integration and ADHD-like traits: Evidence for an abnormal temporal integration window in ADHD.

PubMed

Panagiotidi, Maria; Overton, Paul G; Stafford, Tom

2017-11-01

Abnormalities in multimodal processing have been found in many developmental disorders such as autism and dyslexia. However, surprisingly little empirical work has been conducted to test the integrity of multisensory integration in Attention Deficit Hyperactivity Disorder (ADHD). The main aim of the present study was to examine links between symptoms of ADHD (as measured using a self-report scale in a healthy adult population) and the temporal aspects of multisensory processing. More specifically, a Simultaneity Judgement (SJ) and a Temporal Order Judgement (TOJ) task were used in participants with low and high levels of ADHD-like traits to measure the temporal integration window and Just-Noticeable Difference (JND) (respectively) between the timing of an auditory beep and a visual pattern presented over a broad range of stimulus onset asynchronies. The Point of Subjective Similarity (PSS) was also measured in both cases. In the SJ task, participants with high levels of ADHD-like traits considered significantly fewer stimuli to be simultaneous than participants with high levels of ADHD-like traits, and the former were found to have significantly smaller temporal windows of integration (although no difference was found in the PSS in the SJ or TOJ tasks, or the JND in the latter). This is the first study to identify an abnormal temporal integration window in individuals with ADHD-like traits. Perceived temporal misalignment of two or more modalities can lead to distractibility (e.g., when the stimulus components from different modalities occur separated by too large of a temporal gap). Hence, an abnormality in the perception of simultaneity could lead to the increased distractibility seen in ADHD. Copyright © 2017 Elsevier B.V. All rights reserved.

Neural Consequences of Chronic Short Sleep: Reversible or Lasting?

PubMed Central

Zhao, Zhengqing; Zhao, Xiangxiang; Veasey, Sigrid C.

2017-01-01

Approximately one-third of adolescents and adults in developed countries regularly experience insufficient sleep across the school and/or work week interspersed with weekend catch up sleep. This common practice of weekend recovery sleep reduces subjective sleepiness, yet recent studies demonstrate that one weekend of recovery sleep may not be sufficient in all persons to fully reverse all neurobehavioral impairments observed with chronic sleep loss, particularly vigilance. Moreover, recent studies in animal models demonstrate persistent injury to and loss of specific neuron types in response to chronic short sleep (CSS) with lasting effects on sleep/wake patterns. Here, we provide a comprehensive review of the effects of chronic sleep disruption on neurobehavioral performance and injury to neurons, astrocytes, microglia, and oligodendrocytes and discuss what is known and what is not yet established for reversibility of neural injury. Recent neurobehavioral findings in humans are integrated with animal model research examining long-term consequences of sleep loss on neurobehavioral performance, brain development, neurogenesis, neurodegeneration, and connectivity. While it is now clear that recovery of vigilance following short sleep requires longer than one weekend, less is known of the impact of CSS on cognitive function, mood, and brain health long term. From work performed in animal models, CSS in the young adult and short-term sleep loss in critical developmental windows can have lasting detrimental effects on neurobehavioral performance. PMID:28620347

Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism

PubMed Central

Peñagarikano, Olga; Lázaro, María T.; Lu, Xiao-Hong; Gordon, Aaron; Dong, Hongmei; Lam, Hoa A.; Peles, Elior; Maidment, Nigel T.; Murphy, Niall P.; Yang, X. William; Golshani, Peyman; Geschwind, Daniel H.

2015-01-01

Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homologue of CNTNAP2, in which mutant forms cause Cortical Dysplasia and Focal Epilepsy syndrome (CDFE), displays many features parallel to the human disorder. Since CDFE has high penetrance for autism spectrum disorder (ASD) we performed an in vivo screen for drugs that treat abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment. PMID:25609168

The effects of neonicotinoid exposure on embryonic development and organ mass in northern bobwhite quail (Colinus virginianus).

PubMed

Gobeli, Amanda; Crossley, Dane; Johnson, Jeff; Reyna, Kelly

2017-05-01

Since their emergence in the early 1990s, neonicotinoid use has increased exponentially to make them the world's most prevalent insecticides. Although there has been considerable research concerning the lethality of neonicotinoids, their sub-lethal and developmental effects are still being explored, especially with regard to non-mammalian species. The goal of this research was to investigate the effects of the neonicotinoid imidacloprid on the morphological and physiological development of northern bobwhite quail (Colinus virginianus). Bobwhite eggs (n=390) were injected with imidacloprid concentrations of 0 (sham), 10, 50, 100, and 150mg/kg of egg mass, which was administered at day 0 (pre-incubation), 3, 6, 9, or 12 of growth. Embryos were dissected, weighed, staged, and examined for any overt structural deformities after 19days of incubation. The mass of the embryonic heart, liver, lungs and kidneys was also recorded. The majority of treatments produced no discernible differences in embryo morphology; however, in some instances, embryos were subject to increased frequency of anatomical deformity and altered organ masses. Some impacts were more pronounced in specific dosing periods, implying that there may be critical windows of development when embryos are more susceptible to neonicotinoid exposure. This investigation suggests that imidacloprid has the potential to impact bobwhite quail embryonic development and chick survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural Consequences of Chronic Short Sleep: Reversible or Lasting?

PubMed

Zhao, Zhengqing; Zhao, Xiangxiang; Veasey, Sigrid C

2017-01-01

Approximately one-third of adolescents and adults in developed countries regularly experience insufficient sleep across the school and/or work week interspersed with weekend catch up sleep. This common practice of weekend recovery sleep reduces subjective sleepiness, yet recent studies demonstrate that one weekend of recovery sleep may not be sufficient in all persons to fully reverse all neurobehavioral impairments observed with chronic sleep loss, particularly vigilance. Moreover, recent studies in animal models demonstrate persistent injury to and loss of specific neuron types in response to chronic short sleep (CSS) with lasting effects on sleep/wake patterns. Here, we provide a comprehensive review of the effects of chronic sleep disruption on neurobehavioral performance and injury to neurons, astrocytes, microglia, and oligodendrocytes and discuss what is known and what is not yet established for reversibility of neural injury. Recent neurobehavioral findings in humans are integrated with animal model research examining long-term consequences of sleep loss on neurobehavioral performance, brain development, neurogenesis, neurodegeneration, and connectivity. While it is now clear that recovery of vigilance following short sleep requires longer than one weekend, less is known of the impact of CSS on cognitive function, mood, and brain health long term. From work performed in animal models, CSS in the young adult and short-term sleep loss in critical developmental windows can have lasting detrimental effects on neurobehavioral performance.

Neurexin 1 (NRXN1) Splice Isoform Expression During Human Neocortical Development and Aging

PubMed Central

Jenkins, Aaron K.; Paterson, Clare; Wang, Yanhong; Hyde, Thomas M.; Kleinman, Joel E.; Law, Amanda J.

2015-01-01

Neurexin 1 (NRXN1), a presynaptic adhesion molecule, is implicated in several neurodevelopmental disorders characterized by synaptic dysfunction including, autism, intellectual disability, and schizophrenia. To gain insight into NRXN1’s involvement in human cortical development we used quantitative real time PCR to examine the expression trajectories of NRXN1, and its predominant isoforms NRXN1-α and NRXN1-β in prefrontal cortex from fetal stages to aging. Additionally, we investigated whether prefrontal cortical expression levels of NRXN1 transcripts are altered in schizophrenia or bipolar disorder in comparison to non-psychiatric control subjects. We observed that all three NRXN1 transcripts were highly expressed during human fetal cortical development, dramatically increasing with gestational age. In the postnatal DLPFC, expression levels were negatively correlated with age, peaking at birth until approximately 3 years of age, after which levels declined dramatically to be stable across the lifespan. NRXN1-β expression was modestly but significantly elevated in the brains of patients with schizophrenia compared to non-psychiatric controls, whereas NRXN1-α expression was increased in bipolar disorder. These data provide novel evidence that NRXN1 expression is highest in human prefrontal cortex during critical developmental windows relevant to the onset and diagnosis of a range of neurodevelopmental disorders, and that NRXN1 expression may be differentially altered in neuropsychiatric disorders. PMID:26216298

A Response to Jack R. Fraenkel. An Exchange of Views between Edwin Fenton and Jack R. Fraenkel, the Cognitive-Developmental Approach to Moral Education

ERIC Educational Resources Information Center

Fenton, Edwin

1977-01-01

Responses to Fraenkel's 15 criticisms of the author's article about Kohlberg's cognitive-developmental approach to moral education in the April 1976 issue of "Social Education." Three circumstances are stated as reasons for the differences between the two men: (1) staying up-to-date with research and publications, (2) time consumed in refuting…

Course-Taking Patterns, Policies, and Practices in Developmental Education in the California Community Colleges. A Report to the California Community Colleges Chancellor's Office

ERIC Educational Resources Information Center

Perry, Mary; Bahr, Peter Riley; Rosin, Matthew; Woodward, Kathryn Morgan

2010-01-01

The visibility of developmental education--or basic skills education as it is called most often in California--has increased in recent years. One major catalyst was a comprehensive community college strategic planning process completed in 2004 that listed basic skills as a critical area of focus. Another was an increase in the system's minimum…

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

PubMed Central

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

2017-01-01

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

GEODSS Present Configuration and Potential

DTIC Science & Technology

2014-06-28

to provide critical metric tracking capacity for deep space catalog maintenance. The follow-up TOS designed as a deployable gap filler in SSN deep...CASTOR) - A RAVEN System In Canada [3]WindowPane Observatory Lanphier Shutter System 2014 Retrieved From: http://windowpaneobservatory.com/ [4]J.N

Thermal effects in Cs DPAL and alkali cell window damage

NASA Astrophysics Data System (ADS)

Zhdanov, B. V.; Rotondaro, M. D.; Shaffer, M. K.; Knize, R. J.

2016-10-01

Experiments on power scaling of Diode Pumped Alkali Lasers (DPALs) revealed some limiting parasitic effects such as alkali cell windows and gain medium contamination and damage, output power degradation in time and others causing lasing efficiency decrease or even stop lasing1 . These problems can be connected with thermal effects, ionization, chemical interactions between the gain medium components and alkali cells materials. Study of all these and, possibly, other limiting effects and ways to mitigate them is very important for high power DPAL development. In this talk we present results of our experiments on temperature measurements in the gain medium of operating Cs DPAL at different pump power levels in the range from lasing threshold to the levels causing damage of the alkali cell windows. For precise contactless in situ temperature measurements, we used an interferometric technique, developed in our lab2 . In these experiments we demonstrated that damage of the lasing alkali cell starts in the bulk with thermal breakdown of the hydrocarbon buffer gas. The degradation processes start at definite critical temperatures of the gain medium, different for each mixture of buffer gas. At this critical temperature, the hydrocarbon and the excited alkali metal begin to react producing the characteristic black soot and, possibly, some other chemical compounds, which both harm the laser performance and significantly increase the harmful heat deposition within the laser medium. This soot, being highly absorptive, is catastrophically heated to very high temperatures that visually observed as bulk burning. This process quickly spreads to the cell windows and causes their damage. As a result, the whole cell is also contaminated with products of chemical reactions.

Fabrication of Multi-point Side-Firing Optical Fiber by Laser Micro-ablation

PubMed Central

Nguyen, Hoang; Arnob, Md Masud Parvez; Becker, Aaron T; Wolfe, John C; Hogan, Matthew K; Horner, Philip J; Shih, Wei-Chuan

2018-01-01

A multi-point, side-firing design enables an optical fiber to output light at multiple desired locations along the fiber body. This provides advantages over traditional end-to-end fibers, especially in applications requiring fiber bundles such as brain stimulation or remote sensing. This paper demonstrates that continuous wave (CW) laser micro-ablation can controllably create conical-shaped cavities, or side windows, for outputting light. The dimensions of these cavities determine the amount of firing light and their firing angle. Experimental data show that a single side window on a 730 μm fiber can deliver more than 8 % of the input light. This was increased to more than 19 % on a 65 μm fiber with side windows created using femtosecond (fs) laser ablation and chemical etching. Fine control of light distribution along an optical fiber is critical for various biomedical applications such as light activated drug-release and optogenetics studies. PMID:28454166

Fabrication of multipoint side-firing optical fiber by laser micro-ablation.

PubMed

Nguyen, Hoang; Parvez Arnob, Md Masud; Becker, Aaron T; Wolfe, John C; Hogan, Matthew K; Horner, Philip J; Shih, Wei-Chuan

2017-05-01

A multipoint, side-firing design enables an optical fiber to output light at multiple desired locations along the fiber body. This provides advantages over traditional end-to-end fibers, especially in applications requiring fiber bundles such as brain stimulation or remote sensing. This Letter demonstrates that continuous wave (CW) laser micro-ablation can controllably create conical-shaped cavities, or side windows, for outputting light. The dimensions of these cavities determine the amount of firing light and their firing angle. Experimental data show that a single side window on a 730 μm fiber can deliver more than 8% of the input light. This can be increased to more than 19% on a 65 μm fiber with side windows created using femtosecond laser ablation and chemical etching. Fine control of light distribution along an optical fiber is critical for various biomedical applications such as light-activated drug-release and optogenetics studies.

Effect of temperature and nutrients on the growth and development of seedlings of an invasive plant.

PubMed

Skálová, Hana; Moravcová, Lenka; Dixon, Anthony F G; Kindlmann, P; Pyšek, Petr

2015-04-28

Plant species distributions are determined by the response of populations to regional climates; however, little is known about how alien plants that arrive in central Europe from climatically warmer regions cope with the temperature conditions at the early stage of population development. Ambrosia artemisiifolia (common ragweed) is an invasive annual plant causing considerable health and economic problems in Europe. Although climate-based models predict that the whole of the Czech Republic is climatically suitable for this species, it is confined to the warmest regions. To determine the factors possibly responsible for its restricted occurrence, we investigated the effects of temperature and nutrient availability on its seedlings. The plants were cultivated at one of seven temperature regimes ranging from 10 to 34 °C, combined with three nutrient levels. The data on the rate of leaf development were used to calculate the lower developmental threshold (LDT, the temperature, in °C, below which development ceases), the sum of effective temperatures (SET, the amount of heat needed to complete a developmental stage measured in degree days above LDT) and width of the thermal window. The rate of development decreased with decrease in temperature and nutrient supply. Besides this, the decrease in the availability of nutrients resulted in decreased LDT, increased SET and wider thermal window. The dependence of LDT and SET on the availability of nutrients contradicts the concept that thermal constants do not vary. Our results highlight temperature as the main determinant of common ragweed's distribution and identify nutrient availability as a factor that results in the realized niche being smaller than the fundamental niche; both of these need to be taken into account when predicting the future spread of A. artemisiifolia. Published by Oxford University Press on behalf of the Annals of Botany Company.

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

PubMed Central

Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

2015-01-01

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMN). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30µM). Previous work showed that the paralytic mutant zebrafish known as sofa potato, exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. PMID:25668718

Exposure to butachlor causes thyroid endocrine disruption and promotion of metamorphosis in Xenopus laevis.

PubMed

Li, Shuying; Li, Meng; Wang, Qiangwei; Gui, Wenjun; Zhu, Guonian

2016-06-01

Butachlor is extensively applied in rice paddy ecosystem in china, and has been widespread contaminant in the aquatic environment. Here, Xenopus laevis was used for the evaluation of teratogenesis developmental toxicity, and disruption of thyroid system when exposure to different concentrations of butachlor by window phase exposure. Acute toxicity investigation shown that 96 h-LC50 value of butachlor was 1.424 mg L(-1) and 0.962 mg L(-1) for tadpoles (starting from stages 46/47) and embryos (starting from stages 8/9), respectively. Exposure to butachlor caused malformation, including abnormal eye, pericardial edema, enlarged proctodaeum and bent tail. Window phase exposure test indicated that butachlor significantly promote the contents of whole-body thyroid hormones (THs, T3 and T4) at higher levels, indicating thyroid endocrine disruption. At 7 days, exposure to butachlor up-regulated the mRNA expression of genes involved in THs synthesis and metabolism (tshα, tg, tpo and dio1) and THs receptors (trα and trβ). At 14 days, up-regulation of the mRNA expression of genes related to THs synthesis and metabolism (tshα, tshβ, tg, tpo, dio1, dio2 and ttr) and THs receptors (trβ) were also observed after the exposure to butachlor. At 21 days, butachlor up-regulated the mRNA expression of tshα, tg, tpo genes and down-regulated the mRNA expression of tshβ, tg, dio1, ttr and trα genes. These results showed that butachlor could change the mRNA expression of genes involved in the HPT axis and increase whole-body thyroid hormones levels of X. laevis tadpoles in a dose- and time-dependent manner, causing thyroid endocrine disruption and developmental toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lace plant ethylene receptors, AmERS1a and AmERS1c, regulate ethylene-induced programmed cell death during leaf morphogenesis.

PubMed

Rantong, Gaolathe; Evans, Rodger; Gunawardena, Arunika H L A N

2015-10-01

The lace plant, Aponogeton madagascariensis, is an aquatic monocot that forms perforations in its leaves as part of normal leaf development. Perforation formation occurs through developmentally regulated programmed cell death (PCD). The molecular basis of PCD regulation in the lace plant is unknown, however ethylene has been shown to play a significant role. In this study, we examined the role of ethylene receptors during perforation formation. We isolated three lace plant ethylene receptors AmERS1a, AmERS1b and AmERS1c. Using quantitative PCR, we examined their transcript levels at seven stages of leaf development. Through laser-capture microscopy, transcript levels were also determined in cells undergoing PCD and cells not undergoing PCD (NPCD cells). AmERS1a transcript levels were significantly lower in window stage leaves (in which perforation formation and PCD are occurring) as compared to all other leaf developmental stages. AmERS1a and AmERS1c (the most abundant among the three receptors) had the highest transcript levels in mature stage leaves, where PCD is not occurring. Their transcript levels decreased significantly during senescence-associated PCD. AmERS1c had significantly higher transcript levels in NPCD compared to PCD cells. Despite being significantly low in window stage leaves, AmERS1a transcripts were not differentially expressed between PCD and NPCD cells. The results suggested that ethylene receptors negatively regulate ethylene-controlled PCD in the lace plant. A combination of ethylene and receptor levels determines cell fate during perforation formation and leaf senescence. A new model for ethylene emission and receptor expression during lace plant perforation formation and senescence is proposed.

How climate change will affect sessile stages of brown trout (Salmo trutta) in mountain streams of the Iberian Peninsula

NASA Astrophysics Data System (ADS)

Santiago, José M.; Alonso, Carlos; García de Jalón, Diego; Solana, Joaquín

2017-04-01

Streamflow and temperature regimes are determinant for the availability of suitable physical habitat for instream biological communities. Iberian brown trout (Salmo trutta) populations live in a climatic border in which summer water scarcity and raising temperatures will compromise their viability throughout the current century. Due to their impaired mobility, sessile stages of trout life cycle (i.e. eggs and larvae) are among the most sensitive organisms to environmental changing conditions. At a given spawning redd, thermal habitat is limited by the length of the period at which suitable temperatures occur. At the same time, suitable physical habitat is limited by the instream flow regime during spawning and incubation of eggs and larvae. Temperature and flow do also interact, thus producing synergistic effects on both physical and thermal habitats. This study is aimed at quantitatively predicting thermal and physical habitat loss for the sessile stages of brown trout life cycle due to clime change, in mountain streams at the rear edge of the species natural distribution using high-resolution spatial-temporal simulations of the thermal and physical habitat. Two streams of Central Spain have been studied (Cega and Lozoya streams). Daily temperature and flow data from ad hoc downscaled IPCC (RCP4.5 and RCP8.5) predictions were used as input variables. Physical habitat changes were simulated from previously predicted stream flow data by means of hydraulic simulation tools (River2D). By taking into account the thermal tolerance limits and the proportion of lost physical habitat, limiting factors for the reproduction of brown trout in the study area were determined. The general increase of mean temperatures shortens the duration of the early developmental stages. This reduction of the sessile period is rather similar in both RCP4.5 and RCP8.5 scenarios by 2050. Differences between both scenarios become greater by 2099. The duration of sessile developmental is reduced in 12 days (-10%) according to scenario RCP4.5 and as much as 30 days (-25%) according to RCP8.5 in the Cega stream. Reduction of this sessile period in the Lozoya stream ranges between 14 days (-12%) in RCP4.5 and 35 (-29%) in RCP8.5. However, this acceleration of the development is not sufficient to compensate the much greater reduction of the thermal window in which mean water temperature remain below 10°C (considered a critical threshold). In the Cega stream, suitable thermal window reduction will range between 21% (RCP4.5) and 49% (RCP8.5) by 2099. In contrast, the Lozoya stream will lose much less time of suitable temperatures by 2099: 3% and 21%, according to RCP4.5 and RCP8.5, respectively. Although habitat reductions will be significant during the spawning season, the most important problems for trout population viability seem to be related to the reduction of the available time window for embryos and larvae to complete their development. Besides, due to the differential sensitivity of instream thermal habitat to a general increase in air temperature, it is highly recommendable to address locally adapted mitigation programs to avoid a general retraction of the current native range of this species.

Towards a Philosophically and a Pedagogically Reasonable Nature of Science Curriculum

NASA Astrophysics Data System (ADS)

Yacoubian, Hagop Azad

This study, primarily theoretical in nature, explores a philosophically and pedagogically reasonable way of addressing nature of science (NOS) in school science. NOS encompasses what science is and how scientific knowledge develops. I critically evaluate consensus frameworks of NOS in school science, which converge contentious philosophical viewpoints into general NOS-related ideas. I argue that they (1) lack clarity in terms of how NOS-related ideas could be applied for various ends, (2) portray a distorted image of the substantive content of NOS and the process of its development, and (3) lack a developmental trajectory for how to address NOS at different grade levels. As a remedy to these problems, I envision a NOS curriculum that (1) explicates and targets both NOS as an educational end and NOS as a means for socioscientific decision making, (2) has critical thinking as its foundational pillar, and (3) provides a developmental pathway for NOS learning using critical thinking as a progression unit. Next, I illustrate a framework for addressing NOS in school science referred to as the critical thinking—nature of science (CT-NOS) framework. This framework brings together the first two of the three elements envisioned in the NOS curriculum. I address the third element by situating the CT-NOS framework in a developmental context, borrowing from the literature on learning progressions in science and using critical thinking as a progression unit. Finally, I present an empirical study of experienced secondary science teachers’ views of a NOS lesson prepared using the CT-NOS framework. The teachers attended a professional development workshop at which the lesson, and the characteristics of the CT-NOS framework, were presented. The analysis of the qualitative data revealed that most teachers found the lesson to be somewhat feasible for a secondary science classroom, useful or somewhat useful to their students, and interesting. The teachers focused on 14 features of the lesson in their judgments and recommendations. The study revealed a number of teacher challenges generally related to critical thinking and its teaching as well as to the distinction between critical thinking about NOS and critical thinking with NOS.

Explaining Differences in Age at Autism Spectrum Disorder Diagnosis: A Critical Review

ERIC Educational Resources Information Center

Daniels, Amy M.; Mandell, David S.

2014-01-01

The diagnosis of autism is often delayed, which translates into a missed opportunity to provide treatment during a critical developmental period. This study reviews studies that assessed factors associated with age at autism spectrum disorder diagnosis and provides recommendations on future research, programs, and policies to improve early…

A Matter of Timing: Enhancing Positive Change for the Developing Brain

ERIC Educational Resources Information Center

Fox, Nathan A.; Zeanah, Charles H.; Nelson, Charles A.

2014-01-01

Neuroscientists have long believed that there are sensitive periods in development during which the effects of experience play a critical role. And developmental psychologists have argued for the importance of early experience in the first years of life as being critical for brain and behavioral development. Most of the neuroscience research…

Conducting Informal Developmental Assessments of Toddlers

ERIC Educational Resources Information Center

Gibson, Craig P.

2012-01-01

The transition from infancy to toddlerhood occurs after the youngster's first year of life (12-24 months). This is a critical time in a child's development. In this year, children develop critical thinking skills and begin making connections in the world around them. They demonstrate increased independence and view themselves as the center of…

Metaphor and Metonymy in ASD Children: A Critical Review from a Developmental Perspective

ERIC Educational Resources Information Center

Melogno, Sergio; Pinto, Maria Antonietta; Levi, Gabriel

2012-01-01

The aim of the present article is to critically review the experimental research in the domain of metaphor and metonymy competencies in Autism Spectrum Disorders (ASD) children. After providing some basic definitions of metaphor and metonymy, we consider some major points emerging from studies on metaphorical and metonymical competencies in…

Planar cell polarity pathway in vertebrate epidermal development, homeostasis and repair

PubMed Central

Dworkin, Sebastian; Jane, Stephen M

2011-01-01

The planar cell polarity (PCP) pathway plays a critical role in diverse developmental processes that require coordinated cellular movement, including neural tube closure and renal tubulogenesis. Recent studies have demonstrated that this pathway also has emerging relevance to the epidermis, as PCP signaling underpins many aspects of skin biology and pathology, including epidermal development, hair orientation, stem cell division and cancer. Coordinated cellular movement required for epidermal repair in mammals is also regulated by PCP signaling, and in this context, a new PCP gene encoding the developmental transcription factor Grainyhead-like 3 (Grhl3) is critical. This review focuses on the role that PCP signaling plays in the skin across a variety of epidermal functions and highlights perturbations that induce epidermal pathologies. PMID:22041517

A Window of Opportunity for Cognitive Training in Adolescence

PubMed Central

Knoll, Lisa J.; Fuhrmann, Delia; Sakhardande, Ashok L.; Stamp, Fabian; Speekenbrink, Maarten; Blakemore, Sarah-Jayne

2016-01-01

In the current study, we investigated windows for enhanced learning of cognitive skills during adolescence. Six hundred thirty-three participants (11–33 years old) were divided into four age groups, and each participant was randomly allocated to one of three training groups. Each training group completed up to 20 days of online training in numerosity discrimination (i.e., discriminating small from large numbers of objects), relational reasoning (i.e., detecting abstract relationships between groups of items), or face perception (i.e., identifying differences in faces). Training yielded some improvement in performance on the numerosity-discrimination task, but only in older adolescents or adults. In contrast, training in relational reasoning improved performance on that task in all age groups, but training benefits were greater for people in late adolescence and adulthood than for people earlier in adolescence. Training did not increase performance on the face-perception task for any age group. Our findings suggest that for certain cognitive skills, training during late adolescence and adulthood yields greater improvement than training earlier in adolescence, which highlights the relevance of this late developmental stage for education. PMID:27815519

Patterns of anomalies of structures of the middle ear and the facial nerve as revealed in newborn temporal bones.

PubMed

Tóth, Miklós; Sirirattanapan, Jarinratn; Mann, Wolf

2013-08-01

The purpose of this study is to offer new data about facial nerve malformations in the tympanic cavity. Prospective anatomic study of newborns to demonstrate the submacroscopic anatomy of the intratympanic facial nerve and its surrounding structures by malformations. Step-by-step microdissection of 12 newborn temporal bones and histologic evaluation of 4 middle ears showing multiple malformations. Four of 12 temporal bones presented malformation in the middle ear. All 4 temporal bones showed developmental failures of the stapes, and 3 of them had malposition of the tympanic portion of the facial nerve. In 3 cases, there was an oval window atresia, and in 1 case, the rim of the oval window was not ossified and was positioned medial to the stapes. Malformation or displacement of the stapes can be an indirect sign for facial nerve malformation. The most common site for facial nerve malformation is the tympanic portion. The tympanic segment of the nerve is devoid of bony covering in association with these anomalies of the stapes.

Empathy

ERIC Educational Resources Information Center

Munin, Art

2007-01-01

The unfortunate reality is that racism permeates life. The time that students spend in higher education offers a window of opportunity for educators to confront students' assumptions about the world and challenge them to critically analyze their experience. After students complete their education, they carry their knowledge to offices, law firms,…

36 CFR Appendix A to Part 1234 - Minimum Security Standards for Level III Federal Facilities

Code of Federal Regulations, 2014 CFR

2014-07-01

... technology and blast standards. Immediate review of ongoing projects may generate savings in the... critical systems (alarm systems, radio communications, computer facilities, etc.) Required. Occupant... all exterior windows (shatter protection) Recommended. Review current projects for blast standards...

36 CFR Appendix A to Part 1234 - Minimum Security Standards for Level III Federal Facilities

Code of Federal Regulations, 2013 CFR

2013-07-01

... construction projects should be reviewed if possible, to incorporate current technology and blast standards... critical systems (alarm systems, radio communications, computer facilities, etc.) Required. Occupant... all exterior windows (shatter protection) Recommended. Review current projects for blast standards...

36 CFR Appendix A to Part 1234 - Minimum Security Standards for Level III Federal Facilities

Code of Federal Regulations, 2012 CFR

2012-07-01

... technology and blast standards. Immediate review of ongoing projects may generate savings in the... critical systems (alarm systems, radio communications, computer facilities, etc.) Required. Occupant... all exterior windows (shatter protection) Recommended. Review current projects for blast standards...

ENVIRONMENTAL FACTORS ASSOCIATED WITH MENTAL RETARDATION AND DEVELOPMENT DISABILITY

EPA Science Inventory

Abstract

A number of environmental agents have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. Critical windows of vulnerability to the effects of these agents occur both pre- and postnatally. The nervous system is relatively un...

Mechanical diagnosis of human erythrocytes by ultra-high speed manipulation unraveled critical time window for global cytoskeletal remodeling

NASA Astrophysics Data System (ADS)

Ito, Hiroaki; Murakami, Ryo; Sakuma, Shinya; Tsai, Chia-Hung Dylan; Gutsmann, Thomas; Brandenburg, Klaus; Pöschl, Johannes M. B.; Arai, Fumihito; Kaneko, Makoto; Tanaka, Motomu

2017-02-01

Large deformability of erythrocytes in microvasculature is a prerequisite to realize smooth circulation. We develop a novel tool for the three-step “Catch-Load-Launch” manipulation of a human erythrocyte based on an ultra-high speed position control by a microfluidic “robotic pump”. Quantification of the erythrocyte shape recovery as a function of loading time uncovered the critical time window for the transition between fast and slow recoveries. The comparison with erythrocytes under depletion of adenosine triphosphate revealed that the cytoskeletal remodeling over a whole cell occurs in 3 orders of magnitude longer timescale than the local dissociation-reassociation of a single spectrin node. Finally, we modeled septic conditions by incubating erythrocytes with endotoxin, and found that the exposure to endotoxin results in a significant delay in the characteristic transition time for cytoskeletal remodeling. The high speed manipulation of erythrocytes with a robotic pump technique allows for high throughput mechanical diagnosis of blood-related diseases.

Developmental perspectives on personality: implications for ecological and evolutionary studies of individual differences.

PubMed

Stamps, Judy A; Groothuis, Ton G G

2010-12-27

Developmental processes can have major impacts on the correlations in behaviour across contexts (contextual generality) and across time (temporal consistency) that are the hallmarks of animal personality. Personality can and does change: at any given age or life stage it is contingent upon a wide range of experiential factors that occurred earlier in life, from prior to conception through adulthood. We show how developmental reaction norms that describe the effects of prior experience on a given behaviour can be used to determine whether the effects of a given experience at a given age will affect contextual generality at a later age, and to illustrate how variation within individuals in developmental plasticity leads to variation in contextual generality across individuals as a function of experience. We also show why niche-picking and niche-construction, behavioural processes which allow individuals to affect their own developmental environment, can affect the contextual generality and the temporal consistency of personality. We conclude by discussing how an appreciation of developmental processes can alert behavioural ecologists studying animal personality to critical, untested assumptions that underlie their own research programmes, and outline situations in which a developmental perspective can improve studies of the functional significance and evolution of animal personality.

Catching Fish and Avoiding Sharks: Investigating Factors That Influence Developmentally Appropriate Measurement of Preschoolers' Inhibitory Control.

PubMed

Howard, Steven J; Okely, Anthony D

2015-09-01

Although researchers agree that the first 5 years of life are critical for children's developing executive functions (EFs), further advances are hindered by a lack of consensus on the design and selection of developmentally appropriate EF tasks for young children. Given this debate, well-established adult measures of EF routinely have been adapted for young children. Given young children's comparatively limited cognitive capacities, however, such adaptations do not guarantee that the task's critical EF demands are retained. To investigate this possibility, the current study examined the characteristics that optimize measurement of young children's EFs-specifically, their inhibitory control-using the go/no-go (GNG) task as an exemplar. Sixty preschoolers completed six GNG tasks differing in stimulus animation, presentation time, and response location. Comparison EF tasks were administered to examine concurrent validity of GNG variants. Results indicated effects of stimulus presentation time and response location, with animation further enhancing task validity and reliability. This suggests that current GNG tasks deflate estimates of young children's ability to inhibit, with implications for future design and selection of developmentally appropriate EF tasks.

Environmental and epigenetic effects upon preimplantation embryo metabolism and development

PubMed Central

Chason, Rebecca J; Csokmay, John; Segars, James H.; DeCherney, Alan H.; Armant, D. Randall

2011-01-01

In vitro fertilization has provided a unique window into the metabolic processes that drive embryonic growth and development from a fertilized ovum to a competent blastocyst. Post-fertilization development is dependent upon a dramatic reshuffling of the parental genomes during meiosis, as well as epigenetic changes that provide a new and autonomous set of instructions to guide cellular differentiation both in the embryo and beyond. While early literature focused simply on the substrates and culture conditions required for progress through embryonic development, more recent insights lead us to suggest that the surrounding environment can alter the epigenome, which can, in turn, impact embryonic metabolism and developmental competence. PMID:21741268

Do windows or natural views affect outcomes or costs among patients in ICUs?

PubMed

Kohn, Rachel; Harhay, Michael O; Cooney, Elizabeth; Small, Dylan S; Halpern, Scott D

2013-07-01

To determine whether potential exposure to natural light via windows or to more pleasing views through windows affects outcomes or costs among critically ill patients. Retrospective cohort study. An academic hospital in Philadelphia, PA. Six thousand one hundred thirty-eight patients admitted to a 24-bed medical ICU and 6,631 patients admitted to a 24-bed surgical ICU from July 1, 2006, to June 30, 2010. Assignment to medical ICU rooms with vs. without windows and to surgical ICU rooms with natural vs. industrial views based on bed availability. In primary analyses adjusting for patient characteristics, medical ICU patients admitted to rooms with (n = 4,093) versus without (n = 2,243) windows did not differ in rates of ICU (p = 0.25) or in-hospital (p = 0.94) mortality, ICU readmissions (p = 0.37), or delirium (p = 0.56). Surgical ICU patients admitted to rooms with natural (n = 3,072) versus industrial (n = 3,588) views experienced slightly shorter ICU lengths of stay and slightly lower variable costs. Instrumental variable analyses based on initial bed assignment and exposure time did not show any differences in any outcomes in either the medical ICU or surgical ICU cohorts, and none of the differences noted in primary analyses remained statistically significant when adjusting for multiple comparisons. In a prespecified subgroup analysis among patients with ICU length of stay greater than 72 hours, MICU windows were associated with reduced ICU (p = 0.02) and hospital mortality (p = 0.04); these results did not meet criteria for significance after adjustment for multiple comparisons. ICU rooms with windows or natural views do not improve outcomes or reduce costs of in-hospital care for general populations of medical and surgical ICU patients. Future work is needed to determine whether targeting light from windows directly toward patients influences outcomes and to explore these effects in patients at high risk for adverse outcomes.

Empathy-Related Responding in Chinese Toddlers: Factorial Structure and Cognitive Contributors

ERIC Educational Resources Information Center

Huang, Heqing; Su, Yanjie; Jin, Jian

2017-01-01

The critical role of the second year of life in the development of empathy is well accepted by psychologists. However, the developmental trends of the different components of empathy and the potential factors underlying these components during this critical period remain unclear. Eighty-four Chinese toddlers in the second year of life participated…

Psychology in Education as Developmental Healthcare: A Proposal for Fundamental Change and Survival.

ERIC Educational Resources Information Center

Bagnato, Stephen J.

The survival of psychologists and psychological services in public education is a pressing concern of critical importance to children, families, and school systems. Psychologists advocate that the critical first step for clients to change behavior and personality is to define the problem and to accept its validity. The main problem facing…

Commentary: Youth Are Critical to Stemming the Worldwide Tide of Chronic Disease

ERIC Educational Resources Information Center

Baldwin, Wendy

2013-01-01

Adolescence is a critical developmental stage and an opportunity to set a positive course for future health and well-being. Adolescence may be the "last best chance" to address some of the behaviors that can have significant repercussions for an individual's health trajectory, specifically the path to noncommunicable diseases (NCDs). Why should…

Optimization of ramp area aircraft push back time windows in the presence of uncertainty

NASA Astrophysics Data System (ADS)

Coupe, William Jeremy

It is well known that airport surface traffic congestion at major airports is responsible for increased taxi-out times, fuel burn and excess emissions and there is potential to mitigate these negative consequences through optimizing airport surface traffic operations. Due to a highly congested voice communication channel between pilots and air traffic controllers and a data communication channel that is used only for limited functions, one of the most viable near-term strategies for improvement of the surface traffic is issuing a push back advisory to each departing aircraft. This dissertation focuses on the optimization of a push back time window for each departing aircraft. The optimization takes into account both spatial and temporal uncertainties of ramp area aircraft trajectories. The uncertainties are described by a stochastic kinematic model of aircraft trajectories, which is used to infer distributions of combinations of push back times that lead to conflict among trajectories from different gates. The model is validated and the distributions are included in the push back time window optimization. Under the assumption of a fixed taxiway spot schedule, the computed push back time windows can be integrated with a higher level taxiway scheduler to optimize the flow of traffic from the gate to the departure runway queue. To enable real-time decision making the computational time of the push back time window optimization is critical and is analyzed throughout.

Developmental Neurotoxicology: History and Outline of ...

EPA Pesticide Factsheets

The present work provides a brief review of basic concepts in developmental neurotoxicology, as well as current representative testing guidelines for evaluating developmental neurotoxicity (DNT) of xenobiotics. Historically, DNT was initially recognized as a “functional” teratogenicity: the main concern was that prenatal and/or early postnatal exposures to chemicals during critical periods of central nervous system (CNS) development would cause later functional abnormalities of the brain. Current internationally harmonized DNT study guidelines are thus intended to predict adverse effects of test compounds on the developing CNS by observing such postnatal parameters as motor activity, startle response, and learning and memory, as well as neropathological alterations. The reliability of current DNT study guidelines and sensitivity of testing methodologies recommended in these guidelines have been confirmed by retrospective evaluations of the many international and domestic collaborative validation studies in developed nations including Japan. Invited review with brief review of basic concepts in developmental neurotoxicology, as well as current representative testing guidelines for evaluating developmental neurotoxicity (DNT) of xenobiotics.

Neural Correlates of Multisensory Perceptual Learning

PubMed Central

Powers, Albert R.; Hevey, Matthew A.; Wallace, Mark T.

2012-01-01

The brain’s ability to bind incoming auditory and visual stimuli depends critically on the temporal structure of this information. Specifically, there exists a temporal window of audiovisual integration within which stimuli are highly likely to be perceived as part of the same environmental event. Several studies have described the temporal bounds of this window, but few have investigated its malleability. Recently, our laboratory has demonstrated that a perceptual training paradigm is capable of eliciting a 40% narrowing in the width of this window that is stable for at least one week after cessation of training. In the current study we sought to reveal the neural substrates of these changes. Eleven human subjects completed an audiovisual simultaneity judgment training paradigm, immediately before and after which they performed the same task during an event-related 3T fMRI session. The posterior superior temporal sulcus (pSTS) and areas of auditory and visual cortex exhibited robust BOLD decreases following training, and resting state and effective connectivity analyses revealed significant increases in coupling among these cortices after training. These results provide the first evidence of the neural correlates underlying changes in multisensory temporal binding and that likely represent the substrate for a multisensory temporal binding window. PMID:22553032

A Virtual Study of Grid Resolution on Experiments of a Highly-Resolved Turbulent Plume

NASA Astrophysics Data System (ADS)

Maisto, Pietro M. F.; Marshall, Andre W.; Gollner, Michael J.; Fire Protection Engineering Department Collaboration

2017-11-01

An accurate representation of sub-grid scale turbulent mixing is critical for modeling fire plumes and smoke transport. In this study, PLIF and PIV diagnostics are used with the saltwater modeling technique to provide highly-resolved instantaneous field measurements in unconfined turbulent plumes useful for statistical analysis, physical insight, and model validation. The effect of resolution was investigated employing a virtual interrogation window (of varying size) applied to the high-resolution field measurements. Motivated by LES low-pass filtering concepts, the high-resolution experimental data in this study can be analyzed within the interrogation windows (i.e. statistics at the sub-grid scale) and on interrogation windows (i.e. statistics at the resolved scale). A dimensionless resolution threshold (L/D*) criterion was determined to achieve converged statistics on the filtered measurements. Such a criterion was then used to establish the relative importance between large and small-scale turbulence phenomena while investigating specific scales for the turbulent flow. First order data sets start to collapse at a resolution of 0.3D*, while for second and higher order statistical moments the interrogation window size drops down to 0.2D*.

Temporal relation between neural activity and neurite pruning on a numerical model and a microchannel device with micro electrode array.

PubMed

Kondo, Yohei; Yada, Yuichiro; Haga, Tatsuya; Takayama, Yuzo; Isomura, Takuya; Jimbo, Yasuhiko; Fukayama, Osamu; Hoshino, Takayuki; Mabuchi, Kunihiko

2017-04-29

Synapse elimination and neurite pruning are essential processes for the formation of neuronal circuits. These regressive events depend on neural activity and occur in the early postnatal days known as the critical period, but what makes this temporal specificity is not well understood. One possibility is that the neural activities during the developmentally regulated shift of action of GABA inhibitory transmission lead to the critical period. Moreover, it has been reported that the shifting action of the inhibitory transmission on immature neurons overlaps with synapse elimination and neurite pruning and that increased inhibitory transmission by drug treatment could induce temporal shift of the critical period. However, the relationship among these phenomena remains unclear because it is difficult to experimentally show how the developmental shift of inhibitory transmission influences neural activities and whether the activities promote synapse elimination and neurite pruning. In this study, we modeled synapse elimination in neuronal circuits using the modified Izhikevich's model with functional shifting of GABAergic transmission. The simulation results show that synaptic pruning within a specified period like the critical period is spontaneously generated as a function of the developmentally shifting inhibitory transmission and that the specific firing rate and increasing synchronization of neural circuits are seen at the initial stage of the critical period. This temporal relationship was experimentally supported by an in vitro primary culture of rat cortical neurons in a microchannel on a multi-electrode array (MEA). The firing rate decreased remarkably between the 18-25 days in vitro (DIV), and following these changes in the firing rate, the neurite density was slightly reduced. Our simulation and experimental results suggest that decreasing neural activity due to developing inhibitory synaptic transmission could induce synapse elimination and neurite pruning at particular time such as the critical period. Additionally, these findings indicate that we can estimate the maturity level of inhibitory transmission and the critical period by measuring the firing rate and the degree of synchronization in engineered neural networks. Copyright © 2017 Elsevier Inc. All rights reserved.

Near real-time vaccine safety surveillance with partially accrued data.

PubMed

Greene, Sharon K; Kulldorff, Martin; Yin, Ruihua; Yih, W Katherine; Lieu, Tracy A; Weintraub, Eric S; Lee, Grace M

2011-06-01

The Vaccine Safety Datalink (VSD) Project conducts near real-time vaccine safety surveillance using sequential analytic methods. Timely surveillance is critical in identifying potential safety problems and preventing additional exposure before most vaccines are administered. For vaccines that are administered during a short period, such as influenza vaccines, timeliness can be improved by undertaking analyses while risk windows following vaccination are ongoing and by accommodating predictable and unpredictable data accrual delays. We describe practical solutions to these challenges, which were adopted by the VSD Project during pandemic and seasonal influenza vaccine safety surveillance in 2009/2010. Adjustments were made to two sequential analytic approaches. The Poisson-based approach compared the number of pre-defined adverse events observed following vaccination with the number expected using historical data. The expected number was adjusted for the proportion of the risk window elapsed and the proportion of inpatient data estimated to have accrued. The binomial-based approach used a self-controlled design, comparing the observed numbers of events in risk versus comparison windows. Events were included in analysis only if they occurred during a week that had already passed for both windows. Analyzing data before risk windows fully elapsed improved the timeliness of safety surveillance. Adjustments for data accrual lags were tailored to each data source and avoided biasing analyses away from detecting a potential safety problem, particularly early during surveillance. The timeliness of vaccine and drug safety surveillance can be improved by properly accounting for partially elapsed windows and data accrual delays. Copyright © 2011 John Wiley & Sons, Ltd.

Development of brain-wide connectivity architecture in awake rats.

PubMed

Ma, Zilu; Ma, Yuncong; Zhang, Nanyin

2018-08-01

Childhood and adolescence are both critical developmental periods, evidenced by complex neurophysiological changes the brain undergoes and high occurrence rates of neuropsychiatric disorders during these periods. Despite substantial progress in elucidating the developmental trajectories of individual neural circuits, our knowledge of developmental changes of whole-brain connectivity architecture in animals is sparse. To fill this gap, here we longitudinally acquired rsfMRI data in awake rats during five developmental stages from juvenile to adulthood. We found that the maturation timelines of brain circuits were heterogeneous and system specific. Functional connectivity (FC) tended to decrease in subcortical circuits, but increase in cortical circuits during development. In addition, the developing brain exhibited hemispheric functional specialization, evidenced by reduced inter-hemispheric FC between homotopic regions, and lower similarity of region-to-region FC patterns between the two hemispheres. Finally, we showed that whole-brain network development was characterized by reduced clustering (i.e. local communication) but increased integration (distant communication). Taken together, the present study has systematically characterized the development of brain-wide connectivity architecture from juvenile to adulthood in awake rats. It also serves as a critical reference point for understanding circuit- and network-level changes in animal models of brain development-related disorders. Furthermore, FC data during brain development in awake rodents contain high translational value and can shed light onto comparative neuroanatomy. Copyright © 2018 Elsevier Inc. All rights reserved.

Sensitivity of hiPSC-derived neural stem cells (NSC) to Pyrroloquinoline quinone depends on their developmental stage.

PubMed

Augustyniak, J; Lenart, J; Zychowicz, M; Lipka, G; Gaj, P; Kolanowska, M; Stepien, P P; Buzanska, L

2017-12-01

Pyrroloquinoline quinone (PQQ) is a factor influencing on the mitochondrial biogenesis. In this study the PQQ effect on viability, total cell number, antioxidant capacity, mitochondrial biogenesis and differentiation potential was investigated in human induced Pluripotent Stem Cells (iPSC) - derived: neural stem cells (NSC), early neural progenitors (eNP) and neural progenitors (NP). Here we demonstrated that sensitivity to PQQ is dependent upon its dose and neural stage of development. Induction of the mitochondrial biogenesis by PQQ at three stages of neural differentiation was evaluated at mtDNA, mRNA and protein level. Changes in NRF1, TFAM and PPARGC1A gene expression were observed at all developmental stages, but only at eNP were correlated with the statistically significant increase in the mtDNA copy numbers and enhancement of SDHA, COX-1 protein level. Thus, the "developmental window" of eNP for PQQ-evoked mitochondrial biogenesis is proposed. This effect was independent of high antioxidant capacity of PQQ, which was confirmed in all tested cell populations, regardless of the stage of hiPSC neural differentiation. Furthermore, a strong induction of GFAP, with down regulation of MAP2 gene expression upon PQQ treatment was observed. This indicates a possibility of shifting the balance of cell differentiation in the favor of astroglia, but more research is needed at this point. Copyright © 2017 Elsevier Ltd. All rights reserved.

The neurite growth inhibitory effects of soluble TNFα on developing sympathetic neurons are dependent on developmental age.

PubMed

Nolan, Aoife M; Collins, Louise M; Wyatt, Sean L; Gutierrez, Humberto; O'Keeffe, Gerard W

2014-01-01

During development, the growth of neural processes is regulated by an array of cellular and molecular mechanisms which influence growth rate, direction and branching. Recently, many members of the TNF superfamily have been shown to be key regulators of neurite growth during development. The founder member of this family, TNFα can both promote and inhibit neurite growth depending on the cellular context. Specifically, transmembrane TNFα promotes neurite growth, while soluble TNFα inhibits it. While the growth promoting effects of TNFα are restricted to a defined developmental window of early postnatal development, whether the growth inhibitory effects of soluble TNFα occur throughout development is unknown. In this study we used the extensively studied, well characterised neurons of the superior cervical ganglion to show that the growth inhibitory effects of soluble TNFα are restricted to a specific period of late embryonic and early postnatal development. Furthermore, we show that this growth inhibitory effect of soluble TNFα requires NF-κB signalling at all developmental stages at which soluble TNFα inhibits neurite growth. These findings raise the possibility that increases in the amount of soluble TNFα in vivo, for example as a result of maternal inflammation, could negatively affect neurite growth in developing neurons at specific stages of development. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species.

PubMed

Gee, Dylan G; Fetcho, Robert N; Jing, Deqiang; Li, Anfei; Glatt, Charles E; Drysdale, Andrew T; Cohen, Alexandra O; Dellarco, Danielle V; Yang, Rui R; Dale, Anders M; Jernigan, Terry L; Lee, Francis S; Casey, B J

2016-04-19

Anxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in gene expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) levels, would impact the development of frontolimbic circuitry implicated in anxiety disorders. In a pediatric imaging sample of over 1,000 3- to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that emerge by ∼12 y of age and are paralleled by changes in anxiety-related behavior. Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environmental backgrounds, we confirm phenotypic differences in frontoamygdala circuitry and anxiety-related behavior by postnatal day 45 (P45), when AEA levels begin to decrease, and also, at P75 but not before. These results, which converge across species and level of analysis, highlight the importance of underlying developmental neurobiology in the emergence of genetic effects on brain circuitry and function. Moreover, the results have important implications for the identification of risk for disease and precise targeting of treatments to the biological state of the developing brain as a function of developmental changes in gene expression and neural circuit maturation.

Understanding mental retardation in Down's syndrome using trisomy 16 mouse models.

PubMed

Galdzicki, Z; Siarey, R J

2003-06-01

Mental retardation in Down's syndrome, human trisomy 21, is characterized by developmental delays, language and memory deficits and other cognitive abnormalities. Neurophysiological and functional information is needed to understand the mechanisms of mental retardation in Down's syndrome. The trisomy mouse models provide windows into the molecular and developmental effects associated with abnormal chromosome numbers. The distal segment of mouse chromosome 16 is homologous to nearly the entire long arm of human chromosome 21. Therefore, mice with full or segmental trisomy 16 (Ts65Dn) are considered reliable animal models of Down's syndrome. Ts65Dn mice demonstrate impaired learning in spatial tests and abnormalities in hippocampal synaptic plasticity. We hypothesize that the physiological impairments in the Ts65Dn mouse hippocampus can model the suboptimal brain function occuring at various levels of Down's syndrome brain hierarchy, starting at a single neuron, and then affecting simple and complex neuronal networks. Once these elements create the gross brain structure, their dysfunctional activity cannot be overcome by extensive plasticity and redundancy, and therefore, at the end of the maturation period the mind inside this brain remains deficient and delayed in its capabilities. The complicated interactions that govern this aberrant developmental process cannot be rescued through existing compensatory mechanisms. In summary, overexpression of genes from chromosome 21 shifts biological homeostasis in the Down's syndrome brain to a new less functional state.

Critical Evaluations and Instructional Potential of Authoring and Titled Program Software.

ERIC Educational Resources Information Center

Reppert, James E.

This paper describes and evaluates the instructional uses of the Claris Works and Ultimedia Tools Series authoring programs and the following titled software programs: CNN Time Capsule: 100 Defining Moments of 1993; Windows Magazine: 1994; Ultimate Digital Studio; Data Trek Manager Series; and Cinemania '95. (AEF)

14 CFR 23.775 - Windshields and windows.

Code of Federal Regulations, 2011 CFR

2011-01-01

... loadings and flight loads, or compliance with the fail-safe requirements of paragraph (d) of this section... loads combined with critical aerodynamic pressure and temperature effects, after failure of any load... in front of the pilots must be arranged so that, assuming the loss of vision through any one panel...

14 CFR 23.775 - Windshields and windows.

Code of Federal Regulations, 2010 CFR

2010-01-01

... loadings and flight loads, or compliance with the fail-safe requirements of paragraph (d) of this section... loads combined with critical aerodynamic pressure and temperature effects, after failure of any load... in front of the pilots must be arranged so that, assuming the loss of vision through any one panel...

14 CFR 23.775 - Windshields and windows.

Code of Federal Regulations, 2014 CFR

2014-01-01

... loadings and flight loads, or compliance with the fail-safe requirements of paragraph (d) of this section... loads combined with critical aerodynamic pressure and temperature effects, after failure of any load... in front of the pilots must be arranged so that, assuming the loss of vision through any one panel...

14 CFR 23.775 - Windshields and windows.

Code of Federal Regulations, 2013 CFR

2013-01-01

... loadings and flight loads, or compliance with the fail-safe requirements of paragraph (d) of this section... loads combined with critical aerodynamic pressure and temperature effects, after failure of any load... in front of the pilots must be arranged so that, assuming the loss of vision through any one panel...

14 CFR 23.775 - Windshields and windows.

Code of Federal Regulations, 2012 CFR

2012-01-01

... loadings and flight loads, or compliance with the fail-safe requirements of paragraph (d) of this section... loads combined with critical aerodynamic pressure and temperature effects, after failure of any load... in front of the pilots must be arranged so that, assuming the loss of vision through any one panel...

Administrator Preparation: Looking Backwards and Forwards

ERIC Educational Resources Information Center

Bridges, Edwin

2012-01-01

Purpose: The purpose of this paper was to conduct a critical analysis of the origins and implementation of problem-based learning in educational administration as a window into the limitations of this approach and more generally administrator preparation. Design/methodology/approach: The author reviewed the published work of the originator from…

Maternal air pollution exposure induces fetal neuroinflammation and predisposes offspring to obesity in aduthood in a sex-specific manner

EPA Science Inventory

Emerging evidence suggests environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal air pollution exposure would predispose the offspring to weight gain in adulthood. Pre...

False Recognition in DRM Lists with Low Association: A Normative Study

ERIC Educational Resources Information Center

Cadavid, Sara; Beato, María Soledad

2017-01-01

A wide array of studies have explored memory distortions with the Deese/Roediger-McDermott (DRM) paradigm, where participants study lists of words (e.g., "door," "glass," "pane," "shade," "ledge," etc.) that are associated to another nonpresented critical word (e.g., WINDOW). On a subsequent memory…

Bayesian multinomial probit modeling of daily windows of susceptibility for maternal PM2.5 exposure and congenital heart defects

EPA Science Inventory

Past epidemiologic studies suggest maternal ambient air pollution exposure during critical periods of the pregnancy is associated with fetal development. We introduce a multinomial probit model that allows for the joint identification of susceptible daily periods during the pregn...

Short-Form Science

ERIC Educational Resources Information Center

Murphy, Beth; Hedwall, Melissa; Dirks, Andrew; Stretch, Elizabeth

2017-01-01

Reading provides a unique window into the history and nature of science and the norms of scientific communication and supports students in developing critical-reading skills in engaging ways. Effective use of reading promotes a spirit of inquiry and an understanding of science concepts while also addressing expectations of the Common Core State…

Climate optimized planting windows for cotton in the lower Mississippi Delta region

USDA-ARS?s Scientific Manuscript database

Unique, variable summer climate of the lower Mississippi Delta region poses a critical challenge to cotton producers in deciding when to plant for optimized production. Traditional 2- to 4-year agronomic field trials conducted in this area fail to capture the effects of long-term climate variabiliti...

Sample Analysis at Mars (SAM) and Mars Organic Molecule Analyzer (MOMA) as Critical In Situ Investigation for Targeting Mars Returned Samples

NASA Astrophysics Data System (ADS)

Freissinet, C.; Glavin, D. P.; Mahaffy, P. R.; Szopa, C.; Buch, A.; Goesmann, F.; Goetz, W.; Raulin, F.; SAM Science Team; MOMA Science Team

2018-04-01

SAM (Curiosity) and MOMA (ExoMars) Mars instruments, seeking for organics and biosignatures, are essential to establish taphonomic windows of preservation of molecules, in order to target the most interesting samples to return from Mars.

Quantitative assessment of pheromone-induced Dauer formation in Caenorhabditis elegans.

PubMed

Neal, Scott J; Kim, Kyuhyung; Sengupta, Piali

2013-01-01

Environmental conditions experienced during early larval stages dictate the developmental trajectory of the nematode C. elegans. Favorable conditions such as low population density, abundant food, and lower temperatures allow reproductive growth, while stressful conditions promote entry of second-stage (L2) larvae into the alternate dauer developmental stage. Population density is signaled by the concentration and composition of a complex mixture of small molecules that is produced by all stages of animals, and is collectively referred to as dauer pheromone; pheromone concentration is a major trigger for dauer formation. Here, we describe a quantitative dauer formation assay that provides a measure of the potency of single or mixtures of pheromone components in regulating this critical developmental decision.

Computational Tools for Stem Cell Biology

PubMed Central

Bian, Qin; Cahan, Patrick

2016-01-01

For over half a century, the field of developmental biology has leveraged computation to explore mechanisms of developmental processes. More recently, computational approaches have been critical in the translation of high throughput data into knowledge of both developmental and stem cell biology. In the last several years, a new sub-discipline of computational stem cell biology has emerged that synthesizes the modeling of systems-level aspects of stem cells with high-throughput molecular data. In this review, we provide an overview of this new field and pay particular attention to the impact that single-cell transcriptomics is expected to have on our understanding of development and our ability to engineer cell fate. PMID:27318512

Developmental neurogenetics and neuro-ophthalmology.

PubMed

Bennett, Jeffrey L

2002-12-01

The field of developmental neurogenetics has burgeoned over the past decade. Through the combined efforts of developmental biologists, geneticists, and clinicians, genetic defects resulting in neuro-ophthalmic disorders such as holoprosencephaly, microphthalmia, dominant optic atrophy, and optic nerve colobomas have been identified and characterized at the molecular level. Experimental studies in model organisms are continuing to identify novel genes critical for ocular and central nervous system development. Mutations in some of these genes have revealed a spectrum of pathology similar to that observed in septo-optic dysplasia, Möebius syndrome, and Duane retraction syndrome. This review examines our current knowledge of the molecular genetics of neuro-ophthalmic disease and focuses on several candidate genes for afferent and efferent visual system disorders.

Computational Tools for Stem Cell Biology.

PubMed

Bian, Qin; Cahan, Patrick

2016-12-01

For over half a century, the field of developmental biology has leveraged computation to explore mechanisms of developmental processes. More recently, computational approaches have been critical in the translation of high throughput data into knowledge of both developmental and stem cell biology. In the past several years, a new subdiscipline of computational stem cell biology has emerged that synthesizes the modeling of systems-level aspects of stem cells with high-throughput molecular data. In this review, we provide an overview of this new field and pay particular attention to the impact that single cell transcriptomics is expected to have on our understanding of development and our ability to engineer cell fate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Polycomb group (PcG) proteins and Pax6 cooperate to inhibit in vivo reprogramming of the developing Drosophila eye.

PubMed

Zhu, Jinjin; Ordway, Alison J; Weber, Lena; Buddika, Kasun; Kumar, Justin P

2018-04-04

How different cells and tissues commit to and determine their fates has been a central question in developmental biology since the seminal embryological experiments conducted by Wilhelm Roux and Hans Driesch in sea urchins and frogs. Here, we demonstrate that Polycomb group (PcG) proteins maintain Drosophila eye specification by suppressing the activation of alternative fate choices. The loss of PcG in the developing eye results in a cellular reprogramming event in which the eye is redirected to a wing fate. This fate transformation occurs with either the individual loss of Polycomb proteins or the simultaneous reduction of the Pleiohomeotic repressive complex and Pax6. Interestingly, the requirement for retinal selector genes is limited to Pax6, as the removal of more downstream members does not lead to the eye-wing transformation. We also show that distinct PcG complexes are required during different developmental windows throughout eye formation. These findings build on earlier observations that the eye can be reprogrammed to initiate head epidermis, antennal and leg development. © 2018. Published by The Company of Biologists Ltd.

Audiovisual Simultaneity Judgment and Rapid Recalibration throughout the Lifespan.

PubMed

Noel, Jean-Paul; De Niear, Matthew; Van der Burg, Erik; Wallace, Mark T

2016-01-01

Multisensory interactions are well established to convey an array of perceptual and behavioral benefits. One of the key features of multisensory interactions is the temporal structure of the stimuli combined. In an effort to better characterize how temporal factors influence multisensory interactions across the lifespan, we examined audiovisual simultaneity judgment and the degree of rapid recalibration to paired audiovisual stimuli (Flash-Beep and Speech) in a sample of 220 participants ranging from 7 to 86 years of age. Results demonstrate a surprisingly protracted developmental time-course for both audiovisual simultaneity judgment and rapid recalibration, with neither reaching maturity until well into adolescence. Interestingly, correlational analyses revealed that audiovisual simultaneity judgments (i.e., the size of the audiovisual temporal window of simultaneity) and rapid recalibration significantly co-varied as a function of age. Together, our results represent the most complete description of age-related changes in audiovisual simultaneity judgments to date, as well as being the first to describe changes in the degree of rapid recalibration as a function of age. We propose that the developmental time-course of rapid recalibration scaffolds the maturation of more durable audiovisual temporal representations.

[Children with developmental coordination disorder have difficulty with action representation].

PubMed

Gabbard, Carl; Cacola, Priscila

The study of children with developmental coordination disorder (DCD) has emerged as a vibrant line of inquiry over the last two decades. The literature indicates quite clearly that children with DCD display deficits with an array of perceptual-motor and daily living skills. The movements of children with DCD are often described as clumsy and uncoordinated and lead to difficulties with performing many of the activities of daily living and sports that typically developing children perform easily. It has been hypothesized, based on limited research, that an underlying problem is a deficit in generating and/or monitoring an action representation termed the internal modeling deficit hypothesis. According to the hypothesis, children with DCD have significant limitations in their ability to accurately generate and utilize internal models of motor planning and control. The focus of this review is on one of the methods used to examine action representation-motor imagery, which theorists argue provides a window into the process of action representation. Included are research methods and possible brain structures involved. An addition, a paradigm unique with this population-estimation of reachability (distance) via motor imagery, will be described.

Developmental outcome after a single episode of status epilepticus.

PubMed

Roy, Hélène; Lippé, Sarah; Lussier, Francine; Sauerwein, Hannelore Catherine; Lortie, Anne; Lacroix, Jacques; Lassonde, Maryse

2011-08-01

Consequences of status epilepticus (SE) on psychomotor development and the specific impact of the convulsive event on emerging executive functions remain controversial. Infants treated for a single episode of SE, those treated for a single febrile seizure, and healthy infants were tested with respect to motor development, language, personal, and social skills and self-regulation. The children were divided into two age groups to investigate the impact of the convulsive event at different windows of brain maturation. We found that infants who had had SE were inferior to healthy controls on the development scales. Age differentiated SE impact on visuomotor development versus sociolinguistic development. Children who had been treated for SE had significantly more difficulties delaying a response to an attractive stimulus in one of the long-delay conditions. A single episode of SE can interfere with psychomotor and cognitive development in children without previous developmental delay, and it seems that the functions that are emerging at the time of insult are most vulnerable. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Micronutrient deficiencies and developmental delays among infants: evidence from a cross-sectional survey in rural China

PubMed Central

Luo, Renfu; Shi, Yaojiang; Zhou, Huan; Yue, Ai; Zhang, Linxiu; Sylvia, Sean; Medina, Alexis; Rozelle, Scott

2015-01-01

Objectives Research increasingly indicates the importance of the nutritional programming that occurs in the first 2–3 years of life. Quality nutrition during this brief window has been shown to have large and significant effects on health and development throughout childhood and even into adulthood. Despite the widespread understanding of this critical window, and the long-term consequences of leaving nutritional deficiencies unaddressed, little is known about the status of infant nutrition in rural China, or about the relationship between infant nutrition and cognitive development in rural China. Design, setting and participants In April 2013 and October 2013, we conducted a survey of 1808 infants aged 6–12 months living in 351 villages across 174 townships in nationally designated poverty counties in rural areas of southern Shaanxi Province, China. Main outcome measures Infants were administered a finger prick blood test for haemoglobin and assessed according to the Bayley Scales of Infant Development. They were also measured for length and weight. Caregivers were administered a survey of demographic characteristics and feeding practices. Results We found that 48.8% of sample infants were anaemic, 3.7% were stunted, 1.2% were underweight and 1.6% were wasted. Approximately 20.0% of the sample infants were significantly delayed in their cognitive development, while just over 32.3% of the sample infants were significantly delayed in their psychomotor development. After controlling for potential confounders, infants with lower haemoglobin counts were significantly more likely to be delayed in both their cognitive (p<0.01) and psychomotor development (p<0.01). Conclusions The anaemia rates that we identify in this study classify anaemia as a ‘severe’ public health problem according to the WHO. In contrast, there is virtually no linear growth failure among this population. We find that low haemoglobin levels among our sample population are associated with significant cognitive and psychomotor delays that could eventually affect children's schooling performance and labour force outcomes. Trial registration number ISRCTN44149146. PMID:26438137

Micronutrient deficiencies and developmental delays among infants: evidence from a cross-sectional survey in rural China.

PubMed

Luo, Renfu; Shi, Yaojiang; Zhou, Huan; Yue, Ai; Zhang, Linxiu; Sylvia, Sean; Medina, Alexis; Rozelle, Scott

2015-10-05

Research increasingly indicates the importance of the nutritional programming that occurs in the first 2-3 years of life. Quality nutrition during this brief window has been shown to have large and significant effects on health and development throughout childhood and even into adulthood. Despite the widespread understanding of this critical window, and the long-term consequences of leaving nutritional deficiencies unaddressed, little is known about the status of infant nutrition in rural China, or about the relationship between infant nutrition and cognitive development in rural China. In April 2013 and October 2013, we conducted a survey of 1808 infants aged 6-12 months living in 351 villages across 174 townships in nationally designated poverty counties in rural areas of southern Shaanxi Province, China. Infants were administered a finger prick blood test for haemoglobin and assessed according to the Bayley Scales of Infant Development. They were also measured for length and weight. Caregivers were administered a survey of demographic characteristics and feeding practices. We found that 48.8% of sample infants were anaemic, 3.7% were stunted, 1.2% were underweight and 1.6% were wasted. Approximately 20.0% of the sample infants were significantly delayed in their cognitive development, while just over 32.3% of the sample infants were significantly delayed in their psychomotor development. After controlling for potential confounders, infants with lower haemoglobin counts were significantly more likely to be delayed in both their cognitive (p<0.01) and psychomotor development (p<0.01). The anaemia rates that we identify in this study classify anaemia as a 'severe' public health problem according to the WHO. In contrast, there is virtually no linear growth failure among this population. We find that low haemoglobin levels among our sample population are associated with significant cognitive and psychomotor delays that could eventually affect children's schooling performance and labour force outcomes. ISRCTN44149146. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Making the Invisible Visible: Advancing Quantitative Methods in Higher Education Using Critical Race Theory and Intersectionality

ERIC Educational Resources Information Center

López, Nancy; Erwin, Christopher; Binder, Melissa; Chavez, Mario Javier

2018-01-01

We appeal to critical race theory and intersectionality to examine achievement gaps at a large public university in the American southwest from 2000 to 2015. Using white, high-income women as our reference group, we report linear combinations of marginal effects for six-year graduation rates and developmental course taking across 20 distinct…

HVI Ballistic Limit Characterization of Fused Silica Thermal Panes

NASA Technical Reports Server (NTRS)

Miller, J. E.; Bohl, W. D.; Christiansen, E. L.; Davis, B. A.; Deighton, K. D.

2015-01-01

Fused silica window systems are used heavily on crewed reentry vehicles, and they are currently being used on the next generation of US crewed spacecraft, Orion. These systems improve crew situational awareness and comfort, as well as, insulating the reentry critical components of a spacecraft against the intense thermal environments of atmospheric reentry. Additionally, these materials are highly exposed to space environment hazards like solid particle impacts. This paper discusses impact studies up to 10 km/s on a fused silica window system proposed for the Orion spacecraft. A ballistic limit equation that describes the threshold of perforation of a fuse silica pane over a broad range of impact velocities, obliquities and projectile materials is discussed here.

Failed heart rate recovery at a critical age in 5-HT-deficient mice exposed to episodic anoxia: implications for SIDS

PubMed Central

Commons, Kathryn G.; Hewitt, Julie C.; Daubenspeck, John A.; Li, Aihua; Kinney, Hannah C.; Nattie, Eugene E.

2011-01-01

Mice deficient in the transcription factor Pet-1−/− have a ∼70% deficiency of brainstem serotonin [5-hydroxytryptamine (5-HT)] neurons and exhibit spontaneous bradycardias in room air at postnatal day (P)5 and P12 and delayed gasping in response to a single episode of anoxia at P4.5 and P9.5 (Cummings KJ, Li A, Deneris ES, Nattie EE. Am J Physiol Regul Integr Comp Physiol 298: R1333–R1342, 2010; and Erickson JT, Sposato BC. J Appl Physiol 106: 1785–1792, 2009). We hypothesized that at a critical age Pet-1−/− mice will fail to autoresuscitate during episodic anoxia, ultimately dying from a failure of gasping to restore heart rate (HR). We exposed P5, P8, and P12 Pet-1−/− mice and wild-type littermates (WT) to four 30-s episodes of anoxia (97% N2-3% CO2), separated by 5 min of room air. We observed excess mortality in Pet-1−/− only at P8: 43% of Pet-1−/− animals survived past the third episode of anoxia while ∼95% of WT survived all four episodes (P = 0.004). No deaths occurred at P5 and at P12, and one of six Pet-1−/− mice died after the fourth episode, while all WT animals survived. At P8, dying Pet-1−/− animals had delayed gasping, recovery of HR, and eupnea after the first two episodes of anoxia (P < 0.001 for each); death ultimately occurred when gasping failed to restore HR. Both high- and low-frequency components of HR variability were abnormally elevated in dying Pet-1−/− animals following the first episode of anoxia. Dying P8 Pet-1−/− animals had significantly fewer 5-HT neurons in the raphe magnus than surviving animals (P < 0.001). Our data indicate a critical developmental window at which a brainstem 5-HT deficiency increases the risk of death during episodes of anoxia. They may apply to the sudden infant death syndrome, which occurs at a critical age and is associated with 5-HT deficiency. PMID:21680874

Micromirror-based manipulation of synchrotron x-ray beams

NASA Astrophysics Data System (ADS)

Walko, D. A.; Chen, Pice; Jung, I. W.; Lopez, D.; Schwartz, C. P.; Shenoy, G. K.; Wang, Jin

2017-08-01

Synchrotron beamlines typically use macroscopic, quasi-static optics to manipulate x-ray beams. We present the use of dynamic microelectromechanical systems-based optics (MEMS) to temporally modulate synchrotron x-ray beams. We demonstrate this concept using single-crystal torsional MEMS micromirrors oscillating at frequencies of 75 kHz. Such a MEMS micromirror, with lateral dimensions of a few hundred micrometers, can interact with x rays by operating in grazing-incidence reflection geometry; x rays are deflected only when an x-ray pulse is incident on the rotating micromirror under appropriate conditions, i.e., at an angle less than the critical angle for reflectivity. The time window for such deflections depends on the frequency and amplitude of the MEMS rotation. We demonstrate that reflection geometry can produce a time window of a few microseconds. We further demonstrate that MEMS optics can isolate x rays from a selected synchrotron bunch or group of bunches. With ray-trace simulations we explain the currently achievable time windows and suggest a path toward improvements.

Accessing thermoplastic processing windows in metallic glasses using rapid capacitive discharge

PubMed Central

Kaltenboeck, Georg; Harris, Thomas; Sun, Kerry; Tran, Thomas; Chang, Gregory; Schramm, Joseph P.; Demetriou, Marios D.; Johnson, William L.

2014-01-01

The ability of the rapid-capacitive discharge approach to access optimal viscosity ranges in metallic glasses for thermoplastic processing is explored. Using high-speed thermal imaging, the heating uniformity and stability against crystallization of Zr35Ti30Cu7.5Be27.5 metallic glass heated deeply into the supercooled region is investigated. The method enables homogeneous volumetric heating of bulk samples throughout the entire supercooled liquid region at high rates (~105 K/s) sufficient to bypass crystallization throughout. The crystallization onsets at temperatures in the vicinity of the “crystallization nose” were identified and a Time-Temperature-Transformation diagram is constructed, revealing a “critical heating rate” for the metallic glass of ~1000 K/s. Thermoplastic process windows in the optimal viscosity range of 100–104 Pa·s are identified, being confined between the glass relaxation and the eutectic crystallization transition. Within this process window, near-net forging of a fine precision metallic glass part is demonstrated. PMID:25269892

Flexible thermochromic window based on hybridized VO2/graphene.

PubMed

Kim, Hyeongkeun; Kim, Yena; Kim, Keun Soo; Jeong, Hu Young; Jang, A-Rang; Han, Seung Ho; Yoon, Dae Ho; Suh, Kwang S; Shin, Hyeon Suk; Kim, TaeYoung; Yang, Woo Seok

2013-07-23

Large-scale integration of vanadium dioxide (VO2) on mechanically flexible substrates is critical to the realization of flexible smart window films that can respond to environmental temperatures to modulate light transmittance. Until now, the formation of highly crystalline and stoichiometric VO2 on flexible substrate has not been demonstrated due to the high-temperature condition for VO2 growth. Here, we demonstrate a VO2-based thermochromic film with unprecedented mechanical flexibility by employing graphene as a versatile platform for VO2. The graphene effectively functions as an atomically thin, flexible, yet robust support which enables the formation of stoichiometric VO2 crystals with temperature-driven phase transition characteristics. The graphene-supported VO2 was capable of being transferred to a plastic substrate, forming a new type of flexible thermochromic film. The flexible VO2 films were then integrated into the mock-up house, exhibiting its efficient operation to reduce the in-house temperature under infrared irradiation. These results provide important progress for the fabrication of flexible thermochromic films for energy-saving windows.

Developmentally Sensitive Diagnostic Criteria for Mental Health Disorders in Early Childhood: The Diagnostic and Statistical Manual of Mental Disorders-IV, the Research Diagnostic Criteria-Preschool Age, and the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood-Revised

ERIC Educational Resources Information Center

Egger, Helen L.; Emde, Robert N.

2011-01-01

As the infant mental health field has turned its focus to the presentation, course, and treatment of clinically significant mental health disorders, the need for reliable and valid criteria for identifying and assessing mental health symptoms and disorders in early childhood has become urgent. In this article we offer a critical perspective on…

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

PubMed Central

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 hand, unexpected senescence-related genes might also be involved in the early developmental process and its regulation. The ease of manipulation using the zebrafish system allows us to conduct an exhaustive exploration of novel genes/genotypes and epigenotype that can be linked to the senescence phenotype, and thereby facilitates searching for the evolutionary and developmental origins of aging in vertebrates. PMID:24239812

Early life nutrition, epigenetics and programming of later life disease.

PubMed

Vickers, Mark H

2014-06-02

The global pandemic of obesity and type 2 diabetes 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, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA) and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how these effects may be transmitted across generations is essential for the implementation of initiatives aimed at curbing the current obesity and diabetes crisis.

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

PubMed

Hiura, Lisa C; Ophir, Alexander G

2018-05-31

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

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

PubMed

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.

Transcriptome profiles of embryos before and after cleavage in Eriocheir sinensis: identification of developmental genes at the earliest stages

NASA Astrophysics Data System (ADS)

Hui, Min; Cui, Zhaoxia; Liu, Yuan; Song, Chengwen

2017-07-01

In crab, embryogenesis is a complicated developmental program marked by a series of critical events. RNA-Sequencing technology offers developmental biologists a way to identify many more developmental genes than ever before. Here, we present a comprehensive analysis of the transcriptomes of Eriocheir sinensis oosperms (Os) and embryos at the 2-4 cell stage (Cs), which are separated by a cleavage event. A total of 18 923 unigenes were identified, and 403 genes matched with gene ontology (GO) terms related to developmental processes. In total, 432 differentially expressed genes (DEGs) were detected between the two stages. Nine DEGs were specifically expressed at only one stage. These DEGs may be relevant to stage-specific molecular events during development. A number of DEGs related to `hedgehog signaling pathway', `Wnt signaling pathway' `germplasm', `nervous system', `sensory perception' and `segment polarity' were identified as being up-regulated at the Cs stage. The results suggest that these embryonic developmental events begin before the early cleavage event in crabs, and that many of the genes expressed in the two transcriptomes might be maternal genes. Our study provides ample information for further research on the molecular mechanisms underlying crab development.

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

PubMed Central

Rao, Uma; Chen, Li-Ann

2009-01-01

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

The common marmoset monkey: avenues for exploring the prenatal, placental, and postnatal mechanisms in developmental programming of pediatric obesity.

PubMed

Riesche, Laren; Tardif, Suzette D; Ross, Corinna N; deMartelly, Victoria A; Ziegler, Toni; Rutherford, Julienne N

2018-05-01

Animal models have been critical in building evidence that the prenatal experience and intrauterine environment are capable of exerting profound and permanent effects on metabolic health through developmental programming of obesity. However, despite physiological and evolutionary similarities, nonhuman primate models are relatively rare. The common marmoset monkey ( Callithrix jacchus) is a New World monkey that has been used as a biomedical model for well more than 50 years and has recently been framed as an appropriate model for exploring early-life impacts on later health and disease. The spontaneous, multifactorial, and early-life development of obesity in the common marmoset make it a valuable research model for advancing our knowledge about the role of the prenatal and placental mechanisms involved in developmental programming of obesity. This paper provides a brief overview of obesity in the common marmoset, followed by a discussion of marmoset reproduction and placental characteristics. We then discuss the occurrence and utility of variable intrauterine environments in developmental programming in marmosets. Evidence of developmental programming of obesity will be given, and finally, we put forward future directions and innovations for including the placenta in developmental programming of obesity in the common marmoset.

Environmental Estrogens Differentially Engage the Histone Methyltransferase EZH2 to Increase Risk of Uterine Tumorigenesis

PubMed Central

Greathouse, K. Leigh; Bredfeldt, Tiffany; Everitt, Jeffrey I.; Lin, Kevin; Berry, Tia; Kannan, Kurunthachalam; Mittelstadt, Megan L.; Ho, Shuk-mei; Walker, Cheryl L.

2013-01-01

Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. For example, exposure to the xenoestrogen diethylstilbestrol (DES) during reproductive tract development can reprogram estrogen-responsive gene expression in the myometrium, resulting in hyper-responsiveness to hormone in the adult uterus and promotion of hormone-dependent uterine leiomyoma. We show here that the environmental estrogens genistein (GEN), a soy phytoestrogen, and the plasticizer bisphenol A (BPA), differ in their pattern of developmental reprogramming and promotion of tumorigenesis (leiomyomas) in the uterus. While both GEN and BPA induce genomic estrogen receptor (ER) signaling in the developing uterus, only GEN induced PI3K/AKT non-genomic ER signaling to the histone methyltransferase Enhancer of Zeste homolog 2 (EZH2). As a result, this “pre-genomic” signaling phosphorylates and represses EZH2, and reduces levels of H3K27 repressive mark in chromatin. Furthermore, only GEN caused estrogen-responsive genes in the adult myometrium to become hyper-responsive to hormone; estrogen-responsive genes were repressed in BPA exposed uteri. Importantly, this pattern of EZH2 engagement to decrease versus increase H3K27 methylation correlated with the effect of these xenoestrogens on tumorigenesis. Developmental reprogramming by GEN promoted development of uterine leiomyomas, increasing tumor incidence and multiplicity, while BPA did not. These data demonstrate that environmental estrogens have distinct non-genomic effects in the developing uterus that determines their ability to engage the epigenetic regulator EZH2, decrease levels of the repressive epigenetic histone H3K27 methyl mark in chromatin during developmental reprogramming, and promote uterine tumorigenesis. PMID:22504913

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

PubMed Central

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

2013-01-01

Most researchers in the field of neural plasticity are familiar with the “Kennard Principle,” which purports a positive relationship between age at brain injury and severity of subsequent deficits (plateauing in adulthood). As an example, a child with left hemispherectomy can recover seemingly normal language, while an adult with focal injury to sub-regions of left temporal and/or frontal cortex can suffer dramatic and permanent language loss. Here we present data regarding the impact of early brain injury in rat models as a function of type and timing, measuring long-term behavioral outcomes via auditory discrimination tasks varying in temporal demand. These tasks were created to model (in rodents) aspects of human sensory processing that may correlate—both developmentally and functionally—with typical and atypical language. We found that bilateral focal lesions to the cortical plate in rats during active neuronal migration led to worse auditory outcomes than comparable lesions induced after cortical migration was complete. Conversely, unilateral hypoxic-ischemic (HI) injuries (similar to those seen in premature infants and term infants with birth complications) led to permanent auditory processing deficits when induced at a neurodevelopmental point comparable to human “term,” but only transient deficits (undetectable in adulthood) when induced in a “preterm” window. Convergent evidence suggests that regardless of when or how disruption of early neural development occurs, the consequences may be particularly deleterious to rapid auditory processing (RAP) outcomes when they trigger developmental alterations that extend into subcortical structures (i.e., lower sensory processing stations). Collective findings hold implications for the study of behavioral outcomes following early brain injury as well as genetic/environmental disruption, and are relevant to our understanding of the neurologic risk factors underlying developmental language disability in human populations. PMID:24155699

Interactions between Auxin Transport and the Actin Cytoskeleton in Developmental Polarity of Fucus distichus Embryos in Response to Light and Gravity1

PubMed Central

Sun, Haiguo; Basu, Swati; Brady, Shari R.; Luciano, Randy L.; Muday, Gloria K.

2004-01-01

Land plants orient their growth relative to light and gravity through complex mechanisms that require auxin redistribution. Embryos of brown algae use similar environmental stimuli to orient their developmental polarity. These studies of the brown algae Fucus distichus examined whether auxin and auxin transport are also required during polarization in early embryos and to orient growth in already developed tissues. These embryos polarize with the gravity vector in the absence of a light cue. The auxin, indole-3-acetic acid (IAA), and auxin efflux inhibitors, such as naphthylphthalamic acid (NPA), reduced environmental polarization in response to gravity and light vectors. Young rhizoids are negatively phototropic, and NPA also inhibits rhizoid phototropism. The effect of IAA and NPA on gravity and photopolarization is maximal within 2.5 to 4.5 h after fertilization (AF). Over the first 6 h AF, auxin transport is relatively constant, suggesting that developmentally controlled sensitivity to auxin determines the narrow window during which NPA and IAA reduce environmental polarization. Actin patches were formed during the first hour AF and began to photolocalize within 3 h, coinciding with the time of NPA and IAA action. Treatment with NPA reduced the polar localization of actin patches but not patch formation. Latrunculin B prevented environmental polarization in a time frame that overlaps the formation of actin patches and IAA and NPA action. Latrunculin B also altered auxin transport. Together, these results indicate a role for auxin in the orientation of developmental polarity and suggest interactions between the actin cytoskeleton and auxin transport in F. distichus embryos. PMID:15122028

Core measures for developmentally supportive care in neonatal intensive care units: theory, precedence and practice

PubMed Central

Coughlin, Mary; Gibbins, Sharyn; Hoath, Steven

2009-01-01

Title Core measures for developmentally supportive care in neonatal intensive care units: theory, precedence and practice. Aim This paper is a discussion of evidence-based core measures for developmental care in neonatal intensive care units. Background Inconsistent definition, application and evaluation of developmental care have resulted in criticism of its scientific merit. The key concept guiding data organization in this paper is the United States of America’s Joint Commission’s concept of ‘core measures’ for evaluating and accrediting healthcare organizations. This concept is applied to five disease- and procedure-independent measures based on the Universe of Developmental Care model. Data sources Electronically accessible, peer reviewed studies on developmental care published in English were culled for data supporting the selected objective core measures between 1978 and 2008. The quality of evidence was based on a structured predetermined format that included three independent reviewers. Systematic reviews and randomized control trials were considered the strongest level of evidence. When unavailable, cohort, case control, consensus statements and qualitative methods were considered the strongest level of evidence for a particular clinical issue. Discussion Five core measure sets for evidence-based developmental care were evaluated: (1) protected sleep, (2) pain and stress assessment and management, (3) developmental activities of daily living, (4) family-centred care, and (5) the healing environment. These five categories reflect recurring themes that emerged from the literature review regarding developmentally supportive care and quality caring practices in neonatal populations. This practice model provides clear metrics for nursing actions having an impact on the hospital experience of infant-family dyads. Conclusion Standardized disease-independent core measures for developmental care establish minimum evidence-based practice expectations and offer an objective basis for cross-institutional comparison of developmental care programmes. PMID:19686402

Anxiety Psychopathology and Alcohol Use among Adolescents: A Critical Review of the Empirical Literature and Recommendations for Future Research.

PubMed

Blumenthal, Heidemarie; Leen-Feldner, Ellen W; Badour, Christal L; Babson, Kimberly A

2011-01-01

Adolescent alcohol use is a critical public health concern; accordingly, a considerable body of work exists identifying developmentally salient risk and protective factors. One area receiving increasing attention among adults is the linkage between specific constellations of anxiety psychopathology and alcohol use problems. Relatively less is known about such linkages among adolescents, despite the onset of both anxiety-type problems and alcohol use during this developmental period. The current review presents a detailed summary and analysis of the empirical literature focused on specific forms of anxiety psychopathology as they relate to alcohol use among adolescents, and provides a number of specific recommendations for future work with an emphasis on the utility of experimental psychopathology techniques for clarifying basic questions and forwarding this body of work.

Relationship of childhood adversity and neighborhood violence to a proinflammatory phenotype in emerging adult African American men: An epigenetic link.

PubMed

Janusek, Linda Witek; Tell, Dina; Gaylord-Harden, Noni; Mathews, Herbert L

2017-02-01

African American men (AAM) who are exposed to trauma and adversity during their early life are at greater risk for poor health over their lifespan. Exposure to adversity during critical developmental windows may embed an epigenetic signature that alters expression of genes that regulate stress response systems, including those genes that regulate the inflammatory response to stress. Such an epigenetic signature may increase risk for diseases exacerbated by inflammation, and may contribute to health disparity. The purpose of this study was to evaluate the extent to which exposure to early life adversity influences the psychological, cortisol, and proinflammatory response to acute stress (Trier Social Stress Test - TSST) in emerging adult AAM, ages 18-25years (N=34). Hierarchical linear modeling was used to examine the cortisol and IL-6 pattern of response to the TSST with respect to childhood adversity factors and DNA methylation of the IL-6 promoter. Findings revealed that in response to the TSST, greater levels of childhood trauma and indirect exposure to neighborhood violence were associated with a greater TSST-induced IL-6 response, and a blunted cortisol response. Reduced methylation of the IL6 promoter was related to increased exposure to childhood trauma and greater TSST-induced IL-6 levels. These results support the concept that exposure to childhood adversity amplifies the adult proinflammatory response to stress, which is related to epigenetic signature. Copyright © 2016 Elsevier Inc. All rights reserved.

Demographic and genetic consequences of disturbed sex determination.

PubMed

Wedekind, Claus

2017-09-19

During sex determination, genetic and/or environmental factors determine the cascade of processes of gonad development. Many organisms, therefore, have a developmental window in which their sex determination can be sensitive to, for example, unusual temperatures or chemical pollutants. Disturbed environments can distort population sex ratios and may even cause sex reversal in species with genetic sex determination. The resulting genotype-phenotype mismatches can have long-lasting effects on population demography and genetics. I review the theoretical and empirical work in this context and explore in a simple population model the role of the fitness v yy of chromosomally aberrant YY genotypes that are a consequence of environmentally induced feminization. Low v yy is mostly beneficial for population growth. During feminization, low v yy reduces the proportion of genetic males and hence accelerates population growth, especially at low rates of feminization and at high fitness costs of the feminization itself (i.e. when feminization would otherwise not affect population dynamics much). When sex reversal ceases, low v yy mitigates the negative effects of feminization and can even prevent population extinction. Little is known about v yy in natural populations. The available models now need to be parametrized in order to better predict the long-term consequences of disturbed sex determination.This article is part of the themed issue 'Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies'. © 2017 The Author(s).

Vitamin D and the brain: key questions for future research.

PubMed

Cui, Xiaoying; Gooch, Helen; Groves, Natalie J; Sah, Pankaj; Burne, Thomas H; Eyles, Darryl W; McGrath, John J

2015-04-01

Over the last decade a convergent body of evidence has emerged from epidemiology, animal experiments and clinical trials which links low vitamin D status with a range of adverse neuropsychiatric outcomes. This research demonstrates that the timing of exposure to low vitamin D influences the nature of brain phenotypes, as exposures during gestation versus adulthood result in different phenotypes. With respect to early life exposures, there is robust evidence from rodent experiments indicating that transient developmental vitamin D (DVD) deficiency is associated with changes in brain structure, neurochemistry, gene and protein expression and behavior. In particular, DVD deficiency is associated with alterations in the dopaminergic neurotransmitter systems. In contrast, recently published animal experiments indicate that adult vitamin D (AVD) deficiency is associated with more subtle neurochemical and behavioral phenotypes. This paper explores key issues that need to be addressed in future research. There is a need to define the timing and duration of the 'critical window' during which low vitamin D status is associated with differential and adverse brain outcomes. We discuss the role for 'two-hit hypotheses', which propose that adult vitamin D deficiency leaves the brain more vulnerable to secondary adverse exposures, and thus may exacerbate disease progression. Finally, we explore the evidence implicating a role for vitamin D in rapid, non-genomic mechanisms that may involve L-type calcium channels and brain function. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism.

PubMed

Peñagarikano, Olga; Lázaro, María T; Lu, Xiao-Hong; Gordon, Aaron; Dong, Hongmei; Lam, Hoa A; Peles, Elior; Maidment, Nigel T; Murphy, Niall P; Yang, X William; Golshani, Peyman; Geschwind, Daniel H

2015-01-21

Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homolog of CNTNAP2 (contactin-associated protein-like 2), in which mutations cause cortical dysplasia and focal epilepsy (CDFE) syndrome, displays many features that parallel those of the human disorder. Because CDFE has high penetrance for autism spectrum disorder (ASD), we performed an in vivo screen for drugs that ameliorate abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment to rectify this deficit. Copyright © 2015, American Association for the Advancement of Science.

Off-Line Quality Control In Integrated Circuit Fabrication Using Experimental Design

NASA Astrophysics Data System (ADS)

Phadke, M. S.; Kackar, R. N.; Speeney, D. V.; Grieco, M. J.

1987-04-01

Off-line quality control is a systematic method of optimizing production processes and product designs. It is widely used in Japan to produce high quality products at low cost. The method was introduced to us by Professor Genichi Taguchi who is a Deming-award winner and a former Director of the Japanese Academy of Quality. In this paper we will i) describe the off-line quality control method, and ii) document our efforts to optimize the process for forming contact windows in 3.5 Aim CMOS circuits fabricated in the Murray Hill Integrated Circuit Design Capability Laboratory. In the fabrication of integrated circuits it is critically important to produce contact windows of size very near the target dimension. Windows which are too small or too large lead to loss of yield. The off-line quality control method has improved both the process quality and productivity. The variance of the window size has been reduced by a factor of four. Also, processing time for window photolithography has been substantially reduced. The key steps of off-line quality control are: i) Identify important manipulatable process factors and their potential working levels. ii) Perform fractional factorial experiments on the process using orthogonal array designs. iii) Analyze the resulting data to determine the optimum operating levels of the factors. Both the process mean and the process variance are considered in this analysis. iv) Conduct an additional experiment to verify that the new factor levels indeed give an improvement.

Photothermal Therapy Generates a Thermal Window of Immunogenic Cell Death in Neuroblastoma.

PubMed

Sweeney, Elizabeth E; Cano-Mejia, Juliana; Fernandes, Rohan

2018-04-17

A thermal "window" of immunogenic cell death (ICD) elicited by nanoparticle-based photothermal therapy (PTT) in an animal model of neuroblastoma is described. In studies using Prussian blue nanoparticles to administer photothermal therapy (PBNP-PTT) to established localized tumors in the neuroblastoma model, it is observed that PBNP-PTT conforms to the "more is better" paradigm, wherein higher doses of PBNP-PTT generates higher cell/local heating and thereby more cell death, and consequently improved animal survival. However, in vitro analysis of the biochemical correlates of ICD (ATP, high-motility group box 1, and calreticulin) elicited by PBNP-PTT demonstrates that PBNP-PTT triggers a thermal window of ICD. ICD markers are highly expressed within an optimal temperature (thermal dose) window of PBNP-PTT (63.3-66.4 °C) as compared with higher (83.0-83.5 °C) and lower PBNP-PTT (50.7-52.7 °C) temperatures, which both yield lower expression. Subsequent vaccination studies in the neuroblastoma model confirm the in vitro findings, wherein PBNP-PTT administered within the optimal temperature window results in long-term survival (33.3% at 100 d) compared with PBNP-PTT administered within the higher (0%) and lower (20%) temperature ranges, and controls (0%). The findings demonstrate a tunable immune response to heat generated by PBNP-PTT, which should be critically engaged in the administration of PTT for maximizing its therapeutic benefits. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Juvenile Sex Offending Through a Developmental Life Course Criminology Perspective.

PubMed

Lussier, Patrick

2017-02-01

Current American policies and responses to juvenile sex offending have been criticized for being based on myths, misconceptions, and unsubstantiated claims. In spite of the criticism, no organizing framework has been proposed to guide policy development with respect to the prevention of juvenile sex offending. This article proposes a developmental life course (DLC) criminology perspective to investigate the origins, development, and termination of sex offending among youth. It also provides a review of the current state of knowledge regarding various parameters characterizing the development of sex offending (e.g., prevalence, age of onset, frequency, persistence, continuity in adulthood, and versatility). The review highlights some heterogeneity across these developmental parameters suggesting the presence of different sex offending patterns among youth. In fact, it is proposed that, based on the current knowledge, such heterogeneity can be accounted for by a dual taxonomy of adolescents involved in sexual offenses: (a) the adolescent-limited and (b) the high-rate/slow-desister. The DLC criminology approach and the dual taxonomy are proposed as organizing frameworks to conduct prospective longitudinal research to better understand the origins and development of sex offending and to guide policy development and responses to at-risk youth and those who have committed sexual offenses.

Environmental Education Activity Guide: Pre K-8.

ERIC Educational Resources Information Center

Iozzi, Lou; Halsey, Brent, Jr.

Project Learning Tree uses the forest as a window on the world to increase students' understanding of the complex environment in the United States; to stimulate critical and creative thinking; to develop the ability to make informed decisions on environmental issues; and to instill the confidence and commitment to take responsible action on behalf…

Ten Keys to the Portal

ERIC Educational Resources Information Center

Schaffhauser, Dian

2011-01-01

Successful web portals help users stay informed, in touch, and up to speed. They are also a telling window into the efficiency of one's institution. To develop a cutting-edge portal takes planning, communication, and research. In this article, the author presents and discusses 10 keys to portal success: (1) make critical info visible; (2) make the…

Comparison of fetal testosterone production in various tissues of the male sprague dawley rat dosed in utero with dipentyl phthalate during the critical window of sexual differentiation

EPA Science Inventory

Phthalate esters are high-production volume chemicals used in the manufacture of numerous plastics and consumer products, which generates major concern for potential human exposure and environmental contamination. Several studies have demonstrated adverse effects associated with ...

14 CFR 25.775 - Windshields and windows.

Code of Federal Regulations, 2010 CFR

2010-01-01

... differential loads combined with critical aerodynamic pressure and temperature effects after any single failure... front of the pilots must be arranged so that, assuming the loss of vision through any one panel, one or... flight and landing. [Doc. No. 5066, 29 FR 18291, Dec. 24, 1964, as amended by Amdt. 25-23, 35 FR 5676...

14 CFR 25.775 - Windshields and windows.

Code of Federal Regulations, 2013 CFR

2013-01-01

... differential loads combined with critical aerodynamic pressure and temperature effects after any single failure... front of the pilots must be arranged so that, assuming the loss of vision through any one panel, one or... flight and landing. [Doc. No. 5066, 29 FR 18291, Dec. 24, 1964, as amended by Amdt. 25-23, 35 FR 5676...

14 CFR 25.775 - Windshields and windows.

Code of Federal Regulations, 2012 CFR

2012-01-01

... differential loads combined with critical aerodynamic pressure and temperature effects after any single failure... front of the pilots must be arranged so that, assuming the loss of vision through any one panel, one or... flight and landing. [Doc. No. 5066, 29 FR 18291, Dec. 24, 1964, as amended by Amdt. 25-23, 35 FR 5676...

14 CFR 25.775 - Windshields and windows.

Code of Federal Regulations, 2014 CFR

2014-01-01

... differential loads combined with critical aerodynamic pressure and temperature effects after any single failure... front of the pilots must be arranged so that, assuming the loss of vision through any one panel, one or... flight and landing. [Doc. No. 5066, 29 FR 18291, Dec. 24, 1964, as amended by Amdt. 25-23, 35 FR 5676...

14 CFR 25.775 - Windshields and windows.

Code of Federal Regulations, 2011 CFR

2011-01-01

... differential loads combined with critical aerodynamic pressure and temperature effects after any single failure... front of the pilots must be arranged so that, assuming the loss of vision through any one panel, one or... flight and landing. [Doc. No. 5066, 29 FR 18291, Dec. 24, 1964, as amended by Amdt. 25-23, 35 FR 5676...

Seizing Teachable Moments to Develop Integrative Middle Level Curriculum

ERIC Educational Resources Information Center

Virtue, David C.

2007-01-01

September 11, 2001, was a critical teachable moment that provided the author of this article and his team with an avenue to middle level curriculum that was relevant, challenging, integrative, and exploratory. Hurricane Katrina opened a similar window of opportunity for middle level educators to focus the minds of young adolescents on important…

Classroom Dynamic Assessment: A Critical Examination of Constructs and Practices

ERIC Educational Resources Information Center

Davin, Kristin J.

2016-01-01

This article explores the implementation of dynamic assessment (DA) in an elementary school foreign language classroom by considering its theoretical basis and its applicability to second language (L2) teaching, learning, and development. In existing applications of L2 classroom DA, errors serve as a window into learners' instructional needs and…

Holography and the conformal window in the Veneziano limit

NASA Astrophysics Data System (ADS)

Järvinen, M.

2017-12-01

We discuss holographic QCD in the Veneziano limit (the V-QCD models), concentrating on phenomena near the “conformal” phase transition taking place at a critical value of the ratio x ≡ Nf/Nc. In particular, we review the results for the S-parameter, the technidilaton, and the masses of the mesons.

The Sensitivity of Memory Consolidation and Reconsolidation to Inhibitors of Protein Synthesis and Kinases: Computational Analysis

ERIC Educational Resources Information Center

Zhang, Yili; Smolen, Paul; Baxter, Douglas A.; Byrne, John H.

2010-01-01

Memory consolidation and reconsolidation require kinase activation and protein synthesis. Blocking either process during or shortly after training or recall disrupts memory stabilization, which suggests the existence of a critical time window during which these processes are necessary. Using a computational model of kinase synthesis and…