WorldWideScience

Sample records for non-mutant developmental phenotypes

  1. Do convergent developmental mechanisms underlie convergent phenotypes?

    Science.gov (United States)

    Wray, Gregory A.

    2002-01-01

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

  2. The phenotypic plasticity of developmental modules

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    Aabha I. Sharma

    2016-08-01

    Full Text Available Abstract Background Organisms develop and evolve in a modular fashion, but how individual modules interact with the environment remains poorly understood. Phenotypically plastic traits are often under selection, and studies are needed to address how traits respond to the environment in a modular fashion. In this study, tissue-specific plasticity of melanic spots was examined in the large milkweed bug, Oncopeltus fasciatus. Results Although the size of the abdominal melanic bands varied according to rearing temperatures, wing melanic bands were more robust. To explore the regulation of abdominal pigmentation plasticity, candidate genes involved in abdominal melanic spot patterning and biosynthesis of melanin were analyzed. While the knockdown of dopa decarboxylase (Ddc led to lighter pigmentation in both the wings and the abdomen, the shape of the melanic elements remained unaffected. Although the knockdown of Abdominal-B (Abd-B partially phenocopied the low-temperature phenotype, the abdominal bands were still sensitive to temperature shifts. These observations suggest that regulators downstream of Abd-B but upstream of DDC are responsible for the temperature response of the abdomen. Ablation of wings led to the regeneration of a smaller wing with reduced melanic bands that were shifted proximally. In addition, the knockdown of the Wnt signaling nuclear effector genes, armadillo 1 and armadillo 2, altered both the melanic bands and the wing shape. Thus, the pleiotropic effects of Wnt signaling may constrain the amount of plasticity in wing melanic bands. Conclusions We propose that when traits are regulated by distinct pre-patterning mechanisms, they can respond to the environment in a modular fashion, whereas when the environment impacts developmental regulators that are shared between different modules, phenotypic plasticity can manifest as a developmentally integrated system.

  3. Developmental sculpting of social phenotype and plasticity.

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    Sakata, Jon T; Crews, David

    2004-04-01

    Early developmental variables engender behavioral and neural variation, especially in species in which embryonic environment determines gonadal sex. In the leopard gecko, Eublepharis macularius, the incubation temperature of the egg (IncT) determines gonadal sex. Moreover, IncT affects the sexual differentiation of the individual and, consequently, within-sex variation. Individuals hatched from eggs incubated at an IncT that produces predominantly males are more masculinized than same-sex counterparts from IncTs that produce predominantly females. Here we review how gonadal sex and IncT interact to affect behavioral, endocrinological, and neural phenotype in the leopard gecko and influence phenotypic plasticity following hormone administration or social experience. We discuss the hormonal dependence of sex- and IncT-dependent behavioral and neural morphological and metabolic differences and highlight the parallels between IncT effects in geckos and intrauterine position effects in rodents. We argue that the leopard gecko is an important model of how the process of sex determination can affect sexual differentiation and of selection forces underlying the evolution of sex ratios. Copyright 2004 Elsevier Ltd.

  4. Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.

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

    2018-01-17

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

  5. RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes.

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    Reijnders, Margot R F; Ansor, Nurhuda M; Kousi, Maria; Yue, Wyatt W; Tan, Perciliz L; Clarkson, Katie; Clayton-Smith, Jill; Corning, Ken; Jones, Julie R; Lam, Wayne W K; Mancini, Grazia M S; Marcelis, Carlo; Mohammed, Shehla; Pfundt, Rolph; Roifman, Maian; Cohn, Ronald; Chitayat, David; Millard, Tom H; Katsanis, Nicholas; Brunner, Han G; Banka, Siddharth

    2017-09-07

    RAC1 is a widely studied Rho GTPase, a class of molecules that modulate numerous cellular functions essential for normal development. RAC1 is highly conserved across species and is under strict mutational constraint. We report seven individuals with distinct de novo missense RAC1 mutations and varying degrees of developmental delay, brain malformations, and additional phenotypes. Four individuals, each harboring one of c.53G>A (p.Cys18Tyr), c.116A>G (p.Asn39Ser), c.218C>T (p.Pro73Leu), and c.470G>A (p.Cys157Tyr) variants, were microcephalic, with head circumferences between -2.5 to -5 SD. In contrast, two individuals with c.151G>A (p.Val51Met) and c.151G>C (p.Val51Leu) alleles were macrocephalic with head circumferences of +4.16 and +4.5 SD. One individual harboring a c.190T>G (p.Tyr64Asp) allele had head circumference in the normal range. Collectively, we observed an extraordinary spread of ∼10 SD of head circumferences orchestrated by distinct mutations in the same gene. In silico modeling, mouse fibroblasts spreading assays, and in vivo overexpression assays using zebrafish as a surrogate model demonstrated that the p.Cys18Tyr and p.Asn39Ser RAC1 variants function as dominant-negative alleles and result in microcephaly, reduced neuronal proliferation, and cerebellar abnormalities in vivo. Conversely, the p.Tyr64Asp substitution is constitutively active. The remaining mutations are probably weakly dominant negative or their effects are context dependent. These findings highlight the importance of RAC1 in neuronal development. Along with TRIO and HACE1, a sub-category of rare developmental disorders is emerging with RAC1 as the central player. We show that ultra-rare disorders caused by private, non-recurrent missense mutations that result in varying phenotypes are challenging to dissect, but can be delineated through focused international collaboration. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  6. Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders.

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    Andrews, Tallulah; Meader, Stephen; Vulto-van Silfhout, Anneke; Taylor, Avigail; Steinberg, Julia; Hehir-Kwa, Jayne; Pfundt, Rolph; de Leeuw, Nicole; de Vries, Bert B A; Webber, Caleb

    2015-03-01

    Readily-accessible and standardised capture of genotypic variation has revolutionised our understanding of the genetic contribution to disease. Unfortunately, the corresponding systematic capture of patient phenotypic variation needed to fully interpret the impact of genetic variation has lagged far behind. Exploiting deep and systematic phenotyping of a cohort of 197 patients presenting with heterogeneous developmental disorders and whose genomes harbour de novo CNVs, we systematically applied a range of commonly-used functional genomics approaches to identify the underlying molecular perturbations and their phenotypic impact. Grouping patients into 408 non-exclusive patient-phenotype groups, we identified a functional association amongst the genes disrupted in 209 (51%) groups. We find evidence for a significant number of molecular interactions amongst the association-contributing genes, including a single highly-interconnected network disrupted in 20% of patients with intellectual disability, and show using microcephaly how these molecular networks can be used as baits to identify additional members whose genes are variant in other patients with the same phenotype. Exploiting the systematic phenotyping of this cohort, we observe phenotypic concordance amongst patients whose variant genes contribute to the same functional association but note that (i) this relationship shows significant variation across the different approaches used to infer a commonly perturbed molecular pathway, and (ii) that the phenotypic similarities detected amongst patients who share the same inferred pathway perturbation result from these patients sharing many distinct phenotypes, rather than sharing a more specific phenotype, inferring that these pathways are best characterized by their pleiotropic effects.

  7. How accurate is the phenotype? – An analysis of developmental noise in a cotton aphid clone

    Directory of Open Access Journals (Sweden)

    Babbitt Gregory A

    2008-02-01

    Full Text Available Abstract Background The accuracy by which phenotype can be reproduced by genotype potentially is important in determining the stability, environmental sensitivity, and evolvability of morphology and other phenotypic traits. Because two sides of an individual represent independent development of the phenotype under identical genetic and environmental conditions, average body asymmetry (or "fluctuating asymmetry" can estimate the developmental instability of the population. The component of developmental instability not explained by intrapopulational differences in gene or environment (or their interaction can be further defined as internal developmental noise. Surprisingly, developmental noise remains largely unexplored despite its potential influence on our interpretations of developmental stability, canalization, and evolvability. Proponents of fluctuating asymmetry as a bioindicator of environmental or genetic stress, often make the assumption that developmental noise is minimal and, therefore, that phenotype can respond sensitively to the environment. However, biologists still have not measured whether developmental noise actually comprises a significant fraction of the overall environmental response of fluctuating asymmetry observed within a population. Results In a morphometric study designed to partition developmental noise from fluctuating asymmetry in the wing morphology of a monoclonal culture of cotton aphid, Aphis gossipyii, it was discovered that fluctuating asymmetry in the aphid wing was nearly four times higher than in other insect species. Also, developmental noise comprised a surprisingly large fraction (≈ 50% of the overall response of fluctuating asymmetry to a controlled graded temperature environment. Fluctuating asymmetry also correlated negatively with temperature, indicating that environmentally-stimulated changes in developmental instability are mediated mostly by changes in the development time of individuals

  8. Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders.

    Directory of Open Access Journals (Sweden)

    Tallulah Andrews

    2015-03-01

    Full Text Available Readily-accessible and standardised capture of genotypic variation has revolutionised our understanding of the genetic contribution to disease. Unfortunately, the corresponding systematic capture of patient phenotypic variation needed to fully interpret the impact of genetic variation has lagged far behind. Exploiting deep and systematic phenotyping of a cohort of 197 patients presenting with heterogeneous developmental disorders and whose genomes harbour de novo CNVs, we systematically applied a range of commonly-used functional genomics approaches to identify the underlying molecular perturbations and their phenotypic impact. Grouping patients into 408 non-exclusive patient-phenotype groups, we identified a functional association amongst the genes disrupted in 209 (51% groups. We find evidence for a significant number of molecular interactions amongst the association-contributing genes, including a single highly-interconnected network disrupted in 20% of patients with intellectual disability, and show using microcephaly how these molecular networks can be used as baits to identify additional members whose genes are variant in other patients with the same phenotype. Exploiting the systematic phenotyping of this cohort, we observe phenotypic concordance amongst patients whose variant genes contribute to the same functional association but note that (i this relationship shows significant variation across the different approaches used to infer a commonly perturbed molecular pathway, and (ii that the phenotypic similarities detected amongst patients who share the same inferred pathway perturbation result from these patients sharing many distinct phenotypes, rather than sharing a more specific phenotype, inferring that these pathways are best characterized by their pleiotropic effects.

  9. Adaptive developmental plasticity: Compartmentalized responses to environmental cues and corresponding internal signals provide phenotypic flexibility

    NARCIS (Netherlands)

    Mateus, A.R.A.; Marques-Pita, M.; Oostra, V.; Lafuente, E.; Brakefield, P.M.; Zwaan, B.J.; Beldade, P.

    2014-01-01

    Background The environmental regulation of development can result in the production of distinct phenotypes from the same genotype and provide the means for organisms to cope with environmental heterogeneity. The effect of the environment on developmental outcomes is typically mediated by hormonal

  10. Phenotypic plasticity in the developmental integration of morphological trade-offs and secondary sexual trait compensation.

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    Tomkins, Joseph L; Kotiaho, Janne S; Lebas, Natasha R

    2005-03-07

    Trait exaggeration through sexual selection will tale place alongside other changes in phenotype. Exaggerated morphology might be compensated by parallel changes in traits that support, enhance or facilitate exaggeration: 'secondary sexual trait compensation' (SSTC). Alternatively, exaggeration might be realized at the expense of other traits through morphological trade-offs. For the most part, SSTC has only been examined interspecifically. For these phenomena to be important intraspecifically, the sexual trait must be developmentally integrated with the compensatory or competing trait. We studied developmental integration in two species with different development: the holometabolous beetle Onthophagus taurus and the hemimetabolous earwig Forficula auricularia. Male-dimorphic variation in trait exaggeration was exploited to expose both trade-offs and SSTC. We found evidence for morphological trade-offs in O. taurus, but no F. auricularia, supporting the notion that trade-offs are more likely in closed developmetal systems. However, we found these trade-offs were not limited solely to traits growing close together. Developmental integration of structures involved in SSTC were detected in both species. The developmental integration of SSTC was phenotypically plastic, such that the compensation for relatively larger sexual traits was greater in the exasperated male morphs. Evidence of intraspecific SSTC demands studies of the selective, genetic and developmental architecture of phenotypic integration.

  11. Developmental phonagnosia: Linking neural mechanisms with the behavioural phenotype.

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    Roswandowitz, Claudia; Schelinski, Stefanie; von Kriegstein, Katharina

    2017-07-15

    Human voice recognition is critical for many aspects of social communication. Recently, a rare disorder, developmental phonagnosia, which describes the inability to recognise a speaker's voice, has been discovered. The underlying neural mechanisms are unknown. Here, we used two functional magnetic resonance imaging experiments to investigate brain function in two behaviourally well characterised phonagnosia cases, both 32 years old: AS has apperceptive and SP associative phonagnosia. We found distinct malfunctioned brain mechanisms in AS and SP matching their behavioural profiles. In apperceptive phonagnosia, right-hemispheric auditory voice-sensitive regions (i.e., Heschl's gyrus, planum temporale, superior temporal gyrus) showed lower responses than in matched controls (n AS =16) for vocal versus non-vocal sounds and for speaker versus speech recognition. In associative phonagnosia, the connectivity between voice-sensitive (i.e. right posterior middle/inferior temporal gyrus) and supramodal (i.e. amygdala) regions was reduced in comparison to matched controls (n SP =16) during speaker versus speech recognition. Additionally, both cases recruited distinct potential compensatory mechanisms. Our results support a central assumption of current two-system models of voice-identity processing: They provide the first evidence that dysfunction of voice-sensitive regions and impaired connectivity between voice-sensitive and supramodal person recognition regions can selectively contribute to deficits in person recognition by voice. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Phenotypic Plasticity, CYP19A1 Pleiotropy, and Maladaptive Selection in Developmental Disorders

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    J. Patrick Malone

    2013-05-01

    Full Text Available The contribution of evolutionary psychology to the study of development and psychopathology depends on adherence to the principles of evolutionary biology. The human brain evolved because selection favored neither size nor complexity but instead the phenotypic plasticity supporting cognitive flexibility. Cell proliferation, migration, elongation, synaptogenesis, synaptic pruning, apoptosis, and myelination occur at varying rates during asynchronous phases of development throughout the brain. Developmentally sensitive periods result from phenotypic plasticity and are vital for adaptation to the environment. The biological systems surrounding the CYP19A1 gene provide mechanisms for neuroprotection and targeted neuronal debridement in response to environmental stress, uniting selection with developmental biology. Updates to Dunbar’s original hypothesis with current primatological data, inclusion of total brain mass, and the introduction of CYP19A1 orthology from nine primate species yields a linear regression, R 2 = .994, adjusted R 2 = .989, F(3, 5 = 143.758, p < .001.

  13. Silver Nanoparticles Incite Size and Dose-Dependent Developmental Phenotypes and Nanotoxicity in Zebrafish Embryos

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    Browning, Lauren M.; Lee, Kerry J.; Nallathamby, Prakash D.; Xu, Xiao-Hong Nancy

    2013-01-01

    Nanomaterials possess distinctive physicochemical properties and promise a wide range of applications, from advanced technology to leading-edge medicine. However, their effects on living organisms remain largely unknown. Here we report that the purified silver nanoparticles (Ag NPs, 97 ± 13 nm) incite specific developmental stage embryonic phenotypes and nanotoxicity in a dose-dependent manner, upon acute exposure of given-stage embryos to the NPs (0–24 pM) for only 2 h. The critical concentrations of the NPs that cause 50% of embryos develop normally for cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stage zebrafish embryos are 3.5, 4, 6, 6, and 8 pM, respectively, showing that the earlier developmental stage embryos are much more sensitive to the effects of the NPs than the later stage. Interestingly, distinctive phenotypes (head abnormality and no eyes) are observed only in cleavage and early-gastrula stage embryos treated with the NPs, showing the stage-specific effects of the NPs. By comparing with our study of the smaller Ag NPs (13.1 ± 2.5 nm), we found that the embryonic phenotypes strikingly depend upon the sizes of Ag NPs and embryonic developmental stages. These notable findings suggest that the Ag NPs are unlike any conventional chemicals or ions. They can potentially enable target specific study and therapy for early embryonic development in size, stage, dose, and exposure-duration dependent manners. PMID:24024906

  14. Silver nanoparticles incite size- and dose-dependent developmental phenotypes and nanotoxicity in zebrafish embryos.

    Science.gov (United States)

    Browning, Lauren M; Lee, Kerry J; Nallathamby, Prakash D; Xu, Xiao-Hong Nancy

    2013-10-21

    Nanomaterials possess distinctive physicochemical properties and promise a wide range of applications, from advanced technology to leading-edge medicine. However, their effects on living organisms remain largely unknown. Here we report that the purified silver nanoparticles (Ag NPs) (97 ± 13 nm) incite specific developmental stage embryonic phenotypes and nanotoxicity in a dose-dependent manner, upon acute exposure of given stage embryos to the NPs (0-24 pM) for only 2 h. The critical concentrations of the NPs that cause 50% of embryos to develop normally for cleavage, early gastrula, early segmentation, late segmentation, and hatching stage zebrafish embryos are 3.5, 4, 6, 6, and 8 pM, respectively, showing that the earlier developmental stage embryos are much more sensitive to the effects of the NPs than the later stage embryos. Interestingly, distinctive phenotypes (head abnormality and no eyes) are observed only in cleavage and early gastrula stage embryos treated with the NPs, showing the stage-specific effects of the NPs. By comparing these Ag NPs with smaller Ag NPs (13.1 ± 2.5 nm), we found that the embryonic phenotypes strikingly depend upon the sizes of Ag NPs and embryonic developmental stages. These notable findings suggest that the Ag NPs are unlike any conventional chemicals or ions. They can potentially enable target-specific study and therapy for early embryonic development in size-, stage-, dose-, and exposure duration-dependent manners.

  15. Deciphering the Mechanisms of Developmental Disorders (DMDD: a new programme for phenotyping embryonic lethal mice

    Directory of Open Access Journals (Sweden)

    Timothy Mohun

    2013-05-01

    International efforts to test gene function in the mouse by the systematic knockout of each gene are creating many lines in which embryonic development is compromised. These homozygous lethal mutants represent a potential treasure trove for the biomedical community. Developmental biologists could exploit them in their studies of tissue differentiation and organogenesis; for clinical researchers they offer a powerful resource for investigating the origins of developmental diseases that affect newborns. Here, we outline a new programme of research in the UK aiming to kick-start research with embryonic lethal mouse lines. The ‘Deciphering the Mechanisms of Developmental Disorders’ (DMDD programme has the ambitious goal of identifying all embryonic lethal knockout lines made in the UK over the next 5 years, and will use a combination of comprehensive imaging and transcriptomics to identify abnormalities in embryo structure and development. All data will be made freely available, enabling individual researchers to identify lines relevant to their research. The DMDD programme will coordinate its work with similar international efforts through the umbrella of the International Mouse Phenotyping Consortium [see accompanying Special Article (Adams et al., 2013] and, together, these programmes will provide a novel database for embryonic development, linking gene identity with molecular profiles and morphology phenotypes.

  16. Phenotypic and genetic effects of contrasting ethanol environments on physiological and developmental traits in Drosophila melanogaster.

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    Luis E Castañeda

    Full Text Available A central problem in evolutionary physiology is to understand the relationship between energy metabolism and fitness-related traits. Most attempts to do so have been based on phenotypic correlations that are not informative for the evolutionary potential of natural populations. Here, we explored the effect of contrasting ethanol environments on physiological and developmental traits, their genetic (covariances and genetic architecture in Drosophila melanogaster. Phenotypic and genetic parameters were estimated in two populations (San Fernando and Valdivia, Chile, using a half-sib family design where broods were split into ethanol-free and ethanol-supplemented conditions. Our findings show that metabolic rate, body mass and development times were sensitive (i.e., phenotypic plasticity to ethanol conditions and dependent on population origin. Significant heritabilities were found for all traits, while significant genetic correlations were only found between larval and total development time and between development time and metabolic rate for flies of the San Fernando population developed in ethanol-free conditions. Posterior analyses indicated that the G matrices differed between ethanol conditions for the San Fernando population (mainly explained by differences in genetic (covariances of developmental traits, whereas the Valdivia population exhibited similar G matrices between ethanol conditions. Our findings suggest that ethanol-free environment increases the energy available to reduce development time. Therefore, our results indicate that environmental ethanol could modify the process of energy allocation, which could have consequences on the evolutionary response of natural populations of D. melanogaster.

  17. Ambient temperature and genotype differentially affect developmental and phenotypic plasticity in Arabidopsis thaliana.

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    Ibañez, Carla; Poeschl, Yvonne; Peterson, Tom; Bellstädt, Julia; Denk, Kathrin; Gogol-Döring, Andreas; Quint, Marcel; Delker, Carolin

    2017-07-06

    Global increase in ambient temperatures constitute a significant challenge to wild and cultivated plant species. Forward genetic analyses of individual temperature-responsive traits have resulted in the identification of several signaling and response components. However, a comprehensive knowledge about temperature sensitivity of different developmental stages and the contribution of natural variation is still scarce and fragmented at best. Here, we systematically analyze thermomorphogenesis throughout a complete life cycle in ten natural Arabidopsis thaliana accessions grown under long day conditions in four different temperatures ranging from 16 to 28 °C. We used Q 10 , GxE, phenotypic divergence and correlation analyses to assess temperature sensitivity and genotype effects of more than 30 morphometric and developmental traits representing five phenotype classes. We found that genotype and temperature differentially affected plant growth and development with variing strengths. Furthermore, overall correlations among phenotypic temperature responses was relatively low which seems to be caused by differential capacities for temperature adaptations of individual accessions. Genotype-specific temperature responses may be attractive targets for future forward genetic approaches and accession-specific thermomorphogenesis maps may aid the assessment of functional relevance of known and novel regulatory components.

  18. Phenotypic and Genetic Effects of Contrasting Ethanol Environments on Physiological and Developmental Traits in Drosophila melanogaster

    Science.gov (United States)

    Castañeda, Luis E.; Nespolo, Roberto F.

    2013-01-01

    A central problem in evolutionary physiology is to understand the relationship between energy metabolism and fitness-related traits. Most attempts to do so have been based on phenotypic correlations that are not informative for the evolutionary potential of natural populations. Here, we explored the effect of contrasting ethanol environments on physiological and developmental traits, their genetic (co)variances and genetic architecture in Drosophila melanogaster. Phenotypic and genetic parameters were estimated in two populations (San Fernando and Valdivia, Chile), using a half-sib family design where broods were split into ethanol-free and ethanol-supplemented conditions. Our findings show that metabolic rate, body mass and development times were sensitive (i.e., phenotypic plasticity) to ethanol conditions and dependent on population origin. Significant heritabilities were found for all traits, while significant genetic correlations were only found between larval and total development time and between development time and metabolic rate for flies of the San Fernando population developed in ethanol-free conditions. Posterior analyses indicated that the G matrices differed between ethanol conditions for the San Fernando population (mainly explained by differences in genetic (co)variances of developmental traits), whereas the Valdivia population exhibited similar G matrices between ethanol conditions. Our findings suggest that ethanol-free environment increases the energy available to reduce development time. Therefore, our results indicate that environmental ethanol could modify the process of energy allocation, which could have consequences on the evolutionary response of natural populations of D. melanogaster. PMID:23505567

  19. Developmental phenotypic plasticity helps bridge stochastic weather events associated with climate change.

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    Burggren, Warren

    2018-05-10

    The slow, inexorable rise in annual average global temperatures and acidification of the oceans are often advanced as consequences of global change. However, many environmental changes, especially those involving weather (as opposed to climate), are often stochastic, variable and extreme, particularly in temperate terrestrial or freshwater habitats. Moreover, few studies of animal and plant phenotypic plasticity employ realistic (i.e. short-term, stochastic) environmental change in their protocols. Here, I posit that the frequently abrupt environmental changes (days, weeks, months) accompanying much longer-term general climate change (e.g. global warming over decades or centuries) require consideration of the true nature of environmental change (as opposed to statistical means) coupled with an expansion of focus to consider developmental phenotypic plasticity. Such plasticity can be in multiple forms - obligatory/facultative, beneficial/deleterious - depending upon the degree and rate of environmental variability at specific points in organismal development. Essentially, adult phenotypic plasticity, as important as it is, will be irrelevant if developing offspring lack sufficient plasticity to create modified phenotypes necessary for survival. © 2018. Published by The Company of Biologists Ltd.

  20. A data-driven weighting scheme for multivariate phenotypic endpoints recapitulates zebrafish developmental cascades

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Guozhu, E-mail: gzhang6@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Roell, Kyle R., E-mail: krroell@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Truong, Lisa, E-mail: lisa.truong@oregonstate.edu [Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR (United States); Tanguay, Robert L., E-mail: robert.tanguay@oregonstate.edu [Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR (United States); Reif, David M., E-mail: dmreif@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC (United States)

    2017-01-01

    Zebrafish have become a key alternative model for studying health effects of environmental stressors, partly due to their genetic similarity to humans, fast generation time, and the efficiency of generating high-dimensional systematic data. Studies aiming to characterize adverse health effects in zebrafish typically include several phenotypic measurements (endpoints). While there is a solid biomedical basis for capturing a comprehensive set of endpoints, making summary judgments regarding health effects requires thoughtful integration across endpoints. Here, we introduce a Bayesian method to quantify the informativeness of 17 distinct zebrafish endpoints as a data-driven weighting scheme for a multi-endpoint summary measure, called weighted Aggregate Entropy (wAggE). We implement wAggE using high-throughput screening (HTS) data from zebrafish exposed to five concentrations of all 1060 ToxCast chemicals. Our results show that our empirical weighting scheme provides better performance in terms of the Receiver Operating Characteristic (ROC) curve for identifying significant morphological effects and improves robustness over traditional curve-fitting approaches. From a biological perspective, our results suggest that developmental cascade effects triggered by chemical exposure can be recapitulated by analyzing the relationships among endpoints. Thus, wAggE offers a powerful approach for analysis of multivariate phenotypes that can reveal underlying etiological processes. - Highlights: • Introduced a data-driven weighting scheme for multiple phenotypic endpoints. • Weighted Aggregate Entropy (wAggE) implies differential importance of endpoints. • Endpoint relationships reveal developmental cascade effects triggered by exposure. • wAggE is generalizable to multi-endpoint data of different shapes and scales.

  1. Fetal brain disruption sequence versus fetal brain arrest: A distinct autosomal recessive developmental brain malformation phenotype.

    Science.gov (United States)

    Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; El-Khayat, Hamed A; Eid, Ola M; Saba, Soliman; Farag, Mona K; Saleem, Sahar N; Gaber, Khaled R

    2015-05-01

    The term fetal brain disruption sequence (FBDS) was coined to describe a number of sporadic conditions caused by numerous external disruptive events presenting with variable imaging findings. However, rare familial occurrences have been reported. We describe five patients (two sib pairs and one sporadic) with congenital severe microcephaly, seizures, and profound intellectual disability. Brain magnetic resonance imaging (MRI) revealed unique and uniform picture of underdeveloped cerebral hemispheres with increased extraxial CSF, abnormal gyral pattern (polymicrogyria-like lesions in two sibs and lissencephaly in the others), loss of white matter, dysplastic ventricles, hypogenesis of corpus callosum, and hypoplasia of the brainstem, but hypoplastic cerebellum in one. Fetal magnetic resonance imaging (FMRI) of two patients showed the same developmental brain malformations in utero. These imaging findings are in accordance with arrested brain development rather than disruption. Molecular analysis excluded mutations in potentially related genes such as NDE1, MKL2, OCLN, and JAM3. These unique clinical and imaging findings were described before among familial reports with FBDS. However, our patients represent a recognizable phenotype of developmental brain malformations, that is, apparently distinguishable from either familial microhydranencephaly or microlissencephaly that were collectively termed FBDS. Thus, the use of the umbrella term FBDS is no longer helpful. Accordingly, we propose the term fetal brain arrest to distinguish them from other familial patients diagnosed as FBDS. The presence of five affected patients from three unrelated consanguineous families suggests an autosomal-recessive mode of inheritance. The spectrum of fetal brain disruption sequence is reviewed. © 2015 Wiley Periodicals, Inc.

  2. The fossil record of phenotypic integration and modularity: A deep-time perspective on developmental and evolutionary dynamics.

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    Goswami, Anjali; Binder, Wendy J; Meachen, Julie; O'Keefe, F Robin

    2015-04-21

    Variation is the raw material for natural selection, but the factors shaping variation are still poorly understood. Genetic and developmental interactions can direct variation, but there has been little synthesis of these effects with the extrinsic factors that can shape biodiversity over large scales. The study of phenotypic integration and modularity has the capacity to unify these aspects of evolutionary study by estimating genetic and developmental interactions through the quantitative analysis of morphology, allowing for combined assessment of intrinsic and extrinsic effects. Data from the fossil record in particular are central to our understanding of phenotypic integration and modularity because they provide the only information on deep-time developmental and evolutionary dynamics, including trends in trait relationships and their role in shaping organismal diversity. Here, we demonstrate the important perspective on phenotypic integration provided by the fossil record with a study of Smilodon fatalis (saber-toothed cats) and Canis dirus (dire wolves). We quantified temporal trends in size, variance, phenotypic integration, and direct developmental integration (fluctuating asymmetry) through 27,000 y of Late Pleistocene climate change. Both S. fatalis and C. dirus showed a gradual decrease in magnitude of phenotypic integration and an increase in variance and the correlation between fluctuating asymmetry and overall integration through time, suggesting that developmental integration mediated morphological response to environmental change in the later populations of these species. These results are consistent with experimental studies and represent, to our knowledge, the first deep-time validation of the importance of developmental integration in stabilizing morphological evolution through periods of environmental change.

  3. Leaf phenotypic variation and developmental instability in relation to different light regimes

    Directory of Open Access Journals (Sweden)

    Henrique Venâncio

    2016-06-01

    Full Text Available ABSTRACT For pioneer plants, shaded habitats represent a stressful condition, where sunlight exposure is below the optimum level and so leaves expand in order to intercept a greater amount of light. We investigated changes in both phenotypic variation and stress of Bauhinia brevipes in sunny and shaded microhabitats. Leaf area was used as a measure of phenotypic variation, whereas leaf asymmetry (difference between right and left sides of leaves, was used as a measure of stress. We hypothesized an increase in leaf area and stress in shaded locations, which might indicate that B. brevipes was compensating for low light absorption, and elevated levels of stress, respectively. Plants in the sun fitted a fluctuating asymmetry pattern (normal distribution of right minus left sides, while shaded plants were clearly antisymmetric (bimodal distribution of leaf side differences. Leaf asymmetry and area were 5% and 26.8% higher in plants in the shade compared to plants in the sun, respectively. These results were expected since B. brevipes is found predominantly in open areas; so sunlight exposure is important for its development. The presence of antisymmetry is rare in studies of developmental instability, and here it might indicate higher stress compared to plants with fluctuating asymmetry.

  4. Empirically Based Phenotypic Profiles of Children with Pervasive Developmental Disorders : Interpretation in the Light of the DSM-5

    NARCIS (Netherlands)

    Greaves-Lord, Kirstin; Eussen, Mart L. J. M.; Verhulst, Frank C.; Minderaa, Ruud B.; Mandy, William; Hudziak, James J.; Steenhuis, Mark Peter; de Nijs, Pieter F.; Hartman, Catharina A.

    This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental

  5. Empirically Based Phenotypic Profiles of Children with Pervasive Developmental Disorders: Interpretation in the Light of the DSM-5

    Science.gov (United States)

    Greaves-Lord, Kirstin; Eussen, Mart L. J. M.; Verhulst, Frank C.; Minderaa, Ruud B.; Mandy, William; Hudziak, James J.; Steenhuis, Mark Peter; de Nijs, Pieter F.; Hartman, Catharina A.

    2013-01-01

    This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental disorder (PDD), and (2) how profiles related to…

  6. Silver nanoparticles induce developmental stage-specific embryonic phenotypes in zebrafish

    Science.gov (United States)

    Lee, Kerry J.; Browning, Lauren M.; Nallathamby, Prakash D.; Osgood, Christopher J.; Xu, Xiao-Hong Nancy

    2013-11-01

    Much is anticipated from the development and deployment of nanomaterials in biological organisms, but concerns remain regarding their biocompatibility and target specificity. Here we report our study of the transport, biocompatibility and toxicity of purified and stable silver nanoparticles (Ag NPs, 13.1 +/- 2.5 nm in diameter) upon the specific developmental stages of zebrafish embryos using single NP plasmonic spectroscopy. We find that single Ag NPs passively diffuse into five different developmental stages of embryos (cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stages), showing stage-independent diffusion modes and diffusion coefficients. Notably, the Ag NPs induce distinctive stage and dose-dependent phenotypes and nanotoxicity, upon their acute exposure to the Ag NPs (0-0.7 nM) for only 2 h. The late-segmentation embryos are most sensitive to the NPs with the lowest critical concentration (CNP,c nanotoxicity, upon their acute exposure to the Ag NPs (0-0.7 nM) for only 2 h. The late-segmentation embryos are most sensitive to the NPs with the lowest critical concentration (CNP,c << 0.02 nM) and highest percentages of cardiac abnormalities, followed by early-segmentation embryos (CNP,c < 0.02 nM), suggesting that disruption of cell differentiation by the NPs causes the most toxic effects on embryonic development. The cleavage-stage embryos treated with the NPs develop into a wide variety of phenotypes (abnormal finfold, tail/spinal cord flexure, cardiac malformation/edema, yolk sac edema, and acephaly). These organ structures are not yet developed in cleavage-stage embryos, suggesting that the earliest determinative events to create these structures are ongoing, and disrupted by NPs, which leads to the downstream effects. In contrast, the hatching embryos are most resistant to the Ag NPs, and majority of embryos (94%) develop normally, and none of them develop abnormally. Interestingly, early-gastrula embryos are less sensitive

  7. Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders

    NARCIS (Netherlands)

    Andrews, T.; Meader, S.; Vulto-van Silfhout, A.T.; Taylor, A.; Steinberg, J.; Hehir-Kwa, J.; Pfundt, R.P.; Leeuw, N. de; Vries, B. de; Webber, C.

    2015-01-01

    Readily-accessible and standardised capture of genotypic variation has revolutionised our understanding of the genetic contribution to disease. Unfortunately, the corresponding systematic capture of patient phenotypic variation needed to fully interpret the impact of genetic variation has lagged far

  8. Past climate change on Sky Islands drives novelty in a core developmental gene network and its phenotype.

    Science.gov (United States)

    Favé, Marie-Julie; Johnson, Robert A; Cover, Stefan; Handschuh, Stephan; Metscher, Brian D; Müller, Gerd B; Gopalan, Shyamalika; Abouheif, Ehab

    2015-09-04

    A fundamental and enduring problem in evolutionary biology is to understand how populations differentiate in the wild, yet little is known about what role organismal development plays in this process. Organismal development integrates environmental inputs with the action of gene regulatory networks to generate the phenotype. Core developmental gene networks have been highly conserved for millions of years across all animals, and therefore, organismal development may bias variation available for selection to work on. Biased variation may facilitate repeatable phenotypic responses when exposed to similar environmental inputs and ecological changes. To gain a more complete understanding of population differentiation in the wild, we integrated evolutionary developmental biology with population genetics, morphology, paleoecology and ecology. This integration was made possible by studying how populations of the ant species Monomorium emersoni respond to climatic and ecological changes across five 'Sky Islands' in Arizona, which are mountain ranges separated by vast 'seas' of desert. Sky Islands represent a replicated natural experiment allowing us to determine how repeatable is the response of M. emersoni populations to climate and ecological changes at the phenotypic, developmental, and gene network levels. We show that a core developmental gene network and its phenotype has kept pace with ecological and climate change on each Sky Island over the last ~90,000 years before present (BP). This response has produced two types of evolutionary change within an ant species: one type is unpredictable and contingent on the pattern of isolation of Sky lsland populations by climate warming, resulting in slight changes in gene expression, organ growth, and morphology. The other type is predictable and deterministic, resulting in the repeated evolution of a novel wingless queen phenotype and its underlying gene network in response to habitat changes induced by climate warming. Our

  9. Developmental Research in Space: Predicting Adult Neurobehavioral Phenotypes via Metabolomic Imaging

    Science.gov (United States)

    Schorn, Julia M.; Moyer, Eric L.; Lowe, Moniece M.; Morgan, Jonathan; Tulbert, Christina D.; Olson, John; Olson, John; Horita, David A.; Kleven, Gale A.

    2017-01-01

    As human habitation and eventual colonization of space becomes an inevitable reality, there is a necessity to understand how organisms develop over the life span in the space environment. Microgravity, altered CO2, radiation and psychological stress are some of the key factors that could affect mammalian reproduction and development in space, however there is a paucity of information on this topic. Here we combine early (neonatal) in vivo spectroscopic imaging with an adult emotionality assay following a common obstetric complication (prenatal asphyxia) likely to occur during gestation in space. The neural metabolome is sensitive to alteration by degenerative changes and developmental disorders, thus we hypothesized that that early neonatal neurometabolite profiles can predict adult response to novelty. Late gestation fetal rats were exposed to moderate asphyxia by occluding the blood supply feeding one of the rats pair uterine horns for 15min. Blood supply to the opposite horn was not occluded (within-litter cesarean control). Further comparisons were made with vaginal (natural) birth controls. In one-week old neonates, we measured neurometabolites in three brain areas (i.e., striatum, prefrontal cortex, and hippocampus). Adult perinatally-asphyxiated offspring exhibited greater anxiety-like behavioral phenotypes (as measured the composite neurobehavioral assay involving open field activity, responses to novel object, quantification of fecal droppings, and resident-intruder tests of social behavior). Further, early neurometabolite profiles predicted adult responses. Non-invasive MRS screening of mammalian offspring is likely to advance ground-based space analogue studies informing mammalian reproduction in space, and achieving high-priority.

  10. Dominant negative mutations of Caenorhabditis elegans daf-7 confer a novel developmental phenotype.

    Science.gov (United States)

    Crook, Matt; Grant, Warwick N

    2013-06-01

    TGF-β signaling pathways are involved in the control of development in every member of the animal kingdom. As such, TGF-β ligands are widely divergent yet retain a set of core conserved features, specifically, a pre-protein cleavage site and several conserved ligand domain residues, the disruption of which produces a dominant negative phenotype. We have extended these observations into an invertebrate system by creating a series of loss-of-function Caenorhabditis elegans daf-7 transgenes. When we tested these mutant transgenes in a daf-7/+ background, we saw a molting and excretory canal phenotype. Members of both pathways downstream of daf-4 were required for this phenotype. Our results show that the basic mechanisms of TGF-β function are conserved across the animal kingdom. A subset of our daf-7 mutations also produced an unexpected and novel phenotype. Epistasis experiments demonstrated that both daf-3/-5 and sma-4/-9 were downstream of our mutant daf-7 transgenes, which suggests not only a role for DAF-7 in the control of molting and the development of the excretory system but also that daf-7 and dbl-1 signaling may converge downstream of their shared Type II receptor, daf-4. Our approach may unveil new roles in development for other invertebrate TGF-β ligands. Copyright © 2013 Wiley Periodicals, Inc.

  11. Developmental plasticity in reptiles: Insights into thermal and maternal effects on chameleon phenotypes.

    Science.gov (United States)

    Andrews, Robin M

    2018-04-23

    Embryonic environments affect a range of phenotypic traits including sex and reproductive success. I determined (1) how the interaction between incubation temperature and egg size affects sex allocation of Chamaeleo calyptratus and (2) how incubation temperature and maternal parent (clutch) affect water uptake by eggs and body size, growth, and climbing speed of hatchlings and juveniles. Eggs from five clutches were exposed to five temperature treatments with clutches replicated within and among treatments. Temperature affected sex, but only when egg size was included as a factor in analyses. At intermediate (28°C) temperatures, daughters were more likely to be produced from large eggs and sons more likely to be produced from small eggs, while at 25 and 30°C, the pattern of sex allocation was reversed. Temperature and clutch affected water uptake and body size. Nonetheless, the direction of temperature and clutch effects on water uptake by eggs and on the size of hatchlings were not the same and the direction of temperature effects on body sizes of hatchlings and juveniles differed as well. Clutch affected hatchling size but not juvenile size and growth rate. Clutch, but not incubation temperature, affected climbing speed, but the fastest hatchlings were not from the same clutches as the fastest juveniles. The independent effects of incubation temperature and clutch indicate that hatchling phenotypes are influenced largely by conditions experienced during incubation, while juvenile phenotypes are influenced largely by conditions experienced in the rearing environment. © 2018 Wiley Periodicals, Inc.

  12. Developmental neurotoxicants target neurodifferentiation into the serotonin phenotype: Chlorpyrifos, diazinon, dieldrin and divalent nickel

    International Nuclear Information System (INIS)

    Slotkin, Theodore A.; Seidler, Frederic J.

    2008-01-01

    Developmental exposure to organophosphates (OP) produces long-term changes in serotonin (5HT) synaptic function and associated behaviors, but there are disparities among the different OPs. We contrasted effects of chlorpyrifos and diazinon, as well as non-OP neurotoxicants (dieldrin, Ni 2+ ) using undifferentiated and differentiating PC12 cells, a well-established neurodevelopmental model. Agents were introduced at 30 μM for 24 or 72 h, treatments devoid of cytotoxicity, and we evaluated the mRNAs encoding the proteins for 5HT biosynthesis, storage and degradation, as well as 5HT receptors. Chlorpyrifos and diazinon both induced tryptophan hydroxylase, the rate-limiting enzyme for 5HT biosynthesis, but chlorpyrifos had a greater effect, and both agents suppressed expression of 5HT transporter genes, effects that would tend to augment extracellular 5HT. However, whereas chlorpyrifos enhanced the expression of most 5HT receptor subtypes, diazinon evoked overall suppression. Dieldrin evoked even stronger induction of tryptophan hydroxylase, and displayed a pattern of receptor effects similar to that of diazinon, even though they come from different pesticide classes. In contrast, Ni 2+ had completely distinct actions, suppressing tryptophan hydroxylase and enhancing the vesicular monoamine transporter, while also reducing 5HT receptor gene expression, effects that would tend to lower net 5HT function. Our findings provide some of the first evidence connecting the direct, initial mechanisms of developmental neurotoxicant action on specific transmitter pathways with their long-term effects on synaptic function and behavior, while also providing support for in vitro test systems as tools for establishing mechanisms and outcomes of related and unrelated neurotoxicants

  13. Overview of Social Cognitive Dysfunctions in Rare Developmental Syndromes With Psychiatric Phenotype

    Directory of Open Access Journals (Sweden)

    Aurore Morel

    2018-05-01

    Full Text Available Rare neurodevelopmental syndromes often present social cognitive deficits that may underlie difficulties in social interactions and increase the risk of psychosis or autism spectrum disorders. However, little is known regarding the specificities of social cognitive impairment across syndromes while it remains a major challenge for the care. Our review provides an overview of social cognitive dysfunctions in rare diseases associated with psychiatric symptoms (with a prevalence estimated between 1 in 1,200 and 1 in 25,000 live births: 22q11.2 deletion syndrome, Angelman syndrome, Fragile X syndrome, Klinefelter syndrome, Prader–Willi syndrome, Rett syndrome, Smith–Magenis syndrome, Turner syndrome, and Williams syndrome and shed some light on the specific mechanisms that may underlie these skills in each clinical presentation. We first detail the different processes included in the generic expression “social cognition” before summarizing the genotype, psychiatric phenotype, and non-social cognitive profile in each syndrome. Then, we offer a systematic review of the social cognitive abilities and the disturbed mechanisms they are likely associated with. We followed the PRISMA process, including the definition of the relevant search terms, the selection of studies based on clear inclusion, and exclusion criteria and the quality appraisal of papers. We finally provide insights that may have considerable influence on the development of adapted therapeutic interventions such as social cognitive training (SCT therapies specifically designed to target the psychiatric phenotype. The results of this review suggest that social cognition impairments share some similarities across syndromes. We propose that social cognitive impairments are strongly involved in behavioral symptoms regardless of the overall cognitive level measured by intelligence quotient. Better understanding the mechanisms underlying impaired social cognition may lead to adapt

  14. Asymmetry in dentition and shape of pharyngeal arches in the clonal fish Chrosomus eos-neogaeus: Phenotypic plasticity and developmental instability.

    Directory of Open Access Journals (Sweden)

    Christelle Leung

    Full Text Available The effect of the environment may result in different developmental outcomes. Extrinsic signals can modify developmental pathways and result in alternative phenotypes (phenotypic plasticity. The environment can also be interpreted as a stressor and increase developmental instability (developmental noise. Directional and fluctuating asymmetry provide a conceptual background to discriminate between these results. This study aims at assessing whether variation in dentition and shape of pharyngeal arches of the clonal fish Chrosomus eos-neogaeus results from developmental instability or environmentally induced changes. A total of 262 specimens of the Chrosomus eos-neogaeus complex from 12 natural sites were analysed. X-ray microcomputed tomography (X-ray micro-CT was used to visualize the pharyngeal arches in situ with high resolution. Variation in the number of pharyngeal teeth is high in hybrids in contrast to the relative stability observed in both parental species. The basal dental formula is symmetric while the most frequent alternative dental formula is asymmetric. Within one lineage, large variation in the proportion of individuals bearing basal or alternative dental formulae was observed among sites in the absence of genetic difference. Both dentition and arch shape of this hybrid lineage were explained significantly by environmental differences. Only individuals bearing asymmetric dental formula displayed fluctuating asymmetry as well as directional left-right asymmetry for the arches. The hybrids appeared sensitive to environmental signals and intraspecific variation on pharyngeal teeth was not random but reflects phenotypic plasticity. Altogether, these results support the influence of the environment as a trigger for an alternative developmental pathway resulting in left-right asymmetry in dentition and shape of pharyngeal arches.

  15. Overlapping Phenotypes in Autism Spectrum Disorder and Developmental Coordination Disorder: A Cross-Syndrome Comparison of Motor and Social Skills

    Science.gov (United States)

    Sumner, Emma; Leonard, Hayley C.; Hill, Elisabeth L.

    2016-01-01

    Motor and social difficulties are often found in children with an autism spectrum disorder (ASD) and with developmental coordination disorder (DCD), to varying degrees. This study investigated the extent of overlap of these problems in children aged 7-10 years who had a diagnosis of either ASD or DCD, compared to typically-developing controls.…

  16. Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish

    International Nuclear Information System (INIS)

    Haggard, Derik E.; Noyes, Pamela D.; Waters, Katrina M.; Tanguay, Robert L.

    2016-01-01

    Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen signaling; therefore, research examining the developmental effects of TCS is warranted. In this study, we used embryonic zebrafish to investigate the developmental toxicity and potential mechanism of action of TCS. Embryos were exposed to graded concentrations of TCS from 6 to 120 hours post-fertilization (hpf) and the concentration where 80% of the animals had mortality or morbidity at 120 hpf (EC 80 ) was calculated. Transcriptomic profiling was conducted on embryos exposed to the EC 80 (7.37 μM). We identified a total of 922 significant differentially expressed transcripts (FDR adjusted P-value ≤ 0.05; fold change ≥ 2). Pathway and gene ontology enrichment analyses identified biological networks and transcriptional hubs involving normal liver functioning, suggesting TCS may be hepatotoxic in zebrafish. Tissue-specific gene enrichment analysis further supported the role of the liver as a target organ for TCS toxicity. We also examined the in vitro bioactivity profile of TCS reported by the ToxCast screening program. TCS had a diverse bioactivity profile and was a hit in 217 of the 385 assay endpoints we identified. We observed similarities in gene expression and hepatic steatosis assays; however, hit data for TCS were more concordant with the hypothesized CAR/PXR activity of TCS from rodent and human in vitro studies. - Highlights: • Triclosan is a common antimicrobial agent with widespread human exposure. • Exposure to the triclosan EC 80 causes robust gene expression changes in zebrafish. • The liver may be a target organ of triclosan toxicity in embryonic zebrafish. • Triclosan disrupts normal liver functioning and development in

  17. Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Haggard, Derik E. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States); Noyes, Pamela D. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States); Office of Science Coordination and Policy (OSCP), Office of Chemical Safety and Pollution Prevention, U.S. Environmental Protection Agency, Washington, DC (United States); Waters, Katrina M. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA (United States); Tanguay, Robert L., E-mail: Robert.Tanguay@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States)

    2016-10-01

    Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen signaling; therefore, research examining the developmental effects of TCS is warranted. In this study, we used embryonic zebrafish to investigate the developmental toxicity and potential mechanism of action of TCS. Embryos were exposed to graded concentrations of TCS from 6 to 120 hours post-fertilization (hpf) and the concentration where 80% of the animals had mortality or morbidity at 120 hpf (EC{sub 80}) was calculated. Transcriptomic profiling was conducted on embryos exposed to the EC{sub 80} (7.37 μM). We identified a total of 922 significant differentially expressed transcripts (FDR adjusted P-value ≤ 0.05; fold change ≥ 2). Pathway and gene ontology enrichment analyses identified biological networks and transcriptional hubs involving normal liver functioning, suggesting TCS may be hepatotoxic in zebrafish. Tissue-specific gene enrichment analysis further supported the role of the liver as a target organ for TCS toxicity. We also examined the in vitro bioactivity profile of TCS reported by the ToxCast screening program. TCS had a diverse bioactivity profile and was a hit in 217 of the 385 assay endpoints we identified. We observed similarities in gene expression and hepatic steatosis assays; however, hit data for TCS were more concordant with the hypothesized CAR/PXR activity of TCS from rodent and human in vitro studies. - Highlights: • Triclosan is a common antimicrobial agent with widespread human exposure. • Exposure to the triclosan EC{sub 80} causes robust gene expression changes in zebrafish. • The liver may be a target organ of triclosan toxicity in embryonic zebrafish. • Triclosan disrupts normal liver functioning and

  18. Developmental Connectivity and Molecular Phenotypes of Unique Cortical Projection Neurons that Express a Synapse-Associated Receptor Tyrosine Kinase.

    Science.gov (United States)

    Kast, Ryan J; Wu, Hsiao-Huei; Levitt, Pat

    2017-11-28

    The complex circuitry and cell-type diversity of the cerebral cortex are required for its high-level functions. The mechanisms underlying the diversification of cortical neurons during prenatal development have received substantial attention, but understanding of neuronal heterogeneity is more limited during later periods of cortical circuit maturation. To address this knowledge gap, connectivity analysis and molecular phenotyping of cortical neuron subtypes that express the developing synapse-enriched MET receptor tyrosine kinase were performed. Experiments used a MetGFP transgenic mouse line, combined with coexpression analysis of class-specific molecular markers and retrograde connectivity mapping. The results reveal that MET is expressed by a minor subset of subcerebral and a larger number of intratelencephalic projection neurons. Remarkably, MET is excluded from most layer 6 corticothalamic neurons. These findings are particularly relevant for understanding the maturation of discrete cortical circuits, given converging evidence that MET influences dendritic elaboration and glutamatergic synapse maturation. The data suggest that classically defined cortical projection classes can be further subdivided based on molecular characteristics that likely influence synaptic maturation and circuit wiring. Additionally, given that MET is classified as a high confidence autism risk gene, the data suggest that projection neuron subpopulations may be differentially vulnerable to disorder-associated genetic variation. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Phenotype-genotype correlation in potential female carriers of X-linked developmental cataract (Nance-Horan syndrome).

    Science.gov (United States)

    Khan, Arif O; Aldahmesh, Mohammed A; Mohamed, Jawahir Y; Alkuraya, Fowzan S

    2012-06-01

    To correlate clinical examination with underlying genotype in asymptomatic females who are potential carriers of X-linked developmental cataract (Nance-Horan syndrome). An ophthalmologist blind to the pedigree performed comprehensive ophthalmic examination for 16 available family members (two affected and six asymptomatic females, five affected and three asymptomatic males). Facial features were also noted. Venous blood was collected for sequencing of the gene NHS. All seven affected family members had congenital or infantile cataract and facial dysmorphism (long face, bulbous nose, abnormal dentition). The six asymptomatic females ranged in age from 4-35 years old. Four had posterior Y-suture centered lens opacities; these four also exhibited the facial dysmorphism of the seven affected family members. The fifth asymptomatic girl had scattered fine punctate lens opacities (not centered on the Y-suture) while the sixth had clear lenses, and neither exhibited the facial dysmorphism. A novel NHS mutation (p.Lys744AsnfsX15 [c.2232delG]) was found in the seven patients with congenital or infantile cataract. This mutation was also present in the four asymptomatic girls with Y-centered lens opacities but not in the other two asymptomatic girls or in the three asymptomatic males (who had clear lenses). Lens opacities centered around the posterior Y-suture in the context of certain facial features were sensitive and specific clinical signs of carrier status for NHS mutation in asymptomatic females. Lens opacities that did not have this characteristic morphology in a suspected female carrier were not a carrier sign, even in the context of her affected family members.

  20. Phenotypic variability in developmental coordination disorder: Clustering of generalized joint hypermobility with attention deficit/hyperactivity disorder, atypical swallowing and narrative difficulties.

    Science.gov (United States)

    Celletti, Claudia; Mari, Giorgia; Ghibellini, Giulia; Celli, Mauro; Castori, Marco; Camerota, Filippo

    2015-03-01

    Developmental coordination disorder (DCD) is a recognized childhood disorder mostly characterized by motor coordination difficulties. Joint hypermobility syndrome, alternatively termed Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly featuring generalized joint hypermobility (gJHM), musculoskeletal pain, and minor skin features. Although these two conditions seem apparently unrelated, recent evidence highlights a high rate of motor and coordination findings in children with gJHM or JHS/EDS-HT. Here, we investigated the prevalence of gJHM in 41 Italian children with DCD in order to check for the existence of recognizable phenotypic subgroups of DCD in relation to the presence/absence of gJHM. All patients were screened for Beighton score and a set of neuropsychological tests for motor competences (Movement Assessment Battery for Children and Visual-Motor Integration tests), and language and learning difficulties (Linguistic Comprehension Test, Peabody Picture Vocabulary Test, Boston Naming Test, Bus Story Test, and Memoria-Training tests). All patients were also screening for selected JHS/EDS-HT-associated features and swallowing problems. Nineteen (46%) children showed gJHM and 22 (54%) did not. Children with DCD and gJHM showed a significant excess of frequent falls (95 vs. 18%), easy bruising (74 vs. 0%), motor impersistence (89 vs. 23%), sore hands for writing (53 vs. 9%), attention deficit/hyperactivity disorder (89 vs. 36%), constipation (53 vs. 0%), arthralgias/myalgias (58 vs. 4%), narrative difficulties (74 vs. 32%), and atypical swallowing (74 vs. 18%). This study confirms the non-causal association between DCD and gJHM, which, in turn, seems to increase the risk for non-random additional features. The excess of language, learning, and swallowing difficulties in patients with DCD and gJHM suggests a wider effect of lax tissues in the development of the nervous system. © 2015 Wiley Periodicals, Inc.

  1. Developmental phenotype in Phelan-McDermid (22q13.3 deletion) syndrome : A systematic and prospective study in 34 children

    NARCIS (Netherlands)

    Zwanenburg, Renée J; Ruiter, Selma A J; van den Heuvel, Edwin R; Flapper, Boudien C T; Van Ravenswaaij-Arts, Conny M A

    2016-01-01

    Background: Phelan- McDermid syndrome (PMS) or 22q13.3 deletion syndrome is characterized by global developmental delay, cognitive deficits, and behaviour in the autism spectrum. Knowledge about developmental and behavioural characteristics of this rare chromosomal disorder is still limited despite

  2. Developmental phenotype in Phelan- McDermid (22q13.3 deletion) syndrome : a systematic and prospective study in 34 children

    NARCIS (Netherlands)

    Zwanenburg, R.J.; Ruiter, S.A.J.; Van Den Heuvel, E.R.; Flapper, B.C.T.; Van Ravenswaaij-Arts, C.M.A.

    2016-01-01

    Background: Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is characterized by global developmental delay, cognitive deficits, and behaviour in the autism spectrum. Knowledge about developmental and behavioural characteristics of this rare chromosomal disorder is still limited despite a

  3. Phenotypic Dichotomy Following Developmental Exposure to Perfluorooctanic Acid (PFOA) Exposure in CD-1 Mice: Low Doses Induce Elevated Serum, Leptin, Insulin, and Overweight in Mid-Life.

    Science.gov (United States)

    The synthetic surfactant, perfluorooctanoic acid (PFOA) is a proven developmental toxicant in mice, causing prenatal pregnancy loss, increased neonatal mortality, delayed eye opening, and abnormal mammary gland growth in animals exposed during fetal life. PFOA is found in the ser...

  4. Chromosome 12q24.31-q24.33 deletion causes multiple dysmorphic features and developmental delay: First mosaic patient and overview of the phenotype related to 12q24qter defects

    Directory of Open Access Journals (Sweden)

    Sakati Nadia

    2011-04-01

    Full Text Available Abstract Background Genomic imbalances of the 12q telomere are rare; only a few patients having 12q24.31-q24.33 deletions were reported. Interestingly none of these were mosaic. Although some attempts have been made to establish phenotype/genotype interaction for the deletions in this region, no clear relationship has been established to date. Results We have clinically screened more than 100 patients with dysmorphic features, mental retardation and normal karyotype using high density oligo array-CGH (aCGH and identified a ~9.2 Mb hemizygous interstitial deletion at the 12q telomere (Chromosome 12: 46,XY,del(12(q24.31q24.33 in a severely developmentally retarded patient having dysmorphic features such as low set ears, microcephaly, undescended testicles, bent elbow, kyphoscoliosis, and micropenis. Parents were found to be not carriers. MLPA experiments confirmed the aCGH result. Interphase FISH revealed mosaicism in cultured peripheral blood lymphocytes. Conclusions Since conventional G-Banding technique missed the abnormality; this work re-confirms that any child with unexplained developmental delay and systemic involvement should be studied by aCGH techniques. The FISH technique, however, would still be useful to further delineate the research work and identify such rare mosaicism. Among the 52 deleted genes, P2RX2, ULK1, FZD10, RAN, NCOR2 STX2, TESC, FBXW8, and TBX3 are noteworthy since they may have a role in observed phenotype.

  5. 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.

    Science.gov (United States)

    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

  6. Poor infant soothability and later insecure-ambivalent attachment: developmental change in phenotypic markers of risk or two measures of the same construct?

    Science.gov (United States)

    Mills-Koonce, W Roger; Propper, Cathi B; Barnett, Melissa

    2012-04-01

    Using data from the Durham Child Health and Development Study (n=148), the current study examines the associations between child and parenting variables at 6 months and child attachment quality at 12 months of age and maternal report of child self regulation at 24 months of age. Child and parent variables predicted distinct forms of insecure attachment relationships. Observations of infant soothability during the reunion session of the Face-to-Face Still Face Paradigm at 6 months differentially predicted children with later insecure-ambivalent attachments from those with secure attachments. Observations of maternal negative intrusiveness at 6 months of age differentially predicted children with insecure-avoidant attachments from those with secure attachments. Maternal sensitivity at 6 months was associated with maternal report of child affective problems at 24 months, but this association was moderated by infant negativity during soothing and later moderated by child attachment quality. Collectively, these results suggest the following two mutually exclusive possibilities regarding infant soothability and later ambivalent attachment quality: either infant soothability is a unique and distinct predictor of later ambivalent attachment quality and this cascade represents a developmental shift in child risk during the first year of life, or that infant soothability following a stressful task at 6 months of age is itself an early indicator of ambivalent attachment behavior with the mother. The data from the current study could not provide differential support for one possibility over the other. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Transgenerational developmental programming.

    Science.gov (United States)

    Aiken, Catherine E; Ozanne, Susan E

    2014-01-01

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

  8. Deep Phenotyping: Deep Learning For Temporal Phenotype/Genotype Classification

    OpenAIRE

    Najafi, Mohammad; Namin, Sarah; Esmaeilzadeh, Mohammad; Brown, Tim; Borevitz, Justin

    2017-01-01

    High resolution and high throughput, genotype to phenotype studies in plants are underway to accelerate breeding of climate ready crops. Complex developmental phenotypes are observed by imaging a variety of accessions in different environment conditions, however extracting the genetically heritable traits is challenging. In the recent years, deep learning techniques and in particular Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs) and Long-Short Term Memories (LSTMs), h...

  9. Developmental Immunotoxicity

    Science.gov (United States)

    Animal models suggest that the immature immune system is more susceptible to xenobiotics than the fully mature system, and sequelae of developmental immunotoxicant exposure may be persistent well into adulthood. Immune maturation may be delayed by xenobiotic exposure and recover...

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

    Science.gov (United States)

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

    2015-10-01

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

  11. Developmental Scaffolding

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio

    2015-01-01

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

  12. Developmental delay

    Science.gov (United States)

    Nutrition support is essential for the care of the child with developmental delay. After a thorough evaluation, an individualized intervention plan that accounts for the child’s nutrition status, feeding ability, and medical condition may be determined. Nutrition assessments may be performed at leas...

  13. Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge; Kristensen, Tage Søndergaard

    2003-01-01

    Human Deveoplment and Working Life - Work for Welfare explores whether the development of human resources at company level can improve individuals' quality of life, companies' possibilities of development, and welfare and democracy in society. Chapter two discuss the concept "developmental work...

  14. Gestational Hyperandrogenism in Developmental Programming

    Science.gov (United States)

    Hakim, Christopher; Padmanabhan, Vasantha

    2017-01-01

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

  15. Developmental programming: the role of growth hormone.

    Science.gov (United States)

    Oberbauer, Anita M

    2015-01-01

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

  16. Childhood asthma-predictive phenotype.

    Science.gov (United States)

    Guilbert, Theresa W; Mauger, David T; Lemanske, Robert F

    2014-01-01

    Wheezing is a fairly common symptom in early childhood, but only some of these toddlers will experience continued wheezing symptoms in later childhood. The definition of the asthma-predictive phenotype is in children with frequent, recurrent wheezing in early life who have risk factors associated with the continuation of asthma symptoms in later life. Several asthma-predictive phenotypes were developed retrospectively based on large, longitudinal cohort studies; however, it can be difficult to differentiate these phenotypes clinically as the expression of symptoms, and risk factors can change with time. Genetic, environmental, developmental, and host factors and their interactions may contribute to the development, severity, and persistence of the asthma phenotype over time. Key characteristics that distinguish the childhood asthma-predictive phenotype include the following: male sex; a history of wheezing, with lower respiratory tract infections; history of parental asthma; history of atopic dermatitis; eosinophilia; early sensitization to food or aeroallergens; or lower lung function in early life. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Developmental programming and transgenerational transmission of obesity.

    Science.gov (United States)

    Vickers, M H

    2014-01-01

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

  18. The phenotypic variance gradient - a novel concept.

    Science.gov (United States)

    Pertoldi, Cino; Bundgaard, Jørgen; Loeschcke, Volker; Barker, James Stuart Flinton

    2014-11-01

    Evolutionary ecologists commonly use reaction norms, which show the range of phenotypes produced by a set of genotypes exposed to different environments, to quantify the degree of phenotypic variance and the magnitude of plasticity of morphometric and life-history traits. Significant differences among the values of the slopes of the reaction norms are interpreted as significant differences in phenotypic plasticity, whereas significant differences among phenotypic variances (variance or coefficient of variation) are interpreted as differences in the degree of developmental instability or canalization. We highlight some potential problems with this approach to quantifying phenotypic variance and suggest a novel and more informative way to plot reaction norms: namely "a plot of log (variance) on the y-axis versus log (mean) on the x-axis, with a reference line added". This approach gives an immediate impression of how the degree of phenotypic variance varies across an environmental gradient, taking into account the consequences of the scaling effect of the variance with the mean. The evolutionary implications of the variation in the degree of phenotypic variance, which we call a "phenotypic variance gradient", are discussed together with its potential interactions with variation in the degree of phenotypic plasticity and canalization.

  19. Developmental Trajectories of Young Girls with Fragile X Syndrome

    Science.gov (United States)

    Hatton, Deborah D.; Wheeler, Anne; Sideris, John; Sullivan, Kelly; Reichardt, Alison; Roberts, Jane; Clark, Renee; Bailey, Donald B., Jr.

    2009-01-01

    To describe the early phenotype of girls with full mutation fragile X, we used 54 observations of 15 girls between the ages of 6 months and 9 years to examine developmental trajectories as measured by the Battelle Development Inventory. In this sample, autistic behavior was associated with poorer developmental outcomes, primarily due to…

  20. The thrifty phenotype hypothesis revisited

    DEFF Research Database (Denmark)

    Vaag, A A; Grunnet, L G; Arora, G P

    2012-01-01

    Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the 'thrifty phenotype hypothesis' in Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal programming could represent an important player in the origin of type 2...... of the underlying molecular mechanisms. Type 2 diabetes is a multiple-organ disease, and developmental programming, with its idea of organ plasticity, is a plausible hypothesis for a common basis for the widespread organ dysfunctions in type 2 diabetes and the metabolic syndrome. Only two among the 45 known type 2...

  1. Intraspecific hybridization, developmental stability and fitness in Drosophila mercatorum

    DEFF Research Database (Denmark)

    Andersen, D.H.; Pertoldi, C.; Scali, V.

    2002-01-01

    One of the possible effects of intraspecific hybridization is outbreeding depression, due to a breakdown of coadapted gene complexes, which can lead to reduced fitness and decreased developmental stability in hybrids. Alternatively, increased fitness and increased developmental stability in hybrids...... (hybrid vigour) may be a result of hybridization, probably due to increased heterozygosity. Developmental stability is assumed to be correlated with fitness and is commonly measured as fluctuating asymmetry or phenotypic variance. Drosophila mercatorum is capable of reproducing sexually, but also...

  2. Do dwarf chameleons ( Bradypodion ) show developmental plasticity?

    African Journals Online (AJOL)

    It has been hypothesized that B. melanocephalum and B. thamnobates may be phenotypically plastic populations of the same species, since environmental conditions, the driving force behind developmental plasticity, varies between the distributions of these two allopatric taxa.We raised juveniles of both species under ...

  3. From genes to brain development to phenotypic behavior: "dorsal-stream vulnerability" in relation to spatial cognition, attention, and planning of actions in Williams syndrome (WS) and other developmental disorders.

    Science.gov (United States)

    Atkinson, Janette; Braddick, Oliver

    2011-01-01

    Visual information is believed to be processed through two distinct, yet interacting cortical streams. The ventral stream performs the computations needed for recognition of objects and faces ("what" and "who"?) and the dorsal stream the computations for registering spatial relationships and for controlling visually guided actions ("where" and "how"?). We initially proposed a model of spatial deficits in Williams syndrome (WS) in which visual abilities subserved by the ventral stream, such as face recognition, are relatively well developed (although not necessarily in exactly the same way as in typical development), whereas dorsal-stream functions, such as visuospatial actions, are markedly impaired. Since these initial findings in WS, deficits of motion coherence sensitivity, a dorsal-stream function has been found in other genetic disorders such as Fragile X and autism, and as a consequence of perinatal events (in hemiplegia, perinatal brain anomalies following very premature birth), leading to the proposal of a general "dorsal-stream vulnerability" in many different conditions of abnormal human development. In addition, dorsal-stream systems provide information used in tasks of visuospatial memory and locomotor planning, and these systems are closely coupled to networks for attentional control. We and several other research groups have previously shown deficits of frontal and parietal lobe function in WS individuals for specific attention tasks [e.g., Atkinson, J., Braddick, O., Anker, S., Curran, W., & Andrew, R. (2003). Neurobiological models of visuospatial cognition in children with Williams Syndrome: Measures of dorsal-stream and frontal function. Developmental Neuropsychology, 23(1/2), 141-174.]. We have used the Test of Everyday Attention for Children (TEA-Ch) which aims to attempt to separate components of attention with distinct brain networks (selective attention, sustained attention, and attention control-executive function) testing a group of older

  4. Mining skeletal phenotype descriptions from scientific literature.

    Directory of Open Access Journals (Sweden)

    Tudor Groza

    Full Text Available Phenotype descriptions are important for our understanding of genetics, as they enable the computation and analysis of a varied range of issues related to the genetic and developmental bases of correlated characters. The literature contains a wealth of such phenotype descriptions, usually reported as free-text entries, similar to typical clinical summaries. In this paper, we focus on creating and making available an annotated corpus of skeletal phenotype descriptions. In addition, we present and evaluate a hybrid Machine Learning approach for mining phenotype descriptions from free text. Our hybrid approach uses an ensemble of four classifiers and experiments with several aggregation techniques. The best scoring technique achieves an F-1 score of 71.52%, which is close to the state-of-the-art in other domains, where training data exists in abundance. Finally, we discuss the influence of the features chosen for the model on the overall performance of the method.

  5. Developmental dyscalculia.

    Science.gov (United States)

    Kucian, Karin; von Aster, Michael

    2015-01-01

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

  6. Delineating the GRIN1 phenotypic spectrum

    DEFF Research Database (Denmark)

    Lemke, Johannes R; Geider, Kirsten; Helbig, Katherine L

    2016-01-01

    consequences of GRIN1 mutations were investigated in Xenopus laevis oocytes. RESULTS: We identified heterozygous de novo GRIN1 mutations in 14 individuals and reviewed the phenotypes of all 9 previously reported patients. These 23 individuals presented with a distinct phenotype of profound developmental delay......, severe intellectual disability with absent speech, muscular hypotonia, hyperkinetic movement disorder, oculogyric crises, cortical blindness, generalized cerebral atrophy, and epilepsy. Mutations cluster within transmembrane segments and result in loss of channel function of varying severity...... impairment as well as oculomotor and movement disorders being discriminating phenotypic features. Loss of NMDA receptor function appears to be the underlying disease mechanism. The identification of both heterozygous and homozygous mutations blurs the borders of dominant and recessive inheritance of GRIN1...

  7. Hsp90 selectively modulates phenotype in vertebrate development.

    Directory of Open Access Journals (Sweden)

    Patricia L Yeyati

    2007-03-01

    Full Text Available Compromised heat shock protein 90 (Hsp90 function reveals cryptic phenotypes in flies and plants. These observations were interpreted to suggest that this molecular stress-response chaperone has a capacity to buffer underlying genetic variation. Conversely, the protective role of Hsp90 could account for the variable penetrance or severity of some heritable developmental malformations in vertebrates. Using zebrafish as a model, we defined Hsp90 inhibitor levels that did not induce a heat shock response or perturb phenotype in wild-type strains. Under these conditions the severity of the recessive eye phenotype in sunrise, caused by a pax6b mutation, was increased, while in dreumes, caused by a sufu mutation, it was decreased. In another strain, a previously unobserved spectrum of severe structural eye malformations, reminiscent of anophthalmia, microphthalmia, and nanophthalmia complex in humans, was uncovered by this limited inhibition of Hsp90 function. Inbreeding of offspring from selected unaffected carrier parents led to significantly elevated malformation frequencies and revealed the oligogenic nature of this phenotype. Unlike in Drosophila, Hsp90 inhibition can decrease developmental stability in zebrafish, as indicated by increased asymmetric presentation of anophthalmia, microphthalmia, and nanophthalmia and sunrise phenotypes. Analysis of the sunrise pax6b mutation suggests a molecular mechanism for the buffering of mutations by Hsp90. The zebrafish studies imply that mild perturbation of Hsp90 function at critical developmental stages may underpin the variable penetrance and expressivity of many developmental anomalies where the interaction between genotype and environment plays a major role.

  8. Revealing plant cryptotypes: defining meaningful phenotypes among infinite traits.

    Science.gov (United States)

    Chitwood, Daniel H; Topp, Christopher N

    2015-04-01

    The plant phenotype is infinite. Plants vary morphologically and molecularly over developmental time, in response to the environment, and genetically. Exhaustive phenotyping remains not only out of reach, but is also the limiting factor to interpreting the wealth of genetic information currently available. Although phenotyping methods are always improving, an impasse remains: even if we could measure the entirety of phenotype, how would we interpret it? We propose the concept of cryptotype to describe latent, multivariate phenotypes that maximize the separation of a priori classes. Whether the infinite points comprising a leaf outline or shape descriptors defining root architecture, statistical methods to discern the quantitative essence of an organism will be required as we approach measuring the totality of phenotype. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Developmental plasticity: re-conceiving the genotype.

    Science.gov (United States)

    Sultan, Sonia E

    2017-10-06

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

  10. Why did the savant syndrome not spread in the population? A psychiatric example of a developmental constraint

    NARCIS (Netherlands)

    Ploeger, A.; van der Maas, H.L.J.; Raijmakers, M.E.J.; Galis, F.

    2009-01-01

    A developmental constraint is a mechanism that limits the possibility of a phenotype to evolve. There is growing evidence for the existence of developmental constraints in the biological literature. We hypothesize that a developmental constraint prevents the savant syndrome, despite its positive

  11. The Domain of Developmental Psychopathology.

    Science.gov (United States)

    Sroufe, L. Alan; Rutter, Michael

    1984-01-01

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

  12. Asthma phenotypes in childhood.

    Science.gov (United States)

    Reddy, Monica B; Covar, Ronina A

    2016-04-01

    This review describes the literature over the past 18 months that evaluated childhood asthma phenotypes, highlighting the key aspects of these studies, and comparing these studies to previous ones in this area. Recent studies on asthma phenotypes have identified new phenotypes on the basis of statistical analyses (using cluster analysis and latent class analysis methodology) and have evaluated the outcomes and associated risk factors of previously established early childhood asthma phenotypes that are based on asthma onset and patterns of wheezing illness. There have also been investigations focusing on immunologic, physiologic, and genetic correlates of various phenotypes, as well as identification of subphenotypes of severe childhood asthma. Childhood asthma remains a heterogeneous condition, and investigations into these various presentations, risk factors, and outcomes are important since they can offer therapeutic and prognostic relevance. Further investigation into the immunopathology and genetic basis underlying childhood phenotypes is important so therapy can be tailored accordingly.

  13. Support for maternal manipulation of developmental nutrition in a facultatively eusocial bee, Megalopta genalis (Halictidae)

    OpenAIRE

    Kapheim, Karen M.; Bernal, Sandra P.; Smith, Adam R.; Nonacs, Peter; Wcislo, William T.

    2011-01-01

    Developmental maternal effects are a potentially important source of phenotypic variation, but they can be difficult to distinguish from other environmental factors. This is an important distinction within the context of social evolution, because if variation in offspring helping behavior is due to maternal manipulation, social selection may act on maternal phenotypes, as well as those of offspring. Factors correlated with social castes have been linked to variation in developmental nutrition...

  14. Trisomy 21 and facial developmental instability.

    Science.gov (United States)

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

    2013-05-01

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

  15. Reproductive and developmental toxicology

    National Research Council Canada - National Science Library

    Gupta, Ramesh C

    2011-01-01

    .... Reproductive and Developmental Toxicology is a comprehensive and authoritative resource providing the latest literature enriched with relevant references describing every aspect of this area of science...

  16. Clinical phenotypes of asthma

    NARCIS (Netherlands)

    Bel, Elisabeth H.

    2004-01-01

    PURPOSE OF REVIEW: Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic

  17. Why the short face? Developmental disintegration of the neurocranium drives convergent evolution in neotropical electric fishes.

    Science.gov (United States)

    Evans, Kory M; Waltz, Brandon; Tagliacollo, Victor; Chakrabarty, Prosanta; Albert, James S

    2017-03-01

    Convergent evolution is widely viewed as strong evidence for the influence of natural selection on the origin of phenotypic design. However, the emerging evo-devo synthesis has highlighted other processes that may bias and direct phenotypic evolution in the presence of environmental and genetic variation. Developmental biases on the production of phenotypic variation may channel the evolution of convergent forms by limiting the range of phenotypes produced during ontogeny. Here, we study the evolution and convergence of brachycephalic and dolichocephalic skull shapes among 133 species of Neotropical electric fishes (Gymnotiformes: Teleostei) and identify potential developmental biases on phenotypic evolution. We plot the ontogenetic trajectories of neurocranial phenotypes in 17 species and document developmental modularity between the face and braincase regions of the skull. We recover a significant relationship between developmental covariation and relative skull length and a significant relationship between developmental covariation and ontogenetic disparity. We demonstrate that modularity and integration bias the production of phenotypes along the brachycephalic and dolichocephalic skull axis and contribute to multiple, independent evolutionary transformations to highly brachycephalic and dolichocephalic skull morphologies.

  18. Life Span Developmental Approach

    Directory of Open Access Journals (Sweden)

    Ali Eryilmaz

    2011-03-01

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

  19. Developmental aspects of ADHD

    NARCIS (Netherlands)

    Belle, J. van

    2015-01-01

    It is increasingly recognized that ADHD is a heterogeneous disorder, both in its clinical presentation (phenotype) and the underlying aetiology. This heterogeneity makes it difficult to identify causal pathways that link the phenotype to brain structure and functioning. In an attempt to go beyond

  20. Reduce, reuse, and recycle: developmental evolution of trait diversification.

    Science.gov (United States)

    Preston, Jill C; Hileman, Lena C; Cubas, Pilar

    2011-03-01

    A major focus of evolutionary developmental (evo-devo) studies is to determine the genetic basis of variation in organismal form and function, both of which are fundamental to biological diversification. Pioneering work on metazoan and flowering plant systems has revealed conserved sets of genes that underlie the bauplan of organisms derived from a common ancestor. However, the extent to which variation in the developmental genetic toolkit mirrors variation at the phenotypic level is an active area of research. Here we explore evidence from the angiosperm evo-devo literature supporting the frugal use of genes and genetic pathways in the evolution of developmental patterning. In particular, these examples highlight the importance of genetic pleiotropy in different developmental modules, thus reducing the number of genes required in growth and development, and the reuse of particular genes in the parallel evolution of ecologically important traits.

  1. Reproductive and developmental toxicology

    National Research Council Canada - National Science Library

    Gupta, Ramesh C

    2011-01-01

    .... With a special focus on placental toxicity, this book is the only available reference to connect the three key risk stages, and is the only resource to include reproductive and developmental toxicity in domestic animals, fish, and wildlife.

  2. Developmental coordination disorder

    Science.gov (United States)

    Developmental coordination disorder can lead to: Learning problems Low self-esteem resulting from poor ability at sports and teasing by other children Repeated injuries Weight gain as a result of not wanting to participate ...

  3. Facts about Developmental Disabilities

    Science.gov (United States)

    ... play, learn, speak, behave, and move (for example, crawling and walking). Children develop at their own pace, ... person’s lifetime. Most developmental disabilities begin before a baby is born, but some can happen after birth ...

  4. The Developmental Brain Disorders Database (DBDB): a curated neurogenetics knowledge base with clinical and research applications.

    Science.gov (United States)

    Mirzaa, Ghayda M; Millen, Kathleen J; Barkovich, A James; Dobyns, William B; Paciorkowski, Alex R

    2014-06-01

    The number of single genes associated with neurodevelopmental disorders has increased dramatically over the past decade. The identification of causative genes for these disorders is important to clinical outcome as it allows for accurate assessment of prognosis, genetic counseling, delineation of natural history, inclusion in clinical trials, and in some cases determines therapy. Clinicians face the challenge of correctly identifying neurodevelopmental phenotypes, recognizing syndromes, and prioritizing the best candidate genes for testing. However, there is no central repository of definitions for many phenotypes, leading to errors of diagnosis. Additionally, there is no system of levels of evidence linking genes to phenotypes, making it difficult for clinicians to know which genes are most strongly associated with a given condition. We have developed the Developmental Brain Disorders Database (DBDB: https://www.dbdb.urmc.rochester.edu/home), a publicly available, online-curated repository of genes, phenotypes, and syndromes associated with neurodevelopmental disorders. DBDB contains the first referenced ontology of developmental brain phenotypes, and uses a novel system of levels of evidence for gene-phenotype associations. It is intended to assist clinicians in arriving at the correct diagnosis, select the most appropriate genetic test for that phenotype, and improve the care of patients with developmental brain disorders. For researchers interested in the discovery of novel genes for developmental brain disorders, DBDB provides a well-curated source of important genes against which research sequencing results can be compared. Finally, DBDB allows novel observations about the landscape of the neurogenetics knowledge base. © 2014 Wiley Periodicals, Inc.

  5. Life Span Developmental Approach

    OpenAIRE

    Ali Eryilmaz

    2011-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  7. The phenotypic spectrum of congenital Zika syndrome.

    Science.gov (United States)

    Del Campo, Miguel; Feitosa, Ian M L; Ribeiro, Erlane M; Horovitz, Dafne D G; Pessoa, André L S; França, Giovanny V A; García-Alix, Alfredo; Doriqui, Maria J R; Wanderley, Hector Y C; Sanseverino, Maria V T; Neri, João I C F; Pina-Neto, João M; Santos, Emerson S; Verçosa, Islane; Cernach, Mirlene C S P; Medeiros, Paula F V; Kerbage, Saile C; Silva, André A; van der Linden, Vanessa; Martelli, Celina M T; Cordeiro, Marli T; Dhalia, Rafael; Vianna, Fernanda S L; Victora, Cesar G; Cavalcanti, Denise P; Schuler-Faccini, Lavinia

    2017-04-01

    In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV. © 2017 Wiley Periodicals, Inc.

  8. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  9. Phenotypic Resistance to Antibiotics

    Directory of Open Access Journals (Sweden)

    Jose L. Martinez

    2013-04-01

    Full Text Available The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented.

  10. Reading in developmental prosopagnosia

    DEFF Research Database (Denmark)

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

    2018-01-01

    exposure durations (targeting the word superiority effect), and d) text reading. RESULTS: Participants with developmental prosopagnosia performed strikingly similar to controls across the four reading tasks. Formal analysis revealed a significant dissociation between word and face recognition......, that is, impaired reading in developmental prosopagnosia. METHOD: We tested 10 adults with developmental prosopagnosia and 20 matched controls. All participants completed the Cambridge Face Memory Test, the Cambridge Face Perception test and a Face recognition questionnaire used to quantify everyday face...... recognition experience. Reading was measured in four experimental tasks, testing different levels of letter, word, and text reading: (a) single word reading with words of varying length,(b) vocal response times in single letter and short word naming, (c) recognition of single letters and short words at brief...

  11. Developmental Plasticity in Child Growth and Maturation

    Directory of Open Access Journals (Sweden)

    Ze'ev eHochberg

    2011-09-01

    Full Text Available The ability of a given genotype to produce different phenotypes in response to different environments is termed "plasticity", and is part of the organism's "adaptability" to environmental cues. The expressions of suites of genes, particularly during development or life-history transitions, probably underlie the fundamental plasticity of an organism. Plasticity in developmental programming has evolved in order to provide the best chances of survival and reproductive success to organisms under changing environments. Environmental conditions that are experienced in early life can profoundly influence human biology, child growth and maturation, and long-term health and longevity. 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 for child growth and maturation in response to local ecological and/or social conditions. The window of developmental plasticity extends from conception to early childhood, and even beyond to the transition from juvenility to adoelscence, and could be transmitted transgenerationally. It involves epigenetic responses to environmental changes, which exert their effects during life history phase-transitions.

  12. The Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge

    2001-01-01

    AbstractIn the nineties, the concept of the developmental work (DW) has become a significant point of orientation for the actors on Danish labour market. The DW has moved the focus of the labour market from wages and working time towards work and production. For employees, the DW promises...... developmental possibilities, influence and responsibility, but also greater social responsibility for the firm. For firms, the DW promises increased competitiveness and better products. In this paper we present the concept of the DW as one which encourages the development of work, production and organisation...... of the firm and show that the DW is different from mainstream management concepts, as the DW...

  13. Arguments from Developmental Order.

    Science.gov (United States)

    Stöckle-Schobel, Richard

    2016-01-01

    In this article, I investigate a special type of argument regarding the role of development in theorizing about psychological processes and cognitive capacities. Among the issues that developmental psychologists study, discovering the ontogenetic trajectory of mechanisms or capacities underpinning our cognitive functions ranks highly. The order in which functions are developed or capacities are acquired is a matter of debate between competing psychological theories, and also philosophical conceptions of the mind - getting the role and the significance of the different steps in this order right could be seen as an important virtue of such theories. Thus, a special kind of strategy in arguments between competing philosophical or psychological theories is using developmental order in arguing for or against a given psychological claim. In this article, I will introduce an analysis of arguments from developmental order, which come in two general types: arguments emphasizing the importance of the early cognitive processes and arguments emphasizing the late cognitive processes. I will discuss their role in one of the central tools for evaluating scientific theories, namely in making inferences to the best explanation. I will argue that appeal to developmental order is, by itself, an insufficient criterion for theory choice and has to be part of an argument based on other core explanatory or empirical virtues. I will end by proposing a more concerted study of philosophical issues concerning (cognitive) development, and I will present some topics that also pertain to a full-fledged 'philosophy of development.'

  14. Developmental Education Evaluation Model.

    Science.gov (United States)

    Perry-Miller, Mitzi; And Others

    A developmental education evaluation model designed to be used at a multi-unit urban community college is described. The purpose of the design was to determine the cost effectiveness/worth of programs in order to initiate self-improvement. A needs assessment was conducted by interviewing and taping the responses of students, faculty, staff, and…

  15. Arguments from Developmental Order

    Directory of Open Access Journals (Sweden)

    Richard eStöckle-Schobel

    2016-05-01

    Full Text Available In this article, I investigate a special type of argument regarding the role of development in theorising about psychological processes and cognitive capacities. Among the issues that developmental psychologists study, discovering the ontogenetic trajectory of mechanisms or capacities underpinning our cognitive functions ranks highly. The order in which functions are developed or capacities are acquired is a matter of debate between competing psychological theories, and also philosophical conceptions of the mind – getting the role and the significance of the different steps in this order right could be seen as an important virtue of such theories.Thus, a special kind of strategy in arguments between competing philosophical or psychological theories is using developmental order in arguing for or against a given psychological claim. In this article, I will introduce an analysis of arguments from developmental order, which come in two general types: arguments emphasising the importance of the early cognitive processes and arguments emphasising the late cognitive processes. I will discuss their role in one of the central tools for evaluating scientific theories, namely in making inferences to the best explanation. I will argue that appeal to developmental order is, by itself, an insufficient criterion for theory choice and has to be part of an argument based on other core explanatory or empirical virtues. I will end by proposing a more concerted study of philosophical issues concerning (cognitive development, and I will present some topics that also pertain to a full-fledged ‘philosophy of development’.

  16. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing

    2015-01-01

    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  17. Developmental plasticity and the evolution of parental effects.

    Science.gov (United States)

    Uller, Tobias

    2008-08-01

    One of the outstanding challenges for evolutionary biologists is to understand how developmental plasticity can influence the evolutionary process. Developmental plasticity frequently involves parental effects, which might enable adaptive and context-dependent transgenerational transmission of phenotypic strategies. However, parent-offspring conflict will frequently result in parental effects that are suboptimal for parents, offspring or both. The fitness consequences of parental effects at evolutionary equilibrium will depend on how conflicts can be resolved by modifications of developmental processes, suggesting that proximate studies of development can inform ultimate questions. Furthermore, recent studies of plants and animals show how studies of parental effects in an ecological context provide important insights into the origin and evolution of adaptation under variable environmental conditions.

  18. NIDCAP and developmental care

    Directory of Open Access Journals (Sweden)

    Dominique Haumont

    2014-06-01

    Full Text Available Perinatal mortality in very low birth weight infants has dramatically decreased during the last decades. However, 15-25% of these infants will show neurodevelopmental impairment later on. The aim of implementing early developmental care (EDC, emerged as a new field in neonatology, is to create an intervention program designed to provide support for optimal neurobehavioral development during this highly vulnerable period of brain growth. The theoretical framework, which underlies the approach, is supported by research in different scientific fields, including neuroscience, psychology, medicine and nursing. EDC utilizes a range of medical and nursing interventions that aim to decrease the stress of preterm neonates in neonatal intensive care units (NICUs. The Neonatal Individualized Developmental Care Assessment Program (NIDCAP is an integrated and holistic form of family-centered developmental care. Changing the traditional NICU towards an EDC-NICU includes training nursing and medical staff, investing in their quality and most importantly keeping parents in proximity to the infants. The new challenge of modern neonatology is to restore the mother-infant dyad applying “couplet care” starting at birth until discharge. Most of the European NICUs apply some elements of EDC, but it is more consistent in northern Europe. The development of NIDCAP training centers in Europe demonstrates the evolution of care. It is likely that future research and intervention programs will optimize our practices. Developmental care could prove to be an important recent step in improving outcome in extremely preterm neonates. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  19. Phenotypic integration of neurocranium and brain.

    Science.gov (United States)

    Richtsmeier, Joan T; Aldridge, Kristina; DeLeon, Valerie B; Panchal, Jayesh; Kane, Alex A; Marsh, Jeffrey L; Yan, Peng; Cole, Theodore M

    2006-07-15

    Evolutionary history of Mammalia provides strong evidence that the morphology of skull and brain change jointly in evolution. Formation and development of brain and skull co-occur and are dependent upon a series of morphogenetic and patterning processes driven by genes and their regulatory programs. Our current concept of skull and brain as separate tissues results in distinct analyses of these tissues by most researchers. In this study, we use 3D computed tomography and magnetic resonance images of pediatric individuals diagnosed with premature closure of cranial sutures (craniosynostosis) to investigate phenotypic relationships between the brain and skull. It has been demonstrated previously that the skull and brain acquire characteristic dysmorphologies in isolated craniosynostosis, but relatively little is known of the developmental interactions that produce these anomalies. Our comparative analysis of phenotypic integration of brain and skull in premature closure of the sagittal and the right coronal sutures demonstrates that brain and skull are strongly integrated and that the significant differences in patterns of association do not occur local to the prematurely closed suture. We posit that the current focus on the suture as the basis for this condition may identify a proximate, but not the ultimate cause for these conditions. Given that premature suture closure reduces the number of cranial bones, and that a persistent loss of skull bones is demonstrated over the approximately 150 million years of synapsid evolution, craniosynostosis may serve as an informative model for evolution of the mammalian skull. Copyright 2006 Wiley-Liss, Inc.

  20. Evolutionary and developmental modules.

    Science.gov (United States)

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

    2013-01-01

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

  1. ADA genetic polymorphism and the effect of smoking on neonatal bilirubinemia and developmental parameters.

    Science.gov (United States)

    Gloria-Bottini, F; Magrini, A; Cozzoli, E; Bergamaschi, A; Bottini, E

    2008-11-01

    Genetic variability of metabolic enzymes may influence the effect of cigarette smoking on intrauterine development and on early neonatal events. To investigate the role of adenosine deaminase genetic polymorphism on the effect of smoking on neonatal bilirubinemia and developmental parameters. Analysis of association between adenosine deaminase phenotypes and neonatal developmental parameters. Prospective study of serum bilirubin level in relation to adenosine deaminase phenotype. We have studied 360 consecutive newborn infants from the Caucasian population of Rome. Serum bilirubin concentration was determined at birth and every 24 h for the first five days. Overall maternal smoking is associated with a slight decrease in the incidence of phototherapy (13.4% in non smoking vs 11.7% in smoking mothers) and with a reduction of birth weight (3374 g in non smoking mothers vs 3133 g in smoking mothers). There is a significant interaction between smoke and adenosine deaminase. While in non smoking mothers the incidence of phototherapy in carriers of ADA 2 allele is higher than in ADA 1 phenotype, in infants from smoking mothers the pattern is reversed and the incidence of phototherapy in carriers of ADA 2 allele is lower than in infants with ADA 1 phenotype. Other neonatal bilirubin parameters follow a similar pattern of interaction between smoking and ADA. The negative effect of smoke on birth weight is much more evident in infant with ADA 1 phenotype than in those carrying the ADA 2 allele. The data suggest that ADA phenotype modifies the effect of smoking on developmental and bilirubin parameters.

  2. Natural variation of model mutant phenotypes in Ciona intestinalis.

    Directory of Open Access Journals (Sweden)

    Paolo Sordino

    Full Text Available BACKGROUND: The study of ascidians (Chordata, Tunicata has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. CONCLUSIONS/SIGNIFICANCE: Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity.

  3. Natural Variation of Model Mutant Phenotypes in Ciona intestinalis

    Science.gov (United States)

    Brown, Euan R.; Leccia, Nicola I.; Squarzoni, Paola; Tarallo, Raffaella; Alfano, Christian; Caputi, Luigi; D'Ambrosio, Palmira; Daniele, Paola; D'Aniello, Enrico; D'Aniello, Salvatore; Maiella, Sylvie; Miraglia, Valentina; Russo, Monia Teresa; Sorrenti, Gerarda; Branno, Margherita; Cariello, Lucio; Cirino, Paola; Locascio, Annamaria; Spagnuolo, Antonietta; Zanetti, Laura; Ristoratore, Filomena

    2008-01-01

    Background The study of ascidians (Chordata, Tunicata) has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. Methodology/Principal Findings Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. Conclusions/Significance Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity. PMID:18523552

  4. Developmental psychopathology in an era of molecular genetics and neuroimaging: A developmental neurogenetics approach.

    Science.gov (United States)

    Hyde, Luke W

    2015-05-01

    The emerging field of neurogenetics seeks to model the complex pathways from gene to brain to behavior. This field has focused on imaging genetics techniques that examine how variability in common genetic polymorphisms predict differences in brain structure and function. These studies are informed by other complimentary techniques (e.g., animal models and multimodal imaging) and have recently begun to incorporate the environment through examination of Imaging Gene × Environment interactions. Though neurogenetics has the potential to inform our understanding of the development of psychopathology, there has been little integration between principles of neurogenetics and developmental psychopathology. The paper describes a neurogenetics and Imaging Gene × Environment approach and how these approaches have been usefully applied to the study of psychopathology. Six tenets of developmental psychopathology (the structure of phenotypes, the importance of exploring mechanisms, the conditional nature of risk, the complexity of multilevel pathways, the role of development, and the importance of who is studied) are identified, and how these principles can further neurogenetics applications to understanding the development of psychopathology is discussed. A major issue of this piece is how neurogenetics and current imaging and molecular genetics approaches can be incorporated into developmental psychopathology perspectives with a goal of providing models for better understanding pathways from among genes, environments, the brain, and behavior.

  5. From metabolome to phenotype

    DEFF Research Database (Denmark)

    Khakimov, Bekzod; Rasmussen, Morten Arendt; Kannangara, Rubini Maya

    2017-01-01

    for ideal vegetable protein production and for augmented β-glucan production. Seeds from three barley lines (Bomi, lys3.a and lys5.f) were sampled eight times during grain filling and analysed for metabolites using gas chromatography-mass spectrometry (GC-MS). The lys3.a mutation disrupts a regulator gene...... their successful application to link genetic and environmental factors with the seed phenotype of unique and agro-economically important barley models for optimal vegetable protein and dietary fibre production......., causing an increase in proteins rich in the essential amino acid lysine, while lys5.f carries a mutation in an ADP-glucose transporter gene leading to a significant increase in production of mixed-linkage β-glucan at the expense of α-glucan. Unique metabolic patterns associated with the tricarboxylic acid...

  6. Deep Learning for Plant Phenotyping

    OpenAIRE

    Mori, Matteo

    2016-01-01

    Plant Phenotyping is an emerging science which provides us the knowledge to better understand plants. Indeed, the study of the link between genetic background and environment in which plants develop can help us to determine cures for plants’ sicknesses and new ways to improve yields using limited resources. In this regard, one of the main aspects of Plant Phenotyping that were studied in the past, was Root Phenotyping, which is based on the study of the root architectures. In particular, toda...

  7. Phenotypic variability in a panel of strawberry cultivars from North America and the European Union

    Science.gov (United States)

    The phenotypic diversity in 96 antique and modern cultivars from the European Union and North America was evaluated in Michigan and Oregon, in 2011 and 2012. A total of thirty-five fruit and developmental characteristics were measured. Significant differences (p < 0.05) were observed among cultivars...

  8. Computational Phenotypes: Where the Theory of Computation Meets Evo-Devo

    Directory of Open Access Journals (Sweden)

    Sergio Balari

    2009-03-01

    Full Text Available This article argues that the Chomsky Hierarchy can be reinterpreted as a developmental morphospace constraining the evolution of a discrete and finite series of computational phenotypes. In doing so, the theory of Morphological Evolution as stated by Pere Alberch, a pioneering figure of Evo–Devo thinking, is adhered to.

  9. Topographic processing in developmental prosopagnosia

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  10. DEVELOPMENTAL TAXONOMY OF CONDUCT DISORDER

    OpenAIRE

    Jelena Kostić; Milkica Nešić; Jasminka Marković; Miodrag Stanković

    2015-01-01

    Conduct disorder is a heterogeneous disorder in terms of etiology, course and prognosis, and currently, there is no singular model that would describe the development of the disorder. The results of empirical research on males confirm this heterogeneity, as they point out to two possible developmental pathways: childhood-onset and adolescentonset type. This paper presents the basic elements of developmental taxonomic theory which argues that there are two different developmental pathways to c...

  11. Developmental plasticity: Friend or foe?

    Science.gov (United States)

    Michels, Karin B

    2017-01-01

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

  12. Qualitative methodology in developmental psychology

    DEFF Research Database (Denmark)

    Demuth, Carolin; Mey, Günter

    2015-01-01

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

  13. Building a developmental toxicity ontology.

    Science.gov (United States)

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

    2018-04-03

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

  14. Neuropsychological phenotype of a patient with a de novo 970 kb interstitial deletion in the distal 16p11.2 region

    NARCIS (Netherlands)

    Egger, J.I.; Verhoeven, W.M.A.; Verbeeck, W.J.C.; Leeuw, N. de

    2014-01-01

    The 16p11.2 microdeletion syndrome is characterized by a wide range of phenotypic expressions and is frequently associated with developmental delay, symptoms from the autism spectrum, epilepsy, congenital anomalies, and obesity. These phenotypes are often related to a proximal 16p11.2 deletion of

  15. Neuropsychological phenotype of a patient with a de novo 970 kb interstitial deletion in the distal 16p11.2 region

    NARCIS (Netherlands)

    J.I.M. Egger (Jos); W.M.A. Verhoeven (Wim); W. Verbeeck (Wim); N. de Leeuw (Nicole)

    2014-01-01

    textabstractThe 16p11.2 microdeletion syndrome is characterized by a wide range of phenotypic expressions and is frequently associated with developmental delay, symptoms from the autism spectrum, epilepsy, congenital anomalies, and obesity. These phenotypes are often related to a proximal 16p11.2

  16. A large de novo distal 16p11.2 deletion in a patient with normal intelligence: Evidence for a neuropsychological phenotype

    NARCIS (Netherlands)

    Egger, J.I.M.; Verhoeven, W.M.A.; Verbeeck, W.J.C.; Leeuw, N. de

    2014-01-01

    Objective: The 16p11.2 microdeletion syndrome is characterized by a wide range of phenotypic expressions and is often associated with developmental delay, symptoms from the autism spectrum, epilepsy, congenital anomalies and obesity. Usually, these phenotypes are related to a proximal 16p11.2

  17. Developmental immunotoxicology of lead

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  18. Hormones and phenotypic plasticity in an ecological context: linking physiological mechanisms to evolutionary processes.

    Science.gov (United States)

    Lema, Sean C

    2014-11-01

    Hormones are chemical signaling molecules that regulate patterns of cellular physiology and gene expression underlying phenotypic traits. Hormone-signaling pathways respond to an organism's external environment to mediate developmental stage-specific malleability in phenotypes, so that environmental variation experienced at different stages of development has distinct effects on an organism's phenotype. Studies of hormone-signaling are therefore playing a central role in efforts to understand how plastic phenotypic responses to environmental variation are generated during development. But, how do adaptive, hormonally mediated phenotypes evolve if the individual signaling components (hormones, conversion enzymes, membrane transporters, and receptors) that comprise any hormone-signaling pathway show expressional flexibility in response to environmental variation? What relevance do these components hold as molecular targets for selection to couple or decouple correlated hormonally mediated traits? This article explores how studying the endocrine underpinnings of phenotypic plasticity in an ecologically relevant context can provide insights into these, and other, crucial questions into the role of phenotypic plasticity in evolution, including how plasticity itself evolves. These issues are discussed in the light of investigations into how thyroid hormones mediate morphological plasticity in Death Valley's clade of pupfishes (Cyprinodon spp.). Findings from this work with pupfish illustrate that the study of hormone-signaling from an ecological perspective can reveal how phenotypic plasticity contributes to the generation of phenotypic novelty, as well as how physiological mechanisms developmentally link an organism's phenotype to its environmental experiences. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  19. Imaging techniques for visualizing and phenotyping congenital heart defects in murine models.

    Science.gov (United States)

    Liu, Xiaoqin; Tobita, Kimimasa; Francis, Richard J B; Lo, Cecilia W

    2013-06-01

    Mouse model is ideal for investigating the genetic and developmental etiology of congenital heart disease. However, cardiovascular phenotyping for the precise diagnosis of structural heart defects in mice remain challenging. With rapid advances in imaging techniques, there are now high throughput phenotyping tools available for the diagnosis of structural heart defects. In this review, we discuss the efficacy of four different imaging modalities for congenital heart disease diagnosis in fetal/neonatal mice, including noninvasive fetal echocardiography, micro-computed tomography (micro-CT), micro-magnetic resonance imaging (micro-MRI), and episcopic fluorescence image capture (EFIC) histopathology. The experience we have gained in the use of these imaging modalities in a large-scale mouse mutagenesis screen have validated their efficacy for congenital heart defect diagnosis in the tiny hearts of fetal and newborn mice. These cutting edge phenotyping tools will be invaluable for furthering our understanding of the developmental etiology of congenital heart disease. Copyright © 2013 Wiley Periodicals, Inc.

  20. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  1. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

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

    Science.gov (United States)

    Card, Noel A

    2017-06-01

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

  3. Constructivist developmental theory is needed in developmental neuroscience

    Science.gov (United States)

    Arsalidou, Marie; Pascual-Leone, Juan

    2016-12-01

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

  4. Plantar lipomatosis, unusual facies, and developmental delay : Confirmation of Pierpont syndrome

    NARCIS (Netherlands)

    Oudesluijs, GG; Hordijk, R; Boon, M; Sijens, PE; Hennekam, RCM

    2005-01-01

    In 1998, Pierpont et al. reported on two unrelated boys with plantar lipomatosis, unusual facial phenotype, and developmental delay as a possible new MR/MCA syndrome. Here we report on a 2-year-old boy with similar manifestations: axial hypotonia in the first few months, prolonged feeding problems,

  5. Introduction to Special Section: Biomedicine and Developmental Psychology: New Areas of Common Ground.

    Science.gov (United States)

    Leavitt, Lewis A.; Goldson, Edward

    1996-01-01

    Introduces a special section of five articles that highlight new collaborative research opportunities for developmental psychologists and other biomedical researchers. Such research has focused on the transition from fetus to newborn, evaluation of early toxin exposure, and the behavioral phenotype associated with genetic syndromes. (MDM)

  6. Phenotypic differentiation is associated with gender plasticity and its responsive delay to environmental changes in Alternanthera philoxeroides--phenotypic differentiation in alligator weed.

    Directory of Open Access Journals (Sweden)

    Wei Liu

    Full Text Available Phenotypic plasticity is common in many taxa, and it may increase an organism's fitness in heterogeneous environments. However, in some cases, the frequency of environmental changes can be faster than the ability of the individual to produce new adaptive phenotypes. The importance of such a time delay in terms of individual fitness and species adaptability has not been well studied. Here, we studied gender plasticity of Alternanthera philoxeroides to address this issue through a reciprocal transplant experiment. We observed that the genders of A. philoxeroides were plastic and reversible between monoclinous and pistillody depending on habitats, the offspring maintained the maternal genders in the first year but changed from year 2 to 5, and there was a cubic relationship between the rate of population gender changes and environmental variations. This relationship indicates that the species must overcome a threshold of environmental variations to switch its developmental path ways between the two genders. This threshold and the maternal gender stability cause a significant delay of gender changes in new environments. At the same time, they result in and maintain the two distinct habitat dependent gender phenotypes. We also observed that there was a significant and adaptive life-history differentiation between monoclinous and pistillody individuals and the gender phenotypes were developmentally linked with the life-history traits. Therefore, the gender phenotypes are adaptive. Low seed production, seed germination failure and matching phenotypes to habitats by gender plasticity indicate that the adaptive phenotypic diversity in A. philoxeroides may not be the result of ecological selection, but of gender plasticity. The delay of the adaptive gender phenotype realization in changing environments can maintain the differentiation between gender systems and their associated life-history traits, which may be an important component in evolution of novel

  7. Developmentally Appropriate Peace Education Curricula

    Science.gov (United States)

    Lewsader, Joellen; Myers-Walls, Judith A.

    2017-01-01

    Peace education has been offered to children for decades, but those curricula have been only minimally guided by children's developmental stages and needs. In this article, the authors apply their research on children's developmental understanding of peace along with peace education principles and Vygotsky's sociocultural theory to present…

  8. Developmental Kindergarten Program Evaluation Report.

    Science.gov (United States)

    Blois, George T.; Cushing, Katherine S.

    The evaluation of the Developmental Kindergarten (DK) Program at the Harrison School District #2, Colorado Springs, Colorado, involved pre- and post-testing of student academic gains and interviewing of principals and teachers. The program aimed to provide developmentally appropriate activities for students believed to be "at risk" of…

  9. Developmental programming of happiness.

    Science.gov (United States)

    Schmidt, Louis A; Fortier, Paz; Lahat, Ayelet; Tang, Alva; Mathewson, Karen J; Saigal, Saroj; Boyle, Michael H; Van Lieshout, Ryan J

    2017-09-01

    Being born at an extremely low birth weight (ELBW; programming hypotheses. Interfacing prenatal programming and differential susceptibility hypotheses, we tested whether individuals with ELBW in different childhood rearing environments showed different attention biases to positive and negative facial emotions in adulthood. Using the oldest known, prospectively followed cohort of ELBW survivors, we found that relative to normal birth weight controls (NBW; >2,500 grams), ELBW survivors displayed the highest and lowest attention bias to happy faces at age 30-35, depending on whether their total family income at age 8 was relatively low (environmental match) or high (environmental mismatch), respectively. This bias to happy faces was associated with a reduced likelihood of emotional problems. Findings suggest that differential susceptibility to positive emotions may be prenatally programmed, with effects lasting into adulthood. We discuss implications for integrating prenatal programming and differential susceptibility hypotheses, and the developmental origins of postnatal plasticity and resilience. © 2017 Wiley Periodicals, Inc.

  10. Developmental colour agnosia.

    Science.gov (United States)

    van Zandvoort, Martine J E; Nijboer, Tanja C W; de Haan, Edward

    2007-08-01

    Colour agnosia concerns the inability to recognise colours despite intact colour perception, semantic memory for colour information, and colour naming. Patients with selective colour agnosia have been described and the deficit is associated with left hemisphere damage. Here we report a case study of a 43-year-old man who was referred to us with a stroke in his right cerebellar hemisphere. During the standard assessment it transpired that he was unable to name coloured patches. Detailed assessment of his colour processing showed that he suffers from a selective colour agnosia. As he claimed to have had this problem all his life, and the fact that the infratentorial infarct that he had incurred was in an area far away from the brain structures that are known to be involved in colour processing, we suggest that he is the first reported case of developmental colour agnosia.

  11. [Behavioral phenotypes of autism spectrum disorder patients and their parents].

    Science.gov (United States)

    Situ, Mingjing; Hu, Xiao; Cai, Jia; Guo, Kuifang; Huang, Yi

    2015-12-01

    To explore the relationship between the behavior phenotypes of patients with autism spectrum disorder (ASD) and their parents through family study. Forty-five core families with ASD and 30 control families from Chengdu area were examined using Autism Spectrum Quotient (AQ). Descriptive statistical analysis, correlation analysis, and Logistic regression analysis were used to investigate the effect of various factors, especially genetic factors that may affect the pathogenesis of ASD. The social skills factor and communication factor of the father's AQ scale, as well as the mother's age of childbearing and AQ social skills factor are related to whether children with ASD (R were 0.46, 0.39, 0.39 and 0.36, Pautism. ASD may be influenced by both genetic and environmental factors. The autistic behavior phenotype of parents is a risk factor for ASD and is associated with developmental anomalies of early childhood.

  12. [Neurotransmission in developmental disorders].

    Science.gov (United States)

    Takeuchi, Yoshihiro

    2008-11-01

    Attention deficit/hyperactivity disorder (AD/HD) is a heterogeneous developmental disorder with an etiology that is not fully understood. AD/HD has been considered to occur due to a disturbance in cathecholaminergic neurotransmission, with particular emphasis on dopamine. The neurotransmission of dopamine in subcortical regions such as the basal ganglia and limbic areas is synaptic; on the other hand, dopamine neurotransmission in the frontal cortex is quite different, because there are very few dopamine transporters (DAT) in the frontal cortex that allow dopamine to diffuse away from the dopamine synapse ("volume transmission"). It is now clear that noradrenergic neurons play a key regulatory role in dopaminergic function in the frontal cortex. Furthermore, serotonergic neurons exert an inhibitory effect on midbrain dopamine cell bodies, and they have an influence on dopamine release in terminal regions. There is accumulating neurobiological evidence pointing toward a role of the serotonin system in AD/HD. The etiology of autism spectrum disorders (ASD) is still unclear, but information from genetics, neuropathology, brain imaging, and basic neuroscience has provided insights into the understanding of this developmental disorder. In addition to abnormal circuitry in specific limbic and neocortical areas of the cerebral cortex, impairments in brainstem, cerebellar, thalamic, and basal ganglia connections have been reported. Numerous studies have pointed to abnormalities in serotonin and glutamate neurotransmission. Three important aspects involved in the pathophysiology of ASD have been proposed. The first is cell migration, the second is unbalanced excitatory-inhibitory networks, and the third is synapse formation and pruning, the key factors being reelin, neurexin, and neuroligin. Serotonin is considered to play an important role in all of these aspects of the pathophysiology of ASD. Finally, I would like to emphasize that it is crucial in the field of child

  13. Developmental evolution in social insects: regulatory networks from genes to societies.

    Science.gov (United States)

    Linksvayer, Timothy A; Fewell, Jennifer H; Gadau, Jürgen; Laubichler, Manfred D

    2012-05-01

    The evolution and development of complex phenotypes in social insect colonies, such as queen-worker dimorphism or division of labor, can, in our opinion, only be fully understood within an expanded mechanistic framework of Developmental Evolution. Conversely, social insects offer a fertile research area in which fundamental questions of Developmental Evolution can be addressed empirically. We review the concept of gene regulatory networks (GRNs) that aims to fully describe the battery of interacting genomic modules that are differentially expressed during the development of individual organisms. We discuss how distinct types of network models have been used to study different levels of biological organization in social insects, from GRNs to social networks. We propose that these hierarchical networks spanning different organizational levels from genes to societies should be integrated and incorporated into full GRN models to elucidate the evolutionary and developmental mechanisms underlying social insect phenotypes. Finally, we discuss prospects and approaches to achieve such an integration. © 2012 WILEY PERIODICALS, INC.

  14. Challenging behavior: Behavioral phenotypes of some genetic syndromes

    Directory of Open Access Journals (Sweden)

    Buha Nataša

    2014-01-01

    Full Text Available Challenging behavior in individuals with mental retardation (MR is relatively frequent, and represents a significant obstacle to adaptive skills. The frequency of specific forms and manifestations of challenging behavior can depend on a variety of personal and environmental factors. There are several prominent theoretical models regarding the etiology of challenging behavior and psychopathology in persons with MR: behavioral, developmental, socio-cultural and biological. The biological model emphasizes the physiological, biochemical and genetic factors as the potential source of challenging behavior. The progress in the field of genetics and neuroscience has opened the opportunity to study and discover the neurobiological basis of phenotypic characteristics. Genetic syndromes associated with MR can be followed by a specific set of problems and disorders which constitutes their behavioral phenotype. The aim of this paper was to present challenging behaviors that manifest in the most frequently studied syndromes: Down syndrome, Fragile X syndrome, Williams syndrome, Prader-Willi syndrome and Angelman syndrome. The concept of behavioral phenotype implies a higher probability of manifesting specific developmental characteristics and specific behaviors in individuals with a certain genetic syndrome. Although the specific set of (possible problems and disorders is distinctive for the described genetic syndromes, the connection between genetics and behavior should be viewed through probabilistic dimension. The probabilistic concept takes into consideration the possibility of intra-syndrome variability in the occurrence, intensity and time onset of behavioral characteristics, at which the higher variability the lower is the specificity of the genetic syndrome. Identifying the specific pattern of behavior can be most important for the process of early diagnosis and prognosis. In addition, having knowledge about behavioral phenotype can be a landmark in

  15. TBC1D24 genotype–phenotype correlation

    Science.gov (United States)

    Balestrini, Simona; Milh, Mathieu; Castiglioni, Claudia; Lüthy, Kevin; Finelli, Mattea J.; Verstreken, Patrik; Cardon, Aaron; Stražišar, Barbara Gnidovec; Holder, J. Lloyd; Lesca, Gaetan; Mancardi, Maria M.; Poulat, Anne L.; Repetto, Gabriela M.; Banka, Siddharth; Bilo, Leonilda; Birkeland, Laura E.; Bosch, Friedrich; Brockmann, Knut; Cross, J. Helen; Doummar, Diane; Félix, Temis M.; Giuliano, Fabienne; Hori, Mutsuki; Hüning, Irina; Kayserili, Hulia; Kini, Usha; Lees, Melissa M.; Meenakshi, Girish; Mewasingh, Leena; Pagnamenta, Alistair T.; Peluso, Silvio; Mey, Antje; Rice, Gregory M.; Rosenfeld, Jill A.; Taylor, Jenny C.; Troester, Matthew M.; Stanley, Christine M.; Ville, Dorothee; Walkiewicz, Magdalena; Falace, Antonio; Fassio, Anna; Lemke, Johannes R.; Biskup, Saskia; Tardif, Jessica; Ajeawung, Norbert F.; Tolun, Aslihan; Corbett, Mark; Gecz, Jozef; Afawi, Zaid; Howell, Katherine B.; Oliver, Karen L.; Berkovic, Samuel F.; Scheffer, Ingrid E.; de Falco, Fabrizio A.; Oliver, Peter L.; Striano, Pasquale; Zara, Federico

    2016-01-01

    Objective: To evaluate the phenotypic spectrum associated with mutations in TBC1D24. Methods: We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24). Results: Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function. Conclusions: TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes. PMID:27281533

  16. Phenotypic plasticity, costs of phenotypes, and costs of plasticity

    DEFF Research Database (Denmark)

    Callahan, Hilary S; Maughan, Heather; Steiner, Uli

    2008-01-01

    Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

  17. Exome sequencing for gene discovery in lethal fetal disorders--harnessing the value of extreme phenotypes.

    Science.gov (United States)

    Filges, Isabel; Friedman, Jan M

    2015-10-01

    Massively parallel sequencing has revolutionized our understanding of Mendelian disorders, and many novel genes have been discovered to cause disease phenotypes when mutant. At the same time, next-generation sequencing approaches have enabled non-invasive prenatal testing of free fetal DNA in maternal blood. However, little attention has been paid to using whole exome and genome sequencing strategies for gene identification in fetal disorders that are lethal in utero, because they can appear to be sporadic and Mendelian inheritance may be missed. We present challenges and advantages of applying next-generation sequencing approaches to gene discovery in fetal malformation phenotypes and review recent successful discovery approaches. We discuss the implication and significance of recessive inheritance and cross-species phenotyping in fetal lethal conditions. Whole exome sequencing can be used in individual families with undiagnosed lethal congenital anomaly syndromes to discover causal mutations, provided that prior to data analysis, the fetal phenotype can be correlated to a particular developmental pathway in embryogenesis. Cross-species phenotyping allows providing further evidence for causality of discovered variants in genes involved in those extremely rare phenotypes and will increase our knowledge about normal and abnormal human developmental processes. Ultimately, families will benefit from the option of early prenatal diagnosis. © 2014 John Wiley & Sons, Ltd.

  18. Mutations of PTPN23 in developmental and epileptic encephalopathy

    KAUST Repository

    Sowada, Nadine

    2017-10-31

    Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of neurodevelopmental disorders with poor prognosis. Recent discoveries have greatly expanded the repertoire of genes that are mutated in epileptic encephalopathies and DEE, often in a de novo fashion, but in many patients, the disease remains molecularly uncharacterized. Here, we describe a new form of DEE in patients with likely deleterious biallelic variants in PTPN23. The phenotype is characterized by early onset drug-resistant epilepsy, severe and global developmental delay, microcephaly, and sometimes premature death. PTPN23 encodes a tyrosine phosphatase with strong brain expression, and its knockout in mouse is embryonically lethal. Structural modeling supports a deleterious effect of the identified alleles. Our data suggest that PTPN23 mutations cause a rare severe form of autosomal-recessive DEE in humans, a finding that requires confirmation.

  19. Developmental plasticity and epigenetic mechanisms underpinning metabolic and cardiovascular diseases.

    Science.gov (United States)

    Low, Felicia M; Gluckman, Peter D; Hanson, Mark A

    2011-06-01

    The importance of developmental factors in influencing the risk of later-life disease has a strong evidence base derived from multiple epidemiological, clinical and experimental studies in animals and humans. During early life, an organism is able to adjust its phenotypic development in response to environmental cues. Such developmentally plastic responses evolved as a fitness-maximizing strategy to cope with variable environments. There are now increasing data that these responses are, at least partially, underpinned by epigenetic mechanisms. A mismatch between the early and later-life environments may lead to inappropriate early life-course epigenomic changes that manifest in later life as increased vulnerability to disease. There is also growing evidence for the transgenerational transmission of epigenetic marks. This article reviews the evidence that susceptibility to metabolic and cardiovascular disease in humans is linked to changes in epigenetic marks induced by early-life environmental cues, and discusses the clinical, public health and therapeutic implications that arise.

  20. Reporter-Based Isolation of Developmental Myogenic Progenitors

    Directory of Open Access Journals (Sweden)

    Eyemen Kheir

    2018-04-01

    Full Text Available The formation and activity of mammalian tissues entail finely regulated processes, involving the concerted organization and interaction of multiple cell types. In recent years the prospective isolation of distinct progenitor and stem cell populations has become a powerful tool in the hands of developmental biologists and has rendered the investigation of their intrinsic properties possible. In this protocol, we describe how to purify progenitors with different lineage history and degree of differentiation from embryonic and fetal skeletal muscle by fluorescence-activated cell sorting (FACS. The approach takes advantage of a panel of murine strains expressing fluorescent reporter genes specifically in the myogenic progenitors. We provide a detailed description of the dissection procedures and of the enzymatic dissociation required to maximize the yield of mononucleated cells for subsequent FACS-based purification. The procedure takes ~6–7 h to complete and allows for the isolation and the subsequent molecular and phenotypic characterization of developmental myogenic progenitors.

  1. Attentional networks in developmental dyscalculia

    Directory of Open Access Journals (Sweden)

    Henik Avishai

    2010-01-01

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

  2. Attentional networks in developmental dyscalculia.

    Science.gov (United States)

    Askenazi, Sarit; Henik, Avishai

    2010-01-07

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

  3. PHENOTYPIC CORRELATIONS AND BODY WEIGHTS ...

    African Journals Online (AJOL)

    Dr Osondu

    Ethiopian Journal of Environmental Studies and Management Vol. 4 No.3 2011. PHENOTYPIC ... because of its high meat quality and acceptance by her populace. The meat is ... commands high price in the restaurants and markets than other ...

  4. Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: an exploratory clinical trial

    OpenAIRE

    Schmidt, Heinrich; Giese, Renate; Enders, Angelika; Kern, W.; Hallschmid, M.

    2009-01-01

    Background: The 22q13 deletion syndrome (Phelan– McDermid syndrome) is characterised by a global developmental delay, absent or delayed speech, generalised hypotonia, autistic behaviour and characteristic phenotypic features. Intranasal insulin has been shown to improve declarative memory in healthy adult subjects and in patients with Alzheimer disease. Aims: To assess if intranasal insulin is also able to improve the developmental delay in children with 22q13 delet...

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

    Science.gov (United States)

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

    2015-01-01

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

  6. Update on neuroimaging phenotypes of mid-hindbrain malformations

    Energy Technology Data Exchange (ETDEWEB)

    Jissendi-Tchofo, Patrice [University Hospital of Lille (CHRU), Department of Neuroradiology, MRI 3T Research, Plateforme Imagerie du vivant, IMPRT-IFR 114, Lille-Cedex (France); CHU Saint-Pierre, Radiology Department, Pediatric Neuroradiology Section, Brussels (Belgium); Severino, Mariasavina [Istituto Giannina Gaslini, Neuroradiology Unit, Genoa (Italy); Nguema-Edzang, Beatrice; Toure, Cisse; Soto Ares, Gustavo [University Hospital of Lille (CHRU), Department of Neuroradiology, MRI 3T Research, Plateforme Imagerie du vivant, IMPRT-IFR 114, Lille-Cedex (France); Barkovich, Anthony James [University of California, Neuroradiology Section, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

    2014-10-23

    Neuroimaging techniques including structural magnetic resonance imaging (MRI) and functional positron emission tomography (PET) are useful in categorizing various midbrain-hindbrain (MHB) malformations, both in allowing diagnosis and in helping to understand the developmental processes that were disturbed. Brain imaging phenotypes of numerous malformations are characteristic features that help in guiding the genetic testing in case of direct neuroimaging-genotype correlation or, at least, to differentiate among MHB malformations entities. The present review aims to provide the reader with an update of the use of neuroimaging applications in the fine analysis of MHB malformations, using a comprehensive, recently proposed developmental and genetic classification. We have performed an extensive systematic review of the literature, from the embryology main steps of MHB development through the malformations entities, with regard to their molecular and genetic basis, conventional MRI features, and other neuroimaging characteristics. We discuss disorders in which imaging features are distinctive and how these features reflect the structural and functional impairment of the brain. Recognition of specific MRI phenotypes, including advanced imaging features, is useful to recognize the MHB malformation entities, to suggest genetic investigations, and, eventually, to monitor the disease outcome after supportive therapies. (orig.)

  7. Developmental transcriptome of Aplysia californica'

    KAUST Repository

    Heyland, Andreas; Vue, Zer; Voolstra, Christian R.; Medina, Mó nica; Moroz, Leonid L.

    2010-01-01

    developmental transcriptome with similar studies in the zebra fish Danio rerio, the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, and other studies on molluscs suggests an overall highly divergent pattern of gene regulatory mechanisms

  8. PREVALENCE AND EFFECT OF DEVELOPMENTAL ...

    African Journals Online (AJOL)

    uvp

    among children might even be higher, as medical and educational systems frequently fail to ... formally diagnosed, but rather described by their teachers as lazy or ..... Developmental Coordination Disorder Questionnaire for Brazilian children.

  9. The Management of Developmental Apraxia.

    Science.gov (United States)

    Gubbay, S. S.

    1978-01-01

    Of 39 children (5-12 years old) with developmental apraxia and agnosia, who were assessed neurologically, 19 were also given simple standarized tests of motor ability. Journal availability: see EC 112 661. (Author/SBH)

  10. Reprogramming to developmental plasticity in cancer stem cells.

    Science.gov (United States)

    O'Brien-Ball, Caitlin; Biddle, Adrian

    2017-10-15

    During development and throughout adult life, sub-populations of cells exist that exhibit phenotypic plasticity - the ability to differentiate into multiple lineages. This behaviour is important in embryogenesis, is exhibited in a more limited context by adult stem cells, and can be re-activated in cancer cells to drive important processes underlying tumour progression. A well-studied mechanism of phenotypic plasticity is the epithelial-to-mesenchymal transition (EMT), a process which has been observed in both normal and cancerous cells. The epigenetic and metabolic modifications necessary to facilitate phenotypic plasticity are first seen in development and can be re-activated both in normal regeneration and in cancer. In cancer, the re-activation of these mechanisms enables tumour cells to acquire a cancer stem cell (CSC) phenotype with enhanced ability to survive in hostile environments, resist therapeutic interventions, and undergo metastasis. However, recent research has suggested that plasticity may also expose weaknesses in cancer cells that could be exploited for future therapeutic development. More research is needed to identify developmental mechanisms that are active in cancer, so that these may be targeted to reduce tumour growth and metastasis and overcome therapeutic resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Developmental toxicity of engineered nanomaterials

    DEFF Research Database (Denmark)

    Hougaard, Karin S.; Hansen, Jitka S.; Jackson, Petra

    2016-01-01

    Study of air pollution indicates that minute particles may adversely interfere with pregnancy and fetal development. As engineering of nanoparticles have emerged, so has concern that these might interfere with reproductive and developmental functions. This is because nanotechnology may potentially...... increase the overall particle burden in air and introduce particles with novel characteristics and surface reactivity. To evaluate safety for pregnant women, we have studied developmental toxicity of engineered nanoparticles (ENPs), following exposure of pregnant mice by inhalation (ENPs of titanium...

  12. Developmental Science: Past, Present, and Future

    Science.gov (United States)

    Lerner, Richard M.

    2012-01-01

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

  13. The Most Developmentally Truncated Fishes Show Extensive Hox Gene Loss and Miniaturized Genomes

    Science.gov (United States)

    Malmstrøm, Martin; Britz, Ralf; Matschiner, Michael; Tørresen, Ole K; Hadiaty, Renny Kurnia; Yaakob, Norsham; Tan, Heok Hui; Jakobsen, Kjetill Sigurd; Salzburger, Walter; Rüber, Lukas

    2018-01-01

    Abstract The world’s smallest fishes belong to the genus Paedocypris. These miniature fishes are endemic to an extreme habitat: the peat swamp forests in Southeast Asia, characterized by highly acidic blackwater. This threatened habitat is home to a large array of fishes, including a number of miniaturized but also developmentally truncated species. Especially the genus Paedocypris is characterized by profound, organism-wide developmental truncation, resulting in sexually mature individuals of <8 mm in length with a larval phenotype. Here, we report on evolutionary simplification in the genomes of two species of the dwarf minnow genus Paedocypris using whole-genome sequencing. The two species feature unprecedented Hox gene loss and genome reduction in association with their massive developmental truncation. We also show how other genes involved in the development of musculature, nervous system, and skeleton have been lost in Paedocypris, mirroring its highly progenetic phenotype. Further, our analyses suggest two mechanisms responsible for the genome streamlining in Paedocypris in relation to other Cypriniformes: severe intron shortening and reduced repeat content. As the first report on the genomic sequence of a vertebrate species with organism-wide developmental truncation, the results of our work enhance our understanding of genome evolution and how genotypes are translated to phenotypes. In addition, as a naturally simplified system closely related to zebrafish, Paedocypris provides novel insights into vertebrate development. PMID:29684203

  14. The Most Developmentally Truncated Fishes Show Extensive Hox Gene Loss and Miniaturized Genomes.

    Science.gov (United States)

    Malmstrøm, Martin; Britz, Ralf; Matschiner, Michael; Tørresen, Ole K; Hadiaty, Renny Kurnia; Yaakob, Norsham; Tan, Heok Hui; Jakobsen, Kjetill Sigurd; Salzburger, Walter; Rüber, Lukas

    2018-04-01

    The world's smallest fishes belong to the genus Paedocypris. These miniature fishes are endemic to an extreme habitat: the peat swamp forests in Southeast Asia, characterized by highly acidic blackwater. This threatened habitat is home to a large array of fishes, including a number of miniaturized but also developmentally truncated species. Especially the genus Paedocypris is characterized by profound, organism-wide developmental truncation, resulting in sexually mature individuals of <8 mm in length with a larval phenotype. Here, we report on evolutionary simplification in the genomes of two species of the dwarf minnow genus Paedocypris using whole-genome sequencing. The two species feature unprecedented Hox gene loss and genome reduction in association with their massive developmental truncation. We also show how other genes involved in the development of musculature, nervous system, and skeleton have been lost in Paedocypris, mirroring its highly progenetic phenotype. Further, our analyses suggest two mechanisms responsible for the genome streamlining in Paedocypris in relation to other Cypriniformes: severe intron shortening and reduced repeat content. As the first report on the genomic sequence of a vertebrate species with organism-wide developmental truncation, the results of our work enhance our understanding of genome evolution and how genotypes are translated to phenotypes. In addition, as a naturally simplified system closely related to zebrafish, Paedocypris provides novel insights into vertebrate development.

  15. CHARGE and Kabuki syndromes: a phenotypic and molecular link.

    Science.gov (United States)

    Schulz, Yvonne; Freese, Luisa; Mänz, Johanna; Zoll, Barbara; Völter, Christiane; Brockmann, Knut; Bögershausen, Nina; Becker, Jutta; Wollnik, Bernd; Pauli, Silke

    2014-08-15

    CHARGE syndrome is a complex developmental disorder caused by mutations in the chromodomain helicase DNA-binding gene CHD7. Kabuki syndrome, another developmental disorder, is characterized by typical facial features in combination with developmental delay, short stature, prominent digit pads and visceral abnormalities. Mutations in the KMT2D gene, which encodes a H3K4 histone methyltransferase, are the major cause of Kabuki syndrome. Here, we report a patient, who was initially diagnosed with CHARGE syndrome based on the spectrum of inner organ malformations like choanal hypoplasia, heart defect, anal atresia, vision problems and conductive hearing impairment. While sequencing and MLPA analysis of all coding exons of CHD7 revealed no pathogenic mutation, sequence analysis of the KMT2D gene identified the heterozygous de novo nonsense mutation c.5263C > T (p.Gln1755*). Thus, our patient was diagnosed with Kabuki syndrome. By using co-immunoprecipitation, immunohistochemistry and direct yeast two hybrid assays, we could show that, like KMT2D, CHD7 interacts with members of the WAR complex, namely WDR5, ASH2L and RbBP5. We therefore propose that CHD7 and KMT2D function in the same chromatin modification machinery, thus pointing out a mechanistic connection, and presenting a probable explanation for the phenotypic overlap between Kabuki and CHARGE syndromes. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.

    Science.gov (United States)

    Mueller, Michael M; Castells-Roca, Laia; Babu, Vipin; Ermolaeva, Maria A; Müller, Roman-Ulrich; Frommolt, Peter; Williams, Ashley B; Greiss, Sebastian; Schneider, Jennifer I; Benzing, Thomas; Schermer, Bernhard; Schumacher, Björn

    2014-12-01

    Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16-mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.

  17. Phenotypic spectrum of GABRA1

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Marini, Carla; Pfeffer, Siona

    2016-01-01

    OBJECTIVE: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. METHODS: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analy...

  18. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape

  19. Delineating SPTAN1 associated phenotypes

    DEFF Research Database (Denmark)

    Syrbe, Steffen; Harms, Frederike L; Parrini, Elena

    2017-01-01

    De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutati...

  20. Neurobehavioural effects of developmental toxicity

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Landrigan, Philip J

    2014-01-01

    Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among...... the known causes for this rise in prevalence. In 2006, we did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental...... chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity. To coordinate these efforts and to accelerate translation of science into prevention, we propose the urgent formation of a new...

  1. DEVELOPMENTAL TAXONOMY OF CONDUCT DISORDER

    Directory of Open Access Journals (Sweden)

    Jelena Kostić

    2015-12-01

    Full Text Available Conduct disorder is a heterogeneous disorder in terms of etiology, course and prognosis, and currently, there is no singular model that would describe the development of the disorder. The results of empirical research on males confirm this heterogeneity, as they point out to two possible developmental pathways: childhood-onset and adolescentonset type. This paper presents the basic elements of developmental taxonomic theory which argues that there are two different developmental pathways to conduct disorder which have different causes and serve as the basis for the current typology of conduct disorders in the classification systems. Such a typology of conduct disorders in the diagnostic classification allows better understanding, prognosis and choice of treatment.

  2. Developmental analytic view on narcissism

    Directory of Open Access Journals (Sweden)

    Polona Matjan Štuhec

    2009-07-01

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

  3. The Phenotypic Effects of Royal Jelly on Wild-Type D. melanogaster Are Strain-Specific

    OpenAIRE

    Morgan, Stefanie L.; Seggio, Joseph A.; Nascimento, Nara F.; Huh, Dana D.; Hicks, Jasmin A.; Sharp, Katherine A.; Axelrod, Jeffrey D.; Wang, Kevin C.

    2016-01-01

    The role for royal jelly (RJ) in promoting caste differentiation of honeybee larvae into queens rather than workers is well characterized. A recent study demonstrated that this poorly understood complex nutrition drives strikingly similar phenotypic effects in Drosophila melanogaster, such as increased body size and reduced developmental time, making possible the use of D. melanogaster as a model system for the genetic analysis of the cellular mechanisms underlying RJ and caste differentiatio...

  4. The phenotype of FancB-mutant mouse embryonic stem cells

    OpenAIRE

    Kim, Tae Moon; Ko, Jun Ho; Choi, Yong Jun; Hu, Lingchuan; Hasty, Paul

    2011-01-01

    Fanconi anemia (FA) is a rare autosomal recessive disease characterized by bone marrow failure, developmental defects and cancer. There are multiple FA genes that enable the repair of interstrand crosslinks (ICLs) in coordination with a variety of other DNA repair pathways in a way that is poorly understood. Here we present the phenotype of mouse embryonic stem (ES) cells mutated for FancB. We found FancB-mutant cells exhibited reduced cellular proliferation, hypersensitivity to the crosslink...

  5. A Bystander Mechanism Explains the Specific Phenotype of a Broadly Expressed Misfolded Protein.

    Directory of Open Access Journals (Sweden)

    Lauren Klabonski

    2016-12-01

    Full Text Available Misfolded proteins in transgenic models of conformational diseases interfere with proteostasis machinery and compromise the function of many structurally and functionally unrelated metastable proteins. This collateral damage to cellular proteins has been termed 'bystander' mechanism. How a single misfolded protein overwhelms the proteostasis, and how broadly-expressed mutant proteins cause cell type-selective phenotypes in disease are open questions. We tested the gain-of-function mechanism of a R37C folding mutation in an endogenous IGF-like C.elegans protein DAF-28. DAF-28(R37C is broadly expressed, but only causes dysfunction in one specific neuron, ASI, leading to a distinct developmental phenotype. We find that this phenotype is caused by selective disruption of normal biogenesis of an unrelated endogenous protein, DAF-7/TGF-β. The combined deficiency of DAF-28 and DAF-7 biogenesis, but not of DAF-28 alone, explains the gain-of-function phenotype-deficient pro-growth signaling by the ASI neuron. Using functional, fluorescently-tagged protein, we find that, in animals with mutant DAF-28/IGF, the wild-type DAF-7/TGF-β is mislocalized to and accumulates in the proximal axon of the ASI neuron. Activation of two different branches of the unfolded protein response can modulate both the developmental phenotype and DAF-7 mislocalization in DAF-28(R37C animals, but appear to act through divergent mechanisms. Our finding that bystander targeting of TGF-β explains the phenotype caused by a folding mutation in an IGF-like protein suggests that, in conformational diseases, bystander misfolding may specify the distinct phenotypes caused by different folding mutations.

  6. Interoperability between phenotype and anatomy ontologies.

    Science.gov (United States)

    Hoehndorf, Robert; Oellrich, Anika; Rebholz-Schuhmann, Dietrich

    2010-12-15

    Phenotypic information is important for the analysis of the molecular mechanisms underlying disease. A formal ontological representation of phenotypic information can help to identify, interpret and infer phenotypic traits based on experimental findings. The methods that are currently used to represent data and information about phenotypes fail to make the semantics of the phenotypic trait explicit and do not interoperate with ontologies of anatomy and other domains. Therefore, valuable resources for the analysis of phenotype studies remain unconnected and inaccessible to automated analysis and reasoning. We provide a framework to formalize phenotypic descriptions and make their semantics explicit. Based on this formalization, we provide the means to integrate phenotypic descriptions with ontologies of other domains, in particular anatomy and physiology. We demonstrate how our framework leads to the capability to represent disease phenotypes, perform powerful queries that were not possible before and infer additional knowledge. http://bioonto.de/pmwiki.php/Main/PheneOntology.

  7. Homogeneous Subgroups of Young Children with Autism Improve Phenotypic Characterization in the Study to Explore Early Development.

    Science.gov (United States)

    Wiggins, Lisa D; Tian, Lin H; Levy, Susan E; Rice, Catherine; Lee, Li-Ching; Schieve, Laura; Pandey, Juhi; Daniels, Julie; Blaskey, Lisa; Hepburn, Susan; Landa, Rebecca; Edmondson-Pretzel, Rebecca; Thompson, William

    2017-11-01

    The objective of this study was to identify homogenous classes of young children with autism spectrum disorder (ASD) to improve phenotypic characterization. Children were enrolled in the Study to Explore Early Development between 2 and 5 years of age. 707 children were classified with ASD after a comprehensive evaluation with strict diagnostic algorithms. Four classes of children with ASD were identified from latent class analysis: mild language delay with cognitive rigidity, mild language and motor delay with dysregulation, general developmental delay, and significant developmental delay with repetitive motor behaviors. We conclude that a four-class phenotypic model of children with ASD best describes our data and improves phenotypic characterization of young children with ASD. Implications for screening, diagnosis, and research are discussed.

  8. PTK7 marks the first human developmental EMT in vitro.

    Directory of Open Access Journals (Sweden)

    David N Chan

    Full Text Available Epithelial to mesenchymal transitions (EMTs are thought to be essential to generate diversity of tissues during early fetal development, but these events are essentially impossible to study at the molecular level in vivo in humans. The first EMT event that has been described morphologically in human development occurs just prior to generation of the primitive streak. Because human embryonic stem cells (hESCs and induced pluripotent stem cells (hiPSCs are thought to most closely resemble cells found in epiblast-stage embryos prior to formation of the primitive streak, we sought to determine whether this first human EMT could be modeled in vitro with pluripotent stem cells. The data presented here suggest that generating embryoid bodies from hESCs or hiPSCs drives a procession of EMT events that can be observed within 24-48 hours after EB generation. These structures possess the typical hallmarks of developmental EMTs, and portions also display evidence of primitive streak and mesendoderm. We identify PTK7 as a novel marker of this EMT population, which can also be used to purify these cells for subsequent analyses and identification of novel markers of human development. Gene expression analysis indicated an upregulation of EMT markers and ECM proteins in the PTK7+ population. We also find that cells that undergo this developmental EMT retain developmental plasticity as sorting, dissociation and re-plating reestablishes an epithelial phenotype.

  9. Developmental orthopaedic diseases in foals

    International Nuclear Information System (INIS)

    Şİrİn, Özlem; Alkan, Zeki

    2010-01-01

    Developmental Orthopaedic Diseases (DOD) is seen frequently in horses which completed their maturity. Osteochondrosis, physitis, angular limb deformities, flexural deformities, juvenil arthritis, cervical vertebral anomalies, cuboidal bone abnormalities are problems investigated under Developmental Orthopaedic Diseases title. This diseases can develop single or some together in fast growing, heavy animals (especially Arabian and English Thoroughbreds). Multifactorial causes of this diseases etiopathogenesis can be listed as genetic predisposition, trauma, nutrition, vitamins/minerals and endocrine disorders. But the exact causes of these diseases are not known. In this review detailed information are given about the diseases mentioned above

  10. PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution

    NARCIS (Netherlands)

    Mirzaa, Ghayda; Timms, Andrew E.; Conti, Valerio; Boyle, Evan August; Girisha, Katta M.; Martin, Beth; Kircher, Martin; Olds, Carissa; Juusola, Jane; Collins, Sarah; Park, Kaylee; Carter, Melissa; Glass, Ian; Krägeloh-Mann, Inge; Chitayat, David; Parikh, Aditi Shah; Bradshaw, Rachael; Torti, Erin; Braddock, Stephen; Burke, Leah; Ghedia, Sondhya; Stephan, Mark; Stewart, Fiona; Prasad, Chitra; Napier, Melanie; Saitta, Sulagna; Straussberg, Rachel; Gabbett, Michael; O'Connor, Bridget C.; Keegan, Catherine E.; Yin, Lim Jiin; Lai, Angeline Hwei Meeng; Martin, Nicole; McKinnon, Margaret; Addor, Marie-Claude; Boccuto, Luigi; Schwartz, Charles E.; Lanoel, Agustina; Conway, Robert L.; Devriendt, Koenraad; Tatton-Brown, Katrina; Pierpont, Mary Ella; Painter, Michael; Worgan, Lisa; Reggin, James; Hennekam, Raoul; Tsuchiya, Karen; Pritchard, Colin C.; Aracena, Mariana; Gripp, Karen W.; Cordisco, Maria; Esch, Hilde Van; Garavelli, Livia; Curry, Cynthia; Goriely, Anne; Kayserilli, Hulya; Shendure, Jay; Graham, John; Guerrini, Renzo; Dobyns, William B.

    2016-01-01

    Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS

  11. Differential effects of developmental thermal plasticity across three generations of guppies (Poecilia reticulata): canalization and anticipatory matching.

    Science.gov (United States)

    Le Roy, Amélie; Loughland, Isabella; Seebacher, Frank

    2017-06-28

    Developmental plasticity can match offspring phenotypes to environmental conditions experienced by parents. Such epigenetic modifications are advantageous when parental conditions anticipate offspring environments. Here we show firstly, that developmental plasticity manifests differently in males and females. Secondly, that under stable conditions, phenotypic responses (metabolism and locomotion) accumulate across several generations. Metabolic scope in males was greater at warmer test temperatures (26-36 °C) in offspring bred at warm temperatures (29-30 °C) compared to those bred at cooler temperatures (22-23 °C), lending support to the predictive adaptive hypothesis. However, this transgenerational matching was not established until the second (F2) generation. For other responses, e.g. swimming performance in females, phenotypes of offspring bred in different thermal environments were different in the first (F1) generation, but became more similar across three generations, implying canalization. Thirdly, when environments changed across generations, the grandparental environment affected offspring phenotypes. In females, the mode of the swimming thermal performance curve shifted to coincide with the grandparental rather than the parental or offspring developmental environments, and this lag in response may represent a cost of plasticity. These findings show that the effects of developmental plasticity differ between traits, and may be modulated by the different life histories of males and females.

  12. The genetic basis of hair whorl, handedness, and other phenotypes

    Science.gov (United States)

    Hatfield, J.S.

    2006-01-01

    Evidence is presented that RHO, RHCE, and other RH genes, may be interesting candidates to consider when searching for the genetic basis of hair whorl rotation (i.e., clockwise or counterclockwise), handedness (i.e., right handed, left handed or ambidextrous), speech laterality (i.e., right brained or left brained), speech dyslexia (e.g., stuttering), sexual orientation (i.e., heterosexual, homosexual, bisexual, or transsexual), schizophrenia, bipolar disorder, and autism spectrum disorder. Such evidence involves the need for a genetic model that includes maternal immunization to explain some of the empirical results reported in the literature. The complex polymorphisms present among the maternally immunizing RH genes can then be used to explain other empirical results. Easily tested hypotheses are suggested, based upon genotypic (but not phenotypic) frequencies of the RH genes. In particular, homozygous dominant individuals are expected to be less common or lacking entirely among the alternative phenotypes. If it is proven that RH genes are involved in brain architecture, it will have a profound effect upon our understanding of the development and organization of the asymmetrical vertebrate brain and may eventually lead to a better understanding of the developmental processes which occur to produce the various alternative phenotypes discussed here. In addition, if RH genes are shown to be involved in the production of these phenotypes, then the evolutionary studies can be performed to demonstrate the beneficial effect of the recessive alleles of RHO and RHCE, and why human evolution appears to be selecting for the recessive alleles even though an increase in the frequency of such alleles may imply lower average fecundity among some individuals possessing them.

  13. A bioimage informatics platform for high-throughput embryo phenotyping.

    Science.gov (United States)

    Brown, James M; Horner, Neil R; Lawson, Thomas N; Fiegel, Tanja; Greenaway, Simon; Morgan, Hugh; Ring, Natalie; Santos, Luis; Sneddon, Duncan; Teboul, Lydia; Vibert, Jennifer; Yaikhom, Gagarine; Westerberg, Henrik; Mallon, Ann-Marie

    2018-01-01

    High-throughput phenotyping is a cornerstone of numerous functional genomics projects. In recent years, imaging screens have become increasingly important in understanding gene-phenotype relationships in studies of cells, tissues and whole organisms. Three-dimensional (3D) imaging has risen to prominence in the field of developmental biology for its ability to capture whole embryo morphology and gene expression, as exemplified by the International Mouse Phenotyping Consortium (IMPC). Large volumes of image data are being acquired by multiple institutions around the world that encompass a range of modalities, proprietary software and metadata. To facilitate robust downstream analysis, images and metadata must be standardized to account for these differences. As an open scientific enterprise, making the data readily accessible is essential so that members of biomedical and clinical research communities can study the images for themselves without the need for highly specialized software or technical expertise. In this article, we present a platform of software tools that facilitate the upload, analysis and dissemination of 3D images for the IMPC. Over 750 reconstructions from 80 embryonic lethal and subviable lines have been captured to date, all of which are openly accessible at mousephenotype.org. Although designed for the IMPC, all software is available under an open-source licence for others to use and develop further. Ongoing developments aim to increase throughput and improve the analysis and dissemination of image data. Furthermore, we aim to ensure that images are searchable so that users can locate relevant images associated with genes, phenotypes or human diseases of interest. © The Author 2016. Published by Oxford University Press.

  14. Neuroimaging of developmental psychopathologies: the importance of self-regulatory and neuroplastic processes in adolescence

    DEFF Research Database (Denmark)

    Spessot, Alexandra L; Plessen, Kerstin J; Peterson, Bradley S

    2004-01-01

    for these developmental and plastic processes during the transition from adolescence into adulthood. Tourette syndrome (TS), defined as the chronic presence of motor and vocal tics, has been increasingly conceptualized as a disorder of impaired self-regulatory control. This disordered control is thought to give rise...... to semicompulsory urges to perform the movements that constitute simple tics, complex tics, or compulsions. Neuroimaging studies suggest that the expression of the genetic diathesis to TS is influenced by genetic and nongenetic factors affecting activity-dependent reorganization of neuroregulatory systems, thereby...... influencing the phenotype, illness severity, and adult outcome of tic disorders. Similar developmental processes during adolescence likely determine the phenotype and natural history of a broad range of other complex neuropsychiatric disorders of childhood onset, and they likely contribute to the acquisition...

  15. Early developmental responses to seedling environment modulate later plasticity to light spectral quality.

    Directory of Open Access Journals (Sweden)

    Eric J B von Wettberg

    Full Text Available Correlations between developmentally plastic traits may constrain the joint evolution of traits. In plants, both seedling de-etiolation and shade avoidance elongation responses to crowding and foliage shade are mediated by partially overlapping developmental pathways, suggesting the possibility of pleiotropic constraints. To test for such constraints, we exposed inbred lines of Impatiens capensis to factorial combinations of leaf litter (which affects de-etiolation and simulated foliage shade (which affects phytochrome-mediated shade avoidance. Increased elongation of hypocotyls caused by leaf litter phenotypically enhanced subsequent elongation of the first internode in response to low red:far red (R:FR. Trait expression was correlated across litter and shade conditions, suggesting that phenotypic effects of early plasticity on later plasticity may affect variation in elongation traits available to selection in different light environments.

  16. The diversification of developmental biology.

    Science.gov (United States)

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

    2015-10-01

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

  17. Transforming Developmental Education in Texas

    Science.gov (United States)

    Journal of Developmental Education, 2014

    2014-01-01

    In recent years, with support from the Texas Legislature, the Texas Higher Education Coordinating Board has funded various developmental education initiatives, including research and evaluation efforts, to help Texas public institutions of higher education provide more effective programs and services to underprepared students. Based on evaluation…

  18. Developmental principles: fact or fiction.

    Science.gov (United States)

    Durston, A J

    2012-01-01

    While still at school, most of us are deeply impressed by the underlying principles that so beautifully explain why the chemical elements are ordered as they are in the periodic table, and may wonder, with the theoretician Brian Goodwin, "whether there might be equally powerful principles that account for the awe-inspiring diversity of body forms in the living realm". We have considered the arguments for developmental principles, conclude that they do exist and have specifically identified features that may generate principles associated with Hox patterning of the main body axis in bilaterian metazoa in general and in the vertebrates in particular. We wonder whether this exercise serves any purpose. The features we discuss were already known to us as parts of developmental mechanisms and defining developmental principles (how, and at which level?) adds no insight. We also see little profit in the proposal by Goodwin that there are principles outside the emerging genetic mechanisms that need to be taken into account. The emerging developmental genetic hierarchies already reveal a wealth of interesting phenomena, whatever we choose to call them.

  19. Developmental Principles: Fact or Fiction

    Directory of Open Access Journals (Sweden)

    A. J. Durston

    2012-01-01

    Full Text Available While still at school, most of us are deeply impressed by the underlying principles that so beautifully explain why the chemical elements are ordered as they are in the periodic table, and may wonder, with the theoretician Brian Goodwin, “whether there might be equally powerful principles that account for the awe-inspiring diversity of body forms in the living realm”. We have considered the arguments for developmental principles, conclude that they do exist and have specifically identified features that may generate principles associated with Hox patterning of the main body axis in bilaterian metazoa in general and in the vertebrates in particular. We wonder whether this exercise serves any purpose. The features we discuss were already known to us as parts of developmental mechanisms and defining developmental principles (how, and at which level? adds no insight. We also see little profit in the proposal by Goodwin that there are principles outside the emerging genetic mechanisms that need to be taken into account. The emerging developmental genetic hierarchies already reveal a wealth of interesting phenomena, whatever we choose to call them.

  20. Measuring Developmental Students' Mathematics Anxiety

    Science.gov (United States)

    Ding, Yanqing

    2016-01-01

    This study conducted an item-level analysis of mathematics anxiety and examined the dimensionality of mathematics anxiety in a sample of developmental mathematics students (N = 162) by Multi-dimensional Random Coefficients Multinominal Logit Model (MRCMLM). The results indicate a moderately correlated factor structure of mathematics anxiety (r =…

  1. Developmental dyscalculia: a dysconnection syndrome?

    Science.gov (United States)

    Kucian, Karin; Ashkenazi, Simone Schwizer; Hänggi, Jürgen; Rotzer, Stephanie; Jäncke, Lutz; Martin, Ernst; von Aster, Michael

    2014-09-01

    Numerical understanding is important for everyday life. For children with developmental dyscalculia (DD), numbers and magnitudes present profound problems which are thought to be based upon neuronal impairments of key regions for numerical understanding. The aim of the present study was to investigate possible differences in white matter fibre integrity between children with DD and controls using diffusion tensor imaging. White matter integrity and behavioural measures were evaluated in 15 children with developmental dyscalculia aged around 10 years and 15 matched controls. The main finding, obtained by a whole brain group comparison, revealed reduced fractional anisotropy in the superior longitudinal fasciculus in children with developmental dyscalculia. In addition, a region of interest analysis exhibited prominent deficits in fibres of the superior longitudinal fasciculus adjacent to the intraparietal sulcus, which is thought to be the core region for number processing. To conclude, our results outline deficient fibre projection between parietal, temporal and frontal regions in children with developmental dyscalculia, and therefore raise the question of whether dyscalculia can be seen as a dysconnection syndrome. Since the superior longitudinal fasciculus is involved in the integration and control of distributed brain processes, the present results highlight the importance of considering broader domain-general mechanisms in the diagnosis and therapy of dyscalculia.

  2. Neuropsychological Aspects of Developmental Dyscalculia.

    Science.gov (United States)

    Shalev, R. S.; Manor, O.; Gross-Tsur, V.

    1997-01-01

    Classification of arithmetic disorders is predicated on neuropsychological features and associated learning disabilities. Assesses the compatibility of these classifications on a nonreferred, population-based cohort of children (N=139) with developmental dyscalculia. Concludes that children with dyscalculia and disabilities in reading and/or…

  3. Developmental trends in adaptive memory.

    Science.gov (United States)

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

    2014-01-01

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

  4. Developmental control of cell division

    NARCIS (Netherlands)

    Boxem, M. (Mike)

    2002-01-01

    During development of multicellular organisms, cell divisions need to be coordinated with the developmental program of the entire organism. Although the mechanisms that drive cells through the division cycle are well understood, very little is known about the pathways that link extracellular signals

  5. Student Development and Developmental Studies.

    Science.gov (United States)

    Champaigne, John

    1982-01-01

    Reviews the nine-stage Perry Scheme of Intellectual and Ethical Development, detailing three major student orientations--dualism, multiplicity, and commitments in relativism. Suggests techniques developmental educators can use to communicate with, support, and challenge students to promote intellectual development. Underscores the importance of…

  6. Automated phenotyping of permanent crops

    Science.gov (United States)

    McPeek, K. Thomas; Steddom, Karl; Zamudio, Joseph; Pant, Paras; Mullenbach, Tyler

    2017-05-01

    AGERpoint is defining a new technology space for the growers' industry by introducing novel applications for sensor technology and data analysis to growers of permanent crops. Serving data to a state-of-the-art analytics engine from a cutting edge sensor platform, a new paradigm in precision agriculture is being developed that allows growers to understand the unique needs of each tree, bush or vine in their operation. Autonomous aerial and terrestrial vehicles equipped with multiple varieties of remote sensing technologies give AGERpoint the ability to measure key morphological and spectral features of permanent crops. This work demonstrates how such phenotypic measurements combined with machine learning algorithms can be used to determine the variety of crops (e.g., almond and pecan trees). This phenotypic and varietal information represents the first step in enabling growers with the ability to tailor their management practices to individual plants and maximize their economic productivity.

  7. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  8. Phenotypic deconstruction of gene circuitry

    Science.gov (United States)

    Lomnitz, Jason G.; Savageau, Michael A.

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  9. Wine Expertise Predicts Taste Phenotype.

    Science.gov (United States)

    Hayes, John E; Pickering, Gary J

    2012-03-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

  10. From plant genomes to phenotypes

    OpenAIRE

    Bolger, Marie; Gundlach, Heidrun; Scholz, Uwe; Mayer, Klaus; Usadel, Björn; Schwacke, Rainer; Schmutzer, Thomas; Chen, Jinbo; Arend, Daniel; Oppermann, Markus; Weise, Stephan; Lange, Matthias; Fiorani, Fabio; Spannagl, Manuel

    2017-01-01

    Recent advances in sequencing technologies have greatly accelerated the rate of plant genome and applied breeding research. Despite this advancing trend, plant genomes continue to present numerous difficulties to the standard tools and pipelines not only for genome assembly but also gene annotation and downstream analysis.Here we give a perspective on tools, resources and services necessary to assemble and analyze plant genomes and link them to plant phenotypes.

  11. What Is a Developmental-Behavioral Pediatrician?

    Science.gov (United States)

    ... social worker. Developmental-behavioral pediatricians work closely with parents, families, and schools. Developmental-behavioral pediatricians understand that children’s development and behavior happen first and foremost in the ...

  12. 29 CFR 1902.33 - Developmental period.

    Science.gov (United States)

    2010-07-01

    ... consideration of developmental changes by OSHA. Generally, whenever a State completes a developmental step, it must submit the resulting plan change as a supplement to its plan to OSHA for approval. OSHA's approval...

  13. Ethiopia: A Democratic Developmental State?

    Directory of Open Access Journals (Sweden)

    Fesseha Mulu Gebremariam

    2017-12-01

    Full Text Available The ruling Ethiopia People’s Revolutionary Democratic Front (EPRDF in its notable second reform appraisal held in the aftermath of the 2005 national election concluded that the utmost priority of the government should be realizing fastest and sustainable economic growth that fairly benefits its citizens’ unless the very existence of the country wouldn’t be guaranteed. Given the history of poverty reduction in developing countries, particularly in Africa, EPRDF realized that it is unthinkable to eradicate poverty from Ethiopia adopting neo-liberalism. Above all, the miraculous economic transformation of the South East Asian countries like South Korea, Taiwan, Singapore and Hong Kong has proved that there is another way to development, not just neo-liberalism. Accordingly, EPRDF, after examining South Korea’s and Taiwan’s history of economic development in particular where both countries have had a large section of rural population unlike Hong Kong and Singapore where both are urban, found ‘developmental state’ relevant to Ethiopia. However, unlike these countries which were originally under non-democratic regimes where their leaders fear the rural peasant and external aggression from their communist rivals, EPRDF has had a great support of rural and urban population with no imminent foreign threat(s, and decided to execute the ideology rather under the umbrella of democracy. Therefore, employing secondary sources, this desk study aims to analyze whether Ethiopia is a ‘democratic developmental state?’ And, concludes that given the practices of the government vis-a-vis the principles of democracy and developmental state, Ethiopia couldn’t be taken as best model for democratic developmental state, rather emerging developmental state.

  14. Velo-cardio-facial and partial DiGeorge phenotype in a child with interstitial deletion at 10p13 - implications for cytogenetics and molecular biology

    Energy Technology Data Exchange (ETDEWEB)

    Lipson, A.; Sholler, G.; Issacs, D. [Royal Alexandra Hospital for Children, Sydney (Australia)] [and others

    1996-11-11

    We report on a female with a interstitial deletion of 10p13 and a phenotype similar to that seen with the 22q deletion syndromes (DiGeorge/velo-cardio-facial). She had a posterior cleft palate, perimembranous ventricular septal defect, dyscoordinate swallowing, T-cell subset abnormalities, small ears, maxillary and mandibular hypoplasia, broad nasal bridge, deficient alae nasi, contractures of fingers and developmental delay. This could indicate homology of some developmental genes at 22q and 10p so that patients with the velocardiofacial phenotype who do not prove to be deleted on 22q are candidates for a 10p deletion. 58 refs., 3 figs.

  15. Phenotypic covariance at species' borders.

    Science.gov (United States)

    Caley, M Julian; Cripps, Edward; Game, Edward T

    2013-05-28

    Understanding the evolution of species limits is important in ecology, evolution, and conservation biology. Despite its likely importance in the evolution of these limits, little is known about phenotypic covariance in geographically marginal populations, and the degree to which it constrains, or facilitates, responses to selection. We investigated phenotypic covariance in morphological traits at species' borders by comparing phenotypic covariance matrices (P), including the degree of shared structure, the distribution of strengths of pair-wise correlations between traits, the degree of morphological integration of traits, and the ranks of matricies, between central and marginal populations of three species-pairs of coral reef fishes. Greater structural differences in P were observed between populations close to range margins and conspecific populations toward range centres, than between pairs of conspecific populations that were both more centrally located within their ranges. Approximately 80% of all pair-wise trait correlations within populations were greater in the north, but these differences were unrelated to the position of the sampled population with respect to the geographic range of the species. Neither the degree of morphological integration, nor ranks of P, indicated greater evolutionary constraint at range edges. Characteristics of P observed here provide no support for constraint contributing to the formation of these species' borders, but may instead reflect structural change in P caused by selection or drift, and their potential to evolve in the future.

  16. Adaptive evolution of molecular phenotypes

    International Nuclear Information System (INIS)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-01-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak. (paper)

  17. Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

    Science.gov (United States)

    Wilson, Robert; Geyer, Stefan H.; Reissig, Lukas; Rose, Julia; Szumska, Dorota; Hardman, Emily; Prin, Fabrice; McGuire, Christina; Ramirez-Solis, Ramiro; White, Jacqui; Galli, Antonella; Tudor, Catherine; Tuck, Elizabeth; Mazzeo, Cecilia Icoresi; Smith, James C.; Robertson, Elizabeth; Adams, David J.; Mohun, Timothy; Weninger, Wolfgang J.

    2017-01-01

    Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates. PMID:27996060

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

    Science.gov (United States)

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

    2015-01-01

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

  19. Conserved patterns of integrated developmental plasticity in a group of polyphenic tropical butterflies.

    Science.gov (United States)

    van Bergen, Erik; Osbaldeston, Dave; Kodandaramaiah, Ullasa; Brattström, Oskar; Aduse-Poku, Kwaku; Brakefield, Paul M

    2017-02-27

    Developmental plasticity is thought to have profound macro-evolutionary effects, for example, by increasing the probability of establishment in new environments and subsequent divergence into independently evolving lineages. In contrast to plasticity optimized for individual traits, phenotypic integration, which enables a concerted response of plastic traits to environmental variability, may affect the rate of local adaptation by constraining independent responses of traits to selection. Using a comparative framework, this study explores the evolution of reaction norms for a variety of life history and morphological traits across five related species of mycalesine butterflies from the Old World tropics. Our data indicate that an integrated response of a suite of key traits is shared amongst these species. Interestingly, the traits that make up the functional suite are all known to be regulated by ecdysteroid signalling in Bicyclus anynana, one of the species included in this study, suggesting the same underlying hormonal regulator may be conserved within this group of polyphenic butterflies. We also detect developmental thresholds for the expression of alternative morphs. The phenotypic plasticity of a broad suite of morphological and life history traits is integrated and shared among species from three geographically independent lineages of mycalesine butterflies, despite considerable periods of independent evolution and exposure to disparate environments. At the same time, we have detected examples of evolutionary change where independent traits show different patterns of reaction norms. We argue that the expression of more robust phenotypes may occur by shifting developmental thresholds beyond the boundaries of the typical environmental variation.

  20. RNAi Screen in Drosophila melanogastor Identifies Regulators of Steroidogenesis and Developmental Maturation

    DEFF Research Database (Denmark)

    Danielsen, Erik Thomas

    and duration required for juvenile-adult transition. This PhD project demonstrates the power of Drosophila genetics by taking an in vivo genome-wide RNAi screening approach to uncover genes required for the function of steroid producing tissue and developmental maturation. In total, 1909 genes were found...... to be required for the prothoracic gland function and affected the developmental timing for the juvenile-adult transition. Among the screen hits, we focused on an uncharacterized gene, sit (CG5278), which is highly expressed in the gland and is required for ecdysone production. Sit is a homolog of mammalian very...... flux of cholesterol uptake in the gland cells and affected the endosomal trafficking. Therefore this gene was suggested to be named stuck in traffic (sit). Sit’s role in cholesterol uptake was also supported by the observation that the developmental delayed phenotype from loss of sit expression...

  1. The broader autism phenotype in infancy: when does it emerge?

    Science.gov (United States)

    Ozonoff, Sally; Young, Gregory S; Belding, Ashleigh; Hill, Monique; Hill, Alesha; Hutman, Ted; Johnson, Scott; Miller, Meghan; Rogers, Sally J; Schwichtenberg, A J; Steinfeld, Marybeth; Iosif, Ana-Maria

    2014-04-01

    This study had 3 goals, which were to examine the following: the frequency of atypical development, consistent with the broader autism phenotype, in high-risk infant siblings of children with autism spectrum disorder (ASD); the age at which atypical development is first evident; and which developmental domains are affected. A prospective longitudinal design was used to compare 294 high-risk infants and 116 low-risk infants. Participants were tested at 6, 12, 18, 24, and 36 months of age. At the final visit, outcome was classified as ASD, Typical Development (TD), or Non-TD (defined as elevated Autism Diagnostic Observation Schedule [ADOS] score, low Mullen Scale scores, or both). Of the high-risk group, 28% were classified as Non-TD at 36 months of age. Growth curve models demonstrated that the Non-TD group could not be distinguished from the other groups at 6 months of age, but differed significantly from the Low-Risk TD group by 12 months on multiple measures. The Non-TD group demonstrated atypical development in cognitive, motor, language, and social domains, with differences particularly prominent in the social-communication domain. These results demonstrate that features of atypical development, consistent with the broader autism phenotype, are detectable by the first birthday and affect development in multiple domains. This highlights the necessity for close developmental surveillance of infant siblings of children with ASD, along with implementation of appropriate interventions as needed. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Adaptive developmental delay in Chagas disease vectors: an evolutionary ecology approach.

    Directory of Open Access Journals (Sweden)

    Frédéric Menu

    2010-05-01

    Full Text Available The developmental time of vector insects is important in population dynamics, evolutionary biology, epidemiology and in their responses to global climatic change. In the triatomines (Triatominae, Reduviidae, vectors of Chagas disease, evolutionary ecology concepts, which may allow for a better understanding of their biology, have not been applied. Despite delay in the molting in some individuals observed in triatomines, no effort was made to explain this variability.We applied four methods: (1 an e-mail survey sent to 30 researchers with experience in triatomines, (2 a statistical description of the developmental time of eleven triatomine species, (3 a relationship between development time pattern and climatic inter-annual variability, (4 a mathematical optimization model of evolution of developmental delay (diapause.85.6% of responses informed on prolonged developmental times in 5(th instar nymphs, with 20 species identified with remarkable developmental delays. The developmental time analysis showed some degree of bi-modal pattern of the development time of the 5(th instars in nine out of eleven species but no trend between development time pattern and climatic inter-annual variability was observed. Our optimization model predicts that the developmental delays could be due to an adaptive risk-spreading diapause strategy, only if survival throughout the diapause period and the probability of random occurrence of "bad" environmental conditions are sufficiently high.Developmental delay may not be a simple non-adaptive phenotypic plasticity in development time, and could be a form of adaptive diapause associated to a physiological mechanism related to the postponement of the initiation of reproduction, as an adaptation to environmental stochasticity through a spreading of risk (bet-hedging strategy. We identify a series of parameters that can be measured in the field and laboratory to test this hypothesis. The importance of these findings is

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

    Science.gov (United States)

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

    2010-01-01

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

  4. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  5. Pregnancy-associated plasma protein-A (PAPP-A) modulates early developmental rate in zebrafish independent of its proteolytic activity

    DEFF Research Database (Denmark)

    Kjær-Sørensen, Kasper; Engholm, Ditte Høyer; Kamei, Hiroyasu

    2013-01-01

    the developmental rate beginning during gastrulation without affecting the normal patterning of the embryo. This phenotype is different from those resulting from deficiency of Igf receptor or ligand in zebrafish, suggesting a function of Papp-a outside the Igf system. Biochemical analysis of recombinant zebrafish...... Papp-a demonstrates conservation of proteolytic activity, specificity, and intrinsic regulatory mechanism. However, in vitro transcribed mRNA, which encodes a proteolytically inactive Papp-a mutant, recues the papp-a knockdown phenotype as efficient as wild-type Papp-a. Thus, the developmental...

  6. NIH Mouse Metabolic Phenotyping Centers: the power of centralized phenotyping.

    Science.gov (United States)

    Laughlin, Maren R; Lloyd, K C Kent; Cline, Gary W; Wasserman, David H

    2012-10-01

    The Mouse Metabolic Phenotyping Centers (MMPCs) were founded in 2001 by the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high-quality phenotyping services for mouse models of diabetes, obesity, and their complications. The intent is to allow researchers to take optimum advantage of the many new mouse models produced in labs and in high-throughput public efforts. The six MMPCs are located at universities around the country and perform complex metabolic tests in intact mice and hormone and analyte assays in tissues on a fee-for-service basis. Testing is subsidized by the NIH in order to reduce the barriers for mouse researchers. Although data derived from these tests belong to the researcher submitting mice or tissues, these data are archived after publication in a public database run by the MMPC Coordinating and Bioinformatics Unit. It is hoped that data from experiments performed in many mouse models of metabolic diseases, using standard protocols, will be useful in understanding the nature of these complex disorders. The current areas of expertise include energy balance and body composition, insulin action and secretion, whole-body and tissue carbohydrate and lipid metabolism, cardiovascular and renal function, and metabolic pathway kinetics. In addition to providing services, the MMPC staff provides expertise and advice to researchers, and works to develop and refine test protocols to best meet the community's needs in light of current scientific developments. Test technology is disseminated by publications and through annual courses.

  7. Ribosomal protein gene knockdown causes developmental defects in zebrafish.

    Directory of Open Access Journals (Sweden)

    Tamayo Uechi

    Full Text Available The ribosomal proteins (RPs form the majority of cellular proteins and are mandatory for cellular growth. RP genes have been linked, either directly or indirectly, to various diseases in humans. Mutations in RP genes are also associated with tissue-specific phenotypes, suggesting a possible role in organ development during early embryogenesis. However, it is not yet known how mutations in a particular RP gene result in specific cellular changes, or how RP genes might contribute to human diseases. The development of animal models with defects in RP genes will be essential for studying these questions. In this study, we knocked down 21 RP genes in zebrafish by using morpholino antisense oligos to inhibit their translation. Of these 21, knockdown of 19 RPs resulted in the development of morphants with obvious deformities. Although mutations in RP genes, like other housekeeping genes, would be expected to result in nonspecific developmental defects with widespread phenotypes, we found that knockdown of some RP genes resulted in phenotypes specific to each gene, with varying degrees of abnormality in the brain, body trunk, eyes, and ears at about 25 hours post fertilization. We focused further on the organogenesis of the brain. Each knocked-down gene that affected the morphogenesis of the brain produced a different pattern of abnormality. Among the 7 RP genes whose knockdown produced severe brain phenotypes, 3 human orthologs are located within chromosomal regions that have been linked to brain-associated diseases, suggesting a possible involvement of RP genes in brain or neurological diseases. The RP gene knockdown system developed in this study could be a powerful tool for studying the roles of ribosomes in human diseases.

  8. Developmental insights into mature cognition.

    Science.gov (United States)

    Keil, Frank C

    2015-02-01

    Three cases are described that illustrate new ways in which developmental research is informing the study of cognition in adults: statistical learning, neural substrates of cognition, and extended concepts. Developmental research has made clear the ubiquity of statistical learning while also revealing is limitations as a stand-alone way to acquire knowledge. With respect to neural substrates, development has uncovered links between executive processing and fronto-striatal circuits while also pointing to many aspects of high-level cognition that may not be neatly reducible to coherent neural descriptions. For extended concepts, children have made especially clear the weaknesses of intuitive theories in both children and adults while also illustrating other cognitive capacities that are used at all ages to navigate the socially distributed aspects of knowledge. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Developmental language and speech disability.

    Science.gov (United States)

    Spiel, G; Brunner, E; Allmayer, B; Pletz, A

    2001-09-01

    Speech disabilities (articulation deficits) and language disorders--expressive (vocabulary) receptive (language comprehension) are not uncommon in children. An overview of these along with a global description of the impairment of communication as well as clinical characteristics of language developmental disorders are presented in this article. The diagnostic tables, which are applied in the European and Anglo-American speech areas, ICD-10 and DSM-IV, have been explained and compared. Because of their strengths and weaknesses an alternative classification of language and speech developmental disorders is proposed, which allows a differentiation between expressive and receptive language capabilities with regard to the semantic and the morphological/syntax domains. Prevalence and comorbidity rates, psychosocial influences, biological factors and the biological social interaction have been discussed. The necessity of the use of standardized examinations is emphasised. General logopaedic treatment paradigms, specific therapy concepts and an overview of prognosis have been described.

  10. Developmental Plasticity and Language: A Comparative Perspective.

    Science.gov (United States)

    Griebel, Ulrike; Pepperberg, Irene M; Oller, D Kimbrough

    2016-04-01

    The growing field of evo-devo is increasingly demonstrating the complexity of steps involved in genetic, intracellular regulatory, and extracellular environmental control of the development of phenotypes. A key result of such work is an account for the remarkable plasticity of organismal form in many species based on relatively minor changes in regulation of highly conserved genes and genetic processes. Accounting for behavioral plasticity is of similar potential interest but has received far less attention. Of particular interest is plasticity in communication systems, where human language represents an ultimate target for research. The present paper considers plasticity of language capabilities in a comparative framework, focusing attention on examples of a remarkable fact: Whereas there exist design features of mature human language that have never been observed to occur in non-humans in the wild, many of these features can be developed to notable extents when non-humans are enculturated through human training (especially with intensive social interaction). These examples of enculturated developmental plasticity across extremely diverse taxa suggest, consistent with the evo-devo theme of highly conserved processes in evolution, that human language is founded in part on cognitive capabilities that are indeed ancient and that even modern humans show self-organized emergence of many language capabilities in the context of rich enculturation, built on the special social/ecological history of the hominin line. Human culture can thus be seen as a regulatory system encouraging language development in the context of a cognitive background with many highly conserved features. Copyright © 2016 Cognitive Science Society, Inc.

  11. The Human Phenotype Ontology in 2017

    International Nuclear Information System (INIS)

    Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark; Foster, Erin; McMurry, Julie

    2016-01-01

    Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

  12. Ecdysone Control of Developmental Transitions

    DEFF Research Database (Denmark)

    Rewitz, Kim; Yamanaka, Naoki; O'Connor, Michael B.

    2013-01-01

    The steroid hormone ecdysone is the central regulator of insect developmental transitions. Recent new advances in our understanding of ecdysone action have relied heavily on the application of Drosophila melanogaster molecular genetic tools to study insect metamorphosis. In this review, we focus...... on three major aspects of Drosophila ecdysone biology: (a) factors that regulate the timing of ecdysone release, (b) molecular basis of stage- and tissue-specific responses to ecdysone, and (c) feedback regulation and coordination of ecdysone signaling....

  13. Phenotypic variability in Meesmann's dystrophy

    DEFF Research Database (Denmark)

    Ehlers, Niels; Hjortdal, Jesper; Nielsen, Kim

    2008-01-01

    symptoms often include blurred vision and ocular irritation. Typical cases may be entirely free of complaints. Intermittent pain episodes, such as occur in recurrent erosion syndrome, are not the rule. Genetic sequencing indicated a familial relationship with the originally described Meesmann family......'s dystrophy occurs worldwide. The largest family described is the original German one, now supplemented with a Danish branch. Despite the presence of an identical genetic defect, the clinical phenotype varies. This suggests that non-KRT12-related mechanisms are responsible for the variation....

  14. 20170312 - Computer Simulation of Developmental ...

    Science.gov (United States)

    Rationale: Recent progress in systems toxicology and synthetic biology have paved the way to new thinking about in vitro/in silico modeling of developmental processes and toxicities, both for embryological and reproductive impacts. Novel in vitro platforms such as 3D organotypic culture models, engineered microscale tissues and complex microphysiological systems (MPS), together with computational models and computer simulation of tissue dynamics, lend themselves to a integrated testing strategies for predictive toxicology. As these emergent methodologies continue to evolve, they must be integrally tied to maternal/fetal physiology and toxicity of the developing individual across early lifestage transitions, from fertilization to birth, through puberty and beyond. Scope: This symposium will focus on how the novel technology platforms can help now and in the future, with in vitro/in silico modeling of complex biological systems for developmental and reproductive toxicity issues, and translating systems models into integrative testing strategies. The symposium is based on three main organizing principles: (1) that novel in vitro platforms with human cells configured in nascent tissue architectures with a native microphysiological environments yield mechanistic understanding of developmental and reproductive impacts of drug/chemical exposures; (2) that novel in silico platforms with high-throughput screening (HTS) data, biologically-inspired computational models of

  15. Developmental transcriptome of Aplysia californica'

    KAUST Repository

    Heyland, Andreas

    2010-12-06

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

  16. Psychotherapy with people with developmental disabilities

    Directory of Open Access Journals (Sweden)

    Barbara Zafošnik

    2011-08-01

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

  17. Phenotypic and evolutionary implications of modulating the ERK-MAPK cascade using the dentition as a model

    Science.gov (United States)

    Marangoni, Pauline; Charles, Cyril; Tafforeau, Paul; Laugel-Haushalter, Virginie; Joo, Adriane; Bloch-Zupan, Agnès; Klein, Ophir D.; Viriot, Laurent

    2015-06-01

    The question of phenotypic convergence across a signalling pathway has important implications for both developmental and evolutionary biology. The ERK-MAPK cascade is known to play a central role in dental development, but the relative roles of its components remain unknown. Here we investigate the diversity of dental phenotypes in Spry2-/-, Spry4-/-, and Rsk2-/Y mice, including the incidence of extra teeth, which were lost in the mouse lineage 45 million years ago (Ma). In addition, Sprouty-specific anomalies mimic a phenotype that is absent in extant mice but present in mouse ancestors prior to 9 Ma. Although the mutant lines studied display convergent phenotypes, each gene has a specific role in tooth number determination and crown patterning. The similarities found between teeth in fossils and mutants highlight the pivotal role of the ERK-MAPK cascade during the evolution of the dentition in rodents.

  18. ACE phenotyping in Gaucher disease.

    Science.gov (United States)

    Danilov, Sergei M; Tikhomirova, Victoria E; Metzger, Roman; Naperova, Irina A; Bukina, Tatiana M; Goker-Alpan, Ozlem; Tayebi, Nahid; Gayfullin, Nurshat M; Schwartz, David E; Samokhodskaya, Larisa M; Kost, Olga A; Sidransky, Ellen

    2018-04-01

    Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes. We show that in patients with Gaucher disease, the dramatically increased levels of ACE originate from activated splenic and/or hepatic macrophages (Gaucher cells), and that both its conformational fingerprint and kinetic characteristics (ZPHL/HHL ratio) differ from controls and from patients with sarcoid granulomas. Furthermore, normal spleen was found to produce high levels of endogenous ACE inhibitors and a novel, tightly-bound 10-30 kDa ACE effector which is deficient in Gaucher spleen. The conformation of ACE is tissue-specific. In Gaucher disease, ACE produced by activated splenic macrophages differs from that in hepatic macrophages, as well as from macrophages and dendritic cells in sarcoid granulomas. The observed differences are likely due to altered ACE glycosylation or sialylation in these diseased organs. The conformational differences in ACE may serve as a specific biomarker for Gaucher disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies.

    Science.gov (United States)

    Ilkovski, Biljana; Pagnamenta, Alistair T; O'Grady, Gina L; Kinoshita, Taroh; Howard, Malcolm F; Lek, Monkol; Thomas, Brett; Turner, Anne; Christodoulou, John; Sillence, David; Knight, Samantha J L; Popitsch, Niko; Keays, David A; Anzilotti, Consuelo; Goriely, Anne; Waddell, Leigh B; Brilot, Fabienne; North, Kathryn N; Kanzawa, Noriyuki; Macarthur, Daniel G; Taylor, Jenny C; Kini, Usha; Murakami, Yoshiko; Clarke, Nigel F

    2015-11-01

    Glycosylphosphatidylinositol (GPI)-anchored proteins are ubiquitously expressed in the human body and are important for various functions at the cell surface. Mutations in many GPI biosynthesis genes have been described to date in patients with multi-system disease and together these constitute a subtype of congenital disorders of glycosylation. We used whole exome sequencing in two families to investigate the genetic basis of disease and used RNA and cellular studies to investigate the functional consequences of sequence variants in the PIGY gene. Two families with different phenotypes had homozygous recessive sequence variants in the GPI biosynthesis gene PIGY. Two sisters with c.137T>C (p.Leu46Pro) PIGY variants had multi-system disease including dysmorphism, seizures, severe developmental delay, cataracts and early death. There were significantly reduced levels of GPI-anchored proteins (CD55 and CD59) on the surface of patient-derived skin fibroblasts (∼20-50% compared with controls). In a second, consanguineous family, two siblings had moderate development delay and microcephaly. A homozygous PIGY promoter variant (c.-540G>A) was detected within a 7.7 Mb region of autozygosity. This variant was predicted to disrupt a SP1 consensus binding site and was shown to be associated with reduced gene expression. Mutations in PIGY can occur in coding and non-coding regions of the gene and cause variable phenotypes. This article contributes to understanding of the range of disease phenotypes and disease genes associated with deficiencies of the GPI-anchor biosynthesis pathway and also serves to highlight the potential importance of analysing variants detected in 5'-UTR regions despite their typically low coverage in exome data. © The Author 2015. Published by Oxford University Press.

  20. Reduced prostasin (CAP1/PRSS8) activity eliminates HAI-1 and HAI-2 deficiency-associated developmental defects by preventing matriptase activation

    DEFF Research Database (Denmark)

    Szabo, Roman; Uzzun Sales, Katiuchia; Kosa, Peter

    2012-01-01

    is a critical developmental target for both protease inhibitors. Here, we performed a genetic epistasis analysis to identify additional components of this pathway by generating mice with combined deficiency in either HAI-1 or HAI-2, along with genes encoding developmentally co-expressed candidate matriptase......-prostasin activity causes developmental failure independent of aberrant c-Met and PAR-2 signaling or impaired epithelial sodium transport. Furthermore, phenotypic analysis of PAR-1 and matriptase double-deficient embryos suggests that the protease may not be critical for focal proteolytic activation of PAR-2 during...

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

    Science.gov (United States)

    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.

  2. Evolution of branched regulatory genetic pathways: directional selection on pleiotropic loci accelerates developmental system drift.

    Science.gov (United States)

    Johnson, Norman A; Porter, Adam H

    2007-01-01

    Developmental systems are regulated by a web of interacting loci. One common and useful approach in studying the evolution of development is to focus on classes of interacting elements within these systems. Here, we use individual-based simulations to study the evolution of traits controlled by branched developmental pathways involving three loci, where one locus regulates two different traits. We examined the system under a variety of selective regimes. In the case where one branch was under stabilizing selection and the other under directional selection, we observed "developmental system drift": the trait under stabilizing selection showed little phenotypic change even though the loci underlying that trait showed considerable evolutionary divergence. This occurs because the pleiotropic locus responds to directional selection and compensatory mutants are then favored in the pathway under stabilizing selection. Though developmental system drift may be caused by other mechanisms, it seems likely that it is accelerated by the same underlying genetic mechanism as that producing the Dobzhansky-Muller incompatibilities that lead to speciation in both linear and branched pathways. We also discuss predictions of our model for developmental system drift and how different selective regimes affect probabilities of speciation in the branched pathway system.

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

    Science.gov (United States)

    Stotz, Karola

    2017-10-06

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

  4. Why did the savant syndrome not spread in the population? A psychiatric example of a developmental constraint.

    Science.gov (United States)

    Ploeger, Annemie; van der Maas, Han L J; Raijmakers, Maartje E J; Galis, Frietson

    2009-03-31

    A developmental constraint is a mechanism that limits the possibility of a phenotype to evolve. There is growing evidence for the existence of developmental constraints in the biological literature. We hypothesize that a developmental constraint prevents the savant syndrome, despite its positive aspects, from spreading in the population. Here, the developmental constraint is the result of the high interactivity among body parts in an early stage in embryological development, namely early organogenesis or the phylotypic stage. The interactivity during this stage involves all components of the embryo, and as a result mutations that affect one part of the embryo also affect other parts. We hypothesize that a mutation, which gives rise to the development of the positive aspects of the savant syndrome (e.g., an impressive memory capacity), will virtually always have a deleterious effect on the development of other phenotypic traits (e.g., resulting in autism and/or impaired motor coordination). Thus, our hypothesis states that the savant syndrome cannot spread in the population because of this developmental constraint. The finding that children with savant syndrome often have autism and physical anomalies, which are known to be established during early organogenesis, supports our hypothesis.

  5. Autosomal dominant SCN8A mutation with an unusually mild phenotype.

    Science.gov (United States)

    Anand, G; Collett-White, F; Orsini, A; Thomas, S; Jayapal, S; Trump, N; Zaiwalla, Z; Jayawant, S

    2016-09-01

    Mutations in SCN8A, coding for the voltage-gated sodium channel Nav 1.6, have been described in relation to infantile onset epilepsy with developmental delay and cognitive impairment, in particular early onset epileptic encephalopathy (EIEE) type 13. Here we report an infant and his father with early onset focal epileptic seizures but without cognitive or neurological impairment in whom next generation sequence analysis identified a heterozygous mutation (c.5630A > G, p. (Asn1877Ser)) in the SCN8A gene. This mutation, confirmed by Sanger sequence analysis, affects a highly conserved amino acid and in silico tools predicts that it may be pathogenic. The reported infant has a normal developmental profile at 16-month follow-up. His father also had normal development and has no cognitive impairment at 42 years. This is the second known SCN8A mutation associated with a phenotype of benign familial infantile epilepsy. Good seizure control was achieved in our patients with sodium channel blockers. Based on our proband and a recently described group of families with benign familial infantile epilepsy and SCN8A variant we suggest expanding testing to patients with infantile epilepsy and no cognitive impairment. In addition, the same SCN8A variant (c.5630A > G, p. (Asn1877Ser)) is also found in patients with epilepsy and developmental delay highlighting the phenotypic variability and the possible role of other protective genetic factors. Copyright © 2016. Published by Elsevier Ltd.

  6. Refined Phenotyping of Modic Changes

    Science.gov (United States)

    Määttä, Juhani H.; Karppinen, Jaro; Paananen, Markus; Bow, Cora; Luk, Keith D.K.; Cheung, Kenneth M.C.; Samartzis, Dino

    2016-01-01

    Abstract Low back pain (LBP) is the world's most disabling condition. Modic changes (MC) are vertebral bone marrow changes adjacent to the endplates as noted on magnetic resonance imaging. The associations of specific MC types and patterns with prolonged, severe LBP and disability remain speculative. This study assessed the relationship of prolonged, severe LBP and back-related disability, with the presence and morphology of lumbar MC in a large cross-sectional population-based study of Southern Chinese. We addressed the topographical and morphological dimensions of MC along with other magnetic resonance imaging phenotypes (eg, disc degeneration and displacement) on the basis of axial T1 and sagittal T2-weighted imaging of L1-S1. Prolonged severe LBP was defined as LBP lasting ≥30 days during the past year, and a visual analog scale severest pain intensity of at least 6/10. An Oswestry Disability Index score of 15% was regarded as significant disability. We also assessed subject demographics, occupation, and lifestyle factors. In total, 1142 subjects (63% females, mean age 53 years) were assessed. Of these, 282 (24.7%) had MC (7.1% type I, 17.6% type II). MC subjects were older (P = 0.003), had more frequent disc displacements (P disability. The strength of the associations increased with the number of MC. This large-scale study is the first to definitively note MC types and specific morphologies to be independently associated with prolonged severe LBP and back-related disability. This proposed refined MC phenotype may have direct implications in clinical decision-making as to the development and management of LBP. Understanding of these imaging biomarkers can lead to new preventative and personalized therapeutics related to LBP. PMID:27258491

  7. Music cognition: a developmental perspective.

    Science.gov (United States)

    Stalinski, Stephanie M; Schellenberg, E Glenn

    2012-10-01

    Although music is universal, there is a great deal of cultural variability in music structures. Nevertheless, some aspects of music processing generalize across cultures, whereas others rely heavily on the listening environment. Here, we discuss the development of musical knowledge, focusing on four themes: (a) capabilities that are present early in development; (b) culture-general and culture-specific aspects of pitch and rhythm processing; (c) age-related changes in pitch perception; and (d) developmental changes in how listeners perceive emotion in music. Copyright © 2012 Cognitive Science Society, Inc.

  8. Fetal Sex Modulates Developmental Response to Maternal Malnutrition.

    Directory of Open Access Journals (Sweden)

    Antonio Gonzalez-Bulnes

    Full Text Available The incidence of obesity and metabolic diseases is dramatically high in rapidly developing countries. Causes have been related to intrinsic ethnic features with development of a thrifty genotype for adapting to food scarcity, prenatal programming by undernutrition, and postnatal exposure to obesogenic lifestyle. Observational studies in humans and experimental studies in animal models evidence that the adaptive responses of the offspring may be modulated by their sex. In the contemporary context of world globalization, the new question arising is the existence and extent of sex-related differences in developmental and metabolic traits in case of mixed-race. Hence, in the current study, using a swine model, we compared male and female fetuses that were crossbred from mothers with thrifty genotype and fathers without thrifty genotype. Female conceptuses evidence stronger protective strategies for their adequate growth and postnatal survival. In brief, both male and female fetuses developed a brain-sparing effect but female fetuses were still able to maintain the development of other viscerae than the brain (mainly liver, intestine and kidneys at the expense of carcass development. Furthermore, these morphometric differences were reinforced by differences in nutrient availability (glucose and cholesterol favoring female fetuses with severe developmental predicament. These findings set the basis for further studies aiming to increase the knowledge on the interaction between genetic and environmental factors in the determination of adult phenotype.

  9. DAF-12 Regulates a Connected Network of Genes to Ensure Robust Developmental Decisions

    Science.gov (United States)

    Stuckenholz, Carsten; Labhart, Paul; Alexiadis, Vassili; Martin, René; Knölker, Hans-Joachim; Fisher, Alfred L.

    2011-01-01

    The nuclear receptor DAF-12 has roles in normal development, the decision to pursue dauer development in unfavorable conditions, and the modulation of adult aging. Despite the biologic importance of DAF-12, target genes for this receptor are largely unknown. To identify DAF-12 targets, we performed chromatin immunoprecipitation followed by hybridization to whole-genome tiling arrays. We identified 1,175 genomic regions to be bound in vivo by DAF-12, and these regions are enriched in known DAF-12 binding motifs and act as DAF-12 response elements in transfected cells and in transgenic worms. The DAF-12 target genes near these binding sites include an extensive network of interconnected heterochronic and microRNA genes. We also identify the genes encoding components of the miRISC, which is required for the control of target genes by microRNA, as a target of DAF-12 regulation. During reproductive development, many of these target genes are misregulated in daf-12(0) mutants, but this only infrequently results in developmental phenotypes. In contrast, we and others have found that null daf-12 mutations enhance the phenotypes of many miRISC and heterochronic target genes. We also find that environmental fluctuations significantly strengthen the weak heterochronic phenotypes of null daf-12 alleles. During diapause, DAF-12 represses the expression of many heterochronic and miRISC target genes, and prior work has demonstrated that dauer formation can suppress the heterochronic phenotypes of many of these target genes in post-dauer development. Together these data are consistent with daf-12 acting to ensure developmental robustness by committing the animal to adult or dauer developmental programs despite variable internal or external conditions. PMID:21814518

  10. Bioinformatics approaches to single-cell analysis in developmental biology.

    Science.gov (United States)

    Yalcin, Dicle; Hakguder, Zeynep M; Otu, Hasan H

    2016-03-01

    Individual cells within the same population show various degrees of heterogeneity, which may be better handled with single-cell analysis to address biological and clinical questions. Single-cell analysis is especially important in developmental biology as subtle spatial and temporal differences in cells have significant associations with cell fate decisions during differentiation and with the description of a particular state of a cell exhibiting an aberrant phenotype. Biotechnological advances, especially in the area of microfluidics, have led to a robust, massively parallel and multi-dimensional capturing, sorting, and lysis of single-cells and amplification of related macromolecules, which have enabled the use of imaging and omics techniques on single cells. There have been improvements in computational single-cell image analysis in developmental biology regarding feature extraction, segmentation, image enhancement and machine learning, handling limitations of optical resolution to gain new perspectives from the raw microscopy images. Omics approaches, such as transcriptomics, genomics and epigenomics, targeting gene and small RNA expression, single nucleotide and structural variations and methylation and histone modifications, rely heavily on high-throughput sequencing technologies. Although there are well-established bioinformatics methods for analysis of sequence data, there are limited bioinformatics approaches which address experimental design, sample size considerations, amplification bias, normalization, differential expression, coverage, clustering and classification issues, specifically applied at the single-cell level. In this review, we summarize biological and technological advancements, discuss challenges faced in the aforementioned data acquisition and analysis issues and present future prospects for application of single-cell analyses to developmental biology. © The Author 2015. Published by Oxford University Press on behalf of the European

  11. Most Colorful Example of Genetic Assimilation? Exploring the Evolutionary Destiny of Recurrent Phenotypic Accommodation.

    Science.gov (United States)

    Badyaev, Alexander V; Potticary, Ahva L; Morrison, Erin S

    2017-08-01

    Evolution of adaptation requires both generation of novel phenotypic variation and retention of a locally beneficial subset of this variation. Such retention can be facilitated by genetic assimilation, the accumulation of genetic and molecular mechanisms that stabilize induced phenotypes and assume progressively greater control over their reliable production. A particularly strong inference into genetic assimilation as an evolutionary process requires a system where it is possible to directly evaluate the extent to which an induced phenotype is progressively incorporated into preexisting developmental pathways. Evolution of diet-dependent pigmentation in birds-where external carotenoids are coopted into internal metabolism to a variable degree before being integrated with a feather's developmental processes-provides such an opportunity. Here we combine a metabolic network view of carotenoid evolution with detailed empirical study of feather modifications to show that the effect of physical properties of carotenoids on feather structure depends on their metabolic modification, their environmental recurrence, and biochemical redundancy, as predicted by the genetic assimilation hypothesis. Metabolized carotenoids caused less stochastic variation in feather structure and were more closely integrated with feather growth than were dietary carotenoids of the same molecular weight. These patterns were driven by the recurrence of organism-carotenoid associations: commonly used dietary carotenoids and biochemically redundant derived carotenoids caused less stochastic variation in feather structure than did rarely used or biochemically unique compounds. We discuss implications of genetic assimilation processes for the evolutionary diversification of diet-dependent animal coloration.

  12. Cortical plasticity within and across lifetimes: How can development inform us about phenotypic transformations?

    Directory of Open Access Journals (Sweden)

    James C Dooley

    2013-10-01

    Full Text Available The neocortex is the part of the mammalian brain that is involved in perception, cognition, and volitional motor control. It is a highly dynamic structure that is dramatically altered within the lifetime of an animal and in different lineages throughout the course of evolution. These alterations account for the remarkable variations in behavior that species exhibit. Of particular interest is how these cortical phenotypes change within the lifetime of the individual and eventually evolve in species over time. Because we cannot study the evolution of the neocortex directly we use comparative analysis to appreciate the types of changes that have been made to the neocortex and the similarities that exist across taxa. Developmental studies inform us about how these phenotypic transitions may arise by alterations in developmental cascades or changes in the physical environment in which the brain develops. Both genes and the sensory environment contribute to aspects of the phenotype and similar features, such as the size of a cortical field, can be altered in a variety of ways. Although both genes and the laws of physics place constraints on the evolution of the neocortex, mammals have evolved a number of mechanisms that allow them to loosen these constraints and often alter the course of their own evolution.

  13. Integrating evo-devo with ecology for a better understanding of phenotypic evolution.

    Science.gov (United States)

    Santos, M Emília; Berger, Chloé S; Refki, Peter N; Khila, Abderrahman

    2015-11-01

    Evolutionary developmental biology (evo-devo) has provided invaluable contributions to our understanding of the mechanistic relationship between genotypic and phenotypic change. Similarly, evolutionary ecology has greatly advanced our understanding of the relationship between the phenotype and the environment. To fully understand the evolution of organismal diversity, a thorough integration of these two fields is required. This integration remains highly challenging because model systems offering a rich ecological and evolutionary background, together with the availability of developmental genetic tools and genomic resources, are scarce. In this review, we introduce the semi-aquatic bugs (Gerromorpha, Heteroptera) as original models well suited to study why and how organisms diversify. The Gerromorpha invaded water surfaces over 200 mya and diversified into a range of remarkable new forms within this new ecological habitat. We summarize the biology and evolutionary history of this group of insects and highlight a set of characters associated with the habitat change and the diversification that followed. We further discuss the morphological, behavioral, molecular and genomic tools available that together make semi-aquatic bugs a prime model for integration across disciplines. We present case studies showing how the implementation and combination of these approaches can advance our understanding of how the interaction between genotypes, phenotypes and the environment drives the evolution of distinct morphologies. Finally, we explain how the same set of experimental designs can be applied in other systems to address similar biological questions. © The Author 2015. Published by Oxford University Press.

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

    Science.gov (United States)

    Sasaki, Tomoyuki; Kishi, Shuji

    2013-01-01

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

  15. Developmental constraints revealed by co-variation within and among molar rows in two murine rodents.

    Science.gov (United States)

    Renaud, Sabrina; Pantalacci, Sophie; Quéré, Jean-Pierre; Laudet, Vincent; Auffray, Jean-Christophe

    2009-01-01

    Morphological integration corresponds to interdependency between characters that can arise from several causes. Proximal causes of integration include that different phenotypic features may share common genetic sets and/or interact during their development. Ultimate causes may be the prolonged effect of selection favoring integration of functionally interacting characters, achieved by the molding of these proximal causes. Strong and direct interactions among successive teeth of a molar row are predicted by genetic and developmental evidences. Functional constraints related to occlusion, however, should have selected more strongly for a morphological integration of occluding teeth and a corresponding evolution of the underlying developmental and genetic pathways. To investigate how these predictions match the patterns of phenotypic integration, we studied the co-variation among the six molars of the murine molar row, focusing on two populations of house mice (Mus musculus domesticus) and wood mice (Apodemus sylvaticus). The size and shape of the three upper and lower molars were quantified and compared. Our results evidenced similar patterns in both species, size being more integrated than shape among all the teeth, and both size and shape co-varying strongly between adjacent teeth, but also between occluding teeth. Strong co-variation within each molar row is in agreement with developmental models showing a cascade influence of the first molar on the subsequent molars. In contrast, the strong co-variation between molars of the occluding tooth rows confirms that functional constraints molded patterns of integration and probably the underlying developmental pathways despite the low level of direct developmental interactions occurring among molar rows. These patterns of co-variation are furthermore conserved between the house mouse and the wood mouse that diverged >10 Ma, suggesting that they may constitute long-running constraints to the diversification of the murine

  16. Sexual dysfunction within an adult developmental perspective.

    Science.gov (United States)

    Fagan, P J; Meyer, J K; Schmidt, C W

    1986-01-01

    The focus of this paper is on the adult who has adequately mastered the oedipal stage of psychosexual development and who presents with a sexual dysfunction. Drawing on the developmental sequence of Erik Erikson, the authors suggest that failure to address adequately an adult psychosocial crisis may result in sexual dysfunction. There may be both adult developmental deficits and regression to adolescent and adult stages previously negotiated. Both may be symptomatically represented by sexual dysfunction. The authors urge that the sexual and marital problems be evaluated within an adult developmental framework and that the therapy address the psychosocial issues which are appropriate to the developmental stage of the patient.

  17. Developmental constraints on behavioural flexibility.

    Science.gov (United States)

    Holekamp, Kay E; Swanson, Eli M; Van Meter, Page E

    2013-05-19

    We suggest that variation in mammalian behavioural flexibility not accounted for by current socioecological models may be explained in part by developmental constraints. From our own work, we provide examples of constraints affecting variation in behavioural flexibility, not only among individuals, but also among species and higher taxonomic units. We first implicate organizational maternal effects of androgens in shaping individual differences in aggressive behaviour emitted by female spotted hyaenas throughout the lifespan. We then compare carnivores and primates with respect to their locomotor and craniofacial adaptations. We inquire whether antagonistic selection pressures on the skull might impose differential functional constraints on evolvability of skulls and brains in these two orders, thus ultimately affecting behavioural flexibility in each group. We suggest that, even when carnivores and primates would theoretically benefit from the same adaptations with respect to behavioural flexibility, carnivores may nevertheless exhibit less behavioural flexibility than primates because of constraints imposed by past adaptations in the morphology of the limbs and skull. Phylogenetic analysis consistent with this idea suggests greater evolutionary lability in relative brain size within families of primates than carnivores. Thus, consideration of developmental constraints may help elucidate variation in mammalian behavioural flexibility.

  18. A developmental metatheory of psychopathology.

    Science.gov (United States)

    Karasu, T B

    1994-01-01

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

  19. Developmental constraint of insect audition

    Directory of Open Access Journals (Sweden)

    Strauß Johannes

    2006-12-01

    Full Text Available Abstract Background Insect ears contain very different numbers of sensory cells, from only one sensory cell in some moths to thousands of sensory cells, e.g. in cicadas. These differences still await functional explanation and especially the large numbers in cicadas remain puzzling. Insects of the different orders have distinct developmental sequences for the generation of auditory organs. These sensory cells might have different functions depending on the developmental stages. Here we propose that constraints arising during development are also important for the design of insect ears and might influence cell numbers of the adults. Presentation of the hypothesis We propose that the functional requirements of the subadult stages determine the adult complement of sensory units in the auditory system of cicadas. The hypothetical larval sensory organ should function as a vibration receiver, representing a functional caenogenesis. Testing the hypothesis Experiments at different levels have to be designed to test the hypothesis. Firstly, the neuroanatomy of the larval sense organ should be analyzed to detail. Secondly, the function should be unraveled neurophysiologically and behaviorally. Thirdly, the persistence of the sensory cells and the rebuilding of the sensory organ to the adult should be investigated. Implications of the hypothesis Usually, the evolution of insect ears is viewed with respect to physiological and neuronal mechanisms of sound perception. This view should be extended to the development of sense organs. Functional requirements during postembryonic development may act as constraints for the evolution of adult organs, as exemplified with the auditory system of cicadas.

  20. Male-mediated developmental toxicity

    Directory of Open Access Journals (Sweden)

    Diana Anderson

    2014-02-01

    Full Text Available Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

  1. Cattle phenotypes can disguise their maternal ancestry.

    Science.gov (United States)

    Srirattana, Kanokwan; McCosker, Kieren; Schatz, Tim; St John, Justin C

    2017-06-26

    Cattle are bred for, amongst other factors, specific traits, including parasite resistance and adaptation to climate. However, the influence and inheritance of mitochondrial DNA (mtDNA) are not usually considered in breeding programmes. In this study, we analysed the mtDNA profiles of cattle from Victoria (VIC), southern Australia, which is a temperate climate, and the Northern Territory (NT), the northern part of Australia, which has a tropical climate, to determine if the mtDNA profiles of these cattle are indicative of breed and phenotype, and whether these profiles are appropriate for their environments. A phylogenetic tree of the full mtDNA sequences of different breeds of cattle, which were obtained from the NCBI database, showed that the mtDNA profiles of cattle do not always reflect their phenotype as some cattle with Bos taurus phenotypes had Bos indicus mtDNA, whilst some cattle with Bos indicus phenotypes had Bos taurus mtDNA. Using D-loop sequencing, we were able to contrast the phenotypes and mtDNA profiles from different species of cattle from the 2 distinct cattle breeding regions of Australia. We found that 67 of the 121 cattle with Bos indicus phenotypes from NT (55.4%) had Bos taurus mtDNA. In VIC, 92 of the 225 cattle with Bos taurus phenotypes (40.9%) possessed Bos indicus mtDNA. When focusing on oocytes from cattle with the Bos taurus phenotype in VIC, their respective oocytes with Bos indicus mtDNA had significantly lower levels of mtDNA copy number compared with oocytes possessing Bos taurus mtDNA (P cattle with a Bos taurus phenotype. The phenotype of cattle is not always related to their mtDNA profiles. MtDNA profiles should be considered for breeding programmes as they also influence phenotypic traits and reproductive capacity in terms of oocyte quality.

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

    Science.gov (United States)

    Molenaar, Peter C. M.

    2015-01-01

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

  3. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    NARCIS (Netherlands)

    Kohler, S.; Doelken, S.C.; Mungall, C.J.; Bauer, S.; Firth, H.V.; Bailleul-Forestier, I.; Black, G.C.M.; Brown, D.L.; Brudno, M.; Campbell, J.; FitzPatrick, D.R.; Eppig, J.T.; Jackson, A.P.; Freson, K.; Girdea, M.; Helbig, I.; Hurst, J.A.; Jahn, J.; Jackson, L.G.; Kelly, A.M.; Ledbetter, D.H.; Mansour, S.; Martin, C.L.; Moss, C.; Mumford, A.; Ouwehand, W.H.; Park, S.M.; Riggs, E.R.; Scott, R.H.; Sisodiya, S.; Vooren, S. van der; Wapner, R.J.; Wilkie, A.O.; Wright, C.F.; Silfhout, A.T. van; Leeuw, N. de; Vries, B. de; Washingthon, N.L.; Smith, C.L.; Westerfield, M.; Schofield, P.; Ruef, B.J.; Gkoutos, G.V.; Haendel, M.; Smedley, D.; Lewis, S.E.; Robinson, P.N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have

  4. Developmental Origin of Reproductive and Metabolic Dysfunctions: Androgenic Versus Estrogenic Reprogramming

    Science.gov (United States)

    Padmanabhan, Vasantha; Veiga-Lopez, Almudena

    2013-01-01

    Polycystic ovary syndrome (PCOS) is one of the most common fertility disorders, affecting several million women worldwide. Women with PCOS manifest neuroendocrine, ovarian, and metabolic defects. A large number of animal models have evolved to understand the etiology of PCOS. These models provide support for the contributing role of excess steroids during development in programming the PCOS phenotype. However, considerable phenotypic variability is evident across animal models, depending on the quality of the steroid administered and the perinatal time of treatment relative to the developmental trajectory of the fetus/offspring. This review focuses on the reproductive and metabolic phenotypes of the various PCOS animal models that have evolved in the last decade to delineate the relative roles of androgens and estrogens in relation to the timing of exposure in programming the various dysfunctions that are part and parcel of the PCOS phenotype. Furthermore, the review addresses the contributory role of the postnatal metabolic environment in exaggerating the severity of the phenotype, the translational relevance of the various animal models to PCOS, and areas for future research. PMID:21710394

  5. Developmental toxicity of engineered nanomaterials in rodents

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-05-15

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

  6. Daddy issues: paternal effects on phenotype.

    Science.gov (United States)

    Rando, Oliver J

    2012-11-09

    The once popular and then heretical idea that ancestral environment can affect the phenotype of future generations is coming back into vogue due to advances in the field of epigenetic inheritance. How paternal environmental conditions influence the phenotype of progeny is now a tractable question, and researchers are exploring potential mechanisms underlying such effects. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Phenotypes of organ involvement in sarcoidosis

    NARCIS (Netherlands)

    Schupp, Jonas Christian; Freitag-Wolf, Sandra; Bargagli, Elena; Mihailović-Vučinić, Violeta; Rottoli, Paola; Grubanovic, Aleksandar; Müller, Annegret; Jochens, Arne; Tittmann, Lukas; Schnerch, Jasmin; Olivieri, Carmela; Fischer, Annegret; Jovanovic, Dragana; Filipovic, Snežana; Videnovic-Ivanovic, Jelica; Bresser, Paul; Jonkers, René; O'Reilly, Kate; Ho, Ling-Pei; Gaede, Karoline I.; Zabel, Peter; Dubaniewicz, Anna; Marshall, Ben; Kieszko, Robert; Milanowski, Janusz; Günther, Andreas; Weihrich, Anette; Petrek, Martin; Kolek, Vitezslav; Keane, Michael P.; O'Beirne, Sarah; Donnelly, Seamas; Haraldsdottir, Sigridur Olina; Jorundsdottir, Kristin B.; Costabel, Ulrich; Bonella, Francesco; Wallaert, Benoît; Grah, Christian; Peroš-Golubičić, Tatjana; Luisetti, Mauritio; Kadija, Zamir; Pabst, Stefan; Grohé, Christian; Strausz, János; Vašáková, Martina; Sterclova, Martina; Millar, Ann; Homolka, Jiří; Slováková, Alena; Kendrick, Yvonne; Crawshaw, Anjali; Wuyts, Wim; Spencer, Lisa; Pfeifer, Michael; Valeyre, Dominique; Poletti, Venerino; Wirtz, Hubertus; Prasse, Antje; Schreiber, Stefan; Krawczak, Michael; Müller-Quernheim, Joachim

    2018-01-01

    Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis. The baseline

  8. Emerging semantics to link phenotype and environment

    Directory of Open Access Journals (Sweden)

    Anne E. Thessen

    2015-12-01

    Full Text Available Understanding the interplay between environmental conditions and phenotypes is a fundamental goal of biology. Unfortunately, data that include observations on phenotype and environment are highly heterogeneous and thus difficult to find and integrate. One approach that is likely to improve the status quo involves the use of ontologies to standardize and link data about phenotypes and environments. Specifying and linking data through ontologies will allow researchers to increase the scope and flexibility of large-scale analyses aided by modern computing methods. Investments in this area would advance diverse fields such as ecology, phylogenetics, and conservation biology. While several biological ontologies are well-developed, using them to link phenotypes and environments is rare because of gaps in ontological coverage and limits to interoperability among ontologies and disciplines. In this manuscript, we present (1 use cases from diverse disciplines to illustrate questions that could be answered more efficiently using a robust linkage between phenotypes and environments, (2 two proof-of-concept analyses that show the value of linking phenotypes to environments in fishes and amphibians, and (3 two proposed example data models for linking phenotypes and environments using the extensible observation ontology (OBOE and the Biological Collections Ontology (BCO; these provide a starting point for the development of a data model linking phenotypes and environments.

  9. Haptoglobin Phenotypes and Hypertension in Indigenous Zambians ...

    African Journals Online (AJOL)

    Haptoglobin Phenotypes and Hypertension in Indigenous Zambians at the University Teaching Hospital, Lusaka, Zambia. MM Phiri, T Kaile, FM Goma. Abstract. Objectives: The aim of the study was to investigate the association between presence of haptoglobin phenotypes and hypertension in indigenous Zambian patients ...

  10. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-01

    a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology

  11. The Neuroanatomy of the Autistic Phenotype

    Science.gov (United States)

    Fahim, Cherine; Meguid, Nagwa A.; Nashaat, Neveen H.; Yoon, Uicheul; Mancini-Marie, Adham; Evans, Alan C.

    2012-01-01

    The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X…

  12. Two developmentally temporal quantitative trait loci underlie convergent evolution of increased branchial bone length in sticklebacks

    Science.gov (United States)

    Erickson, Priscilla A.; Glazer, Andrew M.; Cleves, Phillip A.; Smith, Alyson S.; Miller, Craig T.

    2014-01-01

    In convergent evolution, similar phenotypes evolve repeatedly in independent populations, often reflecting adaptation to similar environments. Understanding whether convergent evolution proceeds via similar or different genetic and developmental mechanisms offers insight towards the repeatability and predictability of evolution. Oceanic populations of threespine stickleback fish, Gasterosteus aculeatus, have repeatedly colonized countless freshwater lakes and streams, where new diets lead to morphological adaptations related to feeding. Here, we show that heritable increases in branchial bone length have convergently evolved in two independently derived freshwater stickleback populations. In both populations, an increased bone growth rate in juveniles underlies the convergent adult phenotype, and one population also has a longer cartilage template. Using F2 crosses from these two freshwater populations, we show that two quantitative trait loci (QTL) control branchial bone length at distinct points in development. In both populations, a QTL on chromosome 21 controls bone length throughout juvenile development, and a QTL on chromosome 4 controls bone length only in adults. In addition to these similar developmental profiles, these QTL show similar chromosomal locations in both populations. Our results suggest that sticklebacks have convergently evolved longer branchial bones using similar genetic and developmental programmes in two independently derived populations. PMID:24966315

  13. High-resolution SNP array analysis of patients with developmental disorder and normal array CGH results

    Directory of Open Access Journals (Sweden)

    Siggberg Linda

    2012-09-01

    Full Text Available Abstract Background Diagnostic analysis of patients with developmental disorders has improved over recent years largely due to the use of microarray technology. Array methods that facilitate copy number analysis have enabled the diagnosis of up to 20% more patients with previously normal karyotyping results. A substantial number of patients remain undiagnosed, however. Methods and Results Using the Genome-Wide Human SNP array 6.0, we analyzed 35 patients with a developmental disorder of unknown cause and normal array comparative genomic hybridization (array CGH results, in order to characterize previously undefined genomic aberrations. We detected no seemingly pathogenic copy number aberrations. Most of the vast amount of data produced by the array was polymorphic and non-informative. Filtering of this data, based on copy number variant (CNV population frequencies as well as phenotypically relevant genes, enabled pinpointing regions of allelic homozygosity that included candidate genes correlating to the phenotypic features in four patients, but results could not be confirmed. Conclusions In this study, the use of an ultra high-resolution SNP array did not contribute to further diagnose patients with developmental disorders of unknown cause. The statistical power of these results is limited by the small size of the patient cohort, and interpretation of these negative results can only be applied to the patients studied here. We present the results of our study and the recurrence of clustered allelic homozygosity present in this material, as detected by the SNP 6.0 array.

  14. Neuroimaging of developmental psychopathologies: the importance of self-regulatory and neuroplastic processes in adolescence.

    Science.gov (United States)

    Spessot, Alexandra L; Plessen, Kerstin J; Peterson, Bradley S

    2004-06-01

    Normal brain maturational and developmental processes, together with plastic reorganization of the brain in response to experiential demands, contribute to the acquisition of improved capacities for self-regulation and impulse control during adolescence. The frontal lobe is a main focus for these developmental and plastic processes during the transition from adolescence into adulthood. Tourette syndrome (TS), defined as the chronic presence of motor and vocal tics, has been increasingly conceptualized as a disorder of impaired self-regulatory control. This disordered control is thought to give rise to semicompulsory urges to perform the movements that constitute simple tics, complex tics, or compulsions. Neuroimaging studies suggest that the expression of the genetic diathesis to TS is influenced by genetic and nongenetic factors affecting activity-dependent reorganization of neuroregulatory systems, thereby influencing the phenotype, illness severity, and adult outcome of tic disorders. Similar developmental processes during adolescence likely determine the phenotype and natural history of a broad range of other complex neuropsychiatric disorders of childhood onset, and they likely contribute to the acquisition of improved self-regulatory capacities that characterize normal adolescent development.

  15. The Phenotypic Effects of Royal Jelly on Wild-Type D. melanogaster Are Strain-Specific.

    Directory of Open Access Journals (Sweden)

    Stefanie L Morgan

    Full Text Available The role for royal jelly (RJ in promoting caste differentiation of honeybee larvae into queens rather than workers is well characterized. A recent study demonstrated that this poorly understood complex nutrition drives strikingly similar phenotypic effects in Drosophila melanogaster, such as increased body size and reduced developmental time, making possible the use of D. melanogaster as a model system for the genetic analysis of the cellular mechanisms underlying RJ and caste differentiation. We demonstrate here that RJ increases the body size of some wild-type strains of D. melanogaster but not others, and report significant delays in developmental time in all flies reared on RJ. These findings suggest that cryptic genetic variation may be a factor in the D. melanogaster response to RJ, and should be considered when attempting to elucidate response mechanisms to environmental changes in non-honeybee species.

  16. Broad spectrum of neuropsychiatric phenotypes associated with white matter disease in PTEN hamartoma tumor syndrome.

    Science.gov (United States)

    Balci, Tugce B; Davila, Jorge; Lewis, Denice; Boafo, Addo; Sell, Erick; Richer, Julie; Nikkel, Sarah M; Armour, Christine M; Tomiak, Eva; Lines, Matthew A; Sawyer, Sarah L

    2018-01-01

    White matter lesions have been described in patients with PTEN hamartoma tumor syndrome (PHTS). How these lesions correlate with the neurocognitive features associated with PTEN mutations, such as autism spectrum disorder (ASD) or developmental delay, has not been well established. We report nine patients with PTEN mutations and white matter changes on brain magnetic resonance imaging (MRI), eight of whom were referred for reasons other than developmental delay or ASD. Their clinical presentations ranged from asymptomatic macrocephaly with normal development/intellect, to obsessive compulsive disorder, and debilitating neurological disease. To our knowledge, this report constitutes the first detailed description of PTEN-related white matter changes in adult patients and in children with normal development and intelligence. We present a detailed assessment of the neuropsychological phenotype of our patients and discuss the relationship between the wide array of neuropsychiatric features and observed white matter findings in the context of these individuals. © 2017 Wiley Periodicals, Inc.

  17. Evolving phenotypic networks in silico.

    Science.gov (United States)

    François, Paul

    2014-11-01

    Evolved gene networks are constrained by natural selection. Their structures and functions are consequently far from being random, as exemplified by the multiple instances of parallel/convergent evolution. One can thus ask if features of actual gene networks can be recovered from evolutionary first principles. I review a method for in silico evolution of small models of gene networks aiming at performing predefined biological functions. I summarize the current implementation of the algorithm, insisting on the construction of a proper "fitness" function. I illustrate the approach on three examples: biochemical adaptation, ligand discrimination and vertebrate segmentation (somitogenesis). While the structure of the evolved networks is variable, dynamics of our evolved networks are usually constrained and present many similar features to actual gene networks, including properties that were not explicitly selected for. In silico evolution can thus be used to predict biological behaviours without a detailed knowledge of the mapping between genotype and phenotype. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  18. Adjusting phenotypes by noise control.

    Directory of Open Access Journals (Sweden)

    Kyung H Kim

    2012-01-01

    Full Text Available Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks.

  19. Federated Tensor Factorization for Computational Phenotyping

    Science.gov (United States)

    Kim, Yejin; Sun, Jimeng; Yu, Hwanjo; Jiang, Xiaoqian

    2017-01-01

    Tensor factorization models offer an effective approach to convert massive electronic health records into meaningful clinical concepts (phenotypes) for data analysis. These models need a large amount of diverse samples to avoid population bias. An open challenge is how to derive phenotypes jointly across multiple hospitals, in which direct patient-level data sharing is not possible (e.g., due to institutional policies). In this paper, we developed a novel solution to enable federated tensor factorization for computational phenotyping without sharing patient-level data. We developed secure data harmonization and federated computation procedures based on alternating direction method of multipliers (ADMM). Using this method, the multiple hospitals iteratively update tensors and transfer secure summarized information to a central server, and the server aggregates the information to generate phenotypes. We demonstrated with real medical datasets that our method resembles the centralized training model (based on combined datasets) in terms of accuracy and phenotypes discovery while respecting privacy. PMID:29071165

  20. Nordic research infrastructures for plant phenotyping

    Directory of Open Access Journals (Sweden)

    Kristiina Himanen

    2018-03-01

    Full Text Available Plant phenomics refers to the systematic study of plant phenotypes. Together with closely monitored, controlled climates, it provides an essential component for the integrated analysis of genotype-phenotype-environment interactions. Currently, several plant growth and phenotyping facilities are under establishment globally, and numerous facilities are already in use. Alongside the development of the research infrastructures, several national and international networks have been established to support shared use of the new methodology. In this review, an overview is given of the Nordic plant phenotyping and climate control facilities. Since many areas of phenomics such as sensor-based phenotyping, image analysis and data standards are still developing, promotion of educational and networking activities is especially important. These facilities and networks will be instrumental in tackling plant breeding and plant protection challenges. They will also provide possibilities to study wild species and their ecological interactions under changing Nordic climate conditions.

  1. The Nature of Stable Insomnia Phenotypes

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L.

    2015-01-01

    Study Objectives: We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Design: Longitudinal. Setting: Urban, community-based. Participants: Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). Interventions: None. Measurements and results: At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the “neither criterion” phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. Conclusions: By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With

  2. The search for Pleiades in trait constellations: functional integration and phenotypic selection in the complex flowers of Morrenia brachystephana (Apocynaceae).

    Science.gov (United States)

    Baranzelli, M C; Sérsic, A N; Cocucci, A A

    2014-04-01

    Pollinator-mediated natural selection on single traits, such as corolla tube or spur length, has been well documented. However, flower phenotypes are usually complex, and selection is expected to act on several traits that functionally interact rather than on a single isolated trait. Despite the fact that selection on complex phenotypes is expectedly widespread, multivariate selection modelling on such phenotypes still remains under-explored in plants. Species of the subfamily Asclepiadoideae (Apocynaceae) provide an opportunity to study such complex flower contrivances integrated by fine-scaled organs from disparate developmental origin. We studied the correlation structure among linear floral traits (i) by testing a priori morphological, functional or developmental hypotheses among traits and (ii) by exploring the organization of flower covariation, considering alternative expectations of modular organization or whole flower integration through conditional dependence analysis (CDA) and integration matrices. The phenotypic selection approach was applied to determine whether floral traits involved in the functioning of the pollination mechanism were affected by natural selection. Floral integration was low, suggesting that flowers are organized in more than just one correlation pleiad; our hypothetical functional correlation matrix was significantly correlated with the empirical matrix, and the CDA revealed three putative modules. Analyses of phenotypic selection showed significant linear and correlational gradients, lending support to expectations of functional interactions between floral traits. Significant correlational selection gradients found involved traits of different floral whorls, providing evidence for the existence of functional integration across developmental domains. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  3. The search for evolutionary developmental origins of aging in zebrafish: a novel intersection of developmental and senescence biology in the zebrafish model system.

    Science.gov (United States)

    Kishi, Shuji

    2011-09-01

    Senescence may be considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena during the process of aging. We investigated whether any relationship exists between the regulatory mechanisms that function in early development and in senescence using the zebrafish (Danio rerio), a small freshwater fish and a useful model animal for genetic studies. We conducted experiments to isolate zebrafish mutants expressing an apparent senescence phenotype during embryogenesis (embryonic senescence). Some of the genes we thereby identified had already been associated with cellular senescence and chronological aging in other organisms, but many had not yet been linked to these processes. Complete loss-of-function of developmentally essential genes induce embryonic (or larval) lethality, whereas it seems like their partial loss-of-function (i.e., decrease-of-function by heterozygote or hypomorphic mutations) still remains sufficient to go through the early developmental process because of its adaptive plasticity or rather heterozygote advantage. However, in some cases, such partial loss-of-function of genes compromise normal homeostasis due to haploinsufficiency later in adult life having many environmental stress challenges. By contrast, any heterozygote-advantageous genes might gain a certain benefit(s) (much more fitness) by such partial loss-of-function later in life. Physiological senescence may evolutionarily arise from both genetic and epigenetic drifts as well as from losing adaptive developmental plasticity in face of stress signals from the external environment that interacts with functions of multiple genes rather than effects of only a single gene mutation or defect. Previously uncharacterized developmental genes may thus mediate the aging process and play a pivotal role in senescence. Moreover, unexpected senescence-related genes might also be involved in the early developmental process and

  4. Rethinking developmental toxicity testing: Evolution or revolution?

    NARCIS (Netherlands)

    Scialli, Anthony R; Daston, George; Chen, Connie; Coder, Prägati S; Euling, Susan Y; Foreman, Jennifer; Hoberman, Alan M; Hui, Julia; Knudsen, Thomas; Makris, Susan L; Morford, LaRonda; Piersma, Aldert H; Stanislaus, Dinesh; Thompson, Kary E

    2018-01-01

    Current developmental toxicity testing adheres largely to protocols suggested in 1966 involving the administration of test compound to pregnant laboratory animals. After more than 50 years of embryo-fetal development testing, are we ready to consider a different approach to human developmental

  5. Developmental neurotoxicity of Propylthiouracil in rats

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Hansen, P.; Christiansen, S.

    2007-01-01

    early in pregnancy may cause adverse effects on the offspring. This has led to increased concern about thyroid hormone disrupting chemicals (TDCs) in our environment. We have studied how developmental exposure to the known antithyroid agent propylthiouracil (PTU) affects the development of rat pups...... behaviour and hearing function. This supports that exposure to TDC's in general may cause long-lasting developmental neurotoxicity....

  6. Are Students with Developmental Dyslexia Neurologically Different?

    Science.gov (United States)

    Goldsmith-Phillips, Josephine

    1994-01-01

    Reviews the controversy over a biological basis for developmental dyslexia and illustrates it with two case studies of junior high school students. Reviews neurological evidence for developmental dyslexia, and proposes seven signs characteristic of reading disability that may qualify as dyslexia. (SR)

  7. Essential Role of Culture in Developmental Psychology

    Science.gov (United States)

    Miller, Joan G.

    2005-01-01

    This chapter argues for the essential role of culture in forming the basic constructs and theories of developmental psychology. The case is made for the need to overcome the cultural insularity of core developmental concepts and methods in order to create a psychology that is more truly universal.

  8. Delaying Developmental Mathematics: The Characteristics and Costs

    Science.gov (United States)

    Johnson, Marianne; Kuennen, Eric

    2004-01-01

    This paper investigates which students delay taking a required developmental mathematics course and the impact of delay on student performance in introductory microeconomics. Analysis of a sample of 1462 students at a large Midwestern university revealed that, although developmental-level mathematics students did not reach the same level of…

  9. Unpacking developmental local government using Soft Systems ...

    African Journals Online (AJOL)

    Unpacking developmental local government using Soft Systems Methodology and MCDA tools. L Scott. Abstract. This paper presents two different analytical approaches that may be useful in developing an understanding of developmental local government (DLG). DLG implies a significant commitment with respect to ...

  10. Desiccation stress induces developmental heterochrony in ...

    Indian Academy of Sciences (India)

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

  11. Psychological Resources of Adults with Developmental Dyslexia

    Science.gov (United States)

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

    2014-01-01

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

  12. Prevalence and sociodemographic determinants of developmental ...

    African Journals Online (AJOL)

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

  13. Introducing Newspapers in Developmental Reading Classes

    Science.gov (United States)

    Karstadt, Roberta; Rey, Victoria M.

    2009-01-01

    Newspapers are an effective educational and motivational tool in developmental reading classes. However, many students are unfamiliar with newspapers and read them infrequently. In order to foster newspaper reading and familiarize the college freshmen enrolled in their developmental reading classes with newspapers, the writers of this article…

  14. Developmental hip dysplasia in adolescence

    Directory of Open Access Journals (Sweden)

    Vukašinović Zoran

    2009-01-01

    Full Text Available The authors define adolescence and developmental dysplasia of the hip (DDH. Special attention is paid to pathological findings characteristic of DDH in adolescence (unrecognized and untreated DDH; treated DDH, but non-terminated treatment; DDH diagnosed with delay, inadequately treated, with complications. The authors emphasise that DDH treatment has to be successfully terminated well before the adolescence; possibilities are explained on management modes at the time of adolescence, and possible persons guilty for the persistence of later hip problems are indicated. Based on the authors' experience and having in mind all surgical possibilities for the treatment (pelvic osteotomies, femoral osteotomies, trochanteroplasties, leg length equalization procedures the authors propose treatment protocols. The intention is to provide better treatment results and to prevent secondary hip arthrosis. Furthermore, how to improve the struggle against DDH is suggested.

  15. Presentations: Adverse Outcome Pathways for Abnormal Phenotypes

    Science.gov (United States)

    Birth defects affect many infants and the etiology for most are unknown. Although environmental factors are known to influence pregnancy outcome, thousands of chemicals, present in the environment, are untested for developmental toxicity potential. Application of computational p...

  16. Future Directions in Sleep and Developmental Psychopathology.

    Science.gov (United States)

    Meltzer, Lisa J

    2017-01-01

    It is critical for psychologists to gain a better understanding about the intersection between sleep and developmental psychopathology. However, while many strive to answer the question of whether sleep causes developmental psychopathology, or vice versa, ultimately the relationship between sleep and developmental psychopathology is complex and dynamic. This article considers future directions in the field of clinical child and adolescent psychology that go beyond this mechanistic question, highlighting areas important to address for clinicians and researchers who strive to better understand how best to serve children and adolescents with developmental psychopathology. Questions are presented about what is normal in terms of sleep across development, the role of individual variability in terms of sleep needs and vulnerability to sleep loss, and how sleep may serve as a risk or resilience factor for developmental psychopathology, concluding with considerations for interventions.

  17. Early Intervention in Children with Developmental Disabilities

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2016-01-01

    Full Text Available Developmental disabilities consist of conditions that delay or impair the physical, cognitive, and/or psychological development of children. If not intervened at the earliest, these disabilities will cause significant negative impact on multiple domains of functioning such as learning, language, self-care and capacity for independent living. Common developmental disabilities include autism spectrum disorders, intellectual disabilities, developmental delay and cerebral palsy. About one fourth of young children in developing countries are at risk for or have developmental delay or disabilities. Inadequate stimulation has significant negative impact on physical, socioemotional and cognitive development of children. Hence early scientific intervention programs are necessary in the management of children at risk for developmental delay.

  18. Developmental environment mediates male seminal protein investment in Drosophila melanogaster.

    Science.gov (United States)

    Wigby, Stuart; Perry, Jennifer C; Kim, Yon-Hee; Sirot, Laura K

    2016-03-01

    Males of many species fine-tune their ejaculates in response to sperm competition risk. Resource availability and the number of competitors during development can also strongly influence sperm production. However, despite the key role of seminal proteins in mediating reproductive processes, it is unclear whether seminal protein investment is dependent on the developmental environment.We manipulated the developmental environment of Drosophila melanogaster by rearing flies at low and high density. As expected, this resulted in large and small (i.e. high and low condition) adult phenotypes, respectively.As predicted, large males produced more of two key seminal proteins, sex peptide (SP) and ovulin, and were more successful at obtaining matings with both virgin and previously mated females. However, there was only a weak and non-significant trend for large males to transfer more absolute quantities of SP at mating, and thus, small males ejaculated proportionally more of their stored accessory gland SP resources.Males transferred more receptivity-inhibiting SP to large females. Despite this, large females remated more quickly than small females and thus responded to their developmental environment over and above the quantity of SP they received.The results are consistent with two non-mutually exclusive hypotheses. First, flies might respond to condition-dependent reproductive opportunities, with (i) small males investing heavily in ejaculates when mating opportunities arise and large males strategically partitioning SP resources and (ii) small females remating at reduced rates because they have higher mating costs or need to replenish sperm less often.Second, flies may be primed by their larval environment to deal with similar adult population densities, with (i) males perceiving high density as signalling increased competition, leading small males to invest proportionally more SP resources at mating and (ii) females perceiving high density as signalling abundant

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

    Science.gov (United States)

    Kearney, Michael; Shine, Richard

    2004-07-01

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

  20. Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

    KAUST Repository

    AlShahrani, Mona; Hoehndorf, Robert

    2018-01-01

    In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease's (or patient's) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

  1. Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

    KAUST Repository

    Alshahrani, Mona

    2018-04-30

    In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease\\'s (or patient\\'s) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

  2. Proteomic analysis uncovers a metabolic phenotype in C. elegans after nhr-40 reduction of function

    International Nuclear Information System (INIS)

    Pohludka, Michal; Simeckova, Katerina; Vohanka, Jaroslav; Yilma, Petr; Novak, Petr; Krause, Michael W.; Kostrouchova, Marta; Kostrouch, Zdenek

    2008-01-01

    Caenorhabditis elegans has an unexpectedly large number (284) of genes encoding nuclear hormone receptors, most of which are nematode-specific and are of unknown function. We have exploited comparative two-dimensional chromatography of synchronized cultures of wild type C. elegans larvae and a mutant in nhr-40 to determine if proteomic approaches will provide additional insight into gene function. Chromatofocusing, followed by reversed-phase chromatography and mass spectrometry, identified altered chromatographic patterns for a set of proteins, many of which function in muscle and metabolism. Prompted by the proteomic analysis, we find that the penetrance of the developmental phenotypes in the mutant is enhanced at low temperatures and by food restriction. The combination of our phenotypic and proteomic analysis strongly suggests that NHR-40 provides a link between metabolism and muscle development. Our results highlight the utility of comparative two-dimensional chromatography to provide a relatively rapid method to gain insight into gene function

  3. Expanding the phenotypic and mutational spectrum in microcephalic osteodysplastic primordial dwarfism type I.

    Science.gov (United States)

    Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Issa, Mahmoud; Magdy, Ahmed; El-Kotoury, Ahmed; Amr, Khalda

    2012-06-01

    Mutations in the RNU4ATAC gene cause microcephalic osteodysplastic primordial dwarfism type I. It encodes U4atac, a small nuclear RNA that is a component of the minor spliceosome. Six distinct mutations in 30 patients diagnosed as microcephalic osteodysplastic primordial dwarfism type I have been described. We report on three additional patients from two unrelated families presenting with a milder phenotype of microcephalic osteodysplastic primordial dwarfism type I and metopic synostosis. Patient 1 had two novel heterozygous mutations in the 3' prime stem-loop, g.66G > C and g.124G > A while Patients 2 and 3 had a homozygous mutation g.55G > A in the 5' prime stem-loop. Although they manifested the known spectrum of clinical features of microcephalic osteodysplastic primordial dwarfism type I, they lacked evidence of severe developmental delay and neurological symptoms. These findings expand the mutational and phenotypic spectrum of this syndrome. Copyright © 2012 Wiley Periodicals, Inc.

  4. Transposition of the great arteries - a phenotype associated with 16p11.2 duplications?

    Science.gov (United States)

    Karunanithi, Zarmiga; Vestergaard, Else Marie; Lauridsen, Mette H

    2017-12-26

    Genetic analyses of patients with transposition of the great arteries have identified rare copy number variations, suggesting that they may be significant to the aetiology of the disease. This paper reports the identification of a 16p11.2 microduplication, a variation that has yet to be reported in association with transposition of the great arteries. The 16p11.2 microduplication is associated with autism spectrum disorder and developmental delay, but with highly variable phenotypic effects. Autism and attention deficit disorders are observed more frequently in children with congenital heart disease than in the general population. Neonatal surgery is proposed as a risk factor, but as yet unidentified genetic abnormalities should also be taken into account. Thus, congenital heart abnormalities may constitute a part of the phenotypic spectrum associated with duplications at 16p11.2. We suggest chromosomal microarray be considered part of the diagnostic work-up in patients with transposition of the great arteries.

  5. Hyperphosphatasia with mental retardation syndrome, expanded phenotype of PIGL related disorders

    Directory of Open Access Journals (Sweden)

    Ruqaiah Altassan

    2018-06-01

    Full Text Available Hypomorphic mutations in six different genes involved in the glycosylphosphatidylinositol (GPI biogenesis pathway are linked to Mabry syndrome (hyperphosphatasia with mental retardation syndrome, HPMRS. This report on the third affected family with a HPMRS phenotype caused by mutations in PIGL, confirming the seventh GPI biogenesis gene linked to HPMRS. Two siblings presented with the main features of HPMRS; developmental delay, cognitive impairment, seizure disorder, skeletal deformities, and high alkaline phosphatase. We identified two heterozygous mutations in the PIGL gene (P.Trp20Ter and p.Arg88Cys. PIGL mutations have been linked to another distinctive neuroectodermal disorder: CHIME syndrome. The clinical picture of our patients expands the spectrum of PIGL-related phenotypes. Keywords: GPI biogenesis, Hyperphosphatasia mental retardation syndrome (HPMRS, Mabry syndrome, PIGL gene, CHIME syndrome

  6. Reversible Age-Related Phenotypes Induced during Larval Quiescence in C. elegans

    Science.gov (United States)

    Roux, Antoine E.; Langhans, Kelley; Huynh, Walter; Kenyon, Cynthia

    2017-01-01

    Summary Cells can enter quiescent states in which cell cycling and growth are suspended. We find that during a long developmental arrest (quiescence) induced by starvation, newly-hatched C. elegans acquire features associated with impaired proteostasis and aging: mitochondrial fission, ROS production, protein aggregation, decreased proteotoxic-stress resistance, and at the organismal level, decline of mobility and high mortality. All signs of aging but one, the presence of protein aggregates, were reversed upon return to development induced by feeding. The endoplasmic reticulum receptor IRE-1 is completely required for recovery, and the downstream transcription factor XBP-1, as well as a protein kinase, KGB-1, are partially required. Interestingly, kgb-1(−) mutants that do recover fail to reverse aging-like mitochondrial phenotypes and have a short adult lifespan. Our study describes the first pathway that reverses phenotypes of aging at the exit of prolonged quiescence. PMID:27304510

  7. 29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype.

    Science.gov (United States)

    Monin, Marie-Lorraine; Mignot, Cyril; De Lonlay, Pascale; Héron, Bénédicte; Masurel, Alice; Mathieu-Dramard, Michèle; Lenaerts, Catherine; Thauvin, Christel; Gérard, Marion; Roze, Emmanuel; Jacquette, Aurélia; Charles, Perrine; de Baracé, Claire; Drouin-Garraud, Valérie; Khau Van Kien, Philippe; Cormier-Daire, Valérie; Mayer, Michèle; Ogier, Hélène; Brice, Alexis; Seta, Nathalie; Héron, Delphine

    2014-12-11

    PMM2-CDG (formerly known as CDG Ia) a deficiency in phosphomannomutase, is the most frequent congenital disorder of glycosylation. The phenotype encompasses a wide range of neurological and non-neurological manifestations comprising cerebellar atrophy and intellectual deficiency. The phenotype of the disorder is well characterized in children but the long term course of the disease is unknown and the phenotype of late onset forms has not been comprehensively described. We thus retrospectively collected the clinical, biological and radiological data of 29 French PMM2-CDG patients aged 15 years or more with a proven molecular diagnosis (16 females and 13 males). In addition, thirteen of these patients were reexamined at the time of the study to obtain detailed information. 27 of the 29 patients had a typical PMM2-CDG phenotype, with infantile hypotonia, strabismus, developmental delay followed by intellectual deficiency, epilepsy, retinitis pigmentosa and/or visceral manifestations. The main health problems for these patients as teenagers and in adulthood were primary ovarian insufficiency, growth retardation, coagulation anomalies and thrombotic events, skeletal deformities and osteopenia/osteoporosis, retinitis pigmentosa, as well as peripheral neuropathy. Three patients had never walked and three lost their ability to walk. The two remaining patients had a late-onset phenotype unreported to date. All patients (n = 29) had stable cerebellar atrophy. Our findings are in line with those of previous adult PMM2-CDG cohorts and points to the need for a multidisciplinary approach to the follow up of PMM2-CDG patients to prevent late complications. Additionally, our findings add weight to the view that PMM2-CDG may be diagnosed in teenage/adult patients with cerebellar atrophy, even in the absence of intellectual deficiency or non-neurological involvement.

  8. Targeting phenotypically tolerant Mycobacterium tuberculosis

    Science.gov (United States)

    Gold, Ben; Nathan, Carl

    2016-01-01

    While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

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

    Science.gov (United States)

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

    2016-05-01

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

  10. ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social-communication difficulties

    OpenAIRE

    St Pourcain, B.; Robinson, E.; Anttila, V.; Sullivan, B.; Maller, J.; Golding, J.; Skuse, D.; Ring, S.; Evans, D.; Zammit, S.; Fisher, S.; Neale, B.; Anney, R.; Ripke, S.; Hollegaard, M.

    2017-01-01

    Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and\\ud schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early\\ud childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether\\ud overlap in common genetic influences between these clinical conditions and impairments in social communication depends ...

  11. PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution

    OpenAIRE

    Mirzaa, Ghayda; Timms, Andrew E.; Conti, Valerio; Boyle, Evan August; Girisha, Katta M.; Martin, Beth; Kircher, Martin; Olds, Carissa; Juusola, Jane; Collins, Sarah; Park, Kaylee; Carter, Melissa; Glass, Ian; Kr?geloh-Mann, Inge; Chitayat, David

    2016-01-01

    Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identifie...

  12. Integrating phenotype ontologies with PhenomeNET

    KAUST Repository

    Rodriguez-Garcia, Miguel Angel

    2017-12-19

    Background Integration and analysis of phenotype data from humans and model organisms is a key challenge in building our understanding of normal biology and pathophysiology. However, the range of phenotypes and anatomical details being captured in clinical and model organism databases presents complex problems when attempting to match classes across species and across phenotypes as diverse as behaviour and neoplasia. We have previously developed PhenomeNET, a system for disease gene prioritization that includes as one of its components an ontology designed to integrate phenotype ontologies. While not applicable to matching arbitrary ontologies, PhenomeNET can be used to identify related phenotypes in different species, including human, mouse, zebrafish, nematode worm, fruit fly, and yeast. Results Here, we apply the PhenomeNET to identify related classes from two phenotype and two disease ontologies using automated reasoning. We demonstrate that we can identify a large number of mappings, some of which require automated reasoning and cannot easily be identified through lexical approaches alone. Combining automated reasoning with lexical matching further improves results in aligning ontologies. Conclusions PhenomeNET can be used to align and integrate phenotype ontologies. The results can be utilized for biomedical analyses in which phenomena observed in model organisms are used to identify causative genes and mutations underlying human disease.

  13. Redefining Aging in HIV Infection Using Phenotypes.

    Science.gov (United States)

    Stoff, David M; Goodkin, Karl; Jeste, Dilip; Marquine, Maria

    2017-10-01

    This article critically reviews the utility of "phenotypes" as behavioral descriptors in aging/HIV research that inform biological underpinnings and treatment development. We adopt a phenotypic redefinition of aging conceptualized within a broader context of HIV infection and of aging. Phenotypes are defined as dimensions of behavior, closely related to fundamental mechanisms, and, thus, may be more informative than chronological age. Primary emphasis in this review is given to comorbid aging and cognitive aging, though other phenotypes (i.e., disability, frailty, accelerated aging, successful aging) are also discussed in relation to comorbid aging and cognitive aging. The main findings that emerged from this review are as follows: (1) the phenotypes, comorbid aging and cognitive aging, are distinct from each other, yet overlapping; (2) associative relationships are the rule in HIV for comorbid and cognitive aging phenotypes; and (3) HIV behavioral interventions for both comorbid aging and cognitive aging have been limited. Three paths for research progress are identified for phenotype-defined aging/HIV research (i.e., clinical and behavioral specification, biological mechanisms, intervention targets), and some important research questions are suggested within each of these research paths.

  14. Evolution of molecular phenotypes under stabilizing selection

    International Nuclear Information System (INIS)

    Nourmohammad, Armita; Schiffels, Stephan; Lässig, Michael

    2013-01-01

    Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution builds on genome evolution in a complicated way, which involves selection, genetic drift, mutations and recombination. Here we develop a coarse-grained evolutionary statistics for phenotypes, which decouples from details of the underlying genotypes. We derive approximate evolution equations for the distribution of phenotype values within and across populations. This dynamics covers evolutionary processes at high and low recombination rates, that is, it applies to sexual and asexual populations. In a fitness landscape with a single optimal phenotype value, the phenotypic diversity within populations and the divergence between populations reach evolutionary equilibria, which describe stabilizing selection. We compute the equilibrium distributions of both quantities analytically and we show that the ratio of mean divergence and diversity depends on the strength of selection in a universal way: it is largely independent of the phenotype’s genomic encoding and of the recombination rate. This establishes a new method for the inference of selection on molecular phenotypes beyond the genome level. We discuss the implications of our findings for the predictability of evolutionary processes. (paper)

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

    Science.gov (United States)

    Xavier-Neto, Jose; Carvalho, Murilo; Pascoalino, Bruno dos Santos; Cardoso, Alisson Campos; Costa, Ângela Maria Sousa; Pereira, Ana Helena Macedo; Santos, Luana Nunes; Saito, Ângela; Marques, Rafael Elias; Smetana, Juliana Helena Costa; Consonni, Silvio Roberto; Bandeira, Carla; Costa, Vivian Vasconcelos; Bajgelman, Marcio Chaim; de Oliveira, Paulo Sérgio Lopes; Cordeiro, Marli Tenorio; Gonzales Gil, Laura Helena Vega; Pauletti, Bianca Alves; Granato, Daniela Campos; Paes Leme, Adriana Franco; Freitas-Junior, Lucio; Holanda de Freitas, Carolina Borsoi Moraes; Teixeira, Mauro Martins; Bevilacqua, Estela; Franchini, Kleber

    2017-01-01

    The teratogenic mechanisms triggered by ZIKV are still obscure due to the lack of a suitable animal model. Here we present a mouse model of developmental disruption induced by ZIKV hematogenic infection. The model utilizes immunocompetent animals from wild-type FVB/NJ and C57BL/6J strains, providing a better analogy to the human condition than approaches involving immunodeficient, genetically modified animals, or direct ZIKV injection into the brain. When injected via the jugular vein into the blood of pregnant females harboring conceptuses from early gastrulation to organogenesis stages, akin to the human second and fifth week of pregnancy, ZIKV infects maternal tissues, placentas and embryos/fetuses. Early exposure to ZIKV at developmental day 5 (second week in humans) produced complex manifestations of anterior and posterior dysraphia and hydrocephalus, as well as severe malformations and delayed development in 10.5 days post-coitum (dpc) embryos. Exposure to the virus at 7.5–9.5 dpc induces intra-amniotic hemorrhage, widespread edema, and vascular rarefaction, often prominent in the cephalic region. At these stages, most affected embryos/fetuses displayed gross malformations and/or intrauterine growth restriction (IUGR), rather than isolated microcephaly. Disrupted conceptuses failed to achieve normal developmental landmarks and died in utero. Importantly, this is the only model so far to display dysraphia and hydrocephalus, the harbinger of microcephaly in humans, as well as arthrogryposis, a set of abnormal joint postures observed in the human setting. Late exposure to ZIKV at 12.5 dpc failed to produce noticeable malformations. We have thus characterized a developmental window of opportunity for ZIKV-induced teratogenesis encompassing early gastrulation, neurulation and early organogenesis stages. This should not, however, be interpreted as evidence for any safe developmental windows for ZIKV exposure. Late developmental abnormalities correlated with

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

    Directory of Open Access Journals (Sweden)

    Jose Xavier-Neto

    2017-02-01

    Full Text Available The teratogenic mechanisms triggered by ZIKV are still obscure due to the lack of a suitable animal model. Here we present a mouse model of developmental disruption induced by ZIKV hematogenic infection. The model utilizes immunocompetent animals from wild-type FVB/NJ and C57BL/6J strains, providing a better analogy to the human condition than approaches involving immunodeficient, genetically modified animals, or direct ZIKV injection into the brain. When injected via the jugular vein into the blood of pregnant females harboring conceptuses from early gastrulation to organogenesis stages, akin to the human second and fifth week of pregnancy, ZIKV infects maternal tissues, placentas and embryos/fetuses. Early exposure to ZIKV at developmental day 5 (second week in humans produced complex manifestations of anterior and posterior dysraphia and hydrocephalus, as well as severe malformations and delayed development in 10.5 days post-coitum (dpc embryos. Exposure to the virus at 7.5-9.5 dpc induces intra-amniotic hemorrhage, widespread edema, and vascular rarefaction, often prominent in the cephalic region. At these stages, most affected embryos/fetuses displayed gross malformations and/or intrauterine growth restriction (IUGR, rather than isolated microcephaly. Disrupted conceptuses failed to achieve normal developmental landmarks and died in utero. Importantly, this is the only model so far to display dysraphia and hydrocephalus, the harbinger of microcephaly in humans, as well as arthrogryposis, a set of abnormal joint postures observed in the human setting. Late exposure to ZIKV at 12.5 dpc failed to produce noticeable malformations. We have thus characterized a developmental window of opportunity for ZIKV-induced teratogenesis encompassing early gastrulation, neurulation and early organogenesis stages. This should not, however, be interpreted as evidence for any safe developmental windows for ZIKV exposure. Late developmental abnormalities

  17. TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features.

    Science.gov (United States)

    Balestrini, Simona; Milh, Mathieu; Castiglioni, Claudia; Lüthy, Kevin; Finelli, Mattea J; Verstreken, Patrik; Cardon, Aaron; Stražišar, Barbara Gnidovec; Holder, J Lloyd; Lesca, Gaetan; Mancardi, Maria M; Poulat, Anne L; Repetto, Gabriela M; Banka, Siddharth; Bilo, Leonilda; Birkeland, Laura E; Bosch, Friedrich; Brockmann, Knut; Cross, J Helen; Doummar, Diane; Félix, Temis M; Giuliano, Fabienne; Hori, Mutsuki; Hüning, Irina; Kayserili, Hulia; Kini, Usha; Lees, Melissa M; Meenakshi, Girish; Mewasingh, Leena; Pagnamenta, Alistair T; Peluso, Silvio; Mey, Antje; Rice, Gregory M; Rosenfeld, Jill A; Taylor, Jenny C; Troester, Matthew M; Stanley, Christine M; Ville, Dorothee; Walkiewicz, Magdalena; Falace, Antonio; Fassio, Anna; Lemke, Johannes R; Biskup, Saskia; Tardif, Jessica; Ajeawung, Norbert F; Tolun, Aslihan; Corbett, Mark; Gecz, Jozef; Afawi, Zaid; Howell, Katherine B; Oliver, Karen L; Berkovic, Samuel F; Scheffer, Ingrid E; de Falco, Fabrizio A; Oliver, Peter L; Striano, Pasquale; Zara, Federico; Campeau, Phillipe M; Sisodiya, S M

    2016-07-05

    To evaluate the phenotypic spectrum associated with mutations in TBC1D24. We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24). Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function. TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes. © 2016 American Academy of Neurology.

  18. Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Robert Wilson

    2017-02-01

    Full Text Available Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates.

  19. The nature of stable insomnia phenotypes.

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L

    2015-01-01

    We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Longitudinal. Urban, community-based. Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). None. At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the 'neither criterion' phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With the exception of daytime sleepiness, few clinical differences are apparent across stable phenotypes.

  20. The insomnia with short sleep duration phenotype: an update on it's importance for health and prevention.

    Science.gov (United States)

    Fernandez-Mendoza, Julio

    2017-01-01

    It was first proposed in the late 1990s that objective markers of sleep disturbance could serve as an index of the biological severity of insomnia. In 2013, a heuristic model of two insomnia phenotypes based on objective sleep duration was proposed. Herein, we review the studies conducted in the past 3 years on the insomnia with short sleep duration phenotype and its implications for a clinical research agenda. Studies have shown that insomnia with objective short sleep duration is associated with physiologic hyperarousal and cardiometabolic and neurocognitive morbidity, whereas insomnia with normal sleep duration is not. Both insomnia phenotypes are associated with psychiatric morbidity albeit through different psychobiological mechanisms. Novel recent studies have included occupational outcomes, developmental approaches, at-home objective sleep testing, diagnostic accuracy measures, and response to cognitive-behavioral treatment. Accumulating evidence in the past years has continued to support that insomnia with short sleep duration is a more severe phenotype of the disorder associated with physiologic changes, significant morbidity and mortality and, potentially, a differential response to treatment.

  1. Dissecting high-dimensional phenotypes with bayesian sparse factor analysis of genetic covariance matrices.

    Science.gov (United States)

    Runcie, Daniel E; Mukherjee, Sayan

    2013-07-01

    Quantitative genetic studies that model complex, multivariate phenotypes are important for both evolutionary prediction and artificial selection. For example, changes in gene expression can provide insight into developmental and physiological mechanisms that link genotype and phenotype. However, classical analytical techniques are poorly suited to quantitative genetic studies of gene expression where the number of traits assayed per individual can reach many thousand. Here, we derive a Bayesian genetic sparse factor model for estimating the genetic covariance matrix (G-matrix) of high-dimensional traits, such as gene expression, in a mixed-effects model. The key idea of our model is that we need consider only G-matrices that are biologically plausible. An organism's entire phenotype is the result of processes that are modular and have limited complexity. This implies that the G-matrix will be highly structured. In particular, we assume that a limited number of intermediate traits (or factors, e.g., variations in development or physiology) control the variation in the high-dimensional phenotype, and that each of these intermediate traits is sparse - affecting only a few observed traits. The advantages of this approach are twofold. First, sparse factors are interpretable and provide biological insight into mechanisms underlying the genetic architecture. Second, enforcing sparsity helps prevent sampling errors from swamping out the true signal in high-dimensional data. We demonstrate the advantages of our model on simulated data and in an analysis of a published Drosophila melanogaster gene expression data set.

  2. Trisomy 12p and monosomy 4p: phenotype-genotype correlation.

    Science.gov (United States)

    Benussi, Daniela Gambel; Costa, Paola; Zollino, Marcella; Murdolo, Marina; Petix, Vincenzo; Carrozzi, Marco; Pecile, Vanna

    2009-04-01

    4p Monosomy and 12p trisomy have been discussed and redefined along with recently reviewed chromosomal syndromes. 12p Trisomy syndrome is characterized by normal or increased birth weight, developmental delay with early hypotonia, psychomotor delay, and typical facial appearance. Most likely, the observed phenotypic variability depends on the type and extent of the associated partial monosomy. Partial deletions of the short arm of one chromosome 4 cause the Wolf-Hirschhorn syndrome (WHS). Affected patients present Greek helmet face, growth and mental retardation, hypotonia, and seizures. The combination of these characteristics constitutes the phenotypic core of WHS. We present a clinical and molecular cytogenetic characterization of a 4-year old mentally retarded girl with macrosomy, facial dysmorphisms, and epilepsy, in whom an unbalanced t(4;12)(p16.3;p13.3) translocation was detected, giving rise to partial 4p monosomy and partial 12p trisomy. Because the patient shows most of the phenotypic characteristics of 12p trisomy, this case could contribute to a better definition of the duplicate critical region that determines the phenotype of the 12p trisomy syndrome.

  3. Phenotyping animal models of diabetic neuropathy

    DEFF Research Database (Denmark)

    Biessels, G J; Bril, V; Calcutt, N A

    2014-01-01

    NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy...... with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence...

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

    Directory of Open Access Journals (Sweden)

    Elena eCid

    2014-04-01

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

  5. Developmental cognitive genetics: How psychology can inform genetics and vice versa

    Science.gov (United States)

    Bishop, Dorothy V. M.

    2006-01-01

    Developmental neuropsychology is concerned with uncovering the underlying basis of developmental disorders such as specific language impairment (SLI), developmental dyslexia, and autistic disorder. Twin and family studies indicate that genetic influences play an important part in the aetiology of all of these disorders, yet progress in identifying genes has been slow. One way forward is to cut loose from conventional clinical criteria for diagnosing disorders and to focus instead on measures of underlying cognitive mechanisms. Psychology can inform genetics by clarifying what the key dimensions are for heritable phenotypes. However, it is not a one-way street. By using genetically informative designs, one can gain insights about causal relationships between different cognitive deficits. For instance, it has been suggested that low-level auditory deficits cause phonological problems in SLI. However, a twin study showed that, although both types of deficit occur in SLI, they have quite different origins, with environmental factors more important for auditory deficit, and genes more important for deficient phonological short-term memory. Another study found that morphosyntactic deficits in SLI are also highly heritable, but have different genetic origins from impairments of phonological short-term memory. A genetic perspective shows that a search for the underlying cause of developmental disorders may be misguided, because they are complex and heterogeneous and are associated with multiple risk factors that only cause serious disability when they occur in combination. PMID:16769616

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

    Science.gov (United States)

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

    2017-12-26

    vulnerability at age 5 years. Prenatal exposure to infectious or noninfectious diseases appear to influence early childhood physical, social, emotional and cognitive developmental vulnerabilities that may represent intermediate phenotypes for subsequent mental disorders. © 2017 Association for Child and Adolescent Mental Health.

  7. Language cannot be reduced to biology: perspectives from neuro-developmental disorders affecting language learning.

    Science.gov (United States)

    Vasanta, D

    2005-02-01

    The study of language knowledge guided by a purely biological perspective prioritizes the study of syntax. The essential process of syntax is recursion--the ability to generate an infinite array of expressions from a limited set of elements. Researchers working within the biological perspective argue that this ability is possible only because of an innately specified genetic makeup that is specific to human beings. Such a view of language knowledge may be fully justified in discussions on biolinguistics, and in evolutionary biology. However, it is grossly inadequate in understanding language-learning problems, particularly those experienced by children with neurodevelopmental disorders such as developmental dyslexia, Williams syndrome, specific language impairment and autism spectrum disorders. Specifically, syntax-centered definitions of language knowledge completely ignore certain crucial aspects of language learning and use, namely, that language is embedded in a social context; that the role of envrironmental triggering as a learning mechanism is grossly underestimated; that a considerable extent of visuo-spatial information accompanies speech in day-to-day communication; that the developmental process itself lies at the heart of knowledge acquisition; and that there is a tremendous variation in the orthographic systems associated with different languages. All these (socio-cultural) factors can influence the rate and quality of spoken and written language acquisition resulting in much variation in phenotypes associated with disorders known to have a genetic component. Delineation of such phenotypic variability requires inputs from varied disciplines such as neurobiology, neuropsychology, linguistics and communication disorders. In this paper, I discuss published research that questions cognitive modularity and emphasises the role of the environment for understanding linguistic capabilities of children with neuro-developmental disorders. The discussion pertains

  8. Phenotypic profiles of Armenian grape cultivars

    Directory of Open Access Journals (Sweden)

    Aroutiounian Rouben

    2015-01-01

    Full Text Available The conservation and sustainable use of grapevine biodiversity in Armenia is particularly important due to the large number of traditional local varieties. Being partially different from European grapevine gene pool, the material of Armenian local cultivars significantly contributes to the understanding of the genetic variation and is valuable source for target selection. During last years many Armenian grapevine cultivars have been already described and their genotypes determined, but some local varieties and wild accessions remain unidentified and their phenotypic characteristics overlooked. The comprehensive analysis of phenotypes is essential for research, including genetic association studies, cultivar evaluation and selection. The goal of our research was the phenotyping on the base of reproductive, carpological and analytical characteristics of 80 Armenian aboriginal and new grape cultivars. Description of phenotypic profiles is important step towards identification and conservation of genetic resources of Armenian grapes. In future, these data can be applied for breeding of improved grape varieties targeted to fresh consumption and wine production.

  9. Phenotypic diversity and phylogenetic relationship between the ...

    African Journals Online (AJOL)

    Phenotypic diversity and phylogenetic relationship between the Bakosi/Baweri and other pig breeds ( Sus scrofa Domesticus ) in the humid forest with monomodal rainfall agro-ecological zone of Cameroon.

  10. Integrating phenotype ontologies with PhenomeNET

    KAUST Repository

    Rodriguez-Garcia, Miguel Angel; Gkoutos, Georgios V.; Schofield, Paul N.; Hoehndorf, Robert

    2017-01-01

    in clinical and model organism databases presents complex problems when attempting to match classes across species and across phenotypes as diverse as behaviour and neoplasia. We have previously developed PhenomeNET, a system for disease gene prioritization

  11. Wiedemann-Rautenstrauch syndrome: A phenotype analysis

    NARCIS (Netherlands)

    Paolacci, Stefano; Bertola, Debora; Franco, José; Mohammed, Shehla; Tartaglia, Marco; Wollnik, Bernd; Hennekam, Raoul C.

    2017-01-01

    Wiedemann-Rautenstrauch syndrome (WRS) is a neonatal progeroid disorder characterized by growth retardation, lipodystrophy, a distinctive face, and dental anomalies. Patients reported to date demonstrate a remarkable variability in phenotype, which hampers diagnostics. We performed a literature

  12. REVIEW ARTICLE One gene, many phenotypes

    African Journals Online (AJOL)

    salah

    Phenotype descriptions are valuable information right at the interface of medi- cine and biology. ... the interaction of alleles at different loci. Modifier genes. 5. ... the amount of normal protein is called ..... Institute, using computer simulations,.

  13. The spatial patterns of directional phenotypic selection

    KAUST Repository

    Siepielski, Adam M.; Gotanda, Kiyoko M.; Morrissey, Michael B.; Diamond, Sarah E.; DiBattista, Joseph; Carlson, Stephanie Marie

    2013-01-01

    the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data

  14. Phenotypic variability among strains of Pasteurella multocida ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-05-02

    May 2, 2008 ... Available online at http://www.academicjournals.org/AJB. ISSN 1684–5315 ... extended phenotypic characterization methods supported by DNA ... septicaemia African (Obudu) strain (E:2) which are currently employed as ...

  15. Developmental programming of auditory learning

    Directory of Open Access Journals (Sweden)

    Melania Puddu

    2012-10-01

    Full Text Available The basic structures involved in the development of auditory function and consequently in language acquisition are directed by genetic code, but the expression of individual genes may be altered by exposure to environmental factors, which if favorable, orient it in the proper direction, leading its development towards normality, if unfavorable, they deviate it from its physiological course. Early sensorial experience during the foetal period (i.e. intrauterine noise floor, sounds coming from the outside and attenuated by the uterine filter, particularly mother’s voice and modifications induced by it at the cochlear level represent the first example of programming in one of the earliest critical periods in development of the auditory system. This review will examine the factors that influence the developmental programming of auditory learning from the womb to the infancy. In particular it focuses on the following points: the prenatal auditory experience and the plastic phenomena presumably induced by it in the auditory system from the basilar membrane to the cortex;the involvement of these phenomena on language acquisition and on the perception of language communicative intention after birth;the consequences of auditory deprivation in critical periods of auditory development (i.e. premature interruption of foetal life.

  16. Executive Functions in Developmental Dyslexia

    Directory of Open Access Journals (Sweden)

    Pamela eVarvara

    2014-03-01

    Full Text Available The present study was aimed at investigating different aspects of Executive Functions (EF in children with Developmental Dyslexia (DD.A neuropsychological battery tapping verbal fluency, spoonerism, attention, verbal shifting, short-term and working memory was used to assess 60 children with DD and 65 with typical reading abilities.Compared to their controls, children with DD showed deficits in several EF domains such as verbal categorical and phonological fluency, visual-spatial and auditory attention, spoonerism, verbal and visual short-term memory, and verbal working memory. Moreover, exploring predictive relationships between EF measures and reading, we found that spoonerism abilities better explained word and non-word reading deficits. Although to a lesser extent, auditory and visual-spatial attention also explained the increased percentage of variance related to reading deficit.EF deficits found in DD are interpreted as an expression of a deficient functioning of the Central Executive System and are discussed in the context of the recent temporal sampling theory.

  17. Pervasive Developmental Disorder with Age?

    Directory of Open Access Journals (Sweden)

    M. Balfe

    2011-01-01

    Full Text Available A survey was undertaken to investigate the prevalence of high-functioning pervasive developmental disorder (HFPDD in a community sample of teenagers and adults aged 13 and above in the city of Sheffield, UK. 112 possible and definite cases were found, of whom 65 (57% had a previous diagnosis. The detected prevalence of possible or definite HFPDD was found to be 0.24 per 1000 of the population of Sheffield city aged 13 or over, but the prevalence by year of age fell from a maximum of 1.1 per 1000 in the group aged 13 to 14 years old (1 young adult in every 900 in this age group to 0.03 per 1000 in the over 60s (1 person in every 38500 in this age group. The results of this study are preliminary and need follow-up investigation in larger studies. We suggest several explanations for the findings, including reduced willingness to participate in a study as people get older, increased ascertainment in younger people, and increased mortality. Another contributory factor might be that the prevalence of high-functioning pervasive development disorder may decline with age. This raises the possibility that AS symptoms might become subclinical in adulthood in a proportion of people with HFPDD.

  18. Fitness consequences of maternal and embryonic responses to environmental variation: using reptiles as models for studies of developmental plasticity.

    Science.gov (United States)

    Warner, Daniel A

    2014-11-01

    Environmental factors strongly influence phenotypic variation within populations. The environment contributes to this variation in two ways: (1) by acting as a determinant of phenotypic variation (i.e., plastic responses) and (2) as an agent of selection that "chooses" among existing phenotypes. Understanding how these two environmental forces contribute to phenotypic variation is a major goal in the field of evolutionary biology and a primary objective of my research program. The objective of this article is to provide a framework to guide studies of environmental sources of phenotypic variation (specifically, developmental plasticity and maternal effects, and their adaptive significance). Two case studies from my research on reptiles are used to illustrate the general approaches I have taken to address these conceptual topics. Some key points for advancing our understanding of environmental influences on phenotypic variation include (1) merging laboratory-based research that identifies specific environmental effects with field studies to validate ecological relevance; (2) using controlled experimental approaches that mimic complex environments found in nature; (3) integrating data across biological fields (e.g., genetics, morphology, physiology, behavior, and ecology) under an evolutionary framework to provide novel insights into the underlying mechanisms that generate phenotypic variation; (4) assessing fitness consequences using measurements of survival and/or reproductive success across ontogeny (from embryos to adults) and under multiple ecologically-meaningful contexts; and (5) quantifying the strength and form of natural selection in multiple populations over multiple periods of time to understand the spatial and temporal consistency of phenotypic selection. Research programs that focus on organisms that are amenable to these approaches will provide the most promise for advancing our understanding of the environmental factors that generate the remarkable

  19. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Levine, Arie; de Bie, Charlotte I; Turner, Dan

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...... of atypical inflammatory bowel disease (IBD) patients. Our aim was to identify the prevalence of atypical disease patterns in new-onset pediatric UC using the Paris classification....

  20. A Regulatory RNA Inducing Transgenerationally Inherited Phenotypes

    DEFF Research Database (Denmark)

    Jensen, Lea Møller

    . The variation in Arabidopsis enables different regulatory networks and mechanisms to shape the phenotypic characteristics. The thesis describes the identification of regulatory RNA encoded by an enzyme encoding gene. The RNA regulates by inducing transgenerationally inherited phenotypes. The function of the RNA...... is dependent on the genetic background illustrating that polymorphisms are found in either interactors or target genes of the RNA. Furthermore, the RNA provides a mechanistic link between accumulation of glucosinolate and onset of flowering....

  1. Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure

    Directory of Open Access Journals (Sweden)

    Nusinowitz Steven

    2001-11-01

    Full Text Available Abstract Background Glaucoma is a blinding disease usually associated with high intraocular pressure (IOP. In some families, abnormal anterior segment development contributes to glaucoma. The genes causing anterior segment dysgenesis and glaucoma in most of these families are not identified and the affected developmental processes are poorly understood. Bone morphogenetic proteins (BMPs participate in various developmental processes. We tested the importance of Bmp4 gene dosage for ocular development and developmental glaucoma. Results Bmp4+/- mice have anterior segment abnormalities including malformed, absent or blocked trabecular meshwork and Schlemm's canal drainage structures. Mice with severe drainage structure abnormalities, over 80% or more of their angle's extent, have elevated IOP. The penetrance and severity of abnormalities is strongly influenced by genetic background, being most severe on the C57BL/6J background and absent on some other backgrounds. On the C57BL/6J background there is also persistence of the hyaloid vasculature, diminished numbers of inner retinal cells, and absence of the optic nerve. Conclusions We demonstrate that heterozygous deficiency of BMP4 results in anterior segment dysgenesis and elevated IOP. The abnormalities are similar to those in human patients with developmental glaucoma. Thus, BMP4 is a strong candidate to contribute to Axenfeld-Rieger anomaly and other developmental conditions associated with human glaucoma. BMP4 also participates in posterior segment development and wild-type levels are usually critical for optic nerve development on the C57BL/6J background. Bmp4+/- mice are useful for studying various components of ocular development, and may allow identification of strain specific modifiers affecting a variety of ocular phenotypes.

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

    Science.gov (United States)

    Kishi, Shuji

    2014-01-01

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

  3. Developmental systems of plasticity and trans-generational epigenetic inheritance in nematodes.

    Science.gov (United States)

    Serobyan, Vahan; Sommer, Ralf J

    2017-08-01

    Several decades of research provided detailed insight into how genes control development and evolution, whereas recent studies have expanded this purely genetic perspective by presenting strong evidence for environmental and epigenetic influences. We summarize examples of phenotypic plasticity and trans-generational epigenetic inheritance in the nematode model organisms Pristionchus pacificus and Caenorhabditis elegans, which indicate that the response of developmental systems to environmental influences is hardwired into the organismś genome. We argue that genetic programs regulating these organismal-environmental interactions are themselves subject to natural selection. Indeed, macro-evolutionary studies of nematode feeding structures indicate evolutionary trajectories in which plasticity followed by genetic assimilation results in extreme diversity highlighting the role of plasticity as major facilitator of phenotypic diversification. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Phenex: ontological annotation of phenotypic diversity.

    Directory of Open Access Journals (Sweden)

    James P Balhoff

    2010-05-01

    Full Text Available Phenotypic differences among species have long been systematically itemized and described by biologists in the process of investigating phylogenetic relationships and trait evolution. Traditionally, these descriptions have been expressed in natural language within the context of individual journal publications or monographs. As such, this rich store of phenotype data has been largely unavailable for statistical and computational comparisons across studies or integration with other biological knowledge.Here we describe Phenex, a platform-independent desktop application designed to facilitate efficient and consistent annotation of phenotypic similarities and differences using Entity-Quality syntax, drawing on terms from community ontologies for anatomical entities, phenotypic qualities, and taxonomic names. Phenex can be configured to load only those ontologies pertinent to a taxonomic group of interest. The graphical user interface was optimized for evolutionary biologists accustomed to working with lists of taxa, characters, character states, and character-by-taxon matrices.Annotation of phenotypic data using ontologies and globally unique taxonomic identifiers will allow biologists to integrate phenotypic data from different organisms and studies, leveraging decades of work in systematics and comparative morphology.

  5. Phenex: ontological annotation of phenotypic diversity.

    Science.gov (United States)

    Balhoff, James P; Dahdul, Wasila M; Kothari, Cartik R; Lapp, Hilmar; Lundberg, John G; Mabee, Paula; Midford, Peter E; Westerfield, Monte; Vision, Todd J

    2010-05-05

    Phenotypic differences among species have long been systematically itemized and described by biologists in the process of investigating phylogenetic relationships and trait evolution. Traditionally, these descriptions have been expressed in natural language within the context of individual journal publications or monographs. As such, this rich store of phenotype data has been largely unavailable for statistical and computational comparisons across studies or integration with other biological knowledge. Here we describe Phenex, a platform-independent desktop application designed to facilitate efficient and consistent annotation of phenotypic similarities and differences using Entity-Quality syntax, drawing on terms from community ontologies for anatomical entities, phenotypic qualities, and taxonomic names. Phenex can be configured to load only those ontologies pertinent to a taxonomic group of interest. The graphical user interface was optimized for evolutionary biologists accustomed to working with lists of taxa, characters, character states, and character-by-taxon matrices. Annotation of phenotypic data using ontologies and globally unique taxonomic identifiers will allow biologists to integrate phenotypic data from different organisms and studies, leveraging decades of work in systematics and comparative morphology.

  6. Phenotypic integration of the cervical vertebrae in the Hominoidea (Primates).

    Science.gov (United States)

    Villamil, Catalina I

    2018-03-01

    Phenotypic integration and modularity represent important factors influencing evolutionary change. The mammalian cervical vertebral column is particularly interesting in regards to integration and modularity because it is highly constrained to seven elements, despite widely variable morphology. Previous research has found a common pattern of integration among quadrupedal mammals, but integration patterns also evolve in response to locomotor selective pressures like those associated with hominin bipedalism. Here, I test patterns of covariation in the cervical vertebrae of three hominoid primates (Hylobates, Pan, Homo) who engage in upright postures and locomotion. Patterns of integration in the hominoid cervical vertebrae correspond generally to those previously found in other mammals, suggesting that integration in this region is highly conserved, even among taxa that engage in novel positional behaviors. These integration patterns reflect underlying developmental as well as functional modules. The strong integration between vertebrae suggests that the functional morphology of the cervical vertebral column should be considered as a whole, rather than in individual vertebrae. Taxa that display highly derived morphologies in the cervical vertebrae are likely exploiting these integration patterns, rather than reorganizing them. Future work on vertebrates without cervical vertebral number constraints will further clarify the evolution of integration in this region. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

  7. Etiology and Treatment of Developmental Stammering

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-01-01

    Full Text Available The etiology and treatment of developmental stammering in childhood (DS, also called idiopathic stammering or stuttering are reviewed by a speech pathologist and psychologist at the University of Reading, UK.

  8. Unpacking developmental local government using Soft Systems ...

    African Journals Online (AJOL)

    Developmental local government, soft systems methodology, multiple criteria ..... land and property), 26 (adequate housing), 27 (access to health care, food, water .... It is important to articulate that any decision making or resource allocation.

  9. Wanted: A Developmentally Oriented Alcohol Prevention Program.

    Science.gov (United States)

    Spoth, Richard; Rosenthal, David

    1980-01-01

    Describes an alcohol prevention program with a comprehensive developmental skills orientation. The program includes values clarification, decision making, career planning and communication skills, assertiveness and relaxation training, and relationship with parents and peers. (Author/JAC)

  10. Developmental and Reproductive Toxicology Database (DART)

    Data.gov (United States)

    U.S. Department of Health & Human Services — A bibliographic database on the National Library of Medicine's (NLM) Toxicology Data Network (TOXNET) with references to developmental and reproductive toxicology...

  11. Characteristics of children with pervasive developmental disorders ...

    African Journals Online (AJOL)

    of children presenting with features of ASD to a developmental clinic in Johannesburg over ... social interaction deficits without meeting the full criteria for PDD were excluded, as were those ..... Recurrent otitis media. 7 (12.1). Myringotomies.

  12. Current status of developmental neurotoxicity: regulatory view

    DEFF Research Database (Denmark)

    Hass, Ulla

    2003-01-01

    in the testing strategy for new and existing substances, and biocides. Hopefully, this will lead to an improved database for risk assessment of potential developmental neurotoxicants. However, the regulatory authorities and toxicologists will also be faced with the challenge that decisions have to be made......The need for developmental neurotoxicity testing has been recognized for decades and guidelines are available, as the USEPA guideline and the OECD draft TG 426. Regulatory testing of industrial chemicals for developmental neurotoxicity is required to some extent, especially for pesticides in the US....... Until recently, however, developmental neurotoxicity testing of industrial chemicals has not been a clear regulatory requirement in EU, probably due to the lack of an accepted OECD TG. The revised EU Technical Guidance Document for Risk Assessment (EU-TGD) has now included the OECD draft TG 426...

  13. Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females: Detailed phenotyping of 10 new cases.

    Science.gov (United States)

    Symonds, Joseph D; Joss, Shelagh; Metcalfe, Kay A; Somarathi, Suresh; Cruden, Jamie; Devlin, Anita M; Donaldson, Alan; DiDonato, Nataliya; Fitzpatrick, David; Kaiser, Frank J; Lampe, Anne K; Lees, Melissa M; McLellan, Ailsa; Montgomery, Tara; Mundada, Vivek; Nairn, Lesley; Sarkar, Ajoy; Schallner, Jens; Pozojevic, Jelena; Parenti, Ilaria; Tan, Jeen; Turnpenny, Peter; Whitehouse, William P; Zuberi, Sameer M

    2017-04-01

    The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in-frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS). Recently, protein truncating mutations in SMC1A have been reported in five females, all of whom have been affected by a drug-resistant epilepsy, and severe developmental impairment. Our objective was to further delineate the phenotype of SMC1A truncation. Female cases with de novo truncation mutations in SMC1A were identified from the Deciphering Developmental Disorders (DDD) study (n = 8), from postmortem testing of an affected twin (n = 1), and from clinical testing with an epilepsy gene panel (n = 1). Detailed information on the phenotype in each case was obtained. Ten cases with heterozygous de novo mutations in the SMC1A gene are presented. All 10 mutations identified are predicted to result in premature truncation of the SMC1A protein. All cases are female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases. Truncation mutations in SMC1A cause a severe epilepsy phenotype with cluster seizures in females. These mutations are likely to be nonviable in males. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  14. Low-dose ionizing radiation alleviates Aβ42-induced defective phenotypes in Drosophila Alzheimer's disease models

    International Nuclear Information System (INIS)

    Hwang, SooJin; Jeong, Hae Min; Nam, Seon Young

    2017-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disease that is characterized by amyloid plaques, progressive neuronal loss, and gradual deterioration of memory. Amyloid imaging using positron emission tomography (PET) radiotracers have been developed and approved for clinical use in the evaluation of suspected neurodegenerative disease, including AD. Particularly, previous studies involving low-dose ionizing radiation on Aβ 42-treated mouse hippocampal neurons have suggested a potential role for low-dose ionizing radiation in the treatment of AD. However, associated in vivo studies involving the therapy effects of low-dose ionizing radiation on AD are still insufficient. As a powerful cell biological system, Drosophila AD models have been generated and established a useful model organism for study on the etiology of human AD. In this study, we investigated the hormesis effects of low-dose ionizing radiation on Drosophila AD models. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation.

  15. Reward-centricity and attenuated aversions: An adolescent phenotype emerging from studies in laboratory animals.

    Science.gov (United States)

    Doremus-Fitzwater, Tamara L; Spear, Linda P

    2016-11-01

    Adolescence is an evolutionarily conserved developmental period, with neural circuits and behaviors contributing to the detection, procurement, and receipt of rewards bearing similarity across species. Studies with laboratory animals suggest that adolescence is typified by a "reward-centric" phenotype-an increased sensitivity to rewards relative to adults. In contrast, adolescent rodents are reportedly less sensitive to the aversive properties of many drugs and naturally aversive stimuli. Alterations within the mesocorticolimbic dopamine and endocannabinoid systems likely contribute to an adolescent reward-sensitive, yet aversion-resistant, phenotype. Although early hypotheses postulated that developmental changes in dopaminergic circuitry would result in a "reward deficiency" syndrome, evidence now suggests the opposite: that adolescents are uniquely poised to seek out hedonic stimuli, experience greater "pleasure" from rewards, and consume rewarding stimuli in excess. Future studies that more clearly define the role of specific brain regions and neurotransmitter systems in the expression of behaviors toward reward- and aversive-related cues and stimuli are necessary to more fully understand an adolescent-proclivity for and vulnerability to rewards and drugs of potential abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Is phenotypic plasticity a key mechanism for responding to thermal stress in ants?

    Science.gov (United States)

    Oms, Cristela Sánchez; Cerdá, Xim; Boulay, Raphaël

    2017-06-01

    Unlike natural selection, phenotypic plasticity allows organisms to respond quickly to changing environmental conditions. However, plasticity may not always be adaptive. In insects, body size and other morphological measurements have been shown to decrease as temperature increases. This relationship may lead to a physiological conflict in ants, where larger body size and longer legs often confer better thermal resistance. Here, we tested the effect of developmental temperature (20, 24, 28 or 32 °C) on adult thermal resistance in the thermophilic ant species Aphaenogaster senilis. We found that no larval development occurred at 20 °C. However, at higher temperatures, developmental speed increased as expected and smaller adults were produced. In thermal resistance tests, we found that ants reared at 28 and 32 °C had half-lethal temperatures that were 2 °C higher than those of ants reared at 24 °C. Thus, although ants reared at higher temperatures were smaller in size, they were nonetheless more thermoresistant. These results show that A. senilis can exploit phenotypic plasticity to quickly adjust its thermal resistance to local conditions and that this process is independent of morphological adaptations. This mechanism may be particularly relevant given current rapid climate warming.

  17. Phonemic restoration in developmental dyslexia

    Directory of Open Access Journals (Sweden)

    Stephanie N. Del Tufo

    2014-06-01

    Full Text Available The comprehension of fluent speech in one’s native language requires that listeners integrate the detailed acoustic-phonetic information available in the sound signal with linguistic knowledge. This interplay is especially apparent in the phoneme restoration effect, a phenomenon in which a missing phoneme is ‘restored’ via the influence of top-down information from the lexicon and through bottom-up acoustic processing. Developmental dyslexia is a disorder characterized by an inability to read at the level of one’s peers without any clear failure due to environmental influences. In the current study we utilized the phonemic restoration illusion paradigm, to examine individual differences in phonemic restoration across a range of reading ability, from very good to dyslexic readers. Results demonstrate that restoration occurs less in those who have high scores on measures of phonological processing. Based on these results, we suggest that the processing or representation of acoustic detail may not be as reliable in poor and dyslexic readers, with the result that lexical information is more likely to override acoustic properties of the stimuli. This pattern of increased restoration could result from a failure of perceptual tuning, in which unstable representations of speech sounds result in the acceptance of non-speech sounds as speech. An additional or alternative theory is that degraded or impaired phonological processing at the speech sound level may reflect architecture that is overly plastic and consequently fails to stabilize appropriately for speech sound representations. Therefore the inability to separate speech and noise may result as a deficit in separating noise from the acoustic signal.

  18. [Contemporary cognitive theories about developmental dyscalculia].

    Science.gov (United States)

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

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

  19. Developmental immunotoxicity testing of 4-methyl anisole.

    Science.gov (United States)

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

    2015-07-01

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

  20. Age is associated with asthma phenotypes.

    Science.gov (United States)

    Ponte, Eduardo V; Lima, Aline; Almeida, Paula C A; de Jesus, Juliana P V; Lima, Valmar B; Scichilone, Nicola; Souza-Machado, Adelmir; Cruz, Álvaro A

    2017-11-01

    The relationship between age and asthma phenotypes is important as population is ageing, asthma is becoming common in older ages and recently developed treatments for asthma are guided by phenotypes. The aim of this study is to evaluate whether age is associated with specific asthma phenotypes. This is a cross-sectional study. We included subjects with asthma of varied degrees of severity. Subjects underwent spirometry, skin prick test to aeroallergens, answered the Asthma Control Questionnaire and had blood samples collected. We performed binary logistic regression analysis to evaluate whether age is associated with asthma phenotypes. We enrolled 868 subjects. In comparison with subjects ≤ 40 years, older subjects had high odds of irreversible airway obstruction (from 41 to 64 years, OR: 1.83 (95% CI: 1.32-2.54); ≥65 years, OR: 3.45 (2.12-5.60)) and severe asthma phenotypes (from 41 to 64 years, OR: 3.23 (2.26-4.62); ≥65 years, OR: 4.55 (2.39-8.67)). Older subjects had low odds of atopic (from 41 to 64 years, OR: 0.56 (0.39-0.79); ≥65 years, OR: 0.47 (0.27-0.84)) and eosinophilic phenotypes (from 41 to 64 years, OR: 0.63 (0.46-0.84); ≥65 years, OR: 0.39 (0.24-0.64)). Older subjects with asthma have low odds of atopic and eosinophilic phenotypes, whereas they present high odds of irreversible airway obstruction and severe asthma. © 2017 Asian Pacific Society of Respirology.

  1. THE INDIVIDUAL AND TYPOLOGICAL CHARACTERISTIC AND FEATURES OF THE LATERAL PHENOTYPE AT YOUNG MEN

    Directory of Open Access Journals (Sweden)

    Анатолий Степанович Пуликов

    2013-04-01

    Full Text Available Purpose: To determine the state of the physical development of the autonomic regulation of the functions and adaptive capacity in relation to the characteristics of the distribution of the lateral phenotype in boys.Methodology: The study on a voluntary basis with the informed consent of 124 apparently healthy young student branch of State Educational Institution of Krasnoyarsk State Pedagogical University V.P. Astafieva in Zheleznogorsk.Anthropometric measurements were carried out by a well-known and accepted techniques that meet modern requirements.Definition of motor and sensory asymmetries person evaluated by the method proposed by N.N. Bragin (1988.Results: In boys, living in the influence of the MCC to the impact of «small and ultra-low doses» of radiation in more than half of the cases, pravolateralny phenotype, regardless of their physical constitution with the highest rate in andromorfnogo type on SDI and voltage adaptation mechanisms, prevalence figures sympathetic tone autonomic regulation. Poor adaptation was observed only in young men with levolateralnym and mixed phenotype. Youth with levolateralnym phenotype were the smallest in size cohort (7,5-12,5%. However, among them there is a tendency to predominance boys and ginekomorfnogo endomorph body types, with poor adaptation, stress adaptation mechanisms and parasympathetic tone of the autonomic regulation. The young men of mixed lateral phenotype was weak distinction constitutional type body, with a predominance of one to ginekomorfnogo and mesomorphic body types on SDI. In the same group, a fairly wide variation between satisfactory and unsatisfactory adaptation and stress coping mechanisms with the same measure of the number of young men from the parasympathetic and sympathetic tone of the autonomic regulation.Practical implications: medicine, psychology, developmental physiology, anthropology, neuroscience.DOI: http://dx.doi.org/10.12731/2218-7405-2013-1-14

  2. In vitro atrazine exposure affects the phenotypic and functional maturation of dendritic cells

    International Nuclear Information System (INIS)

    Pinchuk, Lesya M.; Lee, Sang-Ryul; Filipov, Nikolay M.

    2007-01-01

    Recent data suggest that some of the immunotoxic effects of the herbicide atrazine, a very widely used pesticide, may be due to perturbations in dendritic cell (DC) function. As consequences of atrazine exposure on the phenotypic and functional maturation of DC have not been studied, our objective was, using the murine DC line, JAWSII, to determine whether atrazine will interfere with DC maturation. First, we characterized the maturation of JAWSII cells in vitro by inducing them to mature in the presence of growth factors and selected maturational stimuli in vitro. Next, we exposed the DC cell line to a concentration range of atrazine and examined its effects on phenotypic and functional maturation of DC. Atrazine exposure interfered with the phenotypic and functional maturation of DC at non-cytotoxic concentrations. Among the phenotypic changes caused by atrazine exposure was a dose-dependent removal of surface MHC-I with a significant decrease being observed at 1 μM concentration. In addition, atrazine exposure decreased the expression of the costimulatory molecule CD86 and it downregulated the expression of the CD11b and CD11c accessory molecules and the myeloid developmental marker CD14. When, for comparative purposes, we exposed primary thymic DC to atrazine, MHC-I and CD11c expression was also decreased. Phenotypic changes in JAWSII DC maturation were associated with functional inhibition of maturation as, albeit at higher concentrations, receptor-mediated antigen uptake was increased by atrazine. Thus, our data suggest that atrazine directly targets DC maturation and that toxicants such as atrazine that efficiently remove MHC-I molecules from the DC surface are likely to contribute to immune evasion

  3. Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations.

    Science.gov (United States)

    Fergelot, Patricia; Van Belzen, Martine; Van Gils, Julien; Afenjar, Alexandra; Armour, Christine M; Arveiler, Benoit; Beets, Lex; Burglen, Lydie; Busa, Tiffany; Collet, Marie; Deforges, Julie; de Vries, Bert B A; Dominguez Garrido, Elena; Dorison, Nathalie; Dupont, Juliette; Francannet, Christine; Garciá-Minaúr, Sixto; Gabau Vila, Elisabeth; Gebre-Medhin, Samuel; Gener Querol, Blanca; Geneviève, David; Gérard, Marion; Gervasini, Cristina Giovanna; Goldenberg, Alice; Josifova, Dragana; Lachlan, Katherine; Maas, Saskia; Maranda, Bruno; Moilanen, Jukka S; Nordgren, Ann; Parent, Philippe; Rankin, Julia; Reardon, Willie; Rio, Marlène; Roume, Joëlle; Shaw, Adam; Smigiel, Robert; Sojo, Amaia; Solomon, Benjamin; Stembalska, Agnieszka; Stumpel, Constance; Suarez, Francisco; Terhal, Paulien; Thomas, Simon; Touraine, Renaud; Verloes, Alain; Vincent-Delorme, Catherine; Wincent, Josephine; Peters, Dorien J M; Bartsch, Oliver; Larizza, Lidia; Lacombe, Didier; Hennekam, Raoul C

    2016-12-01

    Rubinstein-Taybi syndrome (RSTS) is a developmental disorder characterized by a typical face and distal limbs abnormalities, intellectual disability, and a vast number of other features. Two genes are known to cause RSTS, CREBBP in 60% and EP300 in 8-10% of clinically diagnosed cases. Both paralogs act in chromatin remodeling and encode for transcriptional co-activators interacting with >400 proteins. Up to now 26 individuals with an EP300 mutation have been published. Here, we describe the phenotype and genotype of 42 unpublished RSTS patients carrying EP300 mutations and intragenic deletions and offer an update on another 10 patients. We compare the data to 308 individuals with CREBBP mutations. We demonstrate that EP300 mutations cause a phenotype that typically resembles the classical RSTS phenotype due to CREBBP mutations to a great extent, although most facial signs are less marked with the exception of a low-hanging columella. The limb anomalies are more similar to those in CREBBP mutated individuals except for angulation of thumbs and halluces which is very uncommon in EP300 mutated individuals. The intellectual disability is variable but typically less marked whereas the microcephaly is more common. All types of mutations occur but truncating mutations and small rearrangements are most common (86%). Missense mutations in the HAT domain are associated with a classical RSTS phenotype but otherwise no genotype-phenotype correlation is detected. Pre-eclampsia occurs in 12/52 mothers of EP300 mutated individuals versus in 2/59 mothers of CREBBP mutated individuals, making pregnancy with an EP300 mutated fetus the strongest known predictor for pre-eclampsia. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Overeating phenotypes in overweight and obese children.

    Science.gov (United States)

    Boutelle, Kerri N; Peterson, Carol B; Crosby, Ross D; Rydell, Sarah A; Zucker, Nancy; Harnack, Lisa

    2014-05-01

    The purpose of this study was to identify overeating phenotypes and their correlates in overweight and obese children. One hundred and seventeen treatment-seeking overweight and obese 8-12year-old children and their parents completed the study. Children completed an eating in the absence of hunger (EAH) paradigm, the Eating Disorder Examination interview, and measurements of height and weight. Parents and children completed questionnaires that evaluated satiety responsiveness, food responsiveness, negative affect eating, external eating and eating in the absence of hunger. Latent profile analysis was used to identify heterogeneity in overeating phenotypes in the child participants. Latent classes were then compared on measures of demographics, obesity status and nutritional intake. Three latent classes of overweight and obese children were identified: High Satiety Responsive, High Food Responsive, and Moderate Satiety and Food Responsive. Results indicated that the High Food Responsive group had higher BMI and BMI-Z scores compared to the High Satiety Responsive group. No differences were found among classes in demographics or nutritional intake. This study identified three overeating phenotypes, supporting the heterogeneity of eating patterns associated with overweight and obesity in treatment-seeking children. These finding suggest that these phenotypes can potentially be used to identify high risk groups, inform prevention and intervention targets, and develop specific treatments for these behavioral phenotypes. Copyright © 2014. Published by Elsevier Ltd.

  5. DEVELOPMENTAL FOLLOW-UP OF A FEMALE INFANT WITH RECOMBINANT DOWN SYNDROME UP TO THREE AND A HALF YEARS

    Directory of Open Access Journals (Sweden)

    Darija Strah

    2018-02-01

    Full Text Available Background: Recombinant Down Syndrome with partial duplication of the long arm of chromosome 21 represents a rare form of partial trisomy 21. The cause is mostly chromosome rearrangement- pericentric inversion of maternal or paternal homologous chromosome 21 and duplication of Down syndrome critical region p11.1q22.1, resulting in a child with phenotypical signs of classical Down syndrome with psychomotorical developmental delay. Methods: We describe a Down sydrome female infant with partial trisomy of chromosome 21. Ultra- sound screening for Down syndrome in the first trimester of pregnancy determined high risk for chromosomal abnormality. Amniocentesis showed normal prenatal karyotype. After birth a female infant started to show symptoms and signs, typical for classical Down syndrome. Postnatal karyotype revealed pericentric inversion and duplication of one chro- mosome 21 of maternal origin in the p11.1q22.1 region. The follow up of female infant up to three and a half years shows signs of psychomotorical delay with no structural defects. Therefore her developmental amelioration is less expressed compared to classical Down syndrome. Conclusions: Developmental follow up of a girl with partial trisomy 21 reveals a lot of similarities with the development of children with classical trisomy 21, but less expressed: facial gestalt, short statue, hypotonia and intellectual disabilities. Global developmental delay in spite of developmental treatment grows more and more evidently.

  6. Male-mediated developmental toxicity

    International Nuclear Information System (INIS)

    Anderson, Diana

    2005-01-01

    In recent years, the public has become more aware that exposure of males to certain agents can adversely affect their offspring and cause infertility and cancer. The hazards associated with exposure to ionising radiation have been recognised for nearly a century, but interest was aroused when a cluster of leukaemia cases was identified in young children living in Seascale, close to the nuclear processing plant at Sellafield in West Cumbria. There was a civil court case on behalf of two of the alleged victims of paternal irradiation at Seascale against British Nuclear Fuels. The case foundered on 'the balance of probabilities'. Nevertheless, there was support for paternal exposure from Japanese experimental X-ray studies in mice. The tumours were clearly heritable as shown by F2 transmission. Also, effects of a relatively non-toxic dose of radiation (1Gy) on cell proliferation transmitted to the embryo were manifested in the germ line of adult male mice even after two generations. In addition in humans, smoking fathers appear to give rise to tumours in the F 1 generation. Using rodent models, developmental abnormalities/congenital malformations and tumours can be studied after exposure of males in an extended dominant lethal assay and congenital malformations can be determined which have similar manifestations in humans. The foetuses can also be investigated for skeletal malformations and litters can be allowed to develop to adulthood when tumours, if present, can be observed. Karyotype analysis can be performed on foetuses and adult offspring to determine if induced genetic damage can be transmitted. Using this study design, cyclophosphamide, 1,3-butadiene and urethane have been examined and each compound produced positive responses: cyclophosphamide in all endpoints examined, 1,3-butadiene in some and urethane only produced liver tumours in F 1 male offspring. This suggests the endpoints are determined by independent genetic events. The results from heritable

  7. Toxic hydrogen sulfide and dark caves: phenotypic and genetic divergence across two abiotic environmental gradients in Poecilia mexicana.

    Science.gov (United States)

    Tobler, Michael; Dewitt, Thomas J; Schlupp, Ingo; García de León, Francisco J; Herrmann, Roger; Feulner, Philine G D; Tiedemann, Ralph; Plath, Martin

    2008-10-01

    Divergent natural selection drives evolutionary diversification. It creates phenotypic diversity by favoring developmental plasticity within populations or genetic differentiation and local adaptation among populations. We investigated phenotypic and genetic divergence in the livebearing fish Poecilia mexicana along two abiotic environmental gradients. These fish typically inhabit nonsulfidic surface rivers, but also colonized sulfidic and cave habitats. We assessed phenotypic variation among a factorial combination of habitat types using geometric and traditional morphometrics, and genetic divergence using quantitative and molecular genetic analyses. Fish in caves (sulfidic or not) exhibited reduced eyes and slender bodies. Fish from sulfidic habitats (surface or cave) exhibited larger heads and longer gill filaments. Common-garden rearing suggested that these morphological differences are partly heritable. Population genetic analyses using microsatellites as well as cytochrome b gene sequences indicate high population differentiation over small spatial scale and very low rates of gene flow, especially among different habitat types. This suggests that divergent environmental conditions constitute barriers to gene flow. Strong molecular divergence over short distances as well as phenotypic and quantitative genetic divergence across habitats in directions classic to fish ecomorphology suggest that divergent selection is structuring phenotypic variation in this system.

  8. Embryonic left-right separation mechanism allows confinement of mutation-induced phenotypes to one lateral body half of bilaterians.

    Science.gov (United States)

    Ma, Kun

    2013-12-01

    A fundamental question in developmental biology is how a chimeric animal such as a bilateral gynandromorphic animal can have different phenotypes confined to different lateral body halves, and how mutation-induced phenotypes, such as genetic diseases, can be confined to one lateral body half in patients. Here, I propose that embryos of many, if not all, bilaterian animals are divided into left and right halves at a very early stage (which may vary among different types of animals), after which the descendants of the left-sided and right-sided cells will almost exclusively remain on their original sides, respectively, throughout the remaining development. This embryonic left-right separation mechanism allows (1) mutations and the mutation-induced phenotypes to be strictly confined to one lateral body half in animals and humans; (2) mothers with bilateral hereditary primary breast cancer to transmit their disease to their offspring at twofold of the rate compared to mothers with unilateral hereditary breast cancer; and (3) a mosaic embryo carrying genetic or epigenetic mutations to develop into either an individual with the mutation-induced phenotype confined unilaterally, or a pair of twins displaying complete, partial, or mirror-image discordance for the phenotype. Further, this left-right separation mechanism predicts that the two lateral halves of a patient carrying a unilateral genetic disease can each serve as a case and an internal control, respectively, for genetic and epigenetic comparative studies to identify the disease causations. © 2013 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2012-01-01

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

  10. Constraints on the evolution of phenotypic plasticity

    DEFF Research Database (Denmark)

    Murren, Courtney J; Auld, Josh R.; Callahan, Hilary S

    2015-01-01

    Phenotypic plasticity is ubiquitous and generally regarded as a key mechanism for enabling organisms to survive in the face of environmental change. Because no organism is infinitely or ideally plastic, theory suggests that there must be limits (for example, the lack of ability to produce...... an optimal trait) to the evolution of phenotypic plasticity, or that plasticity may have inherent significant costs. Yet numerous experimental studies have not detected widespread costs. Explicitly differentiating plasticity costs from phenotype costs, we re-evaluate fundamental questions of the limits...... to the evolution of plasticity and of generalists vs specialists. We advocate for the view that relaxed selection and variable selection intensities are likely more important constraints to the evolution of plasticity than the costs of plasticity. Some forms of plasticity, such as learning, may be inherently...

  11. Phenotype Development in Adolescents With Tourette Syndrome

    DEFF Research Database (Denmark)

    Groth, Camilla; Debes, Nanette Mol; Skov, Liselotte

    2017-01-01

    Tourette syndrome (TS) is a neurodevelopmental disorder characterized by frequent comorbidities and a wide spectrum of phenotype presentations. This study aimed to describe the development of phenotypes in TS and tic-related impairment in a large longitudinal study of 226 children and adolescents...... followed up after 6 years. The participants were clinically examined to assess tic severity and impairment, obsessive compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD). The development in phenotypes changed toward less comorbidity with 40% TS-only (no OCD or ADHD) (TS without...... OCD or ADHD) at baseline and 55% at follow-up.Tic-related impairment was expected to improve with an age-related tic decline, but surprisingly the impairment score did not reflect the tic decline. Sex, vocal and motor tics, and OCD and ADHD severity were highly significantly correlated...

  12. Semi-supervised Learning for Phenotyping Tasks.

    Science.gov (United States)

    Dligach, Dmitriy; Miller, Timothy; Savova, Guergana K

    2015-01-01

    Supervised learning is the dominant approach to automatic electronic health records-based phenotyping, but it is expensive due to the cost of manual chart review. Semi-supervised learning takes advantage of both scarce labeled and plentiful unlabeled data. In this work, we study a family of semi-supervised learning algorithms based on Expectation Maximization (EM) in the context of several phenotyping tasks. We first experiment with the basic EM algorithm. When the modeling assumptions are violated, basic EM leads to inaccurate parameter estimation. Augmented EM attenuates this shortcoming by introducing a weighting factor that downweights the unlabeled data. Cross-validation does not always lead to the best setting of the weighting factor and other heuristic methods may be preferred. We show that accurate phenotyping models can be trained with only a few hundred labeled (and a large number of unlabeled) examples, potentially providing substantial savings in the amount of the required manual chart review.

  13. Relationship between endophenotype and phenotype in ADHD

    Directory of Open Access Journals (Sweden)

    Buitelaar Jan K

    2008-01-01

    Full Text Available Abstract Background It has been hypothesized that genetic and environmental factors relate to psychiatric disorders through the effect of intermediating, vulnerability traits called endophenotypes. The study had a threefold aim: to examine the predictive validity of an endophenotypic construct for the ADHD diagnosis, to test whether the magnitude of group differences at the endophenotypic and phenotypic level is comparable, and to investigate whether four factors (gender, age, IQ, rater bias have an effect (moderation or mediation on the relation between endophenotype and phenotype. Methods Ten neurocognitive tasks were administered to 143 children with ADHD, 68 non-affected siblings, and 120 control children (first-borns and 132 children with ADHD, 78 non-affected siblings, and 113 controls (second-borns (5 – 19 years. The task measures have been investigated previously for their endophenotypic viability and were combined to one component which was labeled 'the endophenotypic construct': one measure representative of endophenotypic functioning across several domains of functioning. Results The endophenotypic construct classified children with moderate accuracy (about 50% for each of the three groups. Non-affected children differed as much from controls at the endophenotypic as at the phenotypic level, but affected children displayed a more severe phenotype than endophenotype. Although a potentially moderating effect (age and several mediating effects (gender, age, IQ were found affecting the relation between endophenotypic construct and phenotype, none of the effects studied could account for the finding that affected children had a more severe phenotype than endophenotype. Conclusion Endophenotypic functioning is moderately predictive of the ADHD diagnosis, though findings suggest substantial overlap exists between endophenotypic functioning in the groups of affected children, non-affected siblings, and controls. Results suggest other

  14. Phenotypic Approaches to Drought in Cassava: Review

    Directory of Open Access Journals (Sweden)

    Emmanuel eOkogbenin

    2013-05-01

    Full Text Available Cassava is an important crop in Africa, Asia, Latin America and the Caribbean. Cassava can be produced adequately in drought conditions making it the ideal food security crop in marginal environments. Although cassava can tolerate drought stress, it can be genetically improved to enhance productivity in such environments. Drought adaptation studies in over three decades in cassava have identified relevant mechanisms which have been explored in conventional breeding. Drought is a quantitative trait and its multigenic nature makes it very challenging to effectively manipulate and combine genes in breeding for rapid genetic gain and selection process. Cassava has a long growth cycle of 12 - 18 months which invariably contributes to a long breeding scheme for the crop. Modern breeding using advances in genomics and improved genotyping, is facilitating the dissection and genetic analysis of complex traits including drought tolerance, thus helping to better elucidate and understand the genetic basis of such traits. A beneficial goal of new innovative breeding strategies is to shorten the breeding cycle using minimized, efficient or fast phenotyping protocols. While high throughput genotyping have been achieved, this is rarely the case for phenotyping for drought adaptation. Some of the storage root phenotyping in cassava are often done very late in the evaluation cycle making selection process very slow. This paper highlights some modified traits suitable for early-growth phase phenotyping that may be used to reduce drought phenotyping cycle in cassava. Such modified traits can significantly complement the high throughput genotyping procedures to fast track breeding of improved drought tolerant varieties. The need for metabolite profiling, improved phenomics to take advantage of next generation sequencing technologies and high throughput phenotyping are basic steps for future direction to improve genetic gain and maximize speed for drought tolerance

  15. Developmental toxicology: adequacy of current methods.

    Science.gov (United States)

    Peters, P W

    1998-01-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

  17. Developmental Transcriptome for a Facultatively Eusocial Bee, Megalopta genalis.

    Science.gov (United States)

    Jones, Beryl M; Wcislo, William T; Robinson, Gene E

    2015-08-14

    Transcriptomes provide excellent foundational resources for mechanistic and evolutionary analyses of complex traits. We present a developmental transcriptome for the facultatively eusocial bee Megalopta genalis, which represents a potential transition point in the evolution of eusociality. A de novo transcriptome assembly of Megalopta genalis was generated using paired-end Illumina sequencing and the Trinity assembler. Males and females of all life stages were aligned to this transcriptome for analysis of gene expression profiles throughout development. Gene Ontology analysis indicates that stage-specific genes are involved in ion transport, cell-cell signaling, and metabolism. A number of distinct biological processes are upregulated in each life stage, and transitions between life stages involve shifts in dominant functional processes, including shifts from transcriptional regulation in embryos to metabolism in larvae, and increased lipid metabolism in adults. We expect that this transcriptome will provide a useful resource for future analyses to better understand the molecular basis of the evolution of eusociality and, more generally, phenotypic plasticity. Copyright © 2015 Jones et al.

  18. Developmentalism: An Obscure but Pervasive Restriction

    Directory of Open Access Journals (Sweden)

    J. E. Stone

    1996-04-01

    Full Text Available Despite continuing criticism of public education, experimentally demonstrated and field tested teaching methods have been ignored, rejected, and abandoned. Instead of a stable consensus regarding best teaching practices, there seems only an unending succession of innovations. A longstanding educational doctrine appears to underlie this anomalous state of affairs. Termed developmentalism, it presumes "natural" ontogenesis to be optimal and it requires experimentally demonstrated teaching practices to overcome a presumption that they interfere with an optimal developmental trajectory. It also discourages teachers and parents from asserting themselves with children. Instead of effective interventions, it seeks the preservation of a postulated natural perfection. Developmentalism's rich history is expressed in a literature extending over 400 years. Its notable exponents include Jean Jacques Rousseau, John Dewey, and Jean Piaget; and its most recent expressions include "developmentally appropriate practice" and "constructivism." In the years during which it gained ascendance, developmentalism served as a basis for rejecting harsh and inhumane teaching methods. Today it impedes efforts to hold schools accountable for student academic achievement.

  19. Assessing the Developmental Neurotoxicity of 27 ...

    Science.gov (United States)

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

  20. Replication and robustness in developmental research.

    Science.gov (United States)

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

    2014-11-01

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

  1. The Comet Cometh: Evolving Developmental Systems.

    Science.gov (United States)

    Jaeger, Johannes; Laubichler, Manfred; Callebaut, Werner

    In a recent opinion piece, Denis Duboule has claimed that the increasing shift towards systems biology is driving evolutionary and developmental biology apart, and that a true reunification of these two disciplines within the framework of evolutionary developmental biology (EvoDevo) may easily take another 100 years. He identifies methodological, epistemological, and social differences as causes for this supposed separation. Our article provides a contrasting view. We argue that Duboule's prediction is based on a one-sided understanding of systems biology as a science that is only interested in functional, not evolutionary, aspects of biological processes. Instead, we propose a research program for an evolutionary systems biology, which is based on local exploration of the configuration space in evolving developmental systems. We call this approach-which is based on reverse engineering, simulation, and mathematical analysis-the natural history of configuration space. We discuss a number of illustrative examples that demonstrate the past success of local exploration, as opposed to global mapping, in different biological contexts. We argue that this pragmatic mode of inquiry can be extended and applied to the mathematical analysis of the developmental repertoire and evolutionary potential of evolving developmental mechanisms and that evolutionary systems biology so conceived provides a pragmatic epistemological framework for the EvoDevo synthesis.

  2. Clinical spectrum and genotype-phenotype associations of KCNA2-related encephalopathies.

    Science.gov (United States)

    Masnada, Silvia; Hedrich, Ulrike B S; Gardella, Elena; Schubert, Julian; Kaiwar, Charu; Klee, Eric W; Lanpher, Brendan C; Gavrilova, Ralitza H; Synofzik, Matthis; Bast, Thomas; Gorman, Kathleen; King, Mary D; Allen, Nicholas M; Conroy, Judith; Ben Zeev, Bruria; Tzadok, Michal; Korff, Christian; Dubois, Fanny; Ramsey, Keri; Narayanan, Vinodh; Serratosa, Jose M; Giraldez, Beatriz G; Helbig, Ingo; Marsh, Eric; O'Brien, Margaret; Bergqvist, Christina A; Binelli, Adrian; Porter, Brenda; Zaeyen, Eduardo; Horovitz, Dafne D; Wolff, Markus; Marjanovic, Dragan; Caglayan, Hande S; Arslan, Mutluay; Pena, Sergio D J; Sisodiya, Sanjay M; Balestrini, Simona; Syrbe, Steffen; Veggiotti, Pierangelo; Lemke, Johannes R; Møller, Rikke S; Lerche, Holger; Rubboli, Guido

    2017-09-01

    Recently, de novo mutations in the gene KCNA2, causing either a dominant-negative loss-of-function or a gain-of-function of the voltage-gated K+ channel Kv1.2, were described to cause a new molecular entity within the epileptic encephalopathies. Here, we report a cohort of 23 patients (eight previously described) with epileptic encephalopathy carrying either novel or known KCNA2 mutations, with the aim to detail the clinical phenotype associated with each of them, to characterize the functional effects of the newly identified mutations, and to assess genotype-phenotype associations. We identified five novel and confirmed six known mutations, three of which recurred in three, five and seven patients, respectively. Ten mutations were missense and one was a truncation mutation; de novo occurrence could be shown in 20 patients. Functional studies using a Xenopus oocyte two-microelectrode voltage clamp system revealed mutations with only loss-of-function effects (mostly dominant-negative current amplitude reduction) in eight patients or only gain-of-function effects (hyperpolarizing shift of voltage-dependent activation, increased amplitude) in nine patients. In six patients, the gain-of-function was diminished by an additional loss-of-function (gain-and loss-of-function) due to a hyperpolarizing shift of voltage-dependent activation combined with either decreased amplitudes or an additional hyperpolarizing shift of the inactivation curve. These electrophysiological findings correlated with distinct phenotypic features. The main differences were (i) predominant focal (loss-of-function) versus generalized (gain-of-function) seizures and corresponding epileptic discharges with prominent sleep activation in most cases with loss-of-function mutations; (ii) more severe epilepsy, developmental problems and ataxia, and atrophy of the cerebellum or even the whole brain in about half of the patients with gain-of-function mutations; and (iii) most severe early-onset phenotypes

  3. Transgenerational transmission of a stress-coping phenotype programmed by early-life stress in the Japanese quail

    Science.gov (United States)

    Zimmer, Cédric; Larriva, Maria; Boogert, Neeltje J.; Spencer, Karen A.

    2017-01-01

    An interesting aspect of developmental programming is the existence of transgenerational effects that influence offspring characteristics and performance later in life. These transgenerational effects have been hypothesized to allow individuals to cope better with predictable environmental fluctuations and thus facilitate adaptation to changing environments. Here, we test for the first time how early-life stress drives developmental programming and transgenerational effects of maternal exposure to early-life stress on several phenotypic traits in their offspring in a functionally relevant context using a fully factorial design. We manipulated pre- and/or post-natal stress in both Japanese quail mothers and offspring and examined the consequences for several stress-related traits in the offspring generation. We show that pre-natal stress experienced by the mother did not simply affect offspring phenotype but resulted in the inheritance of the same stress-coping traits in the offspring across all phenotypic levels that we investigated, shaping neuroendocrine, physiological and behavioural traits. This may serve mothers to better prepare their offspring to cope with later environments where the same stressors are experienced. PMID:28387355

  4. Phenotypical expression of reduced mobility during limb ontogeny in frogs: the knee-joint case

    Directory of Open Access Journals (Sweden)

    Maria Laura Ponssa

    2016-02-01

    Full Text Available Movement is one of the most important epigenetic factors for normal development of the musculoskeletal system, particularly during genesis and joint development. Studies regarding alterations to embryonic mobility, performed on anurans, chickens and mammals, report important phenotypical similarities as a result of the reduction or absence of this stimulus. The precise stage of development at which the stimulus modification generates phenotypic modifications however, is yet to be determined. In this work we explore whether the developmental effects of abnormal mobility can appear at any time during development or whether they begin to express themselves in particular phases of tadpole ontogeny. We conducted five experiments that showed that morphological abnormalities are not visible until Stages 40–42. Morphology in earlier stages remains normal, probably due to the fact that the bones/muscles/tendons have not yet developed and therefore are not affected by immobilization. These results suggest the existence of a specific period of phenotypical expression in which normal limb movement is necessary for the correct development of the joint tissue framework.

  5. Homeostatic properties and phenotypic maturation of murine CD4+ pre-thymic emigrants in the thymus.

    Directory of Open Access Journals (Sweden)

    Jie Dong

    Full Text Available After a tightly regulated developmental program in the thymus, "mature" single positive (SP thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4(+ pre-RTEs, a population of CD4(+ SP thymocytes that have acquired the thymus egress capability. Compared to peripheral naïve T cells, CD4(+ pre-RTEs displayed superior survival capability in lymphoreplete mice and faster proliferation under lymphopenic condition. The differences in Bcl2/Bim expression and/or heightened IL-7 signaling pathway may account for the pre-RTEs' better responsiveness to homeostatic signals. Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4(+ pre-RTEs in thymic perivascular space. Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs. The dendritic cell-driven Qa2 induction of CD4(+ pre-RTEs is independent of MHC class II and Aire molecules.

  6. Social phenotypes of autism spectrum disorders and Williams syndrome: similarities and differences

    Directory of Open Access Journals (Sweden)

    Kosuke eAsada

    2012-07-01

    Full Text Available Autism spectrum disorders (ASD and Williams syndrome (WS both are neurodevelopmental disorders, each with a unique social phenotypic pattern. This review article aims to define the similarities and differences between the social phenotypes of ASD and WS. We review studies that have examined individuals with WS using diagnostic assessments such as the Autism Diagnostic Observation Schedule (ADOS, cross-syndrome direct comparison studies, and studies that have individually examined either disorder. We conclude that (1 Individuals with these disorders show quite contrasting phenotypes for face processing (i.e., preference to faces and eyes and sociability (i.e., interest in and motivation to interact with others, and (2 Although the ADOS and a direct comparison study on pragmatic language ability suggest more deficits in ASD, individuals with WS are similarly impaired on social cognition and communicative skills. In light of these results, we discuss how cross-syndrome comparisons between ASD and WS can contribute to developmental theory, cognitive neuroscience, and the development and choice of clinical treatments.

  7. Phenotype of a child with Angelman syndrome born to a woman with Prader-Willi syndrome.

    Science.gov (United States)

    Ostergaard, John R

    2015-09-01

    This report describes the phenotype, from early childhood to adolescence, of a girl with Angelman syndrome (AS) born following a maternal transmission of a germline paternal 15q11.2-q13 deletion. During early childhood, she showed a typical AS phenotype, such as jerky movements, poor sleep, high voltage electroencephalography pattern, epilepsy, and a severe developmental disability. As she grew older, indications of phenotypical traits similar to Prader-Willi syndrome (PWS) appeared, in particular hyperphagic behavior and a body fat distribution similar to that reported in PWS. She generally showed cheerful AS behavior and had the characteristic outbursts of laughter, but her attitude to other people did not reflect the usual shared enjoyment of interaction seen in children with AS. In unfamiliar surroundings, she withdrew socially, similar to children with PWS, and her insistence on the same, rigid routines was similar to behavior patterns in PWS. The dysmorphic facial features that characterize AS were blurred in adolescence. The specified features that this AS patient had in common with PWS were hardly incidental and, if verified by upcoming case reports of children born to women with a paternal 15q11.2-q13 deletion, they may show new aspects of genetic imprinting. © 2015 Wiley Periodicals, Inc.

  8. Intracranial developmental venous anomaly: is it asymptomatic?

    Science.gov (United States)

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

    2018-03-16

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

  9. Infant developmental milestones and adult intelligence

    DEFF Research Database (Denmark)

    Flensborg-Madsen, Trine; Mortensen, Erik Lykke

    2015-01-01

    Intelligence Scale (WAIS). Associations between motor developmental milestones and IQwere analysed bymultiple linear regression adjusting for potential confounding factors. Results: Later acquisition of infant developmental milestones was associated with lower subsequent IQ, and the majority of significant......Background: A number of studies suggest a positive association between faster infant motor development and intellectual function in childhood and adolescence. However, studies investigating the relationship between infant motor development and intelligence in adulthood are lacking. Aims......: To investigate whether age at achievement of 12 motor developmental milestones was associated with adult intelligence and to evaluate the influence of sex, parental social status, parity,mother's cigarette consumption in the last trimester, gestational age, birthweight, and birth length on this association...

  10. Normal composite face effects in developmental prosopagnosia.

    Science.gov (United States)

    Biotti, Federica; Wu, Esther; Yang, Hua; Jiahui, Guo; Duchaine, Bradley; Cook, Richard

    2017-10-01

    Upright face perception is thought to involve holistic processing, whereby local features are integrated into a unified whole. Consistent with this view, the top half of one face appears to fuse perceptually with the bottom half of another, when aligned spatially and presented upright. This 'composite face effect' reveals a tendency to integrate information from disparate regions when faces are presented canonically. In recent years, the relationship between susceptibility to the composite effect and face recognition ability has received extensive attention both in participants with normal face recognition and participants with developmental prosopagnosia. Previous results suggest that individuals with developmental prosopagnosia may show reduced susceptibility to the effect suggestive of diminished holistic face processing. Here we describe two studies that examine whether developmental prosopagnosia is associated with reduced composite face effects. Despite using independent samples of developmental prosopagnosics and different composite procedures, we find no evidence for reduced composite face effects. The experiments yielded similar results; highly significant composite effects in both prosopagnosic groups that were similar in magnitude to the effects found in participants with normal face processing. The composite face effects exhibited by both samples and the controls were greatly diminished when stimulus arrangements were inverted. Our finding that the whole-face binding process indexed by the composite effect is intact in developmental prosopagnosia indicates that other factors are responsible for developmental prosopagnosia. These results are also inconsistent with suggestions that susceptibility to the composite face effect and face recognition ability are tightly linked. While the holistic process revealed by the composite face effect may be necessary for typical face perception, it is not sufficient; individual differences in face recognition ability

  11. Phenotypic characterisation and molecular polymorphism of ...

    African Journals Online (AJOL)

    The study of the phenotypic characterisation and molecular polymorphism of local chicken populations was carried out in Benin on 326 chickens of the Forest ecological area and 316 of the Savannah ecological area, all were 7 months old at least. The collection of blood for the molecular typing was achieved on 121 ...

  12. Evidence for a Broad Autism Phenotype

    NARCIS (Netherlands)

    K. de Groot (Kristel); J.W. van Strien (Jan)

    2017-01-01

    textabstractThe broad autism phenotype implies the existence of a continuum ranging from individuals displaying almost no autistic traits to severely impaired diagnosed individuals. Recent studies have linked this variation in autistic traits to several domains of functioning. However, studies

  13. phenotype correlation of methylene tetrahydrofolate reductase ...

    African Journals Online (AJOL)

    Rabah M. Shawky

    2014-06-21

    Jun 21, 2014 ... children with autism and to correlate them with different phenotypes. Subjects and ... of impairments in communication, reciprocal social interac- tions, and ... isolation was obtained from peripheral blood samples using the spin ... IQ, while ten of them (50%) had mild mental retardation and six patients (30%) ...

  14. Phenotype Presentation of Hypophosphatemic Rickets in Adults

    DEFF Research Database (Denmark)

    Beck-Nielsen, Signe S; Brusgaard, Klaus; Rasmussen, Lars M

    2010-01-01

    Hypophosphatemic rickets (HR) is a group of rare disorders caused by excessive renal phosphate wasting. The purpose of this cross-sectional study of 38 HR patients was to characterize the phenotype of adult HR patients. Moreover, skeletal and endodontic severity scores were defined to assess poss...

  15. Phenotypic and molecular characterization of Salmonella serotypes ...

    African Journals Online (AJOL)

    The presence of Salmonella and human pathogens in unpasteurized milk remains a public health hazard. The study reported the phenotypic and molecular characterization of Salmonella serotypes in cow raw milk, cheese and traditional yoghurt marketed for man's consumption in Nigeria. Isolation of Salmonella was done ...

  16. (RR) soybean cultivars estimated by phenotypic characteristics

    African Journals Online (AJOL)

    SAM

    2014-06-25

    Jun 25, 2014 ... phenotypic characteristics and microsatellite molecular markers (SSR). ... discriminatory analysis, principal components, coordinate and cluster analysis .... were employed with 10.000 simulations to attribute significance values to ...... association analysis of protein and oil content in food-grade soybeans ...

  17. Colorectal Cancer "Methylator Phenotype": Fact or Artifact?

    Directory of Open Access Journals (Sweden)

    Charles Anacleto

    2005-04-01

    Full Text Available It has been proposed that human colorectal tumors can be classified into two groups: one in which methylation is rare, and another with methylation of several loci associated with a "CpG island methylated phenotype (CIMP," characterized by preferential proximal location in the colon, but otherwise poorly defined. There is considerable overlap between this putative methylator phenotype and the well-known mutator phenotype associated with microsatellite instability (MSI. We have examined hypermethylation of the promoter region of five genes (DAPK, MGMT, hMLH1, p16INK4a, and p14ARF in 106 primary colorectal cancers. A graph depicting the frequency of methylated loci in the series of tumors showed a continuous, monotonically decreasing distribution quite different from the previously claimed discontinuity. We observed a significant association between the presence of three or more methylated loci and the proximal location of the tumors. However, if we remove from analysis the tumors with hMLH1 methylation or those with MSI, the significance vanishes, suggesting that the association between multiple methylations and proximal location was indirect due to the correlation with MSI. Thus, our data do not support the independent existence of the so-called methylator phenotype and suggest that it rather may represent a statistical artifact caused by confounding of associations.

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

    Directory of Open Access Journals (Sweden)

    Wu Dong

    2016-08-01

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

  19. Developmental trajectories and breakdown in F1 interpopulation hybrids of Tribolium castaneum

    Science.gov (United States)

    Drury, Douglas W; Ehmke, Ross C; Jideonwo, Victoria N; Wade, Michael J

    2013-01-01

    When hybrid inviability is an indirect by-product of local adaptation, we expect its degree of severity between pairs of populations to vary and to be sensitive to the environment. While complete reciprocal hybrid inviability is the outcome of the gradual process of local adaptation, it is not representative of the process of accumulation of incompatibility. In the flour beetle, Tribolium castaneum, some pairs of populations exhibit complete, reciprocal F1 hybrid incompatibility while other pairs are fully or partially compatible. We characterize this naturally occurring variation in the degree and timing of expression of the hybrid incompatible phenotype to better understand the number of genes or developmental processes contributing to speciation. We assessed the morphological and developmental variation in four Tribolium castaneum populations and their 12 possible F1 hybrids at each life-history stage from egg to adult. We find that the rate of hybrid larval development is affected in all interpopulation crosses, including those eventually producing viable, fertile adults. Hybrid incompatibility manifests early in development as changes in the duration of instars and diminished success in the transition between instars are relative to the parent populations. Parent populations with similar developmental profiles may produce hybrids with disrupted development. The degree and timing of expression of hybrid inviability depends upon populations crossed, direction of the cross, and environment in which hybrids are raised. Our findings suggest that the coordinated expression of genes involved in transitional periods of development is the underlying cause of hybrid incompatibility in this species. PMID:23919145

  20. Tracking and Quantifying Developmental Processes in C. elegans Using Open-source Tools.

    Science.gov (United States)

    Dutta, Priyanka; Lehmann, Christina; Odedra, Devang; Singh, Deepika; Pohl, Christian

    2015-12-16

    Quantitatively capturing developmental processes is crucial to derive mechanistic models and key to identify and describe mutant phenotypes. Here protocols are presented for preparing embryos and adult C. elegans animals for short- and long-term time-lapse microscopy and methods for tracking and quantification of developmental processes. The methods presented are all based on C. elegans strains available from the Caenorhabditis Genetics Center and on open-source software that can be easily implemented in any laboratory independently of the microscopy system used. A reconstruction of a 3D cell-shape model using the modelling software IMOD, manual tracking of fluorescently-labeled subcellular structures using the multi-purpose image analysis program Endrov, and an analysis of cortical contractile flow using PIVlab (Time-Resolved Digital Particle Image Velocimetry Tool for MATLAB) are shown. It is discussed how these methods can also be deployed to quantitatively capture other developmental processes in different models, e.g., cell tracking and lineage tracing, tracking of vesicle flow.

  1. Tibial and fibular developmental fields defects

    International Nuclear Information System (INIS)

    Khoury, N.J.; Haddad, M.C.; Hourani, M.H.

    1999-01-01

    Malformations of the lower limbs are rare and heterogeneous anomalies. To explain the diversity and complexity of these abnormalities, authors introduced the concept of tibial and fibular developmental fields. Defects in these fields are responsible for different malformations, which have been described, to our knowledge, in only one report in the radiology literature. We present a case of a newborn with femoral bifurcation, absent fibulae and talar bones, ankle and foot malformations, and associated atrial septal defect. Our case is an example of defects in both fibular and tibial developmental fields. (orig.)

  2. Developmental biology in marine invertebrate symbioses.

    Science.gov (United States)

    McFall-Ngai, M J; Ruby, E G

    2000-12-01

    Associations between marine invertebrates and their cooperative bacterial symbionts offer access to an understanding of the roots of host-microbe interaction; for example, several symbioses like the squid-vibrio light organ association serve as models for investigating how each partner affects the developmental biology of the other. Previous results have identified a program of specific developmental events that unfolds as the association is initiated. In the past year, published studies have focused primarily on describing the mechanisms underlying the signaling processes that occur between the juvenile squid and the luminous bacteria that colonize it.

  3. Worm Phenotype Ontology: Integrating phenotype data within and beyond the C. elegans community

    Directory of Open Access Journals (Sweden)

    Yook Karen

    2011-01-01

    Full Text Available Abstract Background Caenorhabditis elegans gene-based phenotype information dates back to the 1970's, beginning with Sydney Brenner and the characterization of behavioral and morphological mutant alleles via classical genetics in order to understand nervous system function. Since then C. elegans has become an important genetic model system for the study of basic biological and biomedical principles, largely through the use of phenotype analysis. Because of the growth of C. elegans as a genetically tractable model organism and the development of large-scale analyses, there has been a significant increase of phenotype data that needs to be managed and made accessible to the research community. To do so, a standardized vocabulary is necessary to integrate phenotype data from diverse sources, permit integration with other data types and render the data in a computable form. Results We describe a hierarchically structured, controlled vocabulary of terms that can be used to standardize phenotype descriptions in C. elegans, namely the Worm Phenotype Ontology (WPO. The WPO is currently comprised of 1,880 phenotype terms, 74% of which have been used in the annotation of phenotypes associated with greater than 18,000 C. elegans genes. The scope of the WPO is not exclusively limited to C. elegans biology, rather it is devised to also incorporate phenotypes observed in related nematode species. We have enriched the value of the WPO by integrating it with other ontologies, thereby increasing the accessibility of worm phenotypes to non-nematode biologists. We are actively developing the WPO to continue to fulfill the evolving needs of the scientific community and hope to engage researchers in this crucial endeavor. Conclusions We provide a phenotype ontology (WPO that will help to facilitate data retrieval, and cross-species comparisons within the nematode community. In the larger scientific community, the WPO will permit data integration, and

  4. Behavioural phenotypes over the lifetime of a holometabolous insect

    Science.gov (United States)

    2015-01-01

    Introduction: Behavioural traits can differ considerably between individuals, and such differences were found to be consistent over the lifetime of an organism in several species. Whether behavioural traits of holometabolous insects, which undergo a metamorphosis, are consistent across ontogeny is virtually unexplored. We investigated several behavioural parameters at five different time points in the lifetime of the holometabolous mustard leaf beetle Phaedon cochleariae (Coleoptera: Chrysomelidae), two times in the larval (second and third larval stage) and three times in the adult stage. We investigated 1) the stability of the behavioural phenotype (population level), 2) whether individuals rank consistently across behavioural traits and over their lifetime (individual level), and 3) in how far behavioural traits are correlated with the developmental time of the individuals. Results: We identified two behavioural dimensions in every life stage of P. cochleariae, activity and boldness (population level). Larvae and young adults ranked consistently across the investigated behavioural traits, whereas consistency over time was only found in adults but not between larvae and adults (individual level). Compared to adult beetles, larvae were less active. Moreover, younger larvae were bolder than all subsequent life stages. Over the adult lifetime of the beetles, males were less active than females. Furthermore, the activity of second instar larvae was significantly negatively correlated with the development time. Conclusions: Our study highlights that, although there is no individual consistency over the larval and the adult life stage, the behavioural clustering shows similar patterns at all tested life stages of a holometabolous insect. Nevertheless, age- and sex-specific differences in behavioural traits occur which may be explained by different challenges an individual faces at each life stage. These differences are presumably related to the tremendous changes in

  5. Phenotypic equilibrium as probabilistic convergence in multi-phenotype cell population dynamics.

    Directory of Open Access Journals (Sweden)

    Da-Quan Jiang

    Full Text Available We consider the cell population dynamics with n different phenotypes. Both the Markovian branching process model (stochastic model and the ordinary differential equation (ODE system model (deterministic model are presented, and exploited to investigate the dynamics of the phenotypic proportions. We will prove that in both models, these proportions will tend to constants regardless of initial population states ("phenotypic equilibrium" under weak conditions, which explains the experimental phenomenon in Gupta et al.'s paper. We also prove that Gupta et al.'s explanation is the ODE model under a special assumption. As an application, we will give sufficient and necessary conditions under which the proportion of one phenotype tends to 0 (die out or 1 (dominate. We also extend our results to non-Markovian cases.

  6. Invasion strategies in clonal aquatic plants: Are phenotypic differences caused by phenotypic plasticity or local adaptation?

    DEFF Research Database (Denmark)

    Riis, Tenna; Lambertini, Carla; Olesen, Birgit

    2010-01-01

    conditions and plant morphological characteristics. Conclusions: The results indicate that at the current stage of spread into New Zealand, the primary adaptive strategy of these three invasive macrophytes is phenotypic plasticity. However, while limited, the possibility that genetic diversity between......Background and Aims: The successful spread of invasive plants in new environments is often linked to multiple introductions and a diverse gene pool that facilitates local adaptation to variable environmental conditions. For clonal plants, however, phenotypic plasticity may be equally important....... Methods: Field populations with a large phenotypic variety were sampled in a range of lakes and streams with different chemical and physical properties. The phenotypic plasticity of the species before and after cultivation was studied in a common garden growth experiment, and the genetic diversity...

  7. The molecular and phenotypic spectrum of IQSEC2-related epilepsy.

    Science.gov (United States)

    Zerem, Ayelet; Haginoya, Kazuhiro; Lev, Dorit; Blumkin, Lubov; Kivity, Sara; Linder, Ilan; Shoubridge, Cheryl; Palmer, Elizabeth Emma; Field, Michael; Boyle, Jackie; Chitayat, David; Gaillard, William D; Kossoff, Eric H; Willems, Marjolaine; Geneviève, David; Tran-Mau-Them, Frederic; Epstein, Orna; Heyman, Eli; Dugan, Sarah; Masurel-Paulet, Alice; Piton, Ame'lie; Kleefstra, Tjitske; Pfundt, Rolph; Sato, Ryo; Tzschach, Andreas; Matsumoto, Naomichi; Saitsu, Hirotomo; Leshinsky-Silver, Esther; Lerman-Sagie, Tally

    2016-11-01

    IQSEC2 is an X-linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants. Forty-eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians. Six affected individuals had an inherited IQSEC2 variant and 12 had a de novo one (male-to-female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic-clonic (GTC) seizures. The electroclinical syndromes could be defined in five patients: late-onset epileptic spasms (three) and Lennox-Gastaut or Lennox-Gastaut-like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging (MRI) were prominent features. The phenotypic spectrum of IQSEC2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical

  8. Lettuce flavonoids screening and phenotyping by chlorophyll fluorescence excitation ratio.

    Science.gov (United States)

    Zivcak, Marek; Brückova, Klaudia; Sytar, Oksana; Brestic, Marian; Olsovska, Katarina; Allakhverdiev, Suleyman I

    2017-06-01

    Environmentally induced variation and the genotypic differences in flavonoid and phenolic content in lettuce can be reliably detected using the appropriate parameters derived from the records of rapid non-invasive fluorescence technique. The chlorophyll fluorescence excitation ratio method was designed as a rapid and non-invasive tool to estimate the content of UV-absorbing phenolic compounds in plants. Using this technique, we have assessed the dynamics of accumulation of flavonoids related to developmental changes and environmental effects. Moreover, we have tested appropriateness of the method to identify the genotypic differences and fluctuations in total phenolics and flavonoid content in lettuce. Six green and two red genotypes of lettuce (Lactuca sativa L.) grown in pots were exposed to two different environments for 50 days: direct sunlight (UV-exposed) and greenhouse conditions (low UV). The indices based on the measurements of chlorophyll fluorescence after red, green and UV excitation indicated increase of the content of UV-absorbing compounds and anthocyanins in the epidermis of lettuce leaves. In similar, the biochemical analyses performed at the end of the experiment confirmed significantly higher total phenolic and flavonoid content in lettuce plants exposed to direct sun compared to greenhouse conditions and in red compared to green genotypes. As the correlation between the standard fluorescence indices and the biochemical records was negatively influenced by the presence of red genotypes, we proposed the use of a new parameter named Modified Flavonoid Index (MFI) taking into an account both absorbance changes due to flavonol and anthocyanin content, for which the correlation with flavonoid and phenolic content was relatively good. Thus, our results confirmed that the fluorescence excitation ratio method is useful for identifying the major differences in phenolic and flavonoid content in lettuce plants and it can be used for high-throughput pre

  9. Low-Normal FMR1 CGG Repeat Length: Phenotypic Associations

    Directory of Open Access Journals (Sweden)

    Marsha eMailick

    2014-09-01

    Full Text Available This population-based study investigates genotype-phenotype correlations of low-normal CGG repeats in the fragile X mental retardation 1 (FMR1 gene. FMR1 plays an important role in brain development and function, and encodes FMRP (fragile X mental retardation protein, an RNA-binding protein that regulates protein synthesis impacting activity-dependent synaptic development and plasticity. Most past research has focused on CGG premutation expansions (41 to 200 CGG repeats and on fragile X syndrome (200+ CGG repeats, with considerably less attention on the other end of the spectrum of CGG repeats. Using existing data, older adults with 23 or fewer CGG repeats (2 SDs below the mean were compared with age-peers who have normal numbers of CGGs (24-40 with respect to cognition, mental health, cancer, and having children with disabilities. Men (n = 341 with an allele in the low-normal range and women (n = 46 with two low-normal alleles had significantly more difficulty with their memory and ability to solve day to day problems. Women with both FMR1 alleles in the low-normal category had significantly elevated odds of feeling that they need to drink more to get the same effect as in the past. These women also had two and one-half times the odds of having had breast cancer and four times the odds of uterine cancer. Men and women with low-normal CGGs had higher odds of having a child with a disability, either a developmental disability or a mental health condition. These findings are in line with the hypothesis that there is a need for tight neuronal homeostatic control mechanisms for optimal cognitive and behavioral functioning, and more generally that low numbers as well as high numbers of CGG repeats may be problematic for health.

  10. Decomposing phenotype descriptions for the human skeletal phenome.

    Science.gov (United States)

    Groza, Tudor; Hunter, Jane; Zankl, Andreas

    2013-01-01

    Over the course of the last few years there has been a significant amount of research performed on ontology-based formalization of phenotype descriptions. The intrinsic value and knowledge captured within such descriptions can only be expressed by taking advantage of their inner structure that implicitly combines qualities and anatomical entities. We present a meta-model (the Phenotype Fragment Ontology) and a processing pipeline that enable together the automatic decomposition and conceptualization of phenotype descriptions for the human skeletal phenome. We use this approach to showcase the usefulness of the generic concept of phenotype decomposition by performing an experimental study on all skeletal phenotype concepts defined in the Human Phenotype Ontology.

  11. A PEX6-defective peroxisomal biogenesis disorder with severe phenotype in an infant, versus mild phenotype resembling Usher syndrome in the affected parents.

    Science.gov (United States)

    Raas-Rothschild, Annick; Wanders, Ronald J A; Mooijer, Petra A W; Gootjes, Jeannette; Waterham, Hans R; Gutman, Alisa; Suzuki, Yasuyuki; Shimozawa, Nobuyuki; Kondo, Naomi; Eshel, Gideon; Espeel, Marc; Roels, Frank; Korman, Stanley H

    2002-04-01

    Sensorineural deafness and retinitis pigmentosa (RP) are the hallmarks of Usher syndrome (USH) but are also prominent features in peroxisomal biogenesis defects (PBDs); both are autosomal recessively inherited. The firstborn son of unrelated parents, who both had sensorineural deafness and RP diagnosed as USH, presented with sensorineural deafness, RP, dysmorphism, developmental delay, hepatomegaly, and hypsarrhythmia and died at age 17 mo. The infant was shown to have a PBD, on the basis of elevated plasma levels of very-long- and branched-chain fatty acids (VLCFAs and BCFAs), deficiency of multiple peroxisomal functions in fibroblasts, and complete absence of peroxisomes in fibroblasts and liver. Surprisingly, both parents had elevated plasma levels of VLCFAs and BCFAs. Fibroblast studies confirmed that both parents had a PBD. The parents' milder phenotypes correlated with relatively mild peroxisomal biochemical dysfunction and with catalase immunofluorescence microscopy demonstrating mosaicism and temperature sensitivity in fibroblasts. The infant and both of his parents belonged to complementation group C. PEX6 gene sequencing revealed mutations on both alleles, in the infant and in his parents. This unique family is the first report of a PBD with which the parents are themselves affected individuals rather than asymptomatic carriers. Because of considerable overlap between USH and milder PBD phenotypes, individuals suspected to have USH should be screened for peroxisomal dysfunction.

  12. Working Memory and Developmental Language Impairments

    Science.gov (United States)

    Henry, Lucy A.; Botting, Nicola

    2017-01-01

    Children with developmental language impairments (DLI) are often reported to show difficulties with working memory. This review describes the four components of the well-established working memory model, and considers whether there is convincing evidence for difficulties within each component in children with DLI. The emphasis is on the most…

  13. Developmental Predictors of Fraction Concepts and Procedures

    Science.gov (United States)

    Jordan, Nancy C.; Hansen, Nicole; Fuchs, Lynn S.; Siegler, Robert S.; Gersten, Russell; Micklos, Deborah

    2013-01-01

    Developmental predictors of children's fraction concepts and procedures at the end of fourth grade were investigated in a 2-year longitudinal study. Participants were 357 children who started the study in third grade. Attentive behavior, language, nonverbal reasoning, number line estimation, calculation fluency, and reading fluency each…

  14. Common Developmental Tasks in Forming Reconstituted Families.

    Science.gov (United States)

    Kleinman, Judith

    1979-01-01

    Developmental tasks common to the formation of a reconstituted family are described, particularly the continued mourning of the old family; the formation of a solid marital relationship despite the difficulties presented by past failures and the presence of children; and the formation of sibling alliances across family lines. (Author)

  15. Unmasking Abilities Hidden by Developmental Conditions.

    Science.gov (United States)

    Mallik, Kalisankar, Ed.; Shaver, Elaine M., Ed.

    This document contains 16 papers that were scheduled to be presented at a conference (which was canceled) on approaches and programs for helping developmentally disabled persons to be more self-sufficient. The book is divided into three sections: (1) unmasking vocational abilities, (2) enhancing functional independence, and (3) medical and…

  16. Developmental Light-Water Reactor Program

    International Nuclear Information System (INIS)

    Forsberg, C.W.

    1989-12-01

    This report summarizes the progress of the Developmental Light-Water Reactor (DLWR) Program at Oak Ridge National Laboratory in FY 1989. It also includes (1) a brief description of the program, (2) definition of goals, (3) earlier achievements, and (4) proposed future activities

  17. Motivation and Student Success in Developmental Education

    Science.gov (United States)

    Livingston, Shannon

    2017-01-01

    Using self-determination theory (Deci & Ryan, 1985) as the theoretical framework, this study explored how high-school GPA and motivation contributed to academic performance and persistence among students enrolled in developmental-education courses during the fall of 2016 at a two-year technical college in the Midwest. A non-random purposive…

  18. Epilepsy and Intellectual and Developmental Disabilities

    Science.gov (United States)

    Oguni, Hirokazu

    2013-01-01

    The co-occurrence of epilepsy in people with intellectual disabilities (ID) and other developmental disabilities (DD) has received attention because it has a significant negative impact on health, well-being, and quality of life. The current research investigating the frequency and form of epilepsy in children with ID and DD is reviewed, with…

  19. NCT and Developmental Psychology: A Welcome Rapprochement

    Science.gov (United States)

    Gauvain, Mary

    2013-01-01

    For over 50 years, developmental psychologists have conducted research around the world to understand the relation between culture and cognition. In fact, psychologists have been interested in this topic for over a century. In the late 1800s, Wundt introduced "Elements of Folk Psychology," the study of how culture becomes part of higher…

  20. Toward Developmental Connectomics of the Human Brain

    OpenAIRE

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorder...

  1. Towards Developmental Connectomics of the Human Brain

    OpenAIRE

    Miao eCao; Hao eHuang; Hao eHuang; Yun ePeng; Qi eDong; Yong eHe

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders...

  2. Screening for Developmental Dysplasia of the Hip

    NARCIS (Netherlands)

    Boere-Boonekamp, Magdalena M.; Verkerk, Paul H.

    1998-01-01

    The success rates of screening programmes for Developmental Dysplasia of the Hip (DDH) vary widely. Studies on screening programmes for DDH based on a Medline search for the years 1966–1997 are reviewed. The percentage treated in most studies, especially those using ultrasound, are high and suggest

  3. Descriptive Developmental Research: Why Only Time?

    Science.gov (United States)

    Labouvie, Erich W.

    1975-01-01

    The usefulness of the concepts of cohort and time of measurement in descriptive developmental research was examined by comparing the time-specific cross-sectional and cohort-specific longitudinal age gradients of stable and unstable children. (Author/ED)

  4. Developmental and Reproductive Toxicology of Methanol

    Science.gov (United States)

    Methanol is a high production volume chemical used as a feedstock for chemical syntheses and as a solvent and fuel additive. Methanol is acutely toxic to humans, causing acidosis, blindness in death at high dosages, but its developmental and reproductive toxicity in humans is poo...

  5. Developmental coordination disorder: evaluation and treatment.

    NARCIS (Netherlands)

    Leemrijse, C.

    2003-01-01

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

  6. Replication and Robustness in Developmental Research

    Science.gov (United States)

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

    2014-01-01

    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key…

  7. Research Models in Developmental Behavioral Toxicology.

    Science.gov (United States)

    Dietrich, Kim N.; Pearson, Douglas T.

    Developmental models currently used by child behavioral toxicologists and teratologists are inadequate to address current issues in these fields. Both child behavioral teratology and toxicology scientifically study the impact of exposure to toxic agents on behavior development: teratology focuses on prenatal exposure and postnatal behavior…

  8. The Developmental Approach to School Readiness.

    Science.gov (United States)

    Ogletree, Earl J.

    In the United States, a psychometric psychology dominates the thinking of educators. For traditional, political, and social reasons, developmental psychology rarely informs educational practices. This is the case even though studies show that the inducing of cognitive learning before a child is ready will reduce the child's learning potential and…

  9. Developmental Physical Education Accountability; Volume I.

    Science.gov (United States)

    Guarnieri, Barbara; Sandeen, Cecile

    Presented in the first of a two volume series is a developmental physical education checklist which provides teachers of trainable mentally retarded students with a permanent and accountable record of pupil progress and needs. The checklist is intended to be used with the accompanying volume of curricular activities in a nongraded enviroment for…

  10. Validating a Spanish Developmental Spelling Test.

    Science.gov (United States)

    Ferroli, Lou; Krajenta, Marilyn

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

  11. What Should We Know about Developmental Education?

    Science.gov (United States)

    Lake, Pat, Ed.

    2001-01-01

    This document argues that the availability of developmental education is essential to the well being of the American economy and social structure. By the year 2050, U.S. citizens will be older and nearly 50% will belong to a minority group. The fastest growing population is Hispanic American, resulting from immigration and higher birth rates. This…

  12. Developmental origins of health and disease

    National Research Council Canada - National Science Library

    Gluckman, Peter D; Hanson, Mark A

    2006-01-01

    ... development and the onset of many chronic diseases such as coronary heart disease, diabetes and osteoporosis also raises important public health issues. Another fascinating theme in the book concerns evolutionary developmental biology and how the 'evo-devo' debate can cast light on these concepts. Clinicians and basic scientists alike will find this an ...

  13. Developmental Trajectories of Early Communication Skills

    Science.gov (United States)

    Maatta, Sira; Laakso, Marja-Leena; Tolvanen, Asko; Ahonen, Timo; Aro, Tuija

    2012-01-01

    Purpose: This study focused on developmental trajectories of prelinguistic communication skills and their connections to later parent-reported language difficulties. Method: The participants represent a subset of a community-based sample of 508 children. Data include parent reports of prelinguistic communication skills at 12, 15, 18, and 21 months…

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

    Science.gov (United States)

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

  15. Gender and Social Exchange: A Developmental Perspective.

    Science.gov (United States)

    Maccoby, Eleanor E.

    2002-01-01

    Uses a developmental perspective on social interaction to trace gender differences in adulthood to relationship patterns that emerge in childhood. Summarizes results of: (1) experimental studies and naturalistic studies of workplace interaction in mixed-sex task-oriented groups; (2) same-sex interaction; (3) adult friendship; and (4) heterosexual…

  16. Science Academies' Refresher Course in Developmental Biology

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 20; Issue 8. Science Academies' Refresher Course in Developmental Biology. Information and Announcements Volume 20 Issue 8 August 2015 pp 756-756. Fulltext. Click here to view fulltext PDF. Permanent link:

  17. Neurogenetics and auditory processing in developmental dyslexia.

    Science.gov (United States)

    Giraud, Anne-Lise; Ramus, Franck

    2013-02-01

    Dyslexia is a polygenic developmental reading disorder characterized by an auditory/phonological deficit. Based on the latest genetic and neurophysiological studies, we propose a tentative model in which phonological deficits could arise from genetic anomalies of the cortical micro-architecture in the temporal lobe. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Developmental Levels of the Child's Storytelling.

    Science.gov (United States)

    Marjanovic-Umek, Ljubica; Kranjc, Simona; Fekonja, Urska

    Noting that examining the storytelling skills of children between 4 and 8 years of age can provide insights into the child's overall language development, this study explored the development of children's storytelling, using story coherence and story cohesion to evaluate the developmental level of the child's storytelling. Participating in the…

  19. Trace elements as paradigms of developmental neurotoxicants

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Herz, Katherine T

    2015-01-01

    Trace elements have contributed unique insights into developmental neurotoxicity and serve as paradigms for such adverse effects. Many trace elements are retained in the body for long periods and can be easily measured to assess exposure by inexpensive analytical methods that became available...

  20. Developmental Social Cognitive Neuroscience: Insights from Deafness

    Science.gov (United States)

    Corina, David; Singleton, Jenny

    2009-01-01

    The condition of deafness presents a developmental context that provides insight into the biological, cultural, and linguistic factors underlying the development of neural systems that impact social cognition. Studies of visual attention, behavioral regulation, language development, and face and human action perception are discussed. Visually…

  1. Biomarkers of adult and developmental neurotoxicity

    International Nuclear Information System (INIS)

    Slikker, William; Bowyer, John F.

    2005-01-01

    Neurotoxicity may be defined as any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical, or physical agent. A multidisciplinary approach is necessary to assess adult and developmental neurotoxicity due to the complex and diverse functions of the nervous system. The overall strategy for understanding developmental neurotoxicity is based on two assumptions: (1) significant differences in the adult versus the developing nervous system susceptibility to neurotoxicity exist and they are often developmental stage dependent; (2) a multidisciplinary approach using neurobiological, including gene expression assays, neurophysiological, neuropathological, and behavioral function is necessary for a precise assessment of neurotoxicity. Application of genomic approaches to developmental studies must use the same criteria for evaluating microarray studies as those in adults including consideration of reproducibility, statistical analysis, homogenous cell populations, and confirmation with non-array methods. A study using amphetamine to induce neurotoxicity supports the following: (1) gene expression data can help define neurotoxic mechanism(s) (2) gene expression changes can be useful biomarkers of effect, and (3) the site-selective nature of gene expression in the nervous system may mandate assessment of selective cell populations

  2. Explaining the VET Applied Research Developmental Framework

    Science.gov (United States)

    Simon, Linda; Beddie, Francesca M.

    2017-01-01

    This document explains the VET Applied Research Developmental Framework, created as part of a project that explored how the vocational education and training (VET) sector could broaden its engagement in Australia's research and development (R&D) and innovation systems. Achieving this engagement will rely significantly on building the…

  3. 48 CFR 919.7011 - Developmental assistance.

    Science.gov (United States)

    2010-10-01

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

  4. Perspectives on Conceptualizing Developmentally Appropriate Sexuality Education

    Science.gov (United States)

    Silvério Marques, Sara; Goldfarb, Eva S.; Deardorff, Julianna; Constantine, Norman A.

    2017-01-01

    Despite recognition of the importance of a developmentally appropriate approach to sexuality education, there is little direct guidance on how to do this. This study employed in-depth interviews with experienced sexuality educators and developers of sexuality education materials to identify how this concept is understood and applied in the field.…

  5. Moral Developmental Science between Changing Paradigms

    Science.gov (United States)

    Keller, Monika

    2012-01-01

    This review encompasses a time-span of about 50 years of research on morality and moral development. It discusses Kohlberg's (1984) work as a milestone that constituted the cognitive developmental viewpoint of morality and that dominated research for about three decades. In this paradigm the role of reasoning and deliberation was emphasized as the…

  6. Numerical Distance Effect in Developmental Dyscalculia

    Science.gov (United States)

    Ashkenazi, Sarit; Mark-Zigdon, Nitza; Henik, Avishai

    2009-01-01

    Children in third and fourth grades suffering from developmental dyscalculia (DD) and typically developing children were asked to compare numbers to a standard. In two separate blocks, they were asked to compare a number between 1 and 9 to 5, or a two-digit number between 10 and 99 to 55. In the single-digit comparisons, DD children were…

  7. Developmental evolution: this side of paradise.

    Science.gov (United States)

    Graham, A; McGonnell, I

    1999-09-09

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

  8. 29 CFR 1952.221 - Developmental schedule.

    Science.gov (United States)

    2010-07-01

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

  9. 29 CFR 1952.341 - Developmental schedule.

    Science.gov (United States)

    2010-07-01

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

  10. 29 CFR 1952.151 - Developmental schedule.

    Science.gov (United States)

    2010-07-01

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

  11. Autism Spectrum Disorders (Pervasive Developmental Disorders)

    Science.gov (United States)

    Strock, Margaret

    2007-01-01

    This booklet focuses on classic autism, pervasive developmental disorder not otherwise specified (PDD-NOS), and Asperger syndrome, with brief descriptions of Rett syndrome and childhood disintegrative disorder. The booklet describes possible indicators of autism spectrum disorders (ASD), their diagnosis, available aids, treatment options, adults…

  12. 48 CFR 819.7110 - Developmental assistance.

    Science.gov (United States)

    2010-10-01

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

  13. 48 CFR 519.7012 - Developmental assistance.

    Science.gov (United States)

    2010-10-01

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

  14. A reflection on African developmental predicament | Nweke ...

    African Journals Online (AJOL)

    Among several issues surrounding scholarly and political discussions about Africa is that of the continent‟s development. Despite the claims that it is the cradle of civilization, Africa, at the moment, remains a developing nation in the global developmental ranking. Efforts to lift Africa from the shackles have included, among ...

  15. Thermal adaptation and phenotypic plasticity in a warming world: Insights from common garden experiments on Alaskan sockeye salmon

    Science.gov (United States)

    Sparks, Morgan M.; Westley, Peter A. H.; Falke, Jeffrey A.; Quinn, Thomas P.

    2017-01-01

    An important unresolved question is how populations of coldwater-dependent fishes will respond to rapidly warming water temperatures. For example, the culturally and economically important group, Pacific salmon (Oncorhynchus spp.), experience site-specific thermal regimes during early development that could be disrupted by warming. To test for thermal local adaptation and heritable phenotypic plasticity in Pacific salmon embryos, we measured the developmental rate, survival, and body size at hatching in two populations of sockeye salmon (Oncorhynchus nerka) that overlap in timing of spawning but incubate in contrasting natural thermal regimes. Using a split half-sibling design, we exposed embryos of 10 families from each of two populations to variable and constant thermal regimes. These represented both experienced temperatures by each population, and predicted temperatures under plausible future conditions based on a warming scenario from the downscaled global climate model (MIROC A1B scenario). We did not find evidence of thermal local adaptation during the embryonic stage for developmental rate or survival. Within treatments, populations hatched within 1 day of each other, on average, and amongtreatments, did not differ in survival in response to temperature. We did detect plasticity to temperature; embryos developed 2.5 times longer (189 days) in the coolest regime compared to the warmest regime (74 days). We also detected variation in developmental rates among families within and among temperature regimes, indicating heritable plasticity. Families exhibited a strong positive relationship between thermal variability and phenotypic variability in developmental rate but body length and mass at hatching were largely insensitive to temperature. Overall, our results indicated a lack of thermal local adaptation, but a presence of plasticity in populations experiencing contrasting conditions, as well as family-specific heritable plasticity that could

  16. Developmental changes in intraepithelial T lymphocytes and NK cells in the small intestine of neonatal rats.

    Science.gov (United States)

    Pérez-Cano, Francisco J; Castellote, Cristina; González-Castro, Ana M; Pelegrí, Carme; Castell, Margarida; Franch, Angels

    2005-11-01

    The main objective of this study was to characterize developmental changes in small intestinal intraepithelial lymphocyte (IEL) subpopulations during the suckling period, thus contributing to the understanding of the development of diffuse gut-associated lymphoid tissue (GALT) and to the identification of early mechanisms that protect the neonate from the first contact with diet and gut microbial antigens. The study was performed by double labeling and flow cytometry in IEL isolated from the proximal and distal small intestine of 1- to 21-d-old Lewis rats. During the suckling period, intraepithelial natural killer (NK) cells changed from a typical systemic phenotype, CD8+, to a specific intestinal phenotype, CD8-. Analysis of CD8+ IEL revealed a progressive increase in the relative number of CD8+ IEL co-expressing TCRalphabeta, cells associated with acquired immunity, whereas the percentage of CD8+ cells expressing the NK receptor, i.e. cells committed to innate immunity, decreased. At weaning, IEL maturity was still not achieved, as revealed by a phenotypic pattern that differed from that of adult rats. Thus, late after weaning, the regulatory CD8+CD4+ T IEL population appeared and the NK population declined. In summary, the intestinal intraepithelial compartment undergoes changes in its lymphocyte composition associated with the first ingestion of food. These changes are focused on a relatively high proportion of NK cells during the suckling period, and after weaning, an expansion of the regulatory CD8+CD4+ T cells.

  17. Tomato Fruits Show Wide Phenomic Diversity but Fruit Developmental Genes Show Low Genomic Diversity.

    Directory of Open Access Journals (Sweden)

    Vijee Mohan

    Full Text Available Domestication of tomato has resulted in large diversity in fruit phenotypes. An intensive phenotyping of 127 tomato accessions from 20 countries revealed extensive morphological diversity in fruit traits. The diversity in fruit traits clustered the accessions into nine classes and identified certain promising lines having desirable traits pertaining to total soluble salts (TSS, carotenoids, ripening index, weight and shape. Factor analysis of the morphometric data from Tomato Analyzer showed that the fruit shape is a complex trait shared by several factors. The 100% variance between round and flat fruit shapes was explained by one discriminant function having a canonical correlation of 0.874 by stepwise discriminant analysis. A set of 10 genes (ACS2, COP1, CYC-B, RIN, MSH2, NAC-NOR, PHOT1, PHYA, PHYB and PSY1 involved in various plant developmental processes were screened for SNP polymorphism by EcoTILLING. The genetic diversity in these genes revealed a total of 36 non-synonymous and 18 synonymous changes leading to the identification of 28 haplotypes. The average frequency of polymorphism across the genes was 0.038/Kb. Significant negative Tajima'D statistic in two of the genes, ACS2 and PHOT1 indicated the presence of rare alleles in low frequency. Our study indicates that while there is low polymorphic diversity in the genes regulating plant development, the population shows wider phenotype diversity. Nonetheless, morphological and genetic diversity of the present collection can be further exploited as potential resources in future.

  18. Advanced phenotyping and phenotype data analysis for the plant growth and development study

    Directory of Open Access Journals (Sweden)

    Md. Matiur eRahaman

    2015-08-01

    Full Text Available Due to increase in the consumption of food, feed, fuel and to ensure global food security for rapidly growing human population, there is need to breed high yielding crops that can adapt to future climate. To solve these global issues, novel approaches are required to provide quantitative phenotypes to elucidate the genetic basis of agriculturally import traits and to screen germplasm with super performance in function under resource-limited environment. At present, plant phenomics has offered and integrated suite technologies for understanding the complete set of phenotypes of plants, towards the progression of the full characteristics of plants with whole sequenced genomes. In this aspect, high-throughput phenotyping platforms have been developed that enables to capture extensive and intensive phenotype data from non-destructive imaging over time. These developments advance our view on plant growth and performance with responses to the changing climate and environment. In this paper, we present a brief review on currently developed high-throughput plant phenotyping infrastructures based on imaging techniques and corresponding principles for phenotype data analysis.

  19. ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

    Science.gov (United States)

    Kanthaswamy, S; Ng, J; Oldt, R F; Valdivia, L; Houghton, P; Smith, D G

    2017-11-01

    A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Elucidating the genotype–phenotype map by automatic enumeration and analysis of the phenotypic repertoire

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2015-01-01

    Background: The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. Methods: The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Results: Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Conclusions: Starting with a system’s relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy. PMID:26998346

  1. Elucidating the genotype-phenotype map by automatic enumeration and analysis of the phenotypic repertoire.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Starting with a system's relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy.

  2. High-Throughput Phenotyping and QTL Mapping Reveals the Genetic Architecture of Maize Plant Growth1[OPEN

    Science.gov (United States)

    Huang, Chenglong; Wu, Di; Qiao, Feng; Li, Wenqiang; Duan, Lingfeng; Wang, Ke; Xiao, Yingjie; Chen, Guoxing; Liu, Qian; Yang, Wanneng

    2017-01-01

    With increasing demand for novel traits in crop breeding, the plant research community faces the challenge of quantitatively analyzing the structure and function of large numbers of plants. A clear goal of high-throughput phenotyping is to bridge the gap between genomics and phenomics. In this study, we quantified 106 traits from a maize (Zea mays) recombinant inbred line population (n = 167) across 16 developmental stages using the automatic phenotyping platform. Quantitative trait locus (QTL) mapping with a high-density genetic linkage map, including 2,496 recombinant bins, was used to uncover the genetic basis of these complex agronomic traits, and 988 QTLs have been identified for all investigated traits, including three QTL hotspots. Biomass accumulation and final yield were predicted using a combination of dissected traits in the early growth stage. These results reveal the dynamic genetic architecture of maize plant growth and enhance ideotype-based maize breeding and prediction. PMID:28153923

  3. Use of drawings in children with pervasive developmental disorder during hospitalization: a developmental perspective.

    Science.gov (United States)

    Stefanatou, Athena

    2008-12-01

    The level and nature of emotional upheaval and relationship to developmental stage was studied in children with pervasive developmental disorder (PDD) hospitalized for head injury. The sample consisted of 25 hospitalized children aged 5-12 years. Children were asked to make the drawing of a ;person in hospital'. The drawings were evaluated by Koppitz's emotional indicators. Punishment and persecution were the main cognitive constructs of children in order to explain hospitalization.

  4. New genes as drivers of phenotypic evolution

    Science.gov (United States)

    Chen, Sidi; Krinsky, Benjamin H.; Long, Manyuan

    2014-01-01

    During the course of evolution, genomes acquire novel genetic elements as sources of functional and phenotypic diversity, including new genes that originated in recent evolution. In the past few years, substantial progress has been made in understanding the evolution and phenotypic effects of new genes. In particular, an emerging picture is that new genes, despite being present in the genomes of only a subset of species, can rapidly evolve indispensable roles in fundamental biological processes, including development, reproduction, brain function and behaviour. The molecular underpinnings of how new genes can develop these roles are starting to be characterized. These recent discoveries yield fresh insights into our broad understanding of biological diversity at refined resolution. PMID:23949544

  5. Animal biometrics: quantifying and detecting phenotypic appearance.

    Science.gov (United States)

    Kühl, Hjalmar S; Burghardt, Tilo

    2013-07-01

    Animal biometrics is an emerging field that develops quantified approaches for representing and detecting the phenotypic appearance of species, individuals, behaviors, and morphological traits. It operates at the intersection between pattern recognition, ecology, and information sciences, producing computerized systems for phenotypic measurement and interpretation. Animal biometrics can benefit a wide range of disciplines, including biogeography, population ecology, and behavioral research. Currently, real-world applications are gaining momentum, augmenting the quantity and quality of ecological data collection and processing. However, to advance animal biometrics will require integration of methodologies among the scientific disciplines involved. Such efforts will be worthwhile because the great potential of this approach rests with the formal abstraction of phenomics, to create tractable interfaces between different organizational levels of life. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Smooth muscle cell phenotypic switching in stroke.

    Science.gov (United States)

    Poittevin, Marine; Lozeron, Pierre; Hilal, Rose; Levy, Bernard I; Merkulova-Rainon, Tatiana; Kubis, Nathalie

    2014-06-01

    Disruption of cerebral blood flow after stroke induces cerebral tissue injury through multiple mechanisms that are not yet fully understood. Smooth muscle cells (SMCs) in blood vessel walls play a key role in cerebral blood flow control. Cerebral ischemia triggers these cells to switch to a phenotype that will be either detrimental or beneficial to brain repair. Moreover, SMC can be primarily affected genetically or by toxic metabolic molecules. After stroke, this pathological phenotype has an impact on the incidence, pattern, severity, and outcome of the cerebral ischemic disease. Although little research has been conducted on the pathological role and molecular mechanisms of SMC in cerebrovascular ischemic diseases, some therapeutic targets have already been identified and could be considered for further pharmacological development. We examine these different aspects in this review.

  7. Risk factors of ophthalmic disorders in children with developmental delay

    DEFF Research Database (Denmark)

    Sandfeld, L.N.; Jensen, H.; Skov, L.

    2008-01-01

    PURPOSE: To identify diagnoses that increase the risk of ophthalmic disorders in developmentally delayed children. METHODS: A cross-sectional study of 1126 Danish children with developmental delay (IQ Udgivelsesdato: 2008/12......PURPOSE: To identify diagnoses that increase the risk of ophthalmic disorders in developmentally delayed children. METHODS: A cross-sectional study of 1126 Danish children with developmental delay (IQ Udgivelsesdato: 2008/12...

  8. Phenotype development in TgHD minipigs

    Czech Academy of Sciences Publication Activity Database

    Ellederová, Zdeňka; Vidinská, Daniela; Mačáková, Monika; Kučerová, S.; Bohuslavová, Božena; Sedláčková, M.; Lišková, Irena; Valeková, Ivona; Baxa, Monika; Ardan, Taras; Juhás, Štefan; Motlík, Jan

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 11-11 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : phenotype * minipig model of Huntington ´s disease * reproductive failure Subject RIV: EB - Genetics ; Molecular Biology

  9. Molecular and phenotypic characterization of anamorphic fungi

    OpenAIRE

    Madrid Lorca, Hugo

    2011-01-01

    Anamorphic fungi (those reproducing asexually) are a big part of kingdom Fungi. Most of them occur as saprobes in nature, but numerous species are pathogenic to plants and animals including man. With the aim of contributing to the knowledge of the diversity and distribution of anamorphic fungi, we performed a phenotypic and molecular characterization of environmental and clinical isolates of these fungi. Based on a polyphasic taxonomy approach which included morphology, physiology and DNA seq...

  10. Connectomic intermediate phenotypes for psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Alex eFornito

    2012-04-01

    Full Text Available Psychiatric disorders are phenotypically heterogeneous entities with a complex genetic basis. To mitigate this complexity, many investigators study so-called intermediate phenotypes that putatively provide a more direct index of the physiological effects of candidate genetic risk variants than overt psychiatric syndromes. Magnetic resonance imaging (MRI is a particularly popular technique for measuring such phenotypes because it allows interrogation of diverse aspects of brain structure and function in vivo. Much of this work however, has focused on relatively simple measures that quantify variations in the physiology or tissue integrity of specific brain regions in isolation, contradicting an emerging consensus that most major psychiatric disorders do not arise from isolated dysfunction in one or a few brain regions, but rather from disturbed interactions within and between distributed neural circuits; i.e., they are disorders of brain connectivity. The recent proliferation of new MRI techniques for comprehensively mapping the entire connectivity architecture of the brain, termed the human connectome, has provided a rich repertoire of tools for understanding how genetic variants implicated in mental disorder impact distinct neural circuits. In this article, we review research using these connectomic techniques to understand how genetic variation influences the connectivity and topology of human brain networks. We highlight recent evidence from twin and imaging genetics studies suggesting that the penetrance of candidate risk variants for mental illness, such as those in SLC6A4, MAOA, ZNF804A and APOE, may be higher for intermediate phenotypes characterised at the level of distributed neural systems than at the level of spatially localised brain regions. The findings indicate that imaging connectomics provides a powerful framework for understanding how genetic risk for psychiatric disease is expressed through altered structure and function of

  11. NF1 Neuronal Genotype Phenotype Relationships

    Science.gov (United States)

    2017-06-01

    interesting results from the Drosophila functional assays, at present we have decided to focus our attention on selected NF1 patient missense mutations...complexity of NF1 disease phenotypes in different tissues, age and sex dependency of symptoms, impact of environmental factors and genetic heterogeneity...suggesting the role of modifier genes [12]. This work aims to shed light on this issue by studying the functional consequences of selected NF1

  12. HIV coreceptor phenotyping in the clinical setting.

    Science.gov (United States)

    Low, Andrew J; Swenson, Luke C; Harrigan, P Richard

    2008-01-01

    The introduction of CCR5 antagonists increases the options available for constructing antiretroviral regimens. However, this option is coupled with the caveat that patients should be tested for HIV coreceptor tropism prior to initiating CCR5 antagonist-based therapy. Failure to screen for CXCR4 usage increases the risk of using an ineffective drug, thus reducing the likelihood of viral suppression and increasing their risk for developing antiretroviral resistance. This review discusses current and future methods of determining HIV tropism, with a focus on their utility in the clinical setting for screening purposes. Some of these methods include recombinant phenotypic tests, such as the Monogram Trofile assay, as well as genotype-based predictors, heteroduplex tracking assays, and flow cytometry based methods. Currently, the best evidence supports the use of phenotypic methods, although other methods of screening for HIV coreceptor usage prior to the administration of CCR5 antagonists may reduce costs and increase turnaround time over phenotypic methods. The presence of low levels of X4 virus is a challenge to all assay methods, resulting in reduced sensitivity in clinical, patient-derived samples when compared to clonally derived samples. Gaining a better understanding of the output of these assays and correlating them with clinical progression and therapy response will provide some indication on how both genotype-based, and phenotypic assays for determining HIV coreceptor usage can be improved. In addition, leveraging new technologies capable of detecting low-level minority species may provide the most significant advances in ensuring that individuals with low levels of dual/mixed tropic virus are not inadvertently prescribed CCR5 antagonists.

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

    Directory of Open Access Journals (Sweden)

    Elahe Ghayebie

    2018-04-01

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

  14. One gene, many phenotypes | Shawky | Egyptian Journal of Medical ...

    African Journals Online (AJOL)

    ... mechanisms underlying genotype-phenotype discrepancies is important, as it will move clinical genetics towards predictive medicine, allowing better selection of therapeutic strategies and individualized counseling of persons affected with genetic disorders. Keywords: Gene, phenotype, mosaicism, epigenetics, pleiotropy ...

  15. A phenotype of early infancy predicts reactivity of the amygdala in male adults.

    Science.gov (United States)

    Schwartz, C E; Kunwar, P S; Greve, D N; Kagan, J; Snidman, N C; Bloch, R B

    2012-10-01

    One of the central questions that has occupied those disciplines concerned with human development is the nature of continuities and discontinuities from birth to maturity. The amygdala has a central role in the processing of novelty and emotion in the brain. Although there is considerable variability among individuals in the reactivity of the amygdala to novel and emotional stimuli, the origin of these individual differences is not well understood. Four-month old infants called high reactive (HR) demonstrate a distinctive pattern of vigorous motor activity and crying to specific unfamiliar visual, auditory and olfactory stimuli in the laboratory. Low-reactive infants show the complementary pattern. Here, we demonstrate that the HR infant phenotype predicts greater amygdalar reactivity to novel faces almost two decades later in adults. A prediction of individual differences in brain function at maturity can be made on the basis of a single behavioral assessment made in the laboratory at 4 months of age. This is the earliest known human behavioral phenotype that predicts individual differences in patterns of neural activity at maturity. These temperamental differences rooted in infancy may be relevant to understanding individual differences in vulnerability and resilience to clinical psychiatric disorder. Males who were HR infants showed particularly high levels of reactivity to novel faces in the amygdala that distinguished them as adults from all other sex/temperament subgroups, suggesting that their amygdala is particularly prone to engagement by unfamiliar faces. These findings underline the importance of taking gender into account when studying the developmental neurobiology of human temperament and anxiety disorders. The genetic study of behavioral and biologic intermediate phenotypes (or 'endophenotypes') indexing anxiety-proneness offers an important alternative to examining phenotypes based on clinically defined disorder. As the HR phenotype is characterized

  16. Phenotypic Variability in the Coccolithophore Emiliania huxleyi.

    Science.gov (United States)

    Blanco-Ameijeiras, Sonia; Lebrato, Mario; Stoll, Heather M; Iglesias-Rodriguez, Debora; Müller, Marius N; Méndez-Vicente, Ana; Oschlies, Andreas

    2016-01-01

    Coccolithophores are a vital part of oceanic phytoplankton assemblages that produce organic matter and calcium carbonate (CaCO3) containing traces of other elements (i.e. Sr and Mg). Their associated carbon export from the euphotic zone to the oceans' interior plays a crucial role in CO2 feedback mechanisms and biogeochemical cycles. The coccolithophore Emiliania huxleyi has been widely studied as a model organism to understand physiological, biogeochemical, and ecological processes in marine sciences. Here, we show the inter-strain variability in physiological and biogeochemical traits in 13 strains of E. huxleyi from various biogeographical provinces obtained from culture collections commonly used in the literature. Our results demonstrate that inter-strain genetic variability has greater potential to induce larger phenotypic differences than the phenotypic plasticity of single strains cultured under a broad range of variable environmental conditions. The range of variation found in physiological parameters and calcite Sr:Ca highlights the need to reconsider phenotypic variability in paleoproxy calibrations and model parameterizations to adequately translate findings from single strain laboratory experiments to the real ocean.

  17. Phenotypic Variability in the Coccolithophore Emiliania huxleyi.

    Directory of Open Access Journals (Sweden)

    Sonia Blanco-Ameijeiras

    Full Text Available Coccolithophores are a vital part of oceanic phytoplankton assemblages that produce organic matter and calcium carbonate (CaCO3 containing traces of other elements (i.e. Sr and Mg. Their associated carbon export from the euphotic zone to the oceans' interior plays a crucial role in CO2 feedback mechanisms and biogeochemical cycles. The coccolithophore Emiliania huxleyi has been widely studied as a model organism to understand physiological, biogeochemical, and ecological processes in marine sciences. Here, we show the inter-strain variability in physiological and biogeochemical traits in 13 strains of E. huxleyi from various biogeographical provinces obtained from culture collections commonly used in the literature. Our results demonstrate that inter-strain genetic variability has greater potential to induce larger phenotypic differences than the phenotypic plasticity of single strains cultured under a broad range of variable environmental conditions. The range of variation found in physiological parameters and calcite Sr:Ca highlights the need to reconsider phenotypic variability in paleoproxy calibrations and model parameterizations to adequately translate findings from single strain laboratory experiments to the real ocean.

  18. A simple phenotypic classification for celiac disease

    Directory of Open Access Journals (Sweden)

    Ajit Sood

    2018-04-01

    Full Text Available Background/Aims : Celiac disease is a global health problem. The presentation of celiac disease has unfolded over years and it is now known that it can manifest at different ages, has varied presentations, and is prone to develop complications, if not managed properly. Although the Oslo definitions provide consensus on the various terminologies used in literature, there is no phenotypic classification providing a composite diagnosis for the disease. Methods : Various variables identified for phenotypic classification included age at diagnosis, age at onset of symptoms, clinical presentation, family history and complications. These were applied to the existing registry of 1,664 patients at Dayanand Medical College and Hospital, Ludhiana, India. In addition, age was evaluated as below 15 and below 18 years. Cross tabulations were used for the verification of the classification using the existing data. Expert opinion was sought from both international and national experts of varying fields. Results : After empirical verification, age at diagnosis was considered appropriate in between A1 (<18 and A2 (≧18. The disease presentation has been classified into 3 types–P1 (classical, P2 (non-classical and P3 (asymptomatic. Complications were considered as absent (C0 or present (C1. A single phenotypic classification based on these 3 characteristics, namely age at the diagnosis, clinical presentation, and intestinal complications (APC classification was derived. Conclusions : APC classification (age at diagnosis, presentation, complications is a simple disease explanatory classification for patients with celiac disease aimed at providing a composite diagnosis.

  19. Dissecting phenotypic variation among AIS patients

    International Nuclear Information System (INIS)

    Wang Minghua; Wang Jiucun; Zhang Zhen; Zhao Zhimin; Zhang Rongmei; Hu Xiaohua; Tan Tao; Luo Shijing; Luo Zewei

    2005-01-01

    We have created genital skin fibroblast cell lines directly from three patients in a Chinese family affected by androgen insensitivity syndrome (AIS). All patients in the family share an identical AR Arg 840 Cys mutant but show different disease phenotypes. By using the cell lines, we find that the mutation has not influenced a normal androgen-binding capacity at 37 deg C but has reduced the affinity for androgens and may cause thermolability of the androgen-receptor complex. The impaired nuclear trafficking of the androgen receptor in the cell lines is highly correlated with the severity of donors' disease phenotype. The transactivity of the mutant is substantially weakened and the extent of the reduced transactivity reflects severity of the donors' disease symptom. Our data reveal that although etiology of AIS is monogenic and the mutant may alter the major biological functions of its wild allele, the function of the mutant AR can also be influenced by the different genetic backgrounds and thus explains the divergent disease phenotypes

  20. Associations between phenotypes of preeclampsia and thrombophilia.

    Science.gov (United States)

    Berks, Durk; Duvekot, Johannes J; Basalan, Hillal; De Maat, Moniek P M; Steegers, Eric A P; Visser, Willy

    2015-11-01

    Preeclampsia complicates 2-8% of all pregnancies. Studies on the association of preeclampsia with thrombophilia are conflicting. Clinical heterogeneity of the disease may be one of the explanations. The present study addresses the question whether different phenotypes of preeclampsia are associated with thrombophilia factors. Study design We planned a retrospective cohort study. From 1985 until 2010 women with preeclampsia were offered postpartum screening for the following thrombophilia factors: anti-phospholipid antibodies, APC-resistance, protein C deficiency and protein S deficiency, hyperhomocysteineamia, factor V Leiden and Prothrombin gene mutation. Hospital records were used to obtain information on phenotypes of the preeclampsia and placental histology. We identified 844 women with singleton pregnancies who were screened for thrombophilia factors. HELLP complicated 49% of pregnancies; Fetal growth restriction complicated 61% of pregnancies. Early delivery (preeclampsia was associated with protein S deficiency (p=0.01). Fetal growth restriction was associated with anti-phospholipid antibodies (ppreeclampsia was associated with anti-phospholipid antibodies (p=0.01). Extensive placental infarction (>10%) was associated with anti-phospholipid antibodies (ppreeclampsia, especially if complicated by fetal growth restriction, are associated with anti-phospholipid antibodies. Other phenotypes of preeclampsia, especially HELLP syndrome, were not associated with thrombophilia. We advise only to test for anti-phospholipid antibodies after early onset preeclampsia, especially if complicated by fetal growth restriction. We suggest enough evidence is presented to justify no further studies are needed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Genetic variants influencing phenotypic variance heterogeneity.

    Science.gov (United States)

    Ek, Weronica E; Rask-Andersen, Mathias; Karlsson, Torgny; Enroth, Stefan; Gyllensten, Ulf; Johansson, Åsa

    2018-03-01

    Most genetic studies identify genetic variants associated with disease risk or with the mean value of a quantitative trait. More rarely, genetic variants associated with variance heterogeneity are considered. In this study, we have identified such variance single-nucleotide polymorphisms (vSNPs) and examined if these represent biological gene × gene or gene × environment interactions or statistical artifacts caused by multiple linked genetic variants influencing the same phenotype. We have performed a genome-wide study, to identify vSNPs associated with variance heterogeneity in DNA methylation levels. Genotype data from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified vSNPs for 7195 CpG sites (P mean DNA methylation levels. We further showed that variance heterogeneity between genotypes mainly represents additional, often rare, SNPs in linkage disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low frequency variants co-segregating with one of the vSNP alleles. Therefore, our results suggest that variance heterogeneity of DNA methylation mainly represents phenotypic effects by multiple SNPs, rather than biological interactions. Such effects may also be important for interpreting variance heterogeneity of more complex clinical phenotypes.

  2. Aberrant phenotypes in peripheral T cell lymphomas.

    Science.gov (United States)

    Hastrup, N; Ralfkiaer, E; Pallesen, G

    1989-01-01

    Seventy six peripheral T cell lymphomas were examined immunohistologically to test their reactivity with a panel of monoclonal antibodies against 11 T cell associated antigens (CD1-8, CD27, UCHL1, and the T cell antigen receptor). Sixty two (82%) lymphomas showed aberrant phenotypes, and four main categories were distinguished as follows: (i) lack of one or several pan-T cell antigens (49, 64% of the cases); (ii) loss of both the CD4 and CD8 antigens (11, 15% of the cases); (iii) coexpression of the CD4 and CD8 antigens (13, 17% of the cases); and (iv) expression of the CD1 antigen (eight, 11% of the cases). No correlation was seen between the occurrence of aberrant phenotypes and the histological subtype. It is concluded that the demonstration of an aberrant phenotype is a valuable supplement to histological assessment in the diagnosis of peripheral T cell lymphomas. It is recommended that the panel of monoclonal antibodies against T cell differentiation antigens should be fairly large, as apparently any antigen may be lost in the process of malignant transformation. Images Figure PMID:2469701

  3. Cluster analysis in phenotyping a Portuguese population.

    Science.gov (United States)

    Loureiro, C C; Sa-Couto, P; Todo-Bom, A; Bousquet, J

    2015-09-03

    Unbiased cluster analysis using clinical parameters has identified asthma phenotypes. Adding inflammatory biomarkers to this analysis provided a better insight into the disease mechanisms. This approach has not yet been applied to asthmatic Portuguese patients. To identify phenotypes of asthma using cluster analysis in a Portuguese asthmatic population treated in secondary medical care. Consecutive patients with asthma were recruited from the outpatient clinic. Patients were optimally treated according to GINA guidelines and enrolled in the study. Procedures were performed according to a standard evaluation of asthma. Phenotypes were identified by cluster analysis using Ward's clustering method. Of the 72 patients enrolled, 57 had full data and were included for cluster analysis. Distribution was set in 5 clusters described as follows: cluster (C) 1, early onset mild allergic asthma; C2, moderate allergic asthma, with long evolution, female prevalence and mixed inflammation; C3, allergic brittle asthma in young females with early disease onset and no evidence of inflammation; C4, severe asthma in obese females with late disease onset, highly symptomatic despite low Th2 inflammation; C5, severe asthma with chronic airflow obstruction, late disease onset and eosinophilic inflammation. In our study population, the identified clusters were mainly coincident with other larger-scale cluster analysis. Variables such as age at disease onset, obesity, lung function, FeNO (Th2 biomarker) and disease severity were important for cluster distinction. Copyright © 2015. Published by Elsevier España, S.L.U.

  4. DMPD: Developmental plasticity of lymphocytes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18472258 Developmental plasticity of lymphocytes. Cobaleda C, Busslinger M. Curr Op...in Immunol. 2008 Apr;20(2):139-48. Epub 2008 May 9. (.png) (.svg) (.html) (.csml) Show Developmental plastic...ity of lymphocytes. PubmedID 18472258 Title Developmental plasticity of lymphocytes. Authors Cobaleda C, Bus

  5. Random phenotypic variation of yeast (Saccharomyces cerevisiae) single-gene knockouts fits a double pareto-lognormal distribution.

    Science.gov (United States)

    Graham, John H; Robb, Daniel T; Poe, Amy R

    2012-01-01

    Distributed robustness is thought to influence the buffering of random phenotypic variation through the scale-free topology of gene regulatory, metabolic, and protein-protein interaction networks. If this hypothesis is true, then the phenotypic response to the perturbation of particular nodes in such a network should be proportional to the number of links those nodes make with neighboring nodes. This suggests a probability distribution approximating an inverse power-law of random phenotypic variation. Zero phenotypic variation, however, is impossible, because random molecular and cellular processes are essential to normal development. Consequently, a more realistic distribution should have a y-intercept close to zero in the lower tail, a mode greater than zero, and a long (fat) upper tail. The double Pareto-lognormal (DPLN) distribution is an ideal candidate distribution. It consists of a mixture of a lognormal body and upper and lower power-law tails. If our assumptions are true, the DPLN distribution should provide a better fit to random phenotypic variation in a large series of single-gene knockout lines than other skewed or symmetrical distributions. We fit a large published data set of single-gene knockout lines in Saccharomyces cerevisiae to seven different probability distributions: DPLN, right Pareto-lognormal (RPLN), left Pareto-lognormal (LPLN), normal, lognormal, exponential, and Pareto. The best model was judged by the Akaike Information Criterion (AIC). Phenotypic variation among gene knockouts in S. cerevisiae fits a double Pareto-lognormal (DPLN) distribution better than any of the alternative distributions, including the right Pareto-lognormal and lognormal distributions. A DPLN distribution is consistent with the hypothesis that developmental stability is mediated, in part, by distributed robustness, the resilience of gene regulatory, metabolic, and protein-protein interaction networks. Alternatively, multiplicative cell growth, and the mixing of

  6. [Non-autistic pervasive developmental disorders: Rett syndrome, disintegrative disorder and pervasive developmental disorder not otherwise specified

    NARCIS (Netherlands)

    Mercadante, M.T.; Gaag, R.J. van der; Schwartzman, J.S.

    2006-01-01

    The category "Pervasive Developmental Disorders" includes autistic disorder, Asperger's syndrome, Rett's syndrome, childhood disintegrative disorder, and a residual category, named pervasive developmental disorder not otherwise specified. In this review, Rett's syndrome and childhood disintegrative

  7. Comparison of environmental risk factors for esophageal atresia, anorectal malformations, and the combined phenotype in 263 German families.

    Science.gov (United States)

    Zwink, N; Choinitzki, V; Baudisch, F; Hölscher, A; Boemers, T M; Turial, S; Kurz, R; Heydweiller, A; Keppler, K; Müller, A; Bagci, S; Pauly, M; Brokmeier, U; Leutner, A; Degenhardt, P; Schmiedeke, E; Märzheuser, S; Grasshoff-Derr, S; Holland-Cunz, S; Palta, M; Schäfer, M; Ure, B M; Lacher, M; Nöthen, M M; Schumacher, J; Jenetzky, E; Reutter, H

    2016-11-01

    Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and anorectal malformations (ARM) represent the severe ends of the fore- and hindgut malformation spectra. Previous research suggests that environmental factors are implicated in their etiology. These risk factors might indicate the influence of specific etiological mechanisms on distinct developmental processes (e.g. fore- vs. hindgut malformation). The present study compared environmental factors in patients with isolated EA/TEF, isolated ARM, and the combined phenotype during the periconceptional period and the first trimester of pregnancy in order to investigate the hypothesis that fore- and hindgut malformations involve differing environmental factors. Patients with isolated EA/TEF (n = 98), isolated ARM (n = 123), and the combined phenotype (n = 42) were included. Families were recruited within the context of two German multicenter studies of the genetic and environmental causes of EA/TEF (great consortium) and ARM (CURE-Net). Exposures of interest were ascertained using an epidemiological questionnaire. Chi-square, Fisher's exact, and Mann-Whitney U-tests were used to assess differences between the three phenotypes. Newborns with isolated EA/TEF and the combined phenotype had significantly lower birth weights than newborns with isolated ARM (P = 0.001 and P studies. © 2015 International Society for Diseases of the Esophagus.

  8. Use of the enhanced frog embryo teratogenesis assay-Xenopus (FETAX) to determine chemically-induced phenotypic effects.

    Science.gov (United States)

    Hu, Lingling; Zhu, Jingmin; Rotchell, Jeanette M; Wu, Lijiao; Gao, Jinjuan; Shi, Huahong

    2015-03-01

    The frog embryo teratogenesis assay-Xenopus (FETAX) is an established method for the evaluation of the developmental toxicities of chemicals. To develop an enhanced FETAX that is appropriate for common environmental contaminants, we exposed Xenopus tropicalis embryos to eight compounds, including tributyltin, triphenyltin, CdCl2, pyraclostrobin, picoxystrobin, coumoxystrobin, all-trans-retinoic acid and 9-cis-retinoic acid. Multiple malformations were induced in embryos particularly following exposure to tributyltin, triphenyltin and pyraclostrobin at environmentally relevant concentrations. Based on the range of observed malformations, we proposed a phenotypic assessment method with 20 phenotypes and a 0-5 scoring system. This derived index exhibited concentration-dependent relationships for all of the chemicals tested. Furthermore, the phenotype profiles were characteristic of the different tested chemicals. Our results indicate that malformation phenotypes can be quantitatively integrated with the primary endpoints in conventional FETAX assessments to allow for increased sensitivity and measurement of quantitative effects and to provide indicative mechanistic information for each tested chemical. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. The Developmental Trajectory of Self-Injurious Behaviours in Individuals with Prader Willi Syndrome, Autism Spectrum Disorder and Intellectual Disability

    Directory of Open Access Journals (Sweden)

    Lauren J. Rice

    2016-02-01

    Full Text Available In the present study we examined the nature and developmental trajectory of self-injurious behaviour in Prader Willi syndrome (PWS and autism spectrum disorder (ASD. The development of interventions is greatly aided by understanding gene to behaviour pathways, and this requires an accurate description of the behaviour phenotype, that is, which types and natural history of self-injurious behaviour are more common in PWS and ASD and which are shared with other forms of developmental disability. Self-injury displayed by individuals with PWS and individuals with ASD was compared with that reported in a group of individuals with intellectual disability due to mixed aetiology (ID group. Three self-injurious behaviours (head banging, skin-picking and hitting and/or biting self were measured on five occasions over 18 years using the Developmental Behaviour Checklist (DBC a well-validated caregiver report measure. Rates of skin picking were higher in individuals with PWS and hitting and/or biting self was higher in individuals with ASD compared to the ID group. Rates of head banging were similar across the three groups. Over time, skin-picking and head banging increased with age for individuals with ASD and hitting and/or biting self increased for the PWS group. In the PWS and mixed ID groups head banging decreased with age. These findings suggest that the typology and developmental trajectories of self-injurious behaviours differ between those with PWS and ASD.

  10. The genotype-phenotype map of an evolving digital organism

    OpenAIRE

    Fortuna, Miguel A.; Zaman, Luis; Ofria, Charles; Wagner, Andreas

    2017-01-01

    To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms fr...

  11. EMPReSS: European mouse phenotyping resource for standardized screens.

    Science.gov (United States)

    Green, Eain C J; Gkoutos, Georgios V; Lad, Heena V; Blake, Andrew; Weekes, Joseph; Hancock, John M

    2005-06-15

    Standardized phenotyping protocols are essential for the characterization of phenotypes so that results are comparable between different laboratories and phenotypic data can be related to ontological descriptions in an automated manner. We describe a web-based resource for the visualization, searching and downloading of standard operating procedures and other documents, the European Mouse Phenotyping Resource for Standardized Screens-EMPReSS. Direct access: http://www.empress.har.mrc.ac.uk e.green@har.mrc.ac.uk.

  12. Syndromic (phenotypic diarrhea in early infancy

    Directory of Open Access Journals (Sweden)

    Bodemer Christine

    2008-02-01

    Full Text Available Abstract Syndromic diarrhea (SD, also known as phenotypic diarrhea (PD or tricho-hepato-enteric syndrome (THE, is a congenital enteropathy presenting with early-onset of severe diarrhea requiring parenteral nutrition (PN. To date, no epidemiological data are available. The estimated prevalence is approximately 1/300,000–400,000 live births in Western Europe. Ethnic origin does not appear to be associated with SD. Infants are born small for gestational age and present with facial dysmorphism including prominent forehead and cheeks, broad nasal root and hypertelorism. Hairs are woolly, easily removed and poorly pigmented. Severe and persistent diarrhea starts within the first 6 months of life (≤ 1 month in most cases and is accompanied by severe malabsorption leading to early and relentless protein energy malnutrition with failure to thrive. Liver disease affects about half of patients with extensive fibrosis or cirrhosis. There is currently no specific biochemical profile, though a functional T-cell immune deficiency with defective antibody production was reported. Microscopic analysis of the hair show twisted hair (pili torti, aniso- and poilkilotrichosis, and trichorrhexis nodosa. Histopathological analysis of small intestine biopsy shows non-specific villous atrophy with low or no mononuclear cell infiltration of the lamina propria, and no specific histological abnormalities involving the epithelium. The etiology remains unknown. The frequent association of the disorder with parental consanguinity and/or affected siblings suggests a genetic origin with an autosomal recessive mode of transmission. Early management consists of total PN. Some infants have a rather milder phenotype with partial PN dependency or require only enteral feeding. Prognosis of this syndrome is poor, but most patients now survive, and about half of the patients may be weaned from PN at adolescence, but experience failure to thrive and final short stature. Disease name

  13. Predictable Phenotypes of Antibiotic Resistance Mutations.

    Science.gov (United States)

    Knopp, M; Andersson, D I

    2018-05-15

    Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions between different resistance mutations are often predictable from the characteristics of the individual mutations. IMPORTANCE The spread of antibiotic-resistant bacteria imposes an urgent threat to public health. The ability to forecast the evolutionary success of resistant mutants would help to combat dissemination of antibiotic resistance. Previous studies have shown that the phenotypic effects (fitness and resistance level) of resistance mutations can vary substantially depending on the genetic context in which they occur. We conducted a broad screen using many different resistance mutations and host strains to identify potential epistatic interactions between various types of resistance mutations and to determine the effect of strain

  14. OCULAR DISORDERS IN CHILDREN WITH DEVELOPMENTAL DELAY

    Directory of Open Access Journals (Sweden)

    Meera Suresh Joshi

    2017-08-01

    Full Text Available BACKGROUND In India, an estimated 1.5-2.5% children below 2 years of age are developmentally delayed. A higher incidence of ocular disability is seen in these children, refractive errors and strabismus being most common. These can add to the overall burden of health as most of them have developmental comorbidities. The aim of the study is to study the ocular disorders in children with developmental delay. MATERIALS AND METHODS We studied 112 children between the 2-12 years of age diagnosed to have developmental delay. All the subjects underwent a detailed ophthalmic evaluation including visual acuity testing using Snellen’s charts (3m and 6m and Log MAR charts (recorded as per Snellen’s vision testing to maintain uniformity, cycloplegic refraction, torchlight and slit-lamp evaluation and dilated fundus examination. The data was tabulated and represented using bar diagrams, Pie charts and graphs. The results were expressed as percentages. Design-Cross-sectional, observational study. RESULTS 66 boys and 46 girls (total 112 were evaluated. The mean age of the study population was 7.8 years ± 2.4 SD. The aetiology of developmental delay was cerebral palsy (64%, Down syndrome (22%, autism (7%, intellectual disability (4.5% and 1 case each of congenital hypothyroidism and ataxia telangiectasia. The prevalence of ocular disorders was found to be 84.8%, which was slightly higher in girls (87% as compared to boys (83%. Refractive error (79.5% was the commonest ocular disorder followed by strabismus (46.4%. Astigmatism (44.6% was the commonest refractive error, which was divided into myopic astigmatism (19.6%, hyperopic astigmatism (13.8% and mixed astigmatism (11.2%. Simple hyperopia was seen in 21.9% subjects and simple myopia in 12.1%. Exotropia (52% was commoner than esotropia (48%. Other ocular abnormalities included optic atrophy, nystagmus, epicanthal folds, cataract, mongoloid slant, ptosis, telecanthus, conjunctival telangiectasia and

  15. Effect of maternal PCOS and PCOS-like phenotype on the offspring’s health

    Science.gov (United States)

    Puttabyatappa, Muraly; Cardoso, Rodolfo C.; Padmanabhan, Vasantha

    2015-01-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities affecting women of reproductive age. While the exact origin of PCOS is unknown, observations from clinical and animal studies suggest that maternal hyperandrogenism may be a contributing factor. Because women with PCOS manifest hyperandrogenism during pregnancy, changes in the gestational endocrine milieu may play a role in the vertical transmission of this syndrome. This review discusses the potential developmental origins of PCOS, the impact of maternal PCOS on the offspring’s health and contributions of the postnatal environment, capitalizing on findings from animal models that exhibit a PCOS-like phenotype. In addition, this review highlights the scarcity of data at early gestational stages in humans and the importance of animal experimentation to better understand the cellular and molecular mechanisms involved in the programming of adult diseases, therefore, helping identify therapeutic targets for preventive and treatment strategies. PMID:26639019

  16. The phenotype of FancB-mutant mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Kim, Tae Moon; Ko, Jun Ho; Choi, Yong Jun; Hu Lingchuan; Hasty, Paul

    2011-01-01

    Fanconi anemia (FA) is a rare autosomal recessive disease characterized by bone marrow failure, developmental defects and cancer. There are multiple FA genes that enable the repair of interstrand crosslinks (ICLs) in coordination with a variety of other DNA repair pathways in a way that is poorly understood. Here we present the phenotype of mouse embryonic stem (ES) cells mutated for FancB. We found FancB-mutant cells exhibited reduced cellular proliferation, hypersensitivity to the crosslinking agent mitomycin C (MMC), increased spontaneous and MMC-induced chromosomal abnormalities, reduced spontaneous sister chromatid exchanges (SCEs), reduced gene targeting, reduced MMC-induced Rad51 foci and absent MMC-induced FancD2 foci. Since FancB is on the X chromosome and since ES cells are typically XY, FancB is an excellent target for an epistatic analysis to elucidate FA's role in ICL repair.

  17. Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD.

    Science.gov (United States)

    Picker-Minh, Sylvie; Mignot, Cyril; Doummar, Diane; Hashem, Mais; Faqeih, Eissa; Josset, Patrice; Dubern, Béatrice; Alkuraya, Fowzan S; Kraemer, Nadine; Kaindl, Angela M

    2016-04-29

    Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity.

  18. The phenotype of FancB-mutant mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Moon; Ko, Jun Ho; Choi, Yong Jun; Hu Lingchuan [Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245 (United States); Hasty, Paul, E-mail: hastye@uthscsa.edu [Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245 (United States)

    2011-07-01

    Fanconi anemia (FA) is a rare autosomal recessive disease characterized by bone marrow failure, developmental defects and cancer. There are multiple FA genes that enable the repair of interstrand crosslinks (ICLs) in coordination with a variety of other DNA repair pathways in a way that is poorly understood. Here we present the phenotype of mouse embryonic stem (ES) cells mutated for FancB. We found FancB-mutant cells exhibited reduced cellular proliferation, hypersensitivity to the crosslinking agent mitomycin C (MMC), increased spontaneous and MMC-induced chromosomal abnormalities, reduced spontaneous sister chromatid exchanges (SCEs), reduced gene targeting, reduced MMC-induced Rad51 foci and absent MMC-induced FancD2 foci. Since FancB is on the X chromosome and since ES cells are typically XY, FancB is an excellent target for an epistatic analysis to elucidate FA's role in ICL repair.

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

    Science.gov (United States)

    Molenaar, Peter C. M.

    2015-01-01

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

  20. GGCX-Associated Phenotypes: An Overview in Search of Genotype-Phenotype Correlations

    Directory of Open Access Journals (Sweden)

    Eva Y. G. De Vilder

    2017-01-01

    Full Text Available Gamma-carboxylation, performed by gamma-glutamyl carboxylase (GGCX, is an enzymatic process essential for activating vitamin K-dependent proteins (VKDP with important functions in various biological processes. Mutations in the encoding GGCX gene are associated with multiple phenotypes, amongst which vitamin K-dependent coagulation factor deficiency (VKCFD1 is best known. Other patients have skin, eye, heart or bone manifestations. As genotype–phenotype correlations were never described, literature was systematically reviewed in search of patients with at least one GGCX mutation with a phenotypic description, resulting in a case series of 47 patients. Though this number was too low for statistically valid correlations—a frequent problem in orphan diseases—we demonstrate the crucial role of the horizontally transferred transmembrane domain in developing cardiac and bone manifestations. Moreover, natural history suggests ageing as the principal determinant to develop skin and eye symptoms. VKCFD1 symptoms seemed more severe in patients with both mutations in the same protein domain, though this could not be linked to a more perturbed coagulation factor function. Finally, distinct GGCX functional domains might be dedicated to carboxylation of very specific VKDP. In conclusion, this systematic review suggests that there indeed may be genotype–phenotype correlations for GGCX-related phenotypes, which can guide patient counseling and management.

  1. Phenotypic plasticity in blood–oxygen transport in highland and lowland deer mice

    Science.gov (United States)

    Tufts, Danielle M.; Revsbech, Inge G.; Cheviron, Zachary A.; Weber, Roy E.; Fago, Angela; Storz, Jay F.

    2013-01-01

    SUMMARY In vertebrates living at high altitude, arterial hypoxemia may be ameliorated by reversible changes in the oxygen-carrying capacity of the blood (regulated by erythropoiesis) and/or changes in blood–oxygen affinity (regulated by allosteric effectors of hemoglobin function). These hematological traits often differ between taxa that are native to different elevational zones, but it is often unknown whether the observed physiological differences reflect fixed, genetically based differences or environmentally induced acclimatization responses (phenotypic plasticity). Here, we report measurements of hematological traits related to blood–O2 transport in populations of deer mice (Peromyscus maniculatus) that are native to high- and low-altitude environments. We conducted a common-garden breeding experiment to assess whether altitude-related physiological differences were attributable to developmental plasticity and/or physiological plasticity during adulthood. Under conditions prevailing in their native habitats, high-altitude deer mice from the Rocky Mountains exhibited a number of pronounced hematological differences relative to low-altitude conspecifics from the Great Plains: higher hemoglobin concentrations, higher hematocrits, higher erythrocytic concentrations of 2,3-diphosphoglycerate (an allosteric regulator of hemoglobin–oxygen affinity), lower mean corpuscular hemoglobin concentrations and smaller red blood cells. However, these differences disappeared after 6 weeks of acclimation to normoxia at low altitude. The measured traits were also indistinguishable between the F1 progeny of highland and lowland mice, indicating that there were no persistent differences in phenotype that could be attributed to developmental plasticity. These results indicate that the naturally occurring hematological differences between highland and lowland mice are environmentally induced and are largely attributable to physiological plasticity during adulthood. PMID

  2. Quantitative Assessment of Eye Phenotypes for Functional Genetic Studies Using Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Janani Iyer

    2016-05-01

    Full Text Available About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net, to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes, and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions.

  3. Cardiorespiratory physiological phenotypic plasticity in developing air-breathing anabantid fishes (Betta splendens and Trichopodus trichopterus).

    Science.gov (United States)

    Mendez-Sanchez, Jose F; Burggren, Warren W

    2017-08-01

    Betta , which inhabits temporary ponds with nocturnal hypoxia. Trichopodus , inhabiting more permanent oxygenated bodies of water, showed few responses to hypoxia, reflecting a lower degree of developmental phenotypic plasticity. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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

    Science.gov (United States)

    Gilbert, Scott F

    2017-12-01

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

  5. Identification of new developmentally regulated genes involved in Streptomyces coelicolor sporulation.

    Science.gov (United States)

    Salerno, Paola; Persson, Jessica; Bucca, Giselda; Laing, Emma; Ausmees, Nora; Smith, Colin P; Flärdh, Klas

    2013-12-05

    The sporulation of aerial hyphae of Streptomyces coelicolor is a complex developmental process. Only a limited number of the genes involved in this intriguing morphological differentiation programme are known, including some key regulatory genes. The aim of this study was to expand our knowledge of the gene repertoire involved in S. coelicolor sporulation. We report a DNA microarray-based investigation of developmentally controlled gene expression in S. coelicolor. By comparing global transcription patterns of the wild-type parent and two mutants lacking key regulators of aerial hyphal sporulation, we found a total of 114 genes that had significantly different expression in at least one of the two mutants compared to the wild-type during sporulation. A whiA mutant showed the largest effects on gene expression, while only a few genes were specifically affected by whiH mutation. Seven new sporulation loci were investigated in more detail with respect to expression patterns and mutant phenotypes. These included SCO7449-7451 that affect spore pigment biogenesis; SCO1773-1774 that encode an L-alanine dehydrogenase and a regulator-like protein and are required for maturation of spores; SCO3857 that encodes a protein highly similar to a nosiheptide resistance regulator and affects spore maturation; and four additional loci (SCO4421, SCO4157, SCO0934, SCO1195) that show developmental regulation but no overt mutant phenotype. Furthermore, we describe a new promoter-probe vector that takes advantage of the red fluorescent protein mCherry as a reporter of cell type-specific promoter activity. Aerial hyphal sporulation in S. coelicolor is a technically challenging process for global transcriptomic investigations since it occurs only as a small fraction of the colony biomass and is not highly synchronized. Here we show that by comparing a wild-type to mutants lacking regulators that are specifically affecting processes in aerial hypha, it is possible to identify previously

  6. Developmental Programming, a Pathway to Disease

    Science.gov (United States)

    Cardoso, Rodolfo C.; Puttabyatappa, Muraly

    2016-01-01

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

  7. Avian models in teratology and developmental toxicology.

    Science.gov (United States)

    Smith, Susan M; Flentke, George R; Garic, Ana

    2012-01-01

    The avian embryo is a long-standing model for developmental biology research. It also has proven utility for toxicology research both in ovo and in explant culture. Like mammals, avian embryos have an allantois and their developmental pathways are highly conserved with those of mammals, thus avian models have biomedical relevance. Fertile eggs are inexpensive and the embryo develops rapidly, allowing for high-throughput. The chick genome is sequenced and significant molecular resources are available for study, including the ability for genetic manipulation. The absence of a placenta permits the direct study of an agent's embryotoxic effects. Here, we present protocols for using avian embryos in toxicology research, including egg husbandry and hatch, toxicant delivery, and assessment of proliferation, apoptosis, and cardiac structure and function.

  8. Petro-States - Predatory or Developmental?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-10-01

    Political attention is increasing on the glaring contradiction in most oil-rich countries between natural abundance and economic and social misery. How can it be that oil is not a blessing, but becomes a curse? Although drawing on economic analysis (Dutch disease), the analytical framework established in this report on Angola and Azerbaijan pays special attention to political and institutional factors and concentrates on the role of the state. Selected variables that are likely to decide whether the petro-states become ''predatory'' or ''developmental'' are studied for both countries. The analysis indicates a danger that oil resources will continue to trickle away instead of trickling down to the benefit of the broader Angolan and Azerbaijani population. Concerted action by international oil companies and the Bretton Woods institutions provides the best hope of moving the present political leadership in Angola and Azerbaijan into a developmental direction. (author)

  9. Developmental toxicity of organotin compounds in animals

    Directory of Open Access Journals (Sweden)

    Lijiao eWu

    2014-09-01

    Full Text Available Organotin compounds (OTs have been used as biocides in antifouling paints and agriculture. The IMO introduced a global ban on the use of OTs in antifouling systems in 2001 due to their high toxicity. However, OTs have still been detected in the environment and pose a threat to the ecosystem. Several research groups have summarized the analytical methods, environmental fate, biochemistry, reproductive toxicity and mechanisms of actions of OTs. Here, we reviewed the developmental toxicity of OTs in various organisms such as sea urchin, ascidian, mussel and fish. The differences in sensitivity to OT exposure exist not only in different species but also at different stages in the same species. Though some hypotheses have been proposed to explain the developmental toxicity of OTs, the solid evidences are greatly in need.

  10. A taxometric investigation of developmental dyslexia subtypes.

    Science.gov (United States)

    O'Brien, Beth A; Wolf, Maryanne; Lovett, Maureen W

    2012-02-01

    Long-standing issues with the conceptualization, identification and subtyping of developmental dyslexia persist. This study takes an alternative approach to examine the heterogeneity of developmental dyslexia using taxometric classification techniques. These methods were used with a large sample of 671 children ages 6-8 who were diagnosed with severe reading disorders. Latent characteristics of the sample are assessed in regard to posited subtypes with phonological deficits and naming speed deficits, thus extending prior work by addressing whether these deficits embody separate classes of individuals. Findings support separate taxa of dyslexia with and without phonological deficits. Different latent structure for naming speed deficits was found depending on the definitional criterion used to define dyslexia. Non-phonologically based forms of dyslexia showed particular difficulty with naming speed and reading fluency. Copyright © 2012 John Wiley & Sons, Ltd.

  11. The "where" and "what" in developmental dyscalculia.

    Science.gov (United States)

    Henik, Avishai; Rubinsten, Orly; Ashkenazi, Sarit

    2011-08-01

    Developmental dyscalculia (DD) is a congenital deficit that affects the ability to acquire arithmetical skills. Individuals with DD have problems learning standard number facts and procedures. Estimates of the prevalence rate of DD are similar to those of developmental dyslexia. Recent reports and discussions suggest that those with DD suffer from specific deficits (e.g., subitizing, comparative judgment). Accordingly, DD has been described as a domain-specific disorder that involves particular brain areas (e.g., intra-parietal sulcus). However, we and others have found that DD is characterized by additional deficiencies and may be affected by domain-general (e.g., attention) factors. Hence "pure DD" might be rather rare and not as pure as one would think. We suggest that the heterogeneity of symptoms that commonly characterize learning disabilities needs to be taken into account in future research and treatment.

  12. Petro-States - Predatory or Developmental?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-10-01

    Political attention is increasing on the glaring contradiction in most oil-rich countries between natural abundance and economic and social misery. How can it be that oil is not a blessing, but becomes a curse? Although drawing on economic analysis (Dutch disease), the analytical framework established in this report on Angola and Azerbaijan pays special attention to political and institutional factors and concentrates on the role of the state. Selected variables that are likely to decide whether the petro-states become ''predatory'' or ''developmental'' are studied for both countries. The analysis indicates a danger that oil resources will continue to trickle away instead of trickling down to the benefit of the broader Angolan and Azerbaijani population. Concerted action by international oil companies and the Bretton Woods institutions provides the best hope of moving the present political leadership in Angola and Azerbaijan into a developmental direction. (author)

  13. PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity.

    NARCIS (Netherlands)

    Tartaglia, M.; Kalidas, K.; Shaw, A.; Song, X.; Musat, D.L.; Burgt, C.J.A.M. van der; Brunner, H.G.; Bertola, D.R.; Crosby, A.; Ion, A.; Kucherlapati, R.S.; Jeffery, S.; Patton, M.A.; Gelb, B.D.

    2002-01-01

    Noonan syndrome (NS) is a developmental disorder characterized by facial dysmorphia, short stature, cardiac defects, and skeletal malformations. We recently demonstrated that mutations in PTPN11, the gene encoding the non-receptor-type protein tyrosine phosphatase SHP-2 (src homology region 2-domain

  14. A mild phenotype of dihydropyrimidine dehydrogenase deficiency and developmental retardation associated with a missense mutation affecting cofactor binding

    NARCIS (Netherlands)

    Weidensee, Sabine; Goettig, Peter; Bertone, Marko; Haas, Dorothea; Magdolen, Viktor; Kiechle, Marion; Meindl, Alfons; van Kuilenburg, André B. P.; Gross, Eva

    2011-01-01

    Evaluation of a non-synonymous mutation associated with dihydropyrimidine dehydrogenase (DPD) deficiency. DPD enzyme analysis, mutation analysis and molecular dynamics simulations based on the 3D-model of DPD. The substitution Lys63Glu is likely to affect the FAD binding pocket within the DPD

  15. Design principles and developmental mechanisms underlying retinal mosaics.

    Science.gov (United States)

    Reese, Benjamin E; Keeley, Patrick W

    2015-08-01

    Most structures within the central nervous system (CNS) are composed of different types of neuron that vary in both number and morphology, but relatively little is known about the interplay between these two features, i.e. about the population dynamics of a given cell type. How such arrays of neurons are distributed within a structure, and how they differentiate their dendrites relative to each other, are issues that have recently drawn attention in the invertebrate nervous system, where the genetic and molecular underpinnings of these organizing principles are being revealed in exquisite detail. The retina is one of the few locations where these principles have been extensively studied in the vertebrate CNS, indeed, where the design principles of 'mosaic regularity' and 'uniformity of coverage' were first explicitly defined, quantified, and related to each other. Recent studies have revealed a number of genes that influence the formation of these histotypical features in the retina, including homologues of those invertebrate genes, although close inspection reveals that they do not always mediate comparable developmental processes nor elucidate fundamental design principles. The present review considers just how pervasive these features of 'mosaic regularity' and 'uniform dendritic coverage' are within the mammalian retina, discussing the means by which such features can be assessed in the mature and developing nervous system and examining the limitations associated with those assessments. We then address the extent to which these two design principles co-exist within different populations of neurons, and how they are achieved during development. Finally, we consider the neural phenotypes obtained in mutant nervous systems, to address whether a prospective gene of interest underlies those very design principles. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  16. Plant phenomics and the need for physiological phenotyping across scales to narrow the genotype-to-phenotype knowledge gap

    Czech Academy of Sciences Publication Activity Database

    Grosskinsky, D. K.; Svensgaard, J.; Christensen, S.; Roitsch, Thomas

    2015-01-01

    Roč. 66, č. 18 (2015), s. 5429-5440 ISSN 0022-0957 Institutional support: RVO:67179843 Keywords : External phenotype * genome–environment–management interaction * genome–phenome map * internal phenotype * phenomics * physiological traits * physiology * plant phenotyping * predictors Subject RIV: EH - Ecology, Behaviour Impact factor: 5.677, year: 2015

  17. Reflections on the old and new developmentalism

    Directory of Open Access Journals (Sweden)

    JAN KREGEL

    2018-03-01

    Full Text Available ABSTRACT New Developmentalism provides a view out how it incorporates the positive contributions of early development theorists concerned with to the past of development theory as well as a view to the future. This assessment points the similar problems of the importance of exchange rates in the development process to provide a contemporary version of the theory adapted to the twentieth century world of globalization and financialization .

  18. Cryptic Genetic Variation in Evolutionary Developmental Genetics

    Directory of Open Access Journals (Sweden)

    Annalise B. Paaby

    2016-06-01

    Full Text Available Evolutionary developmental genetics has traditionally been conducted by two groups: Molecular evolutionists who emphasize divergence between species or higher taxa, and quantitative geneticists who study variation within species. Neither approach really comes to grips with the complexities of evolutionary transitions, particularly in light of the realization from genome-wide association studies that most complex traits fit an infinitesimal architecture, being influenced by thousands of loci. This paper discusses robustness, plasticity and lability, phenomena that we argue potentiate major evolutionary changes and provide a bridge between the conceptual treatments of macro- and micro-evolution. We offer cryptic genetic variation and conditional neutrality as mechanisms by which standing genetic variation can lead to developmental system drift and, sheltered within canalized processes, may facilitate developmental transitions and the evolution of novelty. Synthesis of the two dominant perspectives will require recognition that adaptation, divergence, drift and stability all depend on similar underlying quantitative genetic processes—processes that cannot be fully observed in continuously varying visible traits.

  19. Developmental psychopathology: Attention Deficit Hyperactivity Disorder (ADHD

    Directory of Open Access Journals (Sweden)

    Petermann Franz

    2009-09-01

    Full Text Available Abstract Background Attention Deficit/Hyperactivity Disorder (ADHD, formerly regarded as a typical childhood disorder, is now known as a developmental disorder persisting over the lifespan. Starting in preschool-age, symptoms vary depending on the age group affected. Method According to the variability of ADHD-symptoms and the heterogeneity of comorbid psychiatric disorders, a broad review of recent studies was performed. These findings were summarized in a developmental psychopathological model, documenting relevant facts on a timeline. Results Based on a genetic disposition and a neuropsychological deregulation, there is evidence for factors which persist across the lifespan, change age-dependently, or show validity in a specific developmental phase. Qualitative changes can be found for children in preschool-age and adults. Conclusion These differences have implications for clinical practice as they can be used for prevention, diagnostic proceedings, and therapeutic intervention as well as for planning future studies. The present article is a translated and modified version of the German article "Entwicklungspsychopathologie der ADHS", published in Zeitschrift für Psychiatrie, Psychologie und Psychotherapie, 56, 2008, S. 265-274.

  20. Building clinical networks: a developmental evaluation framework.

    Science.gov (United States)

    Carswell, Peter; Manning, Benjamin; Long, Janet; Braithwaite, Jeffrey

    2014-05-01

    Clinical networks have been designed as a cross-organisational mechanism to plan and deliver health services. With recent concerns about the effectiveness of these structures, it is timely to consider an evidence-informed approach for how they can be developed and evaluated. To document an evaluation framework for clinical networks by drawing on the network evaluation literature and a 5-year study of clinical networks. We searched literature in three domains: network evaluation, factors that aid or inhibit network development, and on robust methods to measure network characteristics. This material was used to build a framework required for effective developmental evaluation. The framework's architecture identifies three stages of clinical network development; partner selection, network design and network management. Within each stage is evidence about factors that act as facilitators and barriers to network growth. These factors can be used to measure progress via appropriate methods and tools. The framework can provide for network growth and support informed decisions about progress. For the first time in one place a framework incorporating rigorous methods and tools can identify factors known to affect the development of clinical networks. The target user group is internal stakeholders who need to conduct developmental evaluation to inform key decisions along their network's developmental pathway.