Full Text Available We describe the creation of a transgenic zebrafish expressing GFP driven by a 7.5 kb promoter region of the tbx16 gene. This promoter segment is sufficient to recapitulate early embryonic expression of endogenous tbx16 in the presomitic mesoderm, the polster and, subsequently, in the hatching gland. Expression of GFP in the transgenic lines later in development diverges to some extent from endogenous tbx16 expression with the serendipitous result that one line expresses GFP specifically in commissural primary ascending (CoPA interneurons of the developing spinal cord. Using this line we demonstrate that the gene mafba (valentino is expressed in CoPA interneurons.
Metalloproteinases have a critical role in a broad spectrum of cellular processes ranging from the break-down of extracellulax matrix to the processing of signal transduction-related proteins. These hydrolyticfunctions underlie a variety of mechanisms related to developmental processes as well as disease states.Structural analysis of metalloproteinases from both invertebrate and vertebrate species indicates that theseenzymes are highly conserved and arose early during metazoan evolution. In this regard, studies from vari-ous laboratories have reported that a number of classes of metalloproteinases are found in hydra, a memberof Cnidaria, the second oldest of existing animal phyla. These studies demonstrate that the hydra genomecontains at least three classes of metalloproteinases to include members of the 1) astacin class, 2) matrix met-alloproteinase class, and 3) neprilysin class. Functional studies indicate that these metalloproteinases playdiverse and important roles in hydra morphogenesis and cell differentiation as well as specialized functionsin adult polyps. This article will review the structure, expression, and function of these metalloproteinasesin hydra.
Nguyen, Tien Dung; Moon, Sunok; Nguyen, Van Ngoc Tuyet; Gho, Yunsil; Chandran, Anil Kumar Nalini; Soh, Moon-Soo; Song, Jong Tae; An, Gynheung; Oh, Sung Aeong; Park, Soon Ki; Jung, Ki-Hong
Microspore production using endogenous developmental programs has not been well studied. The main limitation is the difficulty in identifying genes preferentially expressed in pollen grains at early stages. To overcome this limitation, we collected transcriptome data from anthers and microspore/pollen and performed meta-expression analysis. Subsequently, we identified 410 genes showing preferential expression patterns in early developing pollen samples of both japonica and indica cultivars. The expression patterns of these genes are distinguishable from genes showing pollen mother cell or tapetum-preferred expression patterns. Gene Ontology enrichment and MapMan analyses indicated that microspores in rice are closely linked with protein degradation, nucleotide metabolism, and DNA biosynthesis and regulation, while the pollen mother cell or tapetum are strongly associated with cell wall metabolism, lipid metabolism, secondary metabolism, and RNA biosynthesis and regulation. We also generated transgenic lines under the control of the promoters of eight microspore-preferred genes and confirmed the preferred expression patterns in plants using the GUS reporting system. Furthermore, cis-regulatory element analysis revealed that pollen specific elements such as POLLEN1LELAT52, and 5659BOXLELAT5659 were commonly identified in the promoter regions of eight rice genes with more frequency than estimation. Our study will provide new sights on early pollen development in rice, a model crop plant.
Champhekar, Ameya; Damle, Sagar S; Freedman, George; Carotta, Sebastian; Nutt, Stephen L; Rothenberg, Ellen V
The ETS family transcription factor PU.1 is essential for the development of several blood lineages, including T cells, but its function in intrathymic T-cell precursors has been poorly defined. In the thymus, high PU.1 expression persists through multiple cell divisions in early stages but then falls sharply during T-cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it has remained unknown how PU.1 activities could contribute positively to T-cell development. Here we employed conditional knockout and modified antagonist PU.1 constructs to perturb PU.1 function stage-specifically in early T cells. We show that PU.1 is needed for full proliferation, restricting access to some non-T fates, and controlling the timing of T-cell developmental progression such that removal or antagonism of endogenous PU.1 allows precocious access to T-cell differentiation. Dominant-negative effects reveal that this repression by PU.1 is mediated indirectly. Genome-wide transcriptome analysis identifies novel targets of PU.1 positive and negative regulation affecting progenitor cell signaling and cell biology and indicating distinct regulatory effects on different subsets of progenitor cell transcription factors. Thus, in addition to supporting early T-cell proliferation, PU.1 regulates the timing of activation of the core T-lineage developmental program.
Goetz, Elizabeth; And Others
This document consists of four papers on the acquisition of writing skills by young children. The first paper provides a historical and developmental perspective on early writing. Children's development of manual dexterity is briefly overviewed and aspects of the educational approaches of Pestalozzi, Montessori, Chomsky, Rogers and Ashton-Warner…
Zhang, Jiuli; Li, Jinlong; Zhang, Ziwei; Sun, Bo; Wang, Rihua; Jiang, Zhihui; Li, Shu; Xu, Shiwen
Previous results revealed a ubiquitous expression pattern of selenoprotein N (SelN, SEPN1) in humans, zebrafish, and mouse, suggesting that it plays a potential role during the embryogenesis of these species. However, no information is known about the tissue distribution of SelN and mRNA expression analysis in the muscle tissues during development in birds. We analyzed the mRNA expression of SelN in 26 different tissues of 90-day-old chickens and the expression of SelN in the muscle tissues of 12-day-old chicken embryos and 15-month-old adult chickens by quantitative real-time PCR. The results showed that SelN transcripts were expressed widely in the chicken tissues. Moreover, the expression of SelN mRNA in skeletal muscles was present at a high level in whole embryos and at a lower level in postnatal stages. However, the expression of SelN mRNA in cardiac muscle showed a different expression pattern compared with skeletal muscles. Our data indicate that the expression of the SelN gene in chicken is ubiquitous, suggesting a role of SelN in the development of chick embryo skeletal muscles.
Winter, Klaus; Garcia, Milton; Holtum, Joseph A M
The capacity to induce crassulacean acid metabolism developmentally (constitutive CAM) and to up-regulate CAM expression in response to drought stress (facultative CAM) was studied in whole shoots of seven species by measuring net CO(2) gas exchange for up to 120 day-night cycles during early growth. In Clusia rosea, CAM was largely induced developmentally. Well-watered seedlings began their life cycle as C(3) plants and developed net dark CO(2) fixation indicative of CAM after the initiation of the fourth leaf pair following the cotyledons. Thereafter, CAM activity increased progressively and drought stress led to only small additional, reversible increases in dark CO(2) fixation. In contrast, CAM expression was overwhelmingly under environmental control in seedlings and mature plants of Clusia pratensis. C(3)-type CO(2) exchange was maintained under well-watered conditions, but upon drought stress, CO(2) exchange shifted, in a fully reversible manner, to a CAM-type pattern. Clusia minor showed CO(2) exchange reponses intermediate to those of C. rosea and C. pratensis. Clusia cretosa operated in the C(3) mode at all times. Notably, reversible stress-induced increases of dark CO(2) fixation were also observed during the developmental progression to pronounced CAM in young Kalanchoë daigremontiana and Kalanchoë pinnata, two species considered constitutive CAM species. Drought-induced up-regulation of CAM was even detected in young cladodes of a cactus, Opuntia ficus-indica, an archetypal constitutive CAM species. Evidently, the defining characteristics of constitutive and facultative CAM are shared, to variable degrees, by all CAM species.
Full Text Available Pervasive developmental disorders represent obviously a heterogeneous group of disorders, whose clinical expressions, courses and prospects differ significantly. Common to all these disorders, expect essential diagnostic characteristics, is the fact that they are life-long problems, thus, these are disorders without possibility of complete relief. Although measures of secondary prevention in these disorders do exert a limited effect, it is possible to achieve indubitable improvements in three fields:· well-timed application of adequate treatment may influence the essential characteristics of a disorder in the direction of adaptation to requirements of social environment, improvement of communication and enrichment of poor activity repertoire;· slowing down and delaying of unfavorable disorder evolution and· helping in understanding, accepting and adapting of child’s family to a pervasive developmental disorder.Value of early established diagnosis is not reflected only in foundation of organized adequate treatment. Early established diagnosis enables a well-timed giving of genetic advice to the family which is, as a rule, young, and without genetic load. On the other hand, well-timed diagnosis enables planning of life-long complete care for the patient with the disorder.
Disruption of thyroid hormone (TH) is a known effect of environmental contaminants. Neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been implicated in brain dysfunction resulting from severe developmental TH insufficiency. Neurotrophins are also implicated in activity-dependent plasticity, a process critical for appropriate use-dependent connectivity in the developing brain and for memory formation in the adult. This study examined activity-induced expression of neurotrophin gene products in the hippocampus using the long-term potentiation (LTP) after developmental hypothyroidism induced by propylthiouracil (PTU). Pregnant rats were exposed to PTU (0 or I0ppm) via the drinking water from early gestation to weaning. Adult male offspring were anesthetized with urethane and implanted with electrodes in the dentate gyrus (00) and perforant path (PP). LTP was induced by PP stimulation and responses from 00 were monitored at 15m intervals until sacrifice of the animals 5 h later. The 00 was dissected from the stimulated and nonstimulated hemispheres for rtPCR analysis of the neurotrophins Bdnf, Ngf, Ntf3 and related genes Egrl, Arc, Klf9. We found no PTU-induced difference in basal levels of expression of any of these genes in the nonstimulated 00. LTP increased expression of Bdnf, Ngf, Arc and Klj9 in the control DG, and reduced expression of Ntf3. LTP in DG from PTU animals failed to increase expression of Bdnf,
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.
Abdelkader, Tamer Said; Chang, Seo-Na; Kim, Tae-Hyun; Song, Juha; Kim, Dong Su; Park, Jae-Hak
Caffeine is white crystalline xanthine alkaloid that is naturally found in some plants and can be produced synthetically. It has various biological effects, especially during pregnancy and lactation. We studied the effect of caffeine on heartbeat, survival and the expression of cell damage related genes, including oxidative stress (HSP70), mitochondrial metabolism (Cyclin G1) and apoptosis (Bax and Bcl2), at early developmental stages of zebrafish embryos. We used 100 µm concentration based on the absence of locomotor effects. Neither significant mortality nor morphological changes were detected. We monitored hatching at 48 h post-fertilization (hpf) to 96 hpf. At 60 and 72 hpf, hatching decreased significantly (P caffeine treatment with no significant difference (P > 0.05). Heartbeats per minute were 110, 110 and 112 in control at 48, 72 and 96 hpf, respectively. Caffeine significantly increased heartbeat - 122 and 136 at 72 and 96 hpf, respectively. Quantitative RT-PCR showed significant up-regulation after caffeine exposure in HSP70 at 72 hpf; in Cyclin G1 at 24, 48 and 72 hpf; and in Bax at 48 and 72 hpf. Significant down-regulation was found in Bcl2 at 48 and 72 hpf. The Bax/Bcl2 ratio increased significantly at 48 and 72 hpf. We conclude that increasing exposure time to caffeine stimulates oxidative stress and may trigger apoptosis via a mitochondrial-dependent pathway. Also caffeine increases heartbeat from early phases of development without affecting the morphology and survival but delays hatching. Use of caffeine during pregnancy and lactation may harm the fetus by affecting the expression of cell-damage related genes.
Salti, Ahmad; Nat, Roxana; Neto, Sonya; Puschban, Zoe; Wenning, Gregor; Dechant, Georg
Dopaminergic neurons derived from pluripotent stem cells are among the best investigated products of in vitro stem cell differentiation owing to their potential use for neurorestorative therapy of Parkinson's disease. However, the classical differentiation protocols for both mouse and human pluripotent stem cells generate a limited percentage of dopaminergic neurons and yield a considerable cellular heterogeneity comprising numerous scarcely characterized cell populations. To improve pluripotent stem cell differentiation protocols for midbrain dopaminergic neurons, we established extensive and strictly quantitative gene expression profiles, including markers for pluripotent cells, neural progenitors, non-neural cells, pan-neuronal and glial cells, neurotransmitter phenotypes, midbrain and nonmidbrain populations, floor plate and basal plate populations, as well as for Hedgehog, Fgf, and Wnt signaling pathways. The profiles were applied to discrete stages of in vitro differentiation of mouse embryonic stem cells toward the dopaminergic lineage and after transplantation into the striatum of 6-hydroxy-dopamine-lesioned rats. The comparison of gene expression in vitro with stages in the developing ventral midbrain between embryonic day 11.5 and 13.5 ex vivo revealed dynamic changes in the expression of transcription factors and signaling molecules. Based on these profiles, we propose quantitative gene expression milestones that predict the efficiency of dopaminergic differentiation achieved at the end point of the protocol, already at earlier stages of differentiation.
Taylor, Eric; Rogers, Jody Warner
Background: Knowledge of genetic influences, on developmental disorders such as autism spectrum, attention deficit/hyperactivity disorder and learning disabilities, has increased the opportunities for understanding the influences of the early environment. Methods: This paper provides a selective, narrative review for clinicians of the effects of…
Full Text Available Background: Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods: This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results: Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion: Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting.
Aguado, Fernando; Carmona, Maria A; Pozas, Esther; Aguiló, Agustín; Martínez-Guijarro, Francisco J; Alcantara, Soledad; Borrell, Victor; Yuste, Rafael; Ibañez, Carlos F; Soriano, Eduardo
Spontaneous neural activity is a basic property of the developing brain, which regulates key developmental processes, including migration, neural differentiation and formation and refinement of connections. The mechanisms regulating spontaneous activity are not known. By using transgenic embryos that overexpress BDNF under the control of the nestin promoter, we show here that BDNF controls the emergence and robustness of spontaneous activity in embryonic hippocampal slices. Further, BDNF dramatically increases spontaneous co-active network activity, which is believed to synchronize gene expression and synaptogenesis in vast numbers of neurons. In fact, BDNF raises the spontaneous activity of E18 hippocampal neurons to levels that are typical of postnatal slices. We also show that BDNF overexpression increases the number of synapses at much earlier stages (E18) than those reported previously. Most of these synapses were GABAergic, and GABAergic interneurons showed hypertrophy and a 3-fold increase in GAD expression. Interestingly, whereas BDNF does not alter the expression of GABA and glutamate ionotropic receptors, it does raise the expression of the recently cloned K(+)/Cl(-) KCC2 co-transporter, which is responsible for the conversion of GABA responses from depolarizing to inhibitory, through the control of the Cl(-) potential. Together, results indicate that both the presynaptic and postsynaptic machineries of GABAergic circuits may be essential targets of BDNF actions to control spontaneous activity. The data indicate that BDNF is a potent regulator of spontaneous activity and co-active networks, which is a new level of regulation of neurotrophins. Given that BDNF itself is regulated by neuronal activity, we suggest that BDNF acts as a homeostatic factor controlling the emergence, complexity and networking properties of spontaneous networks.
HUANG XiangWei; ZHANG Wei; LI XinYi; ZHANG XiaoHui; LI BaoJun; MAO BingYu; ZHANG HongWei
Vertebrate RACK1 plays a key role in embryonic development. This paper described the cloning, phyIogenetic analysis and developmental expression of AmphiRACK1, the RACK1 homologous gene in amphioxus. Phylogenetic analysis indicated that amphioxus RACK1 was located at the base of vertebrate clade. AmphiRACK1 expression in lithium-treated embryos was also examined. During embryonic development, AmphiRACK1 was expressed strongly in cerebral vesicles, neural tubes and somites. In lithium-treated embryos, the segmental expression of AmphiRACK1 in somites became blurry and decreased. Its expression in cerebral vesicles and neural tubes was also weaker or disappeared. In the adult animal, AmphiRACK1 transcripts were detected in the epithelium of midgut diverticulus and gut,wheel organ, gill blood vessels and testis.
Vertebrate RACK1 plays a key role in embryonic development. This paper described the cloning, phy- logenetic analysis and developmental expression of AmphiRACK1, the RACK1 homologous gene in amphioxus. Phylogenetic analysis indicated that amphioxus RACK1 was located at the base of verte- brate clade. AmphiRACK1 expression in lithium-treated embryos was also examined. During embryonic development, AmphiRACK1 was expressed strongly in cerebral vesicles, neural tubes and somites. In lithium-treated embryos, the segmental expression of AmphiRACK1 in somites became blurry and decreased. Its expression in cerebral vesicles and neural tubes was also weaker or disappeared. In the adult animal, AmphiRACK1 transcripts were detected in the epithelium of midgut diverticulus and gut, wheel organ, gill blood vessels and testis.
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...
Schober, Michelle E; Block, Benjamin; Beachy, Joanna C; Statler, Kimberly D; Giza, Christopher C; Lane, Robert H
Pediatric traumatic brain injury (pTBI) is the leading cause of traumatic death and disability in children in the United States. Impaired learning and memory in these young survivors imposes a heavy toll on society. In adult TBI (aTBI) models, cognitive outcome improved after administration of erythropoietin (EPO) or insulin-like growth factor-1 (IGF-1). Little is known about the production of these agents in the hippocampus, a brain region critical for learning and memory, after pTBI. Our objective was to describe hippocampal expression of EPO and IGF-1, together with their receptors (EPOR and IGF-1R, respectively), over time after pTBI in 17-day-old rats. We used the controlled cortical impact (CCI) model and measured hippocampal mRNA levels of EPO, IGF-1, EPOR, IGF-1R, and markers of caspase-dependent apoptosis (bcl2, bax, and p53) at post-injury days (PID) 1, 2, 3, 7, and 14. CCI rats performed poorly on Morris water maze testing of spatial working memory, a hippocampally-based cognitive function. Apoptotic markers were present early and persisted for the duration of the study. EPO in our pTBI model increased much later (PID7) than in aTBI models (12 h), while EPOR and IGF-1 increased at PID1 and PID2, respectively, similar to data from aTBI models. Our data indicate that EPO expression showed a delayed upregulation post-pTBI, while EPOR increased early. We speculate that administration of EPO in the first 1-2 days after pTBI would increase hippocampal neuronal survival and function.
Shao-Fei Yan; Xin-Yan Liu; Yun-Fei Cheng; Zhi-Yi Li; Jie Ou; Wei Wang; Feng-Qin Li
Background:Early embryonic developmental arrest is the most commonly understudied adverse outcome of pregnancy.The relevance of intrauterine infection to spontaneous embryonic death is rarely studied and remains unclear.This study aimed to investigate the relationship between intrauterine bacterial infection and early embryonic developmental arrest.Methods:Embryonic chorion tissue and uterine swabs for bacterial detection were obtained from 33 patients who underwent artificial abortion (control group) and from 45 patients who displayed early embryonic developmental arrest (trial group).Results:Intrauterine bacterial infection was discovered in both groups.The infection rate was 24.44％ (11/45) in the early embryonic developmental arrest group and 9.09％ (3/33) in the artificial abortion group.Classification analysis revealed that the highest detection rate for Micrococcus luteus in the early embryonic developmental arrest group was 13.33％ (6/45),and none was detected in the artificial abortion group.M.luteus infection was significantly different between the groups (P ＜ 0.05 as shown by Fisher's exact test).In addition,no correlation was found between intrauterine bacterial infection and history of early embryonic developmental arrest.Conclusions:M.luteus infection is related to early embryonic developmental arrest and might be one of its causative factors.
Activity Regulated Cytoskeleton Associated Protein (Arc) is an immediate early gene that is critical to brain plasticity. In this study, norepinephrine's regulation of Arc expression was examined during different stages of postnatal development. Rats were injected with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a selective noradrenergic neurotoxin, during preadolescence (PND 0 or 13), adolescence (PND 23 or 48) or adulthood (PND 60). After each DSP4 treatment, brains were harvested later in development and Arc mRNA levels analyzed with in situ hybridization. Rats lesioned with DSP4 during preadolescence showed no differences in Arc level compared to saline treated controls. In contrast, adolescence was a time of changing Arc mRNA response to DSP4. Rats lesioned during early adolescence showed Arc expression increases, while rats lesioned during late adolescence showed dramatic Arc expression decreases. Decreases in Arc level caused by late adolescent DSP4 were similar to those found in lesioned adults. These findings highlight a qualitatively different regulation of Arc expression by norepinephrine according to developmental stage, and indicate that mature regulation is not intact until late adolescence. These data point to important developmental differences in norepinephrine's regulation of brain plasticity. These differences may underlie contrasting psychotropic responses in children and adolescents compared to adults.
Rada-Iglesias, Alvaro; Bajpai, Ruchi; Swigut, Tomek; Brugmann, Samantha A; Flynn, Ryan A; Wysocka, Joanna
Cell-fate transitions involve the integration of genomic information encoded by regulatory elements, such as enhancers, with the cellular environment. However, identification of genomic sequences that control human embryonic development represents a formidable challenge. Here we show that in human embryonic stem cells (hESCs), unique chromatin signatures identify two distinct classes of genomic elements, both of which are marked by the presence of chromatin regulators p300 and BRG1, monomethylation of histone H3 at lysine 4 (H3K4me1), and low nucleosomal density. In addition, elements of the first class are distinguished by the acetylation of histone H3 at lysine 27 (H3K27ac), overlap with previously characterized hESC enhancers, and are located proximally to genes expressed in hESCs and the epiblast. In contrast, elements of the second class, which we term 'poised enhancers', are distinguished by the absence of H3K27ac, enrichment of histone H3 lysine 27 trimethylation (H3K27me3), and are linked to genes inactive in hESCs and instead are involved in orchestrating early steps in embryogenesis, such as gastrulation, mesoderm formation and neurulation. Consistent with the poised identity, during differentiation of hESCs to neuroepithelium, a neuroectoderm-specific subset of poised enhancers acquires a chromatin signature associated with active enhancers. When assayed in zebrafish embryos, poised enhancers are able to direct cell-type and stage-specific expression characteristic of their proximal developmental gene, even in the absence of sequence conservation in the fish genome. Our data demonstrate that early developmental enhancers are epigenetically pre-marked in hESCs and indicate an unappreciated role of H3K27me3 at distal regulatory elements. Moreover, the wealth of new regulatory sequences identified here provides an invaluable resource for studies and isolation of transient, rare cell populations representing early stages of human embryogenesis.
Pang, Kevin; Martindale, Mark Q
Homeobox genes are a large family of genes that encode helix-turn-helix transcription factors that play fundamental roles in such developmental processes including body axis formation and cell specification. They have been found in a wide variety of organisms, from fungi to plants and animals, with some classes being specific to the Metazoa. While it was once thought that organismal complexity was tied to gene complexity, sequencing of genomes from a cnidarian, poriferan, and placozoan have shown no clear correlation. However, little attention has been paid to ctenophores, another early branching taxon. Ctenophores are mostly pelagic marine animals, with complex morphological features, so understanding the gene content and expression of this nonbilaterian phylum is of key interest to evolutionary biology. Expression information from developmental genes in ctenophores is sparse. In this study, we isolated seven homeobox genes from the ctenophore Mnemiopsis leidyi and examined their expression through development. Phylogenetic analyses of these genes placed four in the ANTP class and three in the PRD class. These are the first reported full-length PRD class genes, although our analyses could not place them into specific families. We have found that most of these homeobox genes begin expression at gastrulation, and their expression patterns suggest a possible role in patterning of the tentacle apparati and pharynx.
Kirsch, Lior; Chechik, Gal
Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions.
Full Text Available Abstract Background The identification of the adipocyte-derived obesity gene product, leptin (Ob, and subsequently its association with reproduction in rodents and humans led to speculations that leptin may be involved in the regulation of oocyte and preimplantation embryo development. In mice and pigs, in vitro leptin addition significantly increased meiotic resumption and promoted preimplantation embryo development in a dose-dependent manner. This study was conducted to determine whether leptin supplementation during in vitro maturation (IVM to horse oocytes could have effects on their developmental capacity after fertilization by IntraCytoplasmic Sperm Injection (ICSI. Methods Compact and expanded-cumulus horse oocytes were matured in medium containing different concentrations (1, 10, 100, 1000 ng/ml of recombinant human leptin and the effects on maturation, fertilization and embryo cleavage were evaluated. Furthermore, early developmental expression of Ob and leptin receptor (Ob-R was investigated by immunocytochemical staining. Results In expanded-cumulus oocytes, the addition of leptin in IVM medium improved maturation (74% vs 44%, for 100 ng/ml leptin-treated and control groups, respectively; P Conclusion Leptin plays a cumulus cell-mediated role in the regulation of oocyte maturation in the mare. Species-specific differences may exist in oocyte sensitivity to leptin.
Maatta, Sira; Laakso, Marja-Leena; Tolvanen, Asko; Ahonen, Timo; Aro, Tuija
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…
Maatta, Sira; Laakso, Marja-Leena; Tolvanen, Asko; Ahonen, Timo; Aro, Tuija
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…
Shinojima, Naoki; Nakamura, Hideo; Tasaki, Masayoshi; Kameno, Kouki; Anai, Shigeo; Iyama, Ken-ichi; Ando, Yukio; Seto, Hiroshi; Kuratsu, Jun-Ichi
Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups- WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)-since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap-that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.
Cheng, Mei-Fang; Johnson, James E.
Our review examined four early childhood journals ("Early Child Development and Care," "Early Childhood Education Journal," "Journal of Research in Childhood Education," and "Early Childhood Research Quarterly") and four developmental science journals ("Child Development," "Developmental Psychology," "Journal of Applied Developmental…
Cheng, Mei-Fang; Johnson, James E.
Our review examined four early childhood journals ("Early Child Development and Care," "Early Childhood Education Journal," "Journal of Research in Childhood Education," and "Early Childhood Research Quarterly") and four developmental science journals ("Child Development," "Developmental Psychology," "Journal of Applied Developmental…
van den Heuvel, Mathilda
This thesis focuses on the early identification of developmental and behavioral problems in pediatric primary care. The social environment is considered a fundamental determinant of early child development. In our study countries with generous redistributive policies had a better organization of ear
Mengoni, Silvana; Oates, John
The Early Years Developmental Journal is intended as a useful resource for practitioners when monitoring progress, supporting assessments and providing a basis for communicating with parents and other practitioners. In particular it can support the statutory early years progress assessment and child health monitoring when a child is around 2 years of age. It is closely linked with the Early Years Foundation Stage (EYFS) Development Matters and with the Personal Child Health Record (PCHR or ‘r...
Full Text Available Abstract Cathelicidins are a major family of antimicrobial peptides present in vertebrate animals with potent microbicidal and immunomodulatory activities. Four cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1, have been identified in chickens. As a first step to understand their role in early innate host defense of chickens, we examined the tissue and developmental expression patterns of all four cathelicidins. Real-time PCR revealed an abundant expression of four cathelicidins throughout the gastrointestinal, respiratory, and urogenital tracts as well as in all primary and secondary immune organs of chickens. Fowlicidins 1 to 3 exhibited a similar tissue expression pattern with the highest expression in the bone marrow and lung, while cathelicidin B1 was synthesized most abundantly in the bursa of Fabricius. Additionally, a tissue-specific regulatory pattern was evident for all four cathelicidins during the first 28 days after hatching. The expression of fowlicidins 1 to 3 showed an age-dependent increase both in the cecal tonsil and lung, whereas all four cathelicidins were peaked in the bursa on day 4 after hatching, with a gradual decline by day 28. An abrupt augmentation in the expression of fowlicidins 1 to 3 was also observed in the cecum on day 28, while the highest expression of cathelicidin B1 was seen in both the lung and cecal tonsil on day 14. Collectively, the presence of cathelicidins in a broad range of tissues and their largely enhanced expression during development are suggestive of their potential important role in early host defense and disease resistance of chickens.
Dash, P; Patel, S; Dixit, A; Garg, L C; Sahoo, P K
Cytokines are important components of both adaptive and innate immunity, and are required to initiate and regulate immune responses following infection. The ontogeny and tissue specific distribution of four pro-inflammatory cytokines, interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), IL-8 and IL-1β in rohu (Labeo rohita), and their responses by leucocytes from anterior-kidney/head-kidney (HKLs), spleen (SPLs) and peripheral blood (PBLs) following stimulation with concanavalin A (ConA), ConA with phorbol 12-myristate 13-acetate (ConA/PMA) and formalin-killed Aeromonas hydrophila cells (FAH) were studied. In ontogeny study, mRNA levels of IL-6 and IL-1β were evident in unfertilized egg stages of L. rohita whereas IL-8 and TNF-α transcripts were found from 1 to 3 h post-fertilization (hpf) onwards till day 15 post-fertilization, respectively. Basal level of all four cytokines was observed in all twelve tissues (eye, brain, heart, gill, anterior kidney, posterior kidney, spleen, liver, skin, muscle, hindgut and foregut) of L. rohita juveniles. Expression levels of IL-6 and IL-8 were found to be the highest in liver and heart tissues, respectively, while TNF-α transcripts were high in anterior kidney and liver tissues. Transcripts of IL-1β showed high expression in muscle, heart and spleen. Upon in vitro stimulation of leucocytes, there was variable up-regulation of all the four cytokines following different treatments throughout the experimental time period. Induction of cytokines was more pronounced in PBLs stimulated with FAH compared to other stimuli. However, an up-regulated IL-8 expression was evident in all the leucocytes following stimulation with FAH thus indicating IL-8 could be used as an indicator or indirect marker to monitor vaccine status or health status of L. rohita during bacterial infection.
Bonuck, Karen; Grant, Roy
Sleep disorders negatively impact behavior, cognition, and growth--the same areas targeted by early intervention. Conversely, developmental delays and disabilities may themselves precipitate sleep disorders. Young children with developmental delays experience sleep disorders at a higher rate than do typically developing children; the most common…
Bonuck, Karen; Grant, Roy
Sleep disorders negatively impact behavior, cognition, and growth--the same areas targeted by early intervention. Conversely, developmental delays and disabilities may themselves precipitate sleep disorders. Young children with developmental delays experience sleep disorders at a higher rate than do typically developing children; the most common…
Pryor, Laura E.; Mara Brendgen; Richard E Tremblay; Jean-Baptiste Pingault; Xuecheng Liu; Lise Dubois; Evelyne Touchette; Bruno Falissard; Michel Boivin; Sylvana M Côté
Background Research is needed to identify early life risk factors associated with different developmental paths leading to overweight by adolescence. Objectives To model heterogeneity in overweight development during middle childhood and identify factors associated with differing overweight trajectories. Methods Data was drawn from the Quebec Longitudinal Study of Child Development (QLSCD; 1998-2010). Trained research assistants measured height and weight according to a standardized protocol ...
Full Text Available BACKGROUND: Cardiomyocytes derived from murine embryonic stem (ES cells possess various membrane currents and signaling cascades link to that of embryonic hearts. The role of atrial natriuretic peptide (ANP in regulation of membrane potentials and Ca(2+ currents has not been investigated in developmental cardiomyocytes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the role of ANP in regulating L-type Ca(2+ channel current (I(CaL in different developmental stages of cardiomyocytes derived from ES cells. ANP decreased the frequency of action potentials (APs in early developmental stage (EDS cardiomyocytes, embryonic bodies (EB as well as whole embryo hearts. ANP exerted an inhibitory effect on basal I(CaL in about 70% EDS cardiomyocytes tested but only in about 30% late developmental stage (LDS cells. However, after stimulation of I(CaL by isoproterenol (ISO in LDS cells, ANP inhibited the response in about 70% cells. The depression of I(CaL induced by ANP was not affected by either Nomega, Nitro-L-Arginine methyl ester (L-NAME, a nitric oxide synthetase (NOS inhibitor, or KT5823, a cGMP-dependent protein kinase (PKG selective inhibitor, in either EDS and LDS cells; whereas depression of I(CaL by ANP was entirely abolished by erythro-9-(2-Hydroxy-3-nonyl adenine (EHNA, a selective inhibitor of type 2 phosphodiesterase(PDE2 in most cells tested. CONCLUSION/SIGNIFICANCES: Taken together, these results indicate that ANP induced depression of action potentials and I(CaL is due to activation of particulate guanylyl cyclase (GC, cGMP production and cGMP-activation of PDE2 mediated depression of adenosine 3', 5'-cyclic monophophate (cAMP-cAMP-dependent protein kinase (PKA in early cardiomyogenesis.
Laura E Pryor
Full Text Available Research is needed to identify early life risk factors associated with different developmental paths leading to overweight by adolescence.To model heterogeneity in overweight development during middle childhood and identify factors associated with differing overweight trajectories.Data was drawn from the Quebec Longitudinal Study of Child Development (QLSCD; 1998-2010. Trained research assistants measured height and weight according to a standardized protocol and conducted yearly home interviews with the child's caregiver (mother in 98% of cases. Information on several putative early life risk factors for the development of overweight were obtained, including factors related to the child's perinatal, early behavioral family and social environment. Group-based trajectories of the probability of overweight (6-12 years were identified with a semiparametric method (n=1678. Logistic regression analyses were used to identify early risk factors (5 months- 5 years associated with each trajectory.Three trajectories of overweight were identified: "early-onset overweight" (11.0 %, "late-onset overweight" (16.6% and "never overweight" (72.5%. Multinomial analyses indicated that children in the early and late-onset group, compared to the never overweight group, had 3 common types of risk factors: parental overweight, preschool overweight history, and large size for gestational age. Maternal overprotection (OR= 1.12, CI: 1.01-1.25, short nighttime sleep duration (OR=1.66, CI: 1.07-2.57, and immigrant status (OR=2.01, CI: 1.05-3.84 were factors specific to the early-onset group. Finally, family food insufficiency (OR=1.81, CI: 1.00-3.28 was weakly associated with membership in the late-onset trajectory group.The development of overweight in childhood follows two different trajectories, which have common and distinct risk factors that could be the target of early preventive interventions.
Moraleda-Barreno, E; Romero-López, M; Cayetano-Menéndez, M J
Cerebral palsy is usually associated with motor, cognitive, and language deficits, and with other disorders that cause disability in daily living skills, personal independence, social interaction and academic activities. Early detection of these deficits in the clinical setting is essential to anticipate and provide the child with the necessary support for adapting to the environment in all possible areas. The main objective of this study is to demonstrate that these deficits can be detected at an early age and comprehensively through the use of a brief development scale. We studied 100 children between 4 and 70 months old, half of them with cerebral palsy and the other half without any disorder. All subjects were evaluated using the Battelle Developmental Inventory screening test. We compared the developmental quotients in both groups and between the subjects with different motor impairments, using a simple prospective ex post facto design. The test detected statistically significant differences between the clinical group and the control group at all age levels. Statistically significant differences were also found between tetraplegia and other motor disorders. There were no differences by gender. The deficit in development associated with cerebral palsy can be quantified at early ages through the use of a brief development scale, thus we propose that the systematic implementation of protocols with this screening tool would be helpful for treatment and early intervention. This would also help in anticipating and establishing the means for the multidisciplinary actions required, and could provide guidance to other health professionals, to provide adequate school, social, and family support,. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
Aparicio, J G; Hopp, H; Choi, A; Mandayam Comar, J; Liao, V C; Harutyunyan, N; Lee, T C
Human retinal ganglion cells (RGCs) derived from pluripotent stem cells (PSCs) have anticipated value for human disease study, drug screening, and therapeutic applications; however, their full potential remains underdeveloped. To characterize RGCs in human embryonic stem cell (hESC) derived retinal organoids we examined RGC markers and surface antigen expression and made comparisons to human fetal retina. RGCs in both tissues exhibited CD184 and CD171 expression and distinct expression patterns of the RGC markers BRN3 and RBPMS. The retinal progenitor cells (RPCs) of retinal organoids expressed CD184, consistent with its expression in the neuroblastic layer in fetal retina. In retinal organoids CD184 expression was enhanced in RGC competent RPCs and high CD184 expression was retained on post-mitotic RGC precursors; CD171 was detected on maturing RGCs. The differential expression timing of CD184 and CD171 permits identification and enrichment of RGCs from retinal organoids at differing maturation states from committed progenitors to differentiating neurons. These observations will facilitate molecular characterization of PSC-derived RGCs during differentiation, critical knowledge for establishing the veracity of these in vitro produced cells. Furthermore, observations made in the retinal organoid model closely parallel those in human fetal retina further validating use of retinal organoid to model early retinal development.
Sitnick, Stephanie L; Shaw, Daniel S; Hyde, Luke W
This study examined developmentally salient risk and protective factors of adolescent substance use assessed during early childhood and early adolescence using a sample of 310 low-income boys. Child problem behavior and proximal family risk and protective factors (i.e., parenting and maternal depression) during early childhood, as well as child and family factors and peer deviant behavior during adolescence, were explored as potential precursors to later substance use during adolescence using structural equation modeling. Results revealed that early childhood risk and protective factors (i.e., child externalizing problems, mothers' depressive symptomatology, and nurturant parenting) were indirectly related to substance use at the age of 17 via risk and protective factors during early and middle adolescence (i.e., parental knowledge and externalizing problems). The implications of these findings for early prevention and intervention are discussed.
Oleksandr Vasyliovuch Lozinsky
Full Text Available Background: In this study, the toxicity of the different xenobiotics was tested on the fruit fly Drosophila melanogaster model system. Methods: Fly larvae were raised on food supplemented with xenobiotics at different concentrations (sodium nitroprusside (0.1-1.5 mM, S-nitrosoglutathione (0.5-4 mM, and potassium ferrocyanide (1 mM. Emergence of flies, food intake by larvae, and pupation height preference as well as aconitase activity (in 2-day old flies were measured. Results: Food supplementation with xenobiotics caused a developmental delay in the flies and decreased pupation height. Biochemical analyses of oxidative stress markers and activities of antioxidants and their associated enzymes were carried out on 2-day-old flies emerged from control larvae and larvae fed on food supplemented with chemicals. Larval exposure to chemicals resulted in lower activities of aconitase in flies of both sexes and perturbation in activities of antioxidant enzymes. Conclusions: The results of this study showed that among a variety of parameters tested, aconitase activity, developmental endpoints, and pupation height may be used as reliable early indicators of toxicity caused by different chemicals.
Cardiovascular diseases are the major threat to human health and underlie almost half of all deaths in China. Even more serious, obesity and cardiometabolic risk factors have emerged to be prevalent in children and adolescents of some affluent regions. As scientific knowledge emerges on the role of nutritional factors and exposures to environmental risk factors in the developmental origins of health and disease, evidence suggests that it is imperative to create and implement early effective prevention strategies, including optimisation of nutrition at first 1 000 days in life course and reduction of risk factors of obesity exposures during whole childhood, to suppress the rising trend of cardiovascular disease, otherwise, the future costs of diagnosis and treatment are likely to be unaffordable.
Gobert, Geoffrey N; Moertel, Luke; Brindley, Paul J; McManus, Donald P
Background The schistosome blood flukes are complex trematodes and cause a chronic parasitic disease of significant public health importance worldwide, schistosomiasis. Their life cycle is characterised by distinct parasitic and free-living phases involving mammalian and snail hosts and freshwater. Microarray analysis was used to profile developmental gene expression in the Asian species, Schistosoma japonicum. Total RNAs were isolated from the three distinct environmental phases of the lifecycle – aquatic/snail (eggs, miracidia, sporocysts, cercariae), juvenile (lung schistosomula and paired but pre-egg laying adults) and adult (paired, mature males and egg-producing females, both examined separately). Advanced analyses including ANOVA, principal component analysis, and hierarchal clustering provided a global synopsis of gene expression relationships among the different developmental stages of the schistosome parasite. Results Gene expression profiles were linked to the major environmental settings through which the developmental stages of the fluke have to adapt during the course of its life cycle. Gene ontologies of the differentially expressed genes revealed a wide range of functions and processes. In addition, stage-specific, differentially expressed genes were identified that were involved in numerous biological pathways and functions including calcium signalling, sphingolipid metabolism and parasite defence. Conclusion The findings provide a comprehensive database of gene expression in an important human pathogen, including transcriptional changes in genes involved in evasion of the host immune response, nutrient acquisition, energy production, calcium signalling, sphingolipid metabolism, egg production and tegumental function during development. This resource should help facilitate the identification and prioritization of new anti-schistosome drug and vaccine targets for the control of schistosomiasis. PMID:19320991
McManus Donald P
Full Text Available Abstract Background The schistosome blood flukes are complex trematodes and cause a chronic parasitic disease of significant public health importance worldwide, schistosomiasis. Their life cycle is characterised by distinct parasitic and free-living phases involving mammalian and snail hosts and freshwater. Microarray analysis was used to profile developmental gene expression in the Asian species, Schistosoma japonicum. Total RNAs were isolated from the three distinct environmental phases of the lifecycle – aquatic/snail (eggs, miracidia, sporocysts, cercariae, juvenile (lung schistosomula and paired but pre-egg laying adults and adult (paired, mature males and egg-producing females, both examined separately. Advanced analyses including ANOVA, principal component analysis, and hierarchal clustering provided a global synopsis of gene expression relationships among the different developmental stages of the schistosome parasite. Results Gene expression profiles were linked to the major environmental settings through which the developmental stages of the fluke have to adapt during the course of its life cycle. Gene ontologies of the differentially expressed genes revealed a wide range of functions and processes. In addition, stage-specific, differentially expressed genes were identified that were involved in numerous biological pathways and functions including calcium signalling, sphingolipid metabolism and parasite defence. Conclusion The findings provide a comprehensive database of gene expression in an important human pathogen, including transcriptional changes in genes involved in evasion of the host immune response, nutrient acquisition, energy production, calcium signalling, sphingolipid metabolism, egg production and tegumental function during development. This resource should help facilitate the identification and prioritization of new anti-schistosome drug and vaccine targets for the control of schistosomiasis.
Full Text Available Abstract Background Ovarian follicle development is a complex process. Paracrine interactions between somatic and germ cells are critical for normal follicular development and oocyte maturation. Studies have suggested that the health and function of the granulosa and cumulus cells may be reflective of the health status of the enclosed oocyte. The objective of the present study is to assess, using an in vivo immature rat model, gene expression profile in granulosa cells, which may be linked to the developmental competence of the oocyte. We hypothesized that expression of specific genes in granulosa cells may be correlated with the developmental competence of the oocyte. Methods Immature rats were injected with eCG and 24 h thereafter with anti-eCG antibody to induce follicular atresia or with pre-immune serum to stimulate follicle development. A high percentage (30-50%, normal developmental competence, NDC of oocytes from eCG/pre-immune serum group developed to term after embryo transfer compared to those from eCG/anti-eCG (0%, poor developmental competence, PDC. Gene expression profiles of mural granulosa cells from the above oocyte-collected follicles were assessed by Affymetrix rat whole genome array. Results The result showed that twelve genes were up-regulated, while one gene was down-regulated more than 1.5 folds in the NDC group compared with those in the PDC group. Gene ontology classification showed that the up-regulated genes included lysyl oxidase (Lox and nerve growth factor receptor associated protein 1 (Ngfrap1, which are important in the regulation of protein-lysine 6-oxidase activity, and in apoptosis induction, respectively. The down-regulated genes included glycoprotein-4-beta galactosyltransferase 2 (Ggbt2, which is involved in the regulation of extracellular matrix organization and biogenesis. Conclusions The data in the present study demonstrate a close association between specific gene expression in mural granulosa cells and
Flensborg-Madsen, T; Sørensen, H J; Revsbech, Rasmus
Studies investigating early developmental factors in relation to psychopathology have mainly focused on schizophrenia. The personality dimension of neuroticism seems to be a general risk factor for psychopathology, but evidence on associations between early developmental precursors and personalit...... analysed by multiple linear regression adjusting for for sex, single-mother status, parity, mother's age, father's age, parental social status and birth weight....... traits is almost non-existent. This study is therefore the first to investigate associations between early motor developmental milestones and neuroticism in adulthood. Method Mothers of 9125 children of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the child's first year...
Nichols, Sara R; Briggs-Gowan, Margaret J; Estabrook, Ryne; Burns, James L; Kestler, Jacqueline; Berman, Grace; Henry, David B; Wakschlag, Lauren S
Impairment in learning from punishment ("punishment insensitivity") is an established feature of severe antisocial behavior in adults and youth but it has not been well studied as a developmental phenomenon. In early childhood, differentiating a normal: abnormal spectrum of punishment insensitivity is key for distinguishing normative misbehavior from atypical manifestations. This study employed a novel measure, the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB), to examine the distribution, dimensionality, and external validity of punishment insensitivity in a large, demographically diverse community sample of preschoolers (3-5 years) recruited from pediatric clinics (N = 1,855). Caregivers completed surveys from which a seven-item Punishment Insensitivity scale was derived. Findings indicated that Punishment Insensitivity behaviors are relatively common in young children, with at least 50 % of preschoolers exhibiting them sometimes. Item response theory analyses revealed a Punishment Insensitivity spectrum. Items varied along a severity continuum: most items needed to occur "Often" in order to be severe and behaviors that were qualitatively atypical or intense were more severe. Although there were item-level differences across sociodemographic groups, these were small. Construct, convergent, and divergent validity were demonstrated via association to low concern for others and noncompliance, motivational regulation, and a disruptive family context. Incremental clinical utility was demonstrated in relation to impairment. Early childhood punishment insensitivity varies along a severity continuum and is atypical when it predominates. Implications for understanding the phenomenology of emergent disruptive behavior are discussed.
Stuart Ian Hammond
After a brief overview of recent research on early helping, outlining some central problems, and issues, this paper examines children’s early helping through the lens of Piagetian moral and developmental theory, drawing on Piaget’s “Moral Judgment of the Child” (Piaget, 1932/1997), “Play, Dreams, and Imitation in Childhood” (Piaget, 1945/1951), and the “Grasp of Consciousness” (Piaget, 1976). Piaget refers to a level of moral development in action that precedes heteronomous and autonomous mor...
The purposes of this study were (a) to examine early elementary grade teachers' developmentally appropriate beliefs and their teaching practices in public schools in Bangkok, (b) to explore the functioning of developmentally appropriate practice in the two chosen early elementary schools, and (c) to determine the factors that influence the…
Hart, Anthony Richard; Sharma, Ruchi; Atherton, Mark; Alabed, Samer; Simpson, Sally; Barfield, Stuart; Cohen, Judith; McGlashan, Nicholas; Ravi, Asha; Parker, Michael James; Connolly, Daniel Ja
To study the frequency a diagnosis is made in children with early developmental impairment (EDI), and the contribution made to diagnosis by specific investigations. Retrospective case note review. Community, neurodisability and neurology department at a UK tertiary centre. Children referred to determine the aetiology of EDI where a cause was not evident on history and examination. Participants were divided into two groups: EDI and no additional features (EDI-) and EDI with additional features (EDI+). The frequency a cause was found for the child's EDI and which tests contributed to a diagnosis. 699 participants, 68.8% boys, median age at investigation 2 years 8 months (range 3 months to 11 years 5 months). 61 (8.7%) of participants had no investigations, and children with EDIâˆ' were less likely to be investigated (Ï‡(2)=12.5, pdata. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Hammond, Stuart I
After a brief overview of recent research on early helping, outlining some central problems, and issues, this paper examines children's early helping through the lens of Piagetian moral and developmental theory, drawing on Piaget's "Moral Judgment of the Child" (Piaget, 1932/1997), "Play, Dreams, and Imitation in Childhood" (Piaget, 1945/1951), and the "Grasp of Consciousness" (Piaget, 1976). Piaget refers to a level of moral development in action that precedes heteronomous and autonomous moral reasoning. This action level allows children to begin to interact with people and objects. In his later work, Piaget explores the gradual construction of understanding from this activity level. Taken together, these elements of Piagetian theory provide a promising conceptual framework for understanding the development of early helping.
Stuart Ian Hammond
Full Text Available After a brief overview of recent research on early helping, outlining some central problems and issues, this paper examines children’s early helping through the lens of Piagetian moral and developmental theory, drawing on Piaget’s ‘Moral Judgment of the Child’ (1932/1997, ‘Play, Dreams, and Imitation in Childhood’ (1945/1951, and the ‘Grasp of Consciousness’ (1974. Piaget refers to a level of moral development in action that precedes heteronomous and autonomous moral reasoning. This action level allows children to begin to interact with people and objects. In his later work, Piaget explores the gradual construction of understanding from this activity level. Taken together, these elements of Piagetian theory provide a promising conceptual framework for understanding the development of early helping.
Guyer, Amanda E.; Monk, Christopher S.; McClure-Tone, Erin B.; Nelson, Eric E.; Roberson-Nay, Roxann; Adler, Abby D.; Fromm, Stephen J.; Leibenluft, Ellen; Pine, Daniel S.; Ernst, Monique
Several lines of evidence implicate the amygdala in face– emotion processing, particularly for fearful facial expressions. Related findings suggest that face–emotion processing engages the amygdala within an interconnected circuitry that can be studied using a functional-connectivity approach. Past work also underscores important functional changes in the amygdala during development. Taken together, prior research on amygdala function and development reveals a need for more work examining developmental changes in the amygdala’s response to fearful faces and in amygdala functional connectivity during face processing. The present study used event-related functional magnetic resonance imaging to compare 31 adolescents (9–17 years old) and 30 adults (21–40 years old) on activation to fearful faces in the amygdala and other regions implicated in face processing. Moreover, these data were used to compare patterns of amygdala functional connectivity in adolescents and adults. During passive viewing, adolescents demonstrated greater amygdala and fusiform activation to fearful faces than did adults. Functional connectivity analysis revealed stronger connectivity between the amygdala and the hippocampus in adults than in adolescents. Within each group, variability in age did not correlate with amygdala response, and sex-related developmental differences in amygdala response were not found. Eye movement data collected outside of the magnetic resonance imaging scanner using the same task suggested that developmental differences in amygdala activation were not attributable to differences in eye-gaze patterns. Amygdala hyperactivation in response to fearful faces may explain increased vulnerability to affective disorders in adolescence; stronger amygdala–hippocampus connectivity in adults than adolescents may reflect maturation in learning or habituation to facial expressions. PMID:18345988
Gymnopoulos, Marco; Cingolani, Lorenzo A; Pedarzani, Paola; Stocker, Martin
Early electrical activity and calcium influx regulate crucial aspects of neuronal development. Small-conductance calcium-activated potassium (SK) channels regulate action potential firing and shape calcium influx through feedback regulation in mature neurons. These functions, observed in the adult nervous system, make them ideal candidates to regulate activity- and calcium-dependent processes in neurodevelopment. However, to date little is known about the onset of expression and regions expressing SK channel subunits in the embryonic and postnatal development of the central nervous system (CNS). To allow studies on the contribution of SK channels to different phases of development of single neurons and networks, we have performed a detailed in situ hybridization mapping study, providing comprehensive distribution profiles of all three SK subunits (SK1, SK2, and SK3) in the rat CNS during embryonic and postnatal development. SK channel transcripts are expressed at early stages of prenatal CNS development. The three SK channel subunits display different developmental expression gradients in distinct CNS regions, with time points of expression and up- or downregulation that can be associated with a range of diverse developmental events. Their early expression in embryonic development suggests an involvement of SK channels in the regulation of developmental processes. Additionally, this study shows how the postnatal ontogenetic patterns lead to the adult expression map for each SK channel subunit and how their coexpression in the same regions or neurons varies throughout development.
An invertebrate signal transducer and activator of transcription 5 (STAT5) ortholog from the disk abalone, Haliotis discus discus: Genomic structure, early developmental expression, and immune responses to bacterial and viral stresses.
Bathige, S D N K; Umasuthan, Navaneethaiyer; Park, Hae-Chul; Lee, Jehee
Signal transducer and activator of transcription (STAT) family members are key signaling molecules that transduce cellular responses from the cell membrane to the nucleus upon Janus kinase (JAK) activation. Although seven STAT members have been reported in mammals, very limited information on STAT genes in molluscans is available. In this study, we identified and characterized a STAT paralog that is homologous to STAT5 from the disk abalone, Haliotis discus discus, and designated as AbSTAT5. Comparison of the deduced amino acid sequence for AbSTAT5 (790 amino acids) with other counterparts revealed conserved residues important for functions and typical domain regions, including the N-terminal domain, coiled-coil domain, DNA-binding domain, linker domain, and Src homology 2 (SH2) domains as mammalian counterparts. Analysis of STAT phylogeny revealed that AbSTAT5 was clustered with the molluscan subgroup in STAT5 clade with distinct evolution. According to the genomic structure of AbSTAT5, the coding sequence was distributed into 20 exons with 19 introns. Immunologically essential transcription factor-binding sites, such as GATA-1, HNF, SP1, C/EBP, Oct-1, AP1, c-Jun, and Sox-2, were predicted at the 5'-proximal region of AbSTAT5. Expression of AbSTAT5 mRNA was detected in different stages of embryonic development and observed at considerably higher levels in the morula and late veliger stages. Tissue-specific expressional studies revealed that the highest level of AbSTAT5 transcripts was detected in hemocytes, followed by gill tissues. Temporal expressions of AbSTAT5 were analyzed upon live bacterial (Vibrio parahemolyticus and Listeria monocytogenes), viral (viral hemorrhagic septicemia virus), and pathogen-associated molecular pattern (lipopolysaccharides and Poly I:C) stimulations, and significant elevations indicated immune modulation. These results suggest that AbSTAT5 may be involved in maintaining innate immune responses from developmental to adult stages in
Philibert, R A; Winfield, S L; Damschroder-Williams, P; Tengstrom, C; Martin, B M; Ginns, E I
We determined the genomic organization of the human OPA-containing gene (HOPA) and characterized its developmental expression. The gene encoding HOPA, which contains a rare polymorphism tightly associated with non-specific mental retardation, is 25 kb in length and consists of 44 exons. A promoter scan analysis demonstrates two possible transcription initiation sites without TATA boxes upstream from the putative translation initiation start site. Several informative polymorphisms are evident in the sequence including a large pentanucleotide repeat. Northern blot analysis of the gene transcript and its murine orthologue, MOPA-1, demonstrates that only one transcript is expressed throughout the soma and the CNS, and that the transcript is highly expressed during early fetal development. We conclude that the delineation of the function of the HOPA gene locus merits further study.
Flensborg-Madsen, Trine; Sørensen, Holger Jelling; Revsbech, Rasmus
intelligence. CONCLUSIONS: The findings are the first of their kind and suggest that delays in early motor development may not only characterize psychopathological disorders such as schizophrenia, but may also be associated with the personality dimension of neuroticism in adulthood.......BACKGROUND: Studies investigating early developmental factors in relation to psychopathology have mainly focused on schizophrenia. The personality dimension of neuroticism seems to be a general risk factor for psychopathology, but evidence on associations between early developmental precursors...... and personality traits is almost non-existent. This study is therefore the first to investigate associations between early motor developmental milestones and neuroticism in adulthood. Method Mothers of 9125 children of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the child's first...
Full Text Available SUMO proteins are small ubiquitin-related modifiers. All SUMOs are synthesized as propeptides that are post-translationally cleaved prior to conjugation. After processing, SUMOs become covalently conjugated to cellular targets through a pathway that is similar to ubiquitination. Ubiquitin like protein proteases/Sentrin specific proteases (Ulp/SENPs mediate both processing and deconjugation of SUMOs. The action of Ulp/SENPs makes SUMOylation a highly dynamic post-translational modification. To investigate how Ulp/SENPs are regulated in a developmental context, we isolated and characterized all Ulp/SENPs in Xenopus laevis. Xenopus possess homologues of mammalian SENP3, 5, 6 and 7. All of these enzymes reacted with HA-tagged vinyl sulfone derivatives of SUMO-2 (HA-SU2-VS but not SUMO-1 (HA-SU1-VS, suggesting that they act primarily on SUMO-2 and -3. In contrast, Xenopus possess a single member of the SENP1/SENP2 subfamily of Ulp/SENPs, most closely related to mammalian SENP1. Xenopus SENP1 reacted with HA-SU1-VS and HA-SU2-VS, suggesting that it acts on all SUMO paralogues. We analyzed the mRNA and protein levels for each of the Ulp/SENPs through development; we found that they show distinct patterns of expression that may involve both transcriptional and post-transcriptional regulation. Finally, we have characterized the developmental function of the most abundant Ulp/SENP found within Xenopus eggs, SENP3. Depletion of SENP3 using morpholino antisense oligonucleotides (morpholinos caused accumulation of high molecular weight SUMO-2/3 conjugated species, defects in developing embryos and changes in the expression of some genes regulated by the transforming growth factor beta (TGF-beta pathway. These findings collectively indicate that SUMO proteases are both highly regulated and essential for normal development.
Full Text Available We have used Digital Gene Expression analysis to identify, without bilaterian bias, regulators of cnidarian embryonic patterning. Transcriptome comparison between un-manipulated Clytia early gastrula embryos and ones in which the key polarity regulator Wnt3 was inhibited using morpholino antisense oligonucleotides (Wnt3-MO identified a set of significantly over and under-expressed transcripts. These code for candidate Wnt signaling modulators, orthologs of other transcription factors, secreted and transmembrane proteins known as developmental regulators in bilaterian models or previously uncharacterized, and also many cnidarian-restricted proteins. Comparisons between embryos injected with morpholinos targeting Wnt3 and its receptor Fz1 defined four transcript classes showing remarkable correlation with spatiotemporal expression profiles. Class 1 and 3 transcripts tended to show sustained expression at "oral" and "aboral" poles respectively of the developing planula larva, class 2 transcripts in cells ingressing into the endodermal region during gastrulation, while class 4 gene expression was repressed at the early gastrula stage. The preferential effect of Fz1-MO on expression of class 2 and 4 transcripts can be attributed to Planar Cell Polarity (PCP disruption, since it was closely matched by morpholino knockdown of the specific PCP protein Strabismus. We conclude that endoderm and post gastrula-specific gene expression is particularly sensitive to PCP disruption while Wnt-/β-catenin signaling dominates gene regulation along the oral-aboral axis. Phenotype analysis using morpholinos targeting a subset of transcripts indicated developmental roles consistent with expression profiles for both conserved and cnidarian-restricted genes. Overall our unbiased screen allowed systematic identification of regionally expressed genes and provided functional support for a shared eumetazoan developmental regulatory gene set with both predicted and
Watkins, R V; Yairi, E; Ambrose, N G
This investigation evaluated the expressive language abilities of 84 preschool-age children who stuttered, 62 who recovered from stuttering, and 22 who persisted in stuttering. The participants were identical to those identified in E. Yairi and N. G. Ambrose (1999) and E. Paden, E. Yairi, and N. G. Ambrose (1999). A range of lexical, morphological, and syntactic measures--calculated from spontaneous language samples of approximately 250-300 utterances in length collected relatively near stuttering onset--were used to examine the children's expressive language skills. For the purpose of analysis and comparison to normative data, children were grouped into three age intervals, in terms of the age at which they entered the study (2- to 3-year-olds, 3- to 4-year-olds, and 4- to 5-year-olds). Findings revealed similarity in the expressive language abilities of children whose stuttering persisted as opposed to abated at all age intervals. In addition, persistent and recovered stutterers displayed expressive language abilities near or above developmental expectations, based on comparison with normative data, at all age intervals. Children who entered the study at the youngest age level consistently demonstrated expressive language abilities well above normative expectations; this pattern was found for both persistent and recovered groups. These findings provide relatively limited information to assist in the early differentiation of persistence in or recovery from stuttering, but they do shed light on theoretical issues regarding the nature and character of early stuttering and potential associations with language learning.
Hoftman, Gil D; Volk, David W; Bazmi, H Holly; Li, Siyu; Sampson, Allan R; Lewis, David A
Schizophrenia is a neurodevelopmental disorder with altered expression of GABA-related genes in the prefrontal cortex (PFC). However, whether these gene expression abnormalities reflect disturbances in postnatal developmental processes before clinical onset or arise as a consequence of clinical illness remains unclear. Expression levels for 7 GABA-related transcripts (vesicular GABA transporter [vGAT], GABA membrane transporter [GAT1], GABAA receptor subunit α1 [GABRA1] [novel in human and monkey cohorts], glutamic acid decarboxylase 67 [GAD67], parvalbumin, calretinin, and somatostatin [previously reported in human cohort, but not in monkey cohort]) were quantified in the PFC from 42 matched pairs of schizophrenia and comparison subjects and from 49 rhesus monkeys ranging in age from 1 week postnatal to adulthood. Levels of vGAT and GABRA1, but not of GAT1, messenger RNAs (mRNAs) were lower in the PFC of the schizophrenia subjects. As previously reported, levels of GAD67, parvalbumin, and somatostatin, but not of calretinin, mRNAs were also lower in these subjects. Neither illness duration nor age accounted for the levels of the transcripts with altered expression in schizophrenia. In monkey PFC, developmental changes in expression levels of many of these transcripts were in the opposite direction of the changes observed in schizophrenia. For example, mRNA levels for vGAT, GABRA1, GAD67, and parvalbumin all increased with age. Together with published reports, these findings support the interpretation that the altered expression of GABA-related transcripts in schizophrenia reflects a blunting of normal postnatal development changes, but they cannot exclude a decline during the early stages of clinical illness. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: firstname.lastname@example.org.
Copple, Carol, Ed.; Bredekamp, Sue, Ed.
Since the first edition in 1987, National Association for the Education of Young Children's book "Developmentally Appropriate Practice in Early Childhood Programs" has been an essential resource for the early child care field. Now fully revised and expanded, the 2009 version comes with a supplementary CD containing readings on key topics, plus…
Scarborough, Anita A.; Hebbeler, Kathleen M.; Spiker, Donna; Simeonsson, Rune J.
Survival analysis was used to document the developmental achievements of 2298 kindergarten children who participated in the National Early Intervention Longitudinal Study, a study that followed children from entry to Part C early intervention (EI) through kindergarten. Survival functions were produced depicting the percentage of children at…
Zurolo, E; Iyer, A M; Spliet, W G M; Van Rijen, P C; Troost, D; Gorter, J A; Aronica, E
Recent data support the involvement of the endocannabinoid signaling in early brain development, as well as a key role of cannabinoid receptors (CBR) in pathological conditions associated with unbalanced neuronal excitability and inflammation. Using immunocytochemistry, we explored the expression and cellular pattern of CBR 1 and 2 (CB1 and CB2) during prenatal human cortical development, as well as in focal malformations of cortical development associated with intractable epilepsy (focal cortical dysplasia; cortical tubers in patients with the tuberous sclerosis complex and glioneuronal tumors). Strong CB1 immunoreactivity was detected in the cortical plate in developing human brain from the earliest stages tested (gestational week 9) and it persisted throughout prenatal development. Both cannabinoid receptors were not detected in neural progenitor cells located in the ventricular zone. Only CB1 was expressed in the subventricular zone and in Cajal-Retzius cells in the molecular zone of the developing neocortex. CB2 was detected in cells of the microglia/macrophage lineage during development. In malformations of cortical development, prominent CB1 expression was demonstrated in dysplastic neurons. Both CBR were detected in balloon/giant cells, but CB2 appeared to be more frequently expressed than CB1 in these cell types. Reactive astrocytes were mainly stained with CB1, whereas cells of the microglia/macrophage lineage were stained with CB2. These findings confirm the early expression pattern of cannabinoid receptors in the developing human brain, suggesting a function for CB1 in the early stages of corticogenesis. The expression patterns in malformations of cortical development highlight the role of cannabinoid receptors as mediators of the endocannabinoid signaling and as potential pharmacological targets to modulate neuronal and glial cell function in epileptogenic developmental pathologies.
Full Text Available Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL. In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.
Niciu, M J; Ma, X-M; El Meskini, R; Ronnett, G V; Mains, R E; Eipper, B A
ATP7A is a P-type ATPase that transports copper from cytosol into the secretory pathway for loading onto cuproproteins or efflux. Mutations in Atp7a cause Menkes disease, a copper-deficiency disorder fatal in the postnatal period due to severe neurodegeneration. Early postnatal copper injections are known to diminish degenerative changes in some human patients and mice bearing mutations in Atp7a. In situ hybridization studies previously demonstrated that ATP7A transcripts are expressed widely in the brain. ATP7A-specific antibody was used to study the neurodevelopmental expression and localization of ATP7A protein in the mouse brain. Based on immunoblot analyses, ATP7A expression is most abundant in the early postnatal period, reaching peak levels at P4 in neocortex and cerebellum. In the developing and adult brain, ATP7A levels are greatest in the choroid plexus/ependymal cells of the lateral and third ventricles. ATP7A expression decreases in most neuronal subpopulations from birth to adulthood. In contrast, ATP7A expression increases in CA2 hippocampal pyramidal and cerebellar Purkinje neurons. ATP7A is expressed in a subset of astrocytes, microglia, oligodendrocytes, tanycytes and endothelial cells. ATP7A is largely localized to the trans-Golgi network, adopting the cell-specific and developmentally-regulated morphology of this organelle. The presence of ATP7A in the axons of postnatal, but not adult, optic nerve suggests stage-specific roles for this enzyme. In sum, the precisely-regulated neurodevelopmental expression of ATP7A correlates well with the limited therapeutic window for effective treatment of Menkes disease.
Benasich, April A., Ed.; Fitch, R. Holly, Ed.
Understanding the precursors and early indicators of dyslexia is key to early identification and effective intervention. Now there's a single research volume that brings together the very latest knowledge on the earliest stages of dyslexia and the diverse genetic, neurobiological, and cognitive factors that may contribute to it. Based on findings…
Favre, G; Banta Lavenex, P; Lavenex, P
The hippocampal formation is essential for normal memory function and is implicated in many neurodevelopmental, neurodegenerative and neuropsychiatric disorders. In particular, abnormalities in hippocampal structure and function have been identified in schizophrenic subjects. Schizophrenia has a strong polygenic component, but the role of numerous susceptibility genes in normal brain development and function has yet to be investigated. Here we described the expression of schizophrenia susceptibility genes in distinct regions of the monkey hippocampal formation during early postnatal development. We found that, as compared with other genes, schizophrenia susceptibility genes exhibit a differential regulation of expression in the dentate gyrus, CA3 and CA1, over the course of postnatal development. A number of these genes involved in synaptic transmission and dendritic morphology exhibit a developmental decrease of expression in CA3. Abnormal CA3 synaptic organization observed in schizophrenics might be related to some specific symptoms, such as loosening of association. Interestingly, changes in gene expression in CA3 might occur at a time possibly corresponding to the late appearance of the first clinical symptoms. We also found earlier changes in expression of schizophrenia susceptibility genes in CA1, which might be linked to prodromal psychotic symptoms. A number of schizophrenia susceptibility genes including APOE, BDNF, MTHFR and SLC6A4 are involved in other disorders, and thus likely contribute to nonspecific changes in hippocampal structure and function that must be combined with the dysregulation of other genes in order to lead to schizophrenia pathogenesis.
Hogan, Anne E; Quay, Herbert C
There is a pressing need to share advances in developmental science with the large, multidisciplinary professional workforce that serves vulnerable infants and toddlers and their families. Foundational knowledge and conceptual frameworks that integrate material regarding the contents and processes of early development and promotion of their use can assist interventionists and the families they serve. This chapter describes an approach that has been developed over the past 10 years and summarizes key contents with sample practical applications. Topic areas include developmental theories, newborn capacities, a model for synthesizing information about early social competence (including self-regulation, early relationships, social skills, and social cognition), and key current topics in developmental psychopathology. Brief considerations of diversity and stigma for work with young children and families are also included.
Armenti, AnnMarie E; Zama, Aparna Mahakali; Passantino, Lisa; Uzumcu, Mehmet
Methoxychlor (MXC) is an organochlorine pesticide with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether transient developmental exposure to MXC could cause adult ovarian dysfunction, we exposed Fischer rats to 20 microg/kg/day (low dose; environmentally relevant dose) or 100 mg/kg/day (high dose) MXC between 19 days post coitum and postnatal day 7. Multiple reproductive parameters, serum hormone levels, and ovarian morphology and molecular markers were examined from prepubertal through adult stages. High dose MXC accelerated pubertal onset and first estrus, reduced litter size, and increased irregular cyclicity (P<0.05). MXC reduced superovulatory response to exogenous gonadotropins in prepubertal females (P<0.05). Rats exposed to high dose MXC had increasing irregular estrous cyclicity beginning at 4 months of age, with all animals showing abnormal cycles by 6 months. High dose MXC reduced serum progesterone, but increased luteinizing hormone (LH). Follicular composition analysis revealed an increase in the percentage of preantral and early antral follicles and a reduction in the percentage of corpora lutea in high dose MXC-treated ovaries (P<0.05). Immunohistochemical staining and quantification of the staining intensity showed that estrogen receptor beta was reduced by high dose MXC while anti-Mullerian hormone was upregulated by both low- and high dose MXC in preantral and early antral follicles (P<0.05). High dose MXC significantly reduced LH receptor expression in large antral follicles (P<0.01), and down-regulated cytochrome P450 side-chain cleavage. These results demonstrated that developmental MXC exposure results in reduced ovulation and fertility and premature aging, possibly by altering ovarian gene expression and folliculogenesis.
Doczi, Megan A; Vitzthum, Carl M; Forehand, Cynthia J
Specialized hypothalamic neurons integrate the homeostatic balance between food intake and energy expenditure, processes that may become dysregulated during the development of diabetes, obesity, and other metabolic disorders. Shaker family voltage-gated potassium channels (Kv1) contribute to the maintenance of resting membrane potential, action potential characteristics, and neurotransmitter release in many populations of neurons, although hypothalamic Kv1 channel expression has been largely unexplored. Whole-cell patch clamp recordings from avian hypothalamic brain slices demonstrate a developmental shift in the electrophysiological properties of avian arcuate nucleus neurons, identifying an increase in outward ionic current that corresponds with action potential maturation. Additionally, RT-PCR experiments identified the early expression of Kv1.2, Kv1.3, and Kv1.5 mRNA in the embryonic avian hypothalamus, suggesting that these channels may underlie the electrophysiological changes observed in these neurons. Real-time quantitative PCR analysis on intact microdissections of embryonic hypothalamic tissue revealed a concomitant increase in Kv1.2 and Kv1.5 gene expression at key electrophysiological time points during development. This study is the first to demonstrate hypothalamic mRNA expression of Kv1 channels in developing avian embryos and may suggest a role for voltage-gated ion channel regulation in the physiological patterning of embryonic hypothalamic circuits governing energy homeostasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Fish, Richard J; Vorjohann, Silja; Béna, Frédérique; Fort, Alexandre; Neerman-Arbez, Marguerite
The zebrafish is a model organism for studying vertebrate development and many human diseases. Orthologues of the majority of human coagulation factors are present in zebrafish, including fibrinogen. As a first step towards using zebrafish to model human fibrinogen disorders, we cloned the zebrafish fibrinogen cDNAs and made in situ hybridisations and quantitative reverse transcription-polymerase chain reactions (qRT-PCR) to detect zebrafish fibrinogen mRNAs. Prior to liver development or blood flow we detected zebrafish fibrinogen expression in the embryonic yolk syncytial layer and then in the early cells of the developing liver. While human fibrinogen is encoded by a three-gene, 50 kilobase (kb) cluster on chromosome 4 ( FGB-FGA-FGG ), recent genome assemblies showed that the zebrafish fgg gene appears distanced from fga and fgb , which we confirmed by in situ hybridisation. The zebrafish fibrinogen Bβ and γ protein chains are conserved at over 50% of amino acid positions, compared to the human polypeptides. The zebrafish Aα chain is less conserved and its C-terminal region is nearly 200 amino acids shorter than human Aα. We generated transgenic zebrafish which express a green fluorescent protein reporter gene under the control of a 1.6 kb regulatory region from zebrafish fgg . Transgenic embryos showed strong fluorescence in the developing liver, mimicking endogenous fibrinogen expression. This regulatory sequence can now be used for overexpression of transgenes in zebrafish hepatocytes. Our study is a proof-of-concept step towards using zebrafish to model human disease linked to fibrinogen gene mutations.
Lowenthal, Barbara; Lowenthal, Barbara
Describes the unique effects of traumatic brain injury (TBI) on development in early childhood and offers suggestions for interventions in the cognitive, language, social-emotional, motor, and adaptive domains. Urges more intensive, long-term studies on the immediate and long-term effects of TBI. (Author/DB)
Nozadi, Sara S; Spinrad, Tracy L; Eisenberg, Nancy; Bolnick, Rebecca; Eggum-Wilkens, Natalie D; Smith, Cynthia L; Gaertner, Bridget; Kupfer, Anne; Sallquist, Julie
Despite evidence for the importance of individual differences in expressive language during toddlerhood in predicting later literacy skills, few researchers have examined individual and contextual factors related to language abilities across the toddler years. Furthermore, a gap remains in the literature about the extent to which the relations of negative emotions and parenting to language skills may differ for girls and boys. The purpose of this longitudinal study was to investigate the associations among maternal sensitivity, children's observed anger reactivity, and expressive language when children were 18 (T1; n = 247) and 30 (T2; n = 216) months. At each age, mothers reported on their toddlers' expressive language, and mothers' sensitive parenting behavior was observed during an unstructured free-play task. Toddlers' anger expressions were observed during an emotion-eliciting task. Using path modeling, results showed few relations at T1. At T2, maternal sensitivity was negatively related to anger, and in turn, anger was associated with lower language skills. However, moderation analyses showed that these findings were significant for boys but not for girls. In addition, T1 maternal sensitivity and anger positively predicted expressive language longitudinally for both sexes. Findings suggest that the relations between maternal sensitivity, anger reactivity and expressive language may vary depending on the child's developmental stage and sex.
Wakschlag, Lauren S.; Choi, Seung W.; Carter, Alice S.; Hullsiek, Heide; Burns, James; McCarthy, Kimberly; Leibenluft, Ellen; Briggs-Gowan, Margaret J.
Background: Temper modulation problems are both a hallmark of early childhood and a common mental health concern. Thus, characterizing specific behavioral manifestations of temper loss along a dimension from normative misbehaviors to clinically significant problems is an important step toward identifying clinical thresholds. Methods:…
Chapman, Duane C.; George, Amy E.
The early life stages of Asian carp are well described by Yi and others (1988), but since these descriptions are represented by line drawings based only on live individuals and lacked temperature controls, further information on developmental time and stages is of use to expand understanding of early life stages of these species. Bighead carp and silver carp were cultured under two different temperature treatments to the one-chamber gas bladder stage, and a photographic guide is provided for bighead carp and silver carp embryonic and larval development, including notes about egg morphology and larval swimming behavior. Preliminary information on developmental time and hourly thermal units for each stage is also provided. Both carp species developed faster under warmer conditions. Developmental stages and behaviors are generally consistent with earlier works with the exception that strong vertical swimming immediately after hatching was documented in this report.
Sánchez-Ponce, Diana; DeFelipe, Javier; Garrido, Juan José; Muñoz, Alberto
Axonal outgrowth and the formation of the axon initial segment (AIS) are early events in the acquisition of neuronal polarity. The AIS is characterized by a high concentration of voltage-dependent sodium and potassium channels. However, the specific ion channel subunits present and their precise localization in this axonal subdomain vary both during development and among the types of neurons, probably determining their firing characteristics in response to stimulation. Here, we characterize the developmental expression of different subfamilies of voltage-gated potassium channels in the AISs of cultured mouse hippocampal neurons, including subunits Kv1.2, Kv2.2 and Kv7.2. In contrast to the early appearance of voltage-gated sodium channels and the Kv7.2 subunit at the AIS, Kv1.2 and Kv2.2 subunits were tethered at the AIS only after 10 days in vitro. Interestingly, we observed different patterns of Kv1.2 and Kv2.2 subunit expression, with each confined to distinct neuronal populations. The accumulation of Kv1.2 and Kv2.2 subunits at the AIS was dependent on ankyrin G tethering, it was not affected by disruption of the actin cytoskeleton and it was resistant to detergent extraction, as described previously for other AIS proteins. This distribution of potassium channels in the AIS further emphasizes the heterogeneity of this structure in different neuronal populations, as proposed previously, and suggests corresponding differences in action potential regulation. PMID:23119056
Chudotvorova, Ilona; Ivanov, Anton; Rama, Sylvain; Hübner, Christian A; Pellegrino, Christophe; Ben-Ari, Yehezkel; Medina, Igor
The development of GABAergic synapses is associated with an excitatory to inhibitory shift of the actions of GABA because of a reduction of [Cl-]i. This is due to a delayed postnatal expression of the K+ -Cl- cotransporter KCC2, which has low levels at birth and peaks during the first few postnatal weeks. Whether the expression of the cotransporter and the excitatory to inhibitory shift have other consequences on the operation of GABA(A) receptors and synapses is not yet known. We have now expressed KCC2 in immature neurones at an early developmental stage and determined the consequences on the formation of GABA and glutamate synapses. We report that early expression of the cotransporter selectively enhances GABAergic synapses: there is a significant increase of the density of GABA(A) receptors and synapses and an increase of the frequency of GABAergic miniature postsynaptic currents. The density of glutamate synapses and frequency of AMPA miniature postsynaptic currents are not affected. We conclude that the expression of KCC2 and the reduction of [Cl-]i play a critical role in the construction of GABAergic networks that extends beyond the excitatory to inhibitory shift of the actions of GABA.
In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hy...
Developmentally Appropriate Technology in Early Childhood (DATEC) aims to identify themost appropriate applications of Information and Communication Technology to support thedevelopment of children under eight years of age. Botswana has a unique spread ofpopulation density and deep-rooted socio-cultural values. There is a need to address thecompatibility of these aspects with the application of Information and CommunicationTechnology in the proposed Early Childhood Education programmes throug...
Green, Vanessa A.; O'Reilly, Mark; Itchon, Jonathan; Sigafoos, Jeff
This study examined the persistence of early emerging aberrant behavior in 13 preschool children with developmental disabilities. The severity of aberrant behavior was assessed every 6 months over a 3-year period. Teachers completed the assessments using the Aberrant Behavior Checklist [Aman, M. G., & Singh, N. N. (1986). "Aberrant Behavior…
May, Deborah C.; Welch, Edward L.
Examined the relationship between early school retention as a result of preschool and kindergarten developmental testing and children's later academic achievement (N=223). Results showed children who scored as immature on the Gesell Screening Test and who were retained a year had the lowest scores on all measures. (JAC)
Blake, Sally; Winsor, Denise; Burkett, Candice; Allen, Lee
The integration of technology in early childhood classrooms has become a controversial issue among professionals in this field. One issue which may influence technology in these classrooms may be perceptions of what is developmentally appropriate practice (DAP). This article explores perceptions about technology and age appropriate recommendations…
Daugherty, Lindsay; Dossani, Rafiq; Johnson, Erin-Elizabeth; Wright, Cameron
Conversations about what constitutes "developmentally appropriate" use of technology in early childhood education have, to date, focused largely on a single, blunt measure--screen time--that fails to capture important nuances, such as what type of media a child is accessing and whether technology use is taking place solo or with peers.…
Oldehinkel, A.J.; Ormel, J.; Veenstra, R.; De Winter, A.F.; Verhulst, F.C.
In this study, we investigated if the association between parental divorce and depressive symptoms changes during early adolescence and if developmental patterns are similar for boys and girls. Data were collected in a prospective population cohort of Dutch adolescents (N = 2,149), aged 10 - 15 year
Oldehinkel, Albertine J.; Ormel, Johan; Veenstra, Rene; De Winter, Andrea F.; Verhulst, Frank C.
In this study, we investigated if the association between parental divorce and depressive symptoms changes during early adolescence and if developmental patterns are similar for boys and girls. Data were collected in a prospective population cohort of Dutch adolescents (N = 2,149), aged 10 - 15 years. Outcome variables were self-reported and…
Coughlan-Mainard, Kelly A.
School districts in the U.S. are mandated to identify young children with disabilities. Developmental screeners are typically used to screen for such skill deficits. Academic tests are used in older students. A significant challenge is identifying children with potential learning disabilities early in their school career. This study identifies a…
Scarborough, Anita A.; Hebbeler, Kathleen M.; Simeonsson, Rune J.; Spiker, Donna
The present study was conducted to describe the developmental skills of a national sample of infants and toddlers at entry into early intervention services. Caregivers were asked about their child's skills during a telephone interview. Summary values were derived from descriptions of motor, communication, independence, and cognitive skills. More…
Jacob, Udeme Samuel; Olisaemeka, Angela Nneka; Edozie, Isioma Sitamalife
The paper attempts to discuss the place of intervention in the developmental and communication disorders of children with intellectual disability for the purpose of providing effective inclusion programme. The definition of early intervention was stated, areas affected by children communication disorder such as language comprehension, fluency,…
Hoehner, J C; Hedborg, F; Eriksson, L; Sandstedt, B; Grimelius, L; Olsen, L; Påhlman, S
Comparisons of the developing human sympathetic nervous system (SNS) to tumors presumed to derive from these cells may suggest tumor progenitors and predict tumor biologic behavior. Classic neuroblastoma (NB) and its more highly differentiated stroma-rich subtypes, extra-adrenal sympathetic paraganglioma, and pheochromocytoma were examined for the presence of the developmentally characterized gene products NSE, S-100, CD44, Bcl-2, HNK-1, PNMT, TrkA, IGF2, and tyrosine hydroxylase. The marker gene expression profiles of these tumors were compared with those similarly determined for a number of normal prenatal and postnatal human SNS cell types. Sympathetic paraganglioma, pheochromocytoma, and stroma-rich NB display marker expression profiles mimicking those of childhood sympathetic paraganglia, adrenal chromaffin cells, and sympathetic neurons, respectively. A selection of differentiating, extra-adrenal NB tumors with prognostically favorable features possess marker gene expression profiles paralleling that observed for fetal extra-adrenal sympathetic paraganglia/small intensely fluorescent cells. In contrast, undifferentiated, clinically aggressive NB tumors manifest characteristics mirroring that of embryonic/early fetal sympathetic neuroblasts of sympathetic ganglia and of the adrenal gland. These findings suggest that clinical features, such as primary tumor location and age at diagnosis, provide prognostic information for NB patients by virtue of the existence and biology of the presumed tumor progenitor cell type.
Ceballos-Picot, Irene; Mockel, Lionel; Potier, Marie-Claude; Dauphinot, Luce; Shirley, Thomas L; Torero-Ibad, Raoul; Fuchs, Julia; Jinnah, H A
Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency results in Lesch-Nyhan disease (LND), where affected individuals exhibit a characteristic neurobehavioral disorder that has been linked with dysfunction of dopaminergic pathways of the basal ganglia. Since the functions of HPRT, a housekeeping enzyme responsible for recycling purines, have no direct relationships with the dopaminergic pathways, the mechanisms whereby HPRT deficiency affect them remain unknown. The current studies demonstrate that HPRT deficiency influences early developmental processes controlling the dopaminergic phenotype, using several different cell models for HPRT deficiency. Microarray methods and quantitative PCR were applied to 10 different HPRT-deficient (HPRT(-)) sublines derived from the MN9D cell line. Despite the variation inherent in such mutant sublines, several consistent abnormalities were evident. Most notable were increases in the mRNAs for engrailed 1 and 2, transcription factors known to play a key role in the specification and survival of dopamine neurons. The increases in mRNAs were accompanied by increases in engrailed proteins, and restoration of HPRT reverted engrailed expression towards normal levels, demonstrating a functional relationship between HPRT and engrailed. The functional relevance of the abnormal developmental molecular signature of the HPRT(-) MN9D cells was evident in impoverished neurite outgrowth when the cells were forced to differentiate chemically. To verify that these abnormalities were not idiosyncratic to the MN9D line, HPRT(-) sublines from the SK-N-BE(2) M17 human neuroblastoma line were evaluated and an increased expression of engrailed mRNAs was also seen. Over-expression of engrailed occurred even in primary fibroblasts from patients with LND in a manner that suggested a correlation with disease severity. These results provide novel evidence that HPRT deficiency may affect dopaminergic neurons by influencing early developmental
Tain, You-Lin; Hsu, Chien-Ning
Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called “developmental programming” or “developmental origins of health and disease” (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease. PMID:28208659
Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco
Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.
Full Text Available Abstract Background To examine whether whole genome expression profiling could reveal changes in mRNA expression of peripheral blood mononuclear cells (PBMC from allergic patients undergoing rush immunotherapy (RIT that might be manifest within the first few months of treatment. Methods For this study, PBMC from three allergic patients undergoing RIT were assessed at four timepoints: prior to RIT, at 1 week and 7 week post-RIT, during build-up and at 4 months, after establishment of a maintenance dose. PBMC mRNA gene expression changes over time were determined by oligonucleotide microarrays using the Illumina Human-6 BeadChip Platform, which simultaneously interrogates expression profiles of > 47,000 transcripts. Differentially expressed genes were identified using well-established statistical analysis for microarrays. In addition, we analyzed peripheral blood basophil high-affinity IgE receptor (Fc epsilon RI expression and T-regulatory cell frequency as detected by expression of CD3+CD4+CD25bright cells at each timepoint using flow cytometry. Results In comparing the initial 2 timepoints with the final 2 timepoints and analyzing for genes with ≥1.5-fold expression change (p less than or equal to 0.05, BH-FDR, we identified 507 transcripts. At a 2-fold change (p less than or equal to 0.05, BH-FDR, we found 44 transcripts. Of these, 28 were up-regulated and 16 were down-regulated genes. From these datasets, we have identified changes in immunologically relevant genes from both the innate and adaptive response with upregulation of expressed genes for molecules including IL-1β, IL-8, CD40L, BTK and BCL6. At the 4 month timepoint, we noted a downward trend in Fc epsilon RI expression in each of the three patients and increased allergen-specific IgG4 levels. No change was seen in the frequency of peripheral T-regulatory cells expressed over the four timepoints. Conclusions We observed significant changes in gene expression early in peripheral
Steber, C M; Esposito, R E
The UME6 gene of Saccharomyces cerevisiae was identified as a mitotic repressor of early meiosis-specific gene expression. It encodes a Zn2Cys6 DNA-binding protein which binds to URS1, a promoter element needed for both mitotic repression and meiotic induction of early meiotic genes. This paper demonstrates that a complete deletion of UME6 causes not only vegetative derepression of early meiotic genes during vegetative growth but also a significant reduction in induction of meiosis-specific genes, accompanied by a severe defect in meiotic progression. After initiating premeiotic DNA synthesis the vast majority of cells (approximately 85%) become arrested in prophase and fail to execute recombination; a minority of cells (approximately 15%) complete recombination and meiosis I, and half of these form asci. Quantitative analysis of the same early meiotic transcripts that are vegetatively derepressed in the ume6 mutant, SPO11, SPO13, IME2, and SPO1, indicates a low level of induction in meiosis above their vegetative derepressed levels. In addition, the expression of later meiotic transcripts, SPS2 and DIT1, is significantly delayed and reduced. The expression pattern of early meiotic genes in ume6-deleted cells is strikingly similar to that of early meiotic genes with promoter mutations in URS1. These results support the view that UME6 and URS1 are part of a developmental switch that controls both vegetative repression and meiotic induction of meiosis-specific genes. Images Fig. 3 Fig. 4 Fig. 5 PMID:8618927
Chettri, Jiwan Kumar; Raida, Martin Kristian; Kania, Per Walter;
Innate immune factors play a crucial role in survival of young fish especially during early stages of life when adaptive immunity is not fully developed. In the present study, we investigated the immune response of rainbow trout (Oncorhynchus mykiss) larvae and fry at an early stage of development...... trout fry with Y. ruckeri, in contrast, induced a cumulative mortality of 74%. A high expression of cytokines (IL-1b, TNF-a, IL-22, IL-8 and IL- 10), acute phase proteins (SAA, hepcidin, transferrin and precerebellin), complement factors (C3, C5 and factor B), antimicrobial peptide (cathelicidin-2...... at early developmental stages. A dense covering of surfaces of gill filaments by IgT antibody in the young fish suggest a role of this antibody as innate immune factor at early developmental stages....
Itoh, Jun-Ichi; Sato, Yutaka; Sato, Yutaka; Hibara, Ken-Ichiro; Shimizu-Sato, Sae; Kobayashi, Hiromi; Takehisa, Hinako; Sanguinet, Karen A; Namiki, Nobukazu; Nagamura, Yoshiaki
Embryogenesis in rice is different from that of most dicotolydonous plants in that it shows a non-stereotypic cell division pattern, formation of dorsal-ventral polarity, and endogenous initiation of the radicle. To reveal the transcriptional features associated with developmental events during rice early embryogenesis, we used microarray analysis coupled with laser microdissection to obtain both spatial and temporal transcription profiles. Our results allowed us to determine spatial expression foci for each expressed gene in the globular embryo, which revealed the importance of phytohormone-related genes and a suite of transcription factors to early embryogenesis. Our analysis showed the polarized expression of a small number of genes along the apical-basal and dorsal-ventral axes in the globular embryo, which tended to fluctuate in later developmental stages. We also analyzed gene expression patterns in the early globular embryo and how this relates to expression in embryonic organs at later stages. We confirmed the accuracy of the expression patterns found by microarray analysis of embryo subdomains using in situ hybridization. Our study identified homologous genes from Arabidopsis thaliana with known functions in embryogenesis in addition to unique and uncharacterized genes that show polarized expression patterns during embryogenesis. The results of this study are presented in a database to provide a framework for spatiotemporal gene expression during rice embryogenesis, to serve as a resource for future functional analysis of genes, and as a basis for comparative studies of plant embryogenesis.
Leininger, Sven; Adamski, Marcin; Bergum, Brith; Guder, Corina; Liu, Jing; Laplante, Mary; Bråte, Jon; Hoffmann, Friederike; Fortunato, Sofia; Jordal, Signe; Rapp, Hans Tore; Adamska, Maja
Elucidation of macroevolutionary transitions between diverse animal body plans remains a major challenge in evolutionary biology. We address the sponge-eumetazoan transition by analyzing expression of a broad range of eumetazoan developmental regulatory genes in Sycon ciliatum (Calcispongiae). Here we show that many members of surprisingly numerous Wnt and Tgfβ gene families are expressed higher or uniquely in the adult apical end and the larval posterior end. Genes involved in formation of the eumetazoan endomesoderm, such as β-catenin, Brachyury and Gata, as well as germline markers Vasa and Pl10, are expressed during formation and maintenance of choanoderm, the feeding epithelium of sponges. Similarity in developmental gene expression between sponges and eumetazoans, especially cnidarians, is consistent with Haeckel's view that body plans of sponges and cnidarians are homologous. These results provide a framework for further studies aimed at deciphering ancestral developmental regulatory networks and their modifications during animal body plans evolution.
BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.
The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950
Uono, Shota; Sato, Wataru; Toichi, Motomi
Individuals with pervasive developmental disorder (PDD) have difficulty with social communication via emotional facial expressions, but behavioral studies involving static images have reported inconsistent findings about emotion recognition. We investigated whether dynamic presentation of facial expression would enhance subjective perception of…
Weems, Carl F.; Costa, Natalie M.
Objective: To examine age differences in the expression of childhood fears and anxiety symptoms. Method: A cross-sectional design was used to test recently formulated developmental hypotheses regarding the differential expression of childhood anxiety symptoms and fears in a community sample of youths (N = 145). Three groups of youths were…
Full Text Available Early development in humans is characterised by low and variable embryonic viability, reflected in low fecundity and high rates of miscarriage, relative to other mammals. Data from assisted reproduction programmes provides additional evidence that this is largely mediated at the level of embryonic competence and is highly heterogeneous among embryos. Understanding the basis of this heterogeneity has important implications in a number of areas including: the regulation of early human development, disorders of pregnancy, assisted reproduction programmes, the long term health of children which may be programmed in early development, and the molecular basis of pluripotency in human stem cell populations. We have therefore investigated global gene expression profiles using polyAPCR amplification and microarray technology applied to individual human oocytes and 4-cell and blastocyst stage embryos. In order to explore the basis of any variability in detail, each developmental stage is replicated in triplicate. Our data show that although transcript profiles are highly stage-specific, within each stage they are relatively variable. We describe expression of a number of gene families and pathways including apoptosis, cell cycle and amino acid metabolism, which are variably expressed and may be reflective of embryonic developmental competence. Overall, our data suggest that heterogeneity in human embryo developmental competence is reflected in global transcript profiles, and that the vast majority of existing human embryo gene expression data based on pooled oocytes and embryos need to be reinterpreted.
Esham, Michael; Bryan, Kourtney; Milnes, Jennifer; Holmes, William B; Moncman, Carole L
Nebulette, a cardiac homologue of nebulin, colocalizes with alpha-actinin in the pre-myofibrils of spreading cardiomyocytes and has been hypothesized to play a critical role in the formation of the thin-filament-Z-line complex early during myofibrillogenesis. Data from mesodermal explants or whole tissue mounts of developing hearts suggest that the pattern of myofibrillogenesis in situ may differ from observations of spreading cardiomyocytes. To evaluate the role of nebulette in myofibrillogenesis, we have analyzed the expression of nebulette in chicken heart rudiments by immunoblots and immunofluorescence. We detect the 110 kDa nebulette in heart rudiments derived from stage 9-10 using the anti-nebulin mAb, N114, or polyclonal anti-nebulette Abs by immunoblotting. Immunofluorescence analysis of explants stained with anti-nebulette and anti-alpha-actinin Abs demonstrates that both proteins localize along actin filaments in punctate to continuous manner at early stages of cardiac development and later give rise to striations. In both cases, the punctate staining had a periodicity of approximately 1.0 microm indicating a pre-myofibrils distribution at the earliest time points examined. We demonstrate that nebulette is indeed associated with premyofibrils in very early stages of myofibrillogenesis and suggest that nebulette may play an important role in the formation of these structures.
Cuesta, Ines H; Lahiri, Kajori; Lopez-Olmeda, Jose Fernando; Loosli, Felix; Foulkes, Nicholas S; Vallone, Daniela
One key challenge for the field of chronobiology is to identify how circadian clock function emerges during early embryonic development. Teleosts such as the zebrafish are ideal models for studying circadian clock ontogeny since the entire process of development occurs ex utero in an optically transparent chorion. Medaka (Oryzias latipes) represents another powerful fish model for exploring early clock function with, like the zebrafish, many tools available for detailed genetic analysis. However, to date there have been no reports documenting circadian clock gene expression during medaka development. Here we have characterized the expression of key clock genes in various developmental stages and in adult tissues of medaka. As previously reported for other fish, light dark cycles are required for the emergence of clock gene expression rhythms in this species. While rhythmic expression of per and cry genes is detected very early during development and seems to be light driven, rhythmic clock and bmal expression appears much later around hatching time. Furthermore, the maturation of clock function seems to correlate with the appearance of rhythmic expression of these positive elements of the clock feedback loop. By accelerating development through elevated temperatures or by artificially removing the chorion, we show an earlier onset of rhythmicity in clock and bmal expression. Thus, differential maturation of key elements of the medaka clock mechanism depends on the developmental stage and the presence of the chorion.
Yuge, M; Yamori, Y; Kanda, T; Ando, R
We followed 93 infants prospectively who were treated because of moderate and severe grades of cerebral coordination disturbances since less than 6 months of age. They were divided into 3 groups according to developmental prognosis at 4 years of age; normal 44, mental retardation 18, and cerebral palsy 31. We compared the postural findings in supine and prone position, and 7 postural reactions at the first examination with those at discharge about 50 days after the first examination. We assessed the changing pictures of postural findings as improved, not changed or worsened. We analyzed the relationship between the changing pictures of postural findings during the short period in early infancy and the developmental prognosis among the 3 groups. The normal group showed improvement in a larger number of items than the other two groups. The findings of cerebral palsied children showed poor improvement, and more postural reactions changed to be more pathologic than those in the other two groups. Among the cerebral palsied children, ambulatory cases showed better improvement than those who could not crawl. But we found no significant difference between ambulatory and crawling children. This study demonstrated that assessment of changing pictures of postural findings in early infancy was helpful to predict developmental prognosis.
Xiaomei Cong; Wanli Xu; Susan Janton; Henderson, Wendy A.; Adam Matson; McGrath, Jacqueline M.; Kendra Maas; Joerg Graf
Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of li...
Sorenson, J.C.; Scandalios, J.G.
The expression of an endogenous catalase inhibitor has been studied during development of Zea mays. In the 3-day seedling, the inhibitor is expressed primarily in the scutellum and in the aleurone layer of the endosperm. These tissues also show the highest catalase activity at this stage. Inhibitor expression has also been studied temporally in the scutellum, roots, and shoot over the first 12 days of germination. Inhibitor expression shows an inverse relationship with catalase activity in the scutellum and in the shoot. The relationship is less rigid in the root, due probably to the low levels of inhibitor found in that tissue. The role of the inhibitor in catalase regulation is discussed.
Full Text Available Developmentally Appropriate Technology in Early Childhood (DATEC aims to identify themost appropriate applications of Information and Communication Technology to support thedevelopment of children under eight years of age. Botswana has a unique spread ofpopulation density and deep-rooted socio-cultural values. There is a need to address thecompatibility of these aspects with the application of Information and CommunicationTechnology in the proposed Early Childhood Education programmes throughout Botswana.The researcher felt that the views of the in-service teachers, (who are now students of theBachelor of Education Programme in the University of Botswana and have specialized inEarly Childhood Education, would be a valuable input towards an appropriate EarlyChildhood Education curriculum. Hence, a study was proposed to assess the views of theteachers, regarding DATEC in Botswana. Forty (40 fourth year students (Level 400 ofBachelor of Education (Primary Programme of University of Botswana, who specialised inearly years and have a good exposure to Information and Communication Technologyconstituted the sample. Their views were obtained from a semi-structured questionnaire.Both quantitative and qualitative approaches were used for analysis of data. The findings ofthe study showed that the respondents strongly believed that an integration of Informationand Communication Technology with the Early Childhood Education curriculum isnecessary to enhance an overall development of young children. Computers with relevantresources were thought to be the best Information and Communication Technologyapplications in Early Childhood Education for a developmentally appropriate programmethat would provide educational concepts, problem solving skills and creativity. However,they emphasised the need to make the technology socio-culturally compatible to citizens ofBotswana (Batswana to facilitate developmentally appropriate education of young children.The study
Christine E. Moran
Full Text Available American students typically attend kindergarten at the chronological age (CA of five and currently with the implementation of Common Core State Standards, there are expectations that children learn how to read in order to meet these academic standards, despite whether or not they are developmentally ready. This mixed methods study examined age and environmental factors that relate to reading with 83 children from the ages of 4–6½ years. The relationship between developmental age (DA via the Gesell Developmental Observation-Revised and early literacy learning via Marie’s Clay observational tool, Concepts About Print (CAP, were explored. The purpose of the study was to highlight the need for better alignment of educational policies and practices as they relate to child development and to promote more effective synthesis between discoveries in the field of neuroscience about how children learn and what is known about child DAs and stages. The findings revealed a statistically significant relationship between a child’s DA and early literacy learning as measured by the CAP. The descriptive statistics revealed that the DA of the children in this study was younger than their CA. Furthermore, a child’s DA was found to be the strongest predictor of early literacy learning.
Kaitetzidou, E; Xiang, J; Antonopoulou, E; Tsigenopoulos, C S; Sarropoulou, E
Larval and embryonic stages are the most critical period in the life cycle of marine fish. Key developmental events occur early in development and are influenced by external parameters like stress, temperature, salinity, and photoperiodism. Any failure may cause malformations, developmental delays, poor growth, and massive mortalities. Advanced understanding of molecular processes underlying marine larval development may lead to superior larval rearing conditions. Today, the new sequencing and bioinformatic methods allow transcriptome screens comprising messenger (mRNA) and microRNA (miRNA) with the scope of detecting differential expression for any species of interest. In the present study, we applied Illumina technology to investigate the transcriptome of early developmental stages of the European seabass (Dicentrarchus labrax). The European seabass, in its natural environment, is a euryhaline species and has shown high adaptation processes in early life phases. During its embryonic and larval phases the European seabass lives in a marine environment and as a juvenile it migrates to coastal zones, estuaries, and lagoons. Investigating the dynamics of gene expression in its early development may shed light on factors promoting phenotypic plasticity and may also contribute to the improvement and advancement of rearing methods of the European seabass, a species of high economic importance in European and Mediterranean aquaculture. We present the identification, characterization, and expression of mRNA and miRNA, comprising paralogous genes and differentially spliced transcripts from early developmental stages of the European seabass. We further investigated the detection of possible interactions of miRNA with mRNA.
Hefter, Rebecca L; Manoach, Dara S; Barton, Jason J S
It has been hypothesized that the social dysfunction in social developmental disorders (SDDs), such as autism, Asperger disorder, and the socioemotional processing disorder, impairs the acquisition of normal face-processing skills. The authors investigated whether this purported perceptual deficit was generalized to both facial expression and facial identity or whether these different types of facial perception were dissociated in SDDs. They studied 26 adults with a variety of SDD diagnoses, assessing their ability to discriminate famous from anonymous faces, their perception of emotional expression from facial and nonfacial cues, and the relationship between these abilities. They also compared the performance of two defined subgroups of subjects with SDDs on expression analysis: one with normal and one with impaired recognition of facial identity. While perception of facial expression was related to the perception of nonfacial expression, the perception of facial identity was not related to either facial or nonfacial expression. Likewise, subjects with SDDs with impaired facial identity processing perceived facial expression as well as those with normal facial identity processing. The processing of facial identity and that of facial expression are dissociable in social developmental disorders. Deficits in perceiving facial expression may be related to emotional processing more than face processing. Dissociations between the perception of facial identity and facial emotion are consistent with current cognitive models of face processing. The results argue against hypotheses that the social dysfunction in social developmental disorder causes a generalized failure to acquire face-processing skills.
Sadlovsky, Kelly R.
This study uses a basic qualitative research design to uncover and understand how early childhood teachers apply developmentally appropriate practices and what successes and barriers they encounter. The new knowledge produced might help professional development practitioners by increasing their understanding of how developmentally appropriate…
Full Text Available Abstract Background The mitochondria are involved in many basic functions in cells of vertebrates, and can be considered the power generator of the cell. Though the mitochondria have been extensively studied there appear to be only few expression studies of mitochondrial genes involving a large number of tissues and developmental stages. Here, we conduct an analysis using the PigEST resource 1 which contains expression information from 35 tissues distributed on one normalized and 97 non-normalized cDNA libraries of which 24 are from developmental stages. The mitochondrial PigEST resource contains 41,499 mitochondrial sequences. Results The mitochondrial EST (Expressed Sequence Tag sequences were assembled into contigs which covers more than 94 percent of the porcine mitochondrial genome, with an average of 976 EST sequences per nucleotide. This data was converted into expression values for the individual genes in each cDNA library revealing differential expression between genes expressed in cDNA libraries from developmental and adult stages. For the 13 protein coding genes (and several RNA genes, we find one set of six genes, containing all cytochrome oxidases, that are upregulated in developmental tissues, whereas the remaining set of seven genes, containing all ATPases, that are upregulated in adult muscle and brain tissues. Further, the COX I (Cytochrome oxidase subunit one expression profile differs from that of the remaining genes, which could be explained by a tissue specific cleavage event or degradation pattern, and is especially pronounced in developmental tissues. Finally, as expected cDNA libraries from muscle tissues contain by far the largest amount (up to 20% of expressed mitochondrial genes. Conclusion Our results present novel insight into differences in mitochondrial gene expression, emphasizing differences between adult and developmental tissues. Our work indicates that there are presently unknown mechanisms which work to
Full Text Available The establishment of more efficient approaches for developmental neurotoxicity testing (DNT has been an emerging issue for children’s environmental health. Here we describe a systematic approach for DNT using the neuronal differentiation of mouse embryonic stem cells (mESCs as a model of fetal programming. During embryoid body (EB formation, mESCs were exposed to 12 chemicals for 24 h and then global gene expression profiling was performed using whole genome microarray analysis. Gene expression signatures for seven kinds of gene sets related to neuronal development and neuronal diseases were selected for further analysis. At the later stages of neuronal cell differentiation from EBs, neuronal phenotypic parameters were determined using a high-content image analyzer. Bayesian network analysis was then performed based on global gene expression and neuronal phenotypic data to generate comprehensive networks with a linkage between early events and later effects. Furthermore, the probability distribution values for the strength of the linkage between parameters in each network was calculated and then used in principal component analysis. The characterization of chemicals according to their neurotoxic potential reveals that the multi-parametric analysis based on phenotype and gene expression profiling during neuronal differentiation of mESCs can provide a useful tool to monitor fetal programming and to predict developmentally neurotoxic compounds.
Nagano, Reiko; Akanuma, Hiromi; Qin, Xian-Yang; Imanishi, Satoshi; Toyoshiba, Hiroyoshi; Yoshinaga, Jun; Ohsako, Seiichiroh; Sone, Hideko
The establishment of more efficient approaches for developmental neurotoxicity testing (DNT) has been an emerging issue for children's environmental health. Here we describe a systematic approach for DNT using the neuronal differentiation of mouse embryonic stem cells (mESCs) as a model of fetal programming. During embryoid body (EB) formation, mESCs were exposed to 12 chemicals for 24 h and then global gene expression profiling was performed using whole genome microarray analysis. Gene expression signatures for seven kinds of gene sets related to neuronal development and neuronal diseases were selected for further analysis. At the later stages of neuronal cell differentiation from EBs, neuronal phenotypic parameters were determined using a high-content image analyzer. Bayesian network analysis was then performed based on global gene expression and neuronal phenotypic data to generate comprehensive networks with a linkage between early events and later effects. Furthermore, the probability distribution values for the strength of the linkage between parameters in each network was calculated and then used in principal component analysis. The characterization of chemicals according to their neurotoxic potential reveals that the multi-parametric analysis based on phenotype and gene expression profiling during neuronal differentiation of mESCs can provide a useful tool to monitor fetal programming and to predict developmentally neurotoxic compounds.
Reitzel, Adam M; Pang, Kevin; Martindale, Mark Q
An essential developmental pathway in sexually reproducing animals is the specification of germ cells and the differentiation of mature gametes, sperm and oocytes. The "germline" genes vasa, nanos and piwi are commonly identified in primordial germ cells, suggesting a molecular signature for the germline throughout animals. However, these genes are also expressed in a diverse set of somatic stem cells throughout the animal kingdom leaving open significant questions for whether they are required for germline specification. Similarly, members of the Dmrt gene family are essential components regulating sex determination and differentiation in bilaterian animals, but the functions of these transcription factors, including potential roles in sex determination, in early diverging animals remain unknown. The phylogenetic position of ctenophores and the genome sequence of the lobate Mnemiopsis leidyi motivated us to determine the compliment of these gene families in this species and determine expression patterns during development. Our phylogenetic analyses of the vasa, piwi and nanos gene families show that Mnemiopsis has multiple genes in each family with multiple lineage-specific paralogs. Expression domains of Mnemiopsis nanos, vasa and piwi, during embryogenesis from fertilization to the cydippid stage, were diverse, with little overlapping expression and no or little expression in what we think are the germ cells or gametogenic regions. piwi paralogs in Mnemiopsis had distinct expression domains in the ectoderm during development. We observed overlapping expression domains in the apical organ and tentacle apparatus of the cydippid for a subset of "germline genes," which are areas of high cell proliferation, suggesting that these genes are involved with "stem cell" specification and maintenance. Similarly, the five Dmrt genes show diverse non-overlapping expression domains, with no clear evidence for expression in future gametogenic regions of the adult. We also
Hirasawa, Ryutaro; Sasaki, Hiroyuki
The de novo DNA methyltransferases, Dnmt3a and Dnmt3b, are responsible for the creation of DNA methylation patterns in mouse development. Dnmt3b is more highly expressed in early developmental stages than Dnmt3a, and is thought to have an important role in the epigenetic gene regulation during early embryogenesis. Previous reports suggest that Dnmt3b is expressed preferentially in the embryonic lineage, but less in the extra-embryonic lineage, in early post-implantation embryos. However, it is unclear when this lineage-specific differential expression is established. Here we demonstrate that Dnmt3b shows a dynamic expression change during pre- and early post-implantation development. Contrary to the expectation, Dnmt3b is preferentially expressed in the trophectoderm rather than the inner cell mass at the mid blastocyst stage. Subsequently, the spatial Dnmt3b expression gradually changes during pre- and early post-implantation development, and finally Dnmt3b expression is settled in the embryonic lineage at the epiblast stage. The findings are consistent with the role for Dnmt3b in cell-lineage specification and the creation of lineage-specific DNA methylation patterns.
Full Text Available In the composition of one well imagined axis, the approach towards the children with developmental difficulties, integrated rehabilitational system, the most important place takes the basic element, the early and adequate detection and evidence of these children, as essential condition for successful realization of the remained segments in the whole system i. e., building of the whole strategy of the children with developmental difficulties.The main goals of this presentation are:· the objective condition in the early detection, evidence and registration of children with developmental difficulties in the Republic, focusing on the present deficiency and partial solutions in this moment.· our professional and personnel possibilities as base for improvement of this segment;· the objective needs and organizational perspectives for a global system of detection of children with developmental difficulties;· the central evidence of these children, excluding the elements of improvisation and partial working.Absence of one unique methodology of detection, registration and central evidence of these children although there is a legislative regulation for their registration (in the centers for social affairs it puts us in a position only to predict the expected number of children with developmental difficulties ( according to WHO, about 5-7 % in pre-school population .The results of the commissions for categorization, as well as the number of persons with developmental difficulties, can’t be equal with the real position of early detected and evidenced, at this moment.Stressing the importance of the early detection and evidence, as a segment in the preventive health care, from one point of view, and pointing out the insufficient engagement of the health workers (doctors, from another point of view, automatically gives the conclusion, that this problem must be solved at health level, giving directions and education of the teaching staff, on the level of
O. Hanscombe (Olivia); D. Whyatt (David); P.J. Fraser (Peter); N. Yannoutsos (Nikos); D.R. Greaves (David); N.O. Dillon (Niall); F.G. Grosveld (Frank)
textabstractWe have used transgenic mice to study the influence of position of the human globin genes relative to the locus control region (LCR) on their expression pattern during development. The LCR, which is located 5' of the globin gene cluster, is normally required for the activation of all the
de Boer, B.A.; Ruijter, J.M.; Voorbraak, F.P.J.M.; Moorman, A.F.M.
To unravel regulatory networks of genes functioning during embryonic development, information on in situ gene expression is required. Enormous amounts of such data are available in literature, where each paper reports on a limited number of genes and developmental stages. The best way to make these
Simon, Thomas P
Evaluation of trait robustness based on environmental fluctuation in ontogenetic life stages are needed to evaluate stability and trait response during critical developmental events. Hardness, alkalinity, acidity, light intensity, and thermal differences were studied for trait canalization variation in morphometric, meristic, ontogenetic processes, and pigment characteristics. Trait canalization was observed with no statistical differences (p > 0.05) in mixed random two-way ANOVA comparisons between various block and treatment effects for hardness, alkalinity or acidity. Thermal block variation differences in six measures, including mandible length, yolk sac length, midpostanal depth, and head width, incubation, and hatching length, varied significantly (p ≤ 0.05) with declining temperatures. Water quality and thermal attributes exhibited trait canalization and did not increase character state variation in the early life stage morphological expression, which result in stable phenotypic inheritance rather than variable environmental conditions during embryonic and larval development.
Pears, Katherine C; Kim, Hyoun K; Fisher, Philip A; Yoerger, Karen
Two hundred and nine children receiving early childhood special education services for developmental disabilities or delays who also had behavioral, social, or attentional difficulties were included in a study of an intervention to increase school readiness, including early literacy skills. Results showed that the intervention had a significant positive effect on children's literacy skills from baseline to the end of summer before the start of kindergarten (d=.14). The intervention also had significant indirect effects on teacher ratings of children's literacy skills during the fall of their kindergarten year (β=.09). Additionally, when scores were compared to standard benchmarks, a greater percentage of the children who received the intervention moved from being at risk for reading difficulties to having low risk. Overall, this study demonstrates that a school readiness intervention delivered prior to the start of kindergarten may help increase children's early literacy skills.
Guyer, Amanda E.; Monk, Christopher S.; McClure-Tone, Erin B.; Nelson, Eric E.; Roberson-Nay, Roxann; Adler, Abby D.; Fromm, Stephen J.; Leibenluft, Ellen; Daniel S Pine; Ernst, Monique
Several lines of evidence implicate the amygdala in face– emotion processing, particularly for fearful facial expressions. Related findings suggest that face–emotion processing engages the amygdala within an interconnected circuitry that can be studied using a functional-connectivity approach. Past work also underscores important functional changes in the amygdala during development. Taken together, prior research on amygdala function and development reveals a need for more work examining dev...
Dennery, Phyllis A; Lee, Christen S; Ford, Berendera S; Weng, Yi-Hao; Yang, Guang; Rodgers, Pamela A
Heme oxygenase (HO), the rate-limiting enzyme in the formation of bilirubin, is expressed in the lung and may serve as an antioxidant. This enzyme results in the formation of antioxidant bile pigments and the degradation of pro-oxidant heme. We wanted to evaluate the differences in expression of HO-1, the inducible form, and HO-2, the constitutive isoenzyme, during lung maturation and document whether lung HO expression was similar to that of other antioxidant enzymes. Lung total HO activity and HO-1 and HO-2 proteins as well as HO-1 and HO-2 mRNA were evaluated in animals from 16 d of gestation (e(16.5)) to 2 mo of age. Heme content was also evaluated because heme is the substrate of the reaction. HO-1 mRNA was maximal at e(19.5) and e(20.5), whereas HO-2 mRNA was not changed throughout maturation. Lung HO-1 protein was highest on the first days of life and lowest in adults, whereas HO-2 protein was maximally expressed at postnatal d 5 and then declined to reach adult values. As to HO activity, there was a prenatal peak at e(20.5), a second lesser peak at d 5, and thereafter a decline to adult values. Lung heme content was inversely correlated with HO activity or protein as the highest heme values were seen in adults with the lowest HO activity. In response to hyperoxia, HO-1 mRNA was induced only in the adult lungs. A better understanding of the maturational regulation of lung HO will define a role for HO in newborns at risk for oxygen toxicity.
Fairchild, Graeme; Van Goozen, Stephanie H. M.; Calder, Andrew J.; Stollery, Sarah J.; Goodyer, Ian M.
Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…
Fairchild, Graeme; Van Goozen, Stephanie H. M.; Calder, Andrew J.; Stollery, Sarah J.; Goodyer, Ian M.
Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…
Casini, G; Brecha, N C; Bosco, L; Rickman, D W
Tachykinin (TK) peptides act on retinal neurons through neurokinin (NK) receptors. We examined the expression of neurokinin-1 (NK1; the substance P receptor), NK3 [the neurokinin B (NKB) receptor], and TK peptides in developing rat retinas. NK1 immunolabeling was found in newborn retinas in rare amacrine cells and in putative ganglion cells. At postnatal day 2 (PND 2), NK1 immunostaining was reduced greatly among ganglion cells, and it appeared in many amacrine cells and in fibers in the inner plexiform layer (IPL), with the highest density in laminae 1, 3, and 5. A similar pattern was found at PND 7. At PND 12, interplexiform NK1-immunoreactive (-IR) cells were detected, and NK1-IR fibers in the IPL were concentrated in lamina 2, similar to what was seen in adults. NK3 was expressed mainly by OFF-cone bipolar cells, and the developmental pattern of NK3 was compared with that of cone bipolar cells that were labeled with antibodies to recoverin. Immature recoverin-IR cone bipolar cells were seen at PND 2. NK3 immunolabeling was detected first in the outer plexiform layer and in sparse bipolar cell somata at PND 10, when recoverin-IR cone bipolar cells are nearly mature. By PND 15, both the NK3 immunostaining pattern and the recoverin immunostaining pattern were similar to the patterns seen in adults. TK immunoreactivity was present at PND 0 in amacrine cells and displaced amacrine cells. By PND 10, the morphologic maturation of TK-IR cells was complete. These findings indicate that, in early postnatal retinas, substance P may act on NK1 receptors, whereas NKB/NK3 interactions are unlikely, suggesting that there are different levels of importance for different TK peptides in the developing retina. Copyright 2000 Wiley-Liss, Inc.
Tarrant Ann M
Full Text Available Abstract Background Nuclear receptors are a superfamily of metazoan transcription factors that regulate diverse developmental and physiological processes. Sequenced genomes from an increasing number of bilaterians have provided a more complete picture of duplication and loss of nuclear receptors in protostomes and deuterostomes but have left open the question of which nuclear receptors were present in the cnidarian-bilaterian ancestor. In addition, nuclear receptor expression and function are largely uncharacterized within cnidarians, preventing determination of conserved and novel nuclear receptor functions in the context of animal evolution. Results Here we report the first complete set of nuclear receptors from a cnidarian, the starlet sea anemone Nematostella vectensis. Genomic searches using conserved DNA- and ligand-binding domains revealed seventeen nuclear receptors in N. vectensis. Phylogenetic analyses support N. vectensis orthologs of bilaterian nuclear receptors in four nuclear receptor subfamilies within nuclear receptor family 2 (COUP-TF, TLL, HNF4, TR2/4 and one putative ortholog of GCNF (nuclear receptor family 6. Other N. vectensis genes grouped well with nuclear receptor family 2 but represented lineage-specific duplications somewhere within the cnidarian lineage and were not clear orthologs of bilaterian genes. Three nuclear receptors were not well-supported within any particular nuclear receptor family. The seventeen nuclear receptors exhibited distinct developmental expression patterns, with expression of several nuclear receptors limited to a subset of developmental stages. Conclusion N. vectensis contains a diverse complement of nuclear receptors including orthologs of several bilaterian nuclear receptors. Novel nuclear receptors in N. vectensis may be ancient genes lost from triploblastic lineages or may represent cnidarian-specific radiations. Nuclear receptors exhibited distinct developmental expression patterns, which
von Suchodoletz, Waldemar
Children with developmental language disorders have a high risk for their cognitive, social, and emotional development. Therefore, they should be identified and treated as early as possible. This paper reviews the possibilities and limits of methods for such early identification. Language screenings during the first 3 years of life are described and appraised with respect to their diagnostic accuracy. The overview indicates that the current stage of language development can be estimated with high reliability by means of parent questionnaires. The possibility of identifying children with developmental language disorders early on is limited. Precursors and first steps of language acquisition correlate with later language abilities, although the relationship is weak and predicting further language development in a individual child is not possible. At the end of the second year of life, however, late talkers can be identified; these children are at risk of language impairment. But not until the end of the third year can sufficient detection of language-impaired children succeed. Parent questionnaires are the most reliable screening instruments for evaluating language abilities during the first 3 years.
Full Text Available Bacterial communities associated with white shrimp (Litopenaeus vannamei larvae at early developmental stages. Biodiversitas 11 (2: 65-68.Terminal Restriction Fragment Length Polymorphism (T-RFLP was used to monitor the dynamics of the bacterial communities associated with early developmental stages of white shrimp (Litopenaeus vannamei larvae. Samples for analysis were egg, hatching nauplii, 24 hours old nauplii, and 48 hours old nauplii which were collected from one cycle of production at commercial hatchery. T-RFLP results indicated that the bacterial community associated with early stages of shrimp development might be transferred vertically from broodstock via egg. There was no significant difference between bacterial communities investigated, except the bacterial community of 48 hours old nauplii. Diversity analyses showed that the bacterial community of egg had the highest diversity and evenness, meanwhile the bacterial community of 48 hours old nauplii had the lowest diversity. Nine phylotypes were found at all stages with high abundance. Those TRFs were identified as γ- proteobacteria, α-proteobacteria, and bacteroidetes group.
Lendvai, Adám Z; Loiseau, Claire; Sorci, Gabriele; Chastel, Olivier
The short- and long-term consequences of developmental conditions on fitness have received growing attention because the environmental conditions during early life may influence growth, condition at independence, recruitment, reproductive success or survival. We tested here, in a natural house sparrow population, if early conditions during nestling stage affected the stress response of the birds (i) shortly after fledging and (ii) next year, during their first breeding. We experimentally manipulated brood size to mimic different rearing conditions, creating reduced (-2 chicks) and enlarged broods (+2 chicks), while in a third group brood size was not manipulated. Nestling nutrition state decreased with post-manipulation brood sizes as indicated by lower body mass. Fledglings with higher body mass at the age of ten days showed lower stress response than birds that were leaner at the same age. Fledglings reared in large broods showed a higher response to stress protocol than chicks from small broods, and this effect was in significant interaction with the age of fledglings at capture. This interaction indicates that the effects of the brood size became gradually smaller as the fledglings grew older and were further from their nestling period. The effects of early conditions vanished by the next year: the stress response of adult first time breeders was unrelated to the brood size they fledged from. These results suggest that stress response may reflect the actual state of an individual, rather than its developmental history.
Roslyn Holly Fitch
Full Text Available Most researchers in the field of neural plasticity are familiar with the Kennard Principle," which purports a positive relationship between age at brain injury and severity of subsequent deficits (plateauing in adulthood. As an example, a child with left hemispherectomy can recover seemingly normal language, while an adult with focal injury to sub-regions of left temporal and/or frontal cortex can suffer dramatic and permanent language loss. Here we present data regarding the impact of early brain injury in rat models as a function of type and timing, measuring long-term behavioral outcomes via auditory discrimination tasks varying in temporal demand. These tasks were created to model (in rodents aspects of human sensory processing that may correlate – both developmentally and functionally – with typical and atypical language. We found that bilateral focal lesions to the cortical plate in rats during active neuronal migration led to worse auditory outcomes than comparable lesions induced after cortical migration was complete. Conversely, unilateral hypoxic-ischemic injuries (similar to those seen in premature infants and term infants with birth complications led to permanent auditory processing deficits when induced at a neurodevelopmental point comparable to human "term," but only transient deficits (undetectable in adulthood when induced in a "preterm" window. Convergent evidence suggests that regardless of when or how disruption of early neural development occurs, the consequences may be particularly deleterious to rapid auditory processing outcomes when they trigger developmental alterations that extend into subcortical structures (i.e., lower sensory processing stations. Collective findings hold implications for the study of behavioral outcomes following early brain injury as well as genetic/environmental disruption, and are relevant to our understanding of the neurologic risk factors underlying developmental language disability in
Scheibye-Alsing, Karsten; Cirera, Susanna; Gilchrist, Michael J.
BACKGROUND: The mitochondria are involved in many basic functions in cells of vertebrates, and can be considered the power generator of the cell. Though the mitochondria have been extensively studied there appear to be only few expression studies of mitochondrial genes involving a large number......, emphasizing differences between adult and developmental tissues. Our work indicates that there are presently unknown mechanisms which work to customize mitochondrial processes to the specific needs of the cell, illustrated by the different patterns between adult and developmental tissues. Furthermore, our...
Debast, Inge; Rossi, Gina; Feenstra, Dineke; Hutsebaut, Joost
Criterion D of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association [APA], 2013) refers to a possible onset of personality disorders (PDs) in adolescence and in Section II the development/course in adolescence is described by some typical characteristics for several PDs. Yet, age-specific expressions of PDs are lacking in Section III. We urgently need a developmentally sensitive assessment instrument that differentiates developmental and contextual changes on the one hand from expressions of personality pathology on the other hand. Therefore we investigated which items of the Severity Indices for Personality Problems-118 (SIPP-118) were developmentally sensitive throughout adolescence and adulthood and which could be considered more age-specific markers requiring other content or thresholds over age groups. Applying item response theory (IRT) we detected differential item functioning (DIF) in 36% of the items in matched samples of 639 adolescents versus 639 adults. The DIF across age groups mainly reflected a different degree of symptom expressions for the same underlying level of functioning. The threshold for exhibiting symptoms given a certain degree of personality dysfunction was lower in adolescence for areas of personality functioning related to the Self and Interpersonal domains. Some items also measured a latent construct of personality functioning differently across adolescents and adults. This suggests that several facets of the SIPP-118 do not solely measure aspects of personality pathology in adolescents, but likely include more developmental issues. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Santana, Paula A; Guzmán, Fanny; Forero, Juan C; Luna, Omar F; Mercado, Luis
During the early developmental stage of salmonids, high mortality occurs largely as a result of pathogens. These cause low immune competence in fry, producing disease, decreasing production and finally leading to economic losses. Therefore, the aim of this study was to characterise the developmental stages in which rainbow trout acquires immune response capability when challenged with LPS from Pseudomona aeruginosa for 8 h, studying the hepcidin, cathelicidin-1 and IL-8. Total RNA was extracted from fry at 34, 42, 56 and 66 days post hatching (dph). Hepcidin and cathelicidin-1 transcripts were detected only at days 34 and 42, whereas the IL-8 transcript was detected from day 34 to day 66. To analyse the protein expression in the fry, polyclonal anti-peptide antibodies were generated in rabbit. These three immune sera demonstrated the ability to recognise the whole molecule in biological samples. Immunofluorescence showed that skin, gills and intestine mainly responded to the LPS challenge, indicating that these portals of pathogen entry are capturing LPS. This study constitutes a valuable approach, since it has the potential to identify molecules with biological activity that can be used to evaluate the status of fry in culture.
Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Kodama, Itsuo
Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal rat hearts and superior cervical ganglia, and were co-cultured, either in a random or localized way. Neurite growth from SNs toward CMs was assessed by immunohistochemistry for neurofilament M and α-actinin in response to neurotrophic factors-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and a chemical repellent, semaphorin 3A. As a result, GDNF as well as NGF and BDNF stimulated neurite growth. GDNF enhanced neurite outgrowth even under the NGF-depleted culture condition, excluding an indirect effect of GDNF via NGF. Quantification of mRNA and protein by real-time PCR and immunohistochemistry at different developmental stages revealed that GDNF is abundantly expressed in the hearts of embryos and neonates, but not in adult hearts. GDNF plays an important role in inducing cardiac sympathetic innervation at the early developmental stages. A possible role in (re)innervation of injured or transplanted or cultured and transplanted myocardium may deserve investigation.
Watkins, Ruth V.; Yairi, Ehud; Ambrose, Nicoline Grinager
A study compared the expressive language abilities of 22 preschool children whose stuttering persisted and 62 who recovered over a four-year period. Findings revealed similarity in the abilities of children whose stuttering persisted as opposed to abated at all ages. All stutterers displayed abilities near or above developmental expectations. (CR)
Shinzato, Chuya; Iguchi, Akira; Hayward, David C; Technau, Ulrich; Ball, Eldon E; Miller, David J
Sox genes encode transcription factors that function in a wide range of developmental processes across the animal kingdom. To better understand both the evolution of the Sox family and the roles of these genes in cnidarians, we are studying the Sox gene complement of the coral, Acropora millepora (Class Anthozoa). Based on overall domain structures and HMG box sequences, the Acropora Sox genes considered here clearly fall into four of the five major Sox classes. AmSoxC is expressed in the ectoderm during development, in cells whose morphology is consistent with their assignment as sensory neurons. The expression pattern of the Nematostella ortholog of this gene is broadly similar to that of AmSoxC, but there are subtle differences--for example, expression begins significantly earlier in Acropora than in Nematostella. During gastrulation, AmSoxBb and AmSoxB1 transcripts are detected only in the presumptive ectoderm while AmSoxE1 transcription is restricted to the presumptive endoderm, suggesting that these Sox genes might play roles in germ layer specification. A third type B Sox gene, AmSoxBa, and a Sox F gene AmSoxF also have complex and specific expression patterns during early development. Each of these genes has a clear Nematostella ortholog, but in several cases the expression pattern observed in Acropora differs significantly from that reported in Nematostella. These differences in expression patterns between Acropora and Nematostella largely reflect fundamental differences in developmental processes, underscoring the diversity of mechanisms within the anthozoan Sub-Class Hexacorallia (Zoantharia).
Full Text Available The objective of the study was to characterize the developmental sequence of pre- and postnatal risk factors for inattention-hyperactivity symptoms in preschoolers.Longitudinal data came from a French population based birth cohort study (EDEN; N = 1311 mother-child pairs followed from the pregnancy onwards. Inattention-hyperactivity symptoms were assessed with the Strengths and Difficulties Questionnaire when participating children were 3 years of age. Potential risk factors were classified in four domains (fetal exposures and child somatic characteristics, child temperament, child neurodevelopmental status, psychosocial environment and four periods (before pregnancy, prenatal/birth, infancy, toddlerhood. Their role as potential moderator or mediator was tested with path analysis to determine the developmental sequence.A low family socioeconomic status before pregnancy was the main environmental risk factor for inattention-hyperactivity symptoms at 3 years, and its effect occurred via two pathways. The first was a risk pathway, where lower SES was associated with higher maternal depression and anxiety during pregnancy; then to higher maternal and child distress and dysregulation in infancy; and in turn to higher levels of inattention-hyperactivity at 3 years. The second was a protective pathway, where higher SES was associated with longer duration of breastfeeding during infancy; then to better child neurodevelopmental status in toddlerhood; and in turn to lower levels of inattention-hyperactivity at 3 years.This study identified psychosocial factors at several developmental periods that represent potential targets for preventing the emergence of inattention-hyperactivity symptoms in early childhood.
David M. Holloway
Full Text Available Understanding how genetic networks act in embryonic development requires a detailed and statistically significant dataset integrating diverse observational results. The fruit fly (Drosophila melanogaster is used as a model organism for studying developmental genetics. In recent years, several laboratories have systematically gathered confocal microscopy images of patterns of activity (expression for genes governing early Drosophila development. Due to both the high variability between fruit fly embryos and diverse sources of observational errors, some new nontrivial procedures for processing and integrating the raw observations are required. Here we describe processing techniques based on genetic algorithms and discuss their efficacy in decreasing observational errors and illuminating the natural variability in gene expression patterns. The specific developmental problem studied is anteroposterior specification of the body plan.
Missana, Manuela; Grigutsch, Maren; Grossmann, Tobias
We examined the processing of facial expressions of pain and anger in 8-month-old infants and adults by measuring event-related brain potentials (ERPs) and frontal EEG alpha asymmetry. The ERP results revealed that while adults showed a late positive potential (LPP) to emotional expressions that was enhanced to pain expressions, reflecting increased evaluation and emotional arousal to pain expressions, infants showed a negative component (Nc) to emotional expressions that was enhanced to angry expressions, reflecting increased allocation of attention to angry faces. Moreover, infants and adults showed opposite patterns in their frontal asymmetry responses to pain and anger, suggesting developmental differences in the motivational processes engendered by these facial expressions. These findings are discussed in the light of associated individual differences in infant temperament and adult dispositional empathy.
Full Text Available We examined the processing of facial expressions of pain and anger in 8-month-old infants and adults by measuring event-related brain potentials (ERPs and frontal EEG alpha asymmetry. The ERP results revealed that while adults showed a late positive potential (LPP to emotional expressions that was enhanced to pain expressions, reflecting increased evaluation and emotional arousal to pain expressions, infants showed a negative component (Nc to emotional expressions that was enhanced to angry expressions, reflecting increased allocation of attention to angry faces. Moreover, infants and adults showed opposite patterns in their frontal asymmetry responses to pain and anger, suggesting developmental differences in the motivational processes engendered by these facial expressions. These findings are discussed in the light of associated individual differences in infant temperament and adult dispositional empathy.
Bloomquist, R F; Fowler, T E; Sylvester, J B; Miro, R J; Streelman, J T
Lake Malawi cichlids represent one of a growing number of vertebrate models used to uncover the genetic and developmental basis of trait diversity. Rapid evolutionary radiation has resulted in species that share similar genomes but differ markedly in phenotypes including brains and behavior, nuptial coloration and the craniofacial skeleton. Research has begun to identify the genes, as well as the molecular and developmental pathways that underlie trait divergence. We assemble a compendium of gene expression for Lake Malawi cichlids, across pharyngula (the phylotypic stage) and larval stages of development, encompassing hundreds of gene transcripts. We chart patterns of expression in Bone morphogenetic protein (BMP), Fibroblast growth factor (FGF), Hedgehog (Hh), Notch and Wingless (Wnt) signaling pathways, as well as genes involved in neurogenesis, calcium and endocrine signaling, stem cell biology, and numerous homeobox (Hox) factors-in three planes using whole-mount in situ hybridization. Because of low sequence divergence across the Malawi cichlid assemblage, the probes we employ are broadly applicable in hundreds of species. We tabulate gene expression across general tissue domains, and highlight examples of unexpected expression patterns. On the heels of recently published genomes, this compendium of developmental gene expression in Lake Malawi cichlids provides a valuable resource for those interested in the relationship between evolution and development.
Full Text Available This report aimed to assess mothers’ perceptions on normal and deviation of development in their children. The study was done in underfive children and their mothers from May 1st 1999 to June 30th 1999 who visited the Nutrition, Growth & Development Clinic of the Child Health Department, Sanglah Hospital, Denpasar. A total of 76 children between 2 and 59 months of age and their mothers were enrolled. Data were collected by interview with mothers concerning the following items: perception of their children development, age of child, sex, mother’s education, mother’s job, number of sibling, and mother ability in making referral decisions. Denver II screening test was administered to each child to identify of development status as a gold standard. Sixteen (21% children was identified as having developmental deviation (by mother’s perception and 21 (28% by authors using Denver II screening test. The mother’s perception sensitivity was 67% and specificity was 97%. There were no significant differences of development status perception according to child’s age, mother’s education, mother’s job, and number of sibling. Most of mother’s perceptions about normal development were if the body weight increased and had no disability. Most of the sources of information about development was from the relatives. Thirteen of 21 children who had developmental deviation were referred by mothers. We conclude that mother’s perception can be used as early detection of developmental problems. Mother’s concerns of their children growth development had focused on again body weight, physical developmental and gross motor skill.
Bagnato, Stephen J.; Suen, Hoi K.; Brickley, Dale; Smith-Jones, Janell; Dettore, Ernie
This study used an "enhanced constructed comparison group" statistical model to conduct longitudinal research on the child developmental impact of Pittsburgh's early childhood initiative (ECI), a partnership to provide high-quality early care and education for children in high-risk neighborhoods. First-phase findings indicate that…
Hornman, Jorijn; de Winter, Andrea F.; Kerstjens, Jorien M.; Bos, Arend F.; Reijneveld, Sijmen A.
Objective To assess the stability of developmental problems in moderately-late preterm-born children compared with early preterm and full term-born children before school entry at age 4 years and 1 year after school entry at age 5 years. Study design We included 376 early preterm, 688 born
Hornman, Jorijn; de Winter, Andrea F; Kerstjens, Jorien M; Bos, Arend F; Reijneveld, Sijmen A
OBJECTIVE: To assess the stability of developmental problems in moderately-late preterm-born children compared with early preterm and full term-born children before school entry at age 4 years and 1 year after school entry at age 5 years. STUDY DESIGN: We included 376 early preterm, 688 born
Naruse, Susumu; Hashimoto, Toshiaki; Mori, Kenji; Tsuda, Yoshimi; Takahara, Mitsue; Kagami, Shoji
Facial expressions hold abundant information and play a central part in communication. In daily life, we must construct amicable interpersonal relationships by communicating through verbal and nonverbal behaviors. While school-age is a period of rapid social growth, few studies exist that study developmental changes in facial expression recognition during this age. This study investigated developmental changes in facial expression recognition by examining observers' gaze on others' expressions. 87 school-age children from first to sixth grade (41 boys, 46 girls). The Tobii T60 Eye-tracker(Tobii Technologies, Sweden) was used to gauge eye movement during a task of matching pre-instructed emotion words and facial expressions images (neutral, angry, happy, surprised, sad, disgusted) presented on a monitor fixed at a distance of 50 cm. In the task of matching the six facial expression images and emotion words, the mid- and higher-grade children answered more accurately than the lower-grade children in matching four expressions, excluding neutral and happy. For fixation time and fixation count, the lower-grade children scored lower than other grade children, gazing on all facial expressions significantly fewer times and for shorter periods. It is guessed that the stage from lower grades to middle grades is a turning point in facial recognition.
Levorato, Maria Chiara; Nesi, Barbara; Cacciari, Cristina
The aim of the present study was to investigate idiom comprehension in school-age Italian children with different reading comprehension skills. According to our hypothesis, the level of a child's text comprehension skills should predict his/her ability to understand idiomatic meanings. Idiom comprehension in fact requires children to go beyond a simple word-by-word comprehension strategy and to integrate figurative meaning into contextual information. In a preliminary phase, we used a standardized battery of tests (Cornoldi & Colpo, 1998) to assess the ability of second graders and fourth graders to comprehend written texts. Three groups were identified at each age level: good, medium, and poor comprehenders. Children were then presented with familiar idiomatic expressions which also have a literal meaning (e.g., "break the ice"). Idioms were embedded in short stories: in Experiment 1 only the idiomatic interpretation was contextually appropriate, in Experiment 2 a literal reading of the string was also plausible in the context. A multiple-choice task was used in both experiments: children were asked to choose one answer among three corresponding to: (a) the idiomatic meaning; (b) the literal meaning; and (c) an interpretation contextually appropriate but not connected with the idiomatic or literal meaning of the idiom string. The results of both experiments showed that the ability to understand a text indeed predicted children's understanding of idioms in context. To verify whether possible improvements in children's comprehension skills might produce an increase in figurative language understanding, Experiment 3 was carried out. A group of poor comprehenders who participated in Experiments 1 and 2 was tested eight months later. The results of Experiment 3 showed that children whose general comprehension skills improved their performance on an idiom comprehension test.
Arabameri, Elahe; Sotoodeh, Mohammad Saber
Early diagnosis is appropriate and important for developmental disorders such as autism spectrum disorder. In many less developed countries, unfortunately, diagnosis of this disorder is delayed. The aim of the present study is to determine whether this disorder can be screened using simple strategies such as comparison of the age of acquisition of motor skills. For this purpose, 124 children with autism were chosen to enter the study, and their parents were asked to retrospectively specify the age of achieving milestones of sitting without support, standing alone and walking alone. Information obtained from the parents was compared with World Health Organization standards. Results indicate that participants (male and female) have significantly delayed age of acquisition of all three skills. Based on this result, it can be suggested that existing standards, as a simple means with low cost and easy availability, can be used for early screening of the disease at a younger age so that treatment can be provided more quickly.
Cristhyane Garcia Araldi
Full Text Available Araucaria angustifolia seeds are recalcitrant, and their metabolism remains high during storage. This research aimed to describe the initiation of germination in A. angustifolia seeds during storage in order to standardize the assessment of physiological quality and to promote seed conservation. Seeds were collected from two populations and stored for 270 days in the natural laboratory environment and cold chamber. Seeds were classified according to four early developmental stages: I - mature seeds; II - seeds with elongation along the embryonic axis; III - beginning of root protrusion; IV - advanced germination stage, with seedling shoots. After categorization, physical and physiological quality was assessed. In freshly collected seeds, only category I was observed. At 270 days, approximately 40% of seeds were in category III in laboratory conditions, while the maintenance in a cold chamber delayed germinative metabolism. Viability tests showed that seeds in categories III and IV were more susceptible to damage caused by storage. In conclusion, the percentage of viable A. angustifolia seeds depends on the development stage after collection. Seeds that have reached early developmental category III should be prioritized for propagation, while those remaining in categories I and II should be longer stored with periodic assessment for reduction in physiological quality.
Full Text Available The purpose of this study was to use mismatch responses (MMRs to explore the dynamic changes of Mandarin speech perception abilities from early to middle childhood. Twenty preschoolers, 18 school-aged children, and 26 adults participated in this study. Two sets of synthesized speech stimuli varying in Mandarin consonant (alveolo-palatal affricate vs. fricative and lexical tone features (rising vs. contour tone were used to examine the developmental course of speech perception abilities. The results indicated that only the adult group demonstrated typical early mismatch negativity (MMN responses, suggesting that the ability to discriminate specific speech cues in Mandarin consonant and lexical tone is a continuing process in preschool- and school-aged children. Additionally, distinct MMR patterns provided evidence indicating diverse developmental courses to different speech characteristics. By incorporating data from the two speech conditions, we propose using MMR profiles consisting of mismatch negativity (MMN, positive mismatch response (p-MMR, and late discriminative negativity (LDN as possible brain indices to investigate speech perception development.
Filatova, S; Koivumaa-Honkanen, H; Hirvonen, N; Freeman, A; Ivandic, I; Hurtig, T; Khandaker, G M; Jones, P B; Moilanen, K; Miettunen, J
The neurodevelopmental hypothesis of schizophrenia proposes that impaired brain development is a cause of the illness. Early motor developmental milestones, such as learning to walk, are predictors of later schizophrenia but studies have not been systematically reviewed. The aim of the present systematic review and meta-analysis was to explore the association between early motor developmental milestones and the risk of adult schizophrenia. In addition, we updated a systematic review on motor function and risk of schizophrenia. The PubMed, PsycINFO and Scopus databases were searched for original research articles published up to July 2015. Motor milestones were measured between ages 0 and 13years. Random effect meta-analysis calculated effect estimates (Hedges' g) for the association between individual motor milestones and schizophrenia risk. An electronic database and selected articles reference list search identified 5990 articles after removing duplicates. Sixty-nine full text articles were assessed for eligibility of which six were included in the review. Five studies provided sufficient data for meta-analyses. The following motor milestones were significantly associated with adult schizophrenia risk: walking unsupported (g=0.46; 95% CI 0.27-0.64; pmotor milestones in childhood and can contribute to the identification of individuals at risk of psychosis.
Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for many developmental and physiological aspects of CNS function. Severe hypothyroidism in the early neonatal period results in developmental and cognitive impairments and reductions in mRNA and protein expressio...
Goda, Tadahiro; Mirowska, Karolina; Currie, Jake; Kim, Min-Ho; Rao, Neethi Varadaraja; Bonilla, Gloribel; Wijnen, Herman
Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LN(v)s) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LN(v)s resulted in abnormal peptidergic small-LN(v) dorsal projections, and (2) PER expression rhythms in the adult LN(v)s appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex.
XIA Dong; ZHAO Ru-qian; XU Qing-fu; XU Jin-xian; SHI Zi-gang; CHEN Jie
In present study, the developmental patterns of somatostatin (SS) gene expression in gastrictissue were compared between Erhualian and Large White pigs. A semi-quantitative RT-PCR was applied todetermine the levels of SS mRNA. The results indicated that : (1) The gastric SS mRNA expression was high atbirth, followed by a significant decrease (P＜0.05) at 3 days of age in both breeds of pigs; (2) From 3 to 30days of age, the expression of SS mRNA in gastric tissue exhibited remarkable up-regulation in both breeds,after which a strain difference in the developmental pattern was observed. In Erhualian pigs, SS mRNA ex-pression reached a peak at 90 days of age, declined thereafter towards 180 days of age. In Large White pigs,however, the expression of SS mRNA remained constant from 30 days of age onwards; (3) In general, Erhual-ian pigs expressed higher levels of SS mRNA in gastric tissue compared with Large White pigs at the same age.The strain difference was significant from birth to 90 days of age, but vanished at 120 and 180 days of age.The results suggest that the gastric expression of SS in the pig is regulated following an instinct timetable in astrain-specific manner, its relationship with the development of gastric function as well as its interactions withenvironmental factors are to be elucidated.
Norona, A N; Baker, B L
Emotion regulation has been identified as a robust predictor of adaptive functioning across a variety of domains (Aldao et al. ). Furthermore, research examining early predictors of competence and deficits in ER suggests that factors internal to the individual (e.g. neuroregulatory reactivity, behavioural traits and cognitive ability) and external to the individual (e.g. caregiving styles and explicit ER training) contribute to the development of ER (Calkins ). Many studies have focused on internal sources or external sources; however, few have studied them simultaneously within one model, especially in studies examining children with developmental delays (DD). Here, we addressed this specific research gap and examined the contributions of one internal factor and one external factor on emotion dysregulation outcomes in middle childhood. Specifically, our current study used structural equation modelling (SEM) to examine prospective, predictive relationships between DD status, positive parenting at age 4 years and child emotion dysregulation at age 7 years. Participants were 151 families in the Collaborative Family Study, a longitudinal study of young children with and without DD. A positive parenting factor was composed of sensitivity and scaffolding scores from mother-child interactions at home and in the research centre at child age 4 years. A child dysregulation factor was composed of a dysregulation code from mother-child interactions and a parent-report measure of ER and lability/negativity at age 7 years. Finally, we tested the hypothesis that positive parenting would mediate the relationship between DD and child dysregulation. Mothers of children with DD exhibited fewer sensitive and scaffolding behaviours compared with mothers of typically developing children, and children with DD were more dysregulated on all measures of ER. SEM revealed that both DD status and early positive parenting predicted emotion dysregulation in middle childhood. Furthermore
Enlow, Michelle Bosquet; Blood, Emily; Egeland, Byron
Young children are disproportionately exposed to interpersonal trauma (maltreatment, witnessing intimate partner violence [IPV]) and appear particularly susceptible to negative sequelae. Little is known about the factors influencing vulnerability to traumatic stress responses and other negative outcomes in early life. This study examined associations among interpersonal trauma exposure, sociodemographic risk, developmental competence, and posttraumatic stress disorder (PTSD) symptoms in 200 children assessed from birth to first grade via standardized observations, record reviews, and maternal and teacher interviews. More severe PTSD symptoms were predicted by greater trauma exposure (r = .43), greater sociodemographic risk (r = .22), and lower developmental competence (rs=−.31 and −.54 for preschool and school-age developmental competence, respectively). Developmental competence partially mediated the association between trauma exposure and symptoms. Trauma exposure fully mediated the association between sociodemographic risk and symptoms. Neither sociodemographic risk nor developmental competence moderated trauma exposure effects on symptoms. The findings suggest that (a)exposure to maltreatment and IPV has additive effects on posttraumatic stress risk in early life, (b) associations between sociodemographic adversity and poor mental health may be attributable to increased trauma exposure in disadvantaged populations, and (c) early exposures have a negative cascade effect on developmental competence and mental health.
Richard A White
Full Text Available It is acknowledged that some obesity trajectories are set early in life, and that rapid weight gain in infancy is a risk factor for later development of obesity. Identifying modifiable factors associated with early rapid weight gain is a prerequisite for curtailing the growing worldwide obesity epidemic. Recently, much attention has been given to findings indicating that gut microbiota may play a role in obesity development. We aim at identifying how the development of early gut microbiota is associated with expected infant growth. We developed a novel procedure that allows for the identification of longitudinal gut microbiota patterns (corresponding to the gut ecosystem developing, which are associated with an outcome of interest, while appropriately controlling for the false discovery rate. Our method identified developmental pathways of Staphylococcus species and Escherichia coli that were associated with expected growth, and traditional methods indicated that the detection of Bacteroides species at day 30 was associated with growth. Our method should have wide future applicability for studying gut microbiota, and is particularly important for translational considerations, as it is critical to understand the timing of microbiome transitions prior to attempting to manipulate gut microbiota in early life.
Full Text Available The robust axonal growth and regenerative capacities of young neurons decrease substantially with age. This developmental downregulation of axonal growth may facilitate axonal pruning and neural circuit formation but limits functional recovery following nerve damage. While external factors influencing axonal growth have been extensively investigated, relatively little is known about the intrinsic molecular changes underlying the age-dependent reduction in regeneration capacity. We report that developmental downregulation of LIS1 is responsible for the decreased axonal extension capacity of mature dorsal root ganglion (DRG neurons. In contrast, exogenous LIS1 expression or endogenous LIS1 augmentation by calpain inhibition restored axonal extension capacity in mature DRG neurons and facilitated regeneration of the damaged sciatic nerve. The insulator protein CTCF suppressed LIS1 expression in mature DRG neurons, and this reduction resulted in excessive accumulation of phosphoactivated GSK-3β at the axon tip, causing failure of the axonal extension. Conversely, sustained LIS1 expression inhibited developmental axon pruning in the mammillary body. Thus, LIS1 regulation may coordinate the balance between axonal growth and pruning during maturation of neuronal circuits.
Xiao-Nan Dai; Shan Liu; Li Shao; Chao Gao; Li Gao; Jia-Yin Liu; Yu-Gui Cui
SET is a multifunctional protein involved in regulating many biological processes of the cell cycle. It is also a regulator of steroidogenesis in the ovary. However, the expression of SET protein in testis, and its function, still remains ambiguous. In this study, we observed the expression of SET in the testes of mice at different developmental stages, and have discussed its potential function in regulating spermatogenesis and androgen production. Forty‑eight male mice at different developmental stages(1week old as the infancy group; 4weeks old as the prepubertal group; 12weeks old as the adult group; over12months old as the ageing group) were used. Cellular location of SET protein in the testes was observed by immuno‑histochemistry. Expression levels of Set mRNA and SET protein were analyzed by quantitative polymerase chain reaction and Western blotting. SET protein was expressed in spermatogonial cells and spermatocytes; the highest level was mainly in haploid and tetraploid cells of the prepubertal and adult groups, and Leydig cells of the adult and ageing groups. There was a low expression in Sertoli cells. Expression of Set mRNA in the prepubertal group was signiifcantly higher than that in the adult group(P<0.05), while expression of SET protein was at the highest level in the adult group(P<0.05).SET protein is mainly expressed in spermatogonial cells and spermatocytes, and poorly expressed in Sertoli cells, suggesting that it is involved in spermatogenesis. Expression of SET protein in Leydig cells suggests a possible role in steroidogenesis.
Tanaka, Chiaki; Matsui, Mie; Uematsu, Akiko; Noguchi, Kyo; Miyawaki, Toshio
Brain development during early life in healthy individuals is rapid and dynamic, indicating that this period plays a very important role in neural and functional development. The frontal and temporal lobes are known to play a particularly important role in cognition. The study of healthy frontal and temporal lobe development in children is therefore of considerable importance. A better understanding of how these brain regions develop could also aid in the diagnosis and treatment of neurodevelopmental disorders. Some developmental studies have used magnetic resonance imaging (MRI) to examine infant brains, but it remains the case that relatively little is known about cortical brain development in the first few years of life. In the present study we examined whole brain, temporal lobe and frontal lobe developmental trajectories from infancy to early adulthood in healthy individuals, considering gender and brain hemisphere differences. We performed a cross-sectional, longitudinal morphometric MRI study of 114 healthy individuals (54 females and 60 males) aged 1 month to 25 years old (mean age ± SD 8.8 ± 6.9). We measured whole brain, temporal and frontal lobe gray matter (GM)/white matter (WM) volumes, following previously used protocols. There were significant non-linear age-related volume changes in all regions. Peak ages of whole brain, temporal lobe and frontal lobe development occurred around pre-adolescence (9-12 years old). GM volumes for all regions increased significantly as a function of age. Peak age was nevertheless lobe specific, with a pattern of earlier peak ages for females in both temporal and frontal lobes. Growth change in whole brain GM volume was larger in males than in females. However, GM volume growth changes for the temporal and frontal lobes showed a somewhat different pattern. GM volume for both temporal and frontal lobes showed a greater increase in females until around 5-6 years old, at which point this tendency reversed (GM volume
Zurolo, E.; Iyer, A.M.; Spliet, W.G.M.; van Rijen, P.C.; Troost, D.; Gorter, J.A.; Aronica, E.
Recent data support the involvement of the endocannabinoid signaling in early brain development, as well as a key role of cannabinoid receptors (CBR) in pathological conditions associated with unbalanced neuronal excitability and inflammation. Using immunocytochemistry, we explored the expression an
Beesdo-Baum, Katja; Knappe, Susanne; Asselmann, Eva; Zimmermann, Petra; Brückl, Tanja; Höfler, Michael; Behrendt, Silke; Lieb, Roselind; Wittchen, Hans-Ulrich
The "Early Developmental Stages of Psychopathology (EDSP)" study is a prospective-longitudinal study program in a community sample (Munich, Germany) of adolescents and young adults. The program was launched in 1994 to study the prevalence and incidence of psychopathological syndromes and mental disorders, to describe the natural course and to identify vulnerability and risk factors for onset and progression as well as psychosocial consequences. This paper reviews methods and core outcomes of this study program. The EDSP is based on an age-stratified random community sample of originally N = 3021 subjects aged 14-24 years at baseline, followed up over 10 years with up to 3 follow-up waves. The program includes a family genetic supplement and nested cohorts with lab assessments including blood samples for genetic analyses. Psychopathology was assessed with the DSM-IV/M-CIDI; embedded dimensional scales and instruments assessed vulnerability and risk factors. Beyond the provision of age-specific prevalence and incidence rates for a wide range of mental disorders, analyses of their patterns of onset, course and interrelationships, the program identified common and diagnosis-specific distal and proximal vulnerability and risk factors including critical interactions. The EDSP study advanced our knowledge on the developmental pathways and trajectories, symptom progression and unfolding of disorder comorbidity, highlighting the dynamic nature of many disorders and their determinants. The results have been instrumental for defining more appropriate diagnostic thresholds, led to the derivation of symptom progression models and were helpful to identify promising targets for prevention and intervention.
Kellam, S G; Werthamer-Larsson, L; Dolan, L J; Brown, C H; Mayer, L S; Rebok, G W; Anthony, J C; Laudolff, J; Edelsohn, G
Describes a conceptual framework for identifying and targeting developmental antecedents in early childhood that have been shown in previous work to predict delinquency and violent behavior, heavy drug use, depression, and other psychiatric symptoms and possibly disorders in late adolescence and into adulthood. Criteria are described that guided choices of targets for two epidemiologically based, randomized preventive trials carried out in 19 elementary schools in the eastern half of Baltimore, involving more than 2,400 first-grade children over the course of first and second grades. Baseline models derived from the first of two cohorts show the evolving patterns of concurrence among the target antecedents. The central role of concentration problems emerged. From Fall to Spring in first grade, concentration problems led to shy and aggressive behavior and poor achievement in both genders and to depressive symptoms among girls. There was evidence for reciprocal relationships in girls. For example, depressive symptoms led to poor achievement in both girls and boys, whereas poor achievement led to depressive symptoms in girls but not boys, at least over the first-grade year. These results provide important epidemiological data relevant to the developmental paths leading to the problem outcomes and suggest preventive trials.
Full Text Available The cellular composition of heterogeneous samples can be predicted using an expression deconvolution algorithm to decompose their gene expression profiles based on pre-defined, reference gene expression profiles of the constituent populations in these samples. However, the expression profiles of the actual constituent populations are often perturbed from those of the reference profiles due to gene expression changes in cells associated with microenvironmental or developmental effects. Existing deconvolution algorithms do not account for these changes and give incorrect results when benchmarked against those measured by well-established flow cytometry, even after batch correction was applied. We introduce PERT, a new probabilistic expression deconvolution method that detects and accounts for a shared, multiplicative perturbation in the reference profiles when performing expression deconvolution. We applied PERT and three other state-of-the-art expression deconvolution methods to predict cell frequencies within heterogeneous human blood samples that were collected under several conditions (uncultured mono-nucleated and lineage-depleted cells, and culture-derived lineage-depleted cells. Only PERT's predicted proportions of the constituent populations matched those assigned by flow cytometry. Genes associated with cell cycle processes were highly enriched among those with the largest predicted expression changes between the cultured and uncultured conditions. We anticipate that PERT will be widely applicable to expression deconvolution strategies that use profiles from reference populations that vary from the corresponding constituent populations in cellular state but not cellular phenotypic identity.
Qiao, Wenlian; Quon, Gerald; Csaszar, Elizabeth; Yu, Mei; Morris, Quaid; Zandstra, Peter W
The cellular composition of heterogeneous samples can be predicted using an expression deconvolution algorithm to decompose their gene expression profiles based on pre-defined, reference gene expression profiles of the constituent populations in these samples. However, the expression profiles of the actual constituent populations are often perturbed from those of the reference profiles due to gene expression changes in cells associated with microenvironmental or developmental effects. Existing deconvolution algorithms do not account for these changes and give incorrect results when benchmarked against those measured by well-established flow cytometry, even after batch correction was applied. We introduce PERT, a new probabilistic expression deconvolution method that detects and accounts for a shared, multiplicative perturbation in the reference profiles when performing expression deconvolution. We applied PERT and three other state-of-the-art expression deconvolution methods to predict cell frequencies within heterogeneous human blood samples that were collected under several conditions (uncultured mono-nucleated and lineage-depleted cells, and culture-derived lineage-depleted cells). Only PERT's predicted proportions of the constituent populations matched those assigned by flow cytometry. Genes associated with cell cycle processes were highly enriched among those with the largest predicted expression changes between the cultured and uncultured conditions. We anticipate that PERT will be widely applicable to expression deconvolution strategies that use profiles from reference populations that vary from the corresponding constituent populations in cellular state but not cellular phenotypic identity.
Zeanah, Charles H; Carter, Alice S; Cohen, Julie; Egger, Helen; Gleason, Mary Margaret; Keren, Miri; Lieberman, Alicia; Mulrooney, Kathleen; Oser, Cindy
The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-5; ZERO TO THREE) is scheduled to be published in 2016. The articles in this section are selective reviews that have been undertaken as part of the process of refining and updating the nosology. They provide the rationales for new disorders, for disorders that had not been included previously in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-3R; ZERO TO THREE, 2005), and for changes in how certain types of disorders are conceptualized. © 2016 Michigan Association for Infant Mental Health.
Lacoh, Claudia Marvine
BackgroundThe developmental transition from depolarizing to hyperpolarizing γ-aminobutyric acid-mediated neurotransmission is primarily mediated by an increase in the amount of the potassium-chloride cotransporter KCC2 during early postnatal life. However, it is not known whether early neuronal activity plays a modulatory role in the expression of total KCC2 mRNA and protein in the immature brain. As general anaesthetics are powerful modulators of neuronal activity, the purpose of this study was to explore how these drugs affect KCC2 expression during the brain growth spurt.MethodsWistar rat pups were exposed to either a single dose or 6 h of midazolam, propofol, or ketamine anaesthesia at postnatal days 0, 5, 10, or 15. KCC2 expression was assessed using immunoblotting, immunohistochemistry, or quantitative polymerase chain reaction analysis up to 3 days post-exposure in the medial prefrontal cortex.ResultsThere was a progressive and steep increase in the expression of KCC2 between birth and 2 weeks of age. Exposure to midazolam, propofol, or ketamine up to 6 h at any investigated stages of the brain growth spurt did not influence the expression of this cotransporter protein.ConclusionI.V. general anaesthetics do not seem to influence developmental expression of KCC2 during the brain growth spurt. © 2013 © The Author .
Anselmo, Henrique M R; Koerting, Lina; Devito, Sarah; van den Berg, Johannes H J; Dubbeldam, Marco; Kwadijk, Christiaan; Murk, Albertinka J
A new 16-day echinoid early life stage (ELS) bioassay was developed to allow for prolonged observation of possible adverse effects during embryogenesis and larval development of the sea urchin Psammechinus miliaris. Subsequently, the newly developed bioassay was applied to study the effects of key marine persistent organic pollutants (POPs). Mortality, morphological abnormalities and larval development stages were quantified at specific time points during the 16-day experimental period. In contrast to amphibians and fish, P. miliaris early life development was not sensitive to dioxin-like toxicity in the prolonged early life stage test. Triclosan (TCS) levels higher than 500 nM were acutely toxic during embryo development. Morphological abnormalities were induced at concentrations higher than 50 nM hexabromocyclododecane (HBCD) and 1000 nM tetrabromobisphenol A (TBBPA). Larval development was delayed above 25 nM HBCD and 500 nM TBBPA. Heptadecafluorooctane sulfonic acid (PFOS) exposure slightly accelerated larval development at 9 days post-fertilization (dpf). However, the accelerated development was no longer observed at the end of the test period (16 dpf). The newly developed 16-day echinoid ELS bioassay proved to be sensitive to toxic effects of POPs that can be monitored for individual echinoid larvae. The most sensitive and dose related endpoint was the number of developmental penalty points. By manipulation of the housing conditions, the reproductive season could be extended from 3 to 9 months per year and the ELS experiments could be performed in artificial sea water as well.
Honda, Ryoko; Kaido, Takanobu; Sugai, Kenji; Takahashi, Akio; Kaneko, Yuu; Nakagwa, Eiji; Sasaki, Masayuki; Otsuki, Taisuke
This study aimed to identify the effect of early hemispherotomy on development in a consecutive series of 12 infants with hemimegalencephaly (HME) demonstrating epileptic encephalopathy. Mean age at onset was 20.4 days (range, 1-140), mean age at surgery was 4.3 months (range, 2-9), and mean follow-up time was 78.8 months (range, 36-121). Eleven patients had a history of early infantile epileptic encephalopathy. Vertical parasagittal hemispherotomy was performed without mortality or severe morbidities. At follow-up, seizure freedom was obtained in 8 patients (66.7%), who showed significantly higher postoperative developmental quotient (DQ) (mean, 31.3; range, 7-61) than those with seizures (mean, 5.5; range, 3-8) (p=0.02). Within the seizure-free group, postoperative DQ correlated with preoperative seizure duration (r=-0.811, p=0.01). Our results showed that shorter seizure duration during early infancy could provide better postoperative DQ in infants with HME and epileptic encephalopathy. © 2013.
Chen, Y; Huang, L; Russo, A F; Solursh, M
Retinoic acid (RA) has been considered as a potential morphogen in the chicken limb and has also been suggested to be involved in early embryonic development. On the basis of biological activity, previous reports suggest that Hensen's node, the anatomical equivalent in the chicken of the Spemann's organizer, may contain RA. Here, by using a molecular assay system, we demonstrate that Hensen's node contains retinoids in a concentration approximately 20 times more than that in the neighboring tissues. Furthermore, stage 6 Hensen's node contains approximately 3 times more retinoid than that of stage 4 embryos. These endogenous retinoids may establish a concentration gradient from Hensen's node to adjacent tissues and play a role in establishing the primary embryonic axis in the vertebrate. The results also suggest that the retinoid concentration in Hensen's node is developmentally regulated.
Parr, Jeremy R; Le Couteur, Ann; Baird, Gillian; Rutter, Michael; Pickles, Andrew; Fombonne, Eric; Bailey, Anthony J
The characteristics of early developmental regression (EDR) were investigated in individuals with ASD from affected relative pairs recruited to the International Molecular Genetic Study of Autism Consortium (IMGSAC). Four hundred and fifty-eight individuals with ASD were recruited from 226 IMGSAC families. Regression before age 36 months occurred in 23.9% of individuals. The observed concordance rate for EDR within sibling pairs (18.9%) was not significantly above the rate expected under independence (13.5%, p = 0.10). The rate of regression in individuals with ASD from multiplex families was similar to that reported in singleton and epidemiological samples. Regression concordance data were not supportive of a separate familial influence on EDR, other than as a part of autism itself.
Ghobadian, Mehdi; Nabiuni, Mohammad; Parivar, Kazem; Fathi, Mojtaba; Pazooki, Jamileh
Magnesium oxide nanoparticles (MgONPs) are used in medicine, manufacturing and food industries. Because of their extensive application in our daily lives, environmental exposure to these nanoparticles is inevitable. The present study examined the effects of MgONPs on zebrafish (Danio rerio) early developmental stages. The results showed that, at different concentrations, MgONPs induced cellular apoptosis and intracellular reactive oxygen species. The hatching rate and survival of embryos decreased in a dose dependent manner. The 96-h LC50 value of MgONPs on zebrafish survival was 428 mg/l and the 48-h EC50 value of MgONPs on zebrafish embryo hatching rate was 175 mg/l. Moreover different types of malformation were observed in exposed embryos. The results demonstrate the toxic effects of MgONPs on zebrafish embryos and emphasize the need for further studies.
Ye, Jieping; Chen, Jianhui; Janardan, Ravi; Kumar, Sudhir
Gene expression in a developing embryo occurs in particular cells (spatial patterns) in a time-specific manner (temporal patterns), which leads to the differentiation of cell fates. Images of a Drosophila melanogaster embryo at a given developmental stage, showing a particular gene expression pattern revealed by a gene-specific probe, can be compared for spatial overlaps. The comparison is fundamentally important to formulating and testing gene interaction hypotheses. Expression pattern comparison is most biologically meaningful when images from a similar time point (developmental stage) are compared. In this paper, we present LdaPath, a novel formulation of Linear Discriminant Analysis (LDA) for automatic developmental stage range classification. It employs multivariate linear regression with the L(1)-norm penalty controlled by a regularization parameter for feature extraction and visualization. LdaPath computes an entire solution path for all values of regularization parameter with essentially the same computational cost as fitting one LDA model. Thus, it facilitates efficient model selection. It is based on the equivalence relationship between LDA and the least squares method for multi-class classifications. This equivalence relationship is established under a mild condition, which we show empirically to hold for many high-dimensional datasets, such as expression pattern images. Our experiments on a collection of 2705 expression pattern images show the effectiveness of the proposed algorithm. Results also show that the LDA model resulting from LdaPath is sparse, and irrelevant features may be removed. Thus, LdaPath provides a general framework for simultaneous feature selection and feature extraction.
Full Text Available Early diagnosis of children with developmental difficulties is one of the most important segments in the process of rehabilitation. It is not only an assessment and evaluation of the functional conditions, but also and detection of the possibilities for treatment and it’s improvement.In our presentation we give the first noticing for diagnostics of children with developmental difficulties in the Republic of Macedonia, the present capacities, possibilities, needs and suggestions for it’s improvement and advancement. Speaking about that we stress the need of multidisciplinary and complete professional team in the present institutions and solving out a number of problems that exist on that plan. It especially relates to the unique terminology, the procedure and involvement of defectologists in the diagnostic process.Having in mind the bio-psycho and social aspects of the personality of children with developmental difficulties, together with the need of a complex diagnostic procedure, we have tried to give the professional activities of all the profiles of professionals that take part in the diagnostic process. So, we give a review of the work of:· physician-pediatrician who is involved in the diagnostics of all children· audiologist who is involved in the diagnostics of children with damaged hearing from a medical point of view.· the clinical psychologist who works in the institute for medical rehabilitation and whose task is to prepare and realize all the necessary tests for the personality of the child with developmental difficulties.· physiologist for children with somatic damages.· neuropsychiatrist for children with psychological difficulties· specialist for eye diseases giving his report about the child’s damaged eyesight etc.We consider that we shouldn’t neglect the role of the defectologist, his examinations on psycho-motor status, speech, i. e. the functions of the individual in relation to the social aspect in a close
Kung, Tiffany S; Richardson, Jason R; Cooper, Keith R; White, Lori A
Pyrethroids are commonly used insecticides that are considered to pose little risk to human health. However, there is an increasing concern that children are more susceptible to the adverse effects of pesticides. We used the zebrafish model to test the hypothesis that developmental exposure to low doses of the pyrethroid deltamethrin results in persistent alterations in dopaminergic gene expression, neurochemistry, and locomotor activity. Zebrafish embryos were treated with deltamethrin (0.25-0.50 μg/l), at concentrations below the LOAEL, during the embryonic period [3-72 h postfertilization (hpf)], after which transferred to fresh water until the larval stage (2-weeks postfertilization). Deltamethrin exposure resulted in decreased transcript levels of the D1 dopamine (DA) receptor (drd1) and increased levels of tyrosine hydroxylase at 72 hpf. The reduction in drd1 transcripts persisted to the larval stage and was associated with decreased D2 dopamine receptor transcripts. Larval fish, exposed developmentally to deltamethrin, had increased levels of homovanillic acid, a DA metabolite. Since the DA system is involved in locomotor activity, we measured the swim activity of larval fish following a transition to darkness. Developmental exposure to deltamethrin significantly increased larval swim activity which was attenuated by concomitant knockdown of the DA transporter. Acute exposure to methylphenidate, a DA transporter inhibitor, increased swim activity in control larva, while reducing swim activity in larva developmentally exposed to deltamethrin. Developmental exposure to deltamethrin causes locomotor deficits in larval zebrafish, which is likely mediated by dopaminergic dysfunction. This highlights the need to understand the persistent effects of low-dose neurotoxicant exposure during development.
Emily A. Greene-Colozzi
Full Text Available Tuberous sclerosis complex (TSC is an autosomal dominant disorder characterized by tumor growth and neuropsychological symptoms such as autistic behavior, developmental delay, and epilepsy. While research has shed light on the biochemical and genetic etiology of TSC, the pathogenesis of the neurologic and behavioral manifestations remains poorly understood. TSC patients have a greatly increased risk of developmental delay and autism spectrum disorder, rendering the relationship between the two sets of symptoms an extremely pertinent issue for clinicians. We have expanded on previous observations of aberrant vocalizations in Tsc2+/− mice by testing vocalization output and developmental milestones systematically during the early postnatal period. In this study, we have demonstrated that Tsc2 haploinsufficiency in either dams or their pups results in a pattern of developmental delay in sensorimotor milestones and ultrasonic vocalizations.
Full Text Available Detailed information about stage-specific changes in gene expression is crucial for the understanding of the gene regulatory networks underlying development. Here, we describe the global gene expression dynamics during early flower development, a key process in the life cycle of a plant, during which floral patterning and the specification of floral organs is established. We used a novel floral induction system in Arabidopsis, which allows the isolation of a large number of synchronized floral buds, in conjunction with whole-genome microarray analysis to identify genes with differential expression at distinct stages of flower development. We found that the onset of flower formation is characterized by a massive downregulation of genes in incipient floral primordia, which is followed by a predominance of gene activation during the differentiation of floral organs. Among the genes we identified as differentially expressed in the experiment, we detected a significant enrichment of closely related members of gene families. The expression profiles of these related genes were often highly correlated, indicating similar temporal expression patterns. Moreover, we found that the majority of these genes is specifically up-regulated during certain developmental stages. Because co-expressed members of gene families in Arabidopsis frequently act in a redundant manner, these results suggest a high degree of functional redundancy during early flower development, but also that its extent may vary in a stage-specific manner.
Williamson, G. L.
Individual growth curves yield insights about growth that are not available from any other methodology; and, developmental scales based on conjoint measurement models provide unique interpretive advantages for investigations of academic growth. Benefits are demonstrated in three examples. First, a series of fifteen statewide reading growth curves is annotated with historical policy actions related to assessment, accountability and early interventions. Second, a common measurement framework simultaneously addresses five interpretive perspectives—student reading growth; achievement level standards; K-12 text complexity standards; postsecondary reading demands; and, occupational reading demands. Third, incremental velocity norms are introduced for average reading growth based on a parametric mathematical model for individual growth curves.
Vincent eVan Waes
Full Text Available Corticostriatal circuits mediate various aspects of goal-directed behavior and are critically important for basal ganglia-related disorders. Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains. We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. We also assessed changes in CB1 expression in the striatum during development. Our results show that CB1 expression is highest in juveniles (P25 and then progressively decreases towards adolescent (P40 and adult (P70 levels. At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. Moreover, for most corticostriatal circuits there is an inverse relationship between cortical and striatal expression levels. Thus, striatal sectors with high CB1 expression (sensorimotor sectors tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors receive inputs from cortical regions with higher expression (medial prefrontal cortex. In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important.
Pingping QU; Wenru TIAN; Tao LI; Zhongling JIANG; Shansong GAO; Zhongjie TIAN; Mingzhi WANG
Mouse early blastocysts were exposed to temporatures of 39℃ and 41℃ for 2 h,respectively,to determine their developmental competence and uhrastructural changes. The results showed that heat stress at 41 ℃ for 2 h,significantly reduced the percentages of expanded and hatched blastocysts,but not at 39℃ for 2 h. The average cell numbers in expanded blastocysts,which developed from early blastocysts heat-stressed at temperatures of 39℃ and 41 ℃,were significantly reduced. The average cell numbers in hatched blastocysts subjected to heat stress were no different from those in the control group cultured at 37℃ . The mitochondria of the early blastocysts heat-stressed at 39T℃ for 2 h,were slightly swollen,but they had recovered after culturing at 37℃ for 2 h. However,the mitochondria in the blastocysts heat stressed at 41 ℃ for 2 h were severely swollen,and their number increased. The ribosomes shed from the rough endoplasmic reticulum,and the number of secondary lysosomes in the plasma increased. The integrity of desmosomes was disrupted. The space between the nuclear envelope and the perivitelline membrane enlarged. The fibre fraction and the particulate fraction of nucleoli were separated. The heterochromatin in nucleoli was also increased in its quantity. There were some lamellar-shape structures and heterogeneous dense materials exhibiting in the cytoplasm. The ultrastructural changes induced by heat shock at 41 ℃ for 2 h were not reversible. In conclusion,the damage of heat stress to mitochondria,lysosomes,ribosomes and cell nucleus,may be one of the most important factors that inhibit the normal development of mouse early blastocysts.
Kyle E Godden
Full Text Available Hypocretin/Orexin (H/O neuropeptides are released by a discrete group of neurons in the vertebrate hypothalamus which play a pivotal role in the maintenance of waking behavior and brain state control. Previous studies have indicated that the H/O neuronal development differs between mammals and fish; H/O peptide-expressing cells are detectable during the earliest stages of brain morphogenesis in fish, but only towards the end of brain morphogenesis (by ∼ 85% of embryonic development in rats. The developmental emergence of H/O neurons has never been previously described in birds. With the goal of determining whether the chick developmental pattern was more similar to that of mammals or of fish, we investigated the emergence of H/O-expressing cells in the brain of chick embryos of different ages using immunohistochemistry. Post-natal chick brains were included in order to compare the spatial distribution of H/O cells with that of other vertebrates. We found that H/O-expressing cells appear to originate from two separate places in the region of the diencephalic proliferative zone. These developing cells express the H/O neuropeptide at a comparatively early age relative to rodents (already visible at 14% of the way through fetal development, thus bearing a closer resemblance to fish. The H/O-expressing cell population proliferates to a large number of cells by a relatively early embryonic age. As previously suggested, the distribution of H/O neurons is intermediate between that of mammalian and non-mammalian vertebrates. This work suggests that, in addition to its roles in developed brains, the H/O peptide may play an important role in the early embryonic development of non-mammalian vertebrates.
Full Text Available BACKGROUND: MicroRNAs (miRNAs play crucial roles in various physiological processes through post-transcriptional regulation of gene expressions and are involved in development, metabolism, and many other important molecular mechanisms and cellular processes. The Bombyx mori genome sequence provides opportunities for a thorough survey for miRNAs as well as comparative analyses with other sequenced insect species. METHODOLOGY/PRINCIPAL FINDINGS: We identified 114 non-redundant conserved miRNAs and 148 novel putative miRNAs from the B. mori genome with an elaborate computational protocol. We also sequenced 6,720 clones from 14 developmental stage-specific small RNA libraries in which we identified 35 unique miRNAs containing 21 conserved miRNAs (including 17 predicted miRNAs and 14 novel miRNAs (including 11 predicted novel miRNAs. Among the 114 conserved miRNAs, we found six pairs of clusters evolutionarily conserved cross insect lineages. Our observations on length heterogeneity at 5' and/or 3' ends of nine miRNAs between cloned and predicted sequences, and three mature forms deriving from the same arm of putative pre-miRNAs suggest a mechanism by which miRNAs gain new functions. Analyzing development-related miRNAs expression at 14 developmental stages based on clone-sampling and stem-loop RT PCR, we discovered an unusual abundance of 33 sequences representing 12 different miRNAs and sharply fluctuated expression of miRNAs at larva-molting stage. The potential functions of several stage-biased miRNAs were also analyzed in combination with predicted target genes and silkworm's phenotypic traits; our results indicated that miRNAs may play key regulatory roles in specific developmental stages in the silkworm, such as ecdysis. CONCLUSIONS/SIGNIFICANCE: Taking a combined approach, we identified 118 conserved miRNAs and 151 novel miRNA candidates from the B. mori genome sequence. Our expression analyses by sampling miRNAs and real-time PCR over
Bodrova, Elena; Leong, Deborah J.; Paynter, Diane E.; Semenov, Dmitri
This document is designed to establish consistency in the definition and format to be used in developing early literacy standards and benchmarks. It articulates a set of standards and benchmarks that is based on current national and state standards documents and that reflects the foundational knowledge and developmental differences representative…
Ozernov-Palchik, Ola; Gaab, Nadine
Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5-17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in pre-reading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure.
Konishi, Yukihiko; Okubo, Kensuke; Kato, Ikuko; Ijichi, Sonoko; Nishida, Tomoko; Kusaka, Takashi; Isobe, Kenichi; Itoh, Susumu; Kato, Masaharu; Konishi, Yukuo
The purpose of this study was to examine developmental changes in visuocognitive function, particularly face recognition, in early infancy. In this study, we measured eye movement in healthy infants with a preference gaze problem, particularly eye movement between two face stimulations. We used the eye tracker system (Tobii1750, Tobii Technologies, Sweden) to measure eye movement in infants. Subjects were 17 3-month-old infants and 16 4-month-old infants. The subjects looked two types of face stimulation (upright face/scrambled face) at the same time and we measured their visual behavior (preference/looking/eye movement). Our results showed that 4-month-old infants looked at an upright face longer than 3-month infants, and exploratory behavior while comparing two face stimulations significantly increased. In this study, 4-month-old infants showed a preference towards an upright face. The numbers of eye movements between two face stimuli significantly increased in 4-month-old infants. These results suggest that eye movements may be an important index in face cognitive function during early infancy. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Ozernov-Palchik, Ola; Gaab, Nadine
Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5–17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in prereading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure. PMID:26836227
Upstream regulatory region and flanking DNA of yellow gene wereisolated and cloned from a Drosophila genomic library. A vector containing yellow gene and regulatory elements was constructed using the recombinant DNA technique. Then this vector was integrated into Drosophila genome by genetic transformation. Using both FLP/FRT and Cre/LoxP site-specific recombination systems, two new yellow alleles were created at the same position in the genome of transgenic flies. Results from genetic and molecular analysis indicated that transcriptional enhancers regulate the developmental expression of the transgene. Furthermore, interactions between new-created yellow alleles were observed. Such interactions can influence markedly the expression of yellow gene during development. This effect may also be a form of enhancer-mediated gene expression.
Wang, Zheng; Lehr, Nina; Trail, Frances; Townsend, Jeffrey P
Fungal fruiting body size and form are influenced by the ecology of the species, including diverse environmental stimuli. Accordingly, nutritional resources available to the fungus during development can be vital to successful production of fruiting bodies. To investigate the effect of nutrition, perithecial development of Neurospora crassa was induced on two different media, a chemically sparsely nutritive Synthetic Crossing Medium (SCM) and a natural Carrot Agar (CA). Protoperithecia were collected before crossing, and perithecia were collected at 2, 24, 48, 72, 96, 120, and at full maturity 144 h after crossing. No differences in fruiting body morphology were observed between the two media at any time point. A circuit of microarray hybridizations comparing cDNA from all neighboring stages was performed. For a majority of differentially expressed genes, expression was higher in SCM than in CA, and expression of core metabolic genes was particularly affected. Effects of nutrition were highest in magnitude before crossing, lowering in magnitude during early perithecial development. Interestingly, metabolic effects of the media were also large in magnitude during late perithecial development, at which stage the lower expression in CA presumably reflected the continued intake of diverse complex initial compounds, diminishing the need for expression of anabolic pathways. However, for genes with key regulatory roles in sexual development, including pheromone precursor ccg-4 and poi2, expression patterns were similar between treatments. When possible, a common nutritional environment is ideal for comparing transcriptional profiles between different fungi. Nevertheless, the observed consistency of the developmental program across media, despite considerable metabolic differentiation is reassuring. This result facilitates comparative studies that will require different nutritional resources for sexual development in different fungi.
Lee, Young Mee; Yang, In Jung; Noh, Jae Koo; Kim, Hyun Chul; Park, Choul-Ji; Park, Jong-Won; Noh, Gyeong Eon; Kim, Woo-Jin; Kim, Kyung-Kil
Lectins belong to the pattern-recognition receptors (PRRs) class and play important roles in the recognition and elimination of pathogens via the innate immune system. Recently, it was reported that lily-type lectin-1 is involved when a pathogen attacks in the early immune response of fish. However, this study is limited to information that the lectin is involved in the innate immune response against viral infection. In the present study, the lily-type lectin-2 and -3 of Oplegnathus fasciatus (OfLTL-2 and 3) have been presented to be included B-lectin domain and two D-mannose binding sites in the amino acid sequence that an important feature for the fundamental structure. To investigate the functional properties of OfLTLs, the tissue distribution in the healthy rock bream and temporal expression during early developmental stage analysis are performed using quantitative real-time PCR. OfLTL-2 and 3 are predominantly expressed in the liver and skin, but rarely expressed in other organ. Also, the transcripts of OfLTLs are not expressed during the early developmental stage but its transcripts are increased after immune-related organs which are fully formed. In the challenge experiment with RBIV (rock bream iridovirus), the expression of OfLTLs was increased much more strongly in the late response than the early, unlike previously known. These results suggest that OfLTLs are specifically expressed in the immune-related tissues when those organs are fully formed and it can be inferred that the more intensively involved in the second half to the virus infection.
Kathryn C Calhoun
Full Text Available Bisphenol A (BPA exposure results in numerous developmental and functional abnormalities in reproductive organs in rodent models, but limited data are available regarding BPA effects in the primate uterus. To determine if maternal oral BPA exposure affects fetal uterine development in a non-human primate model, pregnant rhesus macaques carrying female fetuses were exposed orally to 400 µg/kg BPA or vehicle control daily from gestation day (GD 50-100 or GD100-165. Fetal uteri were collected at the completion of treatment (GD100 or GD165; tissue histology, cell proliferation, and expression of estrogen receptor alpha (ERα and progesterone receptor (PR were compared to that of controls. Gene expression analysis was conducted using rhesus macaque microarrays. There were no significant differences in histology or in the percentage of cells expressing the proliferation marker Ki-67, ERα, or PR in BPA-exposed uteri compared to controls at GD100 or GD165. Minimal differences in gene expression were observed between BPA-exposed and control GD100 uteri. However, at GD165, BPA-exposed uteri had significant differences in gene expression compared to controls. Several of the altered genes, including HOXA13, WNT4, and WNT5A, are critical for reproductive organ development and/or adult function. We conclude that second or third trimester BPA exposure does not significantly affect fetal uterus development based on morphological, proliferation, and steroid hormone receptor assessments. However, differences in expression of key developmental genes after third trimester exposure suggest that BPA could alter transcriptional signals influencing uterine function later in life.
Arockiaraj, Jesu; Easwvaran, Sarasvathi; Vanaraja, Puganeshwaran; Singh, Arun; Othman, Rofina Yasmin; Bhassu, Subha
This study reports the first full length gene of interferon related developmental regulator-1 (designated as MrIRDR-1), identified from the transcriptome of Macrobrachium rosenbergii. The complete gene sequence of the MrIRDR-1 is 2459 base pair long with an open reading frame of 1308 base pairs and encoding a predicted protein of 436 amino acids with a calculated molecular mass of 48 kDa. The MrIRDR-1 protein contains a long interferon related developmental regulator super family domain between 30 and 330. The mRNA expressions of MrIRDR-1 in healthy and the infectious hypodermal and hematopoietic necrosis virus (IHHNV) infected M. rosenbergii were examined using qRT-PCR. The MrIRDR-1 is highly expressed in hepatopancreas along with all other tissues (walking leg, gills, muscle, haemocyte, pleopods, brain, stomach, intestine and eye stalk). After IHHNV infection, the expression is highly upregulated in hepatopancreas. This result indicates an important role of MrIRDR-1 in prawn defense system.
Lehner, R; Cui, Z; Vance, D E
The mechanism and enzymic activities responsible for the lipolysis of stored cytosolic triacylglycerol in liver and its re-esterification remain obscure. A candidate enzyme for lipolysis, a microsomal triacylglycerol hydrolase (TGH), was recently purified to homogeneity from pig liver and its kinetic properties were determined [Lehner and Verger (1997) Biochemistry 36, 1861-1868]. We have characterized the enzyme with regard to its species distribution, subcellular localization, developmental expression and reaction with lipase inhibitors. The hydrolase co-sediments with endoplasmic reticulum elements and is associated with isolated liver fat droplets. Immunocytochemical studies localize TGH exclusively to liver cells surrounding capillaries. Both TGH mRNA and protein are expressed in rats during weaning. The enzyme covalently binds tetrahydrolipstatin, an inhibitor of lipases and of triacylglycerol hydrolysis. The enzyme is absent from liver-derived cell lines (HepG2 and McArdle RH7777) known to be impaired in very-low-density lipoprotein (VLDL) assembly and secretion. The localization and developmental expression of TGH are consistent with a proposed role in triacylglycerol hydrolysis and with the proposal that some of the resynthesized triacylglycerol is utilized for VLDL secretion.
Kim, Young Ok; Joo, Sung-Pil; Seo, Bo-Ra; Rho, Young Il; Yoon, Woong; Woo, Young Jong
The objective is to clarify the early clinical characteristics in childhood moyamoya disease (MD). Epidemiologic characteristics, symptoms and diagnostic rates were assessed in 64 children (0-18 years) with definite MD according to developmental stage: infancy (5; 0-1 years); toddlerhood/preschool age (22; 2-5 years); school age (29; 6-10 years); and adolescence (8; 11-18 years). The median ages at onset was 6.25 years and the female to male ratio was 1.9 (~2.5 in toddlerhood/preschool age and in adolescence, P=0.71). Previous headache was observed in 23% (14/64): frequently in school age (38%, P=0.02) and within 6 months before main symptoms (6/11). As an initial symptom, weakness was observed in 78% (50/64) mainly as transient ischemic attack (TIA, 61%) in limbs (90%) and unilaterally (82%). TIA was less frequent in infancy (40%, P=0.04). Seizure was observed in 27% (17/64): frequently in infancy (100%, Pchildren ~5 years (P<0.01). Severe headache associated with MD was observed in 14% (9/64). Provoking events were positive in 42% (27/64): in school age, frequently during eating (28%); and in toddlerhood/preschool age, during crying (27%). The diagnostic rates at 3 and 12 months from symptom-onset were 39% (80% during infancy vs. 28% in school age, P=0.14) and 67%, respectively. Symptomatic progression at diagnosis was observed in 38% (24/64). Initial clinical characteristics in childhood definite MD differed according to developmental stage and from at diagnosis.
Full Text Available Nuclear receptors (NRs are transcription factors that are implicated in several biological processes such as embryonic development, homeostasis, and metabolic diseases. To study the role of NRs in development, it is critically important to know when and where individual genes are expressed. Although systematic expression studies using reverse transcriptase PCR and/or DNA microarrays have been performed in classical model systems such as Drosophila and mouse, no systematic atlas describing NR involvement during embryonic development on a global scale has been assembled. Adopting a systems biology approach, we conducted a systematic analysis of the dynamic spatiotemporal expression of all NR genes as well as their main transcriptional coregulators during zebrafish development (101 genes using whole-mount in situ hybridization. This extensive dataset establishes overlapping expression patterns among NRs and coregulators, indicating hierarchical transcriptional networks. This complete developmental profiling provides an unprecedented examination of expression of NRs during embryogenesis, uncovering their potential function during central nervous system and retina formation. Moreover, our study reveals that tissue specificity of hormone action is conferred more by the receptors than by their coregulators. Finally, further evolutionary analyses of this global resource led us to propose that neofunctionalization of duplicated genes occurs at the levels of both protein sequence and RNA expression patterns. Altogether, this expression database of NRs provides novel routes for leading investigation into the biological function of each individual NR as well as for the study of their combinatorial regulatory circuitry within the superfamily.
Full Text Available Nuclear receptors (NRs are transcription factors that are implicated in several biological processes such as embryonic development, homeostasis, and metabolic diseases. To study the role of NRs in development, it is critically important to know when and where individual genes are expressed. Although systematic expression studies using reverse transcriptase PCR and/or DNA microarrays have been performed in classical model systems such as Drosophila and mouse, no systematic atlas describing NR involvement during embryonic development on a global scale has been assembled. Adopting a systems biology approach, we conducted a systematic analysis of the dynamic spatiotemporal expression of all NR genes as well as their main transcriptional coregulators during zebrafish development (101 genes using whole-mount in situ hybridization. This extensive dataset establishes overlapping expression patterns among NRs and coregulators, indicating hierarchical transcriptional networks. This complete developmental profiling provides an unprecedented examination of expression of NRs during embryogenesis, uncovering their potential function during central nervous system and retina formation. Moreover, our study reveals that tissue specificity of hormone action is conferred more by the receptors than by their coregulators. Finally, further evolutionary analyses of this global resource led us to propose that neofunctionalization of duplicated genes occurs at the levels of both protein sequence and RNA expression patterns. Altogether, this expression database of NRs provides novel routes for leading investigation into the biological function of each individual NR as well as for the study of their combinatorial regulatory circuitry within the superfamily.
Mukhopadhyay, Partha; Brock, Guy; Pihur, Vasyl; Webb, Cynthia; Pisano, M. Michele; Greene, Robert M.
BACKGROUND Orofacial development is a multifaceted process involving precise, spatio-temporal expression of a panoply of genes. MicroRNAs (miRNAs), the largest family of noncoding RNAs involved in gene silencing, represent critical regulators of cell and tissue differentiation. MicroRNA gene expression profiling is an effective means of acquiring novel and valuable information regarding the expression and regulation of genes, under the control of miRNA, involved in mammalian orofacial development. METHODS To identify differentially expressed miRNAs during mammalian orofacial ontogenesis, miRNA expression profiles from gestation day (GD) -12, -13 and -14 murine orofacial tissue were compared utilizing miRXplore microarrays from Miltenyi Biotech. Quantitative real-time PCR was utilized for validation of gene expression changes. Cluster analysis of the microarray data was conducted with the clValid R package and the UPGMA clustering method. Functional relationships between selected miRNAs were investigated using Ingenuity Pathway Analysis. RESULTS Expression of over 26% of the 588 murine miRNA genes examined was detected in murine orofacial tissues from GD-12–GD-14. Among these expressed genes, several clusters were seen to be developmentally regulated. Differential expression of miRNAs within such clusters were shown to target genes encoding proteins involved in cell proliferation, cell adhesion, differentiation, apoptosis and epithelial-mesenchymal transformation, all processes critical for normal orofacial development. CONCLUSIONS Using miRNA microarray technology, unique gene expression signatures of hundreds of miRNAs in embryonic orofacial tissue were defined. Gene targeting and functional analysis revealed that the expression of numerous protein-encoding genes, crucial to normal orofacial ontogeny, may be regulated by specific miRNAs. PMID:20589883
Full Text Available Translocator protein (TSPO present in the outer mitochondrial membrane has been suggested to be critical for cholesterol import, a rate-limiting step for steroid hormone biosynthesis. Despite the importance of steroidogenesis in regulating reproductive functions, the developmental profile of TSPO expression in the gonads and accessory sex organs has not been completely characterized. As a first step towards understanding the function of TSPO, we studied its expression in male and female murine reproductive organs. We examined testes and ovaries at embryonic days 14.5 and 18.5, and postnatal days 0, 7, 14, 21 and 56 of development. In the adult testis, TSPO was expressed in both Leydig cells and Sertoli cells. In the developing testes TSPO expression was seen in immature Sertoli cells, fetal Leydig cells and gonocytes. In the ovary, TSPO was expressed in the ovarian surface epithelium, interstitial cells granulosa cells and luteal cells. Corpora lutea of ovaries from pregnant mice showed strong expression of TSPO. In the developing ovary, TSPO expression was seen in the squamous pregranulosa cells associated with germ line cysts, together with progressively increasing expression in interstitial cells and the ovarian surface epithelium. In adult mice, the epithelia of other reproductive tissues like the epididymis, prostate, seminal vesicle, oviduct and uterus also showed distinct patterns of TSPO expression. In summary, TSPO expression in both male and female reproductive tissues was not only restricted to steroidogenic cells. Expression in Sertoli cells, ovarian surface epithelium, efferent ductal epithelium, prostatic epithelium, seminal vesiclular epithelium, uterine epithelium and oviductal epithelium suggest either previously unknown sites for de novo steroidogenesis or functions for TSPO distinct from its well-studied role in steroid hormone production.
Säfholm, Moa; Jansson, Erika; Fick, Jerker; Berg, Cecilia
There is an increasing concern regarding the risks associated with developmental exposure to endocrine disrupting chemicals and the consequences for reproductive capability. The present study aimed to refine the Xenopus (Silurana) tropicalis test system for developmental reproductive toxicity by characterising molecular and histological features of sexual development, and to explore effects of exposure to the progestagen levonorgestrel (LNG). Larvae were exposed to LNG (0, 3, 30, 300 ng/L) over the first three weeks of development, encompassing the beginning of gonadal differentiation. mRNA levels of amh (anti-Müllerian hormone), amhr2 (amh receptor 2), ipgr (intracellular progesterone receptor), mpgr beta (membrane progesterone receptor beta), and cyp19a1 (cytochrome p450 19a1) were quantified in larvae and juveniles (4 weeks post-metamorphosis). Relative cyp19a1 and amh expression was used as a molecular marker for phenotypic sex of larvae. Gonadal and Müllerian duct development were characterised histologically in juveniles. Compared to controls, LNG exposure increased the expression of amh and ipgr in male larvae. In juveniles, mpgr beta expression was increased in both sexes and amhr2 expression was decreased in males, implying persistent effects of developmental progestagen exposure on amh and pgr expression signalling. No effects of LNG on the gonadal or Müllerian duct development were found, implying that the exposure window was not critical with regard to these endpoints. In juveniles, folliculogenesis had initiated and the Müllerian ducts were larger in females than in males. This new knowledge on sexual development in X. tropicalis is useful in the development of early life-stage endpoints for developmental reproductive toxicity.
Conforto Tara L
Full Text Available Abstract Background Early liver development and the transcriptional transitions during hepatogenesis are well characterized. However, gene expression changes during the late postnatal/pre-pubertal to young adulthood period are less well understood, especially with regards to sex-specific gene expression. Methods Microarray analysis of male and female mouse liver was carried out at 3, 4, and 8 wk of age to elucidate developmental changes in gene expression from the late postnatal/pre-pubertal period to young adulthood. Results A large number of sex-biased and sex-independent genes showed significant changes during this developmental period. Notably, sex-independent genes involved in cell cycle, chromosome condensation, and DNA replication were down regulated from 3 wk to 8 wk, while genes associated with metal ion binding, ion transport and kinase activity were up regulated. A majority of genes showing sex differential expression in adult liver did not display sex differences prior to puberty, at which time extensive changes in sex-specific gene expression were seen, primarily in males. Thus, in male liver, 76% of male-specific genes were up regulated and 47% of female-specific genes were down regulated from 3 to 8 wk of age, whereas in female liver 67% of sex-specific genes showed no significant change in expression. In both sexes, genes up regulated from 3 to 8 wk were significantly enriched (p p Ihh; female-specific Cdx4, Cux2, Tox, and Trim24 and may contribute to the developmental changes that lead to global acquisition of liver sex-specificity by 8 wk of age. Conclusions Overall, the observed changes in gene expression during postnatal liver development reflect the deceleration of liver growth and the induction of specialized liver functions, with widespread changes in sex-specific gene expression primarily occurring in male liver.
de Lecea, L; del Río, J A; Soriano, E
Parvalbumin (PARV) belongs to the family of calcium-binding proteins bearing the EF hand domain. Immunocytochemical studies in the cerebral cortex have demonstrated that neurons containing PARV include two types of GABAergic interneurons, namely, basket and axo-axonic chandelier cells. The present study examines the onset and pattern of PARV mRNA expression during the development of rat neocortex and hippocampus by means of 'in situ' hybridization with an oligonucleotide probe corresponding to rat PARV cDNA. In animals aged P0-P6 no signal was detected above background in neocortex or hippocampus. At P8, a few cortical cells displayed a number of silver grains just above background levels. By P10 PARV mRNA-expressing cells in the neocortex were detected almost exclusively in layer V of somatosensory, frontal and cingulate cortices. At P12 PARV mRNA was mainly detected in layers IV, V and VIa. By P14 there was a marked overall increase in the entire neocortex, including layer II-III, both in the number of cells and in their intensity of labelling. Further maturation in the pattern of PARV mRNA concentration was observed between P16 and P21. In the hippocampus low hybridization was observed at P10-P12. In subsequent stages both the number of positive cells and the intensity of labelling increased steadily. No clear-cut radial gradients for the expression of PARV mRNA were observed in the hippocampal region. Our results show that the developmental radial gradient followed by PARV mRNA expression in the neocortex does not follow an 'inside-out' gradient, consistent with previous immunocytochemical findings. Taken together, these data indicate that the developmental sequence followed by the PARV protein directly reflects mRNA abundance and suggest that PARV mRNA expression correlates with the functional maturation of cortical interneurons.
Gissot, Mathieu; Kim, Kami; Schaap, Dick; Ajioka, James W
The phylum Apicomplexa consists of obligate intracellular protistan parasites, some of which are responsible for global disease causing serious morbidity and mortality in humans and animals. Understanding the mechanisms of gene expression that drive the cellular changes required to complete their life cycles will be critical in combating infection and disease. Plasmodium spp. and Toxoplasma gondii have served as good models for growth and development in the Apicomplexa. Elucidating developmental gene expression relies on comparisons with known mechanisms and their DNA, RNA and protein components. Transcriptional profiling across asexual development suggests a model where a cascade of gene expression results in a "just-in-time" production process that makes products only when needed. Some mechanisms that control transcription such as chromatin/histone modification are highly conserved in the phylum compared with the traditional model organisms, yeast, worms, flies and mammals. Studies exploiting this phenomenon show great potential for both investigating the effects of chromatin structure on developmental gene expression, and helping to identify genes that are expressed in a stage-specific manner. Transcription factors and their cognate cis-acting binding sites have been difficult to identify. This may be because the DNA binding motifs that have evolved to act as transcription factors in the Apicomplexa, e.g. the AP2 family, may be more like plants than the traditional model organisms. A new eukaryotic phylogenetic model comprised of six super-groups divides the traditional model organisms, plants and the Apicomplexa into separate super-groups. This phylogenetic model helps explain why basic functions such as transcriptional regulation appear be a composite of mechanisms in the Apicomplexa compared with what is known from other eukaryotes.
Matsuoka, S; Ebihara, Y; Xu, M; Ishii, T; Sugiyama, D; Yoshino, H; Ueda, T; Manabe, A; Tanaka, R; Ikeda, Y; Nakahata, T; Tsuji, K
The CD34 antigen serves as an important marker for primitive hematopoietic cells in therapeutic transplantation of hematopoietic stem cells (HSC) and gene therapy, but it has remained an open question as to whether or not most HSC express CD34. Using a competitive long-term reconstitution assay, the results of this study confirm developmental changes in CD34 expression on murine HSC. In fetuses and neonates, CD34 was expressed on Lin(-)c-Kit(+) long-term repopulating HSC of bone marrow (BM), liver, and spleen. However, CD34 expression on HSC decreased with aging, and in mice older than 10 weeks, HSC were most enriched in the Lin(-)c-Kit(+)CD34(-) marrow cell fraction. A second transplantation was performed from primary recipients who were transplanted with neonatal Lin(-)c-Kit(+) CD34(high) HSC marrow. Although donor-type HSC resided in CD34-expressing cell fraction in BM cells of the first recipients 4 weeks after the first transplantation, the stem cell activity had shifted to Lin(-)c-Kit(+)CD34(-) cells after 16 weeks, indicating that adult Lin(-)c-Kit(+)CD34(-) HSC are the progeny of neonatal CD34-expresssing HSC. Assays for colony-forming cells showed that hematopoietic progenitor cells, unlike HSC, continue to express CD34 throughout murine development. The present findings are important because the clinical application of HSC can be extended, in particular as related to CD34-enriched HSC and umbilical cord blood HSC.
Full Text Available The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v ethanol for the first 8 days of gestation (GD 0.5-8.5. Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60: we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in
Full Text Available Neonatal feeding problems are observed in several genetic diseases including Prader-Willi syndrome (PWS. Later in life, individuals with PWS develop hyperphagia and obesity due to lack of appetite control. We hypothesized that failure to thrive in infancy and later-onset hyperphagia are related and could be due to a defect in the hypothalamus. In this study, we performed gene expression microarray analysis of the hypothalamic response to maternal deprivation in neonatal wild-type and Snord116del mice, a mouse model for PWS in which a cluster of imprinted C/D box snoRNAs is deleted. The neonatal starvation response in both strains was dramatically different from that reported in adult rodents. Genes that are affected by adult starvation showed no expression change in the hypothalamus of 5 day-old pups after 6 hours of maternal deprivation. Unlike in adult rodents, expression levels of Nanos2 and Pdk4 were increased, and those of Pgpep1, Ndp, Brms1l, Mett10d, and Snx1 were decreased after neonatal deprivation. In addition, we compared hypothalamic gene expression profiles at postnatal days 5 and 13 and observed significant developmental changes. Notably, the gene expression profiles of Snord116del deletion mice and wild-type littermates were very similar at all time points and conditions, arguing against a role of Snord116 in feeding regulation in the neonatal period.
Rivers, Elena R; Horton, Anthony J; Hawk, Angela F; Favre, Elizabeth G; Senf, Katherine M; Nietert, Paul J; Chang, Eugene Y; Foley, Ann C; Robinson, Christopher J; Lee, Kyu-Ho
Preeclampsia (PE) affects 2-8% of pregnancies worldwide and is a significant source of maternal and neonatal morbidity and mortality. However, the mechanisms underlying PE are poorly understood and major questions regarding etiology and risk factors remain to be addressed. Our objective was to examine whether abnormal expression of the cardiovascular developmental transcription factor, Nkx2-5, was associated with early onset and severe preeclampsia (EOSPE). Using qPCR and immunohistochemical assay, we examined expression of Nkx2-5 and target gene expression in EOSPE and control placental tissue. We tested resulting mechanistic hypotheses in cultured cells using shRNA knockdown, qPCR, and western blot. Nkx2-5 is highly expressed in racially disparate fashion (Caucasians > African Americans) in a subset of early EOSPE placentae. Nkx2-5 mRNA expression is highly correlated (Caucasians > African Americans) to mRNA expression of the preeclampsia marker sFlt-1, and of the Nkx2-5 target and RNA splicing factor, Sam68. Knockdown of Sam68 expression in cultured cells significantly impacts sFlt-1 mRNA isoform generation in vitro, supporting a mechanistic hypothesis that Nkx2-5 impacts EOSPE severity in a subset of patients via upregulation of Sam68 to increase sFlt-1 expression. Expression of additional Nkx2-5 targets potentially regulating metabolic stress response is also elevated in a racially disparate fashion in EOSPE. Expression of Nkx2-5 and its target genes may directly influence the genesis and racially disparate severity, and define a mechanistically distinct subclass of EOSPE.
Sullivan, Regina; Wilson, Donald A; Feldon, Joram; Yee, Benjamin K; Meyer, Urs; Richter-Levin, Gal; Avi, Avital; Michael, Tsoory; Gruss, Michael; Bock, Jörg; Helmeke, Carina; Braun, Katharina
Decades of research in the area of developmental psychobiology have shown that early life experience alters behavioral and brain development, which canalizes development to suit different environments. Recent methodological advances have begun to identify the mechanisms by which early life experiences cause these diverse adult outcomes. Here we present four different research programs that demonstrate the intricacies of early environmental influences on behavioral and brain development in both pathological and normal development. First, an animal model of schizophrenia is presented that suggests prenatal immune stimulation influences the postpubertal emergence of psychosis-related behavior in mice. Second, we describe a research program on infant rats that demonstrates how early odor learning has unique characteristics due to the unique functioning of the infant limbic system. Third, we present work on the rodent Octodon degus, which shows that early paternal and/or maternal deprivation alters development of limbic system synaptic density that corresponds to heightened emotionality. Fourth, a juvenile model of stress is presented that suggests this developmental period is important in determining adulthood emotional well being. The approach of each research program is strikingly different, yet all succeed in delineating a specific aspect of early development and its effects on infant and adult outcome that expands our understanding of the developmental impact of infant experiences on emotional and limbic system development. Together, these research programs suggest that the developing organism's developmental trajectory is influenced by environmental factors beginning in the fetus and extending through adolescence, although the specific timing and nature of the environmental influence has unique impact on adult mental health.
Schreiner, Felix; Ackermann, Merle; Michalik, Michael; Hucklenbruch-Rother, Eva; Bilkei-Gorzo, Andras; Racz, Ildiko; Bindila, Laura; Lutz, Beat; Dötsch, Jörg; Zimmer, Andreas; Woelfle, Joachim
Nutrient deprivation during early development has been associated with the predisposition to metabolic disorders in adulthood. Considering its interaction with metabolism, appetite and behavior, the endocannabinoid (eCB) system represents a promising target of developmental programming. By cross-fostering and variation of litter size, early postnatal nutrition of CB6F1-hybrid mice was controlled during the lactation period (3, 6, or 10 pups/mother). After weaning and redistribution at P21, all pups received standard chow ad libitum. Gene expression analyses (liver, visceral fat, hypothalamus) were performed at P50, eCB concentrations were determined in liver and visceral fat. Locomotor activity and social behavior were analyzed by means of computer-assisted videotracking. Body growth was permanently altered, with differences for length, weight, body mass index and fat mass persisting beyond P100 (all 3>6>10,peCB system were observed in fat (eCB-synthesis: 3>6>10 (DAGLα peCB-degradation: 3>6>10 (FAAH peCB-receptor transcripts (CB1R peCB system, with long-lasting impact of early postnatal nutrition. Developmental programming of the eCB system in metabolically active tissues, as shown here for liver and fat, may play a role in the formation of the adult cardiometabolic risk profile following perinatal malnutrition in humans.
Aiba, Kazuhiro; Nedorezov, Timur; Piao, Yulan; Nishiyama, Akira; Matoba, Ryo; Sharova, Lioudmila V.; Sharov, Alexei A.; Yamanaka, Shinya; Niwa, Hitoshi; Ko, Minoru S. H.
Biologists rely on morphology, function and specific markers to define the differentiation status of cells. Transcript profiling has expanded the repertoire of these markers by providing the snapshot of cellular status that reflects the activity of all genes. However, such data have been used only to assess relative similarities and differences of these cells. Here we show that principal component analysis of global gene expression profiles map cells in multidimensional transcript profile space and the positions of differentiating cells progress in a stepwise manner along trajectories starting from undifferentiated embryonic stem (ES) cells located in the apex. We present three ‘cell lineage trajectories’, which represent the differentiation of ES cells into the first three lineages in mammalian development: primitive endoderm, trophoblast and primitive ectoderm/neural ectoderm. The positions of the cells along these trajectories seem to reflect the developmental potency of cells and can be used as a scale for the potential of cells. Indeed, we show that embryonic germ cells and induced pluripotent cells are mapped near the origin of the trajectories, whereas mouse embryo fibroblast and fibroblast cell lines are mapped near the far end of the trajectories. We suggest that this method can be used as the non-operational semi-quantitative definition of cell differentiation status and developmental potency. Furthermore, the global expression profiles of cell lineages provide a framework for the future study of in vitro and in vivo cell differentiation. PMID:19112179
Páez-Pineda, Oscar D; Valencia-Valencia, Doris; Ortiz Calderón, Martha Vanessa
Evaluating language development by comparing the Munich Development method to the Early Language Milestone scale for identifying both diagnostic tests' agreement and enriching neurodevelopmental consultation. The clinical histories of a cohort of 129 children were evaluated, as prematurity is a risk factor for deviation in children's language development. The children had less than 40 weeks gestational age and 0 to 12 months corrected age. They were given both tests between 2008 and 2011. The results from both scales were compared regarding receptive and expressive language and visual response (Early Language Milestone scale) and evaluation of verbal response, vocal play, understanding and expression (Munich scale). Student's T-test was used for comparing means for paired samples. Results: A statistically significant correlation (p<0.05) was found between both tests and between them and corrected age. It was seen that the higher the corrected age, the greater correlation there was between tests. The Early Language Milestone and Munich Development scales, regarding their components dealing with language, both represent useful tools for following-up premature children's language development.
Constantinou, Savvas J; Pace, Ryan M; Stangl, A J; Nagy, Lisa M; Williams, Terri A
Wnt genes are a family of conserved glycoprotein ligands that play a role in a wide variety of cell and developmental processes, from cell proliferation to axis elongation. There are 13 Wnt subfamilies found among metazoans. Eleven of these appear conserved in arthropods with a pattern of loss during evolution of as many as six subfamilies among hexapods. Here we report on Wnt genes in the branchiopod crustacean, Thamnocephalus platyurus, including the first documentation of the expression of the complete Wnt gene family in a crustacean. Our results suggest fewer Wnt genes were retained in Thamnocephalus than in the related crustacean, Daphnia, although the Thamnocephalus Wnt repertoire is larger than that found in insects. We also find an intriguing pattern of staggered expression of Wnts-an anterior-posterior stagger within the posterior growth zone and a dorsal-ventral stagger in the developing segments-suggesting a potential for subfunctionalization of Wnts in these regions. © 2016 Wiley Periodicals, Inc.
Serra, M.; Jackson, A. E.; van Geert, P. L. C.; Minderaa, R. B.
A Dutch study failed to find differences in the ability of 31 normally intelligent children (ages 6-12) with pervasive developmental disorder not otherwise specified and matched controls to recognize and label emotional states in various nonverbal expressive modalities, such as facial expressions, bodily postures, and gestures. (CR)
David M Gravano
Full Text Available BACKGROUND: Cellular interactions between thymocytes and thymic stromal cells are critical for normal T cell development. Thymic epithelial cells (TECs are important stromal niche cells that provide essential growth factors, cytokines, and present self-antigens to developing thymocytes. The identification of genes that mediate cellular crosstalk in the thymus is ongoing. One candidate gene, Adam17, encodes a metalloprotease that functions by cleaving the ectodomain of several transmembrane proteins and regulates various developmental processes. In conventional Adam17 knockout mice, a non-cell autonomous role for ADAM17 in adult T cell development was reported, which strongly suggested that expression of ADAM17 in TECs was required for normal T cell development. However, knockdown of Adam17 results in multisystem developmental defects and perinatal lethality, which has made study of the role of Adam17 in specific cell types difficult. Here, we examined T cell and thymic epithelial cell development using a conditional knockout approach. METHODOLOGY/PRINCIPAL FINDINGS: We generated an Adam17 conditional knockout mouse in which floxed Adam17 is deleted specifically in TECs by Cre recombinase under the control of the Foxn1 promoter. Normal T cell lineage choice and development through the canonical αβ T cell stages was observed. Interestingly, Adam17 deficiency in TECs resulted in reduced expression of the transcription factor Aire. However, no alterations in the patterns of TEC phenotypic marker expression and thymus morphology were noted. CONCLUSIONS/SIGNIFICANCE: In contrast to expectation, our data clearly shows that absence of Adam17 in TECs is dispensable for normal T cell development. Differentiation of TECs is also unaffected by loss of Adam17 based on phenotypic markers. Surprisingly, we have uncovered a novel genetic link between Adam17and Aire expression in vivo. The cell type in which ADAM17 mediates its non-cell autonomous impact and
Repolho, Tiago; Baptista, Miguel; Pimentel, Marta S; Dionísio, Gisela; Trübenbach, Katja; Lopes, Vanessa M; Lopes, Ana Rita; Calado, Ricardo; Diniz, Mário; Rosa, Rui
The ability to understand and predict the effects of ocean warming (under realistic scenarios) on marine biota is of paramount importance, especially at the most vulnerable early life stages. Here we investigated the impact of predicted environmental warming (+3 °C) on the development, metabolism, heat shock response and antioxidant defense mechanisms of the early stages of the common octopus, Octopus vulgaris. As expected, warming shortened embryonic developmental time by 13 days, from 38 days at 18 °C to 25 days at 21 °C. Concomitantly, survival decreased significantly (~29.9 %). Size at hatching varied inversely with temperature, and the percentage of smaller premature paralarvae increased drastically, from 0 % at 18 °C to 17.8 % at 21 °C. The metabolic costs of the transition from an encapsulated embryo to a free planktonic form increased significantly with warming, and HSP70 concentrations and glutathione S-transferase activity levels were significantly magnified from late embryonic to paralarval stages. Yet, despite the presence of effective antioxidant defense mechanisms, ocean warming led to an augmentation of malondialdehyde levels (an indicative of enhanced ROS action), a process considered to be one of the most frequent cellular injury mechanisms. Thus, the present study provides clues about how the magnitude and rate of ocean warming will challenge the buffering capacities of octopus embryos and hatchlings' physiology. The prediction and understanding of the biochemical and physiological responses to warmer temperatures (under realistic scenarios) is crucial for the management of highly commercial and ecologically important species, such as O. vulgaris.
Cong, Xiaomei; Xu, Wanli; Janton, Susan; Henderson, Wendy A; Matson, Adam; McGrath, Jacqueline M; Maas, Kendra; Graf, Joerg
Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, pgut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion, infant postnatal age, gender and feeding type significantly contribute to the dynamic development of the gut microbiome in preterm infants.
Murphy, M O; Cohn, D M; Loria, A S
The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood.
Slane, Jennifer D.; Klump, Kelly L.; McGue, Matthew; Iacono, William G.
Objective Research examining changes in eating disorder symptoms across adolescence suggests an increase in disordered eating from early to late adolescence. However, relevant studies have largely been cross-sectional in nature and most have not examined the changes in the attitudinal symptoms of eating disorders (e.g., weight concerns). This longitudinal study aimed to address gaps in the available data by examining the developmental trajectories of disordered eating in females from preadolescence into young adulthood. Method Participants were 745 same-sex female twins from the Minnesota Twin Family Study. Disordered eating was assessed using the Total Score, Body Dissatisfaction subscale, Weight Preoccupation subscale, and a combined Binge Eating and Compensatory Behavior subscale from the Minnesota Eating Behavior Survey assessed at the ages of 11, 14, 18, 21, and 25. Several latent growth models were fit to the data to identify the trajectory that most accurately captures the changes in disordered eating symptoms from 11 to 25 years. Results The best-fitting models for overall levels of disordered eating, body dissatisfaction, and weight preoccupation showed an increase in from 11 through 25 years. In contrast, bulimic behaviors increased to age of 18 and then stabilized to age of 25. Discussion The findings expanded upon extant research by investigating longitudinal, symptom specific, within-person changes and showing an increase in cognitive symptoms into young adulthood and the stability of disordered eating behaviors past late adolescence. PMID:24995824
De la Fuente, M; Llorente, R; Baeza, I; De Castro, N M; Arranz, L; Cruces, J; Viveros, M P
Adult animals that had been subjected to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal day (PND) 9-10] show long-term behavioral alterations that resemble specific symptoms of schizophrenia. Moreover, at adolescence MD rats showed depressive-like behavior and altered motor responses. According to the neurodevelopmental hypothesis, certain behavioral abnormalities observed in MD animals may be related to altered neurodevelopmental processes triggered by MD-induced elevated glucocorticoids in relevant specific brain regions. We review here these neuroendocrine effects and show new data indicating that the MD procedure induces diverse detrimental effects on the immune system that are already revealed in the short term (PND 13) and persist into adulthood. These long-lasting effects might be related to altered hypothalamus-pituitary-adrenal axis activity and to social as well as nutrition-related factors. In fact, MD induces long-lasting decreases in body weight. In view of our findings we propose the present MD procedure as a potentially useful model to analyze developmental interactions between early psychophysiological stress and immunodeficient states.
Full Text Available Recent studies have provided evidence that young children already engage in sharing behavior. The underlying social‐cognitive mechanisms, however, are still under debate. In particular, it is unclear whether or not young children’s sharing is motivated by an appreciation of others’ wealth. Manipulating the material needs of recipients in a sharing task (Experiment 1 and a resource allocation task (Experiment 2, we show that 5‐ but not 3‐year‐old children share more with poor than wealthy individuals. The 3-year-old children even showed a tendency to behave less selfishly towards the rich, yet not the poor recipient. This suggests that very early instances of sharing behavior are not motivated by a consideration of others’ material needs. Moreover, the results show that 5-year-old children were rather inclined to give more to the poor individual than distributing the resources equally, demonstrating that their wish to support the poor overruled the otherwise very prominent inclination to share resources equally. This indicates that charity has strong developmental roots in preschool children.
van Zalk, Maarten Herman Walter; Kerr, Margaret
Adolescence is an important period for the development of relationships between immigrants and non-immigrants, yet little is known about how problematic personality traits affect adolescents' relationships with and attitudes toward immigrants. This work identified the roles of intergroup relationships and one dimension of problematic personality traits, namely callous-unemotional traits, in the development of adolescents' tolerance and prejudice. Three annual measurements of a large community sample (N = 1,542) of non-immigrant adolescents (M age = 15.31 at first measurement; 50.2% girls) were used to show that tolerance and prejudice toward immigrants represent two dimensions with distinct developmental trajectories from early to late adolescence. Callous-unemotional traits predicted fewer decreases in prejudice toward immigrants, yet were not directly associated with tolerance. Intergroup friendships predicted stronger increases in tolerance, which, in turn, predicted decreases in prejudice toward immigrants. Thus, tolerance and prejudice toward immigrants seem to be differentially influenced by social experiences and problematic personality traits.
Wiebe, Sandra A; Clark, Caron A C; De Jong, Desiree M; Chevalier, Nicolas; Espy, Kimberly Andrews; Wakschlag, Lauren
Prenatal tobacco exposure (PTE) has a well-documented association with disruptive behavior in childhood, but the neurocognitive effects of exposure that underlie this link are not sufficiently understood. The present study was designed to address this gap, through longitudinal follow-up in early childhood of a prospectively enrolled cohort with well-characterized prenatal exposure. Three-year-old children (n = 151) were assessed using a developmentally sensitive battery capturing both cognitive and motivational aspects of self-regulation. PTE was related to motivational self-regulation, where children had to delay approach to attractive rewards, but not cognitive self-regulation, where children had to hold information in mind and inhibit prepotent motor responses. Furthermore, PTE predicted motivational self-regulation more strongly in boys than in girls, and when propensity scores were covaried to control for confounding risk factors, the effect of PTE on motivational self-regulation was significant only in boys. These findings suggest that PTE's impact on neurodevelopment may be greater in boys than in girls, perhaps reflecting vulnerability in neural circuits that subserve reward sensitivity and emotion regulation, and may also help to explain why PTE is more consistently related to disruptive behavior disorders than attention problems.
Cui, Meng; Liang, Dong; Wu, Shan; Ma, Fengwang; Lei, Yushan
Myo-inositol (MI) is an important polyol involved in cellular signal transduction, auxin storage, osmotic regulation, and membrane formation. It also serves as a precursor for the production of pinitol, ascorbic acid, and members of the raffinose family. The first committed step for MI formation is catalyzed by L-myo-inositol-1-phosphate synthase (MIPS). We isolated MIPS cDNA sequences from Actinidia eriantha, Actinidia rufa, and Actinidia arguta and compared them with that of Actinidia deliciosa. Each comprised 1533 bp, encoding 510 amino acids with a predicted molecular weight of 56.5 KDa. The MIPS protein was highly conserved in Actinidia, sharing 98.94% identity among species. The MIPS gene was expressed in the flowers, leaves, petioles, and carpopodia. Similarly high levels of expression were detected in the young fruit of all four species. Overall activity of the enzyme was also maximal in young fruit, indicating that this developmental stage is the key point for MI synthesis in Actinidia. Among the four species, A. arguta had the greatest concentration of MI as well as the highest ratios of MI:sucrose and MI:glucose+fructose. This suggests that conversion to MI from carbohydrates was most efficient in A. arguta during early fruit development.
Aluru, Neelakanteswar, E-mail: email@example.com [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Kuo, Elaine [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Stanford University, 450 Serra Mall, Stanford, CA 94305 (United States); Helfrich, Lily W. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Northwestern University, 633 Clark St, Evanston, IL 60208 (United States); Karchner, Sibel I. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Linney, Elwood A. [Department of Molecular Genetics and Microbiology, Duke University Medical Center, Box 3020, Durham, NC 27710 (United States); Pais, June E. [New England Biolabs, 240 County Road, Ipswich, MA 01938 (United States); Franks, Diana G. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States)
DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for 1 h from 4 to 5 h post-fertilization (hpf) and sampled at 12, 24, 48, 72, and 96 hpf to determine dnmt gene expression and DNA methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but the promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2, and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns. - Highlights: • TCDD altered the dnmt expression in a gene and developmental time-specific manner. • TCDD hypermethylated ahrra and hypomethylated c-fos proximal promoter regions. • Functional analysis suggests that ahr2 can regulate dnmt3a1, 3a2, and 3b2 expression. • Dnmt
Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme
In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development.
Jennifer C Olori
Full Text Available The ontogeny of extant amphibians often is used as a model for that of extinct early tetrapods, despite evidence for a spectrum of developmental modes in temnospondyls and a paucity of ontogenetic data for lepospondyls. I describe the skeletal morphogenesis of the extinct lepospondyls Microbrachis pelikani and Hyloplesion longicostatum using the largest samples examined for either taxon. Nearly all known specimens were re-examined, allowing for substantial anatomical revisions that affect the scoring of characters commonly used in phylogenetic analyses of early tetrapods. The palate of H. longicostatum is re-interpreted and suggested to be more similar to that of M. pelikani, especially in the nature of the contact between the pterygoids. Both taxa possess lateral lines, and M. pelikani additionally exhibits branchial plates. However, early and rapid ossification of the postcranial skeleton, including a well-developed pubis and ossified epipodials, suggests that neither taxon metamorphosed nor were they neotenic in the sense of branchiosaurids and salamanders. Morphogenetic patterns in the foot suggest that digit 5 was developmentally delayed and the final digit to ossify in M. pelikani and H. longicostatum. Overall patterns of postcranial ossification may indicate postaxial dominance in limb and digit formation, but also more developmental variation in early tetrapods than has been appreciated. The phylogenetic position and developmental patterns of M. pelikani and H. longicostatum are congruent with the hypothesis that early tetrapods lacked metamorphosis ancestrally and that stem-amniotes exhibited derived features of development, such as rapid and complete ossification of the skeleton, potentially prior to the evolution of the amniotic egg.
Full Text Available Abstract Background Recent evidence supports the proposal that the observed diversity of animal body plans has been produced through alterations to the complexity of the regulatory genome rather than increases in the protein-coding content of a genome. One significant form of gene regulation is the contribution made by the non-coding content of the genome. Non-coding RNAs play roles in embryonic development of animals and these functions might be expected to evolve rapidly. Using next-generation sequencing and in situ hybridization, we have examined the miRNA content of early honeybee embryos. Results Through small RNA sequencing we found that 28% of known miRNAs are expressed in the early embryo. We also identified developmentally expressed microRNAs that are unique to the Apoidea clade. Examination of expression patterns implied these miRNAs have roles in patterning the anterior-posterior and dorso-ventral axes as well as the extraembryonic membranes. Knockdown of Dicer, a key component of miRNA processing, confirmed that miRNAs are likely to have a role in patterning these tissues. Conclusions Examination of the expression patterns of novel miRNAs, some unique to the Apis group, indicated that they are likely to play a role in early honeybee development. Known miRNAs that are deeply conserved in animal phyla display differences in expression pattern between honeybee and Drosophila, particularly at early stages of development. This may indicate miRNAs play a rapidly evolving role in regulating developmental pathways, most likely through changes to the way their expression is regulated.
Raponi, Eric; Agenes, Fabien; Delphin, Christian; Assard, Nicole; Baudier, Jacques; Legraverend, Catherine; Deloulme, Jean-Christophe
Summary During the post-natal development, GFAP-expressing cells in the parenchyma progressively lose their neural stem cell (NSC) potential, whereas this peculiar attribute is preserved in GFAP-expressing cells of adult germinal zones. Although the relationship between astrocytes localized in the parenchyma and those in the germinal zones is elusive, many reports suggest that GFAP-expressing cells contained in germinal zones are maintained in immature developmental stage. Starting from the observation that the pan-astrocytic marker S100B is not expressed in the GFAP-expressing cells of adult germinal zones, we first investigated the relationship between S100B expression and the developmental status of these astrocytic cells. We demonstrated that long after the loss of RC2 and gain of GFAP, the onset of S100B expression characterizes a mature developmental stage in mouse telencephalic GFAP-expressing cells, both in vitro and in vivo. Using a transgenic s100b-EGFP mouse-derived culture model, we next demonstrate that in vitro, S100B expression in GFAP-expressing cells coincides with the loss of their NSC potential. Through a series of ectopic and orthotopic grafting experiments, we found that in the adult subventricular zone, S100B expression is controlled by environmental cues. Furthermore, we showed that treatment with epidermal growth factor represses S100B expression in GFAP-expressing cells in vitro as well as in mouse forebrain. Altogether, our results indicate that the S100B expression defines a late developmental stage after which GFAP-expressing cells lose their NSC potential. PMID:17078026
Christie, Andrew E; Fontanilla, Tiana M; Roncalli, Vittoria; Cieslak, Matthew C; Lenz, Petra H
Neurochemicals are likely to play key roles in physiological/behavioral control in the copepod crustacean Calanus finmarchicus, the biomass dominant zooplankton for much of the North Atlantic Ocean. Previously, a de novo assembled transcriptome consisting of 206,041 unique sequences was used to characterize the peptidergic signaling systems of Calanus. Here, this assembly was mined for transcripts encoding enzymes involved in amine biosynthesis. Using known Drosophila melanogaster proteins as templates, transcripts encoding putative Calanus homologs of tryptophan-phenylalanine hydroxylase (dopamine, octopamine and serotonin biosynthesis), tyrosine hydroxylase (dopamine biosynthesis), DOPA decarboxylase (dopamine and serotonin biosynthesis), histidine decarboxylase (histamine biosynthesis), tyrosine decarboxylase (octopamine biosynthesis), tyramine β-hydroxylase (octopamine biosynthesis) and tryptophan hydroxylase (serotonin biosynthesis) were identified. Reverse BLAST and domain analyses show that the proteins deduced from these transcripts possess sequence homology to and the structural hallmarks of their respective enzyme families. Developmental profiling revealed a remarkably consistent pattern of expression for all transcripts, with the highest levels of expression typically seen in the early nauplius and early copepodite. These expression patterns suggest roles for amines during development, particularly in the metamorphic transitions from embryo to nauplius and from nauplius to copepodite. Taken collectively, the data presented here lay a strong foundation for future gene-based studies of aminergic signaling in this and other copepod species, in particular assessment of the roles they may play in developmental control.
Full Text Available Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05-0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother's own breastmilk (MBM had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types
Simpson, Jeffry A; Collins, W Andrew; Tran, SiSi; Haydon, Katherine C
In this longitudinal study, the authors tested a developmental hypothesis derived from attachment theory and recent empirical findings. Target participants were 78 individuals who have been studied intensively from infancy into their mid-20s. When targets were 20-23 years old, the authors tested the way in which interpersonal experiences at 3 pivotal points in each target's earlier social development--infancy/early childhood, early elementary school, and adolescence--predicted the pattern of positive versus negative emotions experienced with his or her romantic partner. A double-mediation model revealed that targets classified as securely attached at 12 months old were rated as more socially competent during early elementary school by their teachers. Targets' social competence, in turn, forecasted their having more secure relationships with close friends at age 16, which in turn predicted more positive daily emotional experiences in their adult romantic relationships (both self- and partner-reported) and less negative affect in conflict resolution and collaborative tasks with their romantic partners (rated by observers). These results are discussed in terms of attachment theory and how antecedent life experiences may indirectly shape events in current relationships.
Ashtamker, Lilach; Karni, Avi
Are children faster than adults in consolidating procedural knowledge? In adults, the expression of the full benefits of motor practice requires a few hours of consolidation and sleep. Here we show that, although the processes generating the delayed gains continued beyond the first few hours post-training, children expressed significant gains as early as 1 h post-training, in the awake state. Copyright © 2013 Elsevier Inc. All rights reserved.
Harris, Kathleen I.
Although developmentally appropriate practice (DAP) has strong merits, there are considerations pertaining to its development and implementation which must be raised. In order for educators to include diverse voices of young children, the time has come for a new conversation to unfold introducing developmentally universal practice (DUP). With this…
Campbell, P M; de Q Robin, G C; Court, L N; Dorrian, S J; Russell, R J; Oakeshott, J G
Here we show how the 10 genes of the alpha esterase cluster of Drosophila melanogaster have diverged substantially in their expression profiles. Together with previously described sequence divergence this suggests substantial functional diversification. By peptide mass fingerprinting and in vitro gene expression we have also shown that two of the genes encode the isozymes EST9 (formerly ESTC) and EST23. EST9 is the major 'alpha staining' esterase in zymograms of gut tissues in feeding stages while orthologues of EST23 confer resistance to organophosphorus insecticides in other higher Diptera. The results for EST9 and EST23 concur with previous suggestions that the products of the alpha esterase cluster function in digestion and detoxification of xenobiotic esters. However, many of the other genes in the cluster show developmental or tissue-specific expression that seems inconsistent with such roles. Furthermore, there is generally poor correspondence between the mRNA expression patterns of the remaining eight genes and isozymes previously characterized by standard techniques of electrophoresis and staining, suggesting that the alpha cluster might only account for a small minority of the esterase isozyme profile.
Buck, C. R.; Martinez, Humberto J.; Black, Ira B.; Chao, Moses V.
Nerve growth factor (NGF) regulates development and maintenance of function of peripheral sympathetic and sensory neurons. A potential role for the trophic factor in brain has been detected only recently. The ability of a cell to respond to NGF is due, in part, to expression of specific receptors on the cell surface. To study tissue-specific expression of the NGF receptor gene, we have used sensitive cRNA probes for detection of NGF receptor mRNA. Our studies indicate that the receptor gene is selectively and specifically expressed in sympathetic (superior cervical) and sensory (dorsal root) ganglia in the periphery, and by the septum-basal forebrain centrally, in the neonatal rat in vivo. Moreover, examination of tissues from neonatal and adult rats reveals a marked reduction in steady-state NGF receptor mRNA levels in sensory ganglia. In contrast, a 2- to 4-fold increase was observed in the basal forebrain and in the sympathetic ganglia over the same time period. Our observations suggest that NGF receptor mRNA expression is developmentally regulated in specific areas of the nervous system in a differential fashion.
Yu, Yanxue; Zhang, Shangan; Zhang, Long; Zhao, Xingbo
We have investigated the development of chemosensilla and the secretion of odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) in the embryo of Locusta migratoria manilensis. We first report the changes of each sensillum in embryo just preceding hatch in detail and show that different sensilla have different developmental processes. Trichogen cells are first involved in forming the structure of pegs, and then, after retraction, they start secreting OBPs and CSPs in the sensillar lymph. The synthesis of LmigOBP1 starts during the embryogenesis about 0.5 h preceding hatching, specifically in sensilla trichodea and basiconica of the antenna. LmigOBP2, instead, was only found in the outer sensillum lymph (oSl) of sensilla chaetica of the antenna, while we could not detect LmigOBP3 in any type of sensilla of the antenna. The ontogenesis of CSPs in the embryos is similar to that of OBPs. Expression of CSPI homolog in Locusta migratoria is detected using the antiserum raised against SgreCSPI. CSPI is specifically expressed in the outer sensillum lymph of sensilla chaetica of the antenna, and anti-LmigCSPII dose not label any sensilla of the embryos. These data indicate that in locusts, OBPs and CSPs follow different temporal expression patterns, and also that OBPs are expressed in different types of sensilla.
MA Qian; ZHUANG Zhimeng; FENG Wenrong; LIU Shufang; TANG Qisheng
Differential expression of genes is crucial to growth and development of fish. To select the appropriate genes for gene normalization duringCynoglossus semilaevis early developmental process, eight candidate reference genes (ACTB, B2M, EF1A, GADPH, RPL7, TUBA, UBCE and 18S) were tested for their adequacy by using quantitative real-time PCR. The results showed that the expression of all the examined genes exhibited tissue dependent variations in the matureC.semilaevis. EF1A was listed as the most stable reference among the 14 tissues by RefFinder. Furthermore, the recommended comprehensive ranking of the stability determined by RefFinder showed that 18S was the most stable gene during the early developmental stages (from oosphere to 90 days old) in this study. However, when divided theCt value data of the above mentioned early developmental stages into two separate periods (embryo and post-hatching periods), TUBA and 18S represented the most stable references of these two developmental periods, respectively. Consequently, the reference gene should be carefully and accurately chosen even for studies of the same species at various developmental processes. The relevant data may help in selecting appropriate reference genes for mRNA expression analysis, and is of great value in the studies of fish growth and development.
Full Text Available In the last several decades a number of studies on perceptual learning in early infancy have suggested that even infants seem to be sensitive to the way objects move and interact in the world. In order to explain the early emergence of infants’ sensitivity to causal patterns in the world some psychologists have proposed that core knowledge of objects and causal relations is innate (Leslie & Keeble 1987, Carey & Spelke, 1994; Keil, 1995; Spelke et al., 1994. The goal of this paper is to examine the nativist developmental model by investigating the criteria that a mechanistic model needs to fulfill if it is to be explanatory. Craver (2006 put forth a number of such criteria and developed a few very useful distinctions between explanation sketches and proper mechanistic explanations. By applying these criteria to the nativist developmental model I aim to show, firstly, that nativists only partially characterize the phenomenon at stake without giving us the details of when and under which conditions perception and attention in early infancy take place. Secondly, nativist start off with a description of the phenomena to be explained (even if it is only a partial description but import into it a particular theory of perception that requires further empirical evidence and further defense on its own. Furthermore, I argue that innate knowledge is a good candidate for a filler term (a term that is used to name the still unknown processes and parts of the mechanism and is likely to become redundant. Recent extensive research on early intermodal perception indicates that the mechanism enabling the perception of regularities and causal patterns in early infancy is grounded in our neurophysiology. However, this mechanism is fairly basic and does not involve highly sophisticated cognitive structures or innate core knowledge. I conclude with a remark that a closer examination of the mechanisms involved in early perceptual learning indicates that the nativism
Full Text Available Quantitative real-time PCR (qRT-PCR is a reliable and reproducible technique for measuring mRNA expression. To facilitate gene expression studies and obtain more accurate qRT-PCR analysis, normalization relative to stable housekeeping genes is mandatory. In this study, ten housekeeping genes, including beta-actin (Actin , elongation factor 1 α (EF1A , glyceralde hyde-3-phosphate dehydrogenase (GAPDH , ribosomal protein L13 (RPL13 , ribosomal protein 49 (RP49 , α-tubulin (Tubulin , vacuolar-type H+-ATPase (v-ATPase , succinate dehydrogenase subunit A (SDHA , 28S ribosomal RNA (28S , and 18S ribosomal RNA (18S from the two-spotted spider mite, Tetranychus urticae, were selected as the candidate reference genes. Four algorithms, geNorm, Normfinder, BestKeeper, and the ΔCt method, were used to evaluate the performance of these candidates as endogenous controls across different developmental stages. In addition, RefFinder, which integrates the above-mentioned software tools, provided the overall ranking of the stability/suitability of these candidate reference genes. Among them, PRL13 and v-ATPase were the two most stable housekeeping genes across different developmental stages. This work is the first step toward establishing a standardized qRT-PCR analysis in T. urticae following the MIQE guideline. With the recent release of the T. urticae genome, results from this study provide a critical piece for the subsequent genomics and functional genomics research in this emerging model system.
Adam M. Reitzel
Full Text Available Abstract Background An essential developmental pathway in sexually reproducing animals is the specification of germ cells and the differentiation of mature gametes, sperm and oocytes. The “germline” genes vasa, nanos and piwi are commonly identified in primordial germ cells, suggesting a molecular signature for the germline throughout animals. However, these genes are also expressed in a diverse set of somatic stem cells throughout the animal kingdom leaving open significant questions for whether they are required for germline specification. Similarly, members of the Dmrt gene family are essential components regulating sex determination and differentiation in bilaterian animals, but the functions of these transcription factors, including potential roles in sex determination, in early diverging animals remain unknown. The phylogenetic position of ctenophores and the genome sequence of the lobate Mnemiopsis leidyi motivated us to determine the compliment of these gene families in this species and determine expression patterns during development. Results Our phylogenetic analyses of the vasa, piwi and nanos gene families show that Mnemiopsis has multiple genes in each family with multiple lineage-specific paralogs. Expression domains of Mnemiopsis nanos, vasa and piwi, during embryogenesis from fertilization to the cydippid stage, were diverse, with little overlapping expression and no or little expression in what we think are the germ cells or gametogenic regions. piwi paralogs in Mnemiopsis had distinct expression domains in the ectoderm during development. We observed overlapping expression domains in the apical organ and tentacle apparatus of the cydippid for a subset of “germline genes,” which are areas of high cell proliferation, suggesting that these genes are involved with “stem cell” specification and maintenance. Similarly, the five Dmrt genes show diverse non-overlapping expression domains, with no clear evidence for
Levy, C; Brooks, J M; Chen, J; Su, J; Fox, M A
Mounting evidence has demonstrated that a specialized extracellular matrix exists in the mammalian brain and that this glycoprotein-rich matrix contributes to many aspects of brain development and function. The most prominent supramolecular assemblies of these extracellular matrix glycoproteins are perineuronal nets, specialized lattice-like structures that surround the cell bodies and proximal neurites of select classes of interneurons. Perineuronal nets are composed of lecticans, a family of chondroitin sulfate proteoglycans that includes aggrecan, brevican, neurocan, and versican. These lattice-like structures emerge late in postnatal brain development, coinciding with the ending of critical periods of brain development. Despite our knowledge of the presence of lecticans in perineuronal nets and their importance in regulating synaptic plasticity, we know little about the development or distribution of the extracellular proteases that are responsible for their cleavage and turnover. A subset of a large family of extracellular proteases (called a disintegrin and metalloproteinase with thrombospondin motifs [ADAMTS]) is responsible for endogenously cleaving lecticans. We therefore explored the expression pattern of two aggrecan-degrading ADAMTS family members, ADAMTS15 and ADAMTS4, in the hippocampus and neocortex. Here, we show that both lectican-degrading metalloproteases are present in these brain regions and that each exhibits a distinct temporal and spatial expression pattern. Adamts15 mRNA is expressed exclusively by parvalbumin-expressing interneurons during synaptogenesis, whereas Adamts4 mRNA is exclusively generated by telencephalic oligodendrocytes during myelination. Thus, ADAMTS15 and ADAMTS4 not only exhibit unique cellular expression patterns but their developmental upregulation by these cell types coincides with critical aspects of neural development.
Cao, Heping; Shockey, Jay M; Klasson, K Thomas; Chapital, Dorselyn C; Mason, Catherine B; Scheffler, Brian E
Diacylglycerol acyltransferases (DGAT) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. DGAT genes have been identified in numerous organisms. Multiple isoforms of DGAT are present in eukaryotes. We previously cloned DGAT1 and DGAT2 genes of tung tree (Vernicia fordii), whose novel seed TAGs are useful in a wide range of industrial applications. The objective of this study was to understand the developmental regulation of DGAT family gene expression in tung tree. To this end, we first cloned a tung tree gene encoding DGAT3, a putatively soluble form of DGAT that possesses 11 completely conserved amino acid residues shared among 27 DGAT3s from 19 plant species. Unlike DGAT1 and DGAT2 subfamilies, DGAT3 is absent from animals. We then used TaqMan and SYBR Green quantitative real-time PCR, along with northern and western blotting, to study the expression patterns of the three DGAT genes in tung tree tissues. Expression results demonstrate that 1) all three isoforms of DGAT genes are expressed in developing seeds, leaves and flowers; 2) DGAT2 is the major DGAT mRNA in tung seeds, whose expression profile is well-coordinated with the oil profile in developing tung seeds; and 3) DGAT3 is the major form of DGAT mRNA in tung leaves, flowers and immature seeds prior to active tung oil biosynthesis. These results suggest that DGAT2 is probably the major TAG biosynthetic isoform in tung seeds and that DGAT3 gene likely plays a significant role in TAG metabolism in other tissues. Therefore, DGAT2 should be a primary target for tung oil engineering in transgenic organisms.
Jonscher, Karen R; Stewart, Michael S; Alfonso-Garcia, Alba; DeFelice, Brian C; Wang, Xiaoxin X; Luo, Yuhuan; Levi, Moshe; Heerwagen, Margaret J R; Janssen, Rachel C; de la Houssaye, Becky A; Wiitala, Ellen; Florey, Garrett; Jonscher, Raleigh L; Potma, Eric O; Fiehn, Oliver; Friedman, Jacob E
Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity or Western-style diet (WD) increases steatosis and oxidative stress in fetal liver and is associated with lifetime disease risk in the offspring. Pyrroloquinoline quinone (PQQ) is a natural antioxidant found in soil, enriched in human breast milk, and essential for development in mammals. We investigated whether a supplemental dose of PQQ, provided prenatally in a mouse model of diet-induced obesity during pregnancy, could protect obese offspring from progression of NAFLD. PQQ treatment given pre- and postnatally in WD-fed offspring had no effect on weight gain but increased metabolic flexibility while reducing body fat and liver lipids compared with untreated obese offspring. Indices of NAFLD including hepatic ceramide levels, oxidative stress and expression of proinflammatory genes (Nos2, Nlrp3, Il6, and Ptgs2) were decreased in WD PQQ-fed mice, concomitant with increased expression of fatty acid oxidation genes and decreased Pparg expression. Notably, these changes persisted even after PQQ withdrawal at weaning. Our results suggest that supplementation with PQQ, particularly during pregnancy and lactation, protects offspring from WD-induced developmental programming of hepatic lipotoxicity and may help slow the advancing epidemic of NAFLD in the next generation.-Jonscher, K. R., Stewart, M. S., Alfonso-Garcia, A., DeFelice, B. C., Wang, X. X., Luo, Y., Levi, M., Heerwagen, M. J. R., Janssen, R. C., de la Houssaye, B. A., Wiitala, E., Florey, G., Jonscher, R. L., Potma, E. O., Fiehn, O. Friedman, J. E. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice.
Assou, Said; Boumela, Imène; Haouzi, Delphine; Anahory, Tal; Dechaud, Hervé; De Vos, John; Hamamah, Samir
The first week of human embryonic development comprises a series of events that change highly specialized germ cells into undifferentiated human embryonic stem cells (hESCs) that display an extraordinarily broad developmental potential. The understanding of these events is crucial to the improvement of the success rate of in vitro fertilization. With the emergence of new technologies such as Omics, the gene expression profiling of human oocytes, embryos and hESCs has been performed and generated a flood of data related to the molecular signature of early embryo development. In order to understand the complex genetic network that controls the first week of embryo development, we performed a systematic review and study of this issue. We performed a literature search using PubMed and EMBASE to identify all relevant studies published as original articles in English up to March 2010 (n = 165). We also analyzed the transcriptome of human oocytes, embryos and hESCs. Distinct sets of genes were revealed by comparing the expression profiles of oocytes, embryos on Day 3 and hESCs, which are associated with totipotency, pluripotency and reprogramming properties, respectively. Known components of two signaling pathways (WNT and transforming growth factor-β) were linked to oocyte maturation and early embryonic development. Omics analysis provides tools for understanding the molecular mechanisms and signaling pathways controlling early embryonic development. Furthermore, we discuss the clinical relevance of using a non-invasive molecular approach to embryo selection for the single-embryo transfer program.
Aluru, Neelakanteswar; Kuo, Elaine; Helfrich, Lily W.; Karchner, Sibel I.; Linney, Elwood A.; Pais, June E.; Franks, Diana G.
DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for one hour from 4 to 5 hours post-fertilization (hpf) and sampled at 12, 24, 48, 72 and 96 hpf to determine dnmt gene expression and DNA methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2 and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns. PMID:25732252
Kumuda M. Kushalappa; Autar K. Mattoo; Usha Vijayraghavan
To unravel gene expression patterns during rice inflorescence development, particularly at early stages of panicle and floral organ specification, we have characterized random cloned cDNAs from developmental-stage-specific libraries. cDNA libraries were constructed from rice panicles at the stage of branching and flower primordia specification or from panicles undergoing floral organogenesis. Partial sequence analysis and expression patterns of some of these random cDNA clones from these two rice panicle libraries are presented. Sequence comparisons with known DNA sequences in databases reveal that approximately sixtyeight per cent of these expressed rice genes show varying degrees of similarity to genes in other species with assigned functions. In contrast, thirtytwo per cent represent uncharacterized genes. cDNAs reported here code for potential rice homologues of housekeeping molecules, regulators of gene expression, and signal transduction molecules. They comprise both single-copy and multicopy genes, and genes expressed differentially, both spatially and temporally, during rice plant development. New rice cDNAs requiring specific mention are those with similarity to COP1, a regulator of photomorphogenesis in Arabidopsis; sequence-specific DNA binding plant proteins like AP2-domain-containing factors; genes that specify positional information in shoot meristems like leucine-rich-repeat-containing receptor kinases; regulators of chromatin structure like Polycomb domain protein; and also proteins induced by abiotic stresses.
Kung, Karson T F; Browne, Wendy V; Constantinescu, Mihaela; Noorderhaven, Rebecca M; Hines, Melissa
During the first few years of life, girls typically have a larger expressive vocabulary than boys. This sex difference is important since a small vocabulary may predict subsequent language difficulties, which are more prevalent in boys than girls. The masculinizing effects of early androgen exposure on neurobehavioral development are well-documented in nonhuman mammals. The present study conducted the first test of whether early postnatal testosterone concentrations influence sex differences in expressive vocabulary in toddlers. It was found that testosterone measured in saliva samples collected at 1-3 months of age, i.e., during the period called mini-puberty, negatively predicted parent-report expressive vocabulary size at 18-30 months of age in boys and in girls. Testosterone concentrations during mini-puberty also accounted for additional variance in expressive vocabulary after other predictors such as sex, child's age at vocabulary assessment, and paternal education, were taken into account. Furthermore, testosterone concentrations during mini-puberty mediated the sex difference in expressive vocabulary. These results suggest that testosterone during the early postnatal period contributes to early language development and neurobehavioral sexual differentiation in humans.
Diane I Schroeder
Full Text Available Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs and highly methylated domains (HMDs with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo.
Sherman, L.S.; Bennett, P.R.; Moore, G.E. [Queen Charlotte`s and Chelsea Hospital, London (United Kingdom)
Two cases of maternal uniparental (hetero)disomy for human chromosome 21 (mUPD21) have been identified in a systematic search for UPD in 23 cases of early embryonic failure (EEF). Bi-parental origin of the other chromosome pairs was confirmed using specific VNTR probes or dinucleotide repeat analysis. Both maternally and paternally derived isochromosomes 21q have previously been identified in two individuals with normal phenotypes. Full UPD21 has a different mechanism of origin than uniparental isochromosome 21q and its effect on imprinted genes and phenotypic outcome will therefore not necessarily be the same. EEF associated with mUPD21 suggests that developmentally important genes on HSA 21 may be imprinted such that they are only expressed from either the maternally or paternally derived alleles. We have searched for monoallelic expression of candidate genes on HSA 21 in human pregnancy (CBS, IFNAR, COL6A1) using intragenic DNA polymorphisms. These genes were chosen either because their murine homologues lie in imprinted regions or because they are potentially important in embryogenesis. Once imprinted candidate genes have been identified, their methylation status and expression in normal, early embryonic failure and uniparental disomy 21 pregnancies will be studied. At the same time, a larger number of cases of EEF are being examined to further investigate the incidence of UPD21 in this group.
Full Text Available A gene expression atlas is an essential resource to quantify and understand the multiscale processes of embryogenesis in time and space. The automated reconstruction of a prototypic 4D atlas for vertebrate early embryos, using multicolor fluorescence in situ hybridization with nuclear counterstain, requires dedicated computational strategies. To this goal, we designed an original methodological framework implemented in a software tool called Match-IT. With only minimal human supervision, our system is able to gather gene expression patterns observed in different analyzed embryos with phenotypic variability and map them onto a series of common 3D templates over time, creating a 4D atlas. This framework was used to construct an atlas composed of 6 gene expression templates from a cohort of zebrafish early embryos spanning 6 developmental stages from 4 to 6.3 hpf (hours post fertilization. They included 53 specimens, 181,415 detected cell nuclei and the segmentation of 98 gene expression patterns observed in 3D for 9 different genes. In addition, an interactive visualization software, Atlas-IT, was developed to inspect, supervise and analyze the atlas. Match-IT and Atlas-IT, including user manuals, representative datasets and video tutorials, are publicly and freely available online. We also propose computational methods and tools for the quantitative assessment of the gene expression templates at the cellular scale, with the identification, visualization and analysis of coexpression patterns, synexpression groups and their dynamics through developmental stages.
Castro-González, Carlos; Luengo-Oroz, Miguel A; Duloquin, Louise; Savy, Thierry; Rizzi, Barbara; Desnoulez, Sophie; Doursat, René; Kergosien, Yannick L; Ledesma-Carbayo, María J; Bourgine, Paul; Peyriéras, Nadine; Santos, Andrés
A gene expression atlas is an essential resource to quantify and understand the multiscale processes of embryogenesis in time and space. The automated reconstruction of a prototypic 4D atlas for vertebrate early embryos, using multicolor fluorescence in situ hybridization with nuclear counterstain, requires dedicated computational strategies. To this goal, we designed an original methodological framework implemented in a software tool called Match-IT. With only minimal human supervision, our system is able to gather gene expression patterns observed in different analyzed embryos with phenotypic variability and map them onto a series of common 3D templates over time, creating a 4D atlas. This framework was used to construct an atlas composed of 6 gene expression templates from a cohort of zebrafish early embryos spanning 6 developmental stages from 4 to 6.3 hpf (hours post fertilization). They included 53 specimens, 181,415 detected cell nuclei and the segmentation of 98 gene expression patterns observed in 3D for 9 different genes. In addition, an interactive visualization software, Atlas-IT, was developed to inspect, supervise and analyze the atlas. Match-IT and Atlas-IT, including user manuals, representative datasets and video tutorials, are publicly and freely available online. We also propose computational methods and tools for the quantitative assessment of the gene expression templates at the cellular scale, with the identification, visualization and analysis of coexpression patterns, synexpression groups and their dynamics through developmental stages.
Tansey, Emily Phillips; Chow, Alan; Rudy, Bernardo; McBain, Chris J
The developmental expression of the voltage-gated potassium channel subunit, Kv3.2, and its localization within specific mouse hippocampal inhibitory interneuron populations were determined using immunoblotting and immunohistochemical techniques. Using immunoblotting techniques, the Kv3.2 protein was weakly detected at postnatal age day 7 (P7), and full expression was attained at P21 in tissue extracts from homogenized hippocampal preparations. A similar developmental profile was observed using immunohistochemical techniques in hippocampal tissue sections. Kv3.2 protein expression was clustered on the somata and proximal dendrites of presumed inhibitory interneurons. Using double immunofluorescence, Kv3.2 subunit expression was detected on subpopulations of GABAergic inhibitory interneurons. Kv3.2 was detected in approximately 100% of parvalbumin-positive interneurons, 86% of interneurons expressing nitric oxide synthase, and approximately 50% of somatostatin-immunoreactive cells. Kv3.2 expression was absent from both calbindin- and calretinin-containing interneurons. Using immunoprecipitation, we further demonstrate that Kv3.2 and its related subunit Kv3.1b are coexpressed within the same protein complexes in the hippocampus. These data demonstrate that potassium channel subunit Kv3.2 expression is developmentally regulated in a specific set of interneurons. The vast majority of these interneuron subpopulations possess a "fast-spiking" phenotype, consistent with a role for currents through Kv3.2 containing channels in determining action potential kinetics in these cells.
de Wilde, Amber; Koot, Hans M; van Lier, Pol A C
This study assessed the developmental links between children's working memory development and their relations with teachers and peers across 2 years of kindergarten and early elementary school. Kindergarten and first grade children, N = 1109, 50% boys, were followed across 2 school-years. Children were assessed across 3 waves, in the fall and spring of the first school-year (within school-year), and finally in the spring of the second school-year. Working memory was assessed using a visuo-spatial working memory task. The developmental links between working memory and child-reported teacher-child relationship quality (warmth and conflict) and peer-nominated likeability and friendedness were assessed using autoregressive cross-lagged models. Lower working memory scores were related to increases in teacher-child conflict and decreases in teacher-child warmth one school-year later, in addition to decreases in likeability by peers within the same school-year. Conversely, teacher-child conflict was negatively associated with the development of working memory across the studied period. Path estimates between working memory and social relational factors were similar for boys and girls. Findings show developmental links between working memory and social-relational factors and vice versa. These results suggest that children's working memory development can be fostered through pro-social relations with teachers in early elementary school children.
Garner, Andrew S; Shonkoff, Jack P
Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.
Carbone, F.; Preuss, A.; Vos, de C.H.; Amico, d' E.; Perrotta, G.; Bovy, A.G.; Martens, S.; Rosati, C.
The influence of internal (genetic and developmental) and external (environmental) factors on levels of flavonoid gene transcripts, enzyme activity and metabolites was studied in fruit of six cultivated strawberry (Fragaria × ananassa Duch.) genotypes grown at two Italian locations. Gene expression
TIME-DEPENDENT EFFECTS ON GENE EXPRESSION IN RAT SEMINAL VESICLE DEVELOPMENTALLY ALTERED BY IN UTERO EXPOSURE TO TCDD. V M Richardson', J T Hamm2, and L S Birnbaum1. 'USEPA, ORD/NHEERL/ETD, Research Triangle Park, NC, USA, 'Curriculum in Toxicology, University of North Carolina, ...
Zeanah, Charles H; Lieberman, Alicia
Infant mental health is explicitly relational in its focus, and therefore a diagnostic classification system for early childhood disorders should include attention not only to within-the-child psychopathology but also between child and caregiver psychopathology. In this article, we begin by providing a review of previous efforts to introduce this approach that date back more than 30 years. Next, we introduce changes proposed in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood DC:0-5 (ZERO TO THREE, in press). In a major change from previous attempts, the DC:0-5 includes an Axis I "Relationship Specific Disorder of Early Childhood." This disorder intends to capture disordered behavior that is limited to one caregiver relationship rather than cross contextually. An axial characterization is continued from the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood DC:0-3R (ZERO TO THREE, 2005), but two major changes are introduced. First, the DC:0-5 proposes to simplify ratings of relationship adaptation/maladaptation, and to expand what is rated so that in addition to characterizing the child's relationship with his or her primary caregiver, there also is a characterization of the network of family relationships in which the child develops. This includes coparenting relationships and the entire network of close relationships that impinge on the young child's development and adaptation. © 2016 Michigan Association for Infant Mental Health.
Full Text Available Abstract Background Increasing use of zebrafish in drug discovery and mechanistic toxicology demands knowledge of cytochrome P450 (CYP gene regulation and function. CYP enzymes catalyze oxidative transformation leading to activation or inactivation of many endogenous and exogenous chemicals, with consequences for normal physiology and disease processes. Many CYPs potentially have roles in developmental specification, and many chemicals that cause developmental abnormalities are substrates for CYPs. Here we identify and annotate the full suite of CYP genes in zebrafish, compare these to the human CYP gene complement, and determine the expression of CYP genes during normal development. Results Zebrafish have a total of 94 CYP genes, distributed among 18 gene families found also in mammals. There are 32 genes in CYP families 5 to 51, most of which are direct orthologs of human CYPs that are involved in endogenous functions including synthesis or inactivation of regulatory molecules. The high degree of sequence similarity suggests conservation of enzyme activities for these CYPs, confirmed in reports for some steroidogenic enzymes (e.g. CYP19, aromatase; CYP11A, P450scc; CYP17, steroid 17a-hydroxylase, and the CYP26 retinoic acid hydroxylases. Complexity is much greater in gene families 1, 2, and 3, which include CYPs prominent in metabolism of drugs and pollutants, as well as of endogenous substrates. There are orthologous relationships for some CYP1 s and some CYP3 s between zebrafish and human. In contrast, zebrafish have 47 CYP2 genes, compared to 16 in human, with only two (CYP2R1 and CYP2U1 recognized as orthologous based on sequence. Analysis of shared synteny identified CYP2 gene clusters evolutionarily related to mammalian CYP2 s, as well as unique clusters. Conclusions Transcript profiling by microarray and quantitative PCR revealed that the majority of zebrafish CYP genes are expressed in embryos, with waves of expression of different
Full Text Available BACKGROUND: The ascarosides form a family of small molecules that have been isolated from cultures of the nematode Caenorhabditis elegans. They are often referred to as "dauer pheromones" because most of them induce formation of long-lived and highly stress resistant dauer larvae. More recent studies have shown that ascarosides serve additional functions as social signals and mating pheromones. Thus, ascarosides have multiple functions. Until now, it has been generally assumed that ascarosides are constitutively expressed during nematode development. METHODOLOGY/PRINCIPAL FINDINGS: Cultures of C. elegans were developmentally synchronized on controlled diets. Ascarosides released into the media, as well as stored internally, were quantified by LC/MS. We found that ascaroside biosynthesis and release were strongly dependent on developmental stage and diet. The male attracting pheromone was verified to be a blend of at least four ascarosides, and peak production of the two most potent mating pheromone components, ascr#3 and asc#8 immediately preceded or coincided with the temporal window for mating. The concentration of ascr#2 increased under starvation conditions and peaked during dauer formation, strongly supporting ascr#2 as the main population density signal (dauer pheromone. After dauer formation, ascaroside production largely ceased and dauer larvae did not release any ascarosides. These findings show that both total ascaroside production and the relative proportions of individual ascarosides strongly correlate with these compounds' stage-specific biological functions. CONCLUSIONS/SIGNIFICANCE: Ascaroside expression changes with development and environmental conditions. This is consistent with multiple functions of these signaling molecules. Knowledge of such differential regulation will make it possible to associate ascaroside production to gene expression profiles (transcript, protein or enzyme activity and help to determine genetic
Lee, Y C; Damholt, A B; Billestrup, N;
in the developing pancreas. Thus, we have identified a novel PC1/3 mRNA transcript in the rat by using sequence-specific probes and have demonstrated that the developmental expression of prohormone convertase PC1/3 is confined primarily to pancreas and intestine, suggesting that it may play a possible role...... described previously. RT-PCR of RNA isolated from rat embryonic tissues using a primer set corresponding to the 3' end of the PC1/3 sequence showed a steady increase of expression in fetal pancreas and intestine during the course of development. In contrast, comparatively high and constant levels of PC1......We have isolated a clone that has 3' end sequence identity with prohormone convertase 1/3 (PC1/3) from a rat islet cDNA library. Northern blot analysis and immunocytochemical studies have confirmed its presence in the endocrine pancreas. Analysis of poly A mRNA from various adult tissues...
Payyavula, Raja S; Navarre, Duroy A; Kuhl, Joseph; Pantoja, Alberto
Potato phytonutrients include phenolic acids, flavonols, anthocyanins, and carotenoids. Developmental effects on phytonutrient concentrations and gene expression were studied in white, yellow, and purple potatoes. Purple potatoes contained the most total phenolics, which decreased during development (from 14 to 10 mg g(-1)), as did the activity of phenylalanine ammonia-lyase. The major phenolic, 5-chlorogenic acid (5CGA), decreased during development in all cultivars. Products of later branches of the phenylpropanoid pathway also decreased, including quercetin 3-O rutinoside, kaempferol 3-O-rutinoside, and petunidin 3-O-(p-coumaroyl)rutinoside-3-glucoside (from 6.4 to 4.0 mg g(-1)). Violaxanthin and lutein were the two most abundant carotenoids and decreased 30-70% in the yellow and white potatoes. Sucrose, which can regulate phenylpropanoid metabolism, decreased with development in all cultivars and was highest in purple potatoes. Total protein decreased by 15-30% in two cultivars. Expression of most phenylpropanoid and carotenoid structural genes decreased during development. Immature potatoes like those used in this study are marketed as "baby potatoes", and the greater amounts of these dietarily desirable compounds may appeal to health-conscious consumers.
We cloned cDNAs for Xenopus aldolases A, B and C. These three aldolase genes are localized on different chromosomes as a single copy gene. In the adult, the aldolase A gene is expressed extensively in muscle tissues, whereas the aldolase B gene is expressed strongly in kidney, liver, stomach and intestine, while the aldolase C gene is expressed in brain, heart and ovary. In oocytes aldolase A and C mRNAs, but not aldolase B mRNA, are extensively transcribed. Thus, aldolase A and C mRNAs, but not B mRNA, occur abundantly in eggs as maternal mRNAs, and strong expression of aldolase B mRNA is seen only after the late neurula stage. We conclude that aldolase A and C mRNAs are major aldolase mRNAs in early stages of Xenopus embryogenesis which proceeds utilizing yolk as the only energy source, aldolase B mRNA, on the other hand, is expressed only later in development in tissues which are required for dietary fructose metabolism.We also isolated the Xenopus aldolase C genomic gene (ca. 12 kb) and found that its promoter (ca. 2 kb)contains regions necessary for tissue-specific expression and also a GC rich region which is essential for basal transcriptional activity.
Takezawa, D.; Liu, Z. H.; An, G.; Poovaiah, B. W.
Eight genomic clones of potato calmodulin (PCM1 to 8) were isolated and characterized. Sequence comparisons of different genes revealed that the deduced amino acid sequence of PCM1 had several unique substitutions, especially in the fourth Ca(2+)-binding area. The expression patterns of different genes were studied by northern analysis using the 3'-untranslated regions as probes. The expression of PCM1, 5, and 8 was highest in the stolon tip and it decreased during tuber development. The expression of PCM6 did not vary much in the tissues tested, except in the leaves, where the expression was lower; whereas, the expression of PCM4 was very low in all the tissues. The expression of PCM2 and PCM3 was not detected in any of the tissues tested. Among these genes, only PCM1 showed increased expression following touch stimulation. To study the regulation of PCM1, transgenic potato plants carrying the PCM1 promoter fused to the beta-glucuronidase (GUS) reporter gene were produced. GUS expression was found to be developmentally regulated and touch-responsive, indicating a positive correlation between the expression of PCM1 and GUS mRNAs. These results suggest that the 5'-flanking region of PCM1 controls developmental and touch-induced expression. X-Gluc staining patterns revealed that GUS localization is high in meristematic tissues such as the stem apex, stolon tip, and vascular regions.
Full Text Available Malpighian tubules (MT of Drosophila melanogaster are osmoregulatory organs that maintain the ionic balance and remove toxic substances from the body. Additionally they act as autonomous immune sensing organs, which secrete antimicrobial peptides in response to invading microbial pathogens. We show that the antimicrobial peptides (AMP diptericin, cecropinA, drosocin and attacinA are constitutively expressed and are regulated in developmental stage specific manner. Their developmental expression begins from 3(rd instar larval stage and an immune challenge increases the expression several folds. Spatial variations in the level of expression along the MT tissue are observed. The mortality of 3(rd instar larvae fed on bacterial food is much less than that of the earlier larval stages, coinciding with the onset of innate immunity response in MT. Ectopic expression of AMP imparts better resistance to infection while, loss of function of one of the AMP through directed RNAi reduces host survival after immune challenge. The AMP secreted from the MT exhibit bactericidal activity. Expression of the NF-κB transcription factor, Relish, also coincides with activation of immune responsive genes in MT, demonstrating that immune regulation in MT is under developmental control and is governed by the Imd pathway.
Herminia Yohko KANAMURA
Full Text Available Antibodies to a number of parasite antigens are found in schistosomiasis patients, and antibodies to early developmental stages were demonstrated to be efficient immunologic markers for the diagnosis of schistosomiasis. In the present study, decay patterns of IgM and IgG antibodies against cercariae and schistosomula were investigated, in comparison to antibodies against worms and eggs in schistosomiasis patients after chemotherapy, for an investigation of seroepidemiologic aspects. Data obtained in the study of 359 serum samples from patients with Schistosoma mansoni infection, noninfected individuals, and patients followed-up for a period of 12 to 15 months after treatment provided the basis to postulate a general pattern for the kinetics of antibody decay. Before treatment, the antibody pattern was represented by a unimodal curve, which shifted to a bimodal curve after treatment, and ended with a unimodal curve similar to that for the noninfected group. Different types of antibodies were classified into four categories according to their decay features, and anti-schistosomulum IgM was classified into the moderate-decay caterogy, whereas other antibodies to early parasite stages were classified into the slow-decay category. The present methodology permits the identification of the most suitable antibodies to be detected in field control programs for schistosomiasis or other parasitosesEm pacientes com esquistossomose, são encontrados anticorpos contra grande número de antígenos parasitários, e aqueles contra formas evolutivas jovens do parasita demonstraram que eram eficientes marcadores imunológicos para o diagnóstico da esquistossomose. Padrões de queda de anticorpos IgM e IgG contra cercária e esquistossômulo foram aqui estudados, comparativamente aos dos anticorpos contra verme e ovo, em pacientes esquistossomóticos após quimioterapia, abordando aspectos soroepidemiológicos. Dados obtidos no estudo de 359 amostras de soros
Hornman, Jorijn; de Winter, Andrea F; Kerstjens, Jorien M; Bos, Arend F; Reijneveld, Sijmen A
To assess the stability of developmental problems in moderately-late preterm-born children compared with early preterm and full term-born children before school entry at age 4 years and 1 year after school entry at age 5 years. We included 376 early preterm, 688 born moderately-late preterm, and 403 full term-born children from the Longitudinal Preterm Outcome Project (LOLLIPOP) cohort study. Developmental problems were assessed by the total score and the 5 domain scores of the Ages and Stages Questionnaire at ages 4 (ASQ-4) and 5 (ASQ-5). From the combinations of normal and abnormal ASQ-4 and ASQ-5 scores we constructed 4 categories: consistently normal, emerging, resolving, and persistent problems. The ASQ-4 total score was abnormal more frequently in moderately-late preterm (7.9%, P = .016) and early preterm-born children (13.0%, P preterm-born children had persistence and change comparable with full term-born children, and early preterm-born children had significantly greater rates than full term-born children of persistent (8.4% vs 2.2%, P preterm and moderately-late preterm-born children had mainly emerging motor problems and resolving communication problems, but the changing rates of moderately-late preterm-born children were lower. After school entry, the overall development of moderately-late preterm-born children had stability patterns comparable with full term-born children, whereas early preterm-born children had greater rates of persistent and emerging problems. On the underlying domains, moderately-late preterm-born children had patterns comparable with early preterm-born children but at lower rates. Copyright © 2017 Elsevier Inc. All rights reserved.
Zeraik, Ana E.; Rinaldi, Gabriel; Mann, Victoria H.; Popratiloff, Anastas; Araujo, Ana P. U.; DeMarco, Ricardo; Brindley, Paul J.
Septins are a family of eukaryotic GTP binding proteins conserved from yeasts to humans. Originally identified in mutants of budding yeast, septins participate in diverse cellular functions including cytokinesis, organization of actin networks, cell polarity, vesicle trafficking and many others. Septins assemble into heteroligomers to form filaments and rings. Here, four septins of Schistosoma mansoni are described, which appear to be conserved within the phylum Platyhelminthes. These orthologues were related to the SEPT5, SEPT10 and SEPT7 septins of humans, and hence we have termed the schistosome septins SmSEPT5, SmSEPT10, SmSEPT7.1 and SmSEPT7.2. Septin transcripts were detected throughout the developmental cycle of the schistosome and a similar expression profile was observed for septins in the stages examined, consistent with concerted production of these proteins to form heterocomplexes. Immunolocalization analyses undertaken with antibodies specific for SmSEPT5 and SmSEPT10 revealed a broad tissue distribution of septins in the schistosomulum and colocalization of septin and actin in the longitudinal and circular muscles of the sporocyst. Ciliated epidermal plates of the miracidium were rich in septins. Expression levels for these septins were elevated in germ cells in the miracidium and sporocyst. Intriguingly, septins colocalize with the protonephridial system of the cercaria, which extends laterally along the length of this larval stage. Together, the findings revealed that schistosomes expressed several septins which likely form filaments within the cells, as in other eukaryotes. Identification and localization demonstrating a broad distribution of septins across organs and tissues of schistosome contributes towards the understanding of septins in schistosomes and other flatworms. PMID:24367716
Zeraik, Ana E; Rinaldi, Gabriel; Mann, Victoria H; Popratiloff, Anastas; Araujo, Ana P U; Demarco, Ricardo; Brindley, Paul J
Septins are a family of eukaryotic GTP binding proteins conserved from yeasts to humans. Originally identified in mutants of budding yeast, septins participate in diverse cellular functions including cytokinesis, organization of actin networks, cell polarity, vesicle trafficking and many others. Septins assemble into heteroligomers to form filaments and rings. Here, four septins of Schistosoma mansoni are described, which appear to be conserved within the phylum Platyhelminthes. These orthologues were related to the SEPT5, SEPT10 and SEPT7 septins of humans, and hence we have termed the schistosome septins SmSEPT5, SmSEPT10, SmSEPT7.1 and SmSEPT7.2. Septin transcripts were detected throughout the developmental cycle of the schistosome and a similar expression profile was observed for septins in the stages examined, consistent with concerted production of these proteins to form heterocomplexes. Immunolocalization analyses undertaken with antibodies specific for SmSEPT5 and SmSEPT10 revealed a broad tissue distribution of septins in the schistosomulum and colocalization of septin and actin in the longitudinal and circular muscles of the sporocyst. Ciliated epidermal plates of the miracidium were rich in septins. Expression levels for these septins were elevated in germ cells in the miracidium and sporocyst. Intriguingly, septins colocalize with the protonephridial system of the cercaria, which extends laterally along the length of this larval stage. Together, the findings revealed that schistosomes expressed several septins which likely form filaments within the cells, as in other eukaryotes. Identification and localization demonstrating a broad distribution of septins across organs and tissues of schistosome contributes towards the understanding of septins in schistosomes and other flatworms.
Ana E Zeraik
Full Text Available Septins are a family of eukaryotic GTP binding proteins conserved from yeasts to humans. Originally identified in mutants of budding yeast, septins participate in diverse cellular functions including cytokinesis, organization of actin networks, cell polarity, vesicle trafficking and many others. Septins assemble into heteroligomers to form filaments and rings. Here, four septins of Schistosoma mansoni are described, which appear to be conserved within the phylum Platyhelminthes. These orthologues were related to the SEPT5, SEPT10 and SEPT7 septins of humans, and hence we have termed the schistosome septins SmSEPT5, SmSEPT10, SmSEPT7.1 and SmSEPT7.2. Septin transcripts were detected throughout the developmental cycle of the schistosome and a similar expression profile was observed for septins in the stages examined, consistent with concerted production of these proteins to form heterocomplexes. Immunolocalization analyses undertaken with antibodies specific for SmSEPT5 and SmSEPT10 revealed a broad tissue distribution of septins in the schistosomulum and colocalization of septin and actin in the longitudinal and circular muscles of the sporocyst. Ciliated epidermal plates of the miracidium were rich in septins. Expression levels for these septins were elevated in germ cells in the miracidium and sporocyst. Intriguingly, septins colocalize with the protonephridial system of the cercaria, which extends laterally along the length of this larval stage. Together, the findings revealed that schistosomes expressed several septins which likely form filaments within the cells, as in other eukaryotes. Identification and localization demonstrating a broad distribution of septins across organs and tissues of schistosome contributes towards the understanding of septins in schistosomes and other flatworms.
Comparative studies utilizing avian and mammalian embryos and neonates have proven particularly useful in exploring how alterations in sensory experience during the perinatal period can affect subsequent development. This article reviews research drawn from comparative developmental psychobiology and concludes that the effects of modified sensory stimulation on perceptual and behavioral development depend on several related factors, including the timing of stimulation relative to the developmental stage of the young organism, the overall amount of sensory stimulation provided or denied, and the type of sensory stimulation presented. Directions for future research on the care of the high-risk infant are discussed.
Reynolds, Clare M.
Evidence from human clinical, epidemiological, and experimental animal models has clearly highlighted a link between the early life environment and an increased risk for a range of cardiometabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and overnutrition, spanning exposure windows that cover the period from preconception through to early infancy, clearly highlight an increased risk for a range of disorders in offspring in later life. This process, preferentially termed “developmental programming” as part of the developmental origins of health and disease (DOHaD) framework, leads to phenotypic outcomes in offspring that closely resemble those of individuals with untreated growth hormone (GH) deficiency, including increased adiposity and cardiovascular disorders. As such, the use of GH as a potential intervention strategy to mitigate the effects of developmental malprogramming has received some attention in the DOHaD field. In particular, experimental animal models have shown that early GH treatment in the setting of poor maternal nutrition can partially rescue the programmed phenotype, albeit in a sex-specific manner. Although the mechanisms remain poorly defined, they include changes to endothelial function, an altered inflammasome, changes in adipogenesis and cardiovascular function, neuroendocrine effects, and changes in the epigenetic regulation of gene expression. Similarly, GH treatment to adult offspring, where an adverse metabolic phenotype is already manifest, has shown efficacy in reversing some of the metabolic disorders arising from a poor early life environment. Components of the GH-insulin-like growth factor (IGF)-IGF binding protein (GH-IGF-IGFBP) system, including insulin-like growth factor 1 (IGF-1), have also shown promise in ameliorating programmed metabolic disorders, potentially acting via epigenetic processes including changes in miRNA profiles and altered DNA methylation. However
Full Text Available In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.
Kokkinopoulos, Ioannis; Ishida, Hidekazu; Saba, Rie; Ruchaya, Prashant; Cabrera, Claudia; Struebig, Monika; Barnes, Michael; Terry, Anna; Kaneko, Masahiro; Shintani, Yasunori; Coppen, Steven; Shiratori, Hidetaka; Ameen, Torath; Mein, Charles; Hamada, Hiroshi; Suzuki, Ken; Yashiro, Kenta
In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.
Ashton, Chandra K; O'Brien-Langer, Anna; Silverstone, Peter H
There is relatively little research about effective therapeutic approaches for children in middle childhood who have attachment related diagnoses as a result of experiencing significant, early developmental trauma. This study describes findings from an intensive, dyad-based intervention, aimed at stabilizing attachment relationships with primary caregivers, increasing caregiver reflective function skills, and reducing children's trauma-related behavioural sequelae. We analyzed retrospective data from 51 caregiver/child dyads who participated in the Trauma and Attachment Group (TAG) Program from September 2011-December 2014. This data included pre- and post-intervention scores retrieved from the Parenting Relationship Questionnaire (PRQ), the Parent Report of Post-Traumatic Stress Symptoms (PROPS), and the Parental Reflective Functioning Questionnaire (PRFQ-1). The preliminary findings show statistically significant improvements in attachment, communication, discipline practices, involvement, and relational frustration. Additionally there were statistically significant improvements in parental reflective functioning, and a trend towards a reduction in symptoms typical of post-traumatic stress disorder. Poor quality or inconsistent interactions with early caregivers can lead to life-long impairments in physical and mental health. This intensive program shows potential as a way to improve longer-term outcomes for children exposed to early developmental trauma. Longer-term research is required to further substantiate outcomes, appraise cost analysis, as well as to consider evaluation with appropriate comparison groups.
Zhao, Xiaoke; Chen, Mengying; Du, Senjie; Li, Hongying; Li, Xiaonan
The aim of this study was to use the Face, Legs, Activity, Cry, Consolability Scale; salivary cortisol levels; and withdrawal reflex thresholds to assess pain, stress, and pain sensitivity in young children with cerebral palsy during early developmental intervention programs. A total of 40 children with cerebral palsy (age range, 1-4 yrs) participated in the early intervention programs, which included neurodevelopmental treatment, neuromuscular electrical stimulation, occupational therapy, head acupuncture, and Chinese traditional manipulation five times per week for 3 wks. The Face, Legs, Activity, Cry, Consolability Scale was applied during the course of each treatment, and salivary cortisol samples were obtained from each child 10 mins before and 10 mins after each treatment. Withdrawal reflex thresholds were assessed via mechanical stimulation of the foot with von Frey hairs. All treatment programs caused some degree of pain. In descending order, the extents of the pain caused by each treatment were head acupuncture, neurodevelopmental treatment, neuromuscular electrical stimulation, Chinese traditional manipulation, and occupational therapy. There were statistically significant increases in salivary cortisol levels after the head acupuncture (P treatment (P treatments. No significant changes were found in the withdrawal reflex thresholds during the study (P > 0.05). The results of this study demonstrate that early developmental intervention programs cause pain and stress in young children with cerebral palsy.
Miyado, Mami; Ogi, Hidenao; Yamada, Gen; Kitoh, Junzo; Jogahara, Takamichi; Oda, Sen-Ichi; Sato, Iwao; Miyado, Kenji; Sunohara, Masataka
Tooth development is a highly organized process characterized by reciprocal interactions between epithelium and mesenchyme. However, the expression patterns and functions of molecules involved in mouse tooth development are unclear from the viewpoint of explaining human dental malformations and anomalies. Here, we show the expression of sonic hedgehog (Shh), a potent initiator of morphogenesis, during the early stages of tooth development in Suncus murinus. Initially, symmetrical, elongated expression of suncus Shh (sShh) was observed in the thin layer of dental epithelial cells along the mesial-distal axis of both jaws. As the dental epithelium continued to develop, sShh was strictly restricted to the predicted leading parts of the growing, invaginating epithelium corresponding to tooth primordia and enamel knots. We propose that some aspects of Shh function in tooth development are widely conserved in mammalian phylogeny.
Tahmoorespur, Mojtaba; Hosseini, Sayyed Morteza; Ostadhosseini, Somayyeh; Nasiri, Mohammad Reza; Nasr-Esfahani, Mohammad Hossein
Background: Little is understood about the regulation of gene expression during early goat embryo development. This study investigated the expression profile of 19 genes, known to be critical for early embryo development in mouse and human, at five different stages of goat in vitro embryo development (oocyte, 8-16 cell, morula, day-7 blastocyst, and day 14 blastocyst). Materials and Methods: In this experimental study, stage-specific profiling using real time-quantitative polymerase chain reaction (RT-qPCR) revealed robust and dynamic patterns of stage-specific gene activity that fall into four major clusters depending on their respective mRNA profiles. Results: The gradual pattern of reduction in the maternally stored transcripts without renewal thereafter (cluster-1: Lifr1, Bmpr1, Alk4, Id3, Ctnnb, Akt, Oct4, Rex1, Erk1, Smad1 and 5) implies that their protein products are essential during early cleavages when the goat embryo is silent and reliant to the maternal legacy of mRNA. The potential importance of transcription augment at day-3 (cluster-2: Fzd, c-Myc, Cdc25a, Sox2) or day- 14 (cluster-3: Fgfr4, Nanog) suggests that they are nascent embryonic mRNAs which intimately involved in the overriding of MET or regulation of blastocyst formation, respectively. The observation of two expression peaks at both day-3 and day-14 (cluster-4: Gata4, Cdx2) would imply their potential importance during these two critical stages of preand periimplantation development. Conclusion: Evolutionary comparison revealed that the selected subset of genes has been rewired in goat and human/goat similarity is greater than the mouse/goat or bovine/goat similarities. The developed profiles provide a resource for comprehensive understanding of goat preimplantation development and pluripotent stem cell engineering as well. PMID:27695614
Mitchell, D. B.; Hauser-Cram, P.
Background: The importance of positive parent-adolescent relationships is stressed in research on adolescents, although very little is known about this relationship when a teen has developmental disabilities (DD). We investigated the relationships of adolescents with disabilities with their mothers and their fathers in order to answer a number of…
Kavcic, Tina; Podlesek, Anja; Zupancic, Maja
This study explored children, preschool, and family characteristics that contribute to individual differences in the developmental trajectories of social competence and internalizing and externalizing behavior. Teachers reported on personality and social adjustment of 304 children at ages 3, 4, 5, and 6 years. Predictors of social adjustment…
Baker, J. K.; Crnic, K. A.
Background: Children with developmental delays exhibit more difficulty with certain emotional processes than their typically developing peers, which seems to partially account for the increased risk for the development of social problems in this population. Despite considerable study with typically developing populations, research on parental…
Snyder, Patricia; And Others
This paper describes two measurement integrity analyses conducted using data on the Battelle Developmental Inventory, obtained from a sample of 78 children with severe disabilities. Procedures used to conduct internal reliability and construct validity analyses are discussed. Researchers are urged to evaluate a test's construct validity when their…
Amerom, B.A. van
In chapter 1 we give our reasons for carrying out this developmental research project on the transition from arithmetic to algebra, which includes the design of an experimental learning strand on solving equations. Chapter 2 describes the theoretical background of the book: current views on the teac
Font, Sarah A.; Berger, Lawrence M.
Associations between experiencing child maltreatment and adverse developmental outcomes are widely studied, yet conclusions regarding the extent to which effects are bidirectional, and whether they are likely causal, remain elusive. This study uses the Fragile Families and Child Wellbeing Study, a birth cohort of 4,898 children followed from birth…
Mitchell, D. B.; Hauser-Cram, P.
Background: The importance of positive parent-adolescent relationships is stressed in research on adolescents, although very little is known about this relationship when a teen has developmental disabilities (DD). We investigated the relationships of adolescents with disabilities with their mothers and their fathers in order to answer a number of…
Poole, Kristie L; Schmidt, Louis A; Ferro, Mark A; Missiuna, Cheryl; Saigal, Saroj; Boyle, Michael H; Van Lieshout, Ryan J
While the trajectory of self-esteem from adolescence to adulthood varies from person to person, little research has examined how differences in early developmental processes might affect these pathways. This study examined how early motor skill development interacted with preterm birth status to predict self-esteem from adolescence through the early 30s. We addressed this using the oldest known, prospectively followed cohort of extremely low birth weight (self-report, and self-esteem was reported during three follow-up periods (age 12-16, age 22-26, and age 29-36). We found that birth weight status moderated the association between early motor skills and self-esteem. Stable over three decades, the self-esteem of normal birth weight participants was sensitive to early motor skills such that those with poorer motor functioning manifested lower self-esteem, while those with better motor skills manifested higher self-esteem. Conversely, differences in motor skill development did not affect the self-esteem from adolescence to adulthood in individuals born at extremely low birth weight. Early motor skill development may exert differential effects on self-esteem, depending on whether one is born at term or prematurely.
Mishra, A; Reddy, I J; Gupta, Psp; Mondal, S
The objective of this study was to find out the impact of L-carnitine (10 mM) on developmental regulation of preimplantation sheep embryos cultured in vitro when supplemented in maturation medium and post-fertilization medium separately. Subsequent objective was to observe the L-carnitine-mediated alteration in expression of apoptotic genes (Bcl2, Bax, Casp3 and PCNA) in sheep oocytes and developing embryos produced in vitro. Oocytes matured with L-carnitine showed significantly (p carnitine during post-fertilization period. So it is suggested to use L-carnitine during maturation than post-fertilization period. Antiapoptotic and proliferative effects of L-carnitine were confirmed by inducing culture medium with actinomycin D (apoptotic agent) and TNFα (antiproliferative agent), respectively, with and without L-carnitine. Oocytes and embryos cultured with actinomycin D and TNFα showed developmental arrest with significant (p supplementation of L-carnitine to actinomycin D and TNFα induced culture medium showed similar result as that of control. L-carnitine supplementation during IVM significantly (p carnitine upregulated the expression of Bax in initial developmental stages but downregulated at latter part, whereas the expression of Casp3 was upregulated upto 16-cell stage but after that there was no difference in expression. Expression of GAPDH gene was not affected by L-carnitine supplementation. In conclusion, L-carnitine acted as an antiapoptotic and proliferative compound during embryo development and supplementation of L-carnitine during IVM altered the expression of apoptotic genes in the developmental stages of embryos.
Myocyte enhancer factor 2 proteins are members of MADS family of transcription factors, which can control the expression of muscle-specific genes in vertebrates. However, not all Mef2 genes are essential for muscle development in invertebrates. Here we have isolated a full-length cDNA from amphioxus, designated AmphiMef2. The predicted amino acid sequence has highly conserved MADS and MEF2 domains, showing higher identity with the corresponding regions of its homologues in vertebrates than those in invertebrates. Results from whole-mount in situ hybridization show that the expression of AmphiMef2 initially appears in the presomitic mesoderm at early neurula stage, then the transcripts are detected in both the somites and the unsegmented presomitic mesoderm. At 36 h larval stage, the expression is only detected in the posterior somites. By 48 h larval stage, the expression is shifted to the preoral pit (a homologous organ to the vertebrate adenohypophysis) and persists until at least 72 h larval stage. The results suggest that AmphiMef2 may be not only involved in the myogenesis but also the development or function of the preoral pit in amphioxus.
Revel S M Drummond
Full Text Available Analysis of mutants with increased branching has revealed the strigolactone synthesis/perception pathway which regulates branching in plants. However, whether variation in this well conserved developmental signalling system contributes to the unique plant architectures of different species is yet to be determined. We examined petunia orthologues of the Arabidopsis MAX1 and MAX2 genes to characterise their role in petunia architecture. A single orthologue of MAX1, PhMAX1 which encodes a cytochrome P450, was identified and was able to complement the max1 mutant of Arabidopsis. Petunia has two copies of the MAX2 gene, PhMAX2A and PhMAX2B which encode F-Box proteins. Differences in the transcript levels of these two MAX2-like genes suggest diverging functions. Unlike PhMAX2B, PhMAX2A mRNA levels increase as leaves age. Nonetheless, this gene functionally complements the Arabidopsis max2 mutant indicating that the biochemical activity of the PhMAX2A protein is not significantly different from MAX2. The expression of the petunia strigolactone pathway genes (PhCCD7, PhCCD8, PhMAX1, PhMAX2A, and PhMAX2B was then further investigated throughout the development of wild-type petunia plants. Three of these genes showed changes in mRNA levels over the development series. Alterations to the expression of these genes over time, or in different regions of the plant, may influence the branching growth habit of the plant. Alterations to strigolactone production and/or sensitivity could allow both subtle and dramatic changes to branching within and between species.
Wu, X P; Liu, X L; Wang, X L; Blaga, R; Fu, B Q; Liu, P; Bai, X; Wang, Z J; Rosenthal, B M; Shi, H N; Sandrine, L; Vallee, I; Boireau, P; Wang, F; Zhou, X N; Zhao, Y; Liu, M Y
Parasite-induced and parasite-regulated larval capsule formation and host immunosuppression are two major characteristics that are unique in Trichinella spp. infections, but the molecule(s) and mechanism(s) that mediate these processes remain largely unknown. Trichinella pseudospiralis and Trichinella spiralis, are obviously different with respect to these two characteristics. A comparative study of these two species, in particular their antigen expression profiles at different developmental stages (the main molecules involved in the cross-talk or interaction between each parasite and its host), may help us better understand the parasite molecules and mechanisms involved. Here, we constructed cDNA libraries from T. pseudospiralis adults (Ad), newborn larvae (NBL) and muscle larvae (ML) mRNA and screened them with pig anti-T. pseudospiralis serum collected 26, 32 and 60 days post-infection (p.i.). The most abundant antigens were found to vary among life-cycle stages. Pyroglutamy peptidase 1-like and 6-phosphogluconolactonase-like genes predominated in the Ad stage and a serine protease (SS2-1-like gene) predominated in NBL similar to that observed in T. spiralis. Muscle larvae expressed proteasome activator complex subunit 3-like and 21 kDa excretory/secretory protein-like genes. This study indicated that parasites of two species may utilise different molecules and mechanisms for larvae capsule formation and host immunosuppression during their infections. Proteins of antigenic genes identified in this study may be also good candidates for diagnosis, treatment or vaccination for T. pseudospiralis infection, and also for the differential diagnosis of two species' infections.
Acheampong, Atiako Kwame; Hu, Jianhong; Rotman, Ariel; Zheng, Chuanlin; Halaly, Tamar; Takebayashi, Yumiko; Jikumaru, Yusuke; Kamiya, Yuji; Lichter, Amnon; Sun, Tai-Ping; Or, Etti
Gibberellins (GAs) regulate numerous developmental processes in grapevine (Vitis vinifera) such as rachis elongation, fruit set, and fruitlet abscission. The ability of GA to promote berry enlargement has led to its indispensable use in the sternospermocarpic ('seedless') table grape industry worldwide. However, apart from VvGAI1 (VvDELLA1), which regulates internode elongation and fruitfulness, but not berry size of seeded cultivars, little was known about GA signalling in grapevine. We have identified and characterized two additional DELLAs (VvDELLA2 and VvDELLA3), two GA receptors (VvGID1a and VvGID1b), and two GA-specific F-box proteins (VvSLY1a and VvSLY1b), in cv. Thompson seedless. With the exception of VvDELLA3-VvGID1b, all VvDELLAs interacted with the VvGID1s in a GA-dependent manner in yeast two-hybrid assays. Additionally, expression of these grape genes in corresponding Arabidopsis mutants confirmed their functions in planta. Spatiotemporal analysis of VvDELLAs showed that both VvDELLA1 and VvDELLA2 are abundant in most tissues, except in developing fruit where VvDELLA2 is uniquely expressed at high levels, suggesting a key role in fruit development. Our results further suggest that differential organ responses to exogenous GA depend on the levels of VvDELLA proteins and endogenous bioactive GAs. Understanding this interaction will allow better manipulation of GA signalling in grapevine. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.
Borgomaneri, Sara; Vitale, Francesca; Avenanti, Alessio
Quick inhibition of approach tendencies in response to signals of potential threats is thought to promote survival. However, little is known about the effect of viewing fearful expressions on the early dynamics of the human motor system. We used the high temporal resolution of single-pulse and paired-pulse transcranial magnetic stimulation (TMS) over the motor cortex to assess corticospinal excitability (CSE) and intracortical facilitation (ICF) during observation of happy, fearful and neutral body postures. To test motor circuits involved in approach tendencies, CSE and ICF were recorded from the first dorsal interosseous (FDI), a muscle involved in grasping, and the abductor pollicis brevis (APB), which served as a control. To test early motor dynamics, CSE and ICF were measured 70-90 ms after stimulus onset. We found a selective reduction in CSE in the FDI when participants observed fearful body expressions. No changes in ICF or in the excitability of APB were detected. Our study establishes an extremely rapid motor system reaction to observed fearful body expressions. This motor modulation involves corticospinal downstream projections but not cortical excitatory mechanisms, and appears to reflect an inhibition of hand grasping. Our results suggest a fast visuo-motor route that may rapidly inhibit inappropriate approaching actions.
Ragland, Gregory J; Egan, Scott P; Feder, Jeffrey L; Berlocher, Stewart H; Hahn, Daniel A
The timing of dormancy is a rapidly evolving life-history trait playing a crucial role in the synchronization of seasonal life cycles and adaptation to environmental change. But the physiological mechanisms regulating dormancy in animals remain poorly understood. In insects, dormancy (diapause) is a developmentally dynamic state, and the mechanisms that control diapause transitions affect seasonal timing. Here we used microarrays to examine patterns of gene expression during dormancy termination: a crucial life-history transition in the apple maggot fly Rhagoletis pomonella (Walsh). This species is a model system for host race formation and ecological speciation via changes in diapause regulation of seasonality. Our goal was to pinpoint the timing of the transition from diapause to post-diapause development and to identify candidate genes and pathways for regulation of diapause termination. Samples were taken at six metabolically defined developmental landmarks, and time-series analysis suggests that release from metabolic depression coincides with preparation for or resumption of active cell cycling and morphogenesis, defining the 'end' of diapause. However, marked changes in expression, including members of pathways such as Wnt and TOR signaling, also occur prior to the metabolic rate increase, electing these pathways as candidates for early regulation of diapause termination. We discuss these results with respect to generalities in insect diapause physiology and to our long-term goal of identifying mechanisms of diapause adaptation in the Rhagoletis system.
Staal, Ingrid I E; van Stel, Henk F.; Hermanns, Jo M A; Schrijvers, Augustinus J P
Objective: The early detection of parenting and developmental problems by preventive child health care (CHC) services in the Netherlands takes place almost exclusively at the well-baby clinic. This study assesses whether, compared to a visit to the well-baby clinic, a home visit improves early detec
Glanzner, Werner G; Wachter, Audrey; Coutinho, Ana Rita S; Albornoz, Marcelo S; Duggavathi, Raj; GonÇAlves, Paulo B D; Bordignon, Vilceu
Epigenetics is a fundamental regulator underlying many biological functions, such as development and cell differentiation. Epigenetic modifications affect key chromatin regulation, including transcription and DNA repair, which are critical for normal embryo development. In this study, we profiled the expression of epigenetic modifiers and patterns of epigenetic changes in porcine embryos around the period of embryonic genome activation (EGA). We observed that Brahma-related gene 1 (BRG1) and Lysine demethylase 1A (KDM1A), which can alter the methylation status of lysine 4 in histone 3 (H3K4), localize to the nucleus at Day 3-4 of development. We then compared the abundance of epigenetic modifiers between early- and late-cleaving embryos, which were classified based on the time to the first cell cleavage, to investigate if their nuclear localization contributes to developmental competence. The mRNA abundance of BRG1, KDM1A, as well as other lysine demethylases (KDM1B, KDM5A, KDM5B, and KDM5C), were significantly higher in late- compared to early-cleaving embryos near the EGA period, although these difference disappeared at the blastocyst stage. The abundance of H3K4 mono- (H3K4me) and di-methylation (H3K4me2) during the EGA period was reduced in late-cleaving and less developmentally competent embryos. By contrast, BRG1, KDM1A, and H3K4me2 abundance was greater in embryos with more than eight cells at Day 3-4 of development compared to those with fewer than four cells. These findings suggest that altered epigenetic modifications of H3K4 around the EGA period may affect the developmental capacity of porcine embryos to reach the blastocyst stage. Mol. Reprod. Dev. 84: 19-29, 2017. © 2016 Wiley Periodicals, Inc.
Takahashi, Yusuke; Okada, Kensuke; Hoshino, Takahiro; Anme, Tokie
This study used data from a nationwide survey in Japan to model the developmental course of social skills during early childhood. The goals of this study were to identify longitudinal profiles of social skills between 2 and 5 years of age using a group-based trajectory approach, and to investigate whether and to what extent parenting practices at 2 years of age predicted developmental trajectories of social skills during the preschool period. A relatively large sample of boys and girls (N > 1,000) was assessed on three social skill dimensions (Cooperation, Self-control, and Assertion) at four time points (ages 2, 3, 4, and 5), and on four parenting practices (cognitive and emotional involvement, avoidance of restriction and punishment, social stimulation, and social support for parenting) at age 2. The results indicated that for each social skill dimension, group-based trajectory models identified three distinct trajectories: low, moderate, and high. Multinomial regression analysis revealed that parenting practice variables showed differential contributions to development of child social skills. Specifically, Cooperation and Assertion were promoted by cognitive and emotional involvement, Self-control by social stimulation, and Assertion by avoidance of restriction and punishment. Abundant social support for parenting was not associated with higher child social skills trajectories. We found heterogeneity in developmental profiles of social skills during the preschool ages, and we identified parenting practices that contributed to different patterns of social skills development. We discussed the implications of higher-quality parenting practices on the improvement of child social skills across early childhood.
Réus, Gislaine Z; Fernandes, Gabrielly C; de Moura, Airam B; Silva, Ritele H; Darabas, Ana Caroline; de Souza, Thays G; Abelaira, Helena M; Carneiro, Celso; Wendhausen, Diogo; Michels, Monique; Pescador, Bruna; Dal-Pizzol, Felipe; Macêdo, Danielle S; Quevedo, João
This study used an animal model of depression induced by maternal care deprivation (MCD) to investigate whether depressive behaviour, neuroinflammation and oxidative stress were underlying factors in developmental programming after early life stress. At postnatal days (PND) 20, 30, 40, and 60, individual subsets of animals were evaluated in behavioural tests and then euthanized to assess cytokine levels and oxidative stress parameters in the prefrontal cortex (PFC), hippocampus and serum. The results showed that MCD did not induce behavioural changes at PND 30 and 40. However, at PND 20 and 60, the rats displayed a depressive-like behaviour in the forced swimming test, without changes in locomotor spontaneous activity. In the brain and serum, the levels of pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α)) were increased, and the anti-inflammatory cytokine (interleukin-10) level was reduced throughout developmental programming (PND 20, 30, 40 and 60). Protein carbonyl levels increased in the brain at PND 30, 40 and 60. Superoxide dismutase (SOD) activity was decreased during all developmental programming phases evaluated in the brain. Catalase (CAT) activity was decreased at PND 20, 40 and 60 in the brain. Our results revealed that "critical episodes" in early life stressful events are able to induce behavioural alterations that persist into adulthood and can stimulate inflammation and oxidative damage in both central and peripheral systems, which are required for distinct patterns of resilience against psychiatric disorders later in life. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available This study used data from a nationwide survey in Japan to model the developmental course of social skills during early childhood. The goals of this study were to identify longitudinal profiles of social skills between 2 and 5 years of age using a group-based trajectory approach, and to investigate whether and to what extent parenting practices at 2 years of age predicted developmental trajectories of social skills during the preschool period. A relatively large sample of boys and girls (N > 1,000 was assessed on three social skill dimensions (Cooperation, Self-control, and Assertion at four time points (ages 2, 3, 4, and 5, and on four parenting practices (cognitive and emotional involvement, avoidance of restriction and punishment, social stimulation, and social support for parenting at age 2. The results indicated that for each social skill dimension, group-based trajectory models identified three distinct trajectories: low, moderate, and high. Multinomial regression analysis revealed that parenting practice variables showed differential contributions to development of child social skills. Specifically, Cooperation and Assertion were promoted by cognitive and emotional involvement, Self-control by social stimulation, and Assertion by avoidance of restriction and punishment. Abundant social support for parenting was not associated with higher child social skills trajectories. We found heterogeneity in developmental profiles of social skills during the preschool ages, and we identified parenting practices that contributed to different patterns of social skills development. We discussed the implications of higher-quality parenting practices on the improvement of child social skills across early childhood.
Full Text Available Familial Dysautonomia (FD is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population, and leads to death before the age of 40. The disease is characterized by abnormal development and progressive degeneration of the sensory and autonomic nervous system. A single base pair substitution in intron 20 of the Ikbkap gene accounts for 98% of FD cases, and results in the expression of low levels of the full-length mRNA with simultaneous expression of an aberrantly spliced mRNA in which exon 20 is missing. To date, there is no animal model for the disease, and the essential cellular functions of IKAP--the protein encoded by Ikbkap--remain unknown. To better understand the normal function of IKAP and in an effort to generate a mouse model for FD, we have targeted the mouse Ikbkap gene by homologous recombination. We created two distinct alleles that result in either loss of Ikbkap expression, or expression of an mRNA lacking only exon 20. Homozygosity for either mutation leads to developmental delay, cardiovascular and brain malformations, accompanied with early embryonic lethality. Our analyses indicate that IKAP is essential for expression of specific genes involved in cardiac morphogenesis, and that cardiac failure is the likely cause of abnormal vascular development and embryonic lethality. Our results also indicate that deletion of exon 20 abolishes gene function. This implies that the truncated IKAP protein expressed in FD patients does not retain any significant biological function.
SU; Zhixi; DONG; Xinjiao; ZHANG; Bing; ZENG; Yanwu; FU; Yan; YU; Jun; HU; Songnian
A total of 28941 ESTs were sequenced from five 5(-directed non-normalized cDNA libraries, which were assembled into 2212 contigs and 5642 singlets using CAP3. These sequences were annotated and clustered into 6857 unique genes, 2072 of which having no functional annotations were considered as novel genes. These genes were further classified into Gene Ontology categories. By comparing the expression profiles, we identified some breed- and developmental-stage-specific gene groups. These genes may be relative to reproductive performance or play important roles in milk synthesis, secretion and mammary involution. The unknown EST sequences and expression profiles at different developmental stages and breeds are very important resources for further research.
Shulman, Elizabeth P; Harden, K Paige; Chein, Jason M; Steinberg, Laurence
It has been proposed that high rates of risk-taking in adolescence are partly attributable to patterns of neurobiological development that promote an increase in sensation-seeking tendencies at a time when impulse control is still developing. It is not known, however, whether this pattern is the same for males and females. The present study investigates sex differences in the developmental trajectories of self-reported impulse control and sensation-seeking between the ages of 10 and 25 using longitudinal data from the National Longitudinal Study of Youth 1979 Child and Young Adult Survey (N = 8,270; 49% female; 33% Black, 22% Hispanic, 45% Non-Black, Non-Hispanic). Prior work has found that, consistent with the dual-systems model of adolescent neurobiological development, sensation-seeking rises and falls across this age span, whereas impulse control increases into the 20s. In the present study, we find that this same general pattern holds for both males and females, but with some key differences. As expected, males exhibit higher levels of sensation-seeking and lower levels of impulse control than females. Differences also emerged in the shapes of the developmental trajectories. Females reach peak levels of sensation-seeking earlier than males (consistent with the idea that sensation-seeking is linked to pubertal development) and decline in sensation-seeking more rapidly thereafter. Also, males increase in impulse control more gradually than females. Consequently, sex differences in both impulse control and sensation-seeking increase with age. The findings suggest that the window of heightened vulnerability to risk-taking during adolescence may be greater in magnitude and more protracted for males than for females.
Oommen, A; Dixon, R A; Paiva, N L
In legumes, the synthesis of infection- and elicitor-inducible antimicrobial phytoalexins occurs via the isoflavonoid branch of the phenylpropanoid pathway. To study transcriptional regulation of isoflavonoid pathway-specific genes, we have isolated the gene encoding isoflavone reductase (IFR), which is the enzyme that catalyzes the penultimate step in the synthesis of the phytoalexin medicarpin in alfalfa. Chimeric gene fusions were constructed between 765- and 436-bp promoter fragments of the IFR gene and the beta-glucuronidase reporter gene and transferred to alfalfa and tobacco by Agrobacterium-mediated transformation. Both promoter fragments conferred elicitor-mediated expression in cell suspension cultures derived from transgenic plants of both species and fungal infection-mediated expression in leaves of transgenic alfalfa. Developmental expression directed by both promoter fragments in transgenic alfalfa was observed only in the root meristem, cortex, and nodules, which is consistent with the accumulation of endogenous IFR transcripts. However, in transgenic tobacco, expression from the 765-bp promoter was observed in vegetative tissues (root meristem and cortex, inner vascular tissue of stems and petioles, leaf tips, and stem peripheries adjacent to petioles) and in reproductive tissues (stigma, placenta, base of the ovary, receptacle, seed, tapetal layer, and pollen grains), whereas the 436-bp promoter was expressed only in fruits, seed, and pollen. These data indicate that infection/elicitor inducibility of the IFR promoter in both species and developmental expression in alfalfa are determined by sequences downstream of position -436, whereas sequences between -436 and -765 confer a complex pattern of strong ectopic developmental expression in the heterologous species that lacks the isoflavonoid pathway. PMID:7866024
Song, Z-M; Hu, J; Rudy, B; Redman, S J
One class of spinal interneurons, the Renshaw cells, is able to discharge at very high frequencies in adult mammals. Neuronal firing at such high frequencies requires voltage-gated potassium channels to rapidly repolarize the membrane potential after each action potential. We sought to establish the pattern of expression of calbindin and potassium channels with Kv3.1b and Kv3.2 subunits in Renshaw cells at different developmental stages of postnatal mice. The pattern of expression of calbindin changed dramatically during early postnatal development. An adult pattern of calbindin reactive neurons started to emerge from postnatal day 10 to postnatal day 14, with cells in laminae I and II of superficial dorsal horn and the ventral lamina VII. Renshaw cells were identified immunohistochemically by their expression of calbindin and their location in the ventral horn of the spinal cord. Western blot results of the lumbar spinal cord showed that Kv3.1b expression became faintly evident from postnatal day 10, reached a maximum at postnatal day 21 and was maintained through postnatal day 49. Double labeling results showed that all Renshaw cells expressed Kv3.1b weakly from postnatal day 14, and strongly at postnatal day 21. Western blot results showed that Kv3.2 expression became detectable in the lumbar cord from postnatal day 12, and increased steadily until reaching an adult level at postnatal day 28. In contrast to the Kv3.1b results, Kv3.2 was not expressed in Renshaw cells, although some neurons located at laminae VIII and VI expressed Kv3.2. We conclude that Renshaw cells express Kv3.1b but not Kv3.2 from postnatal day 14.
Peter C Brunjes
Full Text Available Neurons in the cerebral cortex stratify on the basis of their time of origin, axonal terminations and the molecular identities assigned during early development. Olfactory cortices share many feature with the neocortex, including clear lamination and similar cell types. The present study demonstrates that the markers differentially expressed in the projection neurons of the cerebral cortex are also found in olfactory areas. Three of the four regions examined (pars principalis of the anterior olfactory nucleus: AONpP, anterior and posterior piriform cortices: APC, PPC, and the olfactory tubercle expressed transcription factors found in deep or superficial neurons in the developing neocortex, though large differences were found between areas. For example, while the AONpP, APC and PPC all broadly expressed the deep cortical marker CTIP2, NOR1 (NR4a3 levels were higher in AONpP and DAARP-32 was more prevalent in the APC and PPC. Similar findings were encountered for superficial cortical markers: all three regions broadly expressed CUX1, but CART was only observed in the APC and PPC. Furthermore, regional variations were observed even within single structures (e.g., NOR1 was found primarily in in the dorsal region of AONpP and CART expression was observed in a discrete band in the middle of layer 2 of both the APC and PPC. Experiments using the mitotic marker EDU verified that the olfactory cortices and neocortex share similar patterns of neuronal production: olfactory cells that express markers found in the deep neocortex are produced earlier than those that express superficial makers. Projection neurons were filled by retrograde tracers injected into the olfactory bulb to see if olfactory neurons with deep and superficial markers had different axonal targets. Unlike the cerebral cortex, no specificity was observed: neurons with each of the transcription factors examined were found to be labelled. Together the results indicate that olfactory
El Meskini, Rajaâ; Cline, Laura B; Eipper, Betty A; Ronnett, Gabriele V
Menkes disease (MD) is a neurodegenerative disorder caused by mutation of the copper transporter ATP7A. While several enzymes expressed in mature neurons require copper, MD neurodegenerative changes cannot be explained by known requirements for ATP7A in neuronal development. To investigate additional roles for ATP7A during development, we characterized its pattern of expression using the olfactory system as a neurodevelopmental model. ATP7A expression in neurons was developmentally regulated rather than constitutively. Initially expressed in the cell bodies of developing neurons, ATP7A protein later shifted to extending axons, peaking prior to synaptogenesis. Similarly, after injury-stimulated neurogenesis, ATP7A expression increased in neurons and axons preceding synaptogenesis. Interestingly, copper-transport-deficient ATP7A still exhibits axonal localization. These results support a role for ATP7A in axon extension, which may contribute to the severe neurodegeneration characteristic of MD.
Brunskill, Eric W; Potter, Andrew S; Distasio, Andrew; Dexheimer, Phillip; Plassard, Andrew; Aronow, Bruce J; Potter, S Steven
We present a gene expression atlas of early mouse craniofacial development. Laser capture microdissection (LCM) was used to isolate cells from the principal critical microregions, whose development, differentiation and signaling interactions are responsible for the construction of the mammalian face. At E8.5, as migrating neural crest cells begin to exit the neural fold/epidermal ectoderm boundary, we examined the cranial mesenchyme, composed of mixed neural crest and paraxial mesoderm cells, as well as cells from adjacent neuroepithelium. At E9.5 cells from the cranial mesenchyme, overlying olfactory placode/epidermal ectoderm, and underlying neuroepithelium, as well as the emerging mandibular and maxillary arches were sampled. At E10.5, as the facial prominences form, cells from the medial and lateral prominences, the olfactory pit, multiple discrete regions of underlying neuroepithelium, the mandibular and maxillary arches, including both their mesenchymal and ectodermal components, as well as Rathke's pouch, were similarly sampled and profiled using both microarray and RNA-seq technologies. Further, we performed single cell studies to better define the gene expression states of the early E8.5 pioneer neural crest cells and paraxial mesoderm. Taken together, and analyzable by a variety of biological network approaches, these data provide a complementing and cross validating resource capable of fueling discovery of novel compartment specific markers and signatures whose combinatorial interactions of transcription factors and growth factors/receptors are responsible for providing the master genetic blueprint for craniofacial development.
Mass, Tali; Putnam, Hollie M; Drake, Jeana L; Zelzion, Ehud; Gates, Ruth D; Bhattacharya, Debashish; Falkowski, Paul G
Reef-building corals begin as non-calcifying larvae that, upon settling, rapidly begin to accrete skeleton and a protein-rich skeletal organic matrix that attach them to the reef. Here, we characterized the temporal and spatial expression pattern of a suite of biomineralization genes during three stages of larval development in the reef-building coral Pocillopora damicornis: stage I, newly released; stage II, oral-aborally compressed and stage III, settled and calcifying spat. Transcriptome analysis revealed 3882 differentially expressed genes that clustered into four distinctly different patterns of expression change across the three developmental stages. Immunolocalization analysis further reveals the spatial arrangement of coral acid-rich proteins (CARPs) in the overall architecture of the emerging skeleton. These results provide the first analysis of the timing of the biomineralization 'toolkit' in the early life history of a stony coral. © 2016 The Author(s).
Severe developmental thyroid hormone (TH) insufficiency results in alterations in brain structure/function and lasting behavioral impairments. Environmental toxicants reduce circulating levels of TH, but the disruption is modest and the doseresponse relationships of TH and neuro...
Sun, Xiao-Jian; Xu, Peng-Fei; Zhou, Ting; Hu, Ming; Fu, Chun-Tang; Zhang, Yong; Jin, Yi; Chen, Yi; Chen, Sai-Juan; Huang, Qiu-Hua; Liu, Ting Xi; Chen, Zhu
.... Since some of these genes have been revealed to be essential for embryonic development, we propose that the zebrafish, a vertebrate model organism possessing many advantages for developmental studies...
Toll, Sylke W. M.; Van Luit, Johannes E. H.
The relationship between basic oral language and early numeracy has been studied extensively, but results hardly include kindergartners' math language, which might mediate this relationship. The aim of this study was to investigate the development of basic language skills--specifically, math language and low early numeracy. Dutch children (4-5…
Taylor, Sophie Jane; Barker, Lynne Ann; Heavey, Lisa; McHale, Sue
Executive functions and social cognition develop through childhood into adolescence and early adulthood and are important for adaptive goal-oriented behavior (Apperly, Samson, & Humphreys, 2009; Blakemore & Choudhury, 2006). These functions are attributed to frontal networks known to undergo protracted maturation into early adulthood…
Hickman, Robbin; McCoy, Sarah Westcott; Long, Toby M.; Rauh, Mitchell J.
Changes in early childhood science, theory, and best practices for improving outcomes of children with motor delay or dysfunction and their families have evolved rapidly since EI began. Changes in daily early intervention (EI) practice have been more elusive. Closing the gap between knowledge and practice requires EI providers to piece together…
Brumberg, H L; Shah, S I
Poverty is associated with adverse long-term cognitive outcomes in children. Poverty is also linked with preterm delivery which, in turn, is associated with adverse cognitive outcomes. However, the extent of the effect of poverty on preterm delivery, as well as proposed mechanisms by which they occur, have not been well described. Further, the impact of poverty on preterm school readiness has not been reviewed. As the childhood poverty level continues to increase in the U.S., we examine the evidence around physiological, neurological, cognitive and learning outcomes associated with prematurity in the context of poverty. We use the evidence gathered to suggest an Eco-Bio-Developmental model, emphasizing poverty as a toxic stress which predisposes preterm birth and which, via epigenetic forces, can continue into the next generation. Continued postnatal social disadvantage for these developmentally high-risk preterm infants is strongly linked with poor neurodevelopmental outcomes, decreased school readiness, and decreased educational attainment which can perpetuate the poverty cycle. We suggest social remedies aimed at decreasing the impact of poverty on mothers, fathers, and children which may be effective in reducing the burden of preterm birth.
Yang, Pu; Chen, Xiao-Ming; Liu, Wei-Wei; Feng, Ying; Sun, Tao
The Chinese white wax scale insect, Ericerus pela, represents one of the most dramatic examples of sexual dimorphism in any insect species. In this study, we showed that although E. pela males display complete metamorphosis similar to holometabolous insects, the species forms the sister group to Acyrthosiphon pisum and cluster with hemimetabolous insects. The gene expression profile and Gene Ontology (GO) analyses revealed that the two sexes engaged in distinct developmental programs. In particular, female development appeared to prioritize the expression of genes related to cellular, metabolic, and developmental processes and to anatomical structure formation in nymphs. By contrast, male nymphal development is characterized by the significant down-regulation of genes involved in chitin, the respiratory system, and neurons. The wing and appendage morphogenesis, anatomical and tissue structure morphogenesis programs activated after male nymphal development. Transcription factors (that convey juvenile hormone or ecdysone signals, and Hox genes) and DNA methyltransferase were also differentially expressed between females and males. These results may indicate the roles that these differentially expressed genes play in regulating sexual dimorphism through orchestrating complex genetic programs. This differential expression was particularly prominent for processes linked to female development and wing development in males.
Full Text Available Huntington's Disease (HD is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480 of the 28,087 confidently detected genes are differentially expressed (FDR<0.05 and are predominantly up-regulated. A novel hypothesis-free geneset enrichment method that dissects large gene lists into functionally and transcriptionally related groups discovers that the differentially expressed genes are enriched for immune response, neuroinflammation, and developmental genes. Markers for all major brain cell types are observed, suggesting that HD invokes a systemic response in the brain area studied. Unexpectedly, the most strongly differentially expressed genes are a homeotic gene set (represented by Hox and other homeobox genes, that are almost exclusively expressed in HD, a profile not widely implicated in HD pathogenesis. The significance of transcriptional changes of developmental processes in the HD brain is poorly understood and warrants further investigation. The role of inflammation and the significance of non-neuronal involvement in HD pathogenesis suggest anti-inflammatory therapeutics may offer important opportunities in treating HD.
Kruszka, Katarzyna; Pacak, Andrzej; Swida-Barteczka, Aleksandra; Stefaniak, Agnieszka K; Kaja, Elzbieta; Sierocka, Izabela; Karlowski, Wojciech; Jarmolowski, Artur; Szweykowska-Kulinska, Zofia
MicroRNAs (miRNAs) regulate gene expression via mRNA cleavage or translation inhibition. In spite of barley being a cereal of great economic importance, very little data is available concerning its miRNA biogenesis. There are 69 barley miRNA and 67 pre-miRNA sequences available in the miRBase (release 19). However, no barley pri-miRNA and MIR gene structures have been shown experimentally. In the present paper, we examine the biogenesis of selected barley miRNAs and the developmental regulation of their pri-miRNA processing to learn more about miRNA maturation in barely. To investigate the organization of barley microRNA genes, nine microRNAs - 156g, 159b, 166n, 168a-5p/168a-3p, 171e, 397b-3p, 1120, and 1126 - were selected. Two of the studied miRNAs originate from one MIR168a-5p/168a-3p gene. The presence of all miRNAs was confirmed using a Northern blot approach. The miRNAs are encoded by genes with diverse organizations, representing mostly independent transcription units with or without introns. The intron-containing miRNA transcripts undergo complex splicing events to generate various spliced isoforms. We identified miRNAs that were encoded within introns of the noncoding genes MIR156g and MIR1126. Interestingly, the intron that encodes miR156g is spliced less efficiently than the intron encoding miR1126 from their specific precursors. miR397b-3p was detected in barley as a most probable functional miRNA, in contrast to rice where it has been identified as a complementary partner miRNA*. In the case of miR168a-5p/168a-3p, we found the generation of stable, mature molecules from both pre-miRNA arms, confirming evolutionary conservation of the stability of both species, as shown in rice and maize. We suggest that miR1120, located within the 3' UTR of a protein-coding gene and described as a functional miRNA in wheat, may represent a siRNA generated from a mariner-like transposable element. Seven of the eight barley miRNA genes characterized in this study contain
This thesis aims to examine the links between exposure to parents’ depression and anxiety in the early years of life, and infants’ socio-emotional development. The thesis first focuses on the associations between infants’ and parents’ emotional expressions, and between infants’ and parents’ reaction
de Winter, M
Early detection of abnormality in young children (aged 0-7) in the Netherlands is to be organized on two levels. First, regional cooperation between child-health professionals and institutions will be stimulated in order to form a nationwide network of 'multidisciplinary teams', with the task of coordinating early detection in a specific area. These teams are to advise parents and professionals in those cases where a child's development is suspected of being 'at risk'. The second part of the program is a campaign to promote the idea of early detection among the population. The aim is to develop the 'signalizing' and diagnostic abilities of parents, teachers and child-health professionals through education and training. The subject of early detection seemed and still seems to be a focus of different interests, and of conflicts of competence between different groups and schools of professionals and different institutions. In this article some of the main conflicting issues are discussed. One of the important problems concerning early detection is the question of defining normality and abnormality. It is concluded that in the case of early detection of both somatic and psychosomatic disorder there can be no such thing as an absolute scientific rationality, as is often suggested. Theoretical frameworks underlying methods of early detection are influenced by social, cultural and historical factors, and thus form a social construction. Finally a protocol-approach is being suggested, a method that might clear some of the problems concerning the content and organizational procedures of the Dutch system for early detection.
Power Deborah M
Full Text Available Abstract Background DAX1 (NR0B1, a member of the nuclear receptors super family, has been shown to be involved in the genetic sex determination and in gonadal differentiation in several vertebrate species. In the aquaculture fish European sea bass, Dicentrarchus labrax, and in the generality of fish species, the mechanisms of sex determination and differentiation have not been elucidated. The present study aimed at characterizing the European DAX1 gene and its developmental expression at the mRNA level. Methods A full length European sea bass DAX1 cDNA (sbDAX1 was isolated by screening a testis cDNA library. The structure of the DAX1 gene was determined by PCR and Southern blot. Multisequence alignments and phylogenetic analysis were used to compare the translated sbDAX1 product to that of other vertebrates. sbDAX1 expression was analysed by Northern blot and relative RT-PCR in adult tissues. Developmental expression of mRNA levels was analysed in groups of larvae grown either at 15°C or 20°C (masculinising temperature during the first 60 days, or two groups of fish selected for fast (mostly females and slow growth. Results The sbDAX1 is expressed as a single transcript in testis and ovary encoding a predicted protein of 301 amino acids. A polyglutamine stretch of variable length in different DAX1 proteins is present in the DNA binding domain. The sbDAX1 gene is composed of two exons, separated by a single 283 bp intron with conserved splice sites in same region of the ligand binding domain as other DAX1 genes. sbDAX1 mRNA is not restricted to the brain-pituitary-gonadal axis and is also detected in the gut, heart, gills, muscle and kidney. sbDAX1 mRNA was detected as early as 4 days post hatching (dph and expression was not affected by incubation temperature. Throughout gonadal sex differentiation (60–300 dph no dimorphic pattern of expression was observed. Conclusion The sbDAX1 gene and putative protein coding region is highly conserved
Francisco Alcantud Marín
Full Text Available This article introduces the System for Early Detection of Developmental Disorders (referred to as SDPTD for its abbreviation in Spanish, a system developed in previous papers. The SDPTD is a developmental screening test that includes seven questionnaires, one for each cutoff of age (3, 6, 9, 12, 18, 24 and 36 months. These questionnaires have been designed to be answered by parents. To study its validity, SDPTD was administered to a sample of 728 children (approximately 100 children in each of the seven cutoff age groups. A development scale known as Merrill-Palmer-Revised (MP-R was used as a criteria test. The development state of the children was tested again one year later. The results show a high level of agreement between parents and professionals. The concurrent validity is high although it varies by cutoff age. Regarding the diagnostic validity a year after the original evaluation, levels of sensitivity and specificity are high enough to consider the system reliable, valid and suitable for screening purposes.
Schlomer, Gabriel L; Cleveland, H Harrington; Vandenbergh, David J; Feinberg, Mark E; Neiderhiser, Jenae M; Greenberg, Mark T; Spoth, Richard; Redmond, Cleve
Aggression-related problems such as assault and homicide among adolescents and young adults exact considerable social and economic costs. Although progress has been made, additional research is needed to help combat this persistent problem. Several lines of research indicate that parental hostility is an especially potent predictor of adolescent aggression, although most longitudinal research has focused on clarifying the direction of effects. In this study, we used longitudinal data from the PROSPER project (N = 580; 54.8% female), a primarily rural Caucasian preventative intervention sample, to examine developmental change in early- to mid-adolescent aggressive behavior problems (age 11-16 years). In addition, we examined maternal hostility as a predictor of developmental change in aggression and the PROSPER preventative intervention, designed to reduce substance use and aggression, as a potential influence on this association. Lastly, several studies indicate that variation in the DRD4 7-repeat gene moderates both parenting and intervention influences on externalizing behavior. Accordingly, we examined the potential moderating role of DRD4. As hypothesized, there was a significant maternal hostility by intervention interaction indicating that the intervention reduced the negative impact of maternal hostility on adolescent change in aggressive behavior problems. DRD4 7-repeat status (7+ vs. 7-) further conditioned this association whereby control group 7+ adolescents with hostile mothers showed increasing aggressive behavior problems. In contrast, aggression decreased for 7+ adolescents with similarly hostile mothers in the intervention. Implications for prevention are discussed as well as current perspectives in candidate gene-by-environment interaction research.
Tariq, Amna; Alam Ansari, Munawar; Owais Ismail, Muhammad; Memon, Zahida
Objective: Our objective of the study was to determine the association between frequent use of Penicillins and Cephalosporins with developmental defects of enamel in pediatric age group. Methods: This is a cross sectional study, conducted at Ziauddin University. A total of 367 children, having the history of either Penicillin or Cephalosporin exposure were included. The parents of children were asked to complete a questionnaire related to disease and drug history. Dental examination was carried out to assess the hypomineralization in tooth enamel based on modified Developmental Defects of Enamel (DDE) index. Results: Out of 367 children, 124 (34%) were males and females were 243(66%). In the study group 22.6% (n= 83) of children were found to be hypomineralized. The maximum type of teeth defects were diffused opacities that was 12.0% (n=44). The statistically significant association (p-value hypomineralization for most teeth. Children who were exposed to either Penicillins or Cephalosporin in early childhood showed significant (p-value hypomineralized enamel. Conclusion: This study concludes that frequent use of antibiotics such as penicillins and cephalosporins has positive association with enamel hypomineralization in developing tooth structure. PMID:24772150
Smidt, M.; Smits, S.; Bouwmeester, H.; Hamers, F.; Hellemons, A.; Burbach, J.P.H.
The mesencephalic dopamine (mesDA) system is involved in the control of movement and behavior. The expression of Pitx3 in the brain is restricted to the mesDA system and the gene is induced relatively late, at E11.5, a time when tyrosine hydroxylase (Th) gene expression is initiated. We show here th
Full Text Available Apart from their remarkable phonological skills young infants prior to their first birthday show ability to match the mouth articulation they see with the speech sounds they hear. They are able to detect the audiovisual conflict of speech and to selectively attend to articulating mouth depending on audiovisual congruency. Early audiovisual speech processing is an important aspect of language development, related not only to phonological knowledge, but also to language production during subsequent years. Th is article reviews recent experimental work delineating the complex developmental trajectory of audiovisual mismatch detection. Th e central issue is the role of age-related changes in visual scanning of audiovisual speech and the corresponding changes in neural signatures of audiovisual speech processing in the second half of the first year of life. Th is phenomenon is discussed in the context of recent theories of perceptual development and existing data on the neural organisation of the infant ‘social brain’.
Laila, Rawnak; Robin, Arif Hasan Khan; Yang, Kiwoung; Park, Jong-In; Suh, Mi Chung; Kim, Juyoung; Nou, Ill-Sup
Cuticular waxes act as a protective barrier against environmental stresses. In the present study, we investigated developmental and genotypic variation in wax formation of cabbage lines, with a view to understand the related morphology, genetics and biochemistry. Our studies revealed that the relative expression levels of wax biosynthetic genes in the first-formed leaf of the highest-wax line remained constantly higher but were decreased in other genotypes with leaf aging. Similarly, the expression of most of the tested genes exhibited decrease from the inner leaves to the outer leaves of 5-month-old cabbage heads in the low-wax lines in contrast to the highest-wax line. In 10-week-old plants, expression of wax biosynthetic genes followed a quadratic function and was generally increased in the early developing leaves but substantially decreased at the older leaves. The waxy compounds in all cabbage lines were predominately C29-alkane, -secondary alcohol, and -ketone. Its deposition was increased with leaf age in 5-month-old plants. The high-wax lines had dense, prominent and larger crystals on the leaf surface compared to low-wax lines under scanning electron microscopy. Principal component analysis revealed that the higher expression of LTP2 genes in the lowest-wax line and the higher expression of CER3 gene in the highest-wax line were probably associated with the comparatively lower and higher wax content in those two lines, respectively. This study furthers our understanding of the relationships between the expression of wax biosynthetic genes and the wax deposition in cabbage lines. Highlight: In cabbage, expression of wax-biosynthetic genes was generally decreased in older and senescing leaves, while wax deposition was increased with leaf aging, and C29-hydrocarbon was predominant in the wax crystals. PMID:28119701
Tanaka-Arakawa, Megumi M; Matsui, Mie; Tanaka, Chiaki; Uematsu, Akiko; Uda, Satoshi; Miura, Kayoko; Sakai, Tomoko; Noguchi, Kyo
Previous research has reported on the development trajectory of the corpus callosum morphology. However, there have been only a few studies that have included data on infants. The goal of the present study was to examine the morphology of the corpus callosum in healthy participants of both sexes, from infancy to early adulthood. We sought to characterize normal development of the corpus callosum and possible sex differences in development. We performed a morphometric magnetic resonance imaging (MRI) study of 114 healthy individuals, aged 1 month to 25 years old, measuring the size of the corpus callosum. The corpus callosum was segmented into seven subareas of the rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus and splenium. Locally weighted regression analysis (LOESS) indicated significant non-linear age-related changes regardless of sex, particularly during the first few years of life. After this increase, curve slopes gradually became flat during adolescence and adulthood in both sexes. Age of local maximum for each subarea of the corpus callosum differed across the sexes. Ratios of total corpus callosum and genu, posterior midbody, as well as splenium to the whole brain were significantly higher in females compared with males. The present results demonstrate that the developmental trajectory of the corpus callosum during early life in healthy individuals is non-linear and dynamic. This pattern resembles that found for the cerebral cortex, further suggesting that this period plays a very important role in neural and functional development. In addition, developmental trajectories and changes in growth do show some sex differences.
Wang, Jiun-Da; Lo, Shuen-Fang; Li, Yan-Suan; Chen, Po-Ju; Lin, Shih-Yun; Ho, Teh-Yuan; Lin, Jenq-Horng; Chen, Liang-Jwu
The rice gene, OsMADS45, which belongs to the MADS-box E class gene, participates in the regulation of floral development. Previous studies have revealed that ectopic expression of OsMADS45 induces early flowering and influences reduced plant height under short-day (SD) conditions. However, the regulation mechanism of OsMADS45 overexpression remains unknown. We introduce an OsMADS45 overexpression construct Ubi:OsMADS45 into TNG67 plants (an Hd1 (Heading date 1) and Ehd1 (Early heading date 1) defective rice cultivar grown in Taiwan), and we analyzed the expression patterns of various floral regulators to understand the regulation pathways affected by OsMADS45 expression. The transgenic rice exhibit a heading date approximately 40 days earlier than that observed in TNG67 plants, and transgenic rice display small plant size and low grain yield. OsMADS45 overexpression did not alter the oscillating rhythm of the examined floral regulatory genes but advanced (by approximately 20 days) the up-regulate of two florigens, Hd3a (Heading Date 3a) and RFT1 (RICE FLOWERING LOCUS T1) and suppressed the expression of Hd1 at the juvenile stage. The expression levels of OsMADS14 and OsMADS18, which are two well-known reproductive phase transition markers, were also increased at early developmental stages and are believed to be the major regulators responsible for early flowering in OsMADS45-overexpressing transgenic rice. OsMADS45 overexpression did not influence other floral regulator genes upstream of Hd1 and Ehd1, such as OsGI (OsGIGANTEA), Ehd2/Osld1/RID1 and OsMADS50. These results indicate that in transgenic rice, OsMADS45 overexpressing ectopically activates the upstream genes Hd3a and RFT1 at early development stage and up-regulates the expression of OsMADS14 and OsMADS18, which induces early flowering.
Al-Hinai, Mohab A; Jones, Shawn W; Papoutsakis, Eleftherios T
Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σ(H) (early), σ(F), σ(E), σ(G), and σ(K) (late). Here we show that the Clostridium acetobutylicum σ(K) acts both early, prior to Spo0A expression, and late, past σ(G) activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σ(G) proteins were not detectable by Western analysis, while σ(F) protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σ(K) is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σ(F), σ(E), and σ(G), but not sporulation, which was blocked past the σ(G) stage of development, thus demonstrating that σ(K) is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles.
Tathyana Rachel Palo Mello
Full Text Available Major developmental transitions in multicellular organisms are driven by steroid hormones. In insects, these, together with juvenile hormone (JH, control development, metamorphosis, reproduction and aging, and are also suggested to play an important role in caste differentiation of social insects. Here, we aimed to determine how EcR transcription and ecdysteroid titers are related during honeybee postembryonic development and what may actually be the role of EcR in caste development of this social insect. In addition, we expected that knocking-down EcR gene expression would give us information on the participation of the respective protein in regulating downstream targets of EcR. We found that in Apis mellifera females, EcR-A is the predominantly expressed variant in postembryonic development, while EcR-B transcript levels are higher in embryos, indicating an early developmental switch in EcR function. During larval and pupal stages, EcR-B expression levels are very low, while EcR-A transcripts are more variable and abundant in workers compared to queens. Strikingly, these transcript levels are opposite to the ecdysteroid titer profile. 20-hydroxyecdysone (20E application experiments revealed that low 20E levels induce EcR expression during development, whereas high ecdysteroid titers seem to be repressive. By means of RNAi-mediated knockdown (KD of both EcR transcript variants we detected the differential expression of 234 poly-A+ transcripts encoding genes such as CYPs, MRJPs and certain hormone response genes (Kr-h1 and ftz-f1. EcR-KD also promoted the differential expression of 70 miRNAs, including highly conserved ones (e.g. miR-133 and miR-375, as well honeybee-specific ones (e.g. miR-3745 and miR-3761. Our results put in evidence a broad spectrum of EcR-controlled gene expression during postembryonic development of honeybees, revealing new facets of EcR biology in this social insect.
Kelly J. Huffman
Full Text Available A hallmark of mammalian development is the generation of functional subdivisions within the nervous system. In humans, this regionalization creates a complex system that regulates behavior, cognition, memory and emotion. During development, specification of neocortical tissue that leads to functional sensory and motor regions results from an interplay between cortically intrinsic, molecular processes, such as gene expression, and extrinsic processes regulated by sensory input. Cortical specification in mice occurs pre- and perinatally, when gene expression is robust and various anatomical distinctions are observed alongside an emergence of physiological function. After patterning, gene expression continues to shift and axonal connections mature into an adult form. The function of adult cortical gene expression may be to maintain neocortical subdivisions that were established during early patterning. As some changes in neocortical gene expression have been observed past early development into late adulthood, gene expression may also play a role in the altered neocortical function observed in age-related cognitive decline and brain dysfunction. This review provides a discussion of how neocortical gene expression and specific patterns of neocortical sensori-motor axonal connections develop and change throughout the lifespan of the animal. We posit that a role of neocortical gene expression in neocortex is to regulate plasticity mechanisms that impact critical periods for sensory and motor plasticity in aging. We describe results from several studies in aging brain that detail changes in gene expression that may relate to microstructural changes observed in brain anatomy. We discuss the role of altered glucocorticoid signaling in age-related cognitive and functional decline, as well as how aging in the brain may result from immune system activation. We describe how caloric restriction or reduction of oxidative stress may ameliorate effects of aging
Pinto, Ana Isabel; Grande, Catarina; Aguiar, Cecilia; de Almeida, Isabel Chaves; Felgueiras, Isabel; Pimentel, Julia Serpa; Serrano, Ana Maria; Carvalho, Leonor; Brandao, Maria Teresa; Boavida, Tania; Santos, Paula; Lopes-dos-Santos, Pedro
Research studies on early childhood intervention (ECI) in Portugal are diffuse regarding both program components and the geographical area under scrutiny. Since the 1990s, a growing body of knowledge and evidence in ECI is being gathered, based on postgraduate teaching, in-service training, and research. This article draws on the systems theory…
Donkelaar, H.J. ten; Wesseling, P.; Lammens, M.M.Y.; Renier, W.O.; Mullaart, R.A.; Thijssen, H.O.M.
The recent discovery of many genes that regulate brain development is revolutionizing our knowledge of neuroembryology and, moreover, our understanding of how gene defects cause human birth defects. The first 8 weeks of the development of the cerebrum can be subdivided into 23 stages, with early
Salley, Brenda; Sheinkopf, Stephen J.; Neal-Beevers, A. Rebecca; Tenenbaum, Elena J.; Miller-Loncar, Cynthia L.; Tronick, Ed; Lagasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles; Whitaker, Toni; Hammond, Jane; Lester, Barry M.
This study examined infants' early visual attention (at 1 month of age) and social engagement (4 months) as predictors of their later joint attention (12 and 18 months). The sample (n = 325), drawn from the Maternal Lifestyle Study, a longitudinal multicenter project conducted at 4 centers of the National Institute of Child Health and Human…
Brook, David W; Brook, Judith S; Zhang, Chenshu; Whiteman, Martin; Cohen, Patricia; Finch, Stephen J
The purpose of this study was to identify distinct trajectories of cigarette smoking from ages 14 to 32, and to examine adolescent personality factors that distinguish trajectories of smoking behavior. Participants (N = 975) were randomly selected and followed prospectively since 1975. Follow-up data on cigarette use and personality and behavioral attributes were collected at five points in time, using structured interviews given in private by trained interviewers. Of these subjects, 746 comprised the cohort used in this study. Growth mixture modeling identified five smoking trajectory groups: nonsmokers, occasional smokers, late starters, quitters, and heavy/continuous smokers. Adolescent personality and behavioral risk factors such as lower ego integration, more externalizing behavior, and lower educational aspirations distinguished the trajectory groups. No gender differences were noted. The findings supported the hypotheses indicating multiple distinct trajectory groups of smoking behavior. Smoking behavior appeared in early adolescence and most often continued into adulthood. Emotional difficulties (i.e., lower ego integration), externalizing behavior, and lower educational aspirations in early adolescence were associated both with smoking at an early age and with continuing to smoke into the thirties. To be more effective, smoking prevention programs should target personality and behavioral variations before smoking becomes habitual, particularly focused on characteristics reflecting behavioral problems as manifested in emotional difficulties, externalizing behavior, and low educational aspirations in early adolescence. The implications for research, prevention, and treatment are discussed.
Sroufe, L. Alan; And Others
Examined Bowlby's proposition that early experiences and the adaptations to which they give rise influence later development, even beyond the influence of current circumstances or very recent adaptation. Groups whose adaptation were similar during preschool years but consistently different earlier were defined and compared. Results supported…
Belsky, Jay; Pluess, Michael
Data from 508 Caucasian children in the NICHD Study of Early Child Care and Youth Development shows that the DRD4 (but not 5-HTTLPR) polymorphism moderates the effect of child-care quality (but not quantity or type) on caregiver-reported externalizing problems at 54 months and in kindergarten and teacher-reported social skills at kindergarten and…
Graue, M. Elizabeth; Kroeger, Janice; Brown, Christopher
This article explores the relationship between notions of development and practice in early education. Through an interpretive study of the experience of the "gift of time," the article follows small groups of children who delayed kindergarten entry, those who were relatively young but entered on time, and children retained in kindergarten to gain…
Tessier, Anne-Michelle; Duncan, Tamara Sorenson; Paradis, Johanne
This study focuses on English onset cluster production in spontaneous speech samples of 10 children aged 5;04-6;09 from Chinese and Hindi/Punjabi first language (L1) backgrounds, each with less than a year of exposure to English. The results suggest commonalities between early second language (L2) learners and both monolingual and adult L2…
Samuels, Alecia M.; Slemming, Wiedaad; Balton, Sadna
As highlighted in recent series in "The Lancet" (2007, 2011), children from low and middle income countries are more likely to be adversely affected by early biological and psychosocial experiences that have their origins in environments characterized by poverty, violence, nutritional deficiencies, HIV infections, substance abuse, and…
Full Text Available Abstract Background Peroxisomes are organelles whose roles in fatty acid metabolism and reactive oxygen species elimination have contributed much attention in understanding their origin and biogenesis. Many studies have shown that de novo peroxisome biogenesis is an important regulatory process, while yeast studies suggest that total peroxisome numbers are in part regulated by proteins such as Pex11, which can facilitate the division of existing peroxisomes. Although de novo biogenesis and divisions are likely important mechanisms, the regulation of peroxisome numbers during embryonic development is poorly understood. Peroxisome number and function are particularly crucial in oviparous animals such as frogs where large embryonic yolk and fatty acid stores must be quickly metabolized, and resulting reactive oxygen species eliminated. Here we elucidate the role of Pex11β in regulating peroxisomal gene expression and number in Xenopus laevis embryogenesis. Results Microinjecting haemagglutinin (HA tagged Pex11β in early embryos resulted in increased RNA levels for peroxisome related genes PMP70 and catalase at developmental stages 10 and 20, versus uninjected embryos. Catalase and PMP70 proteins were found in punctate structures at stage 20 in control embryos, whereas the injection of ectopic HA-Pex11β induced their earlier localization in punctate structures at stage 10. Furthermore, the peroxisomal marker GFP-SKL, which was found localized as peroxisome-like structures at stage 20, was similarly found at stage 10 when co-microinjected with HA-Pex11β. Conclusions Overexpressed Pex11β altered peroxisomal gene levels and induced the early formation of peroxisomes-like structures during development, both of which demonstrate that Pex11β may be a key regulator of peroxisome number in early Xenopus embryos.
Li, Hui; Wang, Yu; Wu, Mei; Li, Lihong; Jin, Chuan; Zhang, Qingli; Chen, Chengbin; Song, Wenqin; Wang, Chunguo
Pollen development is an important and complex biological process in the sexual reproduction of flowering plants. Although the cytological characteristics of pollen development are well defined, the regulation of its early stages remains largely unknown. In the present study, miRNAs were explored in the early development of broccoli (Brassica oleracea var. italica) pollen. A total of 333 known miRNAs that originated from 235 miRNA families were detected. Fifty-five novel miRNA candidates were identified. Sixty of the 333 known miRNAs and 49 of the 55 predicted novel miRNAs exhibited significantly differential expression profiling in the three distinct developmental stages of broccoli pollen. Among these differentially expressed miRNAs, miRNAs that would be involved in the developmental phase transition from uninucleate microspores to binucleate pollen grains or from binucleate to trinucleate pollen grains were identified. miRNAs that showed significantly enriched expression in a specific early stage of broccoli pollen development were also observed. In addition, 552 targets for 127 known miRNAs and 69 targets for 40 predicted novel miRNAs were bioinformatically identified. Functional annotation and GO (Gene Ontology) analysis indicated that the putative miRNA targets showed significant enrichment in GO terms that were related to plant organ formation and morphogenesis. Some of enriched GO terms were detected for the targets directly involved in plant male reproduction development. These findings provided new insights into the functions of miRNA-mediated regulatory networks in broccoli pollen development.
Full Text Available Abstract Background Universally accepted landmark stages are necessary to highlight key events in plant reproductive development and to facilitate comparisons among species. Domestication and selection of tomato resulted in many varieties that differ in fruit shape and size. This diversity is useful to unravel underlying molecular and developmental mechanisms that control organ morphology and patterning. The tomato fruit shape gene SUN controls fruit elongation. The most dramatic effect of SUN on fruit shape occurs after pollination and fertilization although a detailed investigation into the timing of the fruit shape change as well as gene expression profiles during critical developmental stages has not been conducted. Results We provide a description of floral and fruit development in a red-fruited closely related wild relative of tomato, Solanum pimpinellifolium accession LA1589. We use established and propose new floral and fruit landmarks to present a framework for tomato developmental studies. In addition, gene expression profiles of three key stages in floral and fruit development are presented, namely floral buds 10 days before anthesis (floral landmark 7, anthesis-stage flowers (floral landmark 10 and fruit landmark 1, and 5 days post anthesis fruit (fruit landmark 3. To demonstrate the utility of the landmarks, we characterize the tomato shape gene SUN in fruit development. SUN controls fruit shape predominantly after fertilization and its effect reaches a maximum at 8 days post-anthesis coinciding with fruit landmark 4 representing the globular embryo stage of seed development. The expression profiles of the NILs that differ at sun show that only 34 genes were differentially expressed and most of them at a less than 2-fold difference. Conclusion The landmarks for flower and fruit development in tomato were outlined and integrated with the effect of SUN on fruit shape. Although we did not identify many genes differentially expressed in
Xiao, Han; Radovich, Cheryll; Welty, Nicholas; Hsu, Jason; Li, Dongmei; Meulia, Tea; van der Knaap, Esther
Background Universally accepted landmark stages are necessary to highlight key events in plant reproductive development and to facilitate comparisons among species. Domestication and selection of tomato resulted in many varieties that differ in fruit shape and size. This diversity is useful to unravel underlying molecular and developmental mechanisms that control organ morphology and patterning. The tomato fruit shape gene SUN controls fruit elongation. The most dramatic effect of SUN on fruit shape occurs after pollination and fertilization although a detailed investigation into the timing of the fruit shape change as well as gene expression profiles during critical developmental stages has not been conducted. Results We provide a description of floral and fruit development in a red-fruited closely related wild relative of tomato, Solanum pimpinellifolium accession LA1589. We use established and propose new floral and fruit landmarks to present a framework for tomato developmental studies. In addition, gene expression profiles of three key stages in floral and fruit development are presented, namely floral buds 10 days before anthesis (floral landmark 7), anthesis-stage flowers (floral landmark 10 and fruit landmark 1), and 5 days post anthesis fruit (fruit landmark 3). To demonstrate the utility of the landmarks, we characterize the tomato shape gene SUN in fruit development. SUN controls fruit shape predominantly after fertilization and its effect reaches a maximum at 8 days post-anthesis coinciding with fruit landmark 4 representing the globular embryo stage of seed development. The expression profiles of the NILs that differ at sun show that only 34 genes were differentially expressed and most of them at a less than 2-fold difference. Conclusion The landmarks for flower and fruit development in tomato were outlined and integrated with the effect of SUN on fruit shape. Although we did not identify many genes differentially expressed in the NILs that differ at
Dana Charles McCoy
Full Text Available The development of cognitive and socioemotional skills early in life influences later health and well-being. Existing estimates of unmet developmental potential in low- and middle-income countries (LMICs are based on either measures of physical growth or proxy measures such as poverty. In this paper we aim to directly estimate the number of children in LMICs who would be reported by their caregivers to show low cognitive and/or socioemotional development.The present paper uses Early Childhood Development Index (ECDI data collected between 2005 and 2015 from 99,222 3- and 4-y-old children living in 35 LMICs as part of the Multiple Indicator Cluster Survey (MICS and Demographic and Health Surveys (DHS programs. First, we estimate the prevalence of low cognitive and/or socioemotional ECDI scores within our MICS/DHS sample. Next, we test a series of ordinary least squares regression models predicting low ECDI scores across our MICS/DHS sample countries based on country-level data from the Human Development Index (HDI and the Nutrition Impact Model Study. We use cross-validation to select the model with the best predictive validity. We then apply this model to all LMICs to generate country-level estimates of the prevalence of low ECDI scores globally, as well as confidence intervals around these estimates. In the pooled MICS and DHS sample, 14.6% of children had low ECDI scores in the cognitive domain, 26.2% had low socioemotional scores, and 36.8% performed poorly in either or both domains. Country-level prevalence of low cognitive and/or socioemotional scores on the ECDI was best represented by a model using the HDI as a predictor. Applying this model to all LMICs, we estimate that 80.8 million children ages 3 and 4 y (95% CI 48.1 million, 113.6 million in LMICs experienced low cognitive and/or socioemotional development in 2010, with the largest number of affected children in sub-Saharan Africa (29.4.1 million; 43.8% of children ages 3 and 4 y
A group of small signaling molecules called ascarosides, associated with dauer formation, male attraction and social behavior in the nematode Caenorhabditis elegans, are shown to be regulated by developmental stage and environmental factors. The concentration of dauer-inducing ascaroside, ascr#2, i...
M. E. Kotze
Full Text Available Young professional military officers' experience of their internal career development was studied longitudinally from a life-span, life-space approach. Significant transitions between the life roles of worker, student and leisurite, with concomitant changes in their value system, away from traditional military values towards occupationalism, were confirmed. Gender differences were found for the work and community roles as well as in the developmental patterns of the need for authority, creativity, cultural identity, physical activities, social relationships and variety. Significant differences between the career development profiles of military and civilian students with regard to life roles were revealed. Opsomming Jong militere beroepsoffisiere se belewenis van hulle interne loopbaanontwikkeling is longitudinaal uit 'n lewenspan-Iewensruimte benadering bestudeer. Beduidende oorgange tussen die werk-, studie- en ontspanningsrolle met gepaardgaande veranderinge in hulle waardestelsel, weg van tradisionele militere waardes in die rigting van 'n beroepsgeoriënteerde waardestelsel, is bevestig. Geslagsverskille is gevind wat betref die werk- en gemeenskapsrolle sowel as in die volgende ontwikkelingspatrone: 'n behoefte aan outoriteit, kreatiwiteit, kulturele identiteit, fisiese aktiwiteite, sosiale verhoudings en verskeidenheid. Beduidende verskille met betrekking tot lewensrolle het in die loopbaanontwikkelingsprofiele van militere en burgerlike studente aan die lig gekom.
Presently, the incidences of noncommunicable diseases (NCD) have been increasing in both low- and middle-income countries worldwidely. Effective long-term and multigeneration interventions to decrease the risk of NCD should be developed and introduced. The environment in utero alters phenotypes mainly through epigenetic mechanisms. The epigenetic changes induced in an unfavorable developmental environment have lifelong effects on cardiovascular and metabolic functions, susceptibility to cardiovascular disease, obesity, and other NCD. Although compared with animals, epigenetic analysis of human specimens is restricted except for peripheral blood, placental, or umbilical specimens, recently, important human studies have been reported concerning the epigenetic analysis of Line 1 gene from the umbilical blood, umbilical RXRα, or the peripheral nuclear cell IGF-2. The birth weight is an indirect marker of in-the-womb nutritional status. The incidence of low-birth-weight infants, weighing less than 2,500 g, has been increasing in Japan. Presently, it is higher than that in the latter half of the 20 s of the Showa era, and is the highest among the OECD countries. This trend suggests that in Japan the intrauterine nutritional status has been deteriorating. We have to change this trend and put much attention on the prepregnancy and pregnancy nutrition for the present and future generations.
The biological soil crust serves as one of the biological factors contributing to the sand fixation in the Gurbantunggut Desert, the largest fixed and semi-fixed desert in China. This study was conducted to investigate the microstructure and formation of biological soil crusts which develop as a result of occurrence of cryptogams. One year after removal of biological soil crusts, the exposed surface could be fixed by bacteria, which make sand particles cohere by exopolysaccharides. The exopolysaccharides were mainly composed of glucose, mannitol, arabinose and galactose. The intension of pressure for this kind of crust is 13.42±1.38 Pa. After four-year recovery of the exposed sandy surface, the biological soil crust resulting from the colonization of soil surface by communities of filamentous cyanobacteria were mainly dominated by Microcoleus, which occurred as a cluster of filaments surrounded by a gelatinous sheath. At this developmental stage, the main contributors for sand fixation were changed from bacteria to filamentous cyanobacteria. Microscopic examination of this kind of crust revealed an intricate network of filamentous cyanobacteria and extracellular polymer secretions, which binds and entraps mineral particles and finer particles on the filament surface. These effects enhance soil cohesion and resistance to erosion. The intension of pressure for this kind of crust is 32.53±3.08 Pa.
Full Text Available The aim of this study was to assess the impact of terbuthylazine in surface waters on fish under experimental conditions. Subchronic toxic effects on embryos and larvae of common carp (Cyprinus carpio were investigated during a 30-day toxicity test. The exposure to terbuthylazin showed no effect on mortality, but significant differences (P<0.0001 were revealed on weight and growth parameters at concentrations of 520 and 820 μg/L. The inhibition of specific growth rate at concentrations of 520 and 820 μg/L was 14% compared to the control group. No significant negative effects on total body length and body weight were observed at lower concentrations (0.9 and 160 μg/L. The concentrations 520 and 820 μg/L were associated with a delay in development compared to other experimental groups and controls. On the basis of weight and growth rate evaluation and determination of developmental stages, the No Observed Effect Concentration (NOEC of terbuthylazine was estimated at 160 μg/L and the Lowest Observed Effect Concentration (LOEC was 520 μg/L. According to these results, the reported environmental concentration of terbuthylazine in Czech rivers does not impact growth, development, morphology, or histology of carp embryos and larvae.
Lerman, J A; Emans, J B; Millis, M B; Share, J; Zurakowski, D; Kasser, J R
A cohort of 93 patients with developmental dysplasia of the hip (DDH) treated with a Pavlik harness were evaluated to determine predictors of treatment failure. Failure was defined as failure to achieve or maintain hip reduction in the Pavlik harness. Of 93 patients (137 hips), 17 (26 hips) failed Pavlik harness treatment. Univariate risk factors for failure included bilaterality, initial clinical exam, and initial ultrasound (US) percent coverage. Clinical exam and initial percent coverage were multivariate risk factors for failure. Among initially clinically dislocatable hips, a low initial US alpha angle correlated with an increased likelihood of failure. All (6/6) patients with an initially irreducible hip and an initial coverage of <20% by US eventually failed treatment. Gender, side of pathology, and age at diagnosis and initiation of treatment did not correlate with failure. Irreducibility by physical exam combined with US coverage of <20% identified a patient group that uniformly failed Pavlik harness treatment. These patients may be candidates for alternative bracing, traction, or closed or open reduction.
Liao, Dengqun; Wang, Pengfei; Jia, Chan; Sun, Peng; Qi, Jianjun; Zhou, Lili; Li, Xian'en
Alkaloids in bulbs of Corydalis (C.) yanhusuo are the major pharmacologically active compounds in treatment of blood vessel diseases, tumors and various pains. However, due to the absence of gene sequences in C. yanhusuo, the genes involved in alkaloid biosynthesis and their expression during bulb development remain unknown. We therefore established the first transcriptome database of C. yanhusuo via Illumina mRNA-Sequencing of a RNA composite sample collected at Bulb initiation (Day 0), early enlargement (Day 10) and maturation (Day 30). 25,013,630 clean 90 bp paired-end reads were de novo assembled into 47,081 unigenes with an average length of 489 bp, among which 30,868 unigenes (65.56%) were annotated in four protein databases. Of 526 putative unigenes involved in biosynthesis o f various alkaloids, 187 were identified as the candidate genes involved in the biosynthesis of benzylisoquinoline alkaloids (BIAs), the only alkaloid type reported in C. yanhusuo untill now. BIAs biosynthetic genes were highly upregulated in the overall pathway during bulb development. Identification of alkaloid biosynthetic genes in C. yanhusuo provide insights on pathways and molecular regulation of alkaloid biosynthesis, to initiate metabolic engineering in order to improve the yield of interesting alkaloids and to identify potentially new alkaloids predicted from the transcriptomic information.
Full Text Available The successful achievement of early ovarian folliculogenesis is important for fertility and reproductive life span. This complex biological process requires the appropriate expression of numerous genes at each developmental stage, in each follicular compartment. Relatively little is known at present about the molecular mechanisms that drive this process, and most gene expression studies have been performed in rodents and without considering the different follicular compartments.We used RNA-seq technology to explore the sheep transcriptome during early ovarian follicular development in the two main compartments: oocytes and granulosa cells. We documented the differential expression of 3,015 genes during this phase and described the gene expression dynamic specific to these compartments. We showed that important steps occurred during primary/secondary transition in sheep. We also described the in vivo molecular course of a number of pathways. In oocytes, these pathways documented the chronology of the acquisition of meiotic competence, migration and cellular organization, while in granulosa cells they concerned adhesion, the formation of cytoplasmic projections and steroid synthesis. This study proposes the involvement in this process of several members of the integrin and BMP families. The expression of genes such as Kruppel-like factor 9 (KLF9 and BMP binding endothelial regulator (BMPER was highlighted for the first time during early follicular development, and their proteins were also predicted to be involved in gene regulation. Finally, we selected a data set of 24 biomarkers that enabled the discrimination of early follicular stages and thus offer a molecular signature of early follicular growth. This set of biomarkers includes known genes such as SPO11 meiotic protein covalently bound to DSB (SPO11, bone morphogenetic protein 15 (BMP15 and WEE1 homolog 2 (S. pombe(WEE2 which play critical roles in follicular development but other biomarkers
Essex, Marilyn J.; Boyce, W. Thomas; Hertzman, Clyde; Lam, Lucia L.; Armstrong, Jeffrey M.; Neumann, Sarah M.A.; Kobor, Michael S.
Fifteen-year-old adolescents (N=109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents’ infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide (CpG) sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children’s early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children’s gender. To the authors’ knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents’ genomic DNA. PMID:21883162
Chen, Y; Huang, L; Russo, A F; Solursh, M
Retinoic acid (RA) has been considered as a potential morphogen in the chicken limb and has also been suggested to be involved in early embryonic development. On the basis of biological activity, previous reports suggest that Hensen's node, the anatomical equivalent in the chicken of the Spemann's organizer, may contain RA. Here, by using a molecular assay system, we demonstrate that Hensen's node contains retinoids in a concentration approximately 20 times more than that in the neighboring t...
Tungjitwitayakul, Jatuporn; Tatun, Nujira; Vajarasathira, Boongeua; Sakurai, Sho
The maize weevil, Sitophilus zeamais Motschulsky, is a major pest of rice and other postharvest grain stocks in tropical countries. Heating and cooling treatments have been adopted to control this pest. Because heat shock protein (hsp) genes respond to temperature stress, we examined the association of hsp genes with development and thermal stress in S. zeamais. The temperature response of the insect to heat and cold treatments was assessed at four developmental stages: egg, larva, pupa, and adult. LT50 values at high temperatures were similar among the four developmental stages, while adults were the most tolerant to low temperatures, and eggs, larvae, and pupae exhibited similar LT50 values. Expression levels of three hsps--Szhsp70, Szhsc70, and Szhsp90--fluctuated substantially throughout the four stages at a rearing temperature of 28°C. Heat shock and cold shock increased the expression of all three hsps, and the highest upregulation was observed at 40°C, although the intensity of upregulation varied among the three genes: strongly in Szhsp70, moderately in Szhsp90, and slightly in Szhsc70. Basal expression of the three hsps at 28°C and gene responses to heat and cold shock also varied significantly at the tissue level.
Rätzel, Viktoria; Ebeling, Britta; Hoffmann, Xenia-Katharina; Tesmer, Jens; Marwan, Wolfgang
Physarum polycephalum is a lower eukaryote belonging to the amoebozoa group of organisms that forms macroscopic, multinucleate plasmodial cells during its developmental cycle. Plasmodia can exit proliferative growth and differentiate by forming fruiting bodies containing mononucleate, haploid spores. This process, called sporulation, is controlled by starvation and visible light. To genetically dissect the regulatory control of the commitment to sporulation, we have isolated plasmodial mutants that are altered in the photocontrol of sporulation in a phenotypic screen of N-ethyl-N-nitrosourea (ENU) mutagenized cells. Several non-sporulating mutants were analyzed by measuring the light-induced change in the expression pattern of a set of 35 genes using GeXP multiplex reverse transcription-polymerase chain reaction with RNA isolated from individual plasmodial cells. Mutants showed altered patterns of differentially regulated genes in response to light stimulation. Some genes clearly displayed pairwise correlation in terms of their expression level as measured in individual plasmodial cells. The pattern of pairwise correlation differed in various mutants, suggesting that different upstream regulators were disabled in the different mutants. We propose that patterns of pairwise correlation in gene expression might be useful to infer the underlying gene regulatory network. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.
Willoughby, Michael T.; Pek, Jolynn; Greenberg, Mark T.
Although Attention Deficit/Hyperactivity Disorder (ADHD) has increasingly been studied in preschool-aged children, relatively few studies have provided a comprehensive evaluation of the factor structure and patterns of developmental changes in parent-reported ADHD symptomatology across the early childhood period. This study used confirmatory…
Schendel, Diana E.; DiGuiseppi, Carolyn; Croen, Lisa A.; Fallin, M. Daniele; Reed, Philip L.; Schieve, Laura A.; Wiggins, Lisa D.; Daniels, Julie; Grether, Judith; Levy, Susan E.; Miller, Lisa; Newschaffer, Craig; Pinto-Martin, Jennifer; Robinson, Cordelia; Windham, Gayle C.; Alexander, Aimee; Aylsworth, Arthur S.; Bernal, Pilar; Bonner, Joseph D.; Blaskey, Lisa; Bradley, Chyrise; Collins, Jack; Ferretti, Casara J.; Farzadegan, Homayoon; Giarelli, Ellen; Harvey, Marques; Hepburn, Susan; Herr, Matthew; Kaparich, Kristina; Landa, Rebecca; Lee, Li-Ching; Levenseller, Brooke; Meyerer, Stacey; Rahbar, Mohammad H.; Ratchford, Andria; Reynolds, Ann; Rosenberg, Steven; Rusyniak, Julie; Shapira, Stuart K.; Smith, Karen; Souders, Margaret; Thompson, Patrick Aaron; Young, Lisa; Yeargin-Allsopp, Marshalyn
The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal,…
Schendel, Diana E.; DiGuiseppi, Carolyn; Croen, Lisa A.; Fallin, M. Daniele; Reed, Philip L.; Schieve, Laura A.; Wiggins, Lisa D.; Daniels, Julie; Grether, Judith; Levy, Susan E.; Miller, Lisa; Newschaffer, Craig; Pinto-Martin, Jennifer; Robinson, Cordelia; Windham, Gayle C.; Alexander, Aimee; Aylsworth, Arthur S.; Bernal, Pilar; Bonner, Joseph D.; Blaskey, Lisa; Bradley, Chyrise; Collins, Jack; Ferretti, Casara J.; Farzadegan, Homayoon; Giarelli, Ellen; Harvey, Marques; Hepburn, Susan; Herr, Matthew; Kaparich, Kristina; Landa, Rebecca; Lee, Li-Ching; Levenseller, Brooke; Meyerer, Stacey; Rahbar, Mohammad H.; Ratchford, Andria; Reynolds, Ann; Rosenberg, Steven; Rusyniak, Julie; Shapira, Stuart K.; Smith, Karen; Souders, Margaret; Thompson, Patrick Aaron; Young, Lisa; Yeargin-Allsopp, Marshalyn
The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal,…
Giannoni, Peggy P.; Kass, Philip H.
A retrospective cohort study was undertaken to identify risk factors for children at greatest risk of delayed diagnosis of developmental disability. Two thousand four hundred and thirty-nine children were selected for this study due to their participation in the California Early Start (ES) Program in 1998. Comparisons were made among children that…
Full Text Available DNA microarray analysis is an effective method to detect unintended effects by detecting differentially expressed genes (DEG in safety assessment of genetically modified (GM crops. With the aim to reveal the distribution of DEG of GM crops under different conditions, we performed DNA microarray analysis using transgenic rice Huahui 1 (HH1 and its non-transgenic parent Minghui 63 (MH63 at different developmental stages and environmental conditions. Considerable DEG were selected in each group of HH1 under different conditions. For each group of HH1, the number of DEG was different; however, considerable common DEG were shared between different groups of HH1. These findings suggested that both DEG and common DEG were adequate for investigation of unintended effects. Furthermore, a number of significantly changed pathways were found in all groups of HH1, indicating genetic modification caused everlasting changes to plants. To our knowledge, our study for the first time provided the non-uniformly distributed pattern for DEG of GM crops at different developmental stages and environments. Our result also suggested that DEG selected in GM plants at specific developmental stage and environment could act as useful clues for further evaluation of unintended effects of GM plants.
Klin, Ami; Shultz, Sarah; Jones, Warren
Efforts to determine and understand the causes of autism are currently hampered by a large disconnect between recent molecular genetics findings that are associated with the condition and the core behavioral symptoms that define the condition. In this perspective piece, we propose a systems biology framework to bridge that gap between genes and symptoms. The framework focuses on basic mechanisms of socialization that are highly-conserved in evolution and are early-emerging in development. By conceiving of these basic mechanisms of socialization as quantitative endophenotypes, we hope to connect genes and behavior in autism through integrative studies of neurodevelopmental, behavioral, and epigenetic changes. These changes both lead to and are led by the accomplishment of specific social adaptive tasks in a typical infant's life. However, based on recent research that indicates that infants later diagnosed with autism fail to accomplish at least some of these tasks, we suggest that a narrow developmental period, spanning critical transitions from reflexive, subcortically-controlled visual behavior to interactional, cortically-controlled and social visual behavior be prioritized for future study. Mapping epigenetic, neural, and behavioral changes that both drive and are driven by these early transitions may shed a bright light on the pathogenesis of autism.
Klin, Ami; Shultz, Sarah; Jones, Warren
Efforts to determine and understand the causes of autism are currently hampered by a large disconnect between recent molecular genetics findings that are associated with the condition and the core behavioral symptoms that define the condition. In this perspective piece, we propose a systems biology framework to bridge that gap between genes and symptoms. The framework focuses on basic mechanisms of socialization that are highly-conserved in evolution and are early-emerging in development. By conceiving of these basic mechanisms of socialization as quantitative endophenotypes, we hope to connect genes and behavior in autism through integrative studies of neurodevelopmental, behavioral, and epigenetic changes. These changes both lead to and are led by the accomplishment of specific social adaptive tasks in a typical infant's life. However, based on recent research that indicates that infants later diagnosed with autism fail to accomplish at least some of these tasks, we suggest that a narrow developmental period, spanning critical transitions from reflexive, subcortically-controlled visual behavior to interactional, cortically-controlled and social visual behavior be prioritized for future study. Mapping epigenetic, neural, and behavioral changes that both drive and are driven by these early transitions may shed a bright light on the pathogenesis of autism. PMID:25445180
Molina, Brooke S G; Walther, Christine A P; Cheong, Jeewon; Pedersen, Sarah L; Gnagy, Elizabeth M; Pelham, William E
Frequent heavy drinking in early adulthood, particularly prior to age 21, is associated with multiple health and legal consequences including continued problems with drinking later into adulthood. Children with attention-deficit/hyperactivity disorder (ADHD) are at risk of alcohol use disorder in adulthood, but little is known about their frequency of underage drinking as young adults or about mediational pathways that might contribute to this risky outcome. The current study used data from the Pittsburgh ADHD Longitudinal Study to test social impairment and delinquency pathways from childhood ADHD to heavy drinking in early adulthood for individuals with (n = 148) and without (n = 117) childhood ADHD. Although ADHD did not predict heavy drinking, indirect mediating effects in opposing directions were found. A delinquency pathway from childhood ADHD to increased heavy drinking included adolescent and subsequently adult delinquent behavior. A social impairment pathway from childhood ADHD to decreased heavy drinking included adolescent, but not adult, social impairment. These findings help explain the heterogeneity of results for alcohol use among individuals with ADHD and suggest that common ADHD-related impairments may operate differently from each other and distinctly across developmental periods. PsycINFO Database Record (c) 2014 APA, all rights reserved.
Strait, Dana L.; O'Connell, Samantha; Parbery-Clark, Alexandra; Kraus, Nina
The perception and neural representation of acoustically similar speech sounds underlie language development. Music training hones the perception of minute acoustic differences that distinguish sounds; this training may generalize to speech processing given that adult musicians have enhanced neural differentiation of similar speech syllables compared with nonmusicians. Here, we asked whether this neural advantage in musicians is present early in life by assessing musically trained and untrained children as young as age 3. We assessed auditory brainstem responses to the speech syllables /ba/ and /ga/ as well as auditory and visual cognitive abilities in musicians and nonmusicians across 3 developmental time-points: preschoolers, school-aged children, and adults. Cross-phase analyses objectively measured the degree to which subcortical responses differed to these speech syllables in musicians and nonmusicians for each age group. Results reveal that musicians exhibit enhanced neural differentiation of stop consonants early in life and with as little as a few years of training. Furthermore, the extent of subcortical stop consonant distinction correlates with auditory-specific cognitive abilities (i.e., auditory working memory and attention). Results are interpreted according to a corticofugal framework for auditory learning in which subcortical processing enhancements are engendered by strengthened cognitive control over auditory function in musicians. PMID:23599166
Weaver, Chelsea M; Shaw, Daniel S; Crossan, Jennifer L; Dishion, Thomas J; Wilson, Melvin N
Parent-child conflict is central to most intervention models focused on reducing child problem behavior, yet few longitudinal studies have examined these processes during early childhood. The current study investigates (1) growth in mother-child and father figure (FF)-child conflict, (2) associations between trajectories of mother-child and FF-child conflict and children's adjustment; and (3) intervention effects in attenuating conflict. Participants are 195 ethnically diverse mother-FF-child triads drawn from a larger parenting intervention study for families with children at risk for developing conduct problems. Mother-child conflict decreased from ages 2 to 4, but decreases were unrelated to changes in children's adjustment problems. In contrast, the slope of FF-child conflict was positively related to the slope of child externalizing behaviors. Random assignment to a family-centered parenting intervention predicted rate of decline in mother-child conflict. Findings are discussed with respect to developmental patterns of parent-child conflict in early childhood and implications for prevention.
The main aim of this study was to evaluate whether microRNA (miRNA) profiling could be a useful tool for in vitro developmental neurotoxicity (DNT) testing. Therefore, to identify the possible DNT biomarkers among miRNAs, we have studied the changes in miRNA expressions in a mixed neuronal/glial culture derived from carcinoma pluripotent stem cells (NT2 cell line) after exposure to MetHgCl during the process of neuronal differentiation (2-36 DIV). The obtained results identified the presence ...
Wang, Hua-Feng; Friedman, Cynthia Ross; Zhu, Zhi-Xin; Qin, Hai-Ning
Decaisnea insignis, known as 'dead man's fingers' (Lardizabalaceae), is widely distributed in China and the Himalayan foothill countries. This economically important plant, which is the only species in the genus, has not been the subject of any embryological studies aside from one brief, older paper that lacks micrographs. Data on Decaisnea are also important because its systematic position has been unstable since the genus was established in 1855. Therefore, the objectives of this study were: (a) to use modern microscopy to document early reproductive anatomical development in Decaisnea; and (b) to compare qualitatively these early embryological characters with allied taxa in a systematic context. Decaisnea insignis floral buds and inflorescences were regularly collected from Shaanxi Province, China and prepared for light microscopy. The embryological characters studied were qualitatively compared with those of allied taxa via a thorough examination of the existing literature. Early reproductive anatomy in Decaisnea was documented and novel revelations made. It was discovered that the pollen is shed when three-celled (not two-celled, as previously reported), and that endosperm formation is nuclear (not cellular or helobial, as previously reported). These two newly revealed embryological characters are not found in any other members of Lardizabalaceae. Furthermore, neither are persistent antipodal cells, which we confirmed to be present in Decaisnea. Decaisnea and other Lardizabalaceae characteristically have tetrasporangiate anthers, a secretory tapetum, simultaneous microsporocyte cytokinesis, primarily bitegmic, crassinucellate ovules, and a Polygonum type embryo sac. However, in the family, persistent antipodals, nuclear endosperm, and pollen shed at the three-celled stage are only found in Decaisnea. These embryological data prompted the suggestion that Decaisnea needs elevation above the level of genus.
Benarous, Xavier; Consoli, Angèle; Milhiet, Vanessa; Cohen, David
In recent decades, ongoing research programmes on primary prevention and early identification of bipolar disorder (BD) have been developed. The aim of this article is to review the principal forms of evidence that support preventive interventions for BD in children and adolescents and the main challenges associated with these programmes. We performed a literature review of the main computerised databases (MEDLINE, PUBMED) and a manual search of the literature relevant to prospective and retrospective studies of prodromal symptoms, premorbid stages, risk factors, and early intervention programmes for BD. Genetic and environmental risk factors of BD were identified. Most of the algorithms used to measure the risk of developing BD and the early interventions programmes focused on the familial risk. The prodromal signs varied greatly and were age dependent. During adolescence, depressive episodes associated with genetic or environmental risk factors predicted the onset of hypomanic/manic episodes over subsequent years. In prepubertal children, the lack of specificity of clinical markers and difficulties in mood assessment were seen as impeding preventive interventions at these ages. Despite encouraging results, biomarkers have not thus far been sufficiently validated in youth samples to serve as screening tools for prevention. Additional longitudinal studies in youths at high risk of developing BD should include repeated measures of putative biomarkers. Staging models have been developed as an integrative approach to specify the individual level of risk based on clinical (e.g. prodromal symptoms and familial history of BD) and non-clinical (e.g. biomarkers and neuroimaging) data. However, there is still a lack of empirically validated studies that measure the benefits of using these models to design preventive intervention programmes.
Full Text Available Children with autism spectrum disorders have impairment in reciprocal social interaction and impairment in communication skills. They also have repetitive behaviours and preoccupation with stereotyped patterns of behaviours. The most important therapy is early individualized intensive behavioural intervention. Intensive behavioural interventions should be provided to all young children at the onset of symptoms. If not, they will have lifelong difficulties in communication and social interaction. Parent mediated behavioural interventions are effective in the management of young children with autism spectrum disorders. Children with autistic symptoms who receive earlier referrals to specialists and obtain intensive behavioural intervention achieve optimal outcomes.
Santos, Dércia; Matos, Manuela; Coimbra, Ana M
Endocrine disrupting compounds (EDCs) are capable of interfering with the endocrine system and are increasingly widespread in the aquatic environments. In the present study, zebrafish (Danio rerio) embryos and larvae were used to assess how EDCs may interfere with embryogenesis. Therefore, zebrafish embryos were exposed to 17α-ethinylestradiol (EE2: 0.4, 2, 4 and 20 ng/L), genistein (Gen: 2, 20, 200 and 2000 ng/L) and fadrozole (Fad: 2, 10, 50 and 250 μg/L), between 2 and 144 h post-fertilization (hpf). Somite development, heartbeat, malformations, mortality and hatching rates were evaluated. In parallel, the expression patterns of hormone receptors (esr1, esr2a, esr2b and ar) and apoptotic pathways related genes (p53 and c-jun) were determined using quantitative real-time PCR. Results showed that EE2, Gen and Fad caused a higher mortality and also malformations in larvae compared with control. A significant toxic effect was observed in the heartbeat rate, at 144 hpf, in larvae exposed to EE2 and Fad. QPCR revealed alterations in the expression levels of all the evaluated genes, at different time points. esr1 and c-jun genes were upregulated by EE2 and Gen exposure while the expression of esr2a, esr2b and ar genes was downregulated. Fad exposure decreased esr1, p53 and c-jun expression levels. This study shows a toxic effect of EE2, Gen and Fad to vertebrate embryogenesis and a relation between hormones action and apoptosis pathways.
Manuela Missana; Maren Grigutsch; Tobias Grossmann
We examined the processing of facial expressions of pain and anger in 8-month-old infants and adults by measuring event-related brain potentials (ERPs) and frontal EEG alpha asymmetry. The ERP results revealed that while adults showed a late positive potential (LPP) to emotional expressions that was enhanced to pain expressions, reflecting increased evaluation and emotional arousal to pain expressions, infants showed a negative component (Nc) to emotional expressions that was enhanced to angr...
Previous studies of the phenotype of developmental coordination disorder (DCD) have largely concentrated on population-based samples. The present study reports on an in-depth examination of a large Canadian family with eight children, after three children who were suspected to have DCD were referred for evaluation. Subsequently, five of the six children whose motor impairments could be measured, and the mother, met the diagnostic criteria for DCD as per the American Psychiatric Association’s ...
The GH/IGF-1 axis in a critical period early in life determines cellular DNA repair capacity by altering transcriptional regulation of DNA repair-related genes: implications for the developmental origins of cancer.
Podlutsky, Andrej; Valcarcel-Ares, Marta Noa; Yancey, Krysta; Podlutskaya, Viktorija; Nagykaldi, Eszter; Gautam, Tripti; Miller, Richard A; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan
Experimental, clinical, and epidemiological findings support the concept of developmental origins of health and disease (DOHAD), suggesting that early-life hormonal influences during a sensitive period around adolescence have a powerful impact on cancer morbidity later in life. The endocrine changes that occur during puberty are highly conserved across mammalian species and include dramatic increases in circulating GH and IGF-1 levels. Importantly, patients with developmental IGF-1 deficiency due to GH insensitivity (Laron syndrome) do not develop cancer during aging. Rodents with developmental GH/IGF-1 deficiency also exhibit significantly decreased cancer incidence at old age, marked resistance to chemically induced carcinogenesis, and cellular resistance to genotoxic stressors. Early-life treatment of GH/IGF-1-deficient mice and rats with GH reverses the cancer resistance phenotype; however, the underlying molecular mechanisms remain elusive. The present study was designed to test the hypothesis that developmental GH/IGF-1 status impacts cellular DNA repair mechanisms. To achieve that goal, we assessed repair of γ-irradiation-induced DNA damage (single-cell gel electrophoresis/comet assay) and basal and post-irradiation expression of DNA repair-related genes (qPCR) in primary fibroblasts derived from control rats, Lewis dwarf rats (a model of developmental GH/IGF-1 deficiency), and GH-replete dwarf rats (GH administered beginning at 5 weeks of age, for 30 days). We found that developmental GH/IGF-1 deficiency resulted in persisting increases in cellular DNA repair capacity and upregulation of several DNA repair-related genes (e.g., Gadd45a, Bbc3). Peripubertal GH treatment reversed the radiation resistance phenotype. Fibroblasts of GH/IGF-1-deficient Snell dwarf mice also exhibited improved DNA repair capacity, showing that the persisting influence of peripubertal GH/IGF-1 status is not species-dependent. Collectively, GH/IGF-1 levels during a critical period
Lubman, Dan I; Hides, Leanne; Yücel, Murat; Toumbourou, John W
Early-onset or frequent substance use during adolescence increases the risk of developing mental health problems, as well as a range of other adverse outcomes (eg, alcohol or drug dependence, educational underachievement, health problems, social difficulties) during late adolescence and early adulthood. Increases in rates of risky drinking among young people are particularly concerning, suggesting that an effective, evidence-based alcohol policy and preventive framework needs to be developed. Restricting the supply of licit and illicit substances to adolescents, delaying the age that licit substances can be legally purchased, reducing positive media portrayals of substance use, and banning targeted promotions, should be universal, public prevention priorities. Mass-media campaigns need to deliver coherent and credible evidence-based messages to young people, utilising a broad array of dissemination strategies. Clear policy and guidelines for parents regarding appropriate alcohol use for adolescents also need to be developed. Prevention programs should target children and adolescents in families with parents who use drugs, young people who have been suspended from school, or those with mental health problems. Preventive screening and targeted brief interventions can be effectively delivered in a variety of settings by a range of health professionals.
Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H. [West Los Angeles VA Medical Center, CA (United States). Lipid Research Lab.]|[Univ. of California, Los Angeles, CA (United States). Dept. of Medicine; Giometti, C.S.; Mishler, K. [Argonne National Lab., IL (United States); Slavin, B.G. [Univ. of Southern California, Los Angeles, CA (United States)
Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.
Rius, R. Adrian; Barg, Jacob; Bem, Wojciech T.; Coscia, Carmine J.; Loh, Y. Peng
Although the postnatal development of opioid systems of mammalian brain has been well studied, little is known about the ontogeny of and relationship between embryonic (E) opioid peptides and their receptors. Moreover, a simultaneous assessment of levels of the 3 classes of opioid peptides and their putative receptors during embryonal development has not been made. To this end, the ontogeny of opioid peptides and receptors in mouse brain were examined during the period E11.5 to postnatal day 1 (P1). Met-enkephalin, dynorphin and β-endorphin immunoreactivity were detected before their putative opioid receptors. β-Endorphin can be discerned as early as E11.5, whereas μ binding was first observed at E12.5. Although dynorphin and Met-enkephalin were measurable at the same time as β-endorphin, κ-receptors were not detected until E14.5 and δ sites were not found at all prenatally. Differences in immunoreactivity levels of the 3 peptides occur with dynorphin being lower than Met-enkephalin and β-endorphin, consistent with a low Bmax for κ binding. Expression of the 3 opioid peptides as well as μ and κ opioid receptors rapidly increase in parallel from E14.5 to E18.5, Interestingly, levels of β-endorphin diminish by P1, the stage at which a sharp rise of μ receptors occurs. In a comparative study of the binding of β-endorphin1–31, its truncated form (1–27) and their N-acetyl derivatives to E14.5 brain membranes, β-endorphin1–31 exhibited the highest affinity. PMID:1674235
Wang, Ke-Jian; Bo, Jun; Yang, Ming; Hong, Hua-Sheng; Wang, Xin-Hong; Chen, Fang-Yi; Yuan, Jian-Jun
Hepcidin is known to be expressed in fish with bacterial challenge and iron overload. Here we first report the hepcidin expression induced in the developmental stages from embryo to fry of red sea bream (Pagarus major) and in juvenile black porgy (Acanthopagrus schlegelii B.) upon continuous waterborne exposure to BaP. The gene expression of CYP1A1 and IgL (immunoglobulin light chain) were both measured. Expression of the Pagarus major hepcidin gene (PM-hepc) was increased in post hatch fry at 24 h and 120 h exposure to BaP at concentrations of 0.1, 0.5 and 1.0 microg/l, respectively. The gene expression pattern was comparable to that of CYP1A1 but different from that of IgL. In addition, a high number of AS-hepc2 transcripts (Acanthopagrus schlegelii B. hepcidin gene) were detected in the liver upon exposure to 1.0 microg/l BaP. This study demonstrates that hepcidin gene expression is significantly induced in BaP-exposed red sea bream and black porgy.
The "early life" origins of obesity-related health disorders: new discoveries regarding the intergenerational transmission of developmentally programmed traits in the global cardiometabolic health crisis.
Benyshek, Daniel C
Popular media reports concerning the causes of the current global obesity pandemic and its related sequelae-the cardiometabolic syndrome-are often couched in terms of dramatic changes in diet and lifestyle around the world; namely, drastically increasing dietary intakes of high energy foods and plummeting levels of daily physical activity-the hallmarks of the so called "nutrition transition." Far less attention is generally drawn to the important role phenotypic plasticity during early life (i.e., "developmental programming") plays in the cardiometabolic health crisis. Recently, however, researchers working within the field of the developmental origins of health and disease (DOHaD) and epigenetics have extended our understanding of the role played by these developmental processes and capacities in health and disease even further by investigating the transmissible nature of developmentally programmed cardiometabolic traits to subsequent generations. In this review, after briefly revisiting the fundamental discoveries of first-generation DOHaD research, I consider how recent discoveries regarding the transmissibility of developmentally acquired traits are providing new insights into the current global cardiometabolic pandemic, and how a better understanding of developmental programming-including transmissibility-are essential for the conceptualization and implementation of public health initiatives aimed at stemming this global health crisis.
Liseron-Monfils, Christophe; Bi, Yong-Mei; Downs, Gregory S; Wu, Wenqing; Signorelli, Tara; Lu, Guangwen; Chen, Xi; Bondo, Eddie; Zhu, Tong; Lukens, Lewis N; Colasanti, Joseph; Rothstein, Steven J; Raizada, Manish N
Nitrogen is considered the most limiting nutrient for maize (Zea mays L.), but there is limited understanding of the regulation of nitrogen-related genes during maize development. An Affymetrix 82K maize array was used to analyze the expression of ≤ 46 unique nitrogen uptake and assimilation probes in 50 maize tissues from seedling emergence to 31 d after pollination. Four nitrogen-related expression clusters were identified in roots and shoots corresponding to, or overlapping, juvenile, adult, and reproductive phases of development. Quantitative real time PCR data was consistent with the existence of these distinct expression clusters. Promoters corresponding to each cluster were screened for over-represented cis-acting elements. The 8-bp distal motif of the Arabidopsis 43-bp nitrogen response element (NRE) was over-represented in nitrogen-related maize gene promoters. This conserved motif, referred to here as NRE43-d8, was previously shown to be critical for nitrate-activated transcription of nitrate reductase (NIA1) and nitrite reductase (NIR1) by the NIN-LIKE PROTEIN 6 (NLP6) in Arabidopsis. Here, NRE43-d8 was over-represented in the promoters of maize nitrate and ammonium transporter genes, specifically those that showed peak expression during early-stage vegetative development. This result predicts an expansion of the NRE-NLP6 regulon and suggests that it may have a developmental component in maize. We also report leaf expression of putative orthologs of nitrite transporters (NiTR1), a transporter not previously reported in maize. We conclude by discussing how each of the four transcriptional modules may be responsible for the different nitrogen uptake and assimilation requirements of leaves and roots at different stages of maize development.
Horiuchi, Risa; Hirotsu, Naoki; Miyanishi, Nobumitsu
N-Glycosylation is one of the post-translational modifications. In animals, N-glycans linked to proteins function in cell-cell recognition, sorting, transport, and other biological phenomena. However, in plants, N-glycan-mediated biological functions remain obscure. In a previous study, we showed that the main type of N-glycan transition is from the paucimannosidic to complex type before and after germination in Oryza sativa, suggesting that transitions of N-glycan, including those of glycoproteins and glycosyltransferases, are closely associated with plant growth. To further elucidate the relationship between N-glycan structure and plant growth, we analyzed the structures of N-glycans expressed in O. sativa seedlings grown under light conditions and performed comparative analyses of the structures in the shoot and root. The analyses show that fundamental N-glycan structures are common to the shoot and root, whereas paucimannosidic-type N-glycans dramatically decreased in the root grown under light conditions. Further, to investigate the effects of light on N-glycan structures in O. sativa seedlings, we analyzed N-glycan structures in O. sativa seedlings grown in the dark. Understandably, N-glycan expression in the root was almost unaffected by light. However, despite a marked difference in phenotype, N-glycan expression in the shoot was also unaffected by light. This result suggests that the shoot and root of O. sativa have different glycoproteins and distinct N-glycan synthetic systems. Thus, we propose that the N-glycan synthetic system of the O. sativa shoot is almost unaffected by light conditions and that many photosynthesis-related proteins are not modified by N-glycans.
Vasudeva, R; Deeming, D C; Eady, P E
The outcome of post-copulatory sexual selection is determined by a complex set of interactions between the primary reproductive traits of two or more males and their interactions with the reproductive traits of the female. Recently, a number of studies have shown the primary reproductive traits of both males and females express phenotypic plasticity in response to the thermal environment experienced during ontogeny. However, how plasticity in these traits affects the dynamics of sperm competition remains largely unknown. Here, we demonstrate plasticity in testes size, sperm size and sperm number in response to developmental temperature in the bruchid beetle Callosobruchus maculatus. Males reared at the highest temperature eclosed at the smallest body size and had the smallest absolute and relative testes size. Males reared at both the high- and low-temperature extremes produced both fewer and smaller sperm than males reared at intermediate temperatures. In the absence of sperm competition, developmental temperature had no effect on male fertility. However, under conditions of sperm competition, males reared at either temperature extreme were less competitive in terms of sperm offence (P(2)), whereas those reared at the lowest temperature were less competitive in terms of sperm defence (P(1)). This suggests the developmental pathways that regulate the phenotypic expression of these ejaculatory traits are subject to both natural and sexual selection: natural selection in the pre-ejaculatory environment and sexual selection in the post-ejaculatory environment. In nature, thermal heterogeneity during development is commonplace. Therefore, we suggest the interplay between ecology and development represents an important, yet hitherto underestimated component of male fitness via post-copulatory sexual selection.
David A Garfield
Full Text Available Regulatory interactions buffer development against genetic and environmental perturbations, but adaptation requires phenotypes to change. We investigated the relationship between robustness and evolvability within the gene regulatory network underlying development of the larval skeleton in the sea urchin Strongylocentrotus purpuratus. We find extensive variation in gene expression in this network throughout development in a natural population, some of which has a heritable genetic basis. Switch-like regulatory interactions predominate during early development, buffer expression variation, and may promote the accumulation of cryptic genetic variation affecting early stages. Regulatory interactions during later development are typically more sensitive (linear, allowing variation in expression to affect downstream target genes. Variation in skeletal morphology is associated primarily with expression variation of a few, primarily structural, genes at terminal positions within the network. These results indicate that the position and properties of gene interactions within a network can have important evolutionary consequences independent of their immediate regulatory role.
Melo, Carlos Fernando Odir Rodrigues; Esteves, Cibele Zanardi; de Oliveira, Rosimeire Nunes; Guerreiro, Tatiane Melina; de Oliveira, Diogo Noin; Lima, Estela de Oliveira; Miné, Júlio César; Allegretti, Silmara Marques; Catharino, Rodrigo Ramos
Ascaris lumbricoides is responsible for a highly disseminated helminth parasitic disease, ascariosis, a relevant parasitosis that responds for great financial burden on the public health system of developing countries. In this work, metabolic fingerprinting using high-resolution mass spectrometry (HRMS) was employed to identify marker molecules from A. lumbricoides in different development stages. We have identified nine biomarkers, such as pheromones and steroidal prohormones in early stages, among other molecules in late development stages, making up four molecules for fertilized eggs, four marker molecules for first larvae (L1) and one marker molecule for third larvae (L3). Therefore, our findings indicate that this approach is suitable for biochemical characterization of A. lumbricoides development stages. Moreover, the straightforward analytical method employed, with almost no sample preparation from a complex matrix (feces) using high-resolution mass spectrometry, suggests that it is possible to seek for an easier and faster way to study animal molding processes.
The responses of the early development of Laminaria japonica collected from Kiaochow Bay in China to enhanced ultraviolet-B radiation (UV-B, 280—320 nm) were studied in the laboratory. The low UV-B ra-diations (11.7—23.4 J·m-2·d-1) had no significant effects on zoospores attachment, but when the UV-B dose > 35.1 J·m-2·d-1 the attachment decreased significantly compared with the control. Germination of embryospores was >93% under the low (11.7—35.1 J·m-2·d-1) doses, and in the range of 78.5%—88.5% under the high (46.8—70.2 J·m-2·d-1) UV-B doses, indicating a significant radiation effect. Under the higher UV-B exposure (35.1—70.2 J·m-2·d-1), all of the few gametophytes formed from embryospores died 120 h post-release. After exposure to the low UV-B radiation (11.7—23.4 J·m-2·d-1), the formation of sporophytes decreased and the female gametophyte clones increased compared with the control. However, the sex ratio and the relative growth of female gametophytes/sporophytes had not signifi-cantly changed. According to the results, enhanced UV-B radiation has a significant effect on the early development of L. japonica under laboratory conditions, suggesting that the UV-B radiation could not be overlooked as one of the important environmental factors influencing the ontogeny of macroalgae living in marine ecosystems.
LIU Su; ZHANG QuanSheng; WANG You; JU Qing; TANG XueXi
The responses of the early development of Laminaria japonica collected from Kiaochow Bay in China to enhanced ultraviolet-B radiation (UV-B, 280-320 nm) were studied in the laboratory. The low UV-B radiations (11.7-23.4 J·m-2·d-) had no significant effects on zoospores attachment, but when the UV-B dose ＞ 35.1 J·m-2·d-1 the attachment decreased significantly compared with the control. Germination of embryosperes was ＞93% under the low (11.7-35.1 J·m-2·d-1) doses, and in the range of 78.5%-88.5% under the high (46.8-70.2 J·m-2·d-1) UV-B doses, indicating a significant radiation effect. Under the higher UV-B exposure (35.1-70.2 J·m-2·d-1), all of the few gametophytes formed from embryospores died 120 h post-release. After exposure to the low UV-B radiation (11.7-23.4 J·m-2·d-1), the formation of sporophytes decreased and the female gametophyte clones increased compared with the control. However, the sex ratio and the relative growth of female gametophytes/sporophytes had not significantly changed. According to the results, enhanced UV-B radiation has a significant effect on the early development of L. japonica under laboratory conditions, suggesting that the UV-B radiation could not be overlooked as one of the important environmental factors influencing the ontogeny of macroalgae living in marine ecosystems.
Canto-Soler M Valeria
Full Text Available Abstract Background The use of Specific Pathogen Free (SPF eggs in combination with RCAS retrovirus, a member of the Avian Sarcoma-Leukosis Virus (ASLV family, is of standard practice to study gene function and development. SPF eggs are certified free of infection by specific pathogen viruses of either exogenous or endogenous origin, including those belonging to the ASLV family. Based on this, SPF embryos are considered to be free of ASLV viral protein expression, and consequently in developmental research studies RCAS infected cells are routinely identified by immunohistochemistry against the ASLV viral proteins p19 and p27. Contrary to this generally accepted notion, observations in our laboratory suggested that certified SPF chicken embryos may endogenously express ASLV viral proteins p19 and p27. Since these observations may have significant implications for the developmental research field we further investigated this possibility. Results We demonstrate that certified SPF chicken embryos have transcriptionally active endogenous ASLV loci (ev loci capable of expressing ASLV viral proteins, such as p19 and p27, even when those loci are not capable of producing viral particles. We also show that the extent of viral protein expression in embryonic tissues varies not only among flocks but also between embryos of the same flock. In addition, our genetic screening revealed significant heterogeneity in ev loci composition even among embryos of the same flock. Conclusions These observations have critical implications for the developmental biology research field, since they strongly suggest that the current standard methodology used in experimental studies using the chick embryo and RCAS vectors may lead to inaccurate interpretation of results. Retrospectively, our observations suggest that studies in which infected cells have been identified simply by pan-ASLV viral protein expression may need to be considered with caution. For future studies, they
Sankar, Wudbhav N; Gornitzky, Alex L; Clarke, Nicholas M P; Herrera-Soto, José A; Kelley, Simon P; Matheney, Travis; Mulpuri, Kishore; Schaeffer, Emily K; Upasani, Vidyadhar V; Williams, Nicole; Price, Charles T
Closed reduction (CR) is a common treatment for infantile developmental dysplasia of the hip. The purpose of this observational, prospective, multicenter study was to determine the early outcomes following CR. Prospectively collected data from an international multicenter study group was analyzed for patients treated from 2010 to 2014. Baseline demographics, clinical exam, radiographic/ultrasonographic data, and history of previous orthotic treatment were assessed. At minimum 1-year follow-up, failure was defined as an IHDI grade 3 or 4 hip and/or need for open reduction. The incidence of avascular necrosis (AVN), residual dysplasia, and need for further surgery was assessed. A total of 78 patients undergoing CR for 87 hips were evaluated with a median age at initial reduction of 8 months (range, 1 to 20 mo). Of these, 8 hips (9%) were unable to be closed reduced initially. At most recent follow-up (median 22 mo; range, 12 to 36 mo), 72/79 initially successful CRs (91%) remained stable. The likelihood of failure was unaffected by initial clinical reducibility of the hip (P=0.434), age at initial CR (P=0.897), or previous treatment in brace (P=0.222). Excluding those hips that failed initial CR, 18/72 hips (25%) developed AVN, and the risk of osteonecrosis was unaffected by prereduction reducibility of the hip (P=0.586), age at CR (P=0.745), presence of an ossific nucleus (P=0.496), or previous treatment in brace (P=0.662). Mean acetabular index on most recent radiographs was 25 degrees (±6 degrees), and was also unaffected by any of the above variables. During the follow-up period, 8/72 successfully closed reduced hips (11%) underwent acetabular and/or femoral osteotomy for residual dysplasia. Following an initially successful CR, 9% of hips failed reduction and 25% developed radiographic AVN at early-term follow-up. History of femoral head reducibility, previous orthotic bracing, and age at CR did not correlate with success or chances of developing AVN. Further
Yu, Changmao; Wang, Yinan; Zhang, Jing; Fang, Wenzhen; Luo, Damin
In this study we have investigated the anatomic sites of expression and developmental expression patterns of two cathepsin B-like cysteine proteases (AC-cathB-1, -2) of Angiostrongylus cantonensis. The immunolocalization results revealed that native AC-cathBs were found present in the L1 and L3 larvae, female and male adults, and the AC-cathBs were localized mainly on the digestive tract of A. cantonensis and expressed at varied levels and in different patterns in the internal tissues according to their developmental stage. Consistent with the infective stage of L3 is a much more intense staining of AC-cathBs in the esophagus compared with the intestine. In contrast to L3, more abundant signals were located to the intestine of adults, suggesting that nutrition digestion likely to be the main function of the protease at this point. AC-cathBs fluorescent signals were present in excretory pore, excretory tube in lateral cords, and muscular esophagus of larvae, further supported the AC-cathB-1, -2 likely to be released by A. cantonensis as excretory/secretory products. Additionally, only the protein AC-cathB-2 was detected in the reproductive system, especially in the wall of vas deferens, uterus, and oviduct of the parasites, whether the AC-cathB-2 has some function in germ cells development and maturation need to be further characterized. Although the anatomic sites and expression patterns were different in larvae and adults and the corresponding function might not the same, AC-cathB-1 and -2 involved in the host-parasite interaction in addition to digestive function.
Higdon, Charles W; Mitra, Robi D; Johnson, Stephen L
In order to facilitate understanding of pigment cell biology, we developed a method to concomitantly purify melanocytes, iridophores, and retinal pigmented epithelium from zebrafish, and analyzed their transcriptomes. Comparing expression data from these cell types and whole embryos allowed us to reveal gene expression co-enrichment in melanocytes and retinal pigmented epithelium, as well as in melanocytes and iridophores. We found 214 genes co-enriched in melanocytes and retinal pigmented epithelium, indicating the shared functions of melanin-producing cells. We found 62 genes significantly co-enriched in melanocytes and iridophores, illustrative of their shared developmental origins from the neural crest. This is also the first analysis of the iridophore transcriptome. Gene expression analysis for iridophores revealed extensive enrichment of specific enzymes to coordinate production of their guanine-based reflective pigment. We speculate the coordinated upregulation of specific enzymes from several metabolic pathways recycles the rate-limiting substrate for purine synthesis, phosphoribosyl pyrophosphate, thus constituting a guanine cycle. The purification procedure and expression analysis described here, along with the accompanying transcriptome-wide expression data, provide the first mRNA sequencing data for multiple purified zebrafish pigment cell types, and will be a useful resource for further studies of pigment cell biology.
Charles W Higdon
Full Text Available In order to facilitate understanding of pigment cell biology, we developed a method to concomitantly purify melanocytes, iridophores, and retinal pigmented epithelium from zebrafish, and analyzed their transcriptomes. Comparing expression data from these cell types and whole embryos allowed us to reveal gene expression co-enrichment in melanocytes and retinal pigmented epithelium, as well as in melanocytes and iridophores. We found 214 genes co-enriched in melanocytes and retinal pigmented epithelium, indicating the shared functions of melanin-producing cells. We found 62 genes significantly co-enriched in melanocytes and iridophores, illustrative of their shared developmental origins from the neural crest. This is also the first analysis of the iridophore transcriptome. Gene expression analysis for iridophores revealed extensive enrichment of specific enzymes to coordinate production of their guanine-based reflective pigment. We speculate the coordinated upregulation of specific enzymes from several metabolic pathways recycles the rate-limiting substrate for purine synthesis, phosphoribosyl pyrophosphate, thus constituting a guanine cycle. The purification procedure and expression analysis described here, along with the accompanying transcriptome-wide expression data, provide the first mRNA sequencing data for multiple purified zebrafish pigment cell types, and will be a useful resource for further studies of pigment cell biology.
Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E
Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Güngördü, Abbas; Birhanli, Ayse; Ozmen, Murat
The present study was undertaken to determine the toxic effect of a lethal concentration of six different commercially used textile dyes on the 46th stage of Xenopus laevis tadpoles. The tadpoles were exposed to Astrazon Red FBL, Astrazon Blue FGRL, Remazol Red RR, Remazol Turquoise Blue G-A, Cibacron Red FN-3G, and Cibacron Blue FN-R for 168 h in static test conditions, and thus, 168-h median lethal concentrations (LC(50)s) of each dye were determined to be 0.35, 0.13, 112, 7, 359, and 15.8 mg/L, respectively. Also, to evaluate the sublethal effects of each dye, tadpoles were exposed to different concentrations of dyes (with respect to 168-h LC(50)s) for 24 h. The alteration of selected enzyme activities was tested. For this aim, glutathione S-transferase (GST), carboxylesterase, and lactate dehydrogenase (LDH) were assayed. After dye exposure, the GST induction or inhibition and LDH induction indicated some possible mechanisms of oxidative stress and deterioration in aerobic respiration processes induced by the tested dyes. Findings of the study suggest that selected biomarker enzymes are useful in understanding the toxic mechanisms of these dyes in X. laevis tadpoles as early warning indicators. Therefore, these selected biomarkers may evaluate the effect of environmental factors, such as textile dye effluents and other industrial pollutants, on amphibians in biomonitoring studies.
Politis, Sebastian Nikitas; Dahlke, Flemming T.; Butts, Ian A.E.
Offspring, especially during early development, are influenced by both intrinsic properties endowed to them by their parents, extrinsic environmental factors as well as the interplay between genes and the environment. We investigated the effects of paternity (P), temperature (T), and asynchronous...... hatching on larval traits of cod, Gadus morhua from the Atlantic Ocean and the Baltic Sea. Daily cohorts of 4 half-sib families of Atlantic larvae and 5 half-sib families of Baltic larvae were incubated and hatched at 5 temperatures (Atlantic 2.0-10.0°C, Baltic 6.5-12.5°C) and imaged for notochord length......, respectively. In Baltic larvae, size at peak hatch tended to decrease with increasing T and P × T explained 34.6% of the variance. In Atlantic larvae, growth, YUR and YUE were influenced by T while P alone explained 26.0% of the variance in YUE and up to 66.4% of variance in morphological traits at 4 DPH...
Allan, Nicholas P; Capron, Daniel W; Lejuez, Carl W; Reynolds, Elizabeth K; MacPherson, Laura; Schmidt, Norman B
Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity has been identified as an important risk factor in the development of anxiety psychopathology. This study prospectively examined the development of anxiety symptoms in a sample of 277 adolescents (M age = 11.52; 44 % female, 56 % male) over a 3 year period including the influence of anxiety sensitivity on this development. Further, this study investigated whether there were distinct classes of adolescents based on their anxiety symptom trajectories and including anxiety sensitivity as a predictor. Consistent with other reports, findings indicated an overall decline in anxiety symptoms over time in the sample. However, three classes of adolescents were found with distinct anxiety symptom trajectories and anxiety sensitivity was an important predictor of class membership. Adolescents with elevated anxiety sensitivity scores were more likely to be classified as having high and increasing anxiety symptoms over time versus having moderate to low and decreasing anxiety symptoms over time. There are important implications for identification of adolescents and children who are at risk for the development of an anxiety disorder.
Lindeman, Leif C.; Andersen, Ingrid S.; Reiner, Andrew H.
A hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes by modified histones in sperm suggests a predictive...... role of histone marks for ZGA. In zebrafish, pre-ZGA development for ten cell cycles provides an opportunity to examine whether genomic enrichment in modified histones is present before initiation of transcription. By profiling histone H3 trimethylation on all zebrafish promoters before and after ZGA...
Chonchaiya, Weerasak; Tardif, Twila; Mai, Xiaoqin; Xu, Lin; Li, Mingyan; Kaciroti, Niko; Kileny, Paul R; Shao, Jie; Lozoff, Betsy
Auditory processing capabilities at the subcortical level have been hypothesized to impact an individual's development of both language and reading abilities. The present study examined whether auditory processing capabilities relate to language development in healthy 9-month-old infants. Participants were 71 infants (31 boys and 40 girls) with both Auditory Brainstem Response (ABR) and language assessments. At 6 weeks and/or 9 months of age, the infants underwent ABR testing using both a standard hearing screening protocol with 30 dB clicks and a second protocol using click pairs separated by 8, 16, and 64-ms intervals presented at 80 dB. We evaluated the effects of interval duration on ABR latency and amplitude elicited by the second click. At 9 months, language development was assessed via parent report on the Chinese Communicative Development Inventory - Putonghua version (CCDI-P). Wave V latency z-scores of the 64-ms condition at 6 weeks showed strong direct relationships with Wave V latency in the same condition at 9 months. More importantly, shorter Wave V latencies at 9 months showed strong relationships with the CCDI-P composite consisting of phrases understood, gestures, and words produced. Likewise, infants who had greater decreases in Wave V latencies from 6 weeks to 9 months had higher CCDI-P composite scores. Females had higher language development scores and shorter Wave V latencies at both ages than males. Interestingly, when the ABR Wave V latencies at both ages were taken into account, the direct effects of gender on language disappeared. In conclusion, these results support the importance of low-level auditory processing capabilities for early language acquisition in a population of typically developing young infants. Moreover, the auditory brainstem response in this paradigm shows promise as an electrophysiological marker to predict individual differences in language development in young children. © 2012 Blackwell Publishing Ltd.
Pauline C Yu
Full Text Available The Southern Ocean, a region that will be an ocean acidification hotspot in the near future, is home to a uniquely adapted fauna that includes a diversity of lightly-calcified invertebrates. We exposed the larvae of the echinoid Sterechinus neumayeri to environmental levels of CO(2 in McMurdo Sound (control: 410 µatm, Ω = 1.35 and mildly elevated pCO(2 levels, both near the level of the aragonite saturation horizon (510 µatm pCO(2, Ω = 1.12, and to under-saturating conditions (730 µatm, Ω = 0.82. Early embryological development was normal under these conditions with the exception of the hatching process, which was slightly delayed. Appearance of the initial calcium carbonate (CaCO(3 spicule nuclei among the primary mesenchyme cells of the gastrulae was synchronous between control and elevated pCO(2 treatments. However, by prism (7 days after the initial appearance of the spicule nucleus, elongating arm rod spicules were already significantly shorter in the highest CO(2 treatment. Unfed larvae in the 730 µatm pCO(2 treatment remained significantly smaller than unfed control larvae at days 15-30, and larvae in the 510 µatm treatment were significantly smaller at day 20. At day 30, the arm lengths were more differentiated between 730 µatm and control CO(2 treatments than were body lengths as components of total length. Arm length is the most plastic morphological aspect of the echinopluteus, and appears to exhibit the greatest response to high pCO(2/low pH/low carbonate, even in the absence of food. Thus, while the effects of elevated pCO(2 representative of near future climate scenarios are proportionally minor on these early developmental stages, the longer term effects on these long-lived invertebrates is still unknown.
Dishaw, Laura V; Hunter, Deborah L; Padnos, Beth; Padilla, Stephanie; Stapleton, Heather M
Organophosphate flame retardants (OPFRs) are common replacements for the phased-out polybrominated diphenyl ethers (PBDEs) and have been detected at high concentrations in environmental samples. OPFRs are structurally similar to organophosphate pesticides and may adversely affect the developing nervous system. This study evaluated the overt toxicity, uptake, and neurobehavioral effects of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP) in early life stage zebrafish. Chlorpyrifos was used as a positive control. For overt toxicity and neurobehavioral assessments, zebrafish were exposed from 0 to 5 days postfertilization (dpf). Hatching, death, or malformations were evaluated daily. Teratogenic effects were scored by visual examination on 6 dpf. To evaluate uptake and metabolism, zebrafish were exposed to 1 µM of each organophosphate (OP) flame retardant and collected on 1 and 5 dpf to monitor accumulation. Larval swimming activity was measured in 6 dpf larvae to evaluate neurobehavioral effects of exposures below the acute toxicity threshold. TDBPP elicited the greatest toxicity at >1 µM. TDCPP and chlorpyrifos were overtly toxic at concentrations ≥10 µM, TCEP, and TCPP were not overtly toxic at the doses tested. Tissue concentrations increased with increasing hydrophobicity of the parent chemical after 24 h exposures. TDCPP and TDBPP and their respective metabolites were detected in embryos on 5 dpf. For all chemicals tested, developmental exposures that were not overtly toxic significantly altered larval swimming activity. These data indicate that OPFRs adversely affect development of early life stage zebrafish.
Bakkers, J; Semino, C E; Stroband, H; Kijne, J W; Robbins, P W; Spaink, H P
Derivatives of chitin oligosaccharides have been shown to play a role in plant organogenesis at nanomolar concentrations. Here we present data which indicate that chitin oligosaccharides are important for embryogenesis in vertebrates. We characterize chitin oligosaccharides synthesized in vitro by zebrafish and carp embryos in the late gastrulation stage by incorporation of radiolabeled N-acetyl-D-[U14C]glucosamine and by HPLC in combination with enzymatic conversion using the Bradyrhizobium NodZ alpha-1, 6-fucosyltransferase and chitinases. A rapid and sensitive bioassay for chitin oligosaccharides was also used employing suspension-cultured plant cells of Catharanthus roseus. We show that chitin oligosaccharide synthase activity is apparent only during late gastrulation and can be inhibited by antiserum raised against the Xenopus DG42 protein. The DG42 protein, a glycosyltransferase, is transiently expressed between midblastula and neurulation in Xenopus and zebrafish embryogenesis. Microinjection of the DG42 antiserum or the Bradyrhizobium NodZ enzyme in fertilized eggs of zebrafish led to severe defects in trunk and tail development.
Sweetman, Crystal; Wong, Darren Cj; Ford, Christopher M; Drew, Damian P
Vitis vinifera berry development is characterised by an initial phase where the fruit is small, hard and acidic, followed by a lag phase known as veraison. In the final phase, berries become larger, softer and sweeter and accumulate an array of organoleptic compounds. Since the physiological and biochemical makeup of grape berries at harvest has a profound impact on the characteristics of wine, there is great interest in characterising the molecular and biophysical changes that occur from flowering through veraison and ripening, including the coordination and temporal regulation of metabolic gene pathways. Advances in deep-sequencing technologies, combined with the availability of increasingly accurate V. vinifera genomic and transcriptomic data, have enabled us to carry out RNA-transcript expression analysis on a global scale at key points during berry development. A total of 162 million 100-base pair reads were generated from pooled Vitis vinifera (cv. Shiraz) berries sampled at 3-weeks post-anthesis, 10- and 11-weeks post-anthesis (corresponding to early and late veraison) and at 17-weeks post-anthesis (harvest). Mapping reads from each developmental stage (36-45 million) onto the NCBI RefSeq transcriptome of 23,720 V. vinifera mRNAs revealed that at least 75% of these transcripts were detected in each sample. RNA-Seq analysis uncovered 4,185 transcripts that were significantly upregulated at a single developmental stage, including 161 transcription factors. Clustering transcripts according to distinct patterns of transcription revealed coordination in metabolic pathways such as organic acid, stilbene and terpenoid metabolism. From the phenylpropanoid/stilbene biosynthetic pathway at least 46 transcripts were upregulated in ripe berries when compared to veraison and immature berries, and 12 terpene synthases were predominantly detected only in a single sample. Quantitative real-time PCR was used to validate the expression pattern of 12 differentially expressed
ZHOU; Jie; ZHAO; Ruqian; WEI; Xihui; XIA; Dong; XU; Qingfu
The present study was aimed to investigate the developmental patterns of leptin mRNA expression in dorsal subcutaneous adipose tissue and Ob-Rb mRNA expression in hypothalamus in pigs of different breeds and sexes. Erhualian gilts and boars and Large White boars were sampled at birth, 3, 20, 30, 45, 90, 120 and 180 days of age, respectively. Serum concentration of leptin was measured with RIA and single tube semi-quantitative RT-PCR was applied to determine the relative abundances of mRNA expression using 18S rRNA as an internal standard. The results showed that leptin mRNA expression in adipose tissue increased with age and displayed both sex and breed differences. In Erhualian pigs, females expressed higher leptin mRNA compared with males, and Erhualian boars showed higher abundance of leptin mRNA than Large White boars (P＜0.01). Serum leptin levels were in good agreement with adipose leptin mRNA, displaying similar sex and line differences. In contrast, expression of Ob-Rb mRNA in hypothalamus exhibited a distinctive pattern, decreased gradually after birth, and then increased till weaning. After weaning, Ob-Rb gene expression decreased gradually with age but rose gradually again from 120 to 180 days of age in Erhualian pigs. The expression of Ob-Rb mRNA was higher in Large White pigs than that in Erhualian pigs (P＜0.01). The results suggest that the serum leptin level and leptin gene expression in adipose tissue highly correlate with adiposity.
Lu, Yu-Xuan; Denlinger, David L; Xu, Wei-Hua
The decision made by insects to develop into adults or halt development (enter diapause and prolong lifespan) is commonly based on environmental signals that provide reliable predictors of future seasons of adversity. For example, the short day lengths of early autumn accurately foretell the advent of winter, but little is known about the molecular mechanisms that preside over the hormonal events dictating whether the insect proceeds with development or enters diapause. In Helicoverpa armigera we show that day length affects H3K27me3 by affecting polycomb repressive complex 2 (PRC2) protein extra sex comb (ESC) and regulates the prothoracicotropic hormone (PTTH) gene, thus directly influencing developmental timing. ESC expression in brains of developing (nondiapause) pupae is higher than in brains from diapausing pupae. High ESC expression is localized in two pairs of PTTH neurosecretory cells, and H3K27me3 recruits on the PTTH promoter. Double strand ESC and PRC2 inhibitor (DzNep) treatment in vitro show that ESC triggers PTTH promoter activity, which in turn depends on PRC2 methyltransferase activity. Injection of DzNep into pupae programmed for development reduces the H3K27me3 mark and PTTH gene expression, thereby delaying development. Although ESC is best known as a transcriptional repressor, our results show that ESC prompts development and metamorphosis. We believe this is the first report showing that the PRC2 complex functions as an activator and that a low level of H3K27me3 can prolong lifespan (i.e. induce diapause) by controlling PTTH gene expression in insects.
Rohde, Kristian; Klein, David C.; Møller, Morten; Rath, Martin F.
Retina and anterior neural fold homeobox (Rax) gene encodes a transcription factor essential for vertebrate eye development. Recent microarray studies indicate that Rax is expressed in the adult rat pineal gland and retina. The present study reveals that Rax expression levels in the rat change significantly during retinal development with a peak occurring at embryonic day (E) 18, whereas Rax expression in the pineal is relatively delayed and not detectable until E20. In both tissues, Rax is e...
Pramparo, Tiziano; Libiger, Ondrej; Jain, Sonia; Li, Hong; Youn, Yong Ha; Hirotsune, Shinji; Schork, Nicholas J; Wynshaw-Boris, Anthony
Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3ε that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3ε), and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can be used to define
Adam, C L; Bake, T; Findlay, P A; Milne, J S; Aitken, R P; Wallace, J M
Intra-uterine growth restriction (IUGR) is involved in developmental metabolic programming and here we test the hypothesis that IUGR affects the developing hypothalamic energy balance regulatory pathways in a sex-specific manner. This experiment investigated early postnatal hypothalamic gene expression for six primary leptin- and insulin-sensitive neuropeptides and receptors in male and female IUGR (n = 8 and 9, respectively) and normal (N) birth weight lambs (n = 8 per gender) gestated and suckled by overnourished mothers. IUGR lambs were smaller at birth, had increased fractional growth rates (FGR), lower final body weight (11 weeks) and similar body fat content compared with N lambs, while males had higher final body weight and insulinemia but lower body fat and leptinemia than females. In situ hybridization revealed greater gene expression in the hypothalamic arcuate nucleus at 11 weeks for anorexigenic genes in females and orexigenic genes in males, with no effect of IUGR. Leptinemia correlated with gene expression for neuropeptide Y (NPY, negatively) in both sexes and pro-opiomelanocortin (POMC, positively) in females but with leptin receptor (negatively) only in males. Current FGR for girth correlated negatively with gene expression for NPY in males and POMC in females. Neither IUGR nor gender affected suckling activity (proxy for appetite) assessed at 3 weeks, but final NPY gene expression correlated with suckling weight gain in males. This study has revealed no effect of IUGR on early postnatal hypothalamic energy balance gene expression but a major effect of gender associated with major sex differences in adiposity and leptinemia. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.
King, Ashley C; Bjorklund, David F
The field of evolutionary developmental psychology can potentially broaden the horizons of mainstream evolutionary psychology by combining the principles of Darwinian evolution by natural selection with the study of human development, focusing on the epigenetic effects that occur between humans and their environment in a way that attempts to explain how evolved psychological mechanisms become expressed in the phenotypes of adults. An evolutionary developmental perspective includes an appreciation of comparative research and we, among others, argue that contrasting the cognition of humans with that of nonhuman primates can provide a framework with which to understand how human cognitive abilities and intelligence evolved. Furthermore, we argue that several aspects of childhood (e.g., play and immature cognition) serve both as deferred adaptations as well as imparting immediate benefits. Intense selection pressure was surely exerted on childhood over human evolutionary history and, as a result, neglecting to consider the early developmental period of children when studying their later adulthood produces an incomplete picture of the evolved adaptations expressed through human behavior and cognition.
An approach to assess the extent of developmental gene expression of various regions of plastid (pt)DNA in mustard (Sinapis alba L.) is described. It involves cloning of most ptDNA regions. The cloned regions then serve as hybridization probes to detect and assess the abundance of complementary RNA sequences represented in total plastid RNA. By comparison of the hybridization pattern observed with plastid RNA from either dark-grown or light-grown plants it was found that many ptDNA regions are constitutively expressed, while several 'inducible' regions account for much higher transcript levels in the chloroplast than in the etioplast stage. The reverse situation, i.e. 'repressed' regions which would account for higher transcript levels in the etioplast, was not observed. The hybridization results obtained with RNA from 'intermediatetype' plastids suggest that transient gene expression is a common feature during light-induced chloroplast development. The time-course of gene expression differs for various ptDNA regions.
Ahmed, Sheaza; Ariyaratne, Menaka; Patel, Jigar; Howard, Alexander E; Kalinoski, Andrea; Phuntumart, Vipaporn; Morris, Paul F
Changes in the levels of polyamines are correlated with the activation or repression of developmental response pathways, but the role of polyamine transporters in the regulation of polyamine homeostasis and thus indirectly gene expression, has not been previously addressed. Here we show that the A. thaliana and rice transporters AtPUT5 and OsPUT1 were localized to the ER, while the AtPUT2, AtPUT3, and OsPUT3 were localized to the chloroplast by transient expression in N. benthamiana. A. thaliana plants that were transformed with OsPUT1 under the control the PUT5 promoter were delayed in flowering by 16days. In contrast, put5 mutants flowered four days earlier than WT plants. The delay of flowering was associated with significantly higher levels of spermidine and spermidine conjugates in the leaves prior to flowering. A similar delay in flowering was also noted in transgenic lines with constitutive expression of either OsPUT1 or OsPUT3. All three transgenic lines had larger rosette leaves, thicker flowering stems, and produced more siliques than wild type plants. In contrast, put5 plants had smaller leaves, thinner flowering stems, and produced fewer siliques. Constitutive expression of PUTs was also associated with an extreme delay in both plant senescence and maturation rate of siliques. These experiments provide the first genetic evidence of polyamine transport in the timing of flowering, and indicate the importance of polyamine transporters in the regulation of flowering and senescence pathways.
Huang, Jinyu; Jiao, Jinzhen; Tan, Zhi-Liang; He, Zhixiong; Beauchemin, Karen A; Forster, Robert; Han, Xue-Feng; Tang, Shao-Xun; Kang, Jinghe; Zhou, Chuanshe
Thirty-six Xiangdong black goats were used to investigate age-related mRNA and protein expression levels of some genes related to skeletal muscle structural proteins, MRFs and MEF2 family, and skeletal muscle fiber type and composition during skeletal muscle growth under grazing (G) and barn-fed (BF) feeding systems. Goats were slaughtered at six time points selected to reflect developmental changes of skeletal muscle during nonrumination (days 0, 7, and 14), transition (day 42), and rumination phases (days 56 and 70). It was observed that the number of type IIx in the longissimus dorsi was increased quickly while numbers of type IIa and IIb decreased slightly, indicating that these genes were coordinated during the rapid growth and development stages of skeletal muscle. No gene expression was affected (P > 0.05) by feeding system except Myf5 and Myf6. Protein expressions of MYOZ3 and MEF2C were affected (P nutrition or feeding regimen mainly influences the expression of skeletal muscle growth genes.
Nakamura, Aline Minali; Chahad-Ehlers, Samira; Lima, André Luís A.; Taniguti, Cristiane Hayumi; Sobrinho Jr., Iderval; Torres, Felipe Rafael; de Brito, Reinaldo Alves
The West Indian fruit fly, Anastrepha obliqua, is an important agricultural pest in the New World. The use of pesticide-free methods to control invasive species such as this reinforces the search for genes potentially useful in their genetic control. Therefore, the study of chemosensory proteins involved with a range of responses to the chemical environment will help not only on the understanding of the species biology but may also help the development of environmentally friendly pest control strategies. Here we analyzed the expression patterns of three OBP genes, Obp19d_2, Obp56a and Obp99c, across different phases of A. obliqua development by qPCR. In order to do so, we tested eight and identified three reference genes for data normalization, rpl17, rpl18 and ef1a, which displayed stability for the conditions here tested. All OBPs showed differential expression on adults and some differential expression among adult stages. Obp99c had an almost exclusive expression in males and Obp56a showed high expression in virgin females. Thereby, our results provide relevant data not only for other gene expression studies in this species, as well as for the search of candidate genes that may help in the development of new pest control strategies. PMID:26818909
Full Text Available Moods are enduring affective states that we hypothesise should be affected by an individual's developmental experience and its current somatic state. We tested whether early-life adversity, induced by manipulating brood size, subsequently altered juvenile European starlings' (Sturnus vulgaris decisions in a judgment bias task designed to provide a cognitive measure of mood. We predicted that starlings from larger broods, specifically those that had experienced more nest competitors larger than themselves would exhibit reduced expectation of reward, indicative of a 'pessimistic', depression-like mood. We used a go/no-go task, in which 30 starlings were trained to probe a grey card disc associated with a palatable mealworm hidden underneath and avoid a different shade of grey card disc associated with a noxious quinine-injected mealworm hidden underneath. Birds' response latencies to the trained stimuli and also to novel, ambiguous stimuli intermediate between these were subsequently tested. Birds that had experienced greater competition in the nest were faster to probe trained stimuli, and it was therefore necessary to control statistically for this difference in subsequent analyses of the birds' responses to the ambiguous stimuli. As predicted, birds with more, larger nest competitors showed relatively longer latencies to probe ambiguous stimuli, suggesting reduced expectation of reward and a 'pessimistic', depression-like mood. However, birds with greater developmental telomere attrition--a measure of cellular aging associated with increased morbidity and reduced life-expectancy that we argue could be used as a measure of somatic state--showed shorter latencies to probe ambiguous stimuli. This would usually be interpreted as evidence for a more positive or 'optimistic' affective state. Thus, increased competition in the nest and poor current somatic state appear to have opposite effects on cognitive biases. Our results lead us to question
Petit, Nathalie; Lescure, Alain; Rederstorff, Mathieu
Rigid spine muscular dystrophy and the classical form of multiminicore disease are caused by mutations in SEPN1 gene, leading to a new clinical entity referred to as SEPN1-related myopathy. SEPN1 codes for selenoprotein N, a new member of the selenoprotein family, the function of which is still u...
Carter, Mark G.; Hamatani, Toshio; Sharov, Alexei A; Carmack, Condie E; Qian, Yong; Aiba, Kazuhiro; Ko, Naomi T.; Dudekula, Dawood B.; Brzoska, Pius M.; Hwang, S. Stuart; Minoru S.H. Ko
Applications of microarray technologies to mouse embryology/genetics have been limited, due to the nonavailability of microarrays containing large numbers of embryonic genes and the gap between microgram quantities of RNA required by typical microarray methods and the miniscule amounts of tissue available to researchers. To overcome these problems, we have developed a microarray platform containing in situ-synthesized 60-mer oligonucleotide probes representing approximately 22,000 unique mous...
Carter, Mark G.; Hamatani, Toshio; Sharov, Alexei A.; Carmack, Condie E.; Qian, Yong; Aiba, Kazuhiro; Ko, Naomi T.; Dudekula, Dawood B.; Brzoska, Pius M.; Hwang, S. Stuart; Ko, Minoru S.H.
Applications of microarray technologies to mouse embryology/genetics have been limited, due to the nonavailability of microarrays containing large numbers of embryonic genes and the gap between microgram quantities of RNA required by typical microarray methods and the miniscule amounts of tissue available to researchers. To overcome these problems, we have developed a microarray platform containing in situ-synthesized 60-mer oligonucleotide probes representing approximately 22,000 unique mouse transcripts, assembled primarily from sequences of stem cell and embryo cDNA libraries. We have optimized RNA labeling protocols and experimental designs to use as little as 2 ng total RNA reliably and reproducibly. At least 98% of the probes contained in the microarray correspond to clones in our publicly available collections, making cDNAs readily available for further experimentation on genes of interest. These characteristics, combined with the ability to profile very small samples, make this system a resource for stem cell and embryogenomics research. [Supplemental material is available online at www.genome.org and at the NIA Mouse cDNA Project Web site, http://lgsun.grc.nia.nih.gov/cDNA/cDNA.html.] PMID:12727912
刘成龙; 靳安民; 童斌辉
Objective: To study the changes of the gene expression pattern of spinal cord tissues in the early stage after injury by DNA microarray (gene chip). Methods: The contusion model of rat spinal cord was established according to Allen's falling strike method and the gene expression patterns of normal and injured spinal cord tissues were studied by gene chip. Results: The expression of 45 genes was significantly changed in the early stage after spinal cord injury, in which 22 genes up-regulated and 23 genes down-regulated. Conclusions: The expression of some genes changes significantly in the early stage after spinal cord injury, which indicates the complexity of secondary spinal cord injury.
Berland, Robert; Fiering, Steven; Wortis, Henry H
We previously identified an enhancer element upstream of the mouse cd5 gene that was required in reporter assays for the induction of cd5 promoter activity by BCR cross-linking. This element is highly conserved in placental mammals. To determine its physiological role, we have now generated mice with a targeted deletion of the enhancer. The result is the loss of CD5 expression in peritoneal and splenic B-1a cells of adult mice and an inability to induce CD5 by cross-linking of the BCR on splenic B-2 cells. Surprisingly, CD5 expression on B-1a cells of neonatal mice was only minimally compromised. Cd5 enhancer deletion also had only a modest effect on CD5 expression in the T lineage. Thus, this enhancer provides age- and tissue-specific regulation of CD5 expression and is an example of the utilization of different modes of regulation of expression in T and B cells.
Full Text Available Glial fibrillary acidic protein (GFAP is the major intermediate filament (IF protein in astrocytes. In the human brain, GFAP isoforms have unique expression patterns, which indicate that they play distinct functional roles. One isoform, GFAPδ, is expressed by proliferative radial glia in the developing human brain. In the adult human, GFAPδ is a marker for neural stem cells. However, it is unknown whether GFAPδ marks the same population of radial glia and astrocytes in the developing mouse brain as it does in the developing human brain. This study characterizes the expression pattern of GFAPδ throughout mouse embryogenesis and into adolescence. Gfapδ transcripts are expressed from E12, but immunohistochemistry shows GFAPδ staining only from E18. This finding suggests a translational uncoupling. GFAPδ expression increases from E18 to P5 and then decreases until its expression plateaus around P25. During development, GFAPδ is expressed by radial glia, as denoted by the co-expression of markers like vimentin and nestin. GFAPδ is also expressed in other astrocytic populations during development. A similar pattern is observed in the adolescent mouse, where GFAPδ marks both neural stem cells and mature astrocytes. Interestingly, the Gfapδ/Gfapα transcript ratio remains stable throughout development as well as in primary astrocyte and neurosphere cultures. These data suggest that all astroglia cells in the developing and adolescent mouse brain express GFAPδ, regardless of their neurogenic capabilities. GFAPδ may be an integral component of all mouse astrocytes, but it is not a specific neural stem cell marker in mice as it is in humans.
Mamber, Carlyn; Kamphuis, Willem; Haring, Nina L; Peprah, Nuzrat; Middeldorp, Jinte; Hol, Elly M
Glial fibrillary acidic protein (GFAP) is the major intermediate filament (IF) protein in astrocytes. In the human brain, GFAP isoforms have unique expression patterns, which indicate that they play distinct functional roles. One isoform, GFAPδ, is expressed by proliferative radial glia in the developing human brain. In the adult human, GFAPδ is a marker for neural stem cells. However, it is unknown whether GFAPδ marks the same population of radial glia and astrocytes in the developing mouse brain as it does in the developing human brain. This study characterizes the expression pattern of GFAPδ throughout mouse embryogenesis and into adolescence. Gfapδ transcripts are expressed from E12, but immunohistochemistry shows GFAPδ staining only from E18. This finding suggests a translational uncoupling. GFAPδ expression increases from E18 to P5 and then decreases until its expression plateaus around P25. During development, GFAPδ is expressed by radial glia, as denoted by the co-expression of markers like vimentin and nestin. GFAPδ is also expressed in other astrocytic populations during development. A similar pattern is observed in the adolescent mouse, where GFAPδ marks both neural stem cells and mature astrocytes. Interestingly, the Gfapδ/Gfapα transcript ratio remains stable throughout development as well as in primary astrocyte and neurosphere cultures. These data suggest that all astroglia cells in the developing and adolescent mouse brain express GFAPδ, regardless of their neurogenic capabilities. GFAPδ may be an integral component of all mouse astrocytes, but it is not a specific neural stem cell marker in mice as it is in humans.
Koneva, L A; Vyas, A K; McEachin, R C; Puttabyatappa, M; Wang, H-S; Sartor, M A; Padmanabhan, V
Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known. mRNA-seq of myocardium was performed on four groups of four female sheep to assess the effects of prenatal BPA exposure, postnatal overfeeding and their interaction on gene transcription, pathway perturbations and functional effects. The effects of prenatal exposure to BPA, postnatal overfeeding, and prenatal BPA with postnatal overfeeding all resulted in transcriptional changes (85-141 significant differentially expressed genes). Although the effects of prenatal BPA and postnatal overfeeding did not involve dysregulation of many of the same genes, they affected a remarkably similar set of biological pathways. Furthermore, an additive or synergistic effect was not found in the combined treatment group, but rather prenatal BPA treatment led to a partial reversal of the effects of overfeeding alone. Many genes previously known to be affected by BPA and involved in obesity, hypertension, or heart disease were altered following these treatments, and AP-1, EGR1, and EGFR were key hubs affected by BPA and/or overfeeding. Environ. Mol. Mutagen. 58:4-18, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Carbone, Fabrizio; Preuss, Anja; De Vos, Ric C H; D'Amico, Eleonora; Perrotta, Gaetano; Bovy, Arnaud G; Martens, Stefan; Rosati, Carlo
The influence of internal (genetic and developmental) and external (environmental) factors on levels of flavonoid gene transcripts, enzyme activity and metabolites was studied in fruit of six cultivated strawberry (Fragaria x ananassa Duch.) genotypes grown at two Italian locations. Gene expression and enzyme activity showed development- and genotype-associated patterns, revealing gene coordination. Analysis clarified the regulation mechanism of the hydroxylation status of the B-ring of the major flavonoid pools and pointed out examples of genotype-specific post-transcriptional regulation mechanisms and key steps of pathway regulation in strawberry fruits. Metabolite profiles were strongly affected by development and genotype. Flavan-3-ols, their proanthocyanidin (PA) derivatives and anthocyanins were the most abundant metabolites. Flavonol levels and PA-associated traits (epicatechin/catechin ratio and mean degree of polymerization) showed significant environmental effects. Multivariate and correlation analyses determined the relationships among genes, enzymes and metabolites. The combined molecular and biochemical information elucidated more in depth the role of genetic and environmental factors on flavonoid metabolism during strawberry fruit development, highlighting the major impact of developmental processes, and revealing genotype-dependent differences and environmental effects on PA-related traits.
Wagstaff, Carol; Bramke, Irene; Breeze, Emily; Thornber, Sarah; Harrison, Elizabeth; Thomas, Brian; Buchanan-Wollaston, Vicky; Stead, Tony; Rogers, Hilary
Petal development and senescence entails a normally irreversible process. It starts with petal expansion and pigment production, and ends with nutrient remobilization and ultimately cell death. In many species this is accompanied by petal abscission. Post-harvest stress is an important factor in limiting petal longevity in cut flowers and accelerates some of the processes of senescence such as petal wilting and abscission. However, some of the effects of moderate stress in young flowers are reversible with appropriate treatments. Transcriptomic studies have shown that distinct gene sets are expressed during petal development and senescence. Despite this, the overlap in gene expression between developmental and stress-induced senescence in petals has not been fully investigated in any species. Here a custom-made cDNA microarray from Alstroemeria petals was used to investigate the overlap in gene expression between developmental changes (bud to first sign of senescence) and typical post-harvest stress treatments. Young flowers were stressed by cold or ambient temperatures without water followed by a recovery and rehydration period. Stressed flowers were still at the bud stage after stress treatments. Microarray analysis showed that ambient dehydration stress accelerates many of the changes in gene expression patterns that would normally occur during developmental senescence. However, a higher proportion of gene expression changes in response to cold stress were specific to this stimulus and not senescence related. The expression of 21 transcription factors was characterized, showing that overlapping sets of regulatory genes are activated during developmental senescence and by different stresses.
Kristopher M Bunting
Full Text Available Background: Anterograde amnesia is a hallmark effect of volatile anesthetics. Isoflurane is known to affect both the translation and transcription of plasticity-associated genes required for normal memory formation in many brain regions. What is not known is whether isoflurane anesthesia prevents the initiation of transcription or whether it halts transcription already in progress. We tested the hypothesis that general anesthesia with isoflurane prevents learning-induced initiation of transcription of several memory-associated immediate-early genes (IEGs correlated with amnesia; we also assessed whether it stops transcription initiated prior to anesthetic administration.Methods: Using a Tone Fear Conditioning paradigm, rats were trained to associate a tone with foot-shock. Animals received either no anesthesia, anesthesia immediately after training, or anesthesia before, during, and after training. Animals were either sacrificed after training or tested 24 hours later for memory. Using Cellular Compartment Analysis of Temporal Activity by Fluorescence in situ Hybridization (catFISH, we examined the percentage of neurons expressing the IEGs Arc/Arg3.1 and Zif268/Egr1/Ngfi-A/Krox-24 in the dorsal hippocampus, primary somatosensory cortex, and primary auditory cortex.Results: On a cellular level, isoflurane administered at high doses (general anesthesia prevented initiation of transcription, but did not stop transcription of Arc and Zif268 mRNA initiated prior to anesthesia. On a behavioral level, the same level of isoflurane anesthesia produced anterograde amnesia for fear conditioning when administered before and during training, but did not produce retrograde amnesia when administered immediately after training. Conclusions: General anesthesia with isoflurane prevents initiation of learning-related transcription but does not stop ongoing transcription of two plasticity-related IEGs, Arc and Zif268, a pattern of disruption that parallels the
Semino, C E; Specht, C A; Raimondi, A; Robbins, P W
The Xenopus developmental gene DG42 is expressed during early embryonic development, between the midblastula and neurulation stages. The deduced protein sequence of Xenopus DG42 shows similarity to Rhizobium Nod C, Streptococcus Has A, and fungal chitin synthases. Previously, we found that the DG42 protein made in an in vitro transcription/translation system catalyzed synthesis of an array of chitin oligosaccharides. Here we show that cell extracts from early Xenopus and zebrafish embryos also synthesize chitooligosaccharides. cDNA fragments homologous to DG42 from zebrafish and mouse were also cloned and sequenced. Expression of these homologs was similar to that described for Xenopus based on Northern and Western blot analysis. The Xenopus anti-DG42 antibody recognized a 63-kDa protein in extracts from zebrafish embryos that followed a similar developmental expression pattern to that previously described for Xenopus. The chitin oligosaccharide synthase activity found in extracts was inactivated by a specific DG42 antibody; synthesis of hyaluronic acid (HA) was not affected under the conditions tested. Other experiments demonstrate that expression of DG42 under plasmid control in mouse 3T3 cells gives rise to chitooligosaccharide synthase activity without an increase in HA synthase level. A possible relationship between our results and those of other investigators, which show stimulation of HA synthesis by DG42 in mammalian cell culture systems, is provided by structural analyses to be published elsewhere that suggest that chitin oligosaccharides are present at the reducing ends of HA chains. Since in at least one vertebrate system hyaluronic acid formation can be inhibited by a pure chitinase, it seems possible that chitin oligosaccharides serve as primers for hyaluronic acid synthesis.
Aviezer, Hillel; Hassin, Ran R; Perry, Anat; Dudarev, Veronica; Bentin, Shlomo
The current study examined the nature of deficits in emotion recognition from facial expressions in case LG, an individual with a rare form of developmental visual agnosia (DVA). LG presents with profoundly impaired recognition of facial expressions, yet the underlying nature of his deficit remains unknown. During typical face processing, normal sighted individuals extract information about expressed emotions from face regions with activity diagnostic for specific emotion categories. Given LG's impairment, we sought to shed light on his emotion perception by examining if priming facial expressions with diagnostic emotional face components would facilitate his recognition of the emotion expressed by the face. LG and control participants matched isolated face components with components appearing in a subsequently presented full-face and then categorized the face's emotion. Critically, the matched components were from regions which were diagnostic or non-diagnostic of the emotion portrayed by the full face. In experiment 1, when the full faces were briefly presented (150 ms), LG's performance was strongly influenced by the diagnosticity of the components: his emotion recognition was boosted within normal limits when diagnostic components were used and was obliterated when non-diagnostic components were used. By contrast, in experiment 2, when the face-exposure duration was extended (2000 ms), the beneficial effect of the diagnostic matching was diminished as was the detrimental effect of the non-diagnostic matching. These data highlight the impact of diagnostic facial features in normal expression recognition and suggest that impaired emotion recognition in DVA results from deficient visual integration across diagnostic face components.
Lupp, Amelie; Anschütz, Tino; Lindström-Seppä, Pirjo; Müller, Dieter
The aim of the present study was to characterise developmental changes in glutathione S-transferase (GST) isoforms expression and in glutathione conjugation capacity in intrasplenic liver tissue transplants. For this purpose, syngenic fetal liver tissue suspensions were transplanted into the spleens of adult male Fischer 344 rats. Three days, 1, 2, 4 weeks, 2, 4, 6 months and 1 year later, transplant-recipients and control animals were sacrificed and class alpha, mu and pi GST isoforms expression and GST activities using the substrates o-dinitrobenzene and 1-chloro-2,4-dinitrobenzene were assessed in livers and spleens. In the hepatocytes of the adult livers no class pi, but a distinct class alpha and mu GST expression was seen. The bile duct epithelia were class pi GST positive. Fetal livers displayed almost no class alpha and mu, but a slight class pi GST expression. The same pattern was seen in 3-day-old intrasplenic liver tissue transplants. Up to 2 weeks after surgery the class alpha and mu GST expression increased in the hepatocytes of the transplants, whereas the immunostaining for class pi GST disappeared. No remarkable changes were seen thereafter. Normal conjugation capacities were observed with the livers of both groups of rats. Control spleens displayed only low GST activities. From 2 months after transplantation on activities were significantly higher in transplant-containing spleens than in respective control organs with a further increase up to one year after grafting. These results show that intrasplenically transplanted fetal liver cells proliferate and differentiate into mature cells displaying a GST expression pattern with respective enzyme activities similar to adult liver.
Li, Minglan; Reynolds, Clare M.; Segovia, Stephanie A.; Vickers, Mark H.
Nonalcoholic fatty liver disease (NAFLD) is fast becoming the most common liver disease globally and parallels rising obesity rates. The developmental origins of health and disease hypothesis have linked alterations in the early life environment to an increased risk of metabolic disorders in later life. Altered early life nutrition, in addition to increasing risk for the development of obesity, type 2 diabetes, and cardiovascular disease in offspring, is now associated with an increased risk for the development of NAFLD. This review summarizes emerging research on the developmental programming of NAFLD by both maternal obesity and undernutrition with a particular focus on the possible mechanisms underlying the development of hepatic dysfunction and potential strategies for intervention. PMID:26090409
Asadi-Azarbaijani, Babak; Santos, Regiane R; Jahnukainen, Kirsi; Braber, Saskia; van Duursen, Majorie B M; Toppari, Jorma; Saugstad, Ola D; Nurmio, Mirja; Oskam, Irma C
Imatinib mesylate is an anti-cancer agent that competitively inhibits several receptor tyrosine kinases (RTKs). RTKs play important roles in the regulation of primordial follicle formation, the recruitment of primordial follicles into the pool of growing follicles and maturation of the follicles. In the present study, we investigated the effects of the tyrosine kinase inhibitor imatinib on primordial follicle assembly and early folliculogenesis in postnatal rats. Female Sprague-Dawley rats were treated with either imatinib (150mg/kg) or placebo (water) on postnatal days 2-4. Bilateral ovariectomy was performed on postnatal day 2 and 5. Histology, immunohistochemistry, and mRNA analysis were performed. Imatinib treatment was associated with increased density of the multi-oocyte follicles (Pprimordial follicles, increased expression of c-Kit and AMH, and decreased protein expression of Kit-ligand and GDF9 when compared to age-matched controls. In conclusion, imatinib affects folliculogenesis in postnatal rat ovaries by delaying the cluster breakdown, follicular assembly and early activation of the primordial follicle pool. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
Cicin-Sain, Damjan; Pulido, Antonio Hermoso; Crombach, Anton; Wotton, Karl R; Jiménez-Guri, Eva; Taly, Jean-François; Roma, Guglielmo; Jaeger, Johannes
We present SuperFly (http://superfly.crg.eu), a relational database for quantified spatio-temporal expression data of segmentation genes during early development in different species of dipteran insects (flies, midges and mosquitoes). SuperFly has a special focus on emerging non-drosophilid model systems. The database currently includes data of high spatio-temporal resolution for three species: the vinegar fly Drosophila melanogaster, the scuttle fly Megaselia abdita and the moth midge Clogmia albipunctata. At this point, SuperFly covers up to 9 genes and 16 time points per species, with a total of 1823 individual embryos. It provides an intuitive web interface, enabling the user to query and access original embryo images, quantified expression profiles, extracted positions of expression boundaries and integrated datasets, plus metadata and intermediate processing steps. SuperFly is a valuable new resource for the quantitative comparative study of gene expression patterns across dipteran species. Moreover, it provides an interesting test set for systems biologists interested in fitting mathematical gene network models to data. Both of these aspects are essential ingredients for progress toward a more quantitative and mechanistic understanding of developmental evolution.
Rohde, Kristian; Klein, David C; Møller, Morten;
Retina and anterior neural fold homeobox (Rax) gene encodes a transcription factor essential for vertebrate eye development. Recent microarray studies indicate that Rax is expressed in the adult rat pineal gland and retina. The present study reveals that Rax expression levels in the rat change...... significantly during retinal development with a peak occurring at embryonic day (E) 18, whereas Rax expression in the pineal is relatively delayed and not detectable until E20. In both tissues, Rax is expressed throughout postnatal development into adulthood. In the mature rat pineal gland, the abundance of Rax...... transcripts increases 2-fold during the light period with a peak occurring at dusk. These findings are consistent with the evidence that Rax is of functional importance in eye development and suggest a role of Rax in the developing pineal gland. In addition, it would appear possible that Rax contributes...
Willoughby, Michael T.; Pek, Jolynn; Greenberg, Mark T.
Although Attention Deficit/Hyperactivity Disorder (ADHD) has increasingly been studied in preschool-aged children, relatively few studies have provided a comprehensive evaluation of the factor structure and patterns of developmental changes in parent-reported ADHD symptomatology across the early childhood period. This study used confirmatory factor analyses to test for longitudinal measurement invariance of ADHD symptoms and semi-parametric finite mixture models to identify prototypic pattern...
El-Shehabi, Fouad; Vermeire, Jon J.; Yoshino, Timothy P.; Ribeiro, Paula
A Schistosoma mansoni G-protein coupled receptor (SmGPCR) was previously cloned and shown to be activated by the biogenic amine, histamine. Here we report a first investigation of the receptor’s subunit organization, tissue distribution and expression levels in different stages of the parasite. A polyclonal antibody was produced in rabbits against the recombinant third intracellular loop (il3) of SmGPCR. Western blot studies of the native receptor and recombinant protein expressed in HEK293 c...
Inta, Dragos; Vogt, Miriam A; Lima-Ojeda, Juan M; Pfeiffer, Natascha; Schneider, Miriam; Gass, Peter
The early postnatal period represents a critical time window for brain development. Transient Cajal-Retzius cells in layer I of the cortex play an important role in cortical lamination by modulating neuronal migration and maturation. Recent data have demonstrated that the 5-HT(3) receptor antagonist and alpha7 nicotinic receptor partial agonist tropisetron, acting via 5-HT(3) receptors expressed on Cajal-Retzius cells, can disturb the formation of cortical columns at perinatal stages. This process is thought to be involved in several neuropsychiatric disorders. Here we investigated the possible long-term behavioral effects of exposure to tropisetron at early postnatal stages in mice. We found that the administration of 1mg/kg, intraperitoneal (i.p.) tropisetron from postnatal days 2-12 (P2-P12) did not induce significant cognitive, schizophrenia-like or emotional alterations in tropisetron-treated animals as compared to controls, when tested in multiple behavioral assays. These results may be of relevance regarding the possible protracted deleterious neuropsychiatric effects of tropisetron during early life.
Zhao, Dawei; Vaziri Sani, Forugh; Nilsson, Jeanette; Rodenburg, Michaela; Stocking, Carol; Linde, Anders; Gritli-Linde, Amel
Different sodium-dependent inorganic phosphate (P(i)) uptake mechanisms play a major role in cellular P(i) homeostasis. The function and detailed distribution patterns of the type III Na(+)-phosphate cotransporter, PiT-2, in different organs during development are still largely unknown. We therefore examined the temporospatial expression patterns of Pit2 during murine odontogenesis. Odontoblasts were always devoid of Pit2 expression, whereas a transient, but strong, expression was detected in young secretory ameloblasts. However, the stratum intermedium and, later on, the papillary layer and cells of the subodontoblastic layer, exhibited high levels of Pit2 mRNA, which increased gradually as the tooth matured. Hormonal treatment or P(i) starvation of tooth germs in vitro did not alter Pit2 levels or patterns of expression, indicating mechanisms of regulation different from those of PiT-1 or other cell types. PiT-2 also functions as a retroviral receptor, and functional membrane-localized protein was confirmed throughout the dental papilla/pulp by demonstrating cellular permissiveness to infection by a gammaretrovirus that uses PiT-2 as a receptor. The distinct pattern of Pit2 expression during odontogenesis suggests that its P(i)-transporter function may be important for homeostasis of dental cells and not specifically for mineralization of the dental extracellular matrices. The expression of viral receptors in enamel-forming cells and the dental pulp may be of pathological significance.
Full Text Available Abstract Background The kinetoplast DNA (kDNA of trypanosomatids consists of an unusual arrangement of circular molecules catenated into a single network. The diameter of the isolated kDNA network is similar to that of the entire cell. However, within the kinetoplast matrix, the kDNA is highly condensed. Studies in Crithidia fasciculata showed that kinetoplast-associated proteins (KAPs are capable of condensing the kDNA network. However, little is known about the KAPs of Trypanosoma cruzi, a parasitic protozoon that shows distinct patterns of kDNA condensation during their complex morphogenetic development. In epimastigotes and amastigotes (replicating forms the kDNA fibers are tightly packed into a disk-shaped kinetoplast, whereas trypomastigotes (non-replicating present a more relaxed kDNA organization contained within a rounded structure. It is still unclear how the compact kinetoplast disk of epimastigotes is converted into a globular structure in the infective trypomastigotes. Results In this work, we have analyzed KAP coding genes in trypanosomatid genomes and cloned and expressed two kinetoplast-associated proteins in T. cruzi: TcKAP4 and TcKAP6. Such small basic proteins are expressed in all developmental stages of the parasite, although present a differential distribution within the kinetoplasts of epimastigote, amastigote and trypomastigote forms. Conclusion Several features of TcKAPs, such as their small size, basic nature and similarity with KAPs of C. fasciculata, are consistent with a role in DNA charge neutralization and condensation. Additionally, the differential distribution of KAPs in the kinetoplasts of distinct developmental stages of the parasite, indicate that the kDNA rearrangement that takes place during the T. cruzi differentiation process is accompanied by TcKAPs redistribution.
Full Text Available microRNAs (miRNAs are small, endogenous RNAs of 20 approximately 25 nucleotides, processed from stem-loop regions of longer RNA precursors. Plant miRNAs act as negative regulators of target mRNAs predominately by slicing target transcripts, and a number of miRNAs play important roles in development. We analyzed a number of published datasets from Arabidopsis thaliana to characterize novel miRNAs, novel miRNA targets, and miRNA-regulated developmental changes in gene expression. These data include microarray profiling data and small RNA (sRNA deep sequencing data derived from miRNA biogenesis/transport mutants, microarray profiling data of mRNAs in a developmental series, and computational predictions of conserved genomic stem-loop structures. Our conservative analyses identified five novel mature miRNAs and seven miRNA targets, including one novel target gene. Two complementary miRNAs that target distinct mRNAs were encoded by one gene. We found that genes targeted by known miRNAs, and genes up-regulated or down-regulated in miRNA mutant inflorescences, are highly expressed in the wild type inflorescence. In addition, transcripts upregulated within the mutant inflorescences were abundant in wild type leaves and shoot meristems and low in pollen and seed. Downregulated transcripts were abundant in wild type pollen and seed and low in shoot meristems, roots and leaves. Thus, disrupting miRNA function causes the inflorescence transcriptome to resemble the leaf and meristem and to differ from pollen and seed. Applications of our computational approach to other species and the use of more liberal criteria than reported here will further expand the number of identified miRNAs and miRNA targets. Our findings suggest that miRNAs have a global role in promoting vegetative to reproductive transitions in A. thaliana.
Llorens, Franc; Gil, Vanesa; Iraola, Susana; Carim-Todd, Laura; Martí, Eulàlia; Estivill, Xavier; Soriano, Eduardo; del Rio, José Antonio; Sumoy, Lauro
Lingo-1 (also known as Lern1) is a component of the Nogo receptor complex that mediates intracellular signaling in response to myelin associated inhibitors (MAIs): NogoA, MAG, and Omgp. Signaling through Nogo receptor extends to more than its well known role in preventing axon regeneration after lesion in the CNS, being implicated in neuronal functional maturation. Using Lingo-1-deficient mice, it has been demonstrated that Lingo-1 plays relevant roles in oligodendrocyte differentiation during brain development, and that treatment with Lingo-1 antagonists can improve axon regeneration after lesion in adult mice by decreasing MAI mediated signaling. However, a detailed description of the pattern of expression of Lingo-1 protein in correlation with the other partners of Nogo receptor is missing. Here, we show that components of the Nogo receptor complex, Lingo-1, NgR1, p75, and TROY coexist in mouse brain in a defined time window only at later postnatal stages. We have also determined the Lingo-1 distribution showing expression in particular subsets of neurons, but not in myelinating mature oligodendrocytes. Surprisingly, Lingo-1 is expressed at early developmental stages without NgR1, which supports the notion that Lingo-1 may participate in other activities in developing neurons different from oligodendrocyte maturation or axon extension inhibition in the adult. Finally, we propose that the intracellular domain of Lingo-1 contributes to signaling and show that it interacts with the postmitotic neuronal specific zinc finger protein Myt1l, suggesting that Lingo-1 may regulate Myt1l transcription factor activity by affecting its subcellular localization.
Baranwal, Vinay Kumar; Khurana, Paramjit
NAC genes are important transcription factors and forms a large family in plants. They have shown to play an important role in growth and development and have also been shown to involve in regulation of stress-responsive genes. In the present study, a repertoire of NAC genes in recently published mulberry genome has been identified which consists of a total of 79 members. Structural analysis revealed that most of the NAC genes in mulberry contain two introns. The proteins encoded by them show a wide range of isoelectric points suggestive of their varied roles in varying microcellular environment. Phylogenetic and conserved motif analysis elucidate the presence of 15 sub-groups of these genes along with two novel sub-groups having distinct conserved motifs which are not present in Arabidopsis. Gene ontology term enrichment analysis and cis-element identification from their putative 1 K upstream regulatory region indicates their possible role in important biological processes like organ formation, meristem establishment, senescence, and various biotic and abiotic stresses. Expression analysis across various developmental stages led to identification of their preferential expression in diverse tissues. Taken together, this work provides a solid background information related to structure, function, expression and evolution of NAC gene family in mulberry.
Barnwell, Eleanor M; van Deursen, Frederick J; Jeacock, Laura; Smith, Katherine A; Maizels, Rick M; Acosta-Serrano, Alvaro; Matthews, Keith
Trypanosomes evade host immunity by exchanging variant surface glycoprotein (VSG) coats. VSG genes are transcribed from telomeric expression sites, which contain a diverse family of expression-site-associated genes (ESAGs). We have discovered that the mRNAs for one ESAG family, ESAG9, are strongly developmentally regulated, being enriched in stumpy forms, a life-cycle stage in the mammalian bloodstream that is important for the maintenance of chronic parasite infections and for tsetse transmission. ESAG9 gene sequences are highly diverse in the genome and encode proteins with weak similarity to the massively diverse MASP proteins in Trypanosoma cruzi. We demonstrate that ESAG9 proteins are modified by N-glycosylation and can be shed to the external milieu, this being dependent upon coexpression with at least one other family member. The expression profile and extracellular release of ESAG9 proteins represents a novel and unexpected aspect of the transmission biology of trypanosomes in their mammalian host. We suggest that these molecules might interact with the external environment, with possible implications for infection chronicity or parasite transmission.
Kim, Sanghag; Kochanska, Grazyna; Boldt, Lea J; Nordling, Jamie Koenig; O'Bleness, Jessica J
Parent-child relationships are critical in development, but much remains to be learned about the mechanisms of their impact. We examined the early parent-child relationship as a moderator of the developmental trajectory from children's affective and behavioral responses to transgressions to future antisocial, externalizing behavior problems in the Family Study (102 community mothers, fathers, and infants, followed through age 8) and the Play Study (186 low-income, diverse mothers and toddlers, followed for 10 months). The relationship quality was indexed by attachment security in the Family Study and maternal responsiveness in the Play Study. Responses to transgressions (tense discomfort and reparation) were observed in laboratory mishaps wherein children believed they had damaged a valued object. Antisocial outcomes were rated by parents. In both studies, early relationships moderated the future developmental trajectory: diminished tense discomfort predicted more antisocial outcomes, but only in insecure or unresponsive relationships. That risk was defused in secure or responsive relationships. Moderated mediation analyses in the Family Study indicated that the links between diminished tense discomfort and future antisocial behavior in insecure parent-child dyads were mediated by stronger discipline pressure from parents. By indirectly influencing future developmental sequelae, early relationships may increase or decrease the probability that the parent-child dyad will embark on a path toward antisocial outcomes.
Ashton, Chandra K.; O’Brien-Langer, Anna; Olson, Karin; Silverstone, Peter H.
Objective We demonstrated previously that the Trauma and Attachment Group (TAG) program for youth in middle childhood significantly improved caregiver/child attachment relationships, reduced children’s symptoms of attachment trauma, and increased the caregiver’s ability for self-reflection. Here we examine the perspectives of both those administering and those taking part in this intensive dyad-based group intervention. Methods Utilizing an ethnographic design we collected and analyzed qualitative data obtained through a focus group and interviews with program facilitators, as well as interviews with participating caregivers. Data were collected from six TAG facilitators through a formal focus group interview (n=4), and informal interviews with TAG facilitators unable to attend the focus group (n=2). Four interviews were also carried out with caregivers (three females and one male). Thematic analysis of the focus group and interview transcripts was conducted. Results Three key themes were identified in the focus group and interview data: Relationship as locus of change, Group process, and Psychoeducation-based content. That the TAG program provides psychoeducation about the effects of trauma to caregiver/child dyads in a group setting appears important in supporting the effectiveness of the program. Structured parent-child play and sensory activities together (“kit-time”) were also highly valued. Conclusions This qualitative study suggests that establishment of a healthy and focused caregiver/child relationship may be the key mechanism to promoting change in relationships that have been challenged by adverse effects of early developmental trauma. Further evaluation may help to identify other components that contribute to the success of the program.
Kasten-Jolly, Jane; Pabello, Nina; Bolivar, Valerie J; Lawrence, David A
Lead (Pb) was one of the first poisons identified, and the developing nervous system is particularly vulnerable to its toxic effects. Relatively low, subclinical doses, of Pb that produce no overt signs of encephalopathy can affect cognitive, emotional, and motor functions. In the present study, the effects of developmental Pb-exposure on behavioral performance and gene expression in BALB/cAnNTac mice were evaluated. Pups were exposed to Pb from gestational-day (gd) 8 to postnatal-day (pnd) 21 and later evaluated in exploratory behavior, rotarod, Morris water maze, and resident-intruder assays as adults. Pb-exposure caused significant alterations in exploratory behavior and water maze performance during the probe trial, but rotarod performance was not affected. Pb-exposed males displayed violent behavior towards their cage mates, but not to a stranger in the resident-intruder assay. Gene expression analysis at pnd21 by microarray and qRT-PCR was performed to provide a molecular link to the behavior changes that were observed. Pb strongly up-regulated gene expression within the signaling pathways of mitogen activated protein kinases (MAPKs), extra-cellular matrix (ECM) receptor, focal adhesion, and vascular endothelial growth-factor (VEGF), but Pb down-regulated gene expression within the pathways for glycan structures-biosynthesis 1, purine metabolism, and N-glycan biosynthesis. Pb increased transcription of genes for major histocompatibility (MHC) proteins, the chemokine Ccl28, chemokine receptors, IL-7, IL7R, and proteases. The qRT-PCR analysis indicated an increase of gene expression in the whole brain for caspase 1 and NOS2. Analysis of IL-1β, caspase 1, NOS2, Trail, IL-18 and IL-33 gene expression of brain regions indicated that Pb perturbed the inter-regional expression pattern of pro-inflammatory genes. Brain region protein concentrations for IL-10, an anti-inflammatory cytokine, showed a significant decrease only within the cortex region. Results indicate
Farach, M.C.; Valdizan, M.; Park, H.R.; Decker, G.L.; Lennarz, W.J.
The authors have previously used a monoclonal antibody (1223) to identify a 130 Kd cell surface protein involved in skeleton formation is sea urchin embryos. In the current study the authors have examined the expression of the 1223 antigen over the course of development of embryos of two species, Strongylocentrotus purpuratus and Lytechinus pictus. The 130 Kd protein is detected in S. purp eggs on immunoblots. Labeling with (/sup 3/H) leucine and immunoaffinity chromatography show that it also is synthesized shortly after fertilization. Immunofluroescence reveals that at this early stage the 1223 antigen is uniformly distributed on all of the cells. Synthesis decreases to a minimum by the time of hatching (18 h), as does the total amount of antigen present in the embryo. A second period of synthesis commences at the mesenchyme blastula stage, when the spicule-forming primary mesenchyme cells (PMCs) have appeared. During this later stage, synthesis and cell surface expression are restricted to the PMCs. In contrast to S. purp., in L. pictus the 130 Kd protein does not appear until the PMCs are formed. Hybrid embryos demonstrate a pattern of expression of the maternal species. These results suggest that early expression of 1223 antigen in S. purp. is due to utilization of maternal transcripts present in the egg. In both species later expression in PMCs appears to be the result of cell-type specific synthesis, perhaps encoded by embryonic transcripts.
Full Text Available Abstract Background Strict regulation of caste differentiation, at the molecular level, is thought to be important to maintain social structure in insect societies. Previously, a number of extrinsic and intrinsic factors have been shown to influence caste composition in termite colonies. One important factor is the influence of nestmates; in particular, soldier termites are known to inhibit hormone-dependent worker-to-soldier differentiation. However, soldier influences on nestmates at the molecular level are virtually unknown. Here, to test the hypothesis that soldiers can influence nestmate gene expression, we investigated the impact of four treatments on whole-body gene expression in totipotent Reticulitermes flavipes workers: (i juvenile hormone III (JHIII; a morphogenetic hormone, (ii soldier head extracts (SHE, (iii JHIII+SHE, and (iv live soldiers. Results Using quantitative-real-time PCR we determined the expression patterns of 49 previously identified candidate genes in response to the four treatments at assay days 1, 5, and 10. Thirty-eight total genes from three categories (chemical production/degradation, hemolymph protein, and developmental showed significant differential expression among treatments. Most importantly, SHE and live soldier treatments had a significant impact on a number of genes from families known to play roles in insect development, supporting previous findings and hypotheses that soldiers regulate nestmate caste differentiation via terpene primer pheromones contained in their heads. Conclusions This research provides new insights into the impacts that socio-environmental factors (JH, soldiers, primer pheromones can have on termite gene expression and caste differentiation, and reveals a number of socially-relevant genes for investigation in subsequent caste differentiation research.
Eickhoff, René; Bicker, Gerd
We examined the development of olfactory neuropils in the hemimetabolous insect Locusta migratoria with an emphasis on the mushroom bodies, protocerebral integration centers implicated in memory formation. Using a marker of the cyclic adenosine monophosphate (cAMP) signaling cascade and lipophilic dye labeling, we obtained new insights into mushroom body organization by resolving previously unrecognized accessory lobelets arising from Class III Kenyon cells. We utilized antibodies against axonal guidance cues, such as the cell surface glycoproteins Semaphorin 1a (Sema 1a) and Fasciclin I (Fas I), as embryonic markers to compile a comprehensive atlas of mushroom body development. During embryogenesis, all neuropils of the olfactory pathway transiently expressed Sema 1a. The immunoreactivity was particularly strong in developing mushroom bodies. During late embryonic stages, Sema 1a expression in the mushroom bodies became restricted to a subset of Kenyon cells in the core region of the peduncle. Sema 1a was differentially sorted to the Kenyon cell axons and absent in the dendrites. In contrast to Drosophila, locust mushroom bodies and antennal lobes expressed Fas I, but not Fas II. While Fas I immunoreactivity was widely distributed in the midbrain during embryogenesis, labeling persisted into adulthood only in the mushroom bodies and antennal lobes. Kenyon cells proliferated throughout the larval stages. Their neurites retained the embryonic expression pattern of Sema 1a and Fas I, suggesting a role for these molecules in developmental mushroom body plasticity. Our study serves as an initial step toward functional analyses of Sema 1a and Fas I expression during locust mushroom body formation.
Full Text Available Abstract Background Plant growth depends on synergistic interactions between internal and external signals, and yield potential of crops is a manifestation of how these complex factors interact, particularly at critical stages of development. As an initial step towards developing a systems-level understanding of the biological processes underlying the expression of overall agronomic potential in cereal crops, a high-resolution transcriptome analysis of rice was conducted throughout life cycle of rice grown under natural field conditions. Results A wide range of gene expression profiles based on 48 organs and tissues at various developmental stages identified 731 organ/tissue specific genes as well as 215 growth stage-specific expressed genes universally in leaf blade, leaf sheath, and root. Continuous transcriptome profiling of leaf from transplanting until harvesting further elucidated the growth-stage specificity of gene expression and uncovered two major drastic changes in the leaf transcriptional program. The first major change occurred before the panicle differentiation, accompanied by the expression of RFT1, a putative florigen gene in long day conditions, and the downregulation of the precursors of two microRNAs. This transcriptome change was also associated with physiological alterations including phosphate-homeostasis state as evident from the behavior of several key regulators such as miR399. The second major transcriptome change occurred just after flowering, and based on analysis of sterile mutant lines, we further revealed that the formation of strong sink, i.e., a developing grain, is not the major cause but is rather a promoter of this change. Conclusions Our study provides not only the genetic basis for functional genomics in rice but also new insight into understanding the critical physiological processes involved in flowering and seed development, that could lead to novel strategies for optimizing crop productivity.
Gesing, Stefan; Schindler, Daniel; Nowrousian, Minou
Ascomycetes differentiate four major morphological types of fruiting bodies (apothecia, perithecia, pseudothecia and cleistothecia) that are derived from an ancestral fruiting body. Thus, fruiting body differentiation is most likely controlled by a set of common core genes. One way to identify such genes is to search for genes with evolutionary conserved expression patterns. Using suppression subtractive hybridization (SSH), we selected differentially expressed transcripts in Pyronema confluens (Pezizales) by comparing two cDNA libraries specific for sexual and for vegetative development, respectively. The expression patterns of selected genes from both libraries were verified by quantitative real time PCR. Expression of several corresponding homologous genes was found to be conserved in two members of the Sordariales (Sordaria macrospora and Neurospora crassa), a derived group of ascomycetes that is only distantly related to the Pezizales. Knockout studies with N. crassa orthologues of differentially regulated genes revealed a functional role during fruiting body development for the gene NCU05079, encoding a putative MFS peptide transporter. These data indicate conserved gene expression patterns and a functional role of the corresponding genes during fruiting body development; such genes are candidates of choice for further functional analysis.
Full Text Available Regulated proteolysis is known to control a variety of vital processes in apicomplexan parasites including invasion and egress of host cells. Serine proteases have been proposed as targets for drug development based upon inhibitor studies that show parasite attenuation and transmission blockage. Genetic studies suggest that serine proteases, such as subtilisin and rhomboid proteases, are essential but functional studies have proved challenging as active proteases are difficult to express. Proteinaceous Protease Inhibitors (PPIs provide an alternative way to address the role of serine proteases in apicomplexan biology. To validate such an approach, a Neospora caninum Kazal inhibitor (NcPI-S was expressed ectopically in two apicomplexan species, Toxoplasma gondii tachyzoites and Plasmodium berghei ookinetes, with the aim to disrupt proteolytic processes taking place within the secretory pathway. NcPI-S negatively affected proliferation of Toxoplasma tachyzoites, while it had no effect on invasion and egress. Expression of the inhibitor in P. berghei zygotes blocked their development into mature and invasive ookinetes. Moreover, ultra-structural studies indicated that expression of NcPI-S interfered with normal formation of micronemes, which was also confirmed by the lack of expression of the micronemal protein SOAP in these parasites. Our results suggest that NcPI-S could be a useful tool to investigate the function of proteases in processes fundamental for parasite survival, contributing to the effort to identify targets for parasite attenuation and transmission blockage.
Full Text Available Short non-coding transcripts can be transcribed from distant-acting transcriptional enhancer loci, but the prevalence of such enhancer RNAs (eRNAs within the transcriptome, and the association of eRNA expression with tissue-specific enhancer activity in vivo remain poorly understood. Here, we investigated the expression dynamics of tissue-specific non-coding RNAs in embryonic mouse tissues via deep RNA sequencing. Overall, approximately 80% of validated in vivo enhancers show tissue-specific RNA expression that correlates with tissue-specific enhancer activity. Globally, we identified thousands of tissue-specifically transcribed non-coding regions (TSTRs displaying various genomic hallmarks of bona fide enhancers. In transgenic mouse reporter assays, over half of tested TSTRs functioned as enhancers with reproducible activity in the predicted tissue. Together, our results demonstrate that tissue-specific eRNA expression is a common feature of in vivo enhancers, as well as a major source of extragenic transcription, and that eRNA expression signatures can be used to predict tissue-specific enhancers independent of known epigenomic enhancer marks.
Mirrett, Penny L; Bailey, Donald B; Roberts, Jane E; Hatton, Deborah D
Three developmental screening tests (the Denver-II, Battelle Developmental Inventory Screening Test, and Early Language Milestone Scale-2) were administered to 18 infants and toddlers (13 boys and 5 girls) with confirmed diagnoses of fragile X syndrome as part of a comprehensive developmental assessment at 9, 12, and 18 months of age. The Denver-II identified delays for 10 of 11 boys at 9 months of age and the Denver-II and the Early Language Milestone Scale-2 identified delays in 100% of the boys at 12 and 18 months. The Battelle Developmental Inventory Screening Test identified delays in 75% of the children at 12 and 18 months. When compared with more comprehensive developmental tests (Mullen Scales of Early Learning and Receptive-Expressive Emergent Language Scale-2), the screening tests concurred at least 76% of the time at the 12- and 18-month assessments. These results indicate that developmental delays could be detected in most children with fragile X syndrome through routine developmental screening by the age of 9 to 12 months.
Meisner, Jeffrey; Serrano, Monica; Henriques, Adriano O.; Moran, Charles P.; Rudner, David Z.
Sporulation in Bacillus subtilis involves two cells that follow separate but coordinately regulated developmental programs. Late in sporulation, the developing spore (the forespore) resides within a mother cell. The regulation of the forespore transcription factor σG that acts at this stage has remained enigmatic. σG activity requires eight mother-cell proteins encoded in the spoIIIA operon and the forespore protein SpoIIQ. Several of the SpoIIIA proteins share similarity with components of specialized secretion systems. One of them resembles a secretion ATPase and we demonstrate that the ATPase motifs are required for σG activity. We further show that the SpoIIIA proteins and SpoIIQ reside in a multimeric complex that spans the two membranes surrounding the forespore. Finally, we have discovered that these proteins are all required to maintain forespore integrity. In their absence, the forespore develops large invaginations and collapses. Importantly, maintenance of forespore integrity does not require σG. These results support a model in which the SpoIIIA-SpoIIQ proteins form a novel secretion apparatus that allows the mother cell to nurture the forespore, thereby maintaining forespore physiology and σG activity during spore maturation. PMID:19609349
Gaines, Robin; Collins, David; Boycott, Kym; Missiuna, Cheryl; Delaat, Denise; Soucie, Helen
Previous studies of the phenotype of developmental coordination disorder (DCD) have largely concentrated on population-based samples. The present study reports on an in-depth examination of a large Canadian family with eight children, after three children who were suspected to have DCD were referred for evaluation. Subsequently, five of the six children whose motor impairments could be measured, and the mother, met the diagnostic criteria for DCD as per the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders - fourth edition. The family members diagnosed with DCD showed remarkably similar profiles of motor difficulties. Additionally, the five children diagnosed with DCD had current speech articulation difficulties, with four of them having visited speech/language pathologists; the mother had a lateral lisp. More in-depth testing for three children revealed intact intellectual, academic and language comprehension skills. Three of the children diagnosed with DCD were obese. The present report highlights familial clustering of DCD and the presence of comorbid conditions in the affected children.
Dowton, S B; Waggoner, D J; Mandl, K D
The fetal and maternal concentration of various plasma proteins alters during pregnancy. Cells in the livers of fetal hamsters accumulate serum amyloid A (SAA) and C-reactive protein (CRP) mRNA, major acute phase reactants, when lipopolysaccharide is administered to the fetal circulation. No fetal SAA or CRP mRNA response is seen when the mother is stimulated at a remote site by endotoxin or a nonspecific inflammatory agent. In addition, cells of the fetal hamster liver do not respond by accumulating SAA mRNA when exposed to the specific cytokines, tumor necrosis factor, IL-1, and IL-6. CRP mRNA levels increased in fetal livers after administration of tumor necrosis factor and IL-1. These data suggest that cells contained in the fetal liver can respond during an acute phase reaction but that the capacity of some acute phase reactant genes to respond to cytokines may be developmentally regulated. Studies of immature hamsters after birth show that the responses of CRP and SAA genes to lipopolysaccharide, tumor necrosis factor, IL-1, and IL-6 are reduced when compared with induction of mRNA accumulation for these acute phase reactants in adult animals.
Full Text Available Sporulation in the bacterium Bacillus subtilis is a developmental program in which a progenitor cell differentiates into two different cell types, the smaller of which eventually becomes a dormant cell called a spore. The process begins with an asymmetric cell division event, followed by the activation of a transcription factor, σF, specifically in the smaller cell. Here, we show that the structural protein DivIVA localizes to the polar septum during sporulation and is required for asymmetric division and the compartment-specific activation of σF. Both events are known to require a protein called SpoIIE, which also localizes to the polar septum. We show that DivIVA copurifies with SpoIIE and that DivIVA may anchor SpoIIE briefly to the assembling polar septum before SpoIIE is subsequently released into the forespore membrane and recaptured at the polar septum. Finally, using super-resolution microscopy, we demonstrate that DivIVA and SpoIIE ultimately display a biased localization on the side of the polar septum that faces the smaller compartment in which σF is activated.
Sánchez, D; Ganfornina, M D; Bastiani, M J
This article describes the expression pattern and functional analysis of Lazarillo, a novel cell surface glycoprotein expressed in the embryonic grasshopper nervous system, and a member of the lipocalin family. Lazarillo is expressed by a subset of neuroblasts, ganglion mother cells and neurons of the central nervous system, by all sensory neurons of the peripheral nervous system, and by a subset of neurons of the enteric nervous system. It is also present in a few non neuronal cells associated mainly with the excretory system. A monoclonal antibody raised against Lazarillo perturbs the extent and direction of growth of identified commissural pioneer neurons. We propose that Lazarillo is the receptor for a midline morphogen involved in the outgrowth and guidance of these neurons.
Muñoz, Estela M; Bailey, Michael J; Rath, Martin F
NeuroD1/BETA2, a member of the bHLH transcription factor family, is known to influence the fate of specific neuronal, endocrine and retinal cells. We report here that NeuroD1 mRNA is highly abundant in the developing and adult rat pineal gland. Pineal expression begins in the 17-day embryo at which...... time it is also detectable in other brain regions. Expression in the pineal gland increases during the embryonic period and is maintained thereafter at levels equivalent to those found in the cerebellum and retina. In contrast, NeuroD1 mRNA decreases markedly in non-cerebellar brain regions during...... development. Pineal NeuroD1 levels are similar during the day and night, and do not appear to be influenced by sympathetic neural input. Gene expression analysis of the pineal glands from neonatal NeuroD1 knockout mice identifies 127 transcripts that are down-regulated (>twofold, p
Bondy, C; Chin, E.; Smith, B L; Preston, G M; Agre, P
The CHIP28 water channel is a major component of red cell and renal tubule membranes; however, its ontogeny and tissue distribution remain undefined. Three patterns of expression were identified when CHIP28 mRNA was surveyed by in situ hybridization histochemistry in rats between embryonic day 14 and maturity. (i) CHIP28 mRNA and protein were very abundant in hematopoietic tissue and kidneys of mature rats, but strong expression did not occur until after birth, when it appeared in renal proxi...
Dissen, G A; Hirshfield, A N; Malamed, S; Ojeda, S R
An emerging body of evidence suggests that neurotrophins not only promote neuronal survival and differentiation, but can also target nonneuronal cells for their actions. Neurotrophins initiate their biological effects by binding to cell membrane tyrosine kinase receptors of the trk protooncogene family. In addition, all neurotrophins recognize with similar affinity a different receptor molecule known as p75 nerve growth factor receptor (p75 NGFR) or low affinity NGFR, which appears to interact with the trk receptors to potentiate their response to neurotrophins. The mature mammalian ovary has been shown to synthesize several neurotrophins, including nerve growth factor (NGF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5). The ovary also expresses some of the neurotrophin receptors, including p75 NGFR, trkB [the receptor for NT-4/5 and brain-derived neurotropic factor (BDNF)], and trkA (the NGF receptor). The present experiments were undertaken to determine whether neurotrophins and their receptors are expressed at the time of definitive ovarian histogenesis, and whether any of them exhibit a developmental pattern of expression related to the completion of folliculogenesis. Immunohistochemical identification of p75 NGFR in rat embryonic ovaries revealed that the receptor is predominantly expressed in mesenchymal cells. By gestational day 18, these cells have formed pockets that enclose presumptive pregranulosa cells and groups of oocytes into ovigerous cords. Immediately after birth, the ovigerous cords are subdivided, resulting in the abrupt formation of primordial follicles between 24-48 h after birth. Consistent with these observations, the p75 NGFR messenger RNA (mRNA) content increased after birth and remained elevated at the time of follicular assembly. The NGF and trkA genes showed a different pattern of expression, as the ovarian content of both NGF and trkA mRNA decreased at the time of folliculogenesis. In contrast to the drop in NGF and trkA m
Ploskonka, Stephanie D; Eaton, Jennifer L; Carr, Michael S; Schmidt, Jennifer V; Cushing, Bruce S
Here, for the first time, the expression of estrogen receptor beta (ERβ) is characterized in the brains of the highly prosocial prairie vole (Microtus ochrogaster). ERβ immunoreactivity was compared in weanlings (postnatal Day 21) and adult males and females. The results indicate several major findings. First, unlike ERα, ERβ expression is not sexually dimorphic. Second, the adult pattern of ERβ-IR is established at the time of weaning, as there were no age-dependent effects on distribution. Finally, ERβ does not appear to be as widely distributed in voles compared with rats and mice. High levels of ERβ-IR were observed in several regions/nuclei within the medial pre-optic area, ventrolateral pre-optic nuclei, and in the hypothalamus, especially in the paraventricular and supraoptic nuclei. The visualization of ERβ in prairie voles is important as the socially monogamous prairie vole functions as a human relevant model system for studying the expression of social behavior and social deficit disorders. Future studies will now be able to determine the effect of treatments on the expression and/or development of ERβ in this highly social species.
Somm, Emmanuel; Stouder, Christelle; Paoloni-Giacobino, Ariane
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disruptor affecting the reproductive system in humans. The aim of this study was to evaluate the effects of TCDD administered to pregnant mice at two different doses (2-10 ng/kg/day), on imprinted genes in the male offspring. The degree of methylation and the mRNA expression of Snrpn, Peg3 and Igf2r were analyzed in the sperm, skeletal muscle and liver. TCDD administration (10 ng/kg/day) decreased the sperm count in the male offspring. It did not affect methylation but increased mRNA expression of Snrpn, Peg3, Igf2r and Air ncRNA. In muscle and liver, TCDD (10 ng/kg/day) induced increases in methylation and decreases in mRNA expression of Igf2r. These results show that the robust effects of TCDD on the mRNA expression of Snrpn, Peg3 and Igf2r genes in the sperm and of Igf2r in the muscle and liver are unrelated to changes in methylation in their respective genes.
Rohde, Kristian; Klein, David C; Møller, Morten; Rath, Martin F
Retina and anterior neural fold homeobox (Rax) gene encodes a transcription factor essential for vertebrate eye development. Recent microarray studies indicate that Rax is expressed in the adult rat pineal gland and retina. The present study reveals that Rax expression levels in the rat change significantly during retinal development with a peak occurring at embryonic day 18, whereas Rax expression in the pineal is relatively delayed and not detectable until embryonic day 20. In both tissues, Rax is expressed throughout postnatal development into adulthood. In the mature rat pineal gland, the abundance of Rax transcripts increases 2-fold during the light period with a peak occurring at dusk. These findings are consistent with the evidence that Rax is of functional importance in eye development and suggest a role of Rax in the developing pineal gland. In addition, it would appear possible that Rax contributes to phenotype maintenance in the mature retina and pineal gland and may facilitate 24-h changes in the pineal transcriptome.
Scheibye-Alsing, Karsten; Cirera, Susanna; Gilchrist, Michael J.;
BACKGROUND: The mitochondria are involved in many basic functions in cells of vertebrates, and can be considered the power generator of the cell. Though the mitochondria have been extensively studied there appear to be only few expression studies of mitochondrial genes involving a large number...
Izard, Carroll E.; And Others
A longitudinal study addressed the question of stability of individual expressive behaviors and replicated the basic findings of a cross-sectional study. Subjects were 25 infants for whom videotape records were available of four diptheria-pertussis-tetanus (DPT) inocculations scheduled at roughly 2, 4, 6, and 18 months. (Author/RH)
M. van Spronsen (Myrrhe); E.Y. van Battum (Eljo); M. Kuijpers (Marijn); V.R. Vangoor (Vamshidhar); M.L. Rietman (M. Liset); J. Pothof (Joris); L.F. Gumy (Laura); W.F.J. van IJcken (Wilfred); A.S. Akhmanova (Anna); R.J. Pasterkamp (Jeroen); C.C. Hoogenraad (Casper)
textabstractMicroRNAs (miRNAs) are evolutionarily conserved non-coding RNAs of ∼22 nucleotides that regulate gene expression at the level of translation and play vital roles in hippocampal neuron development, function and plasticity. Here, we performed a systematic and in-depth analysis of miRNA exp
Gao, Xiaoqing; Maurer, Daphne
Using 20 levels of intensity, we measured children's thresholds to discriminate the six basic emotional expressions from neutral and their misidentification rates. Combined with the results of a previous study using the same method ("Journal of Experimental Child Psychology, 102" (2009) 503-521), the results indicate that by 5 years of age,…