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Sample records for neural tube development

  1. Shared molecular networks in orofacial and neural tube development.

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    Kousa, Youssef A; Mansour, Tamer A; Seada, Haitham; Matoo, Samaneh; Schutte, Brian C

    2017-01-30

    Single genetic variants can affect multiple tissues during development. Thus it is possible that disruption of shared gene regulatory networks might underlie syndromic presentations. In this study, we explore this idea through examination of two critical developmental programs that control orofacial and neural tube development and identify shared regulatory factors and networks. Identification of these networks has the potential to yield additional candidate genes for poorly understood developmental disorders and assist in modeling and perhaps managing risk factors to prevent morbidly and mortality. We reviewed the literature to identify genes common between orofacial and neural tube defects and development. We then conducted a bioinformatic analysis to identify shared molecular targets and pathways in the development of these tissues. Finally, we examine publicly available RNA-Seq data to identify which of these genes are expressed in both tissues during development. We identify common regulatory factors in orofacial and neural tube development. Pathway enrichment analysis shows that folate, cancer and hedgehog signaling pathways are shared in neural tube and orofacial development. Developing neural tissues differentially express mouse exencephaly and cleft palate genes, whereas developing orofacial tissues were enriched for both clefting and neural tube defect genes. These data suggest that key developmental factors and pathways are shared between orofacial and neural tube defects. We conclude that it might be most beneficial to focus on common regulatory factors and pathways to better understand pathology and develop preventative measures for these birth defects. Birth Defects Research 109:169-179, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Effect of Cyclophosphamide on Neural Tube Development in Chick Embryos

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    SHABANA SULTANA

    2014-06-01

    Full Text Available Cyclophosphamide is a nitrogen mustard alkylating agent. CP has potent immunosuppressive properties and issued clinically in a number of autoimmune disorders like Wegener’s granulomatosis, rheumatoid arthritis, nephritic syndrome, systemic lupus erythematous and has also been used to prevent organ rejection after transplantation. In the present study fertilized eggs were administered with cyclophosphamide and the development of neural tube was studied after 21 days. The histological and gross features of neural tube were identified. Cyclophosphamide cytotoxicity results in depression of proliferation of cell activity associated with malformations and embryonic death. Injection of the drug causes depression of mitotic activity by day 2 which produces malformations.

  3. LRP2 mediates folate uptake in the developing neural tube.

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    Kur, Esther; Mecklenburg, Nora; Cabrera, Robert M; Willnow, Thomas E; Hammes, Annette

    2014-05-15

    The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2) is a multifunctional cell-surface receptor expressed in the embryonic neuroepithelium. Loss of LRP2 in the developing murine central nervous system (CNS) causes impaired closure of the rostral neural tube at embryonic stage (E) 9.0. Similar neural tube defects (NTDs) have previously been attributed to impaired folate metabolism in mice. We therefore asked whether LRP2 might be required for the delivery of folate to neuroepithelial cells during neurulation. Uptake assays in whole-embryo cultures showed that LRP2-deficient neuroepithelial cells are unable to mediate the uptake of folate bound to soluble folate receptor 1 (sFOLR1). Consequently, folate concentrations are significantly reduced in Lrp2(-/-) embryos compared with control littermates. Moreover, the folic-acid-dependent gene Alx3 is significantly downregulated in Lrp2 mutants. In conclusion, we show that LRP2 is essential for cellular folate uptake in the developing neural tube, a crucial step for proper neural tube closure.

  4. Apoptotic gene expression in the neural tube during early human embryonic development

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    Guifang Chen; Tiandong Li; Peipei Ding; Ping Yang; Xiao Zhang

    2011-01-01

    Neural tube development comprises neural induction,neural epithelial cell proliferation,and apoptosis,as well as migration of nerve cells.Too much or too little apoptosis leads to abnormal nervous system development.The present study analyzed expression and distribution of apoptotic-related factors,including Fas,FasL,and caspase-3,during human embryonic neural tube development.Experimental results showed that increased caspase-3 expression promoted neural apoptosis via a mitochondriai-mediated intrinsic pathway at 4 weeks during early human embryonic neural tube development.Subsequently,Fas and FasL expression increased during embryonic development.The results suggest that neural cells influence neural apoptosis through synergistic effects of extrinsic pathways.Therefore,neural apoptosis during the early period of neural tube development in the human embryo might be regulated by the death receptor induced apoptotic extrinsic pathways.

  5. Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation

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    Wang, Guang; Li, Yan; Wang, Xiao-yu [Key Laboratory for Regenerative Medicine of The Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632 (China); Han, Zhe [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Chuai, Manli [College of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH (United Kingdom); Wang, Li-jing [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Ho Lee, Kenneth Ka [Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin (Hong Kong); Geng, Jian-guo, E-mail: jgeng@umich.edu [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510224 (China); Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109 (United States); Yang, Xuesong, E-mail: yang_xuesong@126.com [Key Laboratory for Regenerative Medicine of The Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632 (China)

    2013-05-01

    Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes to block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1{sup +} migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug{sup +} pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1{sup +} migrating NCCs but reduced Pax7 expression and fewer Slug{sup +} pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube

  6. Neural Tube Defects

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    Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In ...

  7. Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation.

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    Wang, Guang; Li, Yan; Wang, Xiao-yu; Han, Zhe; Chuai, Manli; Wang, Li-jing; Ho Lee, Kenneth Ka; Geng, Jian-guo; Yang, Xuesong

    2013-05-01

    Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes to block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1(+) migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug(+) pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1(+) migrating NCCs but reduced Pax7 expression and fewer Slug(+) pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube development by tightly

  8. What Are Neural Tube Defects?

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    ... NICHD Research Information Clinical Trials Resources and Publications Neural Tube Defects (NTDs): Condition Information Skip sharing on social media links Share this: Page Content What are neural tube defects? Neural (pronounced NOOR-uhl ) tube defects are ...

  9. Misexpression of BRE gene in the developing chick neural tube affects neurulation and somitogenesis.

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    Wang, Guang; Li, Yan; Wang, Xiao-Yu; Chuai, Manli; Yeuk-Hon Chan, John; Lei, Jian; Münsterberg, Andrea; Lee, Kenneth Ka Ho; Yang, Xuesong

    2015-03-01

    The brain and reproductive expression (BRE) gene is expressed in numerous adult tissues and especially in the nervous and reproductive systems. However, little is known about BRE expression in the developing embryo or about its role in embryonic development. In this study, we used in situ hybridization to reveal the spatiotemporal expression pattern for BRE in chick embryo during development. To determine the importance of BRE in neurogenesis, we overexpressed BRE and also silenced BRE expression specifically in the neural tube. We established that overexpressing BRE in the neural tube indirectly accelerated Pax7(+) somite development and directly increased HNK-1(+) neural crest cell (NCC) migration and TuJ-1(+) neurite outgrowth. These altered morphogenetic processes were associated with changes in the cell cycle of NCCs and neural tube cells. The inverse effect was obtained when BRE expression was silenced in the neural tube. We also determined that BMP4 and Shh expression in the neural tube was affected by misexpression of BRE. This provides a possible mechanism for how altering BRE expression was able to affect somitogenesis, neurogenesis, and NCC migration. In summary, our results demonstrate that BRE plays an important role in regulating neurogenesis and indirectly somite differentiation during early chick embryo development.

  10. Modeling anterior development in mice: diet as modulator of risk for neural tube defects.

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    Kappen, Claudia

    2013-11-01

    Head morphogenesis is a complex process that is controlled by multiple signaling centers. The most common defects of cranial development are craniofacial defects, such as cleft lip and cleft palate, and neural tube defects, such as anencephaly and encephalocoele in humans. More than 400 genes that contribute to proper neural tube closure have been identified in experimental animals, but only very few causative gene mutations have been identified in humans, supporting the notion that environmental influences are critical. The intrauterine environment is influenced by maternal nutrition, and hence, maternal diet can modulate the risk for cranial and neural tube defects. This article reviews recent progress toward a better understanding of nutrients during pregnancy, with particular focus on mouse models for defective neural tube closure. At least four major patterns of nutrient responses are apparent, suggesting that multiple pathways are involved in the response, and likely in the underlying pathogenesis of the defects. Folic acid has been the most widely studied nutrient, and the diverse responses of the mouse models to folic acid supplementation indicate that folic acid is not universally beneficial, but that the effect is dependent on genetic configuration. If this is the case for other nutrients as well, efforts to prevent neural tube defects with nutritional supplementation may need to become more specifically targeted than previously appreciated. Mouse models are indispensable for a better understanding of nutrient-gene interactions in normal pregnancies, as well as in those affected by metabolic diseases, such as diabetes and obesity.

  11. dNTP deficiency induced by HU via inhibiting ribonucleotide reductase affects neural tube development.

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    Guan, Zhen; Wang, Xiuwei; Dong, Yanting; Xu, Lin; Zhu, Zhiqiang; Wang, Jianhua; Zhang, Ting; Niu, Bo

    2015-02-03

    Exposure to environmental toxic chemicals in utero during the neural tube development period can cause developmental disorders. To evaluate the disruption of neural tube development programming, the murine neural tube defects (NTDs) model was induced by interrupting folate metabolism using methotrexate in our previous study. The present study aimed to examine the effects of dNTP deficiency induced by hydroxyurea (HU), a specific ribonucleotide reductase (RNR) inhibitor, during murine neural tube development. Pregnant C57BL/6J mice were intraperitoneally injected with various doses of HU on gestation day (GD) 7.5, and the embryos were checked on GD 11.5. RNR activity and deoxynucleoside triphosphate (dNTP) levels were measured in the optimal dose. Additionally, DNA damage was examined by comet analysis and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. Cellular behaviors in NTDs embryos were evaluated with phosphorylation of histone H3 (PH-3) and caspase-3 using immunohistochemistry and western blot analysis. The results showed that NTDs were observed mostly with HU treatment at an optimal dose of 225 mg/kg b/w. RNR activity was inhibited and dNTP levels were decreased in HU-treated embryos with NTDs. Additionally, increased DNA damage, decreased proliferation, and increased caspase-3 were significant in NTDs embryos compared to the controls. Results indicated that HU induced murine NTDs model by disturbing dNTP metabolism and further led to the abnormal cell balance between proliferation and apoptosis.

  12. Ablation of Arg-tRNA-protein transferases results in defective neural tube development.

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    Kim, Eunkyoung; Kim, Seonmu; Lee, Jung Hoon; Kwon, Yong Tae; Lee, Min Jae

    2016-08-01

    The arginylation branch of the N-end rule pathway is a ubiquitin-mediated proteolytic system in which post-translational conjugation of Arg by ATE1-encoded Arg-tRNA-protein transferase to N-terminal Asp, Glu, or oxidized Cys residues generates essential degradation signals. Here, we characterized the ATE1-/- mice and identified the essential role of N-terminal arginylation in neural tube development. ATE1-null mice showed severe intracerebral hemorrhages and cystic space near the neural tubes. Expression of ATE1 was prominent in the developing brain and spinal cord, and this pattern overlapped with the migration path of neural stem cells. The ATE1-/- brain showed defective G-protein signaling. Finally, we observed reduced mitosis in ATE1-/- neuroepithelium and a significantly higher nitric oxide concentration in the ATE1-/- brain. Our results strongly suggest that the crucial role of ATE1 in neural tube development is directly related to proper turn-over of the RGS4 protein, which participate in the oxygen-sensing mechanism in the cells. [BMB Reports 2016; 49(8): 443-448].

  13. Distinct regulatory mechanisms act to establish and maintain Pax3 expression in the developing neural tube.

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    Steven Moore

    Full Text Available Pattern formation in developing tissues is driven by the interaction of extrinsic signals with intrinsic transcriptional networks that together establish spatially and temporally restricted profiles of gene expression. How this process is orchestrated at the molecular level by genomic cis-regulatory modules is one of the central questions in developmental biology. Here we have addressed this by analysing the regulation of Pax3 expression in the context of the developing spinal cord. Pax3 is induced early during neural development in progenitors of the dorsal spinal cord and is maintained as pattern is subsequently elaborated, resulting in the segregation of the tissue into dorsal and ventral subdivisions. We used a combination of comparative genomics and transgenic assays to define and dissect several functional cis-regulatory modules associated with the Pax3 locus. We provide evidence that the coordinated activity of two modules establishes and refines Pax3 expression during neural tube development. Mutational analyses of the initiating element revealed that in addition to Wnt signaling, Nkx family homeodomain repressors restrict Pax3 transcription to the presumptive dorsal neural tube. Subsequently, a second module mediates direct positive autoregulation and feedback to maintain Pax3 expression. Together, these data indicate a mechanism by which transient external signals are converted into a sustained expression domain by the activities of distinct regulatory elements. This transcriptional logic differs from the cross-repression that is responsible for the spatiotemporal patterns of gene expression in the ventral neural tube, suggesting that a variety of circuits are deployed within the neural tube regulatory network to establish and elaborate pattern formation.

  14. Neural tube defects

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    M.E. Marshall

    1981-09-01

    Full Text Available Neural tube defects refer to any defect in the morphogenesis of the neural tube, the most common types being spina bifida and anencephaly. Spina bifida has been recognised in skeletons found in north-eastern Morocco and estimated to have an age of almost 12 000 years. It was also known to the ancient Greek and Arabian physicians who thought that the bony defect was due to the tumour. The term spina bifida was first used by Professor Nicolai Tulp of Amsterdam in 1652. Many other terms have been used to describe this defect, but spina bifida remains the most useful general term, as it describes the separation of the vertebral elements in the midline.

  15. Moderate alcohol exposure compromises neural tube midline development in prenatal brain.

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    Zhou, Feng C; Sari, Youssef; Powrozek, Teresa; Goodlett, Charles R; Li, Ting-Kai

    2003-08-12

    We previously reported that fetal alcohol treatment compromised the development of the midline raphe and the serotonin neurons contained in it. In this study, we report that the timely development of midline neural tissue during neural tube formation is sensitive to alcohol exposure. Pregnant dams were treated from embryonic day 7 (E7, prior to neurulation) or E8.5 (at neurulation) with the following diets: (a) alcohol (ALC), given as either a 20% or 25% ethanol-derived calorie (EDC) liquid diet, or (b) isocaloric liquid diet pair-fed (PF), or (c) standard rat chow (Chow). Fetal brains from each group were examined on E13, E15, or E18. Neural tube development was compromised as a result of alcohol exposure in the following ways: (1) approximately 60% of embryos at E13 and 20% at E15 showed perforation of the floor plate in the diencephalic vesicle, (2) although completely closed at E13, 70-80% of embryos failed to complete the formation of neural tissue at the roof as the alcohol exposure continued to E15, and (3) 60-80% of embryos show delayed 'occlusion' of the ventral canal by newly formed nestin-positive neuroepithelial cells and S100beta-positive glia in the brainstem of E15. The compromised (incomplete) neural tube midline (cNTM) occurred near the ventricles at E13 and E15, but was later completed at E18. In all cases, the cNTM was accompanied by an enlarged ventricle, and dose-dependent brain weight reduction. The midline of the neural tube at the roof and floor plates is known to mediate timely trophic induction for neural differentiation. Prenatal midline deficits also have the potential to affect the development of midline neurons such as raphe, septal nuclei, and the timely crossing of commissural fibers. The results of the liquid diet alcohol exposure paradigm suggest it is more a model for Alcohol-Related Neurodevelopmental Disorder (ARND) featuring neuropsychiatric disorders than for full-blown fetal alcohol syndrome (FAS) with noticeable facial

  16. Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain.

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    Albuixech-Crespo, Beatriz; López-Blanch, Laura; Burguera, Demian; Maeso, Ignacio; Sánchez-Arrones, Luisa; Moreno-Bravo, Juan Antonio; Somorjai, Ildiko; Pascual-Anaya, Juan; Puelles, Eduardo; Bovolenta, Paola; Garcia-Fernàndez, Jordi; Puelles, Luis; Irimia, Manuel; Ferran, José Luis

    2017-04-01

    All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice.

  17. Regulation of Patched by Sonic Hedgehog in the Developing Neural Tube

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    Marigo, Valeria; Tabin, Clifford J.

    1996-09-01

    Ventral cell fates in the central nervous system are induced by Sonic hedgehog, a homolog of hedgehog, a secreted Drosophila protein. In the central nervous system, Sonic hedgehog has been identified as the signal inducing floor plate, motor neurons, and dopaminergic neurons. Sonic hedgehog is also involved in the induction of ventral cell type in the developing somites. ptc is a key gene in the Drosophila hedgehog signaling pathway where it is involved in transducing the hedgehog signal and is also a transcriptional target of the signal. PTC, a vertebrate homolog of this Drosophila gene, is genetically downstream of Sonic hedgehog (Shh) in the limb bud. We analyze PTC expression during chicken neural and somite development and find it expressed in all regions of these tissues known to be responsive to Sonic hedgehog signal. As in the limb bud, ectopic expression of Sonic hedgehog leads to ectopic induction of PTC in the neural tube and paraxial mesoderm. This conservation of regulation allows us to use PTC as a marker for Sonic hedgehog response. The pattern of PTC expression suggests that Sonic hedgehog may play an inductive role in more dorsal regions of the neural tube than have been previously demonstrated. Examination of the pattern of PTC expression also suggests that PTC may act in a negative feedback loop to attenuate hedgehog signaling.

  18. Development-on-chip: in vitro neural tube patterning with a microfluidic device

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    Soundararajan, Prabakaran; Chennampally, Phaneendra; Cox, Gregory A.

    2016-01-01

    Embryogenesis is a highly regulated process in which the precise spatial and temporal release of soluble cues directs differentiation of multipotent stem cells into discrete populations of specialized adult cell types. In the spinal cord, neural progenitor cells are directed to differentiate into adult neurons through the action of mediators released from nearby organizing centers, such as the floor plate and paraxial mesoderm. These signals combine to create spatiotemporal diffusional landscapes that precisely regulate the development of the central nervous system (CNS). Currently, in vivo and ex vivo studies of these signaling factors present some inherent ambiguity. In vitro methods are preferred for their enhanced experimental clarity but often lack the technical sophistication required for biological realism. In this article, we present a versatile microfluidic platform capable of mimicking the spatial and temporal chemical environments found in vivo during neural tube development. Simultaneous opposing and/or orthogonal gradients of developmental morphogens can be maintained, resulting in neural tube patterning analogous to that observed in vivo. PMID:27246712

  19. Endocytic recycling protein EHD1 regulates primary cilia morphogenesis and SHH signaling during neural tube development.

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    Bhattacharyya, Sohinee; Rainey, Mark A; Arya, Priyanka; Dutta, Samikshan; George, Manju; Storck, Matthew D; McComb, Rodney D; Muirhead, David; Todd, Gordon L; Gould, Karen; Datta, Kaustubh; Gelineau-van Waes, Janee; Band, Vimla; Band, Hamid

    2016-02-17

    Members of the four-member C-terminal EPS15-Homology Domain-containing (EHD) protein family play crucial roles in endocytic recycling of cell surface receptors from endosomes to the plasma membrane. In this study, we show that Ehd1 gene knockout in mice on a predominantly B6 background is embryonic lethal. Ehd1-null embryos die at mid-gestation with a failure to complete key developmental processes including neural tube closure, axial turning and patterning of the neural tube. We found that Ehd1-null embryos display short and stubby cilia on the developing neuroepithelium at embryonic day 9.5 (E9.5). Loss of EHD1 also deregulates the ciliary SHH signaling with Ehd1-null embryos displaying features indicative of increased SHH signaling, including a significant downregulation in the formation of the GLI3 repressor and increase in the ventral neuronal markers specified by SHH. Using Ehd1-null MEFS we found that EHD1 protein co-localizes with the SHH receptor Smoothened in the primary cilia upon ligand stimulation. Under the same conditions, EHD1 was shown to co-traffic with Smoothened into the developing primary cilia and we identify EHD1 as a direct binding partner of Smoothened. Overall, our studies identify the endocytic recycling regulator EHD1 as a novel regulator of the primary cilium-associated trafficking of Smoothened and Hedgehog signaling.

  20. A Robust Single Primate Neuroepithelial Cell Clonal Expansion System for Neural Tube Development and Disease Studies

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    Xiaoqing Zhu

    2016-02-01

    Full Text Available Developing a model of primate neural tube (NT development is important to promote many NT disorder studies in model organisms. Here, we report a robust and stable system to allow for clonal expansion of single monkey neuroepithelial stem cells (NESCs to develop into miniature NT-like structures. Single NESCs can produce functional neurons in vitro, survive, and extensively regenerate neuron axons in monkey brain. NT formation and NESC maintenance depend on high metabolism activity and Wnt signaling. NESCs are regionally restricted to a telencephalic fate. Moreover, single NESCs can turn into radial glial progenitors (RGPCs. The transition is accurately regulated by Wnt signaling through regulation of Notch signaling and adhesion molecules. Finally, using the “NESC-TO-NTs” system, we model the functions of folic acid (FA on NT closure and demonstrate that FA can regulate multiple mechanisms to prevent NT defects. Our system is ideal for studying NT development and diseases.

  1. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure.

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    Hamblet, Natasha S; Lijam, Nardos; Ruiz-Lozano, Pilar; Wang, Jianbo; Yang, Yasheng; Luo, Zhenge; Mei, Lin; Chien, Kenneth R; Sussman, Daniel J; Wynshaw-Boris, Anthony

    2002-12-01

    The murine dishevelled 2 (Dvl2) gene is an ortholog of the Drosophila segment polarity gene Dishevelled, a member of the highly conserved Wingless/Wnt developmental pathway. Dvl2-deficient mice were produced to determine the role of Dvl2 in mammalian development. Mice containing null mutations in Dvl2 present with 50% lethality in both inbred 129S6 and in a hybrid 129S6-NIH Black Swiss background because of severe cardiovascular outflow tract defects, including double outlet right ventricle, transposition of the great arteries and persistent truncus arteriosis. The majority of the surviving Dvl2(-/-) mice were female, suggesting that penetrance was influenced by sex. Expression of Pitx2 and plexin A2 was attenuated in Dvl2 null mutants, suggesting a defect in cardiac neural crest development during outflow tract formation. In addition, approximately 90% of Dvl2(-/-) mice have vertebral and rib malformations that affect the proximal as well as the distal parts of the ribs. These skeletal abnormalities were more pronounced in mice deficient for both Dvl1 and Dvl2. Somite differentiation markers used to analyze Dvl2(-/-) and Dvl1(-/-);Dvl2(-/-) mutant embryos revealed mildly aberrant expression of Uncx4.1, delta 1 and myogenin, suggesting defects in somite segmentation. Finally, 2-3% of Dvl2(-/-) embryos displayed thoracic spina bifida, while virtually all Dvl1/2 double mutant embryos displayed craniorachishisis, a completely open neural tube from the midbrain to the tail. Thus, Dvl2 is essential for normal cardiac morphogenesis, somite segmentation and neural tube closure, and there is functional redundancy between Dvl1 and Dvl2 in some phenotypes.

  2. [Recent perspectives on the development of the central nervous system and the genetic background of neural tube defects].

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    Joó, József Gábor

    2009-05-10

    Neural tube defects are rare and mostly lethal malformations. The pattern of inheritance of these malformations is multifactorial, rendering the identification of the underlying causes. Numerous studies have been conducted to elucidate the genetic basis of the development of the central nervous system. Essential signaling pathways of the development of the central nervous system include the planar cell polarity pathway, which is important for the initiation of neural tube closure as well as sonic hedgehog pathway, which regulates the neural plate bending. Genes and their mutations influencing the different stages of neurulation have been investigated for their eventual role in the development of these malformations. Among the environmental factors, folic acid seems to be the most important modifier of the risk of human neural tube defects. Genes of the folate metabolism pathways have also been investigated to identify mutations resulting in increased risk of NTDs. In this review the author has attempted to summarize the knowledge on neural tube defects, with special regard to genetic factors of the etiology.

  3. miR-430 regulates oriented cell division during neural tube development in zebrafish.

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    Takacs, Carter M; Giraldez, Antonio J

    2016-01-15

    MicroRNAs have emerged as critical regulators of gene expression. Originally shown to regulate developmental timing, microRNAs have since been implicated in a wide range of cellular functions including cell identity, migration and signaling. miRNA-430, the earliest expressed microRNA during zebrafish embryogenesis, is required to undergo morphogenesis and has previously been shown to regulate maternal mRNA clearance, Nodal signaling, and germ cell migration. The functions of miR-430 in brain morphogenesis, however, remain unclear. Herein we find that miR-430 instructs oriented cell divisions in the neural rod required for neural midline formation. Loss of miR-430 function results in mitotic spindle misorientation in the neural rod, failed neuroepithelial integration after cell division, and ectopic cell accumulation in the dorsal neural tube. We propose that miR-430, independently of canonical apicobasal and planar cell polarity (PCP) pathways, coordinates the stereotypical cell divisions that instruct neural tube morphogenesis.

  4. Neural tube defects in Costa Rica, 1987-2012: origins and development of birth defect surveillance and folic acid fortification.

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    Barboza-Argüello, María de la Paz; Umaña-Solís, Lila M; Azofeifa, Alejandro; Valencia, Diana; Flores, Alina L; Rodríguez-Aguilar, Sara; Alfaro-Calvo, Thelma; Mulinare, Joseph

    2015-03-01

    Our aim was to provide a descriptive overview of how the birth defects surveillance and folic acid fortification programs were implemented in Costa Rica-through the establishment of the Registry Center for Congenital Anomalies (Centro de Registro de Enfermedades Congénitas-CREC), and fortification legislation mandates. We estimated the overall prevalence of neural tube defects (i.e., spina bifida, anencephaly and encephalocele) before and after fortification captured by CREC. Prevalence was calculated by dividing the total number of infants born with neural tube defects by the total number of live births in the country (1987-2012).A total of 1,170 newborns with neural tube defects were identified from 1987 to 2012 (1992-1995 data excluded); 628 were identified during the baseline pre-fortification period (1987-1991; 1996-1998); 191 during the fortification period (1999-2002); and 351 during the post-fortification time period (2003-2012). The overall prevalence of neural tube defects decreased from 9.8 per 10,000 live-births (95 % CI 9.1-10.5) for the pre-fortification period to 4.8 per 10,000 live births (95 % CI 4.3-5.3) for the post-fortification period. Results indicate a statistically significant (P neural tube defects from the pre-fortification period to the post-fortification period. Folic acid fortification via several basic food sources has shown to be a successful public health intervention for Costa Rica. Costa Rica's experience can serve as an example for other countries seeking to develop and strengthen both their birth defects surveillance and fortification programs.

  5. Folate receptors and neural tube closure.

    Science.gov (United States)

    Saitsu, Hirotomo

    2017-02-28

    Neural tube defects (NTD) are among the most common human congenital malformations, affecting 0.5-8/1000 of live births. Human clinical trials have shown that periconceptional folate supplementation significantly decreases the occurrence of NTD in offspring. However, the mechanism by which folate acts on NTD remains largely unknown. Folate receptor (Folr) is one of the three membrane proteins that mediate cellular uptake of folates. Recent studies suggest that mouse Folr1 (formerly referred to as Fbp1) is essential for neural tube closure. Therefore, we examined spatial and temporal expression patterns of Folr1 in developing mouse embryos, showing a close association between Folr1 and anterior neural tube closure. Transient transgenic analysis was performed using lacZ as a reporter; we identified a 1.1-kb enhancer that directs lacZ expression in the neural tube and optic vesicle in a manner that is similar to endogenous Folr1. The 1.1-kb enhancer sequences were highly conserved between humans and mice, suggesting that human FOLR1 is associated with anterior neural tube closure in humans. Several experimental studies in mice and human epidemiological and genetics studies have suggested that folate receptor abnormalities are involved in a portion of human NTDs, although the solo defect of FOLR1 did not cause NTD.

  6. Teratogenic effects of Gabapentin on Neural Tube and skeletal development in mice

    Directory of Open Access Journals (Sweden)

    M. Afshar

    2005-01-01

    Full Text Available Background and purpose : Gabapentin is a new Antiepileptic drugs that introduced for the treatment of partial and second generalized seizures. Other usages of this drug include relief of neuropathic pains such as diabetic and cancers neuropathy and also prophylaxy of migrane. There is little information about the teratogenic effects of this drug. Only few studies reported delay in ossification of bones and hydroureter and hydronephrosis. This study carried out to reveal the macroscopic malformation of this drug when used during the implantation and organogenesis periods.Materials and methods : 30 balb/c virgin females, aged 2.5 months and weighted 30±2 gr were housed in environmentally controlled room. A group of 3 females was caged with a single male of proven fertility overnight. Finding of vaginal plug on the following morning was regarded as gestational day (GD 0. Mice were divided into experimental groups; ex. І=received 1400 mg /day (20mg/kg/day and ex. II=received 1800 mg /day (26mg/kg/day doses of Gabapentin drug for 10 subsequent days and one control group which received disstilled water intraperitoneally. They were dissected in GD18 and embryos were collected and washed with normal saline. Macroscopic observation was made using a stereomicroscope and weighed using a digital scale with 0.01 accuracy. Data were analysed by ANOVA and X2 tests using of SPSS software. Results : Both experimental groups (I, II revealed similar malformations categorized as skeletal malformation and neural tube defects. Skeletal malformation was more frequent than neural tube defects and mostly included limbs defects,distortions and dislocations with significant difference compared with the control group (p<0.05. Spina bifida cystica was the most common form of neural tube defects. In the experimental group II, density and incidence of malformations and also fetuses resorption were higher than those of the other experimental group.Conclusion : This study

  7. Morphogenetic movements in the neural plate and neural tube: mouse.

    Science.gov (United States)

    Massarwa, R'ada; Ray, Heather J; Niswander, Lee

    2014-01-01

    The neural tube (NT), the embryonic precursor of the vertebrate brain and spinal cord, is generated by a complex and highly dynamic morphological process. In mammals, the initially flat neural plate bends and lifts bilaterally to generate the neural folds followed by fusion of the folds at the midline during the process of neural tube closure (NTC). Failures in any step of this process can lead to neural tube defects (NTDs), a common class of birth defects that occur in approximately 1 in 1000 live births. These severe birth abnormalities include spina bifida, a failure of closure at the spinal level; craniorachischisis, a failure of NTC along the entire body axis; and exencephaly, a failure of the cranial neural folds to close which leads to degeneration of the exposed brain tissue termed anencephaly. The mouse embryo presents excellent opportunities to explore the genetic basis of NTC in mammals; however, its in utero development has also presented great challenges in generating a deeper understanding of how gene function regulates the cell and tissue behaviors that drive this highly dynamic process. Recent technological advances are now allowing researchers to address these questions through visualization of NTC dynamics in the mouse embryo in real time, thus offering new insights into the morphogenesis of mammalian NTC.

  8. Microtubules, polarity and vertebrate neural tube morphogenesis.

    Science.gov (United States)

    Cearns, Michael D; Escuin, Sarah; Alexandre, Paula; Greene, Nicholas D E; Copp, Andrew J

    2016-07-01

    Microtubules (MTs) are key cellular components, long known to participate in morphogenetic events that shape the developing embryo. However, the links between the cellular functions of MTs, their effects on cell shape and polarity, and their role in large-scale morphogenesis remain poorly understood. Here, these relationships were examined with respect to two strategies for generating the vertebrate neural tube: bending and closure of the mammalian neural plate; and cavitation of the teleost neural rod. The latter process has been compared with 'secondary' neurulation that generates the caudal spinal cord in mammals. MTs align along the apico-basal axis of the mammalian neuroepithelium early in neural tube closure, participating functionally in interkinetic nuclear migration, which indirectly impacts on cell shape. Whether MTs play other functional roles in mammalian neurulation remains unclear. In the zebrafish, MTs are important for defining the neural rod midline prior to its cavitation, both by localizing apical proteins at the tissue midline and by orienting cell division through a mirror-symmetric MT apparatus that helps to further define the medial localization of apical polarity proteins. Par proteins have been implicated in centrosome positioning in neuroepithelia as well as in the control of polarized morphogenetic movements in the neural rod. Understanding of MT functions during early nervous system development has so far been limited, partly by techniques that fail to distinguish 'cause' from 'effect'. Future developments will likely rely on novel ways to selectively impair MT function in order to investigate the roles they play.

  9. Fat1 interacts with Fat4 to regulate neural tube closure, neural progenitor proliferation and apical constriction during mouse brain development.

    Science.gov (United States)

    Badouel, Caroline; Zander, Mark A; Liscio, Nicole; Bagherie-Lachidan, Mazdak; Sopko, Richelle; Coyaud, Etienne; Raught, Brian; Miller, Freda D; McNeill, Helen

    2015-08-15

    Mammalian brain development requires coordination between neural precursor proliferation, differentiation and cellular organization to create the intricate neuronal networks of the adult brain. Here, we examined the role of the atypical cadherins Fat1 and Fat4 in this process. We show that mutation of Fat1 in mouse embryos causes defects in cranial neural tube closure, accompanied by an increase in the proliferation of cortical precursors and altered apical junctions, with perturbations in apical constriction and actin accumulation. Similarly, knockdown of Fat1 in cortical precursors by in utero electroporation leads to overproliferation of radial glial precursors. Fat1 interacts genetically with the related cadherin Fat4 to regulate these processes. Proteomic analysis reveals that Fat1 and Fat4 bind different sets of actin-regulating and junctional proteins. In vitro data suggest that Fat1 and Fat4 form cis-heterodimers, providing a mechanism for bringing together their diverse interactors. We propose a model in which Fat1 and Fat4 binding coordinates distinct pathways at apical junctions to regulate neural progenitor proliferation, neural tube closure and apical constriction.

  10. Influence of the antifolate drug Methotrexate on the development of murine neural tube defects and genomic instability.

    Science.gov (United States)

    Zhao, Jie; Guan, Tao; Wang, Jianhua; Xiang, Qian; Wang, Mingsheng; Wang, Xiuwei; Guan, Zhen; Xie, Qiu; Niu, Bo; Zhang, Ting

    2013-09-01

    Impaired folate metabolism is considered a risk factor for neural tube defects (NTDs). However, the relationship between folate deficiency and the risk of NTDs remains unclear, because experimentally induced dietary folate deficiency is insufficient to cause NTDs in non-mutant mice. Methotrexate (MTX) is a specific folate antagonist that competitively inhibits dihydrofolate reductase (DHFR) activity. The objective of this study was to develop a folate dysmetabolism murine model, and study the development of NTDs and its mechanism. Pregnant mice were injected with different doses of MTX [0, 0.5, 1.0, 3.0, 4.5 and 6.0 mg kg(-1) body weight (b/w) intraperitoneally (i.p.)] on gestational day 7.5 and sacrificed on gestational day 11.5. DHFR activity in embryonic tissues was detected, and folate concentrations were analyzed using LC/MS/MS. Copy number variations (CNVs) in neural tube tissues were detected using array comparative genomic hybridization (aCGH). A dose of MTX 4.5 mg kg(-1) b/w, resulted in the highest incidence of NTDs (31.4%) compared with the other groups, and DHFR activities, 5-MeTHF and 5-FoTHF concentrations in embryonic tissues decreased significantly after MTX injection. Furthermore, we found three high-confidence CNVs on chromosome X using aCGH, which was confirmed by RT-PCR and MassARRAY. These results indicate that MTX could cause a folate-associated dysmetabolism, which is similar to that of dietary folate deficiency in mice. The presence of CNVs in neural tube tissues was associated with the development of NTDs.

  11. Apoptosis is not required for mammalian neural tube closure.

    Science.gov (United States)

    Massa, Valentina; Savery, Dawn; Ybot-Gonzalez, Patricia; Ferraro, Elisabetta; Rongvaux, Anthony; Cecconi, Francesco; Flavell, Richard; Greene, Nicholas D E; Copp, Andrew J

    2009-05-19

    Apoptotic cell death occurs in many tissues during embryonic development and appears to be essential for processes including digit formation and cardiac outflow tract remodeling. Studies in the chick suggest a requirement for apoptosis during neurulation, because inhibition of caspase activity was found to prevent neural tube closure. In mice, excessive apoptosis occurs in association with failure of neural tube closure in several genetic mutants, but whether regulated apoptosis is also necessary for neural tube closure in mammals is unknown. Here we investigate the possible role of apoptotic cell death during mouse neural tube closure. We confirm the presence of apoptosis in the neural tube before and during closure, and identify a correlation with 3 main events: bending and fusion of the neural folds, postfusion remodeling of the dorsal neural tube and surface ectoderm, and emigration of neural crest cells. Both Casp3 and Apaf1 null embryos exhibit severely reduced apoptosis, yet neurulation proceeds normally in the forebrain and spine. In contrast, the mutant embryos fail to complete neural tube closure in the midbrain and hindbrain. Application of the apoptosis inhibitors z-Vad-fmk and pifithrin-alpha to neurulation-stage embryos in culture suppresses apoptosis but does not prevent initiation or progression of neural tube closure along the entire neuraxis, including the midbrain and hindbrain. Remodeling of the surface ectoderm to cover the closed tube, as well as delamination and migration of neural crest cells, also appear to be normal in the apoptosis-suppressed embryos. We conclude that apoptosis is not required for neural tube closure in the mouse embryo.

  12. Sept6 is required for ciliogenesis in Kupffer's vesicle, the pronephros, and the neural tube during early embryonic development.

    Science.gov (United States)

    Zhai, Gang; Gu, Qilin; He, Jiangyan; Lou, Qiyong; Chen, Xiaowen; Jin, Xia; Bi, Erfei; Yin, Zhan

    2014-04-01

    Septins are conserved filament-forming GTP-binding proteins that act as cellular scaffolds or diffusion barriers in a number of cellular processes. However, the role of septins in vertebrate development remains relatively obscure. Here, we show that zebrafish septin 6 (sept6) is first expressed in the notochord and then in nearly all of the ciliary organs, including Kupffer's vesicle (KV), the pronephros, eye, olfactory bulb, and neural tube. Knockdown of sept6 in zebrafish embryos results in reduced numbers and length of cilia in KV. Consequently, cilium-related functions, such as the left-right patterning of internal organs and nodal/spaw signaling, are compromised. Knockdown of sept6 also results in aberrant cilium formation in the pronephros and neural tube, leading to cilium-related defects in pronephros development and Sonic hedgehog (Shh) signaling. We further demonstrate that SEPT6 associates with acetylated α-tubulin in vivo and localizes along the axoneme in the cilia of zebrafish pronephric duct cells as well as cultured ZF4 cells. Our study reveals a novel role of sept6 in ciliogenesis during early embryonic development in zebrafish.

  13. Neural Tube Defects, Folic Acid and Methylation

    Directory of Open Access Journals (Sweden)

    Henk J. Blom

    2013-09-01

    Full Text Available Neural tube defects (NTDs are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects.

  14. Program Specificity for Ptf1a in Pancreas versus Neural Tube Development Correlates with Distinct Collaborating Cofactors and Chromatin Accessibility

    Science.gov (United States)

    Meredith, David M.; Borromeo, Mark D.; Deering, Tye G.; Casey, Bradford H.; Savage, Trisha K.; Mayer, Paul R.; Hoang, Chinh; Tung, Kuang-Chi; Kumar, Manonmani; Shen, Chengcheng; Swift, Galvin H.

    2013-01-01

    The lineage-specific basic helix-loop-helix transcription factor Ptf1a is a critical driver for development of both the pancreas and nervous system. How one transcription factor controls diverse programs of gene expression is a fundamental question in developmental biology. To uncover molecular strategies for the program-specific functions of Ptf1a, we identified bound genomic regions in vivo during development of both tissues. Most regions bound by Ptf1a are specific to each tissue, lie near genes needed for proper formation of each tissue, and coincide with regions of open chromatin. The specificity of Ptf1a binding is encoded in the DNA surrounding the Ptf1a-bound sites, because these regions are sufficient to direct tissue-restricted reporter expression in transgenic mice. Fox and Sox factors were identified as potential lineage-specific modifiers of Ptf1a binding, since binding motifs for these factors are enriched in Ptf1a-bound regions in pancreas and neural tube, respectively. Of the Fox factors expressed during pancreatic development, Foxa2 plays a major role. Indeed, Ptf1a and Foxa2 colocalize in embryonic pancreatic chromatin and can act synergistically in cell transfection assays. Together, these findings indicate that lineage-specific chromatin landscapes likely constrain the DNA binding of Ptf1a, and they identify Fox and Sox gene families as part of this process. PMID:23754747

  15. Planar cell polarity genes and neural tube closure.

    Science.gov (United States)

    Ueno, Naoto; Greene, Nicholas D E

    2003-11-01

    Closure of the neural tube is essential for normal development of the brain and spinal cord. Failure of closure results in neural tube defects (NTDs), common and clinically severe congenital malformations whose molecular mechanisms remain poorly understood. On the other hand, it is increasingly well established that common molecular mechanisms are employed to regulate morphogenesis of multicellular organisms. For example, signaling triggered by polypeptide growth factors is highly conserved among species and utilized in multiple developmental processes. Recent studies have revealed that the Drosophila planar cell polarity (PCP) pathway, which directs position and direction of wing hairs on the surface of the fly wing, is well conserved, and orthologs of several genes encoding components of the pathway are also found in vertebrates. Interestingly, in vertebrates, this signaling pathway appears to be co-opted to regulate "convergent extension" cell movements during gastrulation. Disruption of vertebrate PCP genes in Xenopus laevis or zebrafish causes severe gastrulation defects or the shortening of the trunk, as well as mediolateral expansion of somites. In Xenopus, in which the neural tube closes by elevation and fusion of neural folds, inhibition of convergent extension can also prevent neural tube closure causing a "spina bifida-like" appearance. Furthermore, several of the genes involved in the PCP pathway have recently been shown to be required for neural tube closure in the mouse, since mutation of these genes causes NTDs. Therefore, understanding the mechanisms underlying the establishment of cell polarity in Drosophila may provide important clues to the molecular basis of NTDs.

  16. Radioactive fallout and neural tube defects

    Directory of Open Access Journals (Sweden)

    Nejat Akar

    2015-10-01

    Full Text Available Possible link between radioactivity and the occurrence of neural tube defects is a long lasting debate since the Chernobyl nuclear fallout in 1986. A recent report on the incidence of neural defects in the west coast of USA, following Fukushima disaster, brought another evidence for effect of radioactive fallout on the occurrence of NTD’s. Here a literature review was performed focusing on this special subject.

  17. Disturbed apoptosis and cell proliferation in developing neuroepithelium of lumbo-sacral neural tubes in retinoic acid-induced spina bifida aperta in rat.

    Science.gov (United States)

    Wei, Xiaowei; Li, Hui; Miao, Jianing; Zhou, Fenghua; Liu, Bo; Wu, Di; Li, Shujing; Wang, Lili; Fan, Yang; Wang, Weilin; Yuan, Zhengwei

    2012-08-01

    Spina bifida is a complex congenital malformation resulting from failure of fusion in the spinal neural tube during embryogenesis. However, the cellular mechanism underlying spina bifida is not fully understood. Here, we investigated cell apoptosis in whole embryos and proliferation of neural progenitor cells in the spinal neural tube during neurulation in all-trans retinoic acid (atRA)-induced spina bifida in fetal rats. Cell apoptosis was assessed by TUNEL assay on whole-mount and serially sectioned samples of rat embryos with spina bifida. Cell proliferation of lumbo-sacral neural progenitor cells was assessed by staining for the mitotic marker Ki67 and pH3. We found an excess of apoptosis in the neuroepithelium of embryos with spina bifida, which became more marked as embryos progress from E11 to E13. Conversely, there was a reduction in cell proliferation in spina bifida embryos, with a progressively greater difference from controls with stage from E11 to 13. Thus, atRA-induced spina bifida in rat shows perturbed apoptosis and proliferation of neural progenitors in the lumbo-sacral spinal cord during embryonic development, which might contribute to the pathogenesis of spina bifida.

  18. How Do Health Care Providers Diagnose Neural Tube Defects?

    Science.gov (United States)

    ... and Publications How do health care providers diagnose neural tube defects? Skip sharing on social media links Share this: Page Content Neural tube defects are usually diagnosed before the infant is ...

  19. Are There Disorders or Conditions Associated with Neural Tube Defects?

    Science.gov (United States)

    ... Publications Are there disorders or conditions associated with neural tube defects? Skip sharing on social media links Share this: Page Content Infants born with neural tube defects that are not immediately fatal may have ...

  20. Role of polarized cell divisions in zebrafish neural tube formation.

    Science.gov (United States)

    Clarke, Jon

    2009-04-01

    Development of epithelial cell polarity and morphogenesis of a central lumen are essential prerequisites for the formation of the vertebrate neural tube. In teleost fish embryos this first involves the formation of a solid neural rod structure that then undergoes a process of cavitation to form a lumen. This process is initiated from a neural plate that has a distinct organization compared to other vertebrates, and involves complex cell intercalations and rearrangements. A key element is a mode of polarized cell division that generates daughters with mirror-image apico-basal polarity. These mirror-symmetric divisions have powerful morphogenetic influence because when they occur in ectopic locations they orchestrate the development of ectopic apical and basal specializations and the development of ectopic neural tubes.

  1. Identification and characterization of secondary neural tube-derived embryonic neural stem cells in vitro.

    Science.gov (United States)

    Shaker, Mohammed R; Kim, Joo Yeon; Kim, Hyun; Sun, Woong

    2015-05-15

    Secondary neurulation is an embryonic progress that gives rise to the secondary neural tube, the precursor of the lower spinal cord region. The secondary neural tube is derived from aggregated Sox2-expressing neural cells at the dorsal region of the tail bud, which eventually forms rosette or tube-like structures to give rise to neural tissues in the tail bud. We addressed whether the embryonic tail contains neural stem cells (NSCs), namely secondary NSCs (sNSCs), with the potential for self-renewal in vitro. Using in vitro neurosphere assays, neurospheres readily formed at the rosette and neural-tube levels, but less frequently at the tail bud tip level. Furthermore, we identified that sNSC-generated neurospheres were significantly smaller in size compared with cortical neurospheres. Interestingly, various cell cycle analyses revealed that this difference was not due to a reduction in the proliferation rate of NSCs, but rather the neuronal commitment of sNSCs, as sNSC-derived neurospheres contain more committed neuronal progenitor cells, even in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). These results suggest that the higher tendency for sNSCs to spontaneously differentiate into progenitor cells may explain the limited expansion of the secondary neural tube during embryonic development.

  2. Cellular mechanisms of posterior neural tube morphogenesis in the zebrafish.

    Science.gov (United States)

    Harrington, Michael J; Chalasani, Kavita; Brewster, Rachel

    2010-03-01

    The zebrafish is a well established model system for studying neural development, yet neurulation remains poorly understood in this organism. In particular, the morphogenetic movements that shape the posterior neural tube (PNT) have not been described. Using tools for imaging neural tissue and tracking the behavior of cells in real time, we provide the first comprehensive analysis of the cellular events shaping the PNT. We observe that this tissue is formed in a stepwise manner, beginning with merging of presumptive neural domains in the tailbud (Stage 1); followed by neural convergence and infolding to shape the neural rod (Stage 2); and continued elongation of the PNT, in absence of further convergence (Stage 3). We further demonstrate that cell proliferation plays only a minimal role in PNT elongation. Overall, these mechanisms resemble those previously described in anterior regions, suggesting that, in contrast to amniotes, neurulation is a fairly uniform process in zebrafish.

  3. Changes in the osmolarity of the embryonic microenvironment induce neural tube defects.

    Science.gov (United States)

    Jin, Yi-Mei; Wang, Guang; Zhang, Nuan; Wei, Yi-Fan; Li, Shuai; Chen, You-Peng; Chuai, Manli; Lee, Henry Siu Sum; Hocher, Berthold; Yang, Xuesong

    2015-05-01

    Many maternal disorders that modify the embryonic microenvironment, such as a change in osmolarity, can affect development, but how these changes influence the early embryo remains obscure. Neural tube defects, for example, are common congenital disorders found in fetus and neonates. In this study, we investigated the impact of anisotonic osmolarity (unequal osmotic pressures) on neural tube development in the early chick embryo, finding that neuronal cell differentiation was impaired in the neural tube due to enhanced apoptosis and repressed cell proliferation. Anisotonic osmolarity also affected normal development of the neural crest, which in turn influenced abnormal development of the neural tube. As neural tube development is highly dependent on the proper expression of bone morphogenetic protein 4 (BMP4), paired box 7 (PAX7), and sonic hedgehog (SHH) genes in the dorsal and ventral regions along the tube, we investigated the impact of anisotonic osmolarity on their expression. Indeed, small changes in osmolarity could positively and negatively impact the expression of these regulatory genes, which profoundly affected neural tube development. Thus, both the central and peripheral nervous systems were perturbed by anisotonic consitions as a consequence of the abnormal expression of key genes within the developing neural tube.

  4. Genes encoding critical transcriptional activators for murine neural tube development and human spina bifida: a case-control study

    Directory of Open Access Journals (Sweden)

    Pisano M Michele

    2010-10-01

    Full Text Available Abstract Background Spina bifida is a malformation of the neural tube and is the most common of neural tube defects (NTDs. The etiology of spina bifida is largely unknown, although it is thought to be multi-factorial, involving multiple interacting genes and environmental factors. Mutations in transcriptional co-activator genes-Cited2, p300, Cbp, Tfap2α, Carm1 and Cart1 result in NTDs in murine models, thus prompt us to investigate whether homologues of these genes are associated with NTDs in humans. Methods Data and biological samples from 297 spina bifida cases and 300 controls were derived from a population-based case-control study conducted in California. 37 SNPs within CITED2, EP300, CREBBP, TFAP2A, CARM1 and ALX1 were genotyped using an ABI SNPlex assay. Odds ratios and 95% confidence intervals were calculated for alleles, genotypes and haplotypes to evaluate the risk for spina bifida. Results Several SNPs showed increased or decreased risk, including CITED2 rs1131431 (OR = 5.32, 1.04~27.30, EP300 rs4820428 (OR = 1.30, 1.01~1.67, EP300 rs4820429 (OR = 0.50, 0.26~0.50, in whites, OR = 0.7, 0.49~0.99 in all subjects, EP300 rs17002284 (OR = 0.43, 0.22~0.84, TFAP2A rs3798691 (OR = 1.78, 1.13~2.87 in Hispanics, CREBBP rs129986 (OR = 0.27, 0.11~0.69, CARM1 rs17616105 (OR = 0.41, 0.22~0.72 in whites. In addition, one haplotype block in EP300 and one in TFAP2A appeared to be associated with increased risk. Conclusions Modest associations were observed in CITED2, EP300, CREBBP, TFAP2A and CARM1 but not ALX1. However, these modest associations were not statistically significant after correction for multiple comparisons. Searching for potential functional variants and rare causal mutations is warranted in these genes.

  5. Developing effective campaign messages to prevent neural tube defects: a qualitative assessment of women's reactions to advertising concepts.

    Science.gov (United States)

    Massi Lindsey, Lisa L; Silk, Kami J; Von Friederichs-Fitzwater, Marlene M; Hamner, Heather C; Prue, Christine E; Boster, Franklin J

    2009-03-01

    The incidence of neural tube defects (NTDs), serious birth defects of the brain and spine that affect approximately 3,000 pregnancies in the United States each year, can be reduced by 50-70% with daily periconceptional consumption of the B vitamin folic acid. Two studies were designed to assess college women's reactions to and perceptions of potential campaign advertising concepts derived from preproduction formative research to increase folic acid consumption through the use of a daily multivitamin. Study one assessed draft advertising concepts in eight focus groups (N = 71) composed of college-enrolled women in four cities geographically dispersed across the United States. Based on study one results, the concepts were revised and reassessed in study two with a different sample (eight focus groups; N = 73) of college women in the same four cities. Results indicated that participants generally responded favorably to concepts in each of the two studies, and provided insight into individual concepts to increase their overall appeal and effectiveness. The specific findings and implications of these results are discussed.

  6. 21 CFR 101.79 - Health claims: Folate and neural tube defects.

    Science.gov (United States)

    2010-04-01

    ... development. Because the neural tube forms and closes during early pregnancy, the defect may occur before a woman realizes that she is pregnant. (2) Relationship. The available data show that diets adequate in... at risk of recurrence of a neural tube defect pregnancy who consumed a supplement containing 4...

  7. Genetic, epigenetic, and environmental contributions to neural tube closure.

    Science.gov (United States)

    Wilde, Jonathan J; Petersen, Juliette R; Niswander, Lee

    2014-01-01

    The formation of the embryonic brain and spinal cord begins as the neural plate bends to form the neural folds, which meet and adhere to close the neural tube. The neural ectoderm and surrounding tissues also coordinate proliferation, differentiation, and patterning. This highly orchestrated process is susceptible to disruption, leading to neural tube defects (NTDs), a common birth defect. Here, we highlight genetic and epigenetic contributions to neural tube closure. We describe an online database we created as a resource for researchers, geneticists, and clinicians. Neural tube closure is sensitive to environmental influences, and we discuss disruptive causes, preventative measures, and possible mechanisms. New technologies will move beyond candidate genes in small cohort studies toward unbiased discoveries in sporadic NTD cases. This will uncover the genetic complexity of NTDs and critical gene-gene interactions. Animal models can reveal the causative nature of genetic variants, the genetic interrelationships, and the mechanisms underlying environmental influences.

  8. Preventing neural tube defects in Europe : A missed opportunity

    NARCIS (Netherlands)

    Busby, A; Armstrong, B; Dolk, H; Armstrong, N; Haeusler, M; Berghold, A; Gillerot, Y; Baguette, A; Gjerga, R; Barisic, [No Value; Christiansen, M; Goujard, J; Steinbicker, [No Value; Rosch, C; McDonnell, R; Scarano, G; Calzolari, E; Neville, A; Cocchi, G; Bianca, S; Gatt, M; De Walle, H; Braz, P; Latos-Bielenska, A; Gener, B; Portillor, [No Value; Addor, MC; Abramsky, L; Ritvanen, A; Robert-Gnansia, E; Daltveit, AK; Aneren, G; Olars, B; Edwards, G

    2005-01-01

    Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects (NTD). Unambiguous evidence of the effectiveness of peri conceptional folic acid in preventing the majority of neural tube defects has been available since 1991. We report on trends in the total prevalenc

  9. Neural tube defects and folate: case far from closed.

    NARCIS (Netherlands)

    Blom, H.J.; Shaw, G.M.; Heijer, M. den; Finnell, R.H.

    2006-01-01

    Neural tube closure takes place during early embryogenesis and requires interactions between genetic and environmental factors. Failure of neural tube closure is a common congenital malformation that results in morbidity and mortality. A major clinical achievement has been the use of periconceptiona

  10. Neural tube closure: cellular, molecular and biomechanical mechanisms.

    Science.gov (United States)

    Nikolopoulou, Evanthia; Galea, Gabriel L; Rolo, Ana; Greene, Nicholas D E; Copp, Andrew J

    2017-02-15

    Neural tube closure has been studied for many decades, across a range of vertebrates, as a paradigm of embryonic morphogenesis. Neurulation is of particular interest in view of the severe congenital malformations - 'neural tube defects' - that result when closure fails. The process of neural tube closure is complex and involves cellular events such as convergent extension, apical constriction and interkinetic nuclear migration, as well as precise molecular control via the non-canonical Wnt/planar cell polarity pathway, Shh/BMP signalling, and the transcription factors Grhl2/3, Pax3, Cdx2 and Zic2. More recently, biomechanical inputs into neural tube morphogenesis have also been identified. Here, we review these cellular, molecular and biomechanical mechanisms involved in neural tube closure, based on studies of various vertebrate species, focusing on the most recent advances in the field.

  11. Neural tube defect and folic acid.

    Science.gov (United States)

    Wani, M A

    2000-01-01

    Neural tube defect (NTD) is a group of congenital anomalies, which include anencephaly, encephalocele, iniencephaly, meningocele, myelomeningocele, myeloschisis, lipomeningocele, and rashischisis. Congenital malformations of the central nervous system constitute more than half of all congenital malformations with an incidence of 1-2/1000 births. The condition is thought to arise from multifactorial etiology with a distinct genetic predisposition. This paper discusses the pathogenesis of NTD and explores the use of folic acid for the prevention of this serious congenital malformation. Two studies, which have shown a significant protective effect of folic acid use on NTD prevention in high-risk mothers, are cited. In considering the effectiveness of folic acid supplementation on NTD prevention, obstetricians, pediatricians, neonatologists, and family doctors are called to initiate a collective effort to increase awareness among women in the childbearing age on the need of daily multivitamin intake with folic acid prior to pregnancy.

  12. The Relationship of Aluminium and Silver to Neural Tube Defects; a Case Control

    Directory of Open Access Journals (Sweden)

    María de Jesús Ramírez-Altamirano

    2012-09-01

    Full Text Available Objective: The purpose of this study was to identify the relationship of neurotoxic inorganic elements in the hair of patients with the diagnosis of Neural Tube Defects. Our initial hypothesis was that neurotoxic inorganic elements were associated with Neural Tube Defects.Methods: Twenty-three samples of hair from newborns were obtained from the General Hospital, “Aurelio Valdivieso” in the city of Oaxaca, Mexico. The study group included 8 newborn infants with neural tube pathology. The control group was composed of 15 newborns without this pathology. The presence of inorganic elements in the hair samples was determined by inductively-coupled plasma spectroscopy(spectroscopic emission of the plasma.Findings: The population of newborns with Neural Tube Defects showed significantly higher values of the following elements than the control group: Aluminium, Neural Tube Defects 152.77±51.06 μg/g, control group 76.24±27.89 μg/g; Silver, Neural Tube Defects 1.45±0.76, control group 0.25±0.53 μg/g; Potassium,Neural Tube Defects 553.87±77.91 μg/g, control group 341.13±205.90 μg/g. Association was found at 75 percentile between aluminium plus silver, aluminium plus potassium, silver plus potassium, and potassium plus sodium.Conclusion: In the hair of newborns with Neural Tube Defects, the following metals were increased:aluminium, silver. Given the neurotoxicity of the same, and association of Neural Tube Defects with aluminum and silver, one may infer that they may be participating as factors in the development of Neural Tube Defects.

  13. Nucleotide precursors prevent folic acid-resistant neural tube defects in the mouse.

    Science.gov (United States)

    Leung, Kit-Yi; De Castro, Sandra C P; Savery, Dawn; Copp, Andrew J; Greene, Nicholas D E

    2013-09-01

    Closure of the neural tube during embryogenesis is a crucial step in development of the central nervous system. Failure of this process results in neural tube defects, including spina bifida and anencephaly, which are among the most common birth defects worldwide. Maternal use of folic acid supplements reduces risk of neural tube defects but a proportion of cases are not preventable. Folic acid is thought to act through folate one-carbon metabolism, which transfers one-carbon units for methylation reactions and nucleotide biosynthesis. Hence suboptimal performance of the intervening reactions could limit the efficacy of folic acid. We hypothesized that direct supplementation with nucleotides, downstream of folate metabolism, has the potential to support neural tube closure. Therefore, in a mouse model that exhibits folic acid-resistant neural tube defects, we tested the effect of specific combinations of pyrimidine and purine nucleotide precursors and observed a significant protective effect. Labelling in whole embryo culture showed that nucleotides are taken up by the neurulating embryo and incorporated into genomic DNA. Furthermore, the mitotic index was elevated in neural folds and hindgut of treated embryos, consistent with a proposed mechanism of neural tube defect prevention through stimulation of cellular proliferation. These findings may provide an impetus for future investigations of supplemental nucleotides as a means to prevent a greater proportion of human neural tube defects than can be achieved by folic acid alone.

  14. G-protein-coupled receptor signaling and neural tube closure defects.

    Science.gov (United States)

    Shimada, Issei S; Mukhopadhyay, Saikat

    2016-10-12

    Disruption of the normal mechanisms that mediate neural tube closure can result in neural tube defects (NTDs) with devastating consequences in affected patients. With the advent of next-generation sequencing, we are increasingly detecting mutations in multiple genes in NTD cases. However, our ability to determine which of these genes contribute to the malformation is limited by our understanding of the pathways controlling neural tube closure. G-protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in humans and have been historically favored as drug targets. Recent studies implicate several GPCRs and downstream signaling pathways in neural tube development and closure. In this review, we will discuss our current understanding of GPCR signaling pathways in pathogenesis of NTDs. Notable examples include the orphan primary cilia-localized GPCR, Gpr161 that regulates the basal suppression machinery of sonic hedgehog pathway by means of activation of cAMP-protein kinase A signaling in the neural tube, and protease-activated receptors that are activated by a local network of membrane-tethered proteases during neural tube closure involving the surface ectoderm. Understanding the role of these GPCR-regulated pathways in neural tube development and closure is essential toward identification of underlying genetic causes to prevent NTDs. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc.

  15. Nodal signaling is required for closure of the anterior neural tube in zebrafish

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    Liu Qin

    2007-11-01

    Full Text Available Abstract Background Nodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish. Results We find that the neural tube in the presumptive forebrain fails to close in zebrafish Nodal signaling mutants. For instance, the cells that will give rise to the pineal organ fail to move from the lateral edges of the neural plate to the midline of the diencephalon. The open neural tube in Nodal signaling mutants may be due in part to reduced function of N-cadherin, a cell adhesion molecule expressed in the neural tube and required for neural tube closure. N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling. Further, N-cadherin mutants and morphants have a pineal phenotype similar to that of mutants with deficiencies in the Nodal pathway. Overexpression of an activated form of the TGFβ Type I receptor Taram-A (Taram-A* cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling. We find that overexpression of Taram-A* also corrects their open neural tube defect. This suggests that, as in mammals, the mesoderm and endoderm have an important role in regulating closure of the anterior neural tube of zebrafish. Conclusion This work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain.

  16. The prevention of neural tube defects by folic acid supplementation

    Directory of Open Access Journals (Sweden)

    H. W. Hitzeroth

    1993-05-01

    Full Text Available Neural tube defects, in particular spina bifida and anencephaly, are serious and relatively common congenital abnormalities worldwide. They also occur in South Africa and affect all population groups to varying degrees. The overall incidence in South Africa is approximately 1-2 per 1000 newborns. Higher incidences, up to 6 per 1000 newborns have been recorded in certain parts, especially in some rural areas of the country. In total as many as 1500 newborns could be affected by a neural tube defect each year. The precise aetiology of neural tube defects is still unknown.

  17. Strategies of vertebrate neurulation and a re-evaluation of teleost neural tube formation.

    Science.gov (United States)

    Lowery, Laura Anne; Sive, Hazel

    2004-10-01

    The vertebrate neural tube develops by two distinct mechanisms. Anteriorly, in the brain and future trunk (cervicothoracic) region, 'primary neurulation' occurs, where an epithelial sheet rolls or bends into a tube. Posteriorly, in the future lumbar and tail region, the neural tube forms by 'secondary neurulation', where a mesenchymal cell population condenses to form a solid rod that undergoes transformation to an epithelial tube. Teleost neurulation has been described as different from that of other vertebrates. This is principally because the teleost trunk neural tube initially forms a solid rod (the neural keel) that later develops a lumen. This process has also been termed secondary neurulation. However, this description is not accurate since the teleost neural tube derives from an epithelial sheet that folds. This best fits the description of primary neurulation. It has also been suggested that teleost neurulation is primitive, however, both primary and secondary neurulation are found in groups with a more ancient origin than the teleosts. The similarity between neurulation in teleosts and other vertebrates indicates that this group includes viable models (such as the zebrafish) for understanding human neural tube development.

  18. Mechanical roles of apical constriction, cell elongation, and cell migration during neural tube formation in Xenopus.

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    Inoue, Yasuhiro; Suzuki, Makoto; Watanabe, Tadashi; Yasue, Naoko; Tateo, Itsuki; Adachi, Taiji; Ueno, Naoto

    2016-12-01

    Neural tube closure is an important and necessary process during the development of the central nervous system. The formation of the neural tube structure from a flat sheet of neural epithelium requires several cell morphogenetic events and tissue dynamics to account for the mechanics of tissue deformation. Cell elongation changes cuboidal cells into columnar cells, and apical constriction then causes them to adopt apically narrow, wedge-like shapes. In addition, the neural plate in Xenopus is stratified, and the non-neural cells in the deep layer (deep cells) pull the overlying superficial cells, eventually bringing the two layers of cells to the midline. Thus, neural tube closure appears to be a complex event in which these three physical events are considered to play key mechanical roles. To test whether these three physical events are mechanically sufficient to drive neural tube formation, we employed a three-dimensional vertex model and used it to simulate the process of neural tube closure. The results suggest that apical constriction cued the bending of the neural plate by pursing the circumference of the apical surface of the neural cells. Neural cell elongation in concert with apical constriction further narrowed the apical surface of the cells and drove the rapid folding of the neural plate, but was insufficient for complete neural tube closure. Migration of the deep cells provided the additional tissue deformation necessary for closure. To validate the model, apical constriction and cell elongation were inhibited in Xenopus laevis embryos. The resulting cell and tissue shapes resembled the corresponding simulation results.

  19. Dynamic behaviors of the non-neural ectoderm during mammalian cranial neural tube closure.

    Science.gov (United States)

    Ray, Heather J; Niswander, Lee A

    2016-08-15

    The embryonic brain and spinal cord initially form through the process of neural tube closure (NTC). NTC is thought to be highly similar between rodents and humans, and studies of mouse genetic mutants have greatly increased our understanding of the molecular basis of NTC with relevance for human neural tube defects. In addition, studies using amphibian and chick embryos have shed light into the cellular and tissue dynamics underlying NTC. However, the dynamics of mammalian NTC has been difficult to study due to in utero development until recently when advances in mouse embryo ex vivo culture techniques along with confocal microscopy have allowed for imaging of mouse NTC in real time. Here, we have performed live imaging of mouse embryos with a particular focus on the non-neural ectoderm (NNE). Previous studies in multiple model systems have found that the NNE is important for proper NTC, but little is known about the behavior of these cells during mammalian NTC. Here we utilized a NNE-specific genetic labeling system to assess NNE dynamics during murine NTC and identified different NNE cell behaviors as the cranial region undergoes NTC. These results bring valuable new insight into regional differences in cellular behavior during NTC that may be driven by different molecular regulators and which may underlie the various positional disruptions of NTC observed in humans with neural tube defects.

  20. Neural tube closure in Xenopus laevis involves medial migration, directed protrusive activity, cell intercalation and convergent extension.

    Science.gov (United States)

    Davidson, L A; Keller, R E

    1999-10-01

    We have characterized the cell movements and prospective cell identities as neural folds fuse during neural tube formation in Xenopus laevis. A newly developed whole-mount, two-color fluorescent RNA in situ hybridization method, visualized with confocal microscopy, shows that the dorsal neural tube gene xpax3 and the neural-crest-specific gene xslug are expressed far lateral to the medial site of neural fold fusion and that expression moves medially after fusion. To determine whether cell movements or dynamic changes in gene expression are responsible, we used low-light videomicroscopy followed by fluorescent in situ and confocal microscopy. These methods revealed that populations of prospective neural crest and dorsal neural tube cells near the lateral margin of the neural plate at the start of neurulation move to the dorsal midline using distinctive forms of motility. Before fold fusion, superficial neural cells apically contract, roll the neural plate into a trough and appear to pull the superficial epidermal cell sheet medially. After neural fold fusion, lateral deep neural cells move medially by radially intercalating between other neural cells using two types of motility. The neural crest cells migrate as individual cells toward the dorsal midline using medially directed monopolar protrusions. These movements combine the two lateral populations of neural crest into a single medial population that form the roof of the neural tube. The remaining cells of the dorsal neural tube extend protrusions both medially and laterally bringing about radial intercalation of deep and superficial cells to form a single-cell-layered, pseudostratified neural tube. While ours is the first description of medially directed cell migration during neural fold fusion and re-establishment of the neural tube, these complex cell behaviors may be involved during cavitation of the zebrafish neural keel and secondary neurulation in the posterior axis of chicken and mouse.

  1. Neural Tube Defects: From a Proteomic Standpoint

    Directory of Open Access Journals (Sweden)

    Tania M. Puvirajesinghe

    2015-03-01

    Full Text Available Neural tube defects (NTDs are congenital birth defects classified according to their resulting morphological characteristics in newborn patients. Current diagnosis of NTDs relies largely on the structural evaluation of fetuses using ultrasound imaging, with biochemical characterization used as secondary screening tools. The multigene etiology of NTDs has been aided by genetic studies, which have discovered panels of genes mutated in these diseases that encode receptors and cytoplasmic signaling molecules with poorly defined functions. Animal models ranging from flies to mice have been used to determine the function of these genes and identify their associated molecular cascades. More emphasis is now being placed on the identification of biochemical markers from clinical samples and model systems based on mass spectrometry, which open novel avenues in the understanding of NTDs at protein, metabolic and molecular levels. This article reviews how the use of proteomics can push forward the identification of novel biomarkers and molecular networks implicated in NTDs, an indispensable step in the improvement of patient management.

  2. Aneuploidy among prenatally detected neural tube defects

    Energy Technology Data Exchange (ETDEWEB)

    Hume, R.F. Jr.; Lampinen, J.; Martin, L.S.; Johnson, M.P.; Evans, M.I. [Wayne State Univ., Detroit, MI (United States)] [and others

    1996-01-11

    We have reported previously a 10% aneuploidy detection rate among 39 cases of fetal neural tube defects (NTD). Subsequently we amassed an additional experience of over 17,000 prenatal diagnosis cases over a 5-year period. During this period 106 cases of NTDs were identified; 44 with anencephaly, 62 with open spina bifida. The average maternal age of this population with NTDs was 29 years (15-40); 6 patients declined amniocentesis. Six of 100 cytogenetic studies were aneuploid; on anencephalic fetus had inherited a maternal marker chromosome, and 5 NTD cases had trisomy 18. The average maternal age of the aneuploid cases was 21 (19-40); 3 were 35 years or older. Four of 5 trisomy 18 cases had multiple congenital anomalies (MCA). The overall aneuploidy detection rate in our cohort was 5-6, while aneuploidy occurred in 2% of the isolated NTD cases, and 24% of the MCA cases. Combining the earlier experience, 4/39 aneuploidy (2 trisomy 18, 4p+, del 13q) yields an aneuploidy detection frequency of 10/145 (7%), of which most (7/10) had trisomy 18. These data support fetal karyotyping for accurate diagnosis, prognosis, and recurrence-risk counseling. 5 refs., 2 tabs.

  3. Distinct enhancers at the Pax3 locus can function redundantly to regulate neural tube and neural crest expressions.

    Science.gov (United States)

    Degenhardt, Karl R; Milewski, Rita C; Padmanabhan, Arun; Miller, Mayumi; Singh, Manvendra K; Lang, Deborah; Engleka, Kurt A; Wu, Meilin; Li, Jun; Zhou, Diane; Antonucci, Nicole; Li, Li; Epstein, Jonathan A

    2010-03-15

    Pax3 is a transcription factor expressed in somitic mesoderm, dorsal neural tube and pre-migratory neural crest during embryonic development. We have previously identified cis-acting enhancer elements within the proximal upstream genomic region of Pax3 that are sufficient to direct functional expression of Pax3 in neural crest. These elements direct expression of a reporter gene to pre-migratory neural crest in transgenic mice, and transgenic expression of a Pax3 cDNA using these elements is sufficient to rescue neural crest development in mice otherwise lacking endogenous Pax3. We show here that deletion of these enhancer sequences by homologous recombination is insufficient to abrogate neural crest expression of Pax3 and results in viable mice. We identify a distinct enhancer in the fourth intron that is also capable of mediating neural crest expression in transgenic mice and zebrafish. Our analysis suggests the existence of functionally redundant neural crest enhancer modules for Pax3.

  4. Diastematomyelia: A Case with Familial Aggregation of Neural Tube Defects

    Directory of Open Access Journals (Sweden)

    Nuray Öksüz Kanbur

    2004-01-01

    Full Text Available Intrauterine neural tube defects, meningomyelocele, and diastematomyelia are developmental errors at different stages of the closure of the neural tube. The familial aggregation of these neural tube defects is not previously reported in the literature and should make one think about a common embryogenesis and a possible common mechanism of etiopathogenesis leading to anomalies at different stages of this embryogenesis. This paper presents a 12-year-old Turkish boy with diastematomyelia who was suspected with a demonstrative dermatologic finding without any neurologic sign and diagnosed with magnetic resonance imaging (MRI. He has a positive family history of a stillbirth with neural tube defect, an exitus with meningomyelocele, and an epileptic child in his female siblings.

  5. Neural tube defects: recent advances, unsolved questions, and controversies.

    Science.gov (United States)

    Copp, Andrew J; Stanier, Philip; Greene, Nicholas D E

    2013-08-01

    Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention with folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in the UK. Genetic predisposition accounts for most of the risk of neural tube defects, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but studies of mouse models of neural tube defects show that anencephaly, open spina bifida, and craniorachischisis result from failure of primary neurulation, whereas skin-covered spinal dysraphism results from defective secondary neurulation. Other malformations, such as encephalocele, are likely to be postneurulation disorders.

  6. Use of high‐frequency ultrasound to study the prenatal development of cranial neural tube defects and hydrocephalus in Gldc‐deficient mice

    Science.gov (United States)

    Autuori, Maria C.; Pai, Yun J.; Stuckey, Daniel J.; Savery, Dawn; Marconi, Anna M.; Massa, Valentina; Lythgoe, Mark F.; Copp, Andrew J.; David, Anna L.

    2017-01-01

    Abstract Objective We used non‐invasive high‐frequency ultrasound (HFUS) imaging to investigate embryonic brain development in a mouse model for neural tube defects (NTDs) and non‐ketotic hyperglycinemia (NKH). Method Using HFUS, we imaged embryos carrying loss of function alleles of Gldc encoding glycine decarboxylase, a component of the glycine cleavage system in mitochondrial folate metabolism, which is known to be associated with cranial NTDs and NKH in humans. We serially examined the same litter during the second half of embryonic development and quantified cerebral structures. Genotype was confirmed using PCR. Histology was used to confirm ultrasound findings. Results High‐frequency ultrasound allowed in utero detection of two major brain abnormalities in Gldc‐deficient mouse embryos, cranial NTDs (exencephaly) and ventriculomegaly (corresponding with the previous finding of post‐natal hydrocephalus). Serial ultrasound allowed individual embryos to be analysed at successive gestational time points. From embryonic day 16.5 to 18.5, the lateral ventricle volume reduced in wild‐type and heterozygous embryos but increased in homozygous Gldc‐deficient embryos. Conclusion Exencephaly and ventriculomegaly were detectable by HFUS in homozygous Gldc‐deficient mouse embryos indicating this to be an effective tool to study CNS development. Longitudinal analysis of the same embryo allowed the prenatal onset and progression of ventricle enlargement in Gldc‐deficient mice to be determined. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. PMID:28056489

  7. [Folic acid: Primary prevention of neural tube defects. Literature Review].

    Science.gov (United States)

    Llamas Centeno, M J; Miguélez Lago, C

    2016-03-01

    Neural tube defects (NTD) are the most common congenital malformations of the nervous system, they have a multifactorial etiology, are caused by exposure to chemical, physical or biological toxic agents, factors deficiency, diabetes, obesity, hyperthermia, genetic alterations and unknown causes. Some of these factors are associated with malnutrition by interfering with the folic acid metabolic pathway, the vitamin responsible for neural tube closure. Its deficit produce anomalies that can cause abortions, stillbirths or newborn serious injuries that cause disability, impaired quality of life and require expensive treatments to try to alleviate in some way the alterations produced in the embryo. Folic acid deficiency is considered the ultimate cause of the production of neural tube defects, it is clear the reduction in the incidence of Espina Bifida after administration of folic acid before conception, this leads us to want to further study the action of folic acid and its application in the primary prevention of neural tube defects. More than 40 countries have made the fortification of flour with folate, achieving encouraging data of decrease in the prevalence of neural tube defects. This paper attempts to make a literature review, which clarify the current situation and future of the prevention of neural tube defects.

  8. Dynamic imaging and quantitative analysis of cranial neural tube closure in the mouse embryo using optical coherence tomography.

    Science.gov (United States)

    Wang, Shang; Garcia, Monica D; Lopez, Andrew L; Overbeek, Paul A; Larin, Kirill V; Larina, Irina V

    2017-01-01

    Neural tube closure is a critical feature of central nervous system morphogenesis during embryonic development. Failure of this process leads to neural tube defects, one of the most common forms of human congenital defects. Although molecular and genetic studies in model organisms have provided insights into the genes and proteins that are required for normal neural tube development, complications associated with live imaging of neural tube closure in mammals limit efficient morphological analyses. Here, we report the use of optical coherence tomography (OCT) for dynamic imaging and quantitative assessment of cranial neural tube closure in live mouse embryos in culture. Through time-lapse imaging, we captured two neural tube closure mechanisms in different cranial regions, zipper-like closure of the hindbrain region and button-like closure of the midbrain region. We also used OCT imaging for phenotypic characterization of a neural tube defect in a mouse mutant. These results suggest that the described approach is a useful tool for live dynamic analysis of normal neural tube closure and neural tube defects in the mouse model.

  9. Reconstitution of a Patterned Neural Tube from Single Mouse Embryonic Stem Cells.

    Science.gov (United States)

    Ishihara, Keisuke; Ranga, Adrian; Lutolf, Matthias P; Tanaka, Elly M; Meinhardt, Andrea

    2017-01-01

    The recapitulation of tissue development and patterning in three-dimensional (3D) culture is an important dimension of stem cell research. Here, we describe a 3D culture protocol in which single mouse ES cells embedded in Matrigel under neural induction conditions clonally form a lumen containing, oval-shaped epithelial structure within 3 days. By Day 7 an apicobasally polarized neuroepithelium with uniformly dorsal cell identity forms. Treatment with retinoic acid at Day 2 results in posteriorization and self-organization of dorsal-ventral neural tube patterning. Neural tube organoid growth is also supported by pure laminin gels as well as poly(ethylene glycol) (PEG)-based artificial extracellular matrix hydrogels, which can be fine-tuned for key microenvironment characteristics. The rapid generation of a simple, patterned tissue in well-defined culture conditions makes the neural tube organoid a tractable model for studying neural stem cell self-organization.

  10. RFX7 is required for the formation of cilia in the neural tube.

    Science.gov (United States)

    Manojlovic, Zarko; Earwood, Ryan; Kato, Akiko; Stefanovic, Branko; Kato, Yoichi

    2014-05-01

    Regulatory Factor X (RFX) transcription factors are important for development and are likely involved in the pathogenesis of serious human diseases including ciliopathies. While seven RFX genes have been identified in vertebrates and several RFX transcription factors have been reported to be regulators of ciliogenesis, the role of RFX7 in development including ciliogenesis is not known. Here we show that RFX7 in Xenopus laevis is expressed in the neural tube, eye, otic vesicles, and somites. Knockdown of RFX7 in Xenopus embryos resulted in a defect of ciliogenesis in the neural tube and failure of neural tube closure. RFX7 controlled the formation of cilia by regulating the expression of RFX4 gene, which has been reported to be required for ciliogenesis in the neural tube. Moreover, ectopic expression of Foxj1, which is a master regulator of motile cilia formation, suppressed the expression of RFX4 but not RFX7. Taken together, RFX7 plays an important role in the process of neural tube closure at the top of the molecular cascade which controls ciliogenesis in the neural tube.

  11. Localization and distribution of superoxide dismutase-1 in the neural tube morphogenesis of chick embryo.

    Science.gov (United States)

    Dhage, Prajakta A; Kamble, Lekha K; Bhargava, Shobha Y

    2017-02-01

    Superoxide dismutase 1 (SOD- 1) is an antioxidant enzyme that regulates the levels of Reactive oxygen species (ROS) by catalyzing the conversion of superoxide radical into hydrogen peroxide (H2O2) and oxygen. ROS are known to play a significant role in various cellular processes, via redox modification of a variety of molecules that participate in signaling pathways involved in this processes. As the levels of ROS in cells are controlled by the levels of antioxidant enzymes, thus SOD-1 may be indirectly involved in regulating different cellular processes by maintaining the required levels of H2O2. Therefore, in the present study we have investigated the possible involvement of SOD- 1 in the neurulation during the development of chick embryo. During gastrulation, SOD- 1 immunoreactivity was observed throughout the ectoderm and cauda mesoderm areas, however, its presence during neurulation was restricted to certain areas of neural tube particularly in the dorsal neural tube where neural tube closure takes place. Assaying enzyme activity revealed a significant increase in the SOD activity during neurulation. Further, inhibition of SOD- 1 by Diethyldithiocarbamate (DDC) induced abnormalities in the development of the neural tube. SOD- 1 inhibition specifically affected the closure of neural tube in the anterior region. Thus, here we report the presence of SOD- 1 mainly in the ectoderm and tissues of ectodermal origin during gastrulation to neurulation which suggests that it may be involved in the regulating the cellular processes during neural tube morphogenesis.

  12. Global Burden of Neural Tube Defects, Risk Factors, and Prevention

    Directory of Open Access Journals (Sweden)

    Joseph E

    2014-11-01

    Full Text Available Neural tube defects (NTDs, serious birth defects of the brain and spine usually resulting in death or paralysis, affect an estimated 300,000 births each year worldwide. Although the majority of NTDs are preventable with adequate folic acid consumption during the preconception period and throughout the first few weeks of gestation, many populations, in particular those in low and middle resource settings, do not have access to fortified foods or vitamin supplements containing folic acid. Further, accurate birth defects surveillance data, which could help inform mandatory fortification and other NTD prevention initiatives, are lacking in many of these settings. The burden of birth defects in South East Asia is among the highest in the world. Expanding global neural tube defects prevention initiatives can support the achievement of the United Nations Millennium Development Goal 4 to reduce child mortality, a goal which many countries in South East Asia are currently not poised to reach, and the 63rd World Health Assembly Resolution on birth defects. More work is needed to develop and implement mandatory folic acid fortification policies, as well as supplementation programs in countries where the reach of fortification is limited.

  13. Temperature Sensitivity of Neural Tube Defects in Zoep Mutants.

    Science.gov (United States)

    Ma, Phyo; Swartz, Morgan R; Kindt, Lexy M; Kangas, Ashley M; Liang, Jennifer Ostrom

    2015-12-01

    Neural tube defects (NTD) occur when the flat neural plate epithelium fails to fold into the neural tube, the precursor to the brain and spinal cord. Squint (Sqt/Ndr1), a Nodal ligand, and One-eyed pinhead (Oep), a component of the Nodal receptor, are required for anterior neural tube closure in zebrafish. The NTD in sqt and Zoep mutants are incompletely penetrant. The penetrance of several defects in sqt mutants increases upon heat or cold shock. In this project, undergraduate students tested whether temperature influences the Zoep open neural tube phenotype. Single pairs of adults were spawned at 28.5°C, the normal temperature for zebrafish, and one half of the resulting embryos were moved to 34°C at different developmental time points. Analysis of variance indicated temperature and clutch/genetic background significantly contributed to the penetrance of the open neural tube phenotype. Heat shock affected the embryos only at or before the midblastula stage. Many factors, including temperature changes in the mother, nutrition, and genetic background, contribute to NTD in humans. Thus, sqt and Zoep mutants may serve as valuable models for studying the interactions between genetics and the environment during neurulation.

  14. Identifying Regulators of Morphogenesis Common to Vertebrate Neural Tube Closure and Caenorhabditis elegans Gastrulation.

    Science.gov (United States)

    Sullivan-Brown, Jessica L; Tandon, Panna; Bird, Kim E; Dickinson, Daniel J; Tintori, Sophia C; Heppert, Jennifer K; Meserve, Joy H; Trogden, Kathryn P; Orlowski, Sara K; Conlon, Frank L; Goldstein, Bob

    2016-01-01

    Neural tube defects including spina bifida are common and severe congenital disorders. In mice, mutations in more than 200 genes can result in neural tube defects. We hypothesized that this large gene set might include genes whose homologs contribute to morphogenesis in diverse animals. To test this hypothesis, we screened a set of Caenorhabditis elegans homologs for roles in gastrulation, a topologically similar process to vertebrate neural tube closure. Both C. elegans gastrulation and vertebrate neural tube closure involve the internalization of surface cells, requiring tissue-specific gene regulation, actomyosin-driven apical constriction, and establishment and maintenance of adhesions between specific cells. Our screen identified several neural tube defect gene homologs that are required for gastrulation in C. elegans, including the transcription factor sptf-3. Disruption of sptf-3 in C. elegans reduced the expression of early endodermally expressed genes as well as genes expressed in other early cell lineages, establishing sptf-3 as a key contributor to multiple well-studied C. elegans cell fate specification pathways. We also identified members of the actin regulatory WAVE complex (wve-1, gex-2, gex-3, abi-1, and nuo-3a). Disruption of WAVE complex members reduced the narrowing of endodermal cells' apical surfaces. Although WAVE complex members are expressed broadly in C. elegans, we found that expression of a vertebrate WAVE complex member, nckap1, is enriched in the developing neural tube of Xenopus. We show that nckap1 contributes to neural tube closure in Xenopus. This work identifies in vivo roles for homologs of mammalian neural tube defect genes in two manipulable genetic model systems.

  15. Coordinating cell and tissue behavior during zebrafish neural tube morphogenesis.

    Science.gov (United States)

    Araya, Claudio; Ward, Laura C; Girdler, Gemma C; Miranda, Miguel

    2016-03-01

    The development of a vertebrate neural epithelium with well-organized apico-basal polarity and a central lumen is essential for its proper function. However, how this polarity is established during embryonic development and the potential influence of surrounding signals and tissues on such organization has remained less understood. In recent years the combined superior transparency and genetics of the zebrafish embryo has allowed for in vivo visualization and quantification of the cellular and molecular dynamics that govern neural tube structure. Here, we discuss recent studies revealing how co-ordinated cell-cell interactions coupled with adjacent tissue dynamics are critical to regulate final neural tissue architecture. Furthermore, new findings show how the spatial regulation and timing of orientated cell division is key in defining precise lumen formation at the tissue midline. In addition, we compare zebrafish neurulation with that of amniotes and amphibians in an attempt to understand the conserved cellular mechanisms driving neurulation and resolve the apparent differences among animals. Zebrafish neurulation not only offers fundamental insights into early vertebrate brain development but also the opportunity to explore in vivo cell and tissue dynamics during complex three-dimensional animal morphogenesis.

  16. Murine dishevelled 3 functions in redundant pathways with dishevelled 1 and 2 in normal cardiac outflow tract, cochlea, and neural tube development.

    Directory of Open Access Journals (Sweden)

    S Leah Etheridge

    2008-11-01

    Full Text Available Dishevelled (Dvl proteins are important signaling components of both the canonical beta-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE movements that produce narrowing and elongation of the tissue. Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls. Dvl3(-/- mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis. These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+. Although neurulation appeared normal in both Dvl3(-/- and LtapLp/+ mutants, Dvl3(+/-;LtapLp/+ combined mutants displayed incomplete neural tube closure. Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2. More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals. In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development. Finally, we establish several developmental processes in which the three Dvls are functionally redundant.

  17. Murine dishevelled 3 functions in redundant pathways with dishevelled 1 and 2 in normal cardiac outflow tract, cochlea, and neural tube development.

    Science.gov (United States)

    Etheridge, S Leah; Ray, Saugata; Li, Shuangding; Hamblet, Natasha S; Lijam, Nardos; Tsang, Michael; Greer, Joy; Kardos, Natalie; Wang, Jianbo; Sussman, Daniel J; Chen, Ping; Wynshaw-Boris, Anthony

    2008-11-01

    Dishevelled (Dvl) proteins are important signaling components of both the canonical beta-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements that produce narrowing and elongation of the tissue. Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls. Dvl3(-/-) mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis. These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+). Although neurulation appeared normal in both Dvl3(-/-) and LtapLp/+ mutants, Dvl3(+/-);LtapLp/+ combined mutants displayed incomplete neural tube closure. Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2. More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals. In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development. Finally, we establish several developmental processes in which the three Dvls are functionally redundant.

  18. Folate receptor alpha is necessary for neural plate cell apical constriction during Xenopus neural tube formation.

    Science.gov (United States)

    Balashova, Olga A; Visina, Olesya; Borodinsky, Laura N

    2017-03-02

    Folate supplementation prevents up to 70% of neural tube defects (NTDs), which result from a failure of neural tube closure during embryogenesis. The elucidation of the mechanisms underlying folate action has been challenging. This study introduces Xenopus laevis as a model to determine the cellular and molecular mechanisms involved in folate action during neural tube formation. We show that knockdown of folate receptor-α (FRα) impairs neural tube formation and leads to NTDs. FRα knockdown in neural plate cells only is necessary and sufficient to induce NTDs. FRα-deficient neural plate cells fail to constrict, resulting in widening of the neural plate midline and defective neural tube closure. Pharmacological inhibition of folate action by methotrexate during neurulation induces NTDs by inhibiting folate interaction with its uptake systems. Our findings support a model for folate receptor interacting with cell adhesion molecules, thus regulating apical cell membrane remodeling and cytoskeletal dynamics necessary for neural plate folding. Further studies in this organism may unveil novel cellular and molecular events mediated by folate and lead to new means for preventing NTDs.

  19. Recent perspectives on the genetic background of neural tube defects with special regard to iniencephaly.

    Science.gov (United States)

    Joó, József Gábor

    2009-04-01

    Iniencephaly is a rare and mostly lethal type of neural tube defect. The pattern of inheritance of this group of malformations is multifactorial, rendering the identification of the underlying causes. Numerous studies have been conducted to elucidate the genetic basis of human neurulation. Essential signaling pathways of the development of the CNS include the planar cell polarity pathway, which is important for the initiation of neural tube closure, as well as the sonic hedgehog pathway, which regulates the neural plate bending. Genes influencing the different stages of neurulation have been investigated for their eventual role in the development of these malformations. Among the environmental factors, folic acid seems to be the most important modifier of the risk of human neural tube defects. Genes of the folate metabolism pathways have also been investigated to identify mutations resulting in increased risk of neural tube defects. In this review we have attempted to summarize the knowledge on iniencephaly and neural tube defects, with special regard to genetic factors of the etiology.

  20. Nutri-epigenomic Studies Related to Neural Tube Defects: Does Folate Affect Neural Tube Closure Via Changes in DNA Methylation?

    Science.gov (United States)

    Rochtus, Anne; Jansen, Katrien; Van Geet, Chris; Freson, Kathleen

    2015-01-01

    Neural tube defects (NTDs), affecting 1-2 per 1000 pregnancies, are severe congenital malformations that arise from the failure of neurulation during early embryonic development. The methylation hypothesis suggests that folate prevents NTDs by stimulating cellular methylation reactions. Folate is central to the one-carbon metabolism that produces pyrimidines and purines for DNA synthesis and for the generation of the methyldonor S-adenosyl-methionine. This review focuses on the relation between the folate-mediated one-carbon metabolism, DNA methylation and NTDs. Studies will be discussed that investigated global or locus-specific DNA methylation differences in patients with NTDs. Folate deficiency may increase NTD risk by decreasing DNA methylation, but to date, human studies vary widely in study design in terms of analyzing different clinical subtypes of NTDs, using different methylation quantification assays and using DNA isolated from diverse types of tissues. Some studies have focused mainly on global DNA methylation differences while others have quantified specific methylation differences for imprinted genes, transposable elements and DNA repair enzymes. Findings of global DNA hypomethylation and LINE-1 hypomethylation suggest that epigenetic alterations may disrupt neural tube closure. However, current research does not support a linear relation between red blood cell folate concentration and DNA methylation. Further studies are required to better understand the interaction between folate, DNA methylation changes and NTDs.

  1. ACAM, a novel member of the neural IgCAM family, mediates anterior neural tube closure in a primitive chordate.

    Science.gov (United States)

    Morales Diaz, Heidi; Mejares, Emil; Newman-Smith, Erin; Smith, William C

    2016-01-01

    The neural IgCAM family of cell adhesion molecules, which includes NCAM and related molecules, has evolved via gene duplication and alternative splicing to allow for a wide range of isoforms with distinct functions and homophilic binding properties. A search for neural IgCAMs in ascidians (Ciona intestinalis, Ciona savignyi, and Phallusia mammillata) has identified a novel set of truncated family members that, unlike the known members, lack fibronectin III domains and consist of only repeated Ig domains. Within the tunicates this form appears to be unique to the ascidians, and it was designated ACAM, for Ascidian Cell Adhesion Molecule. In C. intestinalis ACAM is expressed in the developing neural plate and neural tube, with strongest expression in the anterior sensory vesicle precursor. Unlike the two other conventional neural IgCAMs in C. intestinalis, which are expressed maternally and throughout the morula and blastula stages, ACAM expression initiates at the gastrula stage. Moreover, C. intestinalis ACAM is a target of the homeodomain transcription factor OTX, which plays an essential role in the development of the anterior central nervous system. Morpholino (MO) knockdown shows that ACAM is required for neural tube closure. In MO-injected embryos neural tube closure was normal caudally, but the anterior neuropore remained open. A similar phenotype was seen with overexpression of a secreted version of ACAM. The presence of ACAM in ascidians highlights the diversity of this gene family in morphogenesis and neurodevelopment.

  2. A practical clinical classification of spinal neural tube defects.

    Science.gov (United States)

    McComb, J Gordon

    2015-10-01

    Current commonly used terminology to describe neural tube defects (NTD) is inconsistent, overlapping, contradictory and, at times, inaccurate making it difficult to convey the nature of the malformation and what needs to be done to optimally treat patients with these congenital abnormalities.NTD can be broadly divided into those that are open with exposed neural tissue and leaking cerebrospinal fluid (CSF) and those that are closed with no exposed neural tissue nor loss of CSF. It appears that the loss of CSF during development is the underlying factor that leads to the entire central nervous system involvement with an open NTD and lack thereof with a closed NTD, wherein only the spinal cord is malformed. There are, however, rare transitional cases that bridge the gap between the two forms.Agreeing on a nomenclature that is used in a standard fashion would be of help in addressing this group of congenital anomalies that have a great deal of variability and, at times, can be quite complex.

  3. Screening for fetal aneuploidy and neural tube defects.

    Science.gov (United States)

    Driscoll, Deborah A; Gross, Susan J

    2009-11-01

    Maternal serum screening for neural tube defects and fetal aneuploidy in the second trimester has been incorporated into obstetrical practice over the past two decades. Now, as a result of several multicenter trials, first trimester screening between 11 and 14 weeks has been shown to be an effective and reliable screening test for Down syndrome and trisomy 18. This policy updates the American College of Medical Genetics policy statement entitled Second Trimester Maternal Serum Screening for Fetal Open Neural Tube Defects and Aneuploidy (2004), incorporates First trimester diagnosis and screening for fetal aneuploidy (2008) and complements the sections of American College of Medical Genetic's Standards and Guidelines for Clinical Genetics Laboratories entitled Prenatal Screening for Down syndrome (2005) and Prenatal Screening for Open Neural Tube Defects (2005).

  4. Planar cell polarity, ciliogenesis and neural tube defects.

    Science.gov (United States)

    Wallingford, John B

    2006-10-15

    Cilia are microtubule-based protrusions that are found on the surface of most vertebrate cells. Long studied by cell biologists, these organelles have recently caught the attention of developmental biologists and human geneticists. In this review, I will discuss recent findings suggesting a link between cilia and the planar cell polarity signaling cascade. In particular, I will focus on how this interaction may influence the process of neural tube closure and how these results may be relevant to our understanding of common human birth defects in which neural tube closure is compromised.

  5. Serum zinc levels in newborns with neural tube defects.

    Science.gov (United States)

    Golalipour, Mohammad Jafar; Mansourian, Azad Reza; Keshtkar, Abasali

    2006-09-01

    Neural tube defects (NTD) comprise of a group of congenital malformations that include spina bifida, anencephaly and encephalocele. Reports have implicated zinc deficiency as one of the causative factors of NTDs. We compared the serum zinc level of 23 newborns having neural tube defects with 35 healthy controls by spectrophotometery during 2003-2004. Zinc deficiency was documented in 43.5% of the cases and 8.6% of the controls (P = 0.002). Multivariate logistic regression analysis revealed a significant association between the presence of NTDs and zinc deficiency (OR = 8.2, 95% Cl: 1.9-34.7).

  6. Reduced-folate carrier (RFC is expressed in placenta and yolk sac, as well as in cells of the developing forebrain, hindbrain, neural tube, craniofacial region, eye, limb buds and heart

    Directory of Open Access Journals (Sweden)

    Prasad Puttur

    2003-07-01

    Full Text Available Abstract Background Folate is essential for cellular proliferation and tissue regeneration. As mammalian cells cannot synthesize folates de novo, tightly regulated cellular uptake processes have evolved to sustain sufficient levels of intracellular tetrahydrofolate cofactors to support biosynthesis of purines, pyrimidines, and some amino acids (serine, methionine. Though reduced-folate carrier (RFC is one of the major proteins mediating folate transport, knowledge of the developmental expression of RFC is lacking. We utilized in situ hybridization and immunolocalization to determine the developmental distribution of RFC message and protein, respectively. Results In the mouse, RFC transcripts and protein are expressed in the E10.0 placenta and yolk sac. In the E9.0 to E11.5 mouse embryo RFC is widely detectable, with intense signal localized to cell populations in the neural tube, craniofacial region, limb buds and heart. During early development, RFC is expressed throughout the eye, but by E12.5, RFC protein becomes localized to the retinal pigment epithelium (RPE. Conclusions Clinical studies show a statistical decrease in the number of neural tube defects, craniofacial abnormalities, cardiovascular defects and limb abnormalities detected in offspring of female patients given supplementary folate during pregnancy. The mechanism, however, by which folate supplementation ameliorates the occurrence of developmental defects is unclear. The present work demonstrates that RFC is present in placenta and yolk sac and provides the first evidence that it is expressed in the neural tube, craniofacial region, limb buds and heart during organogenesis. These findings suggest that rapidly dividing cells in the developing neural tube, craniofacial region, limb buds and heart may be particularly susceptible to folate deficiency.

  7. Metamizole Sodium Induces Neural Tube Defects in a Chick Embryo Model.

    Science.gov (United States)

    Guvenc, Yahya; Billur, Deniz; Aydin, Sevim; Ozeren, Ersin; Demirci, Adnan; Alagoz, Fatih; Dalgic, Ali; Belen, Deniz

    The aim of this study was to investigate the effects of metamizole sodium on neural tube development in the early stage chick embryo model that complies with the first month of embryonic development in mammals. A total of 40 fertilized chicken eggs were divided into 4 equal groups. The eggs were incubated in the incubator at a temperature of 37.8±2°C with 60±5% humidity. Group A was the control, Group B was administered physiological saline, Group C was administered 30 mg/kg metamizole sodium (based on the therapeutic index range of it used in humans) and Group D was administered 90 mg/kg metamizole sodium. All embryos were removed from the egg at the 48th hour and morphologically and histologically examined. Normal development was seen and the neural tube was closed in 17 embryos in Groups A and B. A neural tube defect was seen in 2 embryos in group A and in 1 embryo in group B. A neural tube closure defect was seen in all embryos in group C and 9 embryos in group D. There was 1 dead embryo in Group D. Metamizole sodium was seen to produce a neural tube defect in the chicken embyro model.

  8. How Many People Are Affected By or Are at Risk for Neural Tube Defects?

    Science.gov (United States)

    ... are affected by or are at risk for neural tube defects? Skip sharing on social media links Share ... with spina bifida. 1 The other types of neural tube defects are less common. About 340 infants are ...

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  20. SPECTRUM OF NEURAL-TUBE DEFECTS IN 34 INFANTS PRENATALLY EXPOSED TO ANTIEPILEPTIC DRUGS

    NARCIS (Netherlands)

    LINDHOUT, D; OMTZIGT, JGC; CORNEL, MC

    We analyzed the spectrum of neural-tube defects associated with maternal exposure to antiepileptic drugs (AEDs) and the possible contribution of familial and genetic factors to epilepsy or neural-tube defects. No specific association with maternal family history of neural-tube defects or epilepsy

  1. SPECTRUM OF NEURAL-TUBE DEFECTS IN 34 INFANTS PRENATALLY EXPOSED TO ANTIEPILEPTIC DRUGS

    NARCIS (Netherlands)

    LINDHOUT, D; OMTZIGT, JGC; CORNEL, MC

    1992-01-01

    We analyzed the spectrum of neural-tube defects associated with maternal exposure to antiepileptic drugs (AEDs) and the possible contribution of familial and genetic factors to epilepsy or neural-tube defects. No specific association with maternal family history of neural-tube defects or epilepsy wa

  2. Prevention of Neural Tube Defects. ARC Q&A #101-45.

    Science.gov (United States)

    Arc, Arlington, TX.

    This fact sheet uses a question-and-answer format to summarize issues related to the prevention of neural tube defects. Questions and answers address the following topics: what neural tube defects are and the most common types (spina bifida and anencephaly); occurrence of neural tube defects during the first month of pregnancy; the frequency of…

  3. Maternal hyperglycemia activates an ASK1-FoxO3a-caspase 8 pathway that leads to embryonic neural tube defects.

    Science.gov (United States)

    Yang, Peixin; Li, Xuezheng; Xu, Cheng; Eckert, Richard L; Reece, E Albert; Zielke, Horst Ronald; Wang, Fang

    2013-08-27

    Neural tube defects result from failure to completely close neural tubes during development. Maternal diabetes is a substantial risk factor for neural tube defects, and available evidence suggests that the mechanism that links hyperglycemia to neural tube defects involves oxidative stress and apoptosis. We demonstrated that maternal hyperglycemia correlated with activation of the apoptosis signal-regulating kinase 1 (ASK1) in the developing neural tube, and Ask1 gene deletion was associated with reduced neuroepithelial cell apoptosis and development of neural tube defects. ASK1 activation stimulated the activity of the transcription factor FoxO3a, which increased the abundance of the apoptosis-promoting adaptor protein TRADD, leading to activation of caspase 8. Hyperglycemia-induced apoptosis and the development of neural tube defects were reduced with genetic ablation of either FoxO3a or Casp8 or inhibition of ASK1 by thioredoxin. Examination of human neural tissues affected by neural tube defects revealed increased activation or abundance of ASK1, FoxO3a, TRADD, and caspase 8. Thus, activation of an ASK1-FoxO3a-TRADD-caspase 8 pathway participates in the development of neural tube defects, which could be prevented by inhibiting intermediates in this cascade.

  4. Novel Mode of Defective Neural Tube Closure in the Non-Obese Diabetic (NOD) Mouse Strain.

    Science.gov (United States)

    Salbaum, J Michael; Kruger, Claudia; MacGowan, Jacalyn; Herion, Nils J; Burk, David; Kappen, Claudia

    2015-11-23

    Failure to close the neural tube results in birth defects, with severity ranging from spina bifida to lethal anencephaly. Few genetic risk factors for neural tube defects are known in humans, highlighting the critical role of environmental risk factors, such as maternal diabetes. Yet, it is not well understood how altered maternal metabolism interferes with embryonic development, and with neurulation in particular. We present evidence from two independent mouse models of diabetic pregnancy that identifies impaired migration of nascent mesodermal cells in the primitive streak as the morphogenetic basis underlying the pathogenesis of neural tube defects. We conclude that perturbed gastrulation not only explains the neurulation defects, but also provides a unifying etiology for the broad spectrum of congenital malformations in diabetic pregnancies.

  5. Syndecan 4 interacts genetically with Vangl2 to regulate neural tube closure and planar cell polarity.

    Science.gov (United States)

    Escobedo, Noelia; Contreras, Osvaldo; Muñoz, Rosana; Farías, Marjorie; Carrasco, Héctor; Hill, Charlotte; Tran, Uyen; Pryor, Sophie E; Wessely, Oliver; Copp, Andrew J; Larraín, Juan

    2013-07-01

    Syndecan 4 (Sdc4) is a cell-surface heparan sulfate proteoglycan (HSPG) that regulates gastrulation, neural tube closure and directed neural crest migration in Xenopus development. To determine whether Sdc4 participates in Wnt/PCP signaling during mouse development, we evaluated a possible interaction between a null mutation of Sdc4 and the loop-tail allele of Vangl2. Sdc4 is expressed in multiple tissues, but particularly in the non-neural ectoderm, hindgut and otic vesicles. Sdc4;Vangl2(Lp) compound mutant mice have defective spinal neural tube closure, disrupted orientation of the stereocilia bundles in the cochlea and delayed wound healing, demonstrating a strong genetic interaction. In Xenopus, co-injection of suboptimal amounts of Sdc4 and Vangl2 morpholinos resulted in a significantly greater proportion of embryos with defective neural tube closure than each individual morpholino alone. To probe the mechanism of this interaction, we overexpressed or knocked down Vangl2 function in HEK293 cells. The Sdc4 and Vangl2 proteins colocalize, and Vangl2, particularly the Vangl2(Lp) mutant form, diminishes Sdc4 protein levels. Conversely, Vangl2 knockdown enhances Sdc4 protein levels. Overall HSPG steady-state levels were regulated by Vangl2, suggesting a molecular mechanism for the genetic interaction in which Vangl2(Lp/+) enhances the Sdc4-null phenotype. This could be mediated via heparan sulfate residues, as Vangl2(Lp/+) embryos fail to initiate neural tube closure and develop craniorachischisis (usually seen only in Vangl2(Lp/Lp)) when cultured in the presence of chlorate, a sulfation inhibitor. These results demonstrate that Sdc4 can participate in the Wnt/PCP pathway, unveiling its importance during neural tube closure in mammalian embryos.

  6. Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is Crucial for Neural Tube Closure.

    Science.gov (United States)

    Kimura-Yoshida, Chiharu; Mochida, Kyoko; Ellwanger, Kristina; Niehrs, Christof; Matsuo, Isao

    2015-06-01

    During primary neurulation, the separation of a single-layered ectodermal sheet into the surface ectoderm (SE) and neural tube specifies SE and neural ectoderm (NE) cell fates. The mechanisms underlying fate specification in conjunction with neural tube closure are poorly understood. Here, by comparing expression profiles between SE and NE lineages, we observed that uncommitted progenitor cells, expressing stem cell markers, are present in the neural plate border/neural fold prior to neural tube closure. Our results also demonstrated that canonical Wnt and its antagonists, DKK1/KREMEN1, progressively specify these progenitors into SE or NE fates in accord with the progress of neural tube closure. Additionally, SE specification of the neural plate border via canonical Wnt signaling is directed by the grainyhead-like 3 (Grhl3) transcription factor. Thus, we propose that the fate specification of uncommitted progenitors in the neural plate border by canonical Wnt signaling and its downstream effector Grhl3 is crucial for neural tube closure. This study implicates that failure in critical genetic factors controlling fate specification of progenitor cells in the neural plate border/neural fold coordinated with neural tube closure may be potential causes of human neural tube defects.

  7. Cell cycle-related genes p57kip2, Cdk5 and Spin in the pathogenesis of neural tube defects*

    Institute of Scientific and Technical Information of China (English)

    Xinjun Li; Zhong Yang; Yi Zeng; Hong Xu; Hongli Li; Yangyun Han; Xiaodong Long; Chao You

    2013-01-01

    In the field of developmental neurobiology, accurate and ordered regulation of the cel cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified several genes involved in the development of neural tube defects. In this study, we established a model of developmental neural tube defects by administration of retinoic acid to pregnant rats. Gene chip hybridization analysis showed that genes related to the cel cycle and apoptosis, signal transduction, transcription and translation regulation, energy and metabolism, heat shock, and matrix and cytoskeletal proteins were al involved in the formation of developmental neural tube defects. Among these, cel cycle-related genes were predominant. Retinoic acid ment caused differential expression of three cel cycle-related genes p57kip2, Cdk5 and Spin, the expression levels of which were downregulated by retinoic acid and upregulated during normal neural tube formation. The results of this study indicate that cel cycle-related genes play an im-portant role in the formation of neural tube defects. P57kip2, Cdk5 and Spin may be critical genes in the pathogenesis of neural tube defects.

  8. Cell cycle-related genes p57kip2, Cdk5 and Spin in the pathogenesis of neural tube defects.

    Science.gov (United States)

    Li, Xinjun; Yang, Zhong; Zeng, Yi; Xu, Hong; Li, Hongli; Han, Yangyun; Long, Xiaodong; You, Chao

    2013-07-15

    In the field of developmental neurobiology, accurate and ordered regulation of the cell cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified several genes involved in the development of neural tube defects. In this study, we established a model of developmental neural tube defects by administration of retinoic acid to pregnant rats. Gene chip hybridization analysis showed that genes related to the cell cycle and apoptosis, signal transduction, transcription and translation regulation, energy and metabolism, heat shock, and matrix and cytoskeletal proteins were all involved in the formation of developmental neural tube defects. Among these, cell cycle-related genes were predominant. Retinoic acid ment caused differential expression of three cell cycle-related genes p57kip2, Cdk5 and Spin, the expression levels of which were downregulated by retinoic acid and upregulated during normal neural tube formation. The results of this study indicate that cell cycle-related genes play an important role in the formation of neural tube defects. P57kip2, Cdk5 and Spin may be critical genes in the pathogenesis of neural tube defects.

  9. Cats, frogs, and snakes: early concepts of neural tube defects.

    Science.gov (United States)

    Obladen, Michael

    2011-11-01

    Disturbed neurulation fascinated scientists of all times. In Egypt, anencephalic infants were venerated as animal-headed gods. Roman law required them to be killed. The medieval world held the mother responsible, either because of assumed imagination or "miswatching," or because of suspected intercourse with animals or devils. Modern embryology and teratology began with the use of the microscope by Malpighi in 1672. Details of neural tube closure were described by Koelliker in 1861 and by His in 1874. From 1822, genetic disease and familial recurrence due to insufficient nutrition were discerned and lower social class identified as a risk factor. It took a century to define the malnutrition as insufficient folate intake. The mandatory supplementation of folate in staple foods successfully reduced the incidence of neural tube defects in the United States, Australia, Canada, and Chile, but it was not adopted by most European countries.

  10. From the Cover: Exposing Imidacloprid Interferes With Neurogenesis Through Impacting on Chick Neural Tube Cell Survival.

    Science.gov (United States)

    Liu, Meng; Wang, Guang; Zhang, Shi-Yao; Zhong, Shan; Qi, Guo-Long; Wang, Chao-Jie; Chuai, Manli; Lee, Kenneth Ka Ho; Lu, Da-Xiang; Yang, Xuesong

    2016-09-01

    As a neonicotinoid pesticide, imidacloprid is widely used to control insects in agriculture and fleas on domestic animals. However, it is not known whether imidacloprid exposure negatively affects neurogenesis during embryonic development. In this study, using a chick embryo model, we investigated the effects of imidacloprid exposure on neurogenesis at the earliest stage and during late-stage embryo development. Exposing HH0 chick embryos to imidacloprid in EC culture caused neural tube defects (NTDs) and neuronal differentiation dysplasia as determined by NF/Tuj1 labeling. Furthermore, we found that F-actin accumulation on the apical side of the neural tube was suppressed by exposure to imidacloprid, and the expression of BMP4 and Shh on the dorsal and ventral sides of the neural tubes, respectively, were also reduced, which in turn affects the dorsolateral hinge points during bending of the neural plate. In addition, exposure to imidacloprid reduced cell proliferation and increased cell apoptosis, as determined by pHIS3 labeling and TUNEL staining, respectively, also contributing to the malformation. We obtained similar results in late-stage embryos exposed to imidacloprid. Finally, a bioinformatics analysis was employed to determine which genes identified in this study were involved in NTDs. The experimental evidence and bioinformatics analysis suggested that imidacloprid exposure during chick embryo development could increase the risk of NTDs and neural dysplasia.

  11. The Netrin receptor Neogenin is required for neural tube formation and somitogenesis in zebrafish.

    Science.gov (United States)

    Mawdsley, David J; Cooper, Helen M; Hogan, Benjamin M; Cody, Stephen H; Lieschke, Graham J; Heath, Joan K

    2004-05-01

    The Netrin receptor Deleted in colon cancer (Dcc) has been shown to play a pivotal role in the guidance of nascent axons towards the ventral midline in the developing nervous systems of both vertebrates and invertebrates. In contrast, the function during embryogenesis of a second Dcc-like Netrin receptor Neogenin has not yet been defined. We used antisense morpholino oligonucleotides to knockdown Neogenin activity in zebrafish embryos and demonstrate that Neogenin plays an important role in neural tube formation and somitogenesis. In Neogenin knockdown embryos, cavitation within the neural rod failed to occur, producing a neural tube lacking a lumen. Somite formation was also defective, implicating Neogenin in the migration events underlying convergent extension during gastrulation. These observations suggest a role for Neogenin in determining cell polarity or migrational directionality of both neuroectodermal and mesodermal cells during early embryonic development.

  12. The novel mouse mutant, chuzhoi, has disruption of Ptk7 protein and exhibits defects in neural tube, heart and lung development and abnormal planar cell polarity in the ear

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    Paudyal Anju

    2010-08-01

    Full Text Available Abstract Background The planar cell polarity (PCP signalling pathway is fundamental to a number of key developmental events, including initiation of neural tube closure. Disruption of the PCP pathway causes the severe neural tube defect of craniorachischisis, in which almost the entire brain and spinal cord fails to close. Identification of mouse mutants with craniorachischisis has proven a powerful way of identifying molecules that are components or regulators of the PCP pathway. In addition, identification of an allelic series of mutants, including hypomorphs and neomorphs in addition to complete nulls, can provide novel genetic tools to help elucidate the function of the PCP proteins. Results We report the identification of a new N-ethyl-N-nitrosourea (ENU-induced mutant with craniorachischisis, which we have named chuzhoi (chz. We demonstrate that chuzhoi mutant embryos fail to undergo initiation of neural tube closure, and have characteristics consistent with defective convergent extension. These characteristics include a broadened midline and reduced rate of increase of their length-to-width ratio. In addition, we demonstrate disruption in the orientation of outer hair cells in the inner ear, and defects in heart and lung development in chuzhoi mutants. We demonstrate a genetic interaction between chuzhoi mutants and both Vangl2Lp and Celsr1Crsh mutants, strengthening the hypothesis that chuzhoi is involved in regulating the PCP pathway. We demonstrate that chuzhoi maps to Chromosome 17 and carries a splice site mutation in Ptk7. This mutation results in the insertion of three amino acids into the Ptk7 protein and causes disruption of Ptk7 protein expression in chuzhoi mutants. Conclusions The chuzhoi mutant provides an additional genetic resource to help investigate the developmental basis of several congenital abnormalities including neural tube, heart and lung defects and their relationship to disruption of PCP. The chuzhoi mutation

  13. A dynamic code of dorsal neural tube genes regulates the segregation between neurogenic and melanogenic neural crest cells.

    Science.gov (United States)

    Nitzan, Erez; Krispin, Shlomo; Pfaltzgraff, Elise R; Klar, Avihu; Labosky, Patricia A; Kalcheim, Chaya

    2013-06-01

    Understanding when and how multipotent progenitors segregate into diverse fates is a key question during embryonic development. The neural crest (NC) is an exemplary model system with which to investigate the dynamics of progenitor cell specification, as it generates a multitude of derivatives. Based on 'in ovo' lineage analysis, we previously suggested an early fate restriction of premigratory trunk NC to generate neural versus melanogenic fates, yet the timing of fate segregation and the underlying mechanisms remained unknown. Analysis of progenitors expressing a Foxd3 reporter reveals that prospective melanoblasts downregulate Foxd3 and have already segregated from neural lineages before emigration. When this downregulation is prevented, late-emigrating avian precursors fail to upregulate the melanogenic markers Mitf and MC/1 and the guidance receptor Ednrb2, generating instead glial cells that express P0 and Fabp. In this context, Foxd3 lies downstream of Snail2 and Sox9, constituting a minimal network upstream of Mitf and Ednrb2 to link melanogenic specification with migration. Consistent with the gain-of-function data in avians, loss of Foxd3 function in mouse NC results in ectopic melanogenesis in the dorsal tube and sensory ganglia. Altogether, Foxd3 is part of a dynamically expressed gene network that is necessary and sufficient to regulate fate decisions in premigratory NC. Their timely downregulation in the dorsal neural tube is thus necessary for the switch between neural and melanocytic phases of NC development.

  14. An epidemiologic study of mitochondrial membrane transporter protein gene polymorphism and risk factors for neural tube defects in Shanxi, China

    Institute of Scientific and Technical Information of China (English)

    Zhizhen Liu; Jun Xie; Tiane Luo; Tao Zhang; Xia Zhao; Hong Zhao; Peizhen Li

    2012-01-01

    The present study involved a questionnaire survey of 156 mothers that gave birth to children with neural tube defects or had a history of pregnancy resulting in children with neural tube defects (case group) and 156 control mothers with concurrent healthy children (control group) as well as detection of mitochondrial membrane transporter protein gene [uncoupling protein 2 (UCP2)] polymorphism. The maternal UCP2 3' untranslated region (UTR) D/D genotype and D allele frequency were significantly higher in the case group compared with the control group (odds ratio (OR) 3.233; 95% confidence interval (CI) 1.103-9.476; P = 0.040; OR: 3.484; 95% CI: for neural tube defects 2.109-5.753; P < 0.001). Univariate and multivariate logistic regression analysis of risk factors for neural tube defects showed that a maternal UCP2 3' UTR D/D genotype was negatively interacted with the mothers'consumption of frequent fresh fruit and vegetables (S = 0.007), positively interacted with the mothers'frequency of germinated potato consumption (S = 2.15) and positively interacted with the mothers' body mass index (S = 3.50). These findings suggest that maternal UCP2 3' UTR gene polymorphism, pregnancy time, consumption of germinated potatoes and body mass index are associated with an increased risk for neural tube defects in children from mothers living in Shanxi province, China. Moreover, there is an apparent gene-environment interaction involved in the development of neural tube defects in offspring.

  15. parachute/n-cadherin is required for morphogenesis and maintained integrity of the zebrafish neural tube.

    Science.gov (United States)

    Lele, Zsolt; Folchert, Anja; Concha, Miguel; Rauch, Gerd-Jörg; Geisler, Robert; Rosa, Frédéric; Wilson, Steve W; Hammerschmidt, Matthias; Bally-Cuif, Laure

    2002-07-01

    N-cadherin (Ncad) is a classical cadherin that is implicated in several aspects of vertebrate embryonic development, including somitogenesis, heart morphogenesis, neural tube formation and establishment of left-right asymmetry. However, genetic in vivo analyses of its role during neural development have been rather limited. We report the isolation and characterization of the zebrafish parachute (pac) mutations. By mapping and candidate gene analysis, we demonstrate that pac corresponds to a zebrafish n-cadherin (ncad) homolog. Three mutant alleles were sequenced and each is likely to encode a non-functional Ncad protein. All result in a similar neural tube phenotype that is most prominent in the midbrain, hindbrain and the posterior spinal cord. Neuroectodermal cell adhesion is altered, and convergent cell movements during neurulation are severely compromised. In addition, many neurons become progressively displaced along the dorsoventral and the anteroposterior axes. At the cellular level, loss of Ncad affects beta-catenin stabilization/localization and causes mispositioned and increased mitoses in the dorsal midbrain and hindbrain, a phenotype later correlated with enhanced apoptosis and the appearance of ectopic neurons in these areas. Our results thus highlight novel and crucial in vivo roles for Ncad in the control of cell convergence, maintenance of neuronal positioning and dorsal cell proliferation during vertebrate neural tube development.

  16. DNA delivery into anterior neural tube of zebrafish embryos by electroporation.

    Science.gov (United States)

    Teh, Cathleen; Chong, Shang Wei; Korzh, Vladimir

    2003-11-01

    The zebrafish is widely used for functional studies of vertebrate genes. It is accessible to manipulations during all stages of embryogenesis because the embryo develops externally and is optically transparent. However, functional studies conducted on the zebrafish have been generally limited to the earliest phase of activity of the gene of interest, which is a limitation in studies of genes that are expressed at various stages of embryonic development. It is therefore necessary to develop methods that allow for the modulation of gene activity during later stages of zebrafish development while leaving earlier functions intact. We have successfully electroporated the green fluorescent protein (GFP) reporter gene into the neural tube of the zebrafish embryo in a unidirectional or bilateral manner. This approach can be used for the functional analysis of the late role of developmental genes in the neural tube of zebrafish embryo and larvae.

  17. Stretching cell morphogenesis during late neurulation and mild neural tube defects.

    Science.gov (United States)

    Korzh, Vladimir

    2014-08-01

    Neurulation is defined as a process of neural tube closure. Recent reports suggested that upon completion of this process the major factors of neurulation remain in force at least until the central canal of the neural tube is formed. Hence, an idea has been put forward to define the two periods of neurulation: early neurulation corresponds to the period of neural tube closure and late neurulation corresponds to the period of formation of the central canal. These ideas are discussed in a context of neural tube defects that may affect late neurulation and result in distention of the central canal.

  18. Cellular basis of neuroepithelial bending during mouse spinal neural tube closure.

    Science.gov (United States)

    McShane, Suzanne G; Molè, Matteo A; Savery, Dawn; Greene, Nicholas D E; Tam, Patrick P L; Copp, Andrew J

    2015-08-15

    Bending of the neural plate at paired dorsolateral hinge points (DLHPs) is required for neural tube closure in the spinal region of the mouse embryo. As a step towards understanding the morphogenetic mechanism of DLHP development, we examined variations in neural plate cellular architecture and proliferation during closure. Neuroepithelial cells within the median hinge point (MHP) contain nuclei that are mainly basally located and undergo relatively slow proliferation, with a 7 h cell cycle length. In contrast, cells in the dorsolateral neuroepithelium, including the DLHP, exhibit nuclei distributed throughout the apico-basal axis and undergo rapid proliferation, with a 4 h cell cycle length. As the neural folds elevate, cell numbers increase to a greater extent in the dorsolateral neural plate that contacts the surface ectoderm, compared with the more ventromedial neural plate where cells contact paraxial mesoderm and notochord. This marked increase in dorsolateral cell number cannot be accounted for solely on the basis of enhanced cell proliferation in this region. We hypothesised that neuroepithelial cells may translocate in a ventral-to-dorsal direction as DLHP formation occurs, and this was confirmed by vital cell labelling in cultured embryos. The translocation of cells into the neural fold, together with its more rapid cell proliferation, leads to an increase in cell density dorsolaterally compared with the more ventromedial neural plate. These findings suggest a model in which DLHP formation may proceed through 'buckling' of the neuroepithelium at a dorso-ventral boundary marked by a change in cell-packing density.

  19. Epidemiology of the neural tube defects in Kashmir Valley

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    Masood Ahmed Laharwal

    2016-01-01

    Full Text Available Introduction/Background: Neural tube defects (NTD are the most common congenital malformations affecting the brain and spinal cord and have a multifactorial etiology. Genetic and environmental factors have been found to cause these defects, both individually and in combination. Aims and Objectives: The aim of this study was to determine the incidence, types, demographics, risk factors, and other associated anomalies relevant to NTDs in Kashmir Valley. Materials and Methods: A 2-year hospital-based prospective study was carried out from November 2013 to October 2015. A detailed history of the mother was taken along with detailed clinical examination of neonate including measurement of head circumference and checking the status of fontanella, whether - lax/full/bulging/or tense, type of NTD. Investigations that were done included were X-ray skull: Anteroposterior (AP and lateral, X-ray spine: AP and lateral, ultrasonography abdomen, magnetic resonance imaging: Spine and brain. Results: The total number of babies with NTD's was 125 with an overall incidence of 0.503. District Kupwara was having the highest incidence (1.047 and district Srinagar the lowest incidence of NTD's (0.197. The majority of NTD's (116 cases, 92.8% were found in the rural areas. Among the different types of NTD's, spina bifida had an incidence of 0.342 (85 cases, 68%, and anencephaly had an incidence of 0.113 (28 cases, 22.4%. There was a slight preponderance of females over males with NTD's. There were70 females (56% and 55 males (44% respectively with a male:female ratio of 0.8:1. Conclusions: The incidence rates of NTDs are very high for Kashmir Valley. Geographical distribution of NTDs at this place confirms a relationship between the socioeconomic status, educational status, maternal age and environmental factors for the development of an NTD. The results of this study point to the importance establishing a health policy to prevent NTDs in Kashmir Valley.

  20. Mutations in the Motile Cilia Gene DNAAF1 Are Associated with Neural Tube Defects in Humans

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    Chunyue Miao

    2016-10-01

    Full Text Available Neural tube defects (NTDs are severe malformations of the central nervous system caused by complex genetic and environmental factors. Among genes involved in NTD, cilia-related genes have been well defined and found to be essential for the completion of neural tube closure (NTC. We have carried out next-generation sequencing on target genes in 373 NTDs and 222 healthy controls, and discovered eight disease-specific rare mutations in cilia-related gene DNAAF1. DNAAF1 plays a central role in cytoplasmic preassembly of distinct dynein-arm complexes, and is expressed in some key tissues involved in neural system development, such as neural tube, floor plate, embryonic node, and brain ependyma epithelial cells in zebrafish and mouse. Therefore, we evaluated the expression and functions of mutations in DNAAF1 in transfected cells to analyze the potential correlation of these mutants to NTDs in humans. One rare frameshift mutation (p.Gln341Argfs*10 resulted in significantly diminished DNAAF1 protein expression, compared to the wild type. Another mutation, p.Lys231Gln, disrupted cytoplasmic preassembly of the dynein-arm complexes in cellular assay. Furthermore, results from NanoString assay on mRNA from NTD samples indicated that DNAAF1 mutants altered the expression level of NTC-related genes. Altogether, these findings suggest that the rare mutations in DNAAF1 may contribute to the susceptibility for NTDs in humans.

  1. Division of labor during trunk neural crest development.

    Science.gov (United States)

    Gammill, Laura S; Roffers-Agarwal, Julaine

    2010-08-15

    Neural crest cells, the migratory precursors of numerous cell types including the vertebrate peripheral nervous system, arise in the dorsal neural tube and follow prescribed routes into the embryonic periphery. While the timing and location of neural crest migratory pathways has been well documented in the trunk, a comprehensive collection of signals that guides neural crest migration along these paths has only recently been established. In this review, we outline the molecular cascade of events during trunk neural crest development. After describing the sequential routes taken by trunk neural crest cells, we consider the guidance cues that pattern these neural crest trajectories. We pay particular attention to segmental neural crest development and the steps and signals that generate a metameric peripheral nervous system, attempting to reconcile conflicting observations in chick and mouse. Finally, we compare cranial and trunk neural crest development in order to highlight common themes.

  2. Professor John Scott, folate and neural tube defects.

    Science.gov (United States)

    Hoffbrand, A Victor

    2014-02-01

    John Scott (1940-2013) was born in Dublin where he was to spend the rest of his career, both as an undergraduate and subsequently Professor of Biochemistry and Nutrition at Trinity College. His research with the talented group of scientists and clinicians that he led has had a substantial impact on our understanding of folate metabolism, mechanisms of its catabolism and deficiency. His research established the leading theory of folate involvement with vitamin B12 in the pathogenesis of vitamin B12 neuropathy. He helped to establish the normal daily intake of folate and the increased requirements needed either in food or as a supplement before and during pregnancy to prevent neural tube defects. He also suggested a dietary supplement of vitamin B12 before and during pregnancy to reduce the risk of neural tube defects. It would be an appropriate epitaph if fortification of food with folic acid became mandatory in the UK and Ireland, as it is in over 70 other countries. © 2013 John Wiley & Sons Ltd.

  3. Prediction of friction factor of pure water flowing inside vertical smooth and microfin tubes by using artificial neural networks

    Science.gov (United States)

    Çebi, A.; Akdoğan, E.; Celen, A.; Dalkilic, A. S.

    2017-02-01

    An artificial neural network (ANN) model of friction factor in smooth and microfin tubes under heating, cooling and isothermal conditions was developed in this study. Data used in ANN was taken from a vertically positioned heat exchanger experimental setup. Multi-layered feed-forward neural network with backpropagation algorithm, radial basis function networks and hybrid PSO-neural network algorithm were applied to the database. Inputs were the ratio of cross sectional flow area to hydraulic diameter, experimental condition number depending on isothermal, heating, or cooling conditions and mass flow rate while the friction factor was the output of the constructed system. It was observed that such neural network based system could effectively predict the friction factor values of the flows regardless of their tube types. A dependency analysis to determine the strongest parameter that affected the network and database was also performed and tube geometry was found to be the strongest parameter of all as a result of analysis.

  4. Prediction of friction factor of pure water flowing inside vertical smooth and microfin tubes by using artificial neural networks

    Science.gov (United States)

    Çebi, A.; Akdoğan, E.; Celen, A.; Dalkilic, A. S.

    2016-06-01

    An artificial neural network (ANN) model of friction factor in smooth and microfin tubes under heating, cooling and isothermal conditions was developed in this study. Data used in ANN was taken from a vertically positioned heat exchanger experimental setup. Multi-layered feed-forward neural network with backpropagation algorithm, radial basis function networks and hybrid PSO-neural network algorithm were applied to the database. Inputs were the ratio of cross sectional flow area to hydraulic diameter, experimental condition number depending on isothermal, heating, or cooling conditions and mass flow rate while the friction factor was the output of the constructed system. It was observed that such neural network based system could effectively predict the friction factor values of the flows regardless of their tube types. A dependency analysis to determine the strongest parameter that affected the network and database was also performed and tube geometry was found to be the strongest parameter of all as a result of analysis.

  5. C5a receptor signaling prevents folate deficiency-induced neural tube defects in mice.

    Science.gov (United States)

    Denny, Kerina J; Coulthard, Liam G; Jeanes, Angela; Lisgo, Steven; Simmons, David G; Callaway, Leonie K; Wlodarczyk, Bogdan; Finnell, Richard H; Woodruff, Trent M; Taylor, Stephen M

    2013-04-01

    The complement system is involved in a range of diverse developmental processes, including cell survival, growth, differentiation, and regeneration. However, little is known about the role of complement in embryogenesis. In this study, we demonstrate a novel role for the canonical complement 5a receptor (C5aR) in the development of the mammalian neural tube under conditions of maternal dietary folic acid deficiency. Specifically, we found C5aR and C5 to be expressed throughout the period of neurulation in wild-type mice and localized the expression to the cephalic regions of the developing neural tube. C5aR was also found to be expressed in the neuroepithelium of early human embryos. Ablation of the C5ar1 gene or the administration of a specific C5aR peptide antagonist to folic acid-deficient pregnant mice resulted in a high prevalence of severe anterior neural tube defect-associated congenital malformations. These findings provide a new and compelling insight into the role of the complement system during mammalian embryonic development.

  6. Morphogenetic movements during cranial neural tube closure in the chick embryo and the effect of homocysteine.

    NARCIS (Netherlands)

    Brouns, M.R.; Afman, L.A.; Hauten, B.A.M. van; Hekking, J.W.M.; Köhler, E.S.; Straaten, H.W.M. van

    2005-01-01

    In order to unravel morphogenetic mechanisms involved in neural tube closure, critical cell movements that are fundamental to remodelling of the cranial neural tube in the chick embryo were studied in vitro by quantitative time-lapse video microscopy. Two main directions of movements were observed.

  7. Morphogenetic movements during cranial neural tube closure in the chick embryo and the effect of homocysteine

    NARCIS (Netherlands)

    Brouns, M.R.; Afman, L.A.; VanHauten, B.A.M.; Hekking, J.W.M.; Kohler, E.S.; Straaten, van H.W.M.

    2005-01-01

    In order to unravel morphogenetic mechanisms involved in neural tube closure, critical cell movements that are fundamental to remodelling of the cranial neural tube in the chick embryo were studied in vitro by quantitative time-lapse video microscopy. Two main directions of movements were observed.

  8. Birth order and neural tube defects: a reappraisal.

    Science.gov (United States)

    Vieira, Alexandre R

    2004-01-15

    There is evidence that late birth order is associated with some complex disorders. For neural tube defects (NTDs) there is no consensus as to whether first or increased birth order is associated or not. A meta-analysis of published data on NTDs was carried out to ascertain whether there is an increased risk for children first born or of high birth order to have NTDs. All data available with information regarding the frequency of live births and NTDs cases by birth order (1, 2, 3, and 4 or more) were included in the analysis. Effect sizes calculations were performed. Children with higher birth order are more likely to have spina bifida but not anencephaly. This same effect was also seen for all NTDs combined, which probably reflects the association with spina bifida. These results suggest the compilation of anencephaly and spina bifida data can be the explanation for the controversies seen in the literature.

  9. Maternal herpes labialis in pregnancy and neural tube defects.

    Science.gov (United States)

    Nørgård, Bente; Nørgaard, Mette; Czeizel, Andrew E; Puhó, Erzsébet; Sørensen, Henrik T

    2006-08-01

    According to previous case reports, some congenital abnormalities (CAs) of the brain, such as microcephaly, are a result of intrauterine herpes simplex virus infection. A population-based case-control study was conducted to determine the risk of neural tube defects (NTDs) after maternal herpes labialis infection during pregnancy. Data were taken from the Hungarian Case-Control Surveillance of Congenital Abnormalities from 1980 to 1996, which included 1202 children with NTDs and 21641 comparison children with CAs other than NTDs. The adjusted relative risks (odds ratio [OR]) for NTDs associated with maternal herpes labialis in the first trimester of pregnancy was OR 1.19 (95% confidence interval [CI] 0.68-2.06), and in the entire pregnancy was OR 0.94 (95% CI 0.61-1.44). Self-reported maternal herpes labialis during pregnancy was not associated with a substantially increased risk of NTDs in infants.

  10. Chromosomal Abnormalities Associated with Neural Tube Defects (I: Full Aneuploidy

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    Chih-Ping Chen

    2007-12-01

    Full Text Available Fetuses with neural tube defects (NTDs carry a risk of chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with other structural abnormalities, and family history of chromosome aberrations. This article provides an overview of chromosomal abnormalities associated with NTDs in embryos, fetuses, and newborn patients, and a comprehensive review of numerical chromosomal abnormalities associated with NTDs, such as trisomy 18, trisomy 13, triploidy, trisomy 9, trisomy 2, trisomy 21, trisomy 7, trisomy 8, trisomy 14, trisomy 15, trisomy 16, trisomy 5 mosaicism, trisomy 11 mosaicism, trisomy 20 mosaicism, monosomy X, and tetraploidy. NTDs may be associated with aneuploidy. Perinatal identification of NTDs should alert one to the possibility of chromosomal abnormalities and prompt a thorough cytogenetic investigation and genetic counseling.

  11. Implications of Zinc on Fetal Neural Tube Defects

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    Rajeev Vats

    2012-07-01

    Full Text Available Zinc is essential for normal growth and differentiation in all mammalian species and it is reported that folic acid supplementation has reduced the incidence of neural tube defects (NTD. It is still considered one of the important congenital malformations having wide implications. Zinc deficiency has been reported to produce NTD in animals. The present study was undertaken to evaluate zinc status of newborn babies with NTD and their mothers. Blood samples were taken from 287 mothers and their babies having NTD and from 110 controls visiting hospitals and health clinics. Zinc level as µg/ml for blood and serum and µg/g for cell mass were determined on GBC 932 atomic absorption spectrophotometer (Australia by fluorometery. The mean maternal blood, serum and cell mass concentration in NTD group (14.56 ± 1.34 µg/ml, 0.6 ± 0.01 µg/ml, 5.64 ± 0.35 µg/gm respectively were significantly lower than those of the control mothers (24.15 ± 2.95 µg/ml, 0.72 ± 0.03 µg/ml, 7.37 ± 0.44 µg/gm respectively. There is a significant decrease in the concentration of Zinc in newborns having NTD (15.65 ± 3.18 µg/ml, 0.56 ± 0.08 µg/ml, 5.11 ± 0.18 µg/gm respectively as compared with normal newborns (28.04 ± 1.1 µg/ml, 0.59 ± 0.08 µg/ml and 6.08 ± 0.29 µg/gm respectively. Maternal nutritional zinc deficiency in newborns and their mothers is thought to be one of the factors responsible for NTD. However, the lowered zinc concentration may be influencing the causation of NTD. More investigations on zinc status in mothers during antenatal period, especially in the prenatal development and antenatal zinc status including normal babies and NTD babies are required at population level.

  12. Isolation and culture of neural crest cells from embryonic murine neural tube.

    Science.gov (United States)

    Pfaltzgraff, Elise R; Mundell, Nathan A; Labosky, Patricia A

    2012-06-02

    The embryonic neural crest (NC) is a multipotent progenitor population that originates at the dorsal aspect of the neural tube, undergoes an epithelial to mesenchymal transition (EMT) and migrates throughout the embryo, giving rise to diverse cell types. NC also has the unique ability to influence the differentiation and maturation of target organs. When explanted in vitro, NC progenitors undergo self-renewal, migrate and differentiate into a variety of tissue types including neurons, glia, smooth muscle cells, cartilage and bone. NC multipotency was first described from explants of the avian neural tube. In vitro isolation of NC cells facilitates the study of NC dynamics including proliferation, migration, and multipotency. Further work in the avian and rat systems demonstrated that explanted NC cells retain their NC potential when transplanted back into the embryo. Because these inherent cellular properties are preserved in explanted NC progenitors, the neural tube explant assay provides an attractive option for studying the NC in vitro. To attain a better understanding of the mammalian NC, many methods have been employed to isolate NC populations. NC-derived progenitors can be cultured from post-migratory locations in both the embryo and adult to study the dynamics of post-migratory NC progenitors, however isolation of NC progenitors as they emigrate from the neural tube provides optimal preservation of NC cell potential and migratory properties. Some protocols employ fluorescence activated cell sorting (FACS) to isolate a NC population enriched for particular progenitors. However, when starting with early stage embryos, cell numbers adequate for analyses are difficult to obtain with FACS, complicating the isolation of early NC populations from individual embryos. Here, we describe an approach that does not rely on FACS and results in an approximately 96% pure NC population based on a Wnt1-Cre activated lineage reporter. The method presented here is adapted from

  13. A unique missense allele of BAF155, a core BAF chromatin remodeling complex protein, causes neural tube closure defects in mice.

    Science.gov (United States)

    Harmacek, Laura; Watkins-Chow, Dawn E; Chen, Jianfu; Jones, Kenneth L; Pavan, William J; Salbaum, J Michael; Niswander, Lee

    2014-05-01

    Failure of embryonic neural tube closure results in the second most common class of birth defects known as neural tube defects (NTDs). While NTDs are likely the result of complex multigenic dysfunction, it is not known whether polymorphisms in epigenetic regulators may be risk factors for NTDs. Here we characterized Baf155(msp3) , a unique ENU-induced allele in mice. Homozygous Baf155(mps3) embryos exhibit highly penetrant exencephaly, allowing us to investigate the roles of an assembled, but malfunctional BAF chromatin remodeling complex in vivo at the time of neural tube closure. Evidence of defects in proliferation and apoptosis were found within the neural tube. RNA-Seq analysis revealed that surprisingly few genes showed altered expression in Baf155 mutant neural tissue, given the broad epigenetic role of the BAF complex, but included genes involved in neural development and cell survival. Moreover, gene expression changes between individual mutants were variable even though the NTD was consistently observed. This suggests that inconsistent gene regulation contributes to failed neural tube closure. These results shed light on the role of the BAF complex in the process of neural tube closure and highlight the importance of studying missense alleles to understand epigenetic regulation during critical phases of development.

  14. EPIDEMIOLOGY OF NEURAL TUBE DEFECTS IN THE WORLD AND IRAN

    Directory of Open Access Journals (Sweden)

    D.D. Farhud

    2000-08-01

    Full Text Available Statistical data from 1966 till 1995 showed that Neural tube defects, in the American continent, Venezuela had the highest prevalence of 38.9 and some Latin American countries showed the low of 7.7. In Europe, Norway had the highest prevalence of 68, and Denmark the lowest, 5.8. In Asia, India had the highest of 181.8 and Japan the lowest of 10. In Africa, Nigeria had the highest of 70 and Negroes of South Africa had the lowest of 9.9. In Australia the figure was 20.05. According to the statistics available of the years 1967 till 1996, anencephaly in China had the highest prevalence of 87. In the American continent, state of Michigan in the USA had the highest of 10.5 and Jamaica, in Central America, had the lowest of 2.6. In Europe, Turkey with 16.4 and Italy with 2.73; in Asia, China with 87 and Iran with 0.8 had the highest and the lowest prevalence, respectively. In Africa, Nigeria with 3.5, and in Oceania, Newzeland with 7.8 in 10000, were reported. Data available on spina bifida, from the years 1968 till 1991 showed the highest prevalence in China with 36, and the lowest in the Alps Mountains with 0.55 in 10000 individuals. In the American continent, state of Arkansas with 7.8 and California with 3.87; in Europe, England with 23.1 and Rhein-Alp with 0.55 in 10000 had the highest and the lowest prevalence. Finally, in China this rate was 36, in Australia 10, in Newzeland 9.4, and in Nigeria 7/10000. In a study carried out in Tehran, from 1969 till 1978 by the authors, out of 13037 births, (17.6 in 10000 newborns had neural tube defects, with anencephaly 0.8 and spina bifida 3.8/10000. In a new study on 8585 deliveries (1991-1997 in Hamadan (a North West province of Iran, Prevalence of total NTDs was 50.1/10000, anencephaly 15.6 and spin bifida 6.98.

  15. Slit2/Robo1信号对鸡胚早期神经管及体节发育的影响%Role of Slit2/Robo1 signaling in development of neural tube and somites in early chick embryos

    Institute of Scientific and Technical Information of China (English)

    王广; 王晓钰; 李艳; 王丽京; 雷健; 张笑坛; 耿建国; 杨雪松

    2011-01-01

    目的:探讨Slit2/Robo1对鸡胚早期神经管和体节发育的影响.方法:显微注射法将质粒注射入HH10期胚胎神经管内,活体胚胎细胞电穿孔方法转染胚胎半侧神经管,以另一侧神经管为对照侧,原位杂交及免疫荧光方法观察转染10 h后神经管的发育和神经嵴细胞迁移至体节的情况.结果:下调Robo1侧神经管发育较正常对照侧异常,同时发现Slug表达和神经嵴细胞迁移至体节路线发生改变.结论:Slit2/Robo1信号可能通过影响Slug基因表达,对胚胎早期神经管闭合、神经嵴细胞正常产生及迁移方向以及体节分化有重要作用.%AIM: To investigate the effects of Slit2/Robo1 signaling on the development of neural tube and somites in early chick embryos.METHODS: Plasmid DNA was injected into the lumen of the neural tube from dorsal side of HH10 chick embryo using microinjection, and then in ovo electroporation was performed at half - side of neural tube while another side served as control.Subsequent 10 - hour incubation was carried on after transfection until the development of neural tube and neural crest cells migrating to somites were investigated using the methods of immunofluorescence and in situ hybridization.RESULTS: Blocking Slit2/Robo1 signaling resulted in abnormal development of neural tube, while the expression of Slug and neural crest cells migrating to somites pathway were abnormal as well.CONCLUSION: Slit2/Robo1 signaling can affect the expression of Slug and play an important role in the fusion of neural fold, the trajectory of generation and migration of neural crest cells, and the differentiation of somites in early chick embryos.

  16. COMPREHENSIVE STUDY OF NEURAL TUBE DEFECTS IN 1000 FOETUSES WITH CLINICAL SPECTRUM

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    Himabindu. N

    2015-12-01

    Full Text Available Introduction: A variety of malformations are included under the description of Neural tube defects (NTDs. These are abnormalities of the embryonic neuralization process. The congenital malformations of human structure and are of great interest to anatomists, obstetricians, pediatricians and radiologists. NTDs are among the commonest and most severe disorders, affecting 0.5-2 per 1000 established pregnancies, and are second commonest group of birth defects, after congenital heart defects. A valuable contribution of this study, the neural tube defects aimed at clinical methods and refined for the prenatal diagnosis in utero. Materials and Methods: This comprehensive study was undertaken to know the incidence of detail knowledge of neural tube defects in KIMS Narketpally and KAMS & RC Hyderabad, among 1000 births during the period of two years. We found seven fetuses with neural tube defects involving brain and spinal cord. A detailed study was done emphasizing on embryology and genetic and non-genetic concepts. Results & Conclusion: The seven fetuses were stillbirths and aborted babies between 20 to 40 weeks, presented with neural tube defects (0.7%. Five fetuses were females and two fetuses were males. The spinal defects were 0.4%, cranial defects 0.2% and complete neural tube defects is 0.1%. This review article discusses the classification, clinical research and epidemiological understanding of NTDs and correlated with the available literatures.

  17. Folate receptor gene variants and neural tube defect occurrence

    Energy Technology Data Exchange (ETDEWEB)

    Finnell, R.; Greer, K. [Texas A& M Univ., College Station, TX (United States); Lammer, E. [Stanford Univ., Palo Alto, CA (United States)] [and others

    1994-09-01

    Recent epidemiological evidence shows that periconceptional use of folic acid supplements may prevent 40-50% of neural tube defects (NTDs). The FDA has subsequently recommended folic acid supplementation of all women of childbearing potential, even though the mechanism by which folic acid prevents NTDs is unknown. We investigated genetic variation of a candidate gene, the 5-methyltetrahydrofolate (5-MeTHF) receptor, that may mediate this preventive effect. The receptor concentrates folate within cells and we have localized its mRNA to neuroepithelial cells during neurulation. Our hypothesis is that dysfunctional 5-MeTHF receptors inadequately concentrate folate intracellularly, predisposing infants to NTDs. We have completed SSCP analysis on 3 of the 4 coding exons of the 5-MeTHF receptor gene of 474 infants participating in a large population-based epidemiological case-control study of NTDs in California; genotyping of another 500 infants is ongoing. Genomic DNA was extracted from residual blood spots from newborn screening samples of cases and controls. Genotyping was done blinded to case status. Polymorphisms have been detected for exons 4 and 5; fourteen percent of the infants have exon 5 polymorphisms. Data will be presented on the prevalence of 5-MeTHF receptor polymorphisms among cases and controls. Relationships among the polymorphisms and NTD occurrence may shed light on how folic acid supplementation prevents NTDs.

  18. Genetic, chromosomal, and syndromic causes of neural tube defects

    Science.gov (United States)

    Seidahmed, Mohammed Z.; Abdelbasit, Omer B.; Shaheed, Meeralebbae M.; Alhussein, Khalid A.; Miqdad, Abeer M.; Samadi, Abdulmohsen S.; Khalil, Mohammed I.; Al-Mardawi, Elham; Salih, Mustafa A.

    2014-01-01

    Objective: To ascertain the incidence, and describe the various forms of neural tube defects (NTDs) due to genetic, chromosomal, and syndromic causes. Methods: We carried out a retrospective analysis of data retrieved from the medical records of newborn infants admitted to the Neonatal Intensive Care Unit with NTDs and their mothers spanning 14 years (1996-2009) at the Security Forces Hospital, Riyadh, Saudi Arabia. The cases were ascertained by a perinatologist, neonatologist, geneticist, radiologist, and neurologist. The literature was reviewed via a MEDLINE search. Only liveborn babies were included. Permission from the Educational Committee at the Security Forces Hospital was obtained prior to the collection of data. Results: Out of 103 infants with NTDs admitted during this period, 20 (19.4%) were found to have an underlying genetic syndromic, chromosomal and/or other anomalies. There were 5 cases of Meckel-Gruber syndrome, 2 Joubert syndrome, one Waardenburg syndrome, one Walker-Warburg syndrome, 2 chromosomal disorders, 2 caudal regression, one amniotic band disruption sequence, one associated with omphalocele, one with diaphragmatic hernia, and 4 with multiple congenital anomalies. Conclusions: There is a high rate of underlying genetic syndromic and/or chromosomal causes of NTDs in the Saudi Arabian population due to the high consanguinity rate. Identification of such association can lead to more accurate provisions of genetic counseling to the family including preimplantation genetic diagnosis or early termination of pregnancies associated with lethal conditions. PMID:25551112

  19. Understanding the causes and prevention of neural tube defects: Insights from the splotch mouse model.

    Science.gov (United States)

    Greene, Nicholas D E; Massa, Valentina; Copp, Andrew J

    2009-04-01

    Splotch mutant mice develop neural tube defects (NTDs), comprising exencephaly and/or spina bifida, as well as neural crest-related defects and abnormalities of limb musculature. Defects in splotch mice result from mutations in Pax3, and some human NTDs may also result from mutations in the human PAX3 gene. Pax3 encodes a transcription factor whose function may influence expression of multiple downstream genes associated with a variety of cellular properties (including apoptosis, adhesion, proliferation, and differentiation), that could be important for neural tube closure. The frequency of NTDs varies between mutant alleles and is also influenced by genetic background and environmental factors. Notably, splotch provides a model for folic acid-preventable NTDs, and conversely, dietary folate deficiency exacerbates NTDs. Understanding the molecular and cellular basis of splotch NTDs, as well as the mechanisms by which the frequency of defects is influenced by genetic and environmental factors (such as sub-optimal folate status), may provide insight into the causation of these severe congenital malformations in humans.

  20. Development of Zirconium alloys (for pressure tubes)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Suk; Kwon, Sang Chul; Choo, Ki Nam; Jung, Chung Hwan; Yim, Kyong Soo; Kim, Sung Soo; Baek, Jong Hyuk; Jeong, Yong Hwan; Kim, Kyong Ho; Cho, Hae Dong [Korea Atomic Energy Research Inst., Daeduk (Korea, Republic of); Hwang, S. K.; Kim, M. H. [Inha Univ., Incheon (Korea, Republic of); Kwon, S. I [Korea Univ., Seoul (Korea, Republic of); Kim, I. S. [Korea Advanced Inst. of Science and Technology, Taejon (Korea, Republic of)

    1997-09-01

    The objective of this research is to set up the basic technologies for the evaluation of pressure tube integrity and to develop improved zirconium alloys to prevent pressure tube failures due to DHC and hydride blister caused by excessive creep-down of pressure tubes. The experimental procedure and facilities for characterization of pressure tubes were developed. The basic research related to a better understanding of the in-reactor performances of pressure tubes leads to noticeable findings for the first time : the microstructural effect on corrosion and hydrogen pick-up behavior of Zr-2.5Nb pressure tubes, texture effect on strength and DHC resistance and enhanced recrystallization by Fe in zirconium alloys and etc. Analytical methodology for the assessment of pressure tubes with surface flaws was set up. A joint research is being under way with AECL to determine the fracture toughness of O-8 at the EOL (End of Life) that had been quadruple melted and was taken out of the Wolsung Unit-1 after 10 year operation. In addition, pressure tube with texture controlled is being made along with VNINM in Russia as a joint project between KAERI and Russia. Finally, we succeeded in developing 4 different kinds of zirconium alloys with better corrosion resistance, low hydrogen pickup fraction and higher creep strength. (author). 121 refs., 65 tabs., 260 figs

  1. [Neural tube defects and folic acid: a historical overview of a highly successful preventive intervention].

    Science.gov (United States)

    Vásquez, Adriana Ordoñez; Suarez-Obando, Fernando

    2015-12-01

    This article gives a broad overview of part of the historical evolution of medical knowledge about neural tube defects (NTD) and the discovery of vitamin B9 or folic acid, as well as some relevant research events that, over the course of several centuries, defined the relationships between the understanding of central nervous system embryology, the discovery of the vitamin, the correlation between folic acid and cell proliferation and lastly the development of preventive measures for this type of defects. This narrative allows us to examine historically relevant concepts underlying clinical actions with a populational impact that prevent NTDs via folic acid consumption prior to conception.

  2. Population red blood cell folate concentrations for prevention of neural tube defects: bayesian model

    OpenAIRE

    MOLLOY, ANNE

    2014-01-01

    PUBLISHED OBJECTIVE: To determine an optimal population red blood cell (RBC) folate concentration for the prevention of neural tube birth defects. DESIGN: Bayesian model. SETTING: Data from two population based studies in China. PARTICIPANTS: 247,831 participants in a prospective community intervention project in China (1993-95) to prevent neural tube defects with 400 μg/day folic acid supplementation and 1194 participants in a population based randomized trial (20...

  3. Maternal diet modulates the risk for neural tube defects in a mouse model of diabetic pregnancy

    OpenAIRE

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

    2010-01-01

    Pregnancies complicated by maternal diabetes have long been known to carry a higher risk for congenital malformations, such as neural tube defects. Using the FVB inbred mouse strain and the Streptozotocin-induced diabetes model, we tested whether the incidence of neural tube defects in diabetic pregnancies can be modulated by maternal diet. In a comparison of two commercial mouse diets, which are considered nutritionally replete, we found that maternal consumption of the unfavorable diet was ...

  4. Integration of signals along orthogonal axes of the vertebrate neural tube controls progenitor competence and increases cell diversity.

    Directory of Open Access Journals (Sweden)

    Noriaki Sasai

    2014-07-01

    Full Text Available A relatively small number of signals are responsible for the variety and pattern of cell types generated in developing embryos. In part this is achieved by exploiting differences in the concentration or duration of signaling to increase cellular diversity. In addition, however, changes in cellular competence-temporal shifts in the response of cells to a signal-contribute to the array of cell types generated. Here we investigate how these two mechanisms are combined in the vertebrate neural tube to increase the range of cell types and deliver spatial control over their location. We provide evidence that FGF signaling emanating from the posterior of the embryo controls a change in competence of neural progenitors to Shh and BMP, the two morphogens that are responsible for patterning the ventral and dorsal regions of the neural tube, respectively. Newly generated neural progenitors are exposed to FGF signaling, and this maintains the expression of the Nk1-class transcription factor Nkx1.2. Ventrally, this acts in combination with the Shh-induced transcription factor FoxA2 to specify floor plate cells and dorsally in combination with BMP signaling to induce neural crest cells. As development progresses, the intersection of FGF with BMP and Shh signals is interrupted by axis elongation, resulting in the loss of Nkx1.2 expression and allowing the induction of ventral and dorsal interneuron progenitors by Shh and BMP signaling to supervene. Hence a similar mechanism increases cell type diversity at both dorsal and ventral poles of the neural tube. Together these data reveal that tissue morphogenesis produces changes in the coincidence of signals acting along orthogonal axes of the neural tube and this is used to define spatial and temporal transitions in the competence of cells to interpret morphogen signaling.

  5. Integration of signals along orthogonal axes of the vertebrate neural tube controls progenitor competence and increases cell diversity.

    Science.gov (United States)

    Sasai, Noriaki; Kutejova, Eva; Briscoe, James

    2014-07-01

    A relatively small number of signals are responsible for the variety and pattern of cell types generated in developing embryos. In part this is achieved by exploiting differences in the concentration or duration of signaling to increase cellular diversity. In addition, however, changes in cellular competence-temporal shifts in the response of cells to a signal-contribute to the array of cell types generated. Here we investigate how these two mechanisms are combined in the vertebrate neural tube to increase the range of cell types and deliver spatial control over their location. We provide evidence that FGF signaling emanating from the posterior of the embryo controls a change in competence of neural progenitors to Shh and BMP, the two morphogens that are responsible for patterning the ventral and dorsal regions of the neural tube, respectively. Newly generated neural progenitors are exposed to FGF signaling, and this maintains the expression of the Nk1-class transcription factor Nkx1.2. Ventrally, this acts in combination with the Shh-induced transcription factor FoxA2 to specify floor plate cells and dorsally in combination with BMP signaling to induce neural crest cells. As development progresses, the intersection of FGF with BMP and Shh signals is interrupted by axis elongation, resulting in the loss of Nkx1.2 expression and allowing the induction of ventral and dorsal interneuron progenitors by Shh and BMP signaling to supervene. Hence a similar mechanism increases cell type diversity at both dorsal and ventral poles of the neural tube. Together these data reveal that tissue morphogenesis produces changes in the coincidence of signals acting along orthogonal axes of the neural tube and this is used to define spatial and temporal transitions in the competence of cells to interpret morphogen signaling.

  6. Polymorphisms of the maternal Slug gene in fetal neural tube defects in a Chinese population

    Institute of Scientific and Technical Information of China (English)

    Li Guo; Hong Zhao; Yuheng Pei; Quanren He; Wan-I Li; Ting Zhang; Xiaoying Zheng; Ran Zhou; Jun Xie

    2010-01-01

    Several studies have demonstrated that Slug,which encodes a zinc finger of the Snail family of transcription factors,is a potential risk factor for neural tube defects.Neural tube defects tend to occur with a high rate in Shanxi province,China.The present case-control study investigated genotypic distributions and allele frequencies of Slug C1548A polymorphisms in DNA samples from59 women with a history of neural tube defect pregnancies and 73 controls during the same period from Shanxi Province,China.Results demonstrated that women with a history of neural tube defect pregnancies had significantly greater genotypic distributions of Slug AA genotypes and A allele frequencies compared with controls,and A allele Slug C1548A was a risk factor for neural tube defects(odds ratio = 3.444;95% confidence interval;2.021-5.868,P < 0.05).Three-dimensional structure prediction revealed that Slug C1548A resulted in transition of aspartic acid into glutamate at position 119.This indicated that these mutations could lead to damaged protein structure and function.These findings suggest that Slug C1548A gene polymorphism is closely related to neural tube defects in a population of Han Chinese origin from Shanxi Province,China

  7. Failure in closure of the anterior neural tube causes left isomerization of the zebrafish epithalamus.

    Science.gov (United States)

    Lu, Po-Nien; Lund, Caroline; Khuansuwan, Sataree; Schumann, Adelle; Harney-Tolo, Marijah; Gamse, Joshua T; Liang, Jennifer O

    2013-02-15

    Differences between the left and right sides of the brain are present in many animal species. For instance, in humans the left cerebral hemisphere is largely responsible for language and tool use and the right for processing spatial information. Zebrafish have prominent left-right asymmetries in their epithalamus that have been associated with differential left and right eye use and navigational behavior. In wild-type (WT) zebrafish embryos, Nodal pathway genes are expressed in the left side of the pineal anlage. Shortly thereafter, a parapineal organ forms to the left of the pineal. The parapineal organ causes differences in gene expression, neuropil density, and connectivity of the left and right habenula nuclei. In embryos that have an open neural tube, such as embryos that are deficient in Nodal signaling or the cell adhesion protein N-cadherin, the left and right sides of the developing epithalamus remain separated from one another. We find that the brains of these embryos often become left isomerized: both sides of the brain develop morphology and gene expression patterns that are characteristic of the left side. However, other aspects of epithalamic development, such as differentiation of specific neuronal cell types, are intact. We propose that there is a mechanism in embryos with closed neural tubes that prevents both sides from developing like the left side. This mechanism fails when the two sides of the epithalamus are widely separated from one another, suggesting that it is dependent upon a signaling protein with limited range.

  8. Neural Tube Defects in Native Fars Ethnicity in Northern Iran

    Directory of Open Access Journals (Sweden)

    MJ Golalipour

    2010-09-01

    Full Text Available "nBackground: Neural tube defects (NTD are one of the leading causes of infant mortality worldwide. This study was de­signed to determine the prevalence of NTDs among native Fars ethnic groups during 1998-2005, and to identify maternal and demographic factors associated with NTDs. "nMethods: We performed a descriptive cross-sectional hospital-based study in Dezyani Hospital, Gorgan, North of Iran, since January 1998 until December 2005. The design was based on a sample of 30,639 births of native Fars ethnic groups. Data were analyzed by using spss V13.5 software and were compared with the chi-square test."nResults: The prevalence of NTDs in Native Fars during the 8-year period was 25.4 per 10000 births (95% confidence inter­val: 20.1-31.8. The prevalence of NTDs was 20.6/10000 and 30.6/10000 in males and females respectively but this differ­ence was not significant. The prevalence of spina bifida, anencephaly and encephalocele were 12.7, 11.4 and 1.3 per 10000 respec­tively. The rate of NTD was 48.9/10000 in newborns with mothers aged > 35 years. The highest rate of NTDs and spina bi­fida was in 2002. The highest and lowest rate of anencephaly was in 2005 and 2003 respectively. Twenty eight percent of the parents had consanguineous marriages. Degree relatedness 3, 4, 5 and 6 of consanguineous marriages were 12.8%, 9%, 3.8%, 2.5%, respectively. Also 47.5% of the parents resided in rural areas.  "nConclusion: This investigation showed that the rate of NTDs in Native Fars was higher in Iran. In addition, this rate is higher than the Canada and Ukraine and lower than Chinese people.

  9. Descriptive study on neural tube defects in Argentina.

    Science.gov (United States)

    Sargiotto, Carla; Bidondo, María Paz; Liascovich, Rosa; Barbero, Pablo; Groisman, Boris

    2015-06-01

    Neural tube defects (NTDs) are the most common congenital anomalies of the central nervous system. Prevalence of NTDs varies depending on geographic region and folic acid fortification. The main objectives of this study are to analyze the prevalences of NTDs reported to the National Registry of Congenital Anomalies of Argentina (RENAC) during the period 2009 to 2013, to compare them with data from other selected surveillance systems of the Americas, and to evaluate the impact of folic acid fortification on the prevalence of NTDs in Argentina. We analyzed changes in prevalence between 2009 and 2013 for the RENAC, and differences in prevalence between RENAC and other surveillance systems. We evaluated changes for the pre and postfortification time periods in Argentina. In Argentina, anencephaly and spina bifida showed no statistically significant variation between 2009 and 2013, and encephalocele showed a statistically significant decline. The RENAC showed a statistically significant higher prevalence for all three defects when compared with surveillance systems from Chile, Colombia, and Costa Rica, and a statistically significant lower birth prevalence than Cuba for anencephaly. No differences were observed when comparing it to the Atlanta-USA and Mexico systems. A significant decrease in prevalence was observed for all three anomalies for the postfortification period in Argentina. The characteristics of cases reported to the RENAC are similar to those already reported in the literature. The differences in prevalence between the RENAC and other surveillance systems could be artifactual or real. We confirmed the decrease of prevalence of NTDs after folic acid fortification. © 2015 Wiley Periodicals, Inc.

  10. Histological evaluation of acute covering of an experimental neural tube defect with biomatrices in fetal sheep.

    NARCIS (Netherlands)

    Eggink, A.J.; Roelofs, L.A.J.; Lammens, M.M.Y.; Feitz, W.F.J.; Wijnen, R.M.H.; Mullaart, R.A.; Moerkerk, H.T.B. van; Kuppevelt, A.H.M.S.M. van; Crevels, A.J.; Hanssen, A.; Lotgering, F.K.; Berg, P.P. van den

    2006-01-01

    OBJECTIVE: The aim of the study was to determine the histological effect on the neural tissue of in utero covering of an experimental neural tube defect in fetal lambs, with the use of two different biomatrices. MATERIALS AND METHODS: In 23 fetal sheep, surgery was performed at 79 days' gestation. I

  11. Fetal DNA hypermethylation in tight junction pathway is associated with neural tube defects: A genome-wide DNA methylation analysis.

    Science.gov (United States)

    Wang, Linlin; Lin, Shanshan; Zhang, Ji; Tian, Tian; Jin, Lei; Ren, Aiguo

    2017-02-01

    Neural tube defects (NTDs) are a spectrum of severe congenital malformations of fusion failure of the neural tube during early embryogenesis. Evidence on aberrant DNA methylation in NTD development remains scarce, especially when exposure to environmental pollutant is taken into consideration. DNA methylation profiling was quantified using the Infinium HumanMethylation450 array in neural tissues from 10 NTD cases and 8 non-malformed controls (stage 1). Subsequent validation was performed using a Sequenom MassARRAY system in neural tissues from 20 NTD cases and 20 non-malformed controls (stage 2). Correlation analysis of differentially methylated CpG sites in fetal neural tissues and polycyclic aromatic hydrocarbons concentrations in fetal neural tissues and maternal serum was conducted. Differentially methylated CpG sites of neural tissues were further validated in fetal mice with NTDs induced by benzo(a)pyrene given to pregnant mice. Differentially hypermethylated CpG sites in neural tissues from 17 genes and 6 pathways were identified in stage 1. Subsequently, differentially hypermethylated CpG sites in neural tissues from 6 genes (BDKRB2, CTNNA1, CYFIP2, MMP7, MYH2, and TIAM2) were confirmed in stage 2. Correlation analysis showed that methylated CpG sites in CTNNA1 and MYH2 from NTD cases were positively correlated to polycyclic aromatic hydrocarbon level in fetal neural tissues and maternal serum. The correlation was confirmed in NTD-affected fetal mice that were exposed to benzo(a)pyrene in utero. In conclusion, hypermethylation of the CTNNA1 and MYH2 genes in tight junction pathway is associated with the risk for NTDs, and the DNA methylation aberration may be caused by exposure to benzo(a)pyrene.

  12. Gene expression in retinoic acid-induced neural tube defects A cDNA mieroarray analysis

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Long; Zhong Yang; Yi Zeng; Hongli Li; Yangyun Han; Chao You

    2009-01-01

    BACKGROUND: Neural tube defects can be induced by abnormal factors in vivo or in vitro during development. However, the molecular mechanisms of neural tube defect induction, and the related gene expression and regulation are still unknown.OBJECTIVE: To compare the differences in gene expression between normal embryos and those with neural tube defects.DESIGN, TIME AND SETTING: A neural development study was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA between January 2006 and October 2007.MATERIALS: Among 120 adult Kunming mice, 60 pregnant mice were randomly and evenly divided into a retinoic acid group (n = 30) and a normal control group (n =30). The retinoic acid was produced by Sigma, USA, the gene microarray by the Amersham Pharmacia Company, Hong Kong, and the gene sequence was provided by the Incyte database, USA.METHODS: Retinoic acid was administered to prepare models of neural tube defects, and corn oil was similady administered to the normal control group. Total RNA was extracted from embryonic tissue of the two groups using a Trizol kit, and a cDNA microarray containing 1 100 known genes was used to compare differences in gene expression between the normal control group and the retinoic acid group on embryonic (E) clay 10.5 and 11.5. Several differentially expressed genes were randomly selected from the two groups for Northern blotting, to verify the results of the cDNA microarray.MAIN OUTCOME MEASURES: Morphological changes and differential gene expression between the normal control group and the retinoic acid group.RESULTS: Anatomical microscopy demonstrated that an intact closure of the brain was formed in the normal mouse embryos by days E10.5 and E11.5. The cerebral appearance was full and smooth, and the surface of the spine was intact. However, in the retinoic acid group on days E10.5 and E11.5, there were more dead embryos. Morphological malformations typically included non-closure at the top of

  13. An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural Crest Specification and Anterior-Posterior Axis Extension.

    Directory of Open Access Journals (Sweden)

    Matthew J Anderson

    2016-05-01

    Full Text Available During vertebrate axis extension, adjacent tissue layers undergo profound morphological changes: within the neuroepithelium, neural tube closure and neural crest formation are occurring, while within the paraxial mesoderm somites are segmenting from the presomitic mesoderm (PSM. Little is known about the signals between these tissues that regulate their coordinated morphogenesis. Here, we analyze the posterior axis truncation of mouse Fgf3 null homozygotes and demonstrate that the earliest role of PSM-derived FGF3 is to regulate BMP signals in the adjacent neuroepithelium. FGF3 loss causes elevated BMP signals leading to increased neuroepithelium proliferation, delay in neural tube closure and premature neural crest specification. We demonstrate that elevated BMP4 depletes PSM progenitors in vitro, phenocopying the Fgf3 mutant, suggesting that excessive BMP signals cause the Fgf3 axis defect. To test this in vivo we increased BMP signaling in Fgf3 mutants by removing one copy of Noggin, which encodes a BMP antagonist. In such mutants, all parameters of the Fgf3 phenotype were exacerbated: neural tube closure delay, premature neural crest specification, and premature axis termination. Conversely, genetically decreasing BMP signaling in Fgf3 mutants, via loss of BMP receptor activity, alleviates morphological defects. Aberrant apoptosis is observed in the Fgf3 mutant tailbud. However, we demonstrate that cell death does not cause the Fgf3 phenotype: blocking apoptosis via deletion of pro-apoptotic genes surprisingly increases all Fgf3 defects including causing spina bifida. We demonstrate that this counterintuitive consequence of blocking apoptosis is caused by the increased survival of BMP-producing cells in the neuroepithelium. Thus, we show that FGF3 in the caudal vertebrate embryo regulates BMP signaling in the neuroepithelium, which in turn regulates neural tube closure, neural crest specification and axis termination. Uncovering this FGF3

  14. An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural Crest Specification and Anterior-Posterior Axis Extension.

    Science.gov (United States)

    Anderson, Matthew J; Schimmang, Thomas; Lewandoski, Mark

    2016-05-01

    During vertebrate axis extension, adjacent tissue layers undergo profound morphological changes: within the neuroepithelium, neural tube closure and neural crest formation are occurring, while within the paraxial mesoderm somites are segmenting from the presomitic mesoderm (PSM). Little is known about the signals between these tissues that regulate their coordinated morphogenesis. Here, we analyze the posterior axis truncation of mouse Fgf3 null homozygotes and demonstrate that the earliest role of PSM-derived FGF3 is to regulate BMP signals in the adjacent neuroepithelium. FGF3 loss causes elevated BMP signals leading to increased neuroepithelium proliferation, delay in neural tube closure and premature neural crest specification. We demonstrate that elevated BMP4 depletes PSM progenitors in vitro, phenocopying the Fgf3 mutant, suggesting that excessive BMP signals cause the Fgf3 axis defect. To test this in vivo we increased BMP signaling in Fgf3 mutants by removing one copy of Noggin, which encodes a BMP antagonist. In such mutants, all parameters of the Fgf3 phenotype were exacerbated: neural tube closure delay, premature neural crest specification, and premature axis termination. Conversely, genetically decreasing BMP signaling in Fgf3 mutants, via loss of BMP receptor activity, alleviates morphological defects. Aberrant apoptosis is observed in the Fgf3 mutant tailbud. However, we demonstrate that cell death does not cause the Fgf3 phenotype: blocking apoptosis via deletion of pro-apoptotic genes surprisingly increases all Fgf3 defects including causing spina bifida. We demonstrate that this counterintuitive consequence of blocking apoptosis is caused by the increased survival of BMP-producing cells in the neuroepithelium. Thus, we show that FGF3 in the caudal vertebrate embryo regulates BMP signaling in the neuroepithelium, which in turn regulates neural tube closure, neural crest specification and axis termination. Uncovering this FGF3-BMP signaling axis is

  15. Primary cilium and sonic hedgehog signaling during neural tube patterning: role of GPCRs and second messengers.

    Science.gov (United States)

    Pal, Kasturi; Mukhopadhyay, Saikat

    2015-04-01

    The ventral neural tube in vertebrates is patterned by a gradient of sonic hedgehog (Shh) secreted from the notochord and floor plate. Forward genetic screens first pointed to the role of the primary cilium in ventral neural tube patterning. Further research has shown that most components of the Shh pathway localize to or shuttle through the primary cilium. In the absence of Shh, the bifunctional Gli transcription factors are proteolytically processed into repressor forms in a protein kinase A (PKA)- and cilium-dependent manner. Recent work suggests that the orphan G-protein-coupled receptor (GPCR) Gpr161 localizes to cilia, and functions as a negative regulator of Shh signaling by determining Gli processing via cAMP signaling. The primary cilium also functions as a signaling compartment for calcium in the Shh pathway. A better understanding of the role of the cilium as a signaling compartment, and the interplay of second messenger systems that regulate PKA activation and Gli amplification during signaling is critical for deciphering the role of Shh during development, neuronal differentiation, and tumorigenesis.

  16. Prediction of Axial Capacity of Concrete-Filled Square Steel Tubes Using Neural Networks

    Institute of Scientific and Technical Information of China (English)

    Zhu Meichun; Wang Qingxiang; Feng Xiufeng

    2005-01-01

    The application of artificial neural network to predict the ultimate beating capacity of CFST ( concrete-filled square steel tubes)short columns under axial loading is explored. Input parameters consiste of concrete compressive strength, yield strength of steel tube, confinement index, sectional dimension and width-to-thickness ratio. The ultimate bearing capacity is the only output parameter. A multilayer feedforward neural network is used to describe the nonlinear relationships between the input and output variables.Fifty-five experimental data of CFST short columns under axial loading are used to train and test the neural network. A comparison between the neural network model and three parameter models shows that the neural network model possesses good accuracy and could be a practical method for predicting the ultimate strength of axially loaded CFST short columns.

  17. [Fortification of food with folic acid diminishes the number of neural tube defects].

    Science.gov (United States)

    Brouwer, I A

    2008-01-26

    A recent study from a research group from Quebec showed a strong decrease in the number of births affected by a neural tube defect since folic acid fortification was introduced in Canada. The prevalence decreased from 1.58 neural tube defects per 1000 births before the introduction of folic acid fortification to 0.86 per 1000 births in the period of complete fortification. Although folic acid fortification of staple food is probably the most effective way to decrease the incidence of neural tube defects, more knowledge about possible health risks should be obtained before fortification is introduced. More research is needed to determine which population groups are at risk of possible negative effects of folic acid fortification and at which level of fortification. Until then, it is important to generate more attention and publicity in order to increase awareness and knowledge concerning folic acid and to promote its use before and after conception.

  18. NEURAL TUBE DEFECTS PREVALENCE IN A HOSPITAL-BASED STUDY IN URMIA

    Directory of Open Access Journals (Sweden)

    I. Abdi Rad

    2008-06-01

    Full Text Available ObjectiveNeural tube defects including anencephaly, encephalocele, and spina bifida are major congenital malformations with multifactorial etiology, and with a great variation in their prevalence in different populations. The study on the prevalence of these malformations may be helpful in planning strategies for their prevention. The aim of this epidemiologic descriptive study was to determine the prevalence of neural tube defects and to describe their birth characteristics in Motahhari hospital, Urmia, West Azerbaijan.Materials and MethodsA cross-section observational study was carried on the hospital-based charts of consecutive 13997 live-births and 124 stillbirths during the period January 2001 through June 2005. The defects categorized based on the domains of anencephaly, spina bifida, and encephalocele according to standard definitions.ResultsDuring this period, 117 cases were detected with neural tube defects, giving an overall prevalence of 8.29/1000. Of 117 cases, 81 (69.23% cases were seen among stillbirths and 36 (30.77% cases among live-births, that is, the prevalence of neural tube defects for stillbirths and live-births were 653.2/1000 and 2.57/1000 respectively. The yearly prevalence varies between 6.99/1000 and 9.82/1000 over the 4.5-year period. The major lesion was anencephaly with prevalence of 5.52/1000 (66.67% of all neural tube defects. Approximately, two-thirds (66.09% of cases were found in females. Weights of 73.36% of anencephalic cases wereless than 1000 grams.ConclusionIn this study, the prevalence of neural tube defects is among the highest reported rates. There was a significance difference in the prevalence of anencephaly, as the most prevalent NTD, between live-births and stillbirths. These findings may necessitate an intensive approach to periconceptional folic acid supplementation as a possible strategy to reduce the prevalence of these defects.

  19. Invited Commentary: Preventing Neural Tube Defects and More via Food Fortification?

    OpenAIRE

    Mills, James L.; Carter, Tonia C.

    2008-01-01

    Many neural tube defects can be prevented if women take folic acid around the time of conception. However, the majority of women do not take folic acid at the critical time, so the US government required that food be fortified with folic acid effective January 1, 1998. Whether the amount being added was sufficient to prevent all folate-related neural tube defects has been hotly debated. Mosley et al. (Am J Epidemiol. 2008;169(1):9–17) found no evidence that folic acid supplement use or dietar...

  20. Application of artificial neural networks in analysis of CHF experimental data in round tubes

    Institute of Scientific and Technical Information of China (English)

    HUANG Yan-Ping; SHAN Jian-Qiang; CHEN Bing-De; LANG Xue-Mei; JIA Dou-Nan; WANG Xiao-Jun

    2004-01-01

    Artificial neural networks (ANNs) are applied successfully to analyze the critical heat flux (CHF) experimental data from some round tubes in this paper. A set of software adopting artificial neural network method for predicting CHF in round tube and a set of CHF database are gotten. Comparing with common CHF correlations and CHF look-up table, ANN method has stronger ability of allow-wrong and nice robustness. The CHF predicting software adopting artificial neural network technology can improve the predicting accuracy in a wider parameter range,and is easier to update and to use. The artificial neural nefwork method used in this paper can be applied to some similar physical problems.

  1. International retrospective cohort study of neural tube defects in relation to folic acid recommendations : are the recommendations working?

    NARCIS (Netherlands)

    Botto, LD; Lisi, A; Robert-Gnansia, E; Erickson, JD; Vollset, SE; Mastroiacovo, P; Botting, B; Cocchi, G; de Vigan, C; de Walle, H; Feijoo, M; Irgens, LM; McDonnell, B; Merlob, P; Ritvanen, A; Scarano, G; Siffel, C; Metneki, J; Stoll, C; Smithells, R; Goujard, J

    2005-01-01

    Objective To evaluate the effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of neural tube defects. Design Retrospective cohort study of births monitored by birth defect registries. Setting 13 birth defects registries monitoring rates of neural tube defects

  2. International retrospective cohort study of neural tube defects in relation to folic acid recommendations : are the recommendations working?

    NARCIS (Netherlands)

    Botto, LD; Lisi, A; Robert-Gnansia, E; Erickson, JD; Vollset, SE; Mastroiacovo, P; Botting, B; Cocchi, G; de Vigan, C; de Walle, H; Feijoo, M; Irgens, LM; McDonnell, B; Merlob, P; Ritvanen, A; Scarano, G; Siffel, C; Metneki, J; Stoll, C; Smithells, R; Goujard, J

    2005-01-01

    Objective To evaluate the effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of neural tube defects. Design Retrospective cohort study of births monitored by birth defect registries. Setting 13 birth defects registries monitoring rates of neural tube defects

  3. Evaluation of the prenatal diagnosis of neural tube defects by fetal ultrasonographic examination in different centres across Europe

    NARCIS (Netherlands)

    Boyd, PA; Wellesley, DG; De Walle, HEK; Tenconi, R; Garcia-Minaur, S; Zandwijken, GRJ; Stoll, C; Clementi, M

    2000-01-01

    Objective-Evaluation of prenatal diagnosis of neural tube defects by ultrasound examination in unselected populations across Europe. Setting-Prenatal ultrasound units in areas that report to contributing congenital malformation registers. Methods-All cases with a suspected or confirmed neural tube d

  4. β-catenin regulates Pax3 and Cdx2 for caudal neural tube closure and elongation.

    Science.gov (United States)

    Zhao, Tianyu; Gan, Qini; Stokes, Arjun; Lassiter, Rhonda N T; Wang, Yongping; Chan, Jason; Han, Jane X; Pleasure, David E; Epstein, Jonathan A; Zhou, Chengji J

    2014-01-01

    Non-canonical Wnt/planar cell polarity (PCP) signaling plays a primary role in the convergent extension that drives neural tube closure and body axis elongation. PCP signaling gene mutations cause severe neural tube defects (NTDs). However, the role of canonical Wnt/β-catenin signaling in neural tube closure and NTDs remains poorly understood. This study shows that conditional gene targeting of β-catenin in the dorsal neural folds of mouse embryos represses the expression of the homeobox-containing genes Pax3 and Cdx2 at the dorsal posterior neuropore (PNP), and subsequently diminishes the expression of the Wnt/β-catenin signaling target genes T, Tbx6 and Fgf8 at the tail bud, leading to spina bifida aperta, caudal axis bending and tail truncation. We demonstrate that Pax3 and Cdx2 are novel downstream targets of Wnt/β-catenin signaling. Transgenic activation of Pax3 cDNA can rescue the closure defect in the β-catenin mutants, suggesting that Pax3 is a key downstream effector of β-catenin signaling in the PNP closure process. Cdx2 is known to be crucial in posterior axis elongation and in neural tube closure. We found that Cdx2 expression is also repressed in the dorsal PNPs of Pax3-null embryos. However, the ectopically activated Pax3 in the β-catenin mutants cannot restore Cdx2 mRNA in the dorsal PNP, suggesting that the presence of both β-catenin and Pax3 is required for regional Cdx2 expression. Thus, β-catenin signaling is required for caudal neural tube closure and elongation, acting through the transcriptional regulation of key target genes in the PNP.

  5. Dynamic rupture and crushing of an extruded tube using artificial neural network (ANN) approximation method

    Institute of Scientific and Technical Information of China (English)

    Javad Marzbanrad; Behrooz Mashadi; Amir Afkar; Mostafa Pahlavani

    2016-01-01

    A numerical study of the crushing of thin-walled circular aluminum tubes has been carried out to investigate the crashworthiness behaviors under axial impact loading. These kinds of tubes are usually used in automobile and train structures to absorb the impact energy. Previous researches show that thin-walled circular tube has the highest energy absorption under axial impact amongst different structures. In this work, the crushing between two rigid flat plates and the tube rupture by 4 and 6 blades cutting tools is modeled with the help of ductile failure criterion using the numerical method. The tube material is aluminum EN AW-7108 T6 and its length and diameter are 300 mm and 50 mm, respectively. Using the artificial neural network (ANN), the most important surfaces of energy absorption parameters, including the maximum displacement of the striker, the maximum axial force, the specific energy absorption and the crushing force efficiency in terms of impact velocity and tube thickness are obtained and compared to each other. The analyses show that the tube rupture by the 6 blades cutting tool has more energy absorption in comparison with others. Furthermore, the results demonstrate that tube cutting with the help of multi-blades cutting tools is more stable, controllable and predictable than tube folding.

  6. An Expert System Using A Neural Network For Steam Generator Tube Inspection

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kilyoo; Huh, Younghwan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Woo, Heegon; Choi, Sungsoo [Korea Electric Power Corporation, Daejeon (Korea, Republic of)

    1991-04-15

    An expert system using neural network is built to automatically evaluate eddy current (EC) signals generated during steam generator (S/G) tubes inspection. The system consists of three subsystem, i.e., syntactic pattern recognition subsystem, neural network subsystem and rule based production subsystem. The syntactic pattern recognition subsystem makes it easy to process the vast EC signal data, screens EC signals and detects event signals such as defect signals and structural signals. The neural network subsystem is useful to classify the event signals which often contain noise signals. The expert system implemented on HP 9000/370 workstation also supplies a good EC test data management function.

  7. Artificial Neural Networks-Based Software for Measuring Heat Collection Rate and Heat Loss Coefficient of Water-in-Glass Evacuated Tube Solar Water Heaters.

    Science.gov (United States)

    Liu, Zhijian; Liu, Kejun; Li, Hao; Zhang, Xinyu; Jin, Guangya; Cheng, Kewei

    2015-01-01

    Measurements of heat collection rate and heat loss coefficient are crucial for the evaluation of in service water-in-glass evacuated tube solar water heaters. However, conventional measurement requires expensive detection devices and undergoes a series of complicated procedures. To simplify the measurement and reduce the cost, software based on artificial neural networks for measuring heat collection rate and heat loss coefficient of water-in-glass evacuated tube solar water heaters was developed. Using multilayer feed-forward neural networks with back-propagation algorithm, we developed and tested our program on the basis of 915 measured samples of water-in-glass evacuated tube solar water heaters. This artificial neural networks-based software program automatically obtained accurate heat collection rate and heat loss coefficient using simply "portable test instruments" acquired parameters, including tube length, number of tubes, tube center distance, heat water mass in tank, collector area, angle between tubes and ground and final temperature. Our results show that this software (on both personal computer and Android platforms) is efficient and convenient to predict the heat collection rate and heat loss coefficient due to it slow root mean square errors in prediction. The software now can be downloaded from http://t.cn/RLPKF08.

  8. Are omphalocele and neural tube defects related congenital anomalies? : Data from 21 registries in Europe (EUROCAT)

    NARCIS (Netherlands)

    Calzolari, E; Dolk, H; Stone, D; Milan, M

    1997-01-01

    We have analyzed the association between omphalocele and neural tube defects (O/NTD) previously reported in epidemiological studies of EUROCAT registry data [DoIk et al., 1991; Calzolari et al., 1995]. By examining differences in prevalence between the United Kingdom and Ireland (UKI) and Continenta

  9. Folic acid supplementation influences the distribution of neural tube defect subtypes : A registry-based study

    NARCIS (Netherlands)

    Bergman, J. E. H.; Otten, E.; Verheij, J. B. G. M.; de Walle, H. E. K.

    2016-01-01

    Periconceptional folic acid (FA) reduces neural tube defect (NTD) risk, but seems to have a varying effect per NTD subtype. We aimed to study the effect of FA supplementation on NTD subtype distribution using data from EUROCAT Northern Netherlands. We included all birth types with non-syndromal NTDs

  10. Folate and neural tube defects - Recommendations from a Danish working group

    DEFF Research Database (Denmark)

    Rasmussen, Lone Banke; Andersen, Niels Lyhne; Andersson, G.

    1998-01-01

    A working group was established to evaluate the need for an increased folate intake in Danish women to decrease the risk of neural tube defects (NTDs). NTD are birth defects a which include anencephaly, encephalocele and spina bifida. In Denmark the incidence is about 1.4 per 1,000 pregnancies...

  11. Epidemiologic and Genetic Aspects of Spina Bifida and Other Neural Tube Defects

    Science.gov (United States)

    Au, Kit Sing; Ashley-Koch, Allison; Northrup, Hope

    2010-01-01

    The worldwide incidence of neural tube defects (NTDs) ranges from 1.0 to 10.0 per 1,000 births with almost equal frequencies between two major categories: anencephaly and spina bifida (SB). Epidemiological studies have provided valuable insight for (a) researchers to identify nongenetic and genetic factors contributing to etiology, (b) public…

  12. Long term trends in prevalence of neural tube defects in Europe : population based study

    NARCIS (Netherlands)

    Khoshnood, Babak; Loane, Maria; de Walle, Hermien; Arriola, Larraitz; Addor, Marie-Claude; Barisic, Ingeborg; Beres, Judit; Bianchi, Fabrizio; Dias, Carlos; Draper, Elizabeth; Garne, Ester; Gatt, Miriam; Haeusler, Martin; Klungsoyr, Kari; Latos-Bielenska, Anna; Lynch, Catherine; McDonnell, Bob; Nelen, Vera; Neville, Amanda J.; O'Mahony, Mary T.; Queisser-Luft, Annette; Rankin, Judith; Rissmann, Anke; Ritvanen, Annukka; Rounding, Catherine; Sipek, Antonin; Tucker, David; Verellen-Dumoulin, Christine; Wellesley, Diana; Dolk, Helen

    2015-01-01

    STUDY QUESTION What are the long term trends in the total (live births, fetal deaths, and terminations of pregnancy for fetal anomaly) and live birth prevalence of neural tube defects (NTD) in Europe, where many countries have issued recommendations for folic acid supplementation but a policy for ma

  13. Epidemiologic and Genetic Aspects of Spina Bifida and Other Neural Tube Defects

    Science.gov (United States)

    Au, Kit Sing; Ashley-Koch, Allison; Northrup, Hope

    2010-01-01

    The worldwide incidence of neural tube defects (NTDs) ranges from 1.0 to 10.0 per 1,000 births with almost equal frequencies between two major categories: anencephaly and spina bifida (SB). Epidemiological studies have provided valuable insight for (a) researchers to identify nongenetic and genetic factors contributing to etiology, (b) public…

  14. Effects of hyperinsulinemia and obesity on risk of neural tube defects among Mexican Americans.

    Science.gov (United States)

    Hendricks, K A; Nuno, O M; Suarez, L; Larsen, R

    2001-11-01

    Although both maternal obesity and diabetes mellitus increase the risk for neural tube defects, it is unknown whether they are independent risk factors or manifestations of an underlying prediabetic state such as hyperinsulinemia. We investigated whether hyperinsulinemia was a risk factor for neural tube defects independent of obesity and hyperglycemia in Mexican-American women. We identified case and control women from residents delivering or terminating pregnancies in hospitals or birthing centers in any of the 14 Texas-Mexico border counties during 1995-2000. Case women had a pregnancy affected by anencephaly, spina bifida, or encephalocele; randomly selected control women had normal births, frequency matched by year and birth facility. Questionnaire and laboratory values obtained 5-6 weeks postpartum were available for 149 case and 178 control women. Both hyperinsulinemia and obesity were related to increased neural tube defect risk [odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.21-3.01 and OR = 1.73, 95% CI = 1.03-2.92, respectively]. Adjustment for obesity only slightly reduced the effect of hyperinsulinemia (OR = 1.75, 95% CI = 1.09-2.82). Alternatively, a modest effect remained for obesity after adjustment for hyperinsulinemia (OR = 1.45, 95% CI = 0.84-2.51). Hyperinsulinemia is a strong risk factor for neural tube defects and may be the driving force for the observed risk in obese women.

  15. Genetic variation in genes of folate metabolism and neural-tube defect risk.

    NARCIS (Netherlands)

    Linden, I.J. van der; Afman, L.A.; Heil, S.G.; Blom, H.J.

    2006-01-01

    Neural-tube defects (NTD) are common congenital malformations that can lead to severe disability or even death. Periconceptional supplementation with the B-vitamin folic acid has been demonstrated to prevent 50-70% of NTD cases. Since the identification of the first genetic risk factor of NTD, the C

  16. Genetic variation in genes of folate metabolism and neural-tube defect risk

    NARCIS (Netherlands)

    Linden, van der I.J.; Afman, L.A.; Heil, S.G.; Blom, H.J.

    2006-01-01

    Neural-tube defects (NTD) are common congenital malformations that can lead to severe disability or even death. Periconceptional supplementation with the B-vitamin folic acid has been demonstrated to prevent 50–70% of NTD cases. Since the identification of the first genetic risk factor of NTD, the C

  17. Folic Acid for the Prevention of Neural Tube Defects : US Preventive Services Task Force Recommendation Statement

    NARCIS (Netherlands)

    Calonge, Ned; Petitti, Diana B.; DeWitt, Thomas G.; Dietrich, Allen J.; Gregory, Kimberly D.; Grossman, David; Isham, George; LeFevre, Michael L.; Leipzig, Rosanne M.; Marion, Lucy N.; Melnyk, Bernadette; Moyer, Virginia A.; Ockene, Judith K.; Sawaya, George F.; Schwartz, J. Sanford; Wilt, Timothy

    2009-01-01

    Description: In 1996, the U. S. Preventive Services Task Force (USPSTF) recommended that all women planning or capable of pregnancy take a multivitamin supplement containing folic acid for the prevention of neural tube defects. This recommendation is an update of the 1996 USPSTF recommendation. Meth

  18. Planar cell polarity gene mutations contribute to the etiology of human neural tube defects in our population.

    Science.gov (United States)

    De Marco, Patrizia; Merello, Elisa; Piatelli, Gianluca; Cama, Armando; Kibar, Zoha; Capra, Valeria

    2014-08-01

    Neural Tube Defects (NTDs) are congenital malformations that involve failure of the neural tube closure during the early phases of development at any level of the rostro-caudal axis. The planar cell polarity (PCP) pathway is a highly conserved, noncanonical Wnt-Frizzled-Dishevelled signaling cascade, that was first identified in the fruit fly Drosophila. We are here reviewing the role of the PCP pathway genes in the etiology of human NTDs, updating the list of the rare and deleterious mutations identified so far. We report 50 rare nonsynonymous mutations of PCP genes in 54 patients having a pathogenic effect on the protein function. Thirteen mutations that have previously been reported as novel are now reported in public databases, although at very low frequencies. The mutations were private, mostly missense, and transmitted by a healthy parent. To date, no clear genotype-phenotype correlation has been possible to create. Even if PCP pathway genes are involved in the pathogenesis of neural tube defects, future studies will be necessary to better dissect the genetic causes underlying these complex malformations.

  19. Modeling the cooling performance of vortex tube using a genetic algorithm-based artificial neural network

    Directory of Open Access Journals (Sweden)

    Pouraria Hassan

    2016-01-01

    Full Text Available In this study, artificial neural networks (ANNs have been used to model the effects of four important parameters consist of the ratio of the length to diameter(L/D, the ratio of the cold outlet diameter to the tube diameter(d/D, inlet pressure(P, and cold mass fraction (Y on the cooling performance of counter flow vortex tube. In this approach, experimental data have been used to train and validate the neural network model with MATLAB software. Also, genetic algorithm (GA has been used to find the optimal network architecture. In this model, temperature drop at the cold outlet has been considered as the cooling performance of the vortex tube. Based on experimental data, cooling performance of the vortex tube has been predicted by four inlet parameters (L/D, d/D, P, Y. The results of this study indicate that the genetic algorithm-based artificial neural network model is capable of predicting the cooling performance of vortex tube in a wide operating range and with satisfactory precision.

  20. NEURAL TUBE DEFECTS PREVALENCE IN A HOSPITAL-BASED STUDY IN URMIA

    Directory of Open Access Journals (Sweden)

    I. Abdi Rad

    2008-10-01

    Full Text Available AbstractObjectiveNeural tube defects including anencephaly, encephalocele, and spina bifida are major congenital malformations with multifactorial etiology, and with a great variation in their prevalence in different populations. The study on the prevalence of these malformations may be helpful in planning strategies for their prevention. The aim of this epidemiologic descriptive study was to determine the prevalence of neural tube defects and to describe their birth characteristics in Motahhari hospital, Urmia, West Azerbaijan.Materials and MethodsA cross-section observational study was carried on the hospital-based charts of consecutive 13997 live-births and 124 stillbirths during the period January 2001 through June 2005. The defects categorized based on the domains of anencephaly, spina bifida, and encephalocele according to standard definitions.ResultsDuring this period, 117 cases were detected with neural tube defects, giving an overall  prevalence of 8.29/1000. Of 117 cases, 81 (69.23% cases were seen among stillbirths and 36 (30.77% cases among live-births, that is, the prevalence of neural tube defects for stillbirths and live-births were 653.2/1000 and 2.57/1000 respectively. The yearly prevalence varies between 6.99/1000 and 9.82/1000 over the 4.5-year period. The major lesion was  anencephaly with prevalence of 5.52/1000 (66.67% of all neural tube defects. Approximately, two-thirds (66.09% of cases were found in females. Weights of 73.36% of anencephalic cases wereless than 1000 grams.ConclusionIn this study, the prevalence of neural tube defects is among the highest reported rates. There was a significance difference in the prevalence of anencephaly, as the most prevalent NTD, between live-births and stillbirths. These findings may necessitate an intensive approach to periconceptional folic acid supplementation as a possible strategy to reduce the prevalence of these defects. Keywords: Prevalence, Neural Tube Defects, Anencephaly

  1. Zebrafish neural tube morphogenesis requires Scribble-dependent oriented cell divisions.

    Science.gov (United States)

    Žigman, Mihaela; Trinh, Le A; Fraser, Scott E; Moens, Cecilia B

    2011-01-11

    How control of subcellular events in single cells determines morphogenesis on the scale of the tissue is largely unresolved. The stereotyped cross-midline mitoses of progenitors in the zebrafish neural keel provide a unique experimental paradigm for defining the role and control of single-cell orientation for tissue-level morphogenesis in vivo. We show here that the coordinated orientation of individual progenitor cell division in the neural keel is the cellular determinant required for morphogenesis into a neural tube epithelium with a single straight lumen. We find that Scribble is required for oriented cell division and that its function in this process is independent of canonical apicobasal and planar polarity pathways. We identify a role for Scribble in controlling clustering of α-catenin foci in dividing progenitors. Loss of either Scrib or N-cadherin results in abnormally oriented mitoses, reduced cross-midline cell divisions, and similar neural tube defects. We propose that Scribble-dependent nascent cell-cell adhesion clusters between neuroepithelial progenitors contribute to define orientation of their cell division. Finally, our data demonstrate that while oriented mitoses of individual cells determine neural tube architecture, the tissue can in turn feed back on its constituent cells to define their polarization and cell division orientation to ensure robust tissue morphogenesis.

  2. Lack of association between folate-receptor autoantibodies and neural-tube defects.

    LENUS (Irish Health Repository)

    Molloy, Anne M

    2009-07-09

    BACKGROUND: A previous report described the presence of autoantibodies against folate receptors in 75% of serum samples from women with a history of pregnancy complicated by a neural-tube defect, as compared with 10% of controls. We sought to confirm this finding in an Irish population, which traditionally has had a high prevalence of neural-tube defects. METHODS: We performed two studies. Study 1 consisted of analysis of stored frozen blood samples collected from 1993 through 1994 from 103 mothers with a history of pregnancy complicated by a neural-tube defect (case mothers), 103 mothers with a history of pregnancy but no complication by a neural-tube defect (matched with regard to number of pregnancies and sampling dates), 58 women who had never been pregnant, and 36 men. Study 2, conducted to confirm that the storage of samples did not influence the folate-receptor autoantibodies, included fresh samples from 37 case mothers, 22 control mothers, 10 women who had never been pregnant, and 9 men. All samples were assayed for blocking and binding autoantibodies against folate receptors. RESULTS: In Study 1, blocking autoantibodies were found in 17% of case mothers, as compared with 13% of control mothers (odds ratio, 1.54; 95% confidence interval [CI], 0.70 to 3.39), and binding autoantibodies in 29%, as compared with 32%, respectively (odds ratio, 0.82; 95% CI, 0.44 to 1.50). Study 2 showed similar results, indicating that sample degradation was unlikely. CONCLUSIONS: The presence and titer of maternal folate-receptor autoantibodies were not significantly associated with a neural-tube defect-affected pregnancy in this Irish population.

  3. Using artificial neural networks to model extrusion processes for the manufacturing of polymeric micro-tubes

    Science.gov (United States)

    Mekras, N.; Artemakis, I.

    2012-09-01

    In this paper a methodology and an application example are presented aiming to show how Artificial Neural Networks (ANNs) can be used to model manufacturing processes when mathematical models are missing or are not applicable e.g. due to the micro- & nano-scaling, due to non-conventional processes, etc. Besides the ANNs methodology, the results of a Software System developed will be presented, which was used to create ANNs models for micro & nano manufacturing processes. More specifically results of a specific application example will be presented, concerning the modeling of extrusion processes for polymeric micro-tubes. ANNs models are capable for modeling manufacturing processes as far as adequate experimental and/or historical data of processes' inputs & outputs are available for their training. The POLYTUBES ANNs models have been trained and tested with experimental data records of process' inputs and outputs concerning a micro-extrusion process of polymeric micro-tubes for several materials such as: COC, PC, PET, PETG, PP and PVDF. The main ANN model of the extrusion application example has 3 inputs and 9 outputs. The inputs are: tube's inner & outer diameters, and the material density. The model outputs are 9 process parameters, which correspond to the specific inputs e.g. process temperature, die inner & outer diameters, extrusion pressure, draw speed etc. The training of the ANN model was completed, when the errors for the model's outputs, which expressed the difference between the training target values and the ANNs outputs, were minimized to acceptable levels. After the training, the micro-extrusion ANN is capable to simulate the process and can be used to calculate model's outputs, which are the process parameters for any new set of inputs. By this way a satisfactory functional approximation of the whole process is achieved. This research work has been supported by the EU FP7 NMP project POLYTUBES.

  4. Development and Technology Transfer of the Syncro Blue Tube (Gabriel) Magnetically GuidedFeeding Tube

    Science.gov (United States)

    2017-06-01

    pneumonias. Tube placement does not require costly fluroscopy or endoscopy. Any nurse who can place a nasogastric tube can place this feeding tube without...time required to secure FDA 510K 160787 clearance. FDA clearance was awarded August 9, 2016 for 510K160787 Table of Contents I. Introduction...small bowel feeding tube and developing a smaller version of the technology (8 Fr.). The basic design of the technology is to provide an easy and

  5. Development of a gradient tube method for examining microbial ...

    African Journals Online (AJOL)

    2013-06-24

    Jun 24, 2013 ... Development of a gradient tube method for examining microbial ... pathways, and possibly also in wastewater treatment operations, little is ... waters and describe here the development of a novel gradient tube method for ...

  6. Kif11 dependent cell cycle progression in radial glial cells is required for proper neurogenesis in the zebrafish neural tube.

    Science.gov (United States)

    Johnson, Kimberly; Moriarty, Chelsea; Tania, Nessy; Ortman, Alissa; DiPietrantonio, Kristina; Edens, Brittany; Eisenman, Jean; Ok, Deborah; Krikorian, Sarah; Barragan, Jessica; Golé, Christophe; Barresi, Michael J F

    2014-03-01

    Radial glia serve as the resident neural stem cells in the embryonic vertebrate nervous system, and their proliferation must be tightly regulated to generate the correct number of neuronal and glial cell progeny in the neural tube. During a forward genetic screen, we recently identified a zebrafish mutant in the kif11 loci that displayed a significant increase in radial glial cell bodies at the ventricular zone of the spinal cord. Kif11, also known as Eg5, is a kinesin-related, plus-end directed motor protein responsible for stabilizing and separating the bipolar mitotic spindle. We show here that Gfap+ radial glial cells express kif11 in the ventricular zone and floor plate. Loss of Kif11 by mutation or pharmacological inhibition with S-trityl-L-cysteine (STLC) results in monoastral spindle formation in radial glial cells, which is characteristic of mitotic arrest. We show that M-phase radial glia accumulate over time at the ventricular zone in kif11 mutants and STLC treated embryos. Mathematical modeling of the radial glial accumulation in kif11 mutants not only confirmed an ~226× delay in mitotic exit (likely a mitotic arrest), but also predicted two modes of increased cell death. These modeling predictions were supported by an increase in the apoptosis marker, anti-activated Caspase-3, which was also found to be inversely proportional to a decrease in cell proliferation. In addition, treatment with STLC at different stages of neural development uncovered two critical periods that most significantly require Kif11 function for stem cell progression through mitosis. We also show that loss of Kif11 function causes specific reductions in oligodendroglia and secondary interneurons and motorneurons, suggesting these later born populations require proper radial glia division. Despite these alterations to cell cycle dynamics, survival, and neurogenesis, we document unchanged cell densities within the neural tube in kif11 mutants, suggesting that a mechanism of

  7. PREVALENCE OF NEURAL TUBE DEFECTS IN KIMS KARAD, 2012-2013 EFFECTIVENESS AND IMPACT OF PRENATAL DIAGNOSIS

    Directory of Open Access Journals (Sweden)

    Sanjaykumar

    2014-11-01

    Full Text Available : OBJECTIVE: To determine Prevalence of NEURAL TUBE DEFECT in tertiary care center (KIMS Karad during July 2012-July 2013. MATERIAL AND METHODS: Patients referred to KIMS as NTD, Booked Patients diagnosed in KIMS as having neural tube defect based on ultrasound findings. RESULTS: Total prevalence of neural tube defect in KIMS from July 2012-July 2013 was 8.2/1000 births. Prevalence of different types of NTD-Anencephaly was 2.8 and spina bifida was 7.4. CONCLUSION: Aim of this study is to create awareness of NTD in order to prevent NTD by measures like periconceptional folic acid supplementation.

  8. A mutation in the tuft mouse disrupts TET1 activity and alters the expression of genes that are crucial for neural tube closure

    Directory of Open Access Journals (Sweden)

    Keith S. K. Fong

    2016-05-01

    Full Text Available Genetic variations affecting neural tube closure along the head result in malformations of the face and brain. Neural tube defects (NTDs are among the most common birth defects in humans. We previously reported a mouse mutant called tuft that arose spontaneously in our wild-type 3H1 colony. Adult tuft mice present midline craniofacial malformations with or without an anterior cephalocele. In addition, affected embryos presented neural tube closure defects resulting in insufficient closure of the anterior neuropore or exencephaly. Here, through whole-genome sequencing, we identified a nonsense mutation in the Tet1 gene, which encodes a methylcytosine dioxygenase (TET1, co-segregating with the tuft phenotype. This mutation resulted in premature termination that disrupts the catalytic domain that is involved in the demethylation of cytosine. We detected a significant loss of TET enzyme activity in the heads of tuft embryos that were homozygous for the mutation and had NTDs. RNA-Seq transcriptome analysis indicated that multiple gene pathways associated with neural tube closure were dysregulated in tuft embryo heads. Among them, the expressions of Cecr2, Epha7 and Grhl2 were significantly reduced in some embryos presenting neural tube closure defects, whereas one or more components of the non-canonical WNT signaling pathway mediating planar cell polarity and convergent extension were affected in others. We further show that the recombinant mutant TET1 protein was capable of entering the nucleus and affected the expression of endogenous Grhl2 in IMCD-3 (inner medullary collecting duct cells. These results indicate that TET1 is an epigenetic determinant for regulating genes that are crucial to closure of the anterior neural tube and its mutation has implications to craniofacial development, as presented by the tuft mouse.

  9. A mutation in the tuft mouse disrupts TET1 activity and alters the expression of genes that are crucial for neural tube closure.

    Science.gov (United States)

    Fong, Keith S K; Hufnagel, Robert B; Khadka, Vedbar S; Corley, Michael J; Maunakea, Alika K; Fogelgren, Ben; Ahmed, Zubair M; Lozanoff, Scott

    2016-05-01

    Genetic variations affecting neural tube closure along the head result in malformations of the face and brain. Neural tube defects (NTDs) are among the most common birth defects in humans. We previously reported a mouse mutant called tuft that arose spontaneously in our wild-type 3H1 colony. Adult tuft mice present midline craniofacial malformations with or without an anterior cephalocele. In addition, affected embryos presented neural tube closure defects resulting in insufficient closure of the anterior neuropore or exencephaly. Here, through whole-genome sequencing, we identified a nonsense mutation in the Tet1 gene, which encodes a methylcytosine dioxygenase (TET1), co-segregating with the tuft phenotype. This mutation resulted in premature termination that disrupts the catalytic domain that is involved in the demethylation of cytosine. We detected a significant loss of TET enzyme activity in the heads of tuft embryos that were homozygous for the mutation and had NTDs. RNA-Seq transcriptome analysis indicated that multiple gene pathways associated with neural tube closure were dysregulated in tuft embryo heads. Among them, the expressions of Cecr2, Epha7 and Grhl2 were significantly reduced in some embryos presenting neural tube closure defects, whereas one or more components of the non-canonical WNT signaling pathway mediating planar cell polarity and convergent extension were affected in others. We further show that the recombinant mutant TET1 protein was capable of entering the nucleus and affected the expression of endogenous Grhl2 in IMCD-3 (inner medullary collecting duct) cells. These results indicate that TET1 is an epigenetic determinant for regulating genes that are crucial to closure of the anterior neural tube and its mutation has implications to craniofacial development, as presented by the tuft mouse.

  10. Development and formability analysis of TRIP seamless steel tube

    Institute of Scientific and Technical Information of China (English)

    Zhang Zicheng; Zhu Fuxian

    2014-01-01

    In this paper, the production technology of transformation induced plasticity (TRIP) steel was first introduced into the steel tube manufacture field to produce the steel tubes with high strength and plasticity. The TRIP seamless steel tubes with the microstructure of ferrite, bainite, retained austenite and a little martensite were successfully fabricated using a cold-drawn steel tube with two-stage heat treatment technique and continu- ous heat treatment process, respectively. The ring tensile test and cold bend test were carried out to study the formability of the newly developed TRIP seamless steel tube. The results showed that the TRIP seamless steel tubes have a good cold formability, and they are available to be used in the tube hydroforming process. In ad- dition, the equipment of continuous heat treatment developed in the current study can be used to produce TRIP steel tube, and it may serve as an important reference for the industrial production of TRIP steel tube.

  11. Geminin loss causes neural tube defects through disrupted progenitor specification and neuronal differentiation.

    Science.gov (United States)

    Patterson, Ethan S; Waller, Laura E; Kroll, Kristen L

    2014-09-01

    Geminin is a nucleoprotein that can directly bind chromatin regulatory complexes to modulate gene expression during development. Geminin knockout mouse embryos are preimplantation lethal by the 32-cell stage, precluding in vivo study of Geminin's role in neural development. Therefore, here we used a conditional Geminin allele in combination with several Cre-driver lines to define an essential role for Geminin during mammalian neural tube (NT) formation and patterning. Geminin was required in the NT within a critical developmental time window (embryonic day 8.5-10.5), when NT patterning and closure occurs. Geminin excision at these stages resulted in strongly diminished expression of genes that mark and promote dorsal NT identities and decreased differentiation of ventral motor neurons, resulting in completely penetrant NT defects, while excision after embryonic day 10.5 did not result in NT defects. When Geminin was deleted specifically in the spinal NT, both NT defects and axial skeleton defects were observed, but neither defect occurred when Geminin was excised in paraxial mesenchyme, indicating a tissue autonomous requirement for Geminin in developing neuroectoderm. Despite a potential role for Geminin in cell cycle control, we found no evidence of proliferation defects or altered apoptosis. Comparisons of gene expression in the NT of Geminin mutant versus wild-type siblings at embryonic day 10.5 revealed decreased expression of key regulators of neurogenesis, including neurogenic bHLH transcription factors and dorsal interneuron progenitor markers. Together, these data demonstrate a requirement for Geminin for NT patterning and neuronal differentiation during mammalian neurulation in vivo.

  12. Perinatal factors associated with neural tube defects (anencephaly [correction of anancephaly], spina bifida and encephalocele).

    Science.gov (United States)

    Ogata, A J; Camano, L; Brunoni, D

    1992-01-01

    The objective of the present study was to determine the presence of risk factors for the occurrence of neural tube defects. Data for 33,535 births which occurred at Hospital do Servidor Público Estadual de São Paulo from July 1973 to December 1986 were collected in a prospective manner as recommended by "Estudo Colaborativo Latino-Americano de Malformações Congênitas" (ECLAMC, Collaborative Latin American Study on Congenital Malformations). Twenty-six cases of neural tube defects were detected (0.77/1000 births). Of these, 11 were cases of spina bifida (0.39/1000 births), 9 of anencephaly (0.27/1000 births) and 6 of encephalocele (0.18/1000 births). We observed a higher frequency of polyhydramnios, premature labor, Apgar scores of less than 7 at the first and fifth minutes, low birth weight and intrauterine growth retardation.

  13. Maternal bereavement in the antenathal period and Neural tube defect in the offspring

    DEFF Research Database (Denmark)

    Ingstrup, Katja Glejsted; Olsen, Jørn; Bech, Bodil Hammer

    2013-01-01

    is the best-known cause of the disease. Objective: To investigate if severe emotional stress exposure related to maternal bereavement due to loss of a close relative in the antenatal period is associated with neural tube defect in the offspring. Methods: A nationwide register-based follow-up study including...... all children born in Denmark from 1978-2008 and their mothers (n=1,734,190). In the time window of one year before pregnancy or during the first trimester of pregnancy 34,407 mothers were exposed to bereavement. Results: A total of 5,031 cases of neural tube defects were identified: 889 with spina...... pregnancy in exposed and unexposed mothers. Results would be biased if more exposed mothers accept prenatal ultrasound screening and select induced abortion. If so a measure of association would be biased for more recent years. Conclusion: Bereavement due to death of an older child may be a risk factor...

  14. Neural Tube Defect in Alive Neonates: Incidence Rate and Predisposing Factors

    Directory of Open Access Journals (Sweden)

    F Haghollahi

    2008-06-01

    Full Text Available Background: Neural Tube Defect (NTD characterized by failure of neural tube to close properly be the second most common born defect after congenital heart disease. The most prevalent forms of NTD are Anencephaly and Spinal-bifida. Many factors are involved in this anomaly. New researches suggest environmental factors like radiation, hyperthermia, Vitamin A and acid folic deficiency, anti epileptic drug like Carbamazepine, Phenobarbital, phenytoin, Folic acid antagonist like Sulfasalazine, Triametherine and systemic disease like diabet mellitus, obesity, genetic factors, the most schance 40 to 70 percentages.Methods: In this survey cross sectional study was conducted in five hospitals depend to Tehran university during three years. Study subject identified through review of admission and discharge at major hospital through regular contact with newborn nurseries and birth hospital.Results: In 38473 reported cases, 143 cases have neural tube defect. Among NTD cases, 11.9% of mothers had medical diseases in their previous history such as diabetes mellitus, epilepsy-psychiatric, and disorder-heart diseases. In this study group, 5.6% have preclampsia during pregnancy period. The most common NTD anomaly in this study was anencephaly and meningomyelocele that was different from studies in literature.Conclusion: NTD result from failure of neural tube close threats fetus health up to 28 days after conception. When is often prior to the recognition of pregnancy since many pregnancy are unplanned NTD prevention is best achieve by adequate daily folic acid intake thought of reproductive ages .educational effort to promote daily intake of folic acid supplemental by women of reproductive age and NTD risk factor should be done. Early diagnostic procedure for high risk pregnancy advised.

  15. Primary prevention of neural tube defects: data from the portuguese national registry of congenital anomalies (RENAC)

    OpenAIRE

    Braz, Paula; Machado, Ausenda; Matias Dias, Carlos

    2016-01-01

    Background: In Portugal folic acid supplementation is recommended to start at least 2-3 months before conception for primary prevention of Neural Tube Defects. The aim of this study was to evaluate, within gestations with at least one congenital anomaly, possible association between maternal socio-demographic factors and the use of folic acid. Methods: Using data from the Portuguese national registry of congenital anomalies, for the 2004-2013 period, the association between folic acid use dur...

  16. Prevention of neural tube defects with folic acid: The Chinese experience.

    Science.gov (United States)

    Ren, Ai-Guo

    2015-08-08

    Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28(th) day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a post-program survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs.

  17. Serum Copper Concentration in Newborns with Neural Tube Defects in Northern Iran; A Case Control Study

    Directory of Open Access Journals (Sweden)

    Azad-Reza Mansourian

    2009-04-01

    Full Text Available Objective: This study was conducted to determine the eventual association between copper deficiency in newborns with neural tube defects (NTD in Northern Iran. A high prevalence of neural tube defects has been reported from this region.Methods: This hospital based case control study was carried out on 13 newborns having neural tube defects and 35 healthy controls in Northern Iran during 2005-2006. Serum copper was measured by spectrophotometery.Findings: Serum copper level in newborns with NTD and healthy normal newborns was 16.5 (±7.2 μmol/l and 16.7 (±6.6 μmol/l, respectively. In case group 38.5% of newborns and in control group 28.6% had copper deficiency. Logistic regression analysis showed no association between the presence of NTD and copper deficiency (OR:1.6, 95% CI=0.3-7.1, P=0.5.Conclusion :This study showed no association between NTD and copper deficiency in newborns.

  18. Suppressed expression of mitogen-activated protein kinases in hyperthermia induced defective neural tube.

    Science.gov (United States)

    Zhang, Tianliang; Leng, Zhaoting; Liu, Wenjing; Wang, Xia; Yan, Xue; Yu, Li

    2015-05-06

    Neural tube defects (NTDs) are common congenital malformations. Mitogen-activated protein kinases (MAPKs) pathway is involved in many physiological processes. HMGB1 has been showed closely associated with neurulation and NTDs induced by hyperthermia and could activate MAPKs pathway. Since hyperthermia caused increased activation of MAPKs in many systems, the present study aims to investigate whether HMGB1 contributes to hyperthermia induced NTDs through MAPKs pathway. The mRNA levels of MAPKs and HMGB1 between embryonic day 8.5 and 10 (E8.5-10) in hyperthermia induced defective neural tube were detected by real-time quantitative polymerase chain reaction (qPCR). By immunofluorescence and western blotting, the expressions of HMGB1 and phosphorylated MAPKs (ERK1/2, JNK and p38) in neural tubes after hyperthermia were studied. The mRNA levels of MAPKs and HMGB1, as well as the expressions of HMGB1 along with phosphorylated JNK, p38 and ERK, were downregulated in NTDs groups induced by hyperthermia compared with control. The findings suggested that HMGB1 may contribute to hyperthermia induced NTDs formation through decreased cell proliferation due to inhibited phosphorylated ERK1/2 MAPK.

  19. Impact of Periconceptional Use of Nitrosatable Drugs on the Risk of Neural Tube Defects.

    Science.gov (United States)

    Benedum, Corey M; Yazdy, Mahsa M; Mitchell, Allen A; Werler, Martha M

    2015-10-15

    Nitrosatable drugs (NSDs) can, in the presence of nitrosating agents and highly acidic conditions, form N-nitroso compounds that have been found to be teratogenic in animal models. Using data from the Slone Epidemiology Center Birth Defects Study collected from 1998 to 2012, we compared maternal periconceptional NSD use between 334 neural tube defect cases and 7,619 nonmalformed controls. We categorized NSDs according to their functional group (secondary amine, tertiary amine, and amide). With logistic regression models, we estimated adjusted odds ratios and 95% confidence intervals. Neural tube defect risk was associated with maternal periconceptional use of secondary (adjusted odds ratio (aOR) = 1.7, 95% confidence interval (CI): 1.1, 2.4) and tertiary (aOR = 1.7, 95% CI: 1.2, 2.5) amines; an association was observed for amides, but the 95% confidence interval included the null (aOR = 1.4, 95% CI: 0.7, 2.5). Within the secondary amine group, elevated adjusted odds ratios were observed for 3 drugs but were null for the remaining medications. Increases in risk were observed for both strata of folic acid intake (neural tube defects and periconceptional exposure to NSDs containing a secondary or tertiary amine or amide.

  20. Genomic DNA hypomethylation is associated with neural tube defects induced by methotrexate inhibition of folate metabolism.

    Directory of Open Access Journals (Sweden)

    Xiuwei Wang

    Full Text Available DNA methylation is thought to be involved in the etiology of neural tube defects (NTDs. However, the exact mechanism between DNA methylation and NTDs remains unclear. Herein, we investigated the change of methylation in mouse model of NTDs associated with folate dysmetabolism by use of ultraperformance liquid chromatography tandem mass spectrometry (UPLC/MS/MS, liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS, microarray, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and Real time quantitative PCR. Results showed that NTD neural tube tissues had lower concentrations of 5-methyltetrahydrofolate (5-MeTHF, P = 0.005, 5-formyltetrahydrofolate (5-FoTHF, P = 0.040, S-adenosylmethionine (SAM, P = 0.004 and higher concentrations of folic acid (P = 0.041, homocysteine (Hcy, P = 0.006 and S-adenosylhomocysteine (SAH, P = 0.045 compared to control. Methylation levels of genomic DNA decreased significantly in the embryonic neural tube tissue of NTD samples. 132 differentially methylated regions (35 low methylated regions and 97 high methylated regions were selected by microarray. Two genes (Siah1b, Prkx in Wnt signal pathway demonstrated lower methylated regions (peak and higher expression in NTDs (P<0.05; P<0.05. Results suggest that DNA hypomethylation was one of the possible epigenetic variations correlated with the occurrence of NTDs induced by folate dysmetabolism and that Siah1b, Prkx in Wnt pathway may be candidate genes for NTDs.

  1. Genomic DNA hypomethylation is associated with neural tube defects induced by methotrexate inhibition of folate metabolism.

    Science.gov (United States)

    Wang, Xiuwei; Guan, Zhen; Chen, Yan; Dong, Yanting; Niu, Yuhu; Wang, Jianhua; Zhang, Ting; Niu, Bo

    2015-01-01

    DNA methylation is thought to be involved in the etiology of neural tube defects (NTDs). However, the exact mechanism between DNA methylation and NTDs remains unclear. Herein, we investigated the change of methylation in mouse model of NTDs associated with folate dysmetabolism by use of ultraperformance liquid chromatography tandem mass spectrometry (UPLC/MS/MS), liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS), microarray, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and Real time quantitative PCR. Results showed that NTD neural tube tissues had lower concentrations of 5-methyltetrahydrofolate (5-MeTHF, P = 0.005), 5-formyltetrahydrofolate (5-FoTHF, P = 0.040), S-adenosylmethionine (SAM, P = 0.004) and higher concentrations of folic acid (P = 0.041), homocysteine (Hcy, P = 0.006) and S-adenosylhomocysteine (SAH, P = 0.045) compared to control. Methylation levels of genomic DNA decreased significantly in the embryonic neural tube tissue of NTD samples. 132 differentially methylated regions (35 low methylated regions and 97 high methylated regions) were selected by microarray. Two genes (Siah1b, Prkx) in Wnt signal pathway demonstrated lower methylated regions (peak) and higher expression in NTDs (P<0.05; P<0.05). Results suggest that DNA hypomethylation was one of the possible epigenetic variations correlated with the occurrence of NTDs induced by folate dysmetabolism and that Siah1b, Prkx in Wnt pathway may be candidate genes for NTDs.

  2. The study of neural tube defects after the Human Genome Project and folic acid fortification of foods.

    Science.gov (United States)

    Graf, W D; Oleinik, O E

    2000-12-01

    The implementation of folic acid fortification will eliminate a proportion of neural tube defects (NTD). As a result, the etiologic and clinical profiles of the developmental disorder may both change. In the assessment of NTD as it evolves, the bioinformatics structure and content of the Human Genome Project will find vital application. One important development will be an enhanced understanding of the role of folic acid in global regulation of gene expression through epigenetic processes. In addition, bioinformatics will facilitate coordination of research in the basic sciences with clinical investigations to better define remaining etiologic factors.

  3. Neural tube defects and polymorphism of methylenetetrahydrofolate reductase gene in Kazakh population

    Directory of Open Access Journals (Sweden)

    Zhanar Makhmutova

    2011-04-01

    Full Text Available The mutations of MTHFR gene in various populations are considered as risk factors for neural tube defects. The frequencies of MTHFR genotypes among the mothers of NTD cases were: ССаа - 15,4%, ССас - 15.4%, ССсс - 10%, СТаа - 16.9%, СТас - 30.8%, СТсс - 6.9%, ТТаа - 3.8%, ТТас - 0.8%. The frequencies of this genotypes among controls were: ССаа - 29%, ССас - 21%, ССсс - 6%, СТаа - 30%, СТас - 13%, СТсс - 1%, ТТаа - 1%. Thus, the frequencies of СТас, СТсс, ТТаа, ТТас genotypes of С677Т and А1298С polymorphisms of MTHFR in the basic group authentically exceed similar parameters in the group of healthy control (р<0.05.The research indicates on presence of clinical and diagnostic significance of the investigated polymorphisms of the MTHFR gene in the development of NTDs. Ascertainment of the etiologic aspects of fetal NTDs in the Kazakh population makes it possible to develop preventive measures and optimization of medical genetic counseling in order to reduce fetal NTDs in the population.

  4. Prediction of CHF in concentric-tube open thermosiphon using artificial neural network and genetic algorithm

    Science.gov (United States)

    Chen, R. H.; Su, G. H.; Qiu, S. Z.; Fukuda, Kenji

    2010-03-01

    In this paper, an artificial neural network (ANN) for predicting critical heat flux (CHF) of concentric-tube open thermosiphon has been trained successfully based on the experimental data from the literature. The dimensionless input parameters of the ANN are density ratio, ρ l/ ρ v; the ratio of the heated tube length to the inner diameter of the outer tube, L/ D i; the ratio of frictional area, d i/( D i + d o); and the ratio of equivalent heated diameter to characteristic bubble size, D he/[ σ/ g( ρ l- ρ v)]0.5, the output is Kutateladze number, Ku. The predicted values of ANN are found to be in reasonable agreement with the actual values from the experiments with a mean relative error (MRE) of 8.46%. New correlations for predicting CHF were also proposed by using genetic algorithm (GA) and succeeded to correlate the existing CHF data with better accuracy than the existing empirical correlations.

  5. Development boiling to sprinkled tube bundle

    Directory of Open Access Journals (Sweden)

    Kracík Petr

    2016-01-01

    Full Text Available This paper presents results of a studied heat transfer coefficient at the surface of a sprinkled tube bundle where boiling occurs. Research in the area of sprinkled exchangers can be divided into two major parts. The first part is research on heat transfer and determination of the heat transfer coefficient at sprinkled tube bundles for various liquids, whether boiling or not. The second part is testing of sprinkle modes for various tube diameters, tube pitches and tube materials and determination of individual modes’ interface. All results published so far for water as the falling film liquid apply to one to three tubes for which the mentioned relations studied are determined in rigid laboratory conditions defined strictly in advance. The sprinkled tubes were not viewed from the operational perspective where there are more tubes and various modes may occur in different parts with various heat transfer values. The article focuses on these processes. The tube is located in a low-pressure chamber where vacuum is generated using an exhauster via ejector. The tube consists of smooth copper tubes of 12 mm diameter placed horizontally one above another.

  6. Development boiling to sprinkled tube bundle

    Science.gov (United States)

    Kracík, Petr; Pospíšil, Jiří

    2016-03-01

    This paper presents results of a studied heat transfer coefficient at the surface of a sprinkled tube bundle where boiling occurs. Research in the area of sprinkled exchangers can be divided into two major parts. The first part is research on heat transfer and determination of the heat transfer coefficient at sprinkled tube bundles for various liquids, whether boiling or not. The second part is testing of sprinkle modes for various tube diameters, tube pitches and tube materials and determination of individual modes' interface. All results published so far for water as the falling film liquid apply to one to three tubes for which the mentioned relations studied are determined in rigid laboratory conditions defined strictly in advance. The sprinkled tubes were not viewed from the operational perspective where there are more tubes and various modes may occur in different parts with various heat transfer values. The article focuses on these processes. The tube is located in a low-pressure chamber where vacuum is generated using an exhauster via ejector. The tube consists of smooth copper tubes of 12 mm diameter placed horizontally one above another.

  7. N-cadherin-mediated cell adhesion restricts cell proliferation in the dorsal neural tube.

    Science.gov (United States)

    Chalasani, Kavita; Brewster, Rachel M

    2011-05-01

    Neural progenitors are organized as a pseudostratified epithelium held together by adherens junctions (AJs), multiprotein complexes composed of cadherins and α- and β-catenin. Catenins are known to control neural progenitor division; however, it is not known whether they function in this capacity as cadherin binding partners, as there is little evidence that cadherins themselves regulate neural proliferation. We show here that zebrafish N-cadherin (N-cad) restricts cell proliferation in the dorsal region of the neural tube by regulating cell-cycle length. We further reveal that N-cad couples cell-cycle exit and differentiation, as a fraction of neurons are mitotic in N-cad mutants. Enhanced proliferation in N-cad mutants is mediated by ligand-independent activation of Hedgehog (Hh) signaling, possibly caused by defective ciliogenesis. Furthermore, depletion of Hh signaling results in the loss of junctional markers. We therefore propose that N-cad restricts the response of dorsal neural progenitors to Hh and that Hh signaling limits the range of its own activity by promoting AJ assembly. Taken together, these observations emphasize a key role for N-cad-mediated adhesion in controlling neural progenitor proliferation. In addition, these findings are the first to demonstrate a requirement for cadherins in synchronizing cell-cycle exit and differentiation and a reciprocal interaction between AJs and Hh signaling.

  8. Progress in CPI Microwave Tube Development

    Science.gov (United States)

    Wright, Edward L.; Bohlen, Heinz

    2006-01-01

    CPI continues its role as a leading supplier of state-of-the-art, high-power microwave tubes; from linear beam, velocity- and density-modulated devices, to high frequency gyro-devices. Klystrons are the device-of-choice for many high-power microwave applications, and can provide multi-megawatts to multi-kilowatts of power from UHF to W-band, respectively. A number of recent and on-going developments will be described. At UHF frequencies, the inductive output tube (IOT) has replaced the klystron for terrestrial NTSC and HDTV broadcast, due to its high efficiency and linearity, and is beginning to see use in scientific applications requiring 300 kW or less. Recent advances have enabled use well into L-band. CPI has developed a number of multiple-beam amplifiers. The VKL-8301 multiple-beam klystron (MBK) was built for the TESLA V/UV and x-ray FEL projects, and is a candidate RF source for the International Linear Collider (ILC). We have also contributed to the development of the U.S. Naval Research Laboratory (NRL) high-power fundamental-mode S-band MBK. The VHP-8330B multiple-beam, high-order mode (HOM) IOT shows great promise as a compact, CW UHF source for high power applications. These topics will be discussed, along with CPI's development capabilities for new and novel applications. Most important is our availability to provide design and fabrication services to organizations requiring CPI's manufacturing and process control infrastructure to build and test state-of-the-art devices.

  9. The role of folic acid fortification in neural tube defects: a review.

    Science.gov (United States)

    Osterhues, Anja; Ali, Nyima S; Michels, Karin B

    2013-01-01

    The worldwide prevalence of neural tube defects (NTDs) has fallen noticeably during the past 30 years, but the specific etiology and causative mechanism of NTDs remain unknown. Since introduction of mandatory fortification of grains with folic acid, a further decrease in NTD prevalence has been reported in North America and other countries with large variations among ethnic subgroups. However, a significant portion of NTDs still persists. Population data suggest that women of childbearing age may not yet be adequately targeted, while the general population may be overfortified with folic acid. While an excessive folate intake may be associated with adverse effects, there remains uncertainty about the minimum effective folate intake and status required for NTD prevention, and the safe upper folate level. Besides folate, several other lifestyle and environmental factors as well as genetic variations may influence NTD development, possibly by affecting one-carbon metabolism and thus epigenetic events. In conclusion, mandatory folic acid fortification plays a significant part in the reduction of NTD prevalence, but possibly at a cost and with a portion of NTDs remaining. More effective preventive strategies require better understanding of the etiology of this group of birth defects.

  10. DNA methylation analysis of Homeobox genes implicates HOXB7 hypomethylation as risk factor for neural tube defects.

    Science.gov (United States)

    Rochtus, Anne; Izzi, Benedetta; Vangeel, Elise; Louwette, Sophie; Wittevrongel, Christine; Lambrechts, Diether; Moreau, Yves; Winand, Raf; Verpoorten, Carla; Jansen, Katrien; Van Geet, Chris; Freson, Kathleen

    2015-01-01

    Neural tube defects (NTDs) are common birth defects of complex etiology. Though family- and population-based studies have confirmed a genetic component, the responsible genes for NTDs are still largely unknown. Based on the hypothesis that folic acid prevents NTDs by stimulating methylation reactions, epigenetic factors, such as DNA methylation, are predicted to be involved in NTDs. Homeobox (HOX) genes play a role in spinal cord development and are tightly regulated in a spatiotemporal and collinear manner, partly by epigenetic modifications. We have quantified DNA methylation for the different HOX genes by subtracting values from a genome-wide methylation analysis using leukocyte DNA from 10 myelomeningocele (MMC) patients and 6 healthy controls. From the 1575 CpGs profiled for the 4 HOX clusters, 26 CpGs were differentially methylated (P-value 0.05) between MMC patients and controls. Seventy-seven percent of these CpGs were located in the HOXA and HOXB clusters, with the most profound difference for 3 CpGs within the HOXB7 gene body. A validation case-control study including 83 MMC patients and 30 unrelated healthy controls confirmed a significant association between MMC and HOXB7 hypomethylation (-14.4%; 95% CI: 11.9-16.9%; P-value T genotype. Significant HOXB7 hypomethylation was also present in 12 unaffected siblings, each related to a MMC patient, suggestive of an epigenetic change induced by the mother. The inclusion of a neural tube formation model using zebrafish showed that Hoxb7a overexpression but not depletion resulted in deformed body axes with dysmorphic neural tube formation. Our results implicate HOXB7 hypomethylation as risk factor for NTDs and highlight the importance for future genome-wide DNA methylation analyses without preselecting candidate pathways.

  11. Abnormal O-GlcNAcylation of Pax3 Occurring from Hyperglycemia-Induced Neural Tube Defects Is Ameliorated by Carnosine But Not Folic Acid in Chicken Embryos.

    Science.gov (United States)

    Tan, Rui-Rong; Li, Yi-Fang; Zhang, Shi-Jie; Huang, Wen-Shan; Tsoi, Bun; Hu, Dan; Wan, Xin; Yang, Xuesong; Wang, Qi; Kurihara, Hiroshi; He, Rong-Rong

    2017-01-01

    Neural tube defects (NTDs) are among the most common of the embryonic abnormalities associated with hyperglycemic gestation. In this study, the molecular mechanisms of embryonic neurogenesis influenced by hyperglycemia was investigated using chicken embryo models. High-concentration glucose was administered into chicken eggs and resulted in increased plasma and brain tissue glucose, and suppressed expression of glucose transporters (GLUTs). The rate of NTD positively correlated with hyperglycemia. Furthermore, abnormally increased O-GlcNAcylation, a nutritionally responsive modification, of the key neural tube marker Pax3 protein led to the loss of this protein. This loss was not observed in a folate-deficiency NTD induced by methotrexate. Carnosine, an endogenous dipeptide, showed significant recovery effects on neural tube development. In contrast, folic acid, a well-known periconceptional agent, surprisingly showed relatively minimal effect. Higher expression levels of the Pax3 protein were found in the carnosine-treated groups, while lower expression levels were found in folic acid groups. Furthermore, the abnormal O-GlcNAcylation of the Pax3 protein was restored by carnosine. These results suggest new insights into using endogenous nutrients for the protection of embryonic neurodevelopment affected by diabetes gestation. The abnormal excessive O-GlcNAcylation of Pax3 may be responsible for the neural tube defects associated with hyperglycemia.

  12. Epidemiology of the neural tube defects in Kashmir Valley

    Directory of Open Access Journals (Sweden)

    Masood Ahmed Laharwal

    2016-01-01

    Conclusions: The incidence rates of NTDs is very high for Kashmir Valley. Geographical distribution of NTDs at this place confirms a relationship between the socioeconomic status, educational status, maternal too young or advanced age, and environmental factors for the development of a NTD. The results of this study point to the importance establishing a health policy to prevent NTD in Kashmir Valley.

  13. Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog.

    Directory of Open Access Journals (Sweden)

    Eric Dessaud

    Full Text Available Morphogens are secreted signalling molecules that act in a graded manner to control the pattern of cellular differentiation in developing tissues. An example is Sonic hedgehog (Shh, which acts in several developing vertebrate tissues, including the central nervous system, to provide positional information during embryonic patterning. Here we address how Shh signalling assigns the positional identities of distinct neuronal subtype progenitors throughout the ventral neural tube. Assays of intracellular signal transduction and gene expression indicate that the duration as well as level of signalling is critical for morphogen interpretation. Progenitors of the ventral neuronal subtypes are established sequentially, with progressively more ventral identities requiring correspondingly higher levels and longer periods of Shh signalling. Moreover, cells remain sensitive to changes in Shh signalling for an extended time, reverting to antecedent identities if signalling levels fall below a threshold. Thus, the duration of signalling is important not only for the assignment but also for the refinement and maintenance of positional identity. Together the data suggest a dynamic model for ventral neural tube patterning in which positional information corresponds to the time integral of Shh signalling. This suggests an alternative to conventional models of morphogen action that rely solely on the level of signalling.

  14. Neural tube defects in mice with reduced levels of inositol 1,3,4-trisphosphate 5/6-kinase.

    Science.gov (United States)

    Wilson, Monita P; Hugge, Christopher; Bielinska, Malgorzata; Nicholas, Peter; Majerus, Philip W; Wilson, David B

    2009-06-16

    Inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) is a key regulatory enzyme at the branch point for the synthesis of inositol hexakisphosphate (IP(6)), an intracellular signaling molecule implicated in the regulation of ion channels, endocytosis, exocytosis, transcription, DNA repair, and RNA export from the nucleus. IP(6) also has been shown to be an integral structural component of several proteins. We have generated a mouse strain harboring a beta-galactosidase (betagal) gene trap cassette in the second intron of the Itpk1 gene. Animals homozygous for this gene trap are viable, fertile, and produce less ITPK1 protein than wild-type and heterozygous animals. Thus, the gene trap represents a hypomorphic rather than a null allele. Using a combination of immunohistochemistry, in situ hybridization, and betagal staining of mice heterozygous for the hypomorphic allele, we found high expression of Itpk1 in the developing central and peripheral nervous systems and in the paraxial mesoderm. Examination of embryos resulting from homozygous matings uncovered neural tube defects (NTDs) in some animals and axial skeletal defects or growth retardation in others. On a C57BL/6 x 129(P2)Ola background, 12% of mid-gestation embryos had spina bifida and/or exencephaly, whereas wild-type animals of the same genetic background had no NTDs. We conclude that ITPK1 is required for proper development of the neural tube and axial mesoderm.

  15. Junctional neurulation: a unique developmental program shaping a discrete region of the spinal cord highly susceptible to neural tube defects.

    Science.gov (United States)

    Dady, Alwyn; Havis, Emmanuelle; Escriou, Virginie; Catala, Martin; Duband, Jean-Loup

    2014-09-24

    In higher vertebrates, the primordium of the nervous system, the neural tube, is shaped along the rostrocaudal axis through two consecutive, radically different processes referred to as primary and secondary neurulation. Failures in neurulation lead to severe anomalies of the nervous system, called neural tube defects (NTDs), which are among the most common congenital malformations in humans. Mechanisms causing NTDs in humans remain ill-defined. Of particular interest, the thoracolumbar region, which encompasses many NTD cases in the spine, corresponds to the junction between primary and secondary neurulations. Elucidating which developmental processes operate during neurulation in this region is therefore pivotal to unraveling the etiology of NTDs. Here, using the chick embryo as a model, we show that, at the junction, the neural tube is elaborated by a unique developmental program involving concerted movements of elevation and folding combined with local cell ingression and accretion. This process ensures the topological continuity between the primary and secondary neural tubes while supplying all neural progenitors of both the junctional and secondary neural tubes. Because it is distinct from the other neurulation events, we term this phenomenon junctional neurulation. Moreover, the planar-cell-polarity member, Prickle-1, is recruited specifically during junctional neurulation and its misexpression within a limited time period suffices to cause anomalies that phenocopy lower spine NTDs in human. Our study thus provides a molecular and cellular basis for understanding the causality of NTD prevalence in humans and ascribes to Prickle-1 a critical role in lower spinal cord formation.

  16. Hoxb1b controls oriented cell division, cell shape and microtubule dynamics in neural tube morphogenesis.

    Science.gov (United States)

    Zigman, Mihaela; Laumann-Lipp, Nico; Titus, Tom; Postlethwait, John; Moens, Cecilia B

    2014-02-01

    Hox genes are classically ascribed to function in patterning the anterior-posterior axis of bilaterian animals; however, their role in directing molecular mechanisms underlying morphogenesis at the cellular level remains largely unstudied. We unveil a non-classical role for the zebrafish hoxb1b gene, which shares ancestral functions with mammalian Hoxa1, in controlling progenitor cell shape and oriented cell division during zebrafish anterior hindbrain neural tube morphogenesis. This is likely distinct from its role in cell fate acquisition and segment boundary formation. We show that, without affecting major components of apico-basal or planar cell polarity, Hoxb1b regulates mitotic spindle rotation during the oriented neural keel symmetric mitoses that are required for normal neural tube lumen formation in the zebrafish. This function correlates with a non-cell-autonomous requirement for Hoxb1b in regulating microtubule plus-end dynamics in progenitor cells in interphase. We propose that Hox genes can influence global tissue morphogenesis by control of microtubule dynamics in individual cells in vivo.

  17. Deciphering axonal pathways of genetically defined groups of neurons in the chick neural tube utilizing in ovo electroporation.

    Science.gov (United States)

    Avraham, Oshri; Zisman, Sophie; Hadas, Yoav; Vald, Lilach; Klar, Avihu

    2010-05-02

    Employment of enhancer elements to drive expression of reporter genes in neurons is a widely used paradigm for tracking axonal projection. For tracking axonal projection of spinal interneurons in vertebrates, germ line-targeted reporter genes yield bilaterally symmetric labeling. Therefore, it is hard to distinguish between the ipsi- and contra-laterally projecting axons. Unilateral electroporation into the chick neural tube provides a useful means to restrict expression of a reporter gene to one side of the central nervous system, and to follow axonal projection on both sides. This video demonstrates first how to handle the eggs prior to injection. At HH stage 18-20, DNA is injected into the sacral level of the neural tube, then tungsten electrodes are placed parallel to the embryo and short electrical pulses are administered with a pulse generator. The egg is sealed with tape and placed back into an incubator for further development. Three days later (E6) the spinal cord is removed as an open book preparation from embryo, fixed, and processed for whole mount antibody staining. The stained spinal cord is mounted on slide and visualized using confocal microscopy.

  18. Folate-related gene variants in Irish families affected by neural tube defects

    Directory of Open Access Journals (Sweden)

    Ridgely eFisk Green

    2013-11-01

    Full Text Available Periconceptional folic acid use can often prevent neural tube defects (NTDs. Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative (risk genotypes and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p=0.017. We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential

  19. Puerto Rican primary physicians' knowledge about folic acid supplementation for the prevention of neural tube defects.

    Science.gov (United States)

    Miranda, Ana; Dávila Torres, René R; Gorrín Peralta, José J; Montes de Longo, Idalina

    2003-12-01

    We conducted a study of a group of primary physicians in Puerto Rico to evaluate their knowledge about folic acid supplementation to prevent neural tube defects. The study design was transverse-correlational. A total of 66 primary physicians in two hospitals (public and private) participated in the study. The sample was nonrandom and opportunistic, and only those physicians present in the hospitals at the moment of distribution of the questionnaires participated. A self-administered and anonymous questionnaire was used. Descriptive statistics and cross-tabular analysis were used to describe the results of this study. Inferential statistics were also used, including Chi square and t-tests to establish the associations/differences between physician knowledge and the independent variables. Of the participants, 87.9% demonstrated an inadequate knowledge about folic acid supplementation for the prevention of neural tube defects as part of preconception care and only 12.1% demonstrated adequate knowledge. Older physicians had greater knowledge about folic acid. Also, women demonstrated greater knowledge about folic acid than did men. Most of the physicians who always recommend supplementation to their patients demonstrated a greater knowledge about folic acid, and all participants with adequate knowledge came from the public hospital. Despite a concerted effort by the Health Department of Puerto Rico to provide education in the importance of folic acid supplementation to reduce the incidence of neural tube defects, primary physicians in two Puerto Rican hospitals generally have not availed themselves of this training and showed a lack of knowledge on this important clinical issue. Copyright 2003 Wiley-Liss, Inc.

  20. Neuropathic Ulcers Among Children With Neural Tube Defects: A Review of Literature.

    Science.gov (United States)

    Pandey, Anand; Gupta, Vipin; Singh, Shailendra P; Kumar, Vijendra; Verma, Rajesh

    2015-12-01

    A trophic ulcer is a pressure ulcer caused by external trauma to a part of the body that is compromised due to disease, vascular insufficiency, or loss of afferent nerve fibers. Spinal dysraphism (ie, neural tube defects [NTD]) such as meningomyelocele is a risk factor for developing these ulcers in adults and pediatric patients. Information regarding the occurrence of trophic ulcers in pediatric patients with NTD is lacking. A review of the English-language literature on skin/neuropathic ulcers in patients with NTDs, irrespective of study design, published between 1975 and 2014, was undertaken using the PubMed database. Search terms included trophic ulcer, neuropathic ulcer, NTDs, and meningomyelocele. From among the more than 200 papers related to skin care in neonates and pediatric patients, 11 addressed skin ulcers in patients of NTD - 1 in French (a review article), 1 in German (a case report), and 9 in English (7 cohort studies and 2 reviewing surgical techniques). Typically, ulcers in patients with NTD are neuropathic (ie, related to nerve pathology). The most common type is meningomyelocele. Patients with NTD present with a spectrum of functional and sensory deficits that impair mobility; other causative factors that may contribute to the occurrence of ulcers include stress to the tissue, the length of time the stress occurs, muscle spasticity, infection, moisture, and nutritional status of the patient. Awareness of ulcer risk and preventive measures, such as maintaining foot flexibility or careful handling bony prominences such as kyphosis, is important. Once an ulcer occurs, management is challenging and involves collaboration of multiple medical, surgical, nutrition, and other specialists. If an ulcer develops and NTD has not been previously treated surgically or the MRI shows evidence of retethering, surgical treatment is needed. More research is needed to help guide ulcer prevention and treatment strategies in pediatric patients with NTD.

  1. Punicalagin exerts protective effect against high glucose-induced cellular stress and neural tube defects.

    Science.gov (United States)

    Zhong, Jianxiang; Reece, E Albert; Yang, Peixin

    2015-11-13

    Maternal diabetes-induced birth defects remain a significant health problem. Studying the effect of natural compounds with antioxidant properties and minimal toxicities on diabetic embryopathy may lead to the development of new and safe dietary supplements. Punicalagin is a primary polyphenol found in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumorigenic properties, suggesting a protective effect of punicalagin on diabetic embryopathy. Here, we examined whether punicalagin could reduce high glucose-induced neural tube defects (NTDs), and if this rescue occurs through blockage of cellular stress and caspase activation. Embryonic day 8.5 (E8.5) mouse embryos were cultured for 24 or 36 h with normal (5 mM) glucose or high glucose (16.7 mM), in presence or absence of 10 or 20 μM punicalagin. 10 μM punicalagin slightly reduced NTD formation under high glucose conditions; however, 20 μM punicalagin significantly inhibited high glucose-induced NTD formation. Punicalagin suppressed high glucose-induced lipid peroxidation marker 4-hydroxynonenal, nitrotyrosine-modified proteins, and lipid peroxides. Moreover, punicalagin abrogated endoplasmic reticulum stress by inhibiting phosphorylated protein kinase ribonucleic acid (RNA)-like ER kinase (p-PERK), phosphorylated inositol-requiring protein-1α (p-IRE1α), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), binding immunoglobulin protein (BiP) and x-box binding protein 1 (XBP1) mRNA splicing. Additionally, punicalagin suppressed high glucose-induced caspase 3 and caspase 8 cleavage. Punicalagin reduces high glucose-induced NTD formation by blocking cellular stress and caspase activation. These observations suggest punicalagin supplements could mitigate the teratogenic effects of hyperglycemia in the developing embryo, and possibly prevent diabetes-induced NTDs.

  2. Prenatal Diagnosis, Fetal Surgery, Recurrence Risk and Differential Diagnosis of Neural Tube Defects

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-09-01

    Full Text Available Prenatal screening with α-fetoprotein (AFP and ultrasonography have allowed the prenatal diagnosis of neural tube defects (NTDs in current obstetric care, and open spina bifida has been considered a potential candidate for in utero treatment in modern pediatric surgery. This article provides an overview of maternal serum AFP screening, amniotic fluid AFP assays, amniotic fluid acetylcholinesterase immunoassays and level II ultrasound for NTDs, prenatal repair of fetal myelomeningocele, recurrence risk of NTDs, and differential diagnosis of NTDs on prenatal ultrasound.

  3. Disrupted dorsal neural tube BMP signaling in the cilia mutant Arl13b hnn stems from abnormal Shh signaling.

    Science.gov (United States)

    Horner, Vanessa L; Caspary, Tamara

    2011-07-01

    In the embryonic neural tube, multiple signaling pathways work in concert to create functional neuronal circuits in the adult spinal cord. In the ventral neural tube, Sonic hedgehog (Shh) acts as a graded morphogen to specify neurons necessary for movement. In the dorsal neural tube, bone morphogenetic protein (BMP) and Wnt signals cooperate to specify neurons involved in sensation. Several signaling pathways, including Shh, rely on primary cilia in vertebrates. In this study, we used a mouse mutant with abnormal cilia, Arl13b(hnn), to study the relationship between cilia, cell signaling, and neural tube patterning. Arl13b(hnn) mutants have abnormal ventral neural tube patterning due to disrupted Shh signaling; in addition, dorsal patterning defects occur, but the cause of these is unknown. Here we show that the Arl13b(hnn) dorsal patterning defects result from abnormal BMP signaling. In addition, we find that Wnt ligands are abnormally expressed in Arl13b(hnn) mutants; surprisingly, however, downstream Wnt signaling is normal. We demonstrate that Arl13b is required non-autonomously for BMP signaling and Wnt ligand expression, indicating that the abnormal Shh signaling environment in Arl13b(hnn) embryos indirectly causes dorsal defects.

  4. Communications technology satellite output-tube design and development

    Science.gov (United States)

    Connolly, D. J.; Forman, R.; Jones, C. L.; Kosmahl, H.; Sharp, G. R.

    1977-01-01

    The design and development of a 200-watt-output, traveling-wave tube (TWT) for the Communications Technology Satellite (CTS) is discussed, with emphasis on the design evolution during the manufacturing phase of the development program. Possible further improvements to the tube design are identified.

  5. VANGL1 rare variants associated with neural tube defects affect convergent extension in zebrafish.

    Science.gov (United States)

    Reynolds, Annie; McDearmid, Jonathan R; Lachance, Stephanie; De Marco, Patrizia; Merello, Elisa; Capra, Valeria; Gros, Philippe; Drapeau, Pierre; Kibar, Zoha

    2010-01-01

    In humans, rare non-synonymous variants in the planar cell polarity gene VANGL1 are associated with neural tube defects (NTDs). These variants were hypothesized to be pathogenic based mainly on genetic studies in a large cohort of NTD patients. In this study, we validate the potential pathogenic effect of these mutations in vivo by investigating their effect on convergent extension in zebrafish. Knocking down the expression of tri, the ortholog of Vangl2, using an antisense morpholino (MO), as shown previously, led to a defective convergent extension (CE) manifested by a shortened body axis and widened somites. Co-injection of the human VANGL1 with the tri-MO was able to partially rescue the tri-MO induced phenotype in zebrafish. In contrast, co-injection of two human VANGL1 variants, p.Val239Ile and p.Met328Thr, failed to rescue this phenotype. We next carried out overexpression studies where we measured the ability of the human VANGL1 alleles to induce a CE phenotype when injected at high doses in zebrafish embryos. While overexpressing the wild-type allele led to a severely defective CE, overexpression of either p.Val239Ile or p.Met328Thr variant failed to do so. Results from both tri-MO knockdown/rescue results and overexpression assays suggest that these two variants most likely represent "loss-of-function" alleles that affect protein function during embryonic development. Our study demonstrates a high degree of functional conservation of VANGL genes across evolution and provides a model system for studying potential variants identified in human NTDs.

  6. Prevention of neural tube defects by folic acid - awareness among women of childbearing age in Slovakia.

    Science.gov (United States)

    Horn, F; Sabova, L; Pinterova, E; Hornova, J; Trnka, J

    2014-01-01

    Folic acid deficiency plays a central role in the aetiology of many congenital anomalies including neural tube defects. Protective effect of folic acid on embryo may be acquired only if taken periconceptionally. The aim of the study was to investigate the awareness about folic acid among women of childbearing age in Bratislava, Slovakia. There were 130 respondents involved in the research (106 pregnant women, 24 female students of medical faculty). Using questionnaire we acquired following data: pregnancy details, interest in diet before and during pregnancy, recommendations regarding nutrition and supplementation pre- and post-conception, knowledge about folic and other acid in 2004 and 2009. More than half of the respondents knew the sources of folic acid. The interest in the nutrition facts of the food dropped from 91 % to 58.5 %. The number of pregnant women advised about correct nutrition and folic acid supplementation before and during pregnancy increased from 16 % to 37 %. Planning the next gravidity with folic acid supplementation became greater than 21 % (38 % in 2009). Nevertheless, only 46 % of these women believed that proper food content with folic acid may prevent congenital anomalies. In a group of students planning to take folic acid periconceptionally the number raised up to 62.5 %. The results revealed low knowledge about the effect of folic acid on developing embryo among women of childbearing age. Effective intervention programs are needed with the aim to improve periconceptional intake of folic acid in 2004 and 2009. The results in both periods show low knowledge about this essential vitamin (Tab. 1, Fig. 8, Ref. 31).

  7. Maternal bereavement in the antenathal period and Neural tube defect in the offspring

    DEFF Research Database (Denmark)

    Ingstrup, Katja Glejsted; Olsen, Jørn; Bech, Bodil Hammer

    2013-01-01

    was seen (OR 1.61, 95% CI: 1.07; 2.41). Discussion: We only studied live born children but about 2/3 of children with spina bifida survive the birth or longer with corrective surgery. We did not adjust for folic acid, but a sub-analysis of approximately 85,000 mothers showed no difference in intake during...... all children born in Denmark from 1978-2008 and their mothers (n=1,734,190). In the time window of one year before pregnancy or during the first trimester of pregnancy 34,407 mothers were exposed to bereavement. Results: A total of 5,031 cases of neural tube defects were identified: 889 with spina...... bifida and 2,095 with hydrocephalous. For all neural tube defects combined no significant association was seen (OR 1.07, 95% CI: 0.88; 1.31), however stratified on sex a higher risk was seen in girls compared to boys. Moreover, when bereavement was due to death of an older child an increased risk...

  8. Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube.

    Science.gov (United States)

    Stockinger, Petra; Maître, Jean-Léon; Heisenberg, Carl-Philipp

    2011-11-01

    Facial branchiomotor neurons (FBMNs) in zebrafish and mouse embryonic hindbrain undergo a characteristic tangential migration from rhombomere (r) 4, where they are born, to r6/7. Cohesion among neuroepithelial cells (NCs) has been suggested to function in FBMN migration by inhibiting FBMNs positioned in the basal neuroepithelium such that they move apically between NCs towards the midline of the neuroepithelium instead of tangentially along the basal side of the neuroepithelium towards r6/7. However, direct experimental evaluation of this hypothesis is still lacking. Here, we have used a combination of biophysical cell adhesion measurements and high-resolution time-lapse microscopy to determine the role of NC cohesion in FBMN migration. We show that reducing NC cohesion by interfering with Cadherin 2 (Cdh2) activity results in FBMNs positioned at the basal side of the neuroepithelium moving apically towards the neural tube midline instead of tangentially towards r6/7. In embryos with strongly reduced NC cohesion, ectopic apical FBMN movement frequently results in fusion of the bilateral FBMN clusters over the apical midline of the neural tube. By contrast, reducing cohesion among FBMNs by interfering with Contactin 2 (Cntn2) expression in these cells has little effect on apical FBMN movement, but reduces the fusion of the bilateral FBMN clusters in embryos with strongly diminished NC cohesion. These data provide direct experimental evidence that NC cohesion functions in tangential FBMN migration by restricting their apical movement.

  9. Application of GIS-Based Spatial Filtering Method for Neural Tube Defects Disease Mapping

    Institute of Scientific and Technical Information of China (English)

    CHI Wenxue; WANG Jinfeng; LI Xinhu; ZHENG Xiaoying; LIAO Yilan

    2007-01-01

    This study is to assess the prevalence rates spatial pattern of neural tube defects with geographic information system and spatial filtering technique. A total of 80 infants who diagnosed from neural tube defects in the area being studied between 1998 and 2001 were analyzed. Firstly, the geographic information system (GIS) software ArcGIS was used to map the crude prevalence rates. Secondly, the data were smoothed by the method of spatial filtering. We evaluated that the effect of changes in spatial filtering radius size was assessed by creating maps based on various filtering radius sizes, The 3 miles or larger filtering radius gives better sec tion variability than the 2 and 2.5 miles or smaller ones. The maps produced by the spatial filtering technique indicate that prevalence rates in the villages in the southeastern region are to produce higher prevalence than that in the other regions. The smoothed maps based on Heshun County display a more adequate data representation than the raw prevalence rate map.

  10. Neural tube defect surveillance and folic acid intervention--Texas-Mexico border, 1993-1998.

    Science.gov (United States)

    2000-01-14

    Neural tube defects (NTDs) are common and serious malformations that originate early in pregnancy. In the United States, approximately 4000 pregnancies each year are affected by the two most common NTDs (spina bifida and anencephaly). In 1992, the Texas Department of Health (TDH), with support from a CDC cooperative agreement, implemented the Texas Neural Tube Defect Project (TNTDP), a program of NTD surveillance and risk-reduction activities in the 14 counties that border Mexico. The project was initiated in response to an anencephaly cluster identified during 1990-1991 in Brownsville (Cameron County), Texas (1). Whether the high anencephaly rate (19.7 per 10,000 live births) was unique to Cameron County or was characteristic of the entire border was unknown. This report summarizes NTD surveillance rates for the 14 Texas-Mexico border counties for 1993-1998 and presents preliminary results of TNTDP efforts to prevent the recurrence of NTDs by providing folic acid to high-risk women. Findings indicate that the baseline rate along the border is high (13.4 per 10,000 live births) and largely reflects the rate among Hispanics (13.8). Although a longer period is needed to obtain definitive results, folic acid appears to be effective for reducing the risk for NTD recurrence in Hispanics.

  11. Chromosomal anomalies and additional sonographic findings in fetuses with open neural tube defects.

    Science.gov (United States)

    Yazici, Lutfiye Eren Ensari; Malatyalioglu, Erdal; Sakinci, Mehmet; Tosun, Migraci; Bildircin, Fatma Devran; Ogur, Gonul; Karayel, Metin

    2012-12-01

    To evaluate the results and the necessity of chromosome analysis in fetuses prenatally detected with a neural tube defect and to determine the significance of ultrasonographic evaluation for the identification of underlying or accompanying chromosomal anomalies. Ninety fetuses that underwent prenatal and/or postnatal chromosome analysis after being diagnosed with open neural tube defects (NTD) between the years 2006 and 2010 in the Department of Obstetrics and Gynecology at Ondokuz Mayis University School of Medicine were included in this study. Detailed fetal ultrasonography was performed in all cases in order to investigate any additional anomalies. Karyotype was determined in the prenatal period by amniocentesis in 72 (80%) of the 90 fetuses, and by cordocentesis in 5 (5.5%). In 13 (13.3%) fetuses, karyotype was determined in the postnatal period by blood sampling. Fourteen (15.5%) of the 90 fetuses were diagnosed with acrania/anencephaly, 14 (15.5%) with encephalocele, 2 (2.2%) with iniencephaly, 60 (66.6%) with open spina bifida. None of the 90 fetuses with open NTD who had undergone chromosome analysis was diagnosed with chromosomal anomalies. None of the 19 (21.1%) fetuses diagnosed with additional ultrasound findings had a chromosomal abnormality, either. Seventy-one (78.9%) fetuses having sonograhically isolated NTD were also isolated in postmortem examination. In fetuses with open NTD, we could not find the chromosomal anomaly rate as high as reported in previous literature. The necessity of fetal karyotyping should be questioned especially in isolated cases.

  12. Role of folic acid supplementation in prevention of neural tube defects: physicians yet unaware!

    Science.gov (United States)

    Aggarwal, A; Kumhar, G Das; Harit, D; Faridi, M M A

    2010-09-01

    Folic acid supplementation is important in the prevention of Neural Tube Defects (NTD). The study was conducted to assess the awareness amongst physicians regarding the role of Folic Acid (FA) in the prevention of NTD. Physicians were interviewed regarding the awareness of FA dose, timing of supplementation and knowledge about its role in prevention of neural tube defects using a semistructured questionnaire. Among 202 physicians interviewed (48 pediatricians, 54 obstetricians, 100 recently qualified medical graduates) overall awareness about FA was present in 92.07%, similar in three groups (P > 0.05). Only 47.52% were aware of preconception administration, 61.38% about dose of supplementation and 11.88% about recurrence rate of NTD. Only 15 (7.4%) knew all these. Regarding the etiology of NTDs only 26.7% said both FA and genetic factors are involved. Though majority were aware that folic acid has a role in prevention of NTDs, their knowledge about timing and dose of supplementation was lacking. Hence attempts should be made to increase the awareness regarding prevention of NTD's by FA supplementation at a proper time.

  13. Development and formability analysis of TRIP seamless steel tube

    Institute of Scientific and Technical Information of China (English)

    Zhang Zicheng; Zhu Fuxian

    2014-01-01

    In this paper,the production technology of transformation induced plasticity (TRIP) steel was first introduced into the steel tube manufacture field to produce the steel tubes with high strength and plasticity. The TRIP seamless steel tubes with the microstructure of ferrite,bainite,retained austenite and a little martensite were successfully fabricated using a cold-drawn steel tube with two-stage heat treatment technique and continu-ous heat treatment process,respectively. The ring tensile test and cold bend test were carried out to study the formability of the newly developed TRIP seamless steel tube. The results showed that the TRIP seamless steel tubes have a good cold formability,and they are available to be used in the tube hydroforming process. In ad-dition,the equipment of continuous heat treatment developed in the current study can be used to produce TRIP steel tube,and it may serve as an important reference for the industrial production of TRIP steel tube.

  14. Signi fi cance of Neural Crest in Tooth Development: The Molecular Signature

    Directory of Open Access Journals (Sweden)

    VP Jayasekharan

    2014-07-01

    Full Text Available The neural crest originates from cells located along the lateral margins of the neural plate. Neural crest cells arise as the result of an inductive action by the non-neural ectoderm adjacent to the neural plate and possibly by nearby mesoderm as well. As the neural tube forms, a group of cells separate from the neuro- ectoderm. These cells have the capacity to migrate and differen- tiate extensively within the developing embryo and they are the basis of structures such as spinal sensory ganglia, sympathetic neurons, Schwann cells, pigment cells and meninges. Speci fi c interactions occur during the development of tooth and recent research has concentrated more on the molecular aspects of these interactions. Thus, it is highly imperative to understand and digress the complex mechanisms involved in these processes

  15. Birth prevalence of neural tube defects and orofacial clefts in India: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Komal Preet Allagh

    Full Text Available In the last two decades, India has witnessed a substantial decrease in infant mortality attributed to infectious disease and malnutrition. However, the mortality attributed to birth defects remains constant. Studies on the prevalence of birth defects such as neural tube defects and orofacial clefts in India have reported inconsistent results. Therefore, we conducted a systematic review of observational studies to document the birth prevalence of neural tube defects and orofacial clefts.A comprehensive literature search for observational studies was conducted in MEDLINE and EMBASE databases using key MeSH terms (neural tube defects OR cleft lip OR cleft palate AND Prevalence AND India. Two reviewers independently reviewed the retrieved studies, and studies satisfying the eligibility were included. The quality of included studies was assessed using selected criteria from STROBE statement.The overall pooled birth prevalence (random effect of neural tube defects in India is 4.5 per 1000 total births (95% CI 4.2 to 4.9. The overall pooled birth prevalence (random effect of orofacial clefts is 1.3 per 1000 total births (95% CI 1.1 to 1.5. Subgroup analyses were performed by region, time period, consanguinity, and gender of newborn.The overall prevalence of neural tube defects from India is high compared to other regions of the world, while that of orofacial clefts is similar to other countries. The majority of studies included in the review were hospital based. The quality of these studies ranged from low to moderate. Further well-designed, high quality community-based observational studies are needed to accurately estimate the burden of neural tube defects and orofacial clefts in India.

  16. Hox genes: choreographers in neural development, architects of circuit organization.

    Science.gov (United States)

    Philippidou, Polyxeni; Dasen, Jeremy S

    2013-10-02

    The neural circuits governing vital behaviors, such as respiration and locomotion, are comprised of discrete neuronal populations residing within the brainstem and spinal cord. Work over the past decade has provided a fairly comprehensive understanding of the developmental pathways that determine the identity of major neuronal classes within the neural tube. However, the steps through which neurons acquire the subtype diversities necessary for their incorporation into a particular circuit are still poorly defined. Studies on the specification of motor neurons indicate that the large family of Hox transcription factors has a key role in generating the subtypes required for selective muscle innervation. There is also emerging evidence that Hox genes function in multiple neuronal classes to shape synaptic specificity during development, suggesting a broader role in circuit assembly. This Review highlights the functions and mechanisms of Hox gene networks and their multifaceted roles during neuronal specification and connectivity.

  17. Assessment of knowledge of female students from the Medical Department of the University of Rzeszow regarding isolated neural tube defects

    Directory of Open Access Journals (Sweden)

    Milewska Natalia

    2016-06-01

    Full Text Available Introduction: Dysraphic defects are malformations resulting from a failed neural tube closure in a critical moment of embryogenesis. These structural alterations may include contractures, varus and valgus deformities, scoliosis or hip joint dislocations. According to the literature of the subject, the incidence of dysraphic defects ranges from 1.2% to 4.0% of live births. It is believed that 30% of cases are caused by genetic and environmental factors. The aim of the work was to assess the knowledge of female students of medical courses regarding isolated neural tube defects and their prevention.

  18. Melatonin prevents neural tube defects in the offspring of diabetic pregnancy.

    Science.gov (United States)

    Liu, Shangming; Guo, Yuji; Yuan, Qiuhuan; Pan, Yan; Wang, Liyan; Liu, Qian; Wang, Fuwu; Wang, Jingjing; Hao, Aijun

    2015-11-01

    Melatonin, an endogenous neurohormone secreted by the pineal gland, has a variety of physiological functions and neuroprotective effects. However, its protective role on the neural tube defects (NTDs) was not very clear. The aim of this study was to investigate the effects of melatonin on the incidence of NTDs (including anencephaly, encephalocele, and spina bifida) of offspring from diabetic pregnant mice as well as its underlying mechanisms. Pregnant mice were given 10 mg/kg melatonin by daily i.p. injection from embryonic day (E) 0.5 until being killed on E11.5. Here, we showed that melatonin decreased the NTDs (especially exencephaly) rate of embryos exposed to maternal diabetes. Melatonin stimulated proliferation of neural stem cells (NSCs) under hyperglycemic condition through the extracellular regulated protein kinases (ERK) pathway. Furthermore, as a direct free radical scavenger, melatonin decreased apoptosis of NSCs exposed to hyperglycemia. In the light of these findings, it suggests that melatonin supplementation may play an important role in the prevention of neural malformations in diabetic pregnancy.

  19. Mechanics of neurulation: From classical to current perspectives on the physical mechanics that shape, fold, and form the neural tube.

    Science.gov (United States)

    Vijayraghavan, Deepthi S; Davidson, Lance A

    2016-09-13

    Neural tube defects arise from mechanical failures in the process of neurulation. At the most fundamental level, formation of the neural tube relies on coordinated, complex tissue movements that mechanically transform the flat neural epithelium into a lumenized epithelial tube (Davidson, 2012). The nature of this mechanical transformation has mystified embryologists, geneticists, and clinicians for more than 100 years. Early embryologists pondered the physical mechanisms that guide this transformation. Detailed observations of cell and tissue movements as well as experimental embryological manipulations allowed researchers to generate and test elementary hypotheses of the intrinsic and extrinsic forces acting on the neural tissue. Current research has turned toward understanding the molecular mechanisms underlying neurulation. Genetic and molecular perturbation have identified a multitude of subcellular components that correlate with cell behaviors and tissue movements during neural tube formation. In this review, we focus on methods and conceptual frameworks that have been applied to the study of amphibian neurulation that can be used to determine how molecular and physical mechanisms are integrated and responsible for neurulation. We will describe how qualitative descriptions and quantitative measurements of strain, force generation, and tissue material properties as well as simulations can be used to understand how embryos use morphogenetic programs to drive neurulation. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc.

  20. Raphe of the posterior neural tube in the chick embryo: its closure and reopening as studied in living embryos with a high definition light microscope.

    Science.gov (United States)

    van Straaten, H W; Jaskoll, T; Rousseau, A M; Terwindt-Rouwenhorst, E A; Greenberg, G; Shankar, K; Melnick, M

    1993-09-01

    Chick embryos cultured on a curved substratum show a transient enlargement of the posterior neuropore (PN), mimicking the temporary delay of PN closure as seen in the curly tail (ct) mouse mutant (van Straaten et al. [1993] Development 117:1163-1172). In the present study the PN enlargement in the chick embryo was investigated further with a high definition light microscope (HDmic), allowing high resolution viewing of living embryos in vitro. The temporary PN enlargement appeared due to considerable reopening of the raphe of the posterior neural tube, which was followed by reclosure after several hours. The raphe was subsequently studied in detail. It appeared very irregular, with small zones of apposed, open and fused neural folds. During closure, these raphe features shifted posteriorly. A distinct fusion sequence between surface epithelium and neuroepithelium was not seen. During experimental reopening of the raphe in vitro, small bridges temporarily arose, broke and disappeared quickly; they likely represented the first adhesion sites between the neural folds. More prominent adhesion sites partly detached, resulting in bridging filopodia-like connections; they probably represented the first anteroposterior locations of neural fold fusion. Our observations in the living chick embryo in vitro thus show that the caudal neural tube has an irregular raphe with few adhesion sites, which can be readily reopened. As a result of the irregularity, the PN does not close zipper-like, but button-like by forming multiple closure sites.

  1. Explosively Bonded Gun Tube Liner Development

    Science.gov (United States)

    2015-04-01

    level (MRL 10) measures aspects of lean practices and continuous improvement for systems in production. C.1 MRL 1: Basic Manufacturing Implications...the art is assessed through the use of Technology and Manufacturing Readiness Levels. 15. SUBJECT TERMS Ta alloys, gun-tube liners, explosive...bonding, firing tests, Technology Readiness Level, Manufacturing Readiness Level 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18

  2. Neural induction and factors that stabilize a neural fate

    OpenAIRE

    Rogers, Crystal; Moody, Sally A.; Casey, Elena

    2009-01-01

    The neural ectoderm of vertebrates forms when the BMP signaling pathway is suppressed. Herein we review the molecules that directly antagonize extracellular BMP and the signaling pathways that further contribute to reduce BMP activity in the neural ectoderm. Downstream of neural induction, a large number of “neural fate stabilizing” (NFS) transcription factors are expressed in the presumptive neural ectoderm, developing neural tube, and ultimately in neural stem cells. Herein we review what i...

  3. Folic acid and the decline in neural tube defects in Arkansas.

    Science.gov (United States)

    Mosley, Bridget S; Hobbs, Charlotte A; Flowers, Bettye S; Smith, Veronica; Robbins, James M

    2007-04-01

    Folic acid has been shown to reduce the risk of pregnancies affected by neural tube defects (NTDs) by as much as 70%. Cereal grains sold in the U.S. have been fortified with folic acid since 1998. The Arkansas Reproductive Health Monitoring System and the Arkansas Folic Acid Coalition have encouraged use of folic acid and monitored the impact of increased consumption of folic acid among Arkansans. NTDs in Arkansas have declined 40% since intervention programs were implemented. The greatest decline has been observed among white and Hispanic women. Efforts to encourage folic acid consumption should continue to target Arkansas women. NTDs include anencephaly and spina bifida. These birth defects result from incomplete closure of the fetal neural tube during the first month of pregnancy. Infants with anencephaly are born without all or most of their brain and die within a few days of life. Infants with spina bifida have varying degrees of impairment ranging from little noticeable disability to severe, lifelong disability. Folic acid, when taken in supplement form has been shown to reduce the risk of a pregnancy affected by a neural tube defect by as much as 70%. As a result of this finding, the U.S. Federal Drug Administration mandated that cereal grains sold in this country be fortified with at least 140 mcg of folic acid per 100 grams of grain by January 1, 1998. Prior to mandatory fortification, the March of Dimes and the U.S. Public Health Service released statements encouraging all women of reproductive age who are capable of becoming pregnant to take 400 mcg 'of synthetic folic acid daily. The Arkansas Reproductive Health Monitoring System (ARHMS) has monitored rates of NTDs in Arkansas since 1980. ARHMS is the lead agency of the Arkansas Folic Acid Coalition whose mission is to encourage folic acid use among all Arkansas women of reproductive age. In this report, we summarize efforts by ARHMS and the Arkansas Folic Acid Coalition to increase the awareness and

  4. Streak tube photocathode development program. Phase 2, Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    1993-11-20

    This report details the progress made toward developing a streak tube with greater than 1% quantum efficiency at a wavelength of 1300 nm. The achieved performance is the result of approximately three years of effort. The goal of Phase 2 of this contract was to seal a working 1.3 {mu}m streak tube. This effort was focused in two areas. First there was a continuing effort to further develop and demonstrate the cathodes ability to meet the stated requirements. The second effort was aimed at solving the mechanical and process related problems related to sealing this cathode onto a EG&G streak tube.

  5. High glucose-induced oxidative stress represses sirtuin deacetylase expression and increases histone acetylation leading to neural tube defects.

    Science.gov (United States)

    Yu, Jingwen; Wu, Yanqing; Yang, Peixin

    2016-05-01

    Aberrant epigenetic modifications are implicated in maternal diabetes-induced neural tube defects (NTDs). Because cellular stress plays a causal role in diabetic embryopathy, we investigated the possible role of the stress-resistant sirtuin (SIRT) family histone deacetylases. Among the seven sirtuins (SIRT1-7), pre-gestational maternal diabetes in vivo or high glucose in vitro significantly reduced the expression of SIRT 2 and SIRT6 in the embryo or neural stem cells, respectively. The down-regulation of SIRT2 and SIRT6 was reversed by superoxide dismutase 1 (SOD1) over-expression in the in vivo mouse model of diabetic embryopathy and the SOD mimetic, tempol and cell permeable SOD, PEGSOD in neural stem cell cultures. 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a superoxide generating agent, mimicked high glucose-suppressed SIRT2 and SIRT6 expression. The acetylation of histone 3 at lysine residues 56 (H3K56), H3K14, H3K9, and H3K27, putative substrates of SIRT2 and SIRT6, was increased by maternal diabetes in vivo or high glucose in vitro, and these increases were blocked by SOD1 over-expression or tempol treatment. SIRT2 or SIRT6 over-expression abrogated high glucose-suppressed SIRT2 or SIRT6 expression, and prevented the increase in acetylation of their histone substrates. The potent sirtuin activator (SRT1720) blocked high glucose-increased histone acetylation and NTD formation, whereas the combination of a pharmacological SIRT2 inhibitor and a pan SIRT inhibitor mimicked the effect of high glucose on increased histone acetylation and NTD induction. Thus, diabetes in vivo or high glucose in vitro suppresses SIRT2 and SIRT6 expression through oxidative stress, and sirtuin down-regulation-induced histone acetylation may be involved in diabetes-induced NTDs. The mechanism underlying pre-gestational diabetes-induced neural tube defects (NTDs) is still elusive. Our study unravels a new epigenetic mechanism in which maternal diabetes-induced oxidative stress represses

  6. Stage-specific roles of FGF2 signaling in human neural development.

    Science.gov (United States)

    Grabiec, Marta; Hříbková, Hana; Vařecha, Miroslav; Střítecká, Dana; Hampl, Aleš; Dvořák, Petr; Sun, Yuh-Man

    2016-09-01

    This study elucidated the stage-specific roles of FGF2 signaling during neural development using in-vitro human embryonic stem cell-based developmental modeling. We found that the dysregulation of FGF2 signaling prior to the onset of neural induction resulted in the malformation of neural rosettes (a neural tube-like structure), despite cells having undergone neural induction. The aberrant neural rosette formation may be attributed to the misplacement of ZO-1, which is a polarized tight junction protein and shown co-localized with FGF2/FGFR1 in the apical region of neural rosettes, subsequently led to abnormal neurogenesis. Moreover, the FGF2 signaling inhibition at the stage of neural rosettes caused a reduction in cell proliferation, an increase in numbers of cells with cell-cycle exit, and premature neurogenesis. These effects may be mediated by NUMB, to which expression was observed enriched in the apical region of neural rosettes after FGF2 signaling inhibition coinciding with the disappearance of PAX6(+)/Ki67(+) neural stem cells and the emergence of MAP2(+) neurons. Moreover, our results suggested that the hESC-based developmental system reserved a similar neural stem cell niche in vivo.

  7. Methylenetetrahydrofolate reductase mutations, a genetic cause for familial recurrent neural tube defects

    Directory of Open Access Journals (Sweden)

    Laxmi V Yaliwal

    2012-01-01

    Full Text Available Methylenetetrahydrofolate reductase (MTHFR gene mutations have been implicated as risk factors for neural tube defects (NTDs. The best-characterized MTHFR genetic mutation 677C→T is associated with a 2-4 fold increased risk of NTD if patient is homozygous for this mutation. This risk factor is modulated by folate levels in the body. A second mutation in the MTHFR gene is an A→C transition at position 1298. The 1298A→C mutation is also a risk factor for NTD, but with a smaller relative risk than 677C→T mutation. Under conditions of low folate intake or high folate requirements, such as pregnancy, this mutation could become of clinical importance. We present a case report with MTHFR genetic mutation, who presented with recurrent familial pregnancy losses due to anencephaly/NTDs.

  8. Folic acid supplementation influences the distribution of neural tube defect subtypes: A registry-based study.

    Science.gov (United States)

    Bergman, J E H; Otten, E; Verheij, J B G M; de Walle, H E K

    2016-01-01

    Periconceptional folic acid (FA) reduces neural tube defect (NTD) risk, but seems to have a varying effect per NTD subtype. We aimed to study the effect of FA supplementation on NTD subtype distribution using data from EUROCAT Northern Netherlands. We included all birth types with non-syndromal NTDs born in 1997-2012. By Fisher's exact test we analyzed possible differences in NTD subtype distribution between a correct FA supplementation group and incorrect FA supplementation group. We found proportionally fewer cervical/thoracic spina bifida cases and more lumbar/sacral spina bifida cases in the correct FA supplementation group, irrespective of the presence of the main NTD risk factors. The effect on NTD subtype distribution was only seen when FA supplementation was started before conception. We conclude that FA not only prevents the occurrence of a significant proportion of NTDs, but might also decrease the severity of NTDs, as long as supplementation is started before conception.

  9. Trends in neural tube defect prevalence, folic acid fortification, and vitamin supplement use.

    Science.gov (United States)

    Olney, Richard S; Mulinare, Joseph

    2002-08-01

    In this review, the authors analyze international trends in rates of neural tube defects (NTDs) during the past three decades. Population-based data sources include the Metropolitan Atlanta Congenital Defects Program and other US birth defects surveillance programs in the National Birth Defects Prevention Network, the International Clearinghouse for Birth Defects Monitoring Systems, and US and Canadian vital records. To analyze trends in vitamin consumption, we review data from the US National Health and Nutrition Examination Surveys and international surveys of multivitamin use. We discuss the role of factors associated with historic and continuing declines in NTD rates in most countries. These factors include the introduction and increased utilization of prenatal diagnosis, recommendations for multivitamin use in women of childbearing age, and population-wide increases in blood folate levels that have occurred since food fortification was mandated. We also discuss research needs for further NTD prevention. This is a US government work. There are no restrictions on its use.

  10. Folate and neural tube defects: The role of supplements and food fortification.

    Science.gov (United States)

    Ami, Noam; Bernstein, Mark; Boucher, François; Rieder, Michael; Parker, Louise

    2016-04-01

    Periconceptional folic acid significantly reduces the risk of neural tube defects. It is difficult to achieve optimal levels of folate by diet alone, even with fortification of flour, especially because flour consumption in Canada is slightly decreasing. Intermittent concerns have been raised concerning possible deleterious effects of folate supplementation, including the masking of symptoms of vitamin B12 deficiency and an association with cancer, especially colorectal cancer. Both concerns have been disproved. The Canadian Paediatric Society endorses the following steps to enhance folate intake in women of child-bearing age: encouraging the consumption of folate-rich foods such as leafy vegetables, increasing the level of folate food fortification, taking a supplement containing folate and B12, and providing free folate supplementation to disadvantaged women of child-bearing age. These recommendations are consistent with those of the Society of Obstetricians and Gynaecologists of Canada.

  11. Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VI

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-09-01

    Full Text Available Neural tube defects (NTDs may be associated with syndromes, disorders, and maternal and fetal risk factors. This article provides a comprehensive review of the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, including maternal fumonisin consumption, periconceptional zinc deficiency, parental occupational exposure and residential proximity to pesticides, lower socioeconomic status, fetal alcohol syndrome, mutations in the VANGL1 gene, human athymic Nude/SCID fetus, and single nucleotide polymorphism in the NOS3 gene. NTDs associated with these syndromes, disorders, and maternal and fetal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

  12. Maternal Serum α-Fetoprotein Screening for the Detection of Neural Tube Defects—Report of a Pilot Program

    Science.gov (United States)

    Crandall, Barbara F.; Robertson, Robert D.; Lebherz, Thomas B.; King, William; Schroth, Phillip C.

    1983-01-01

    We tested 10,715 low-risk pregnancies in a voluntary maternal serum α-fetoprotein screening program for the detection of neural tube defects in California. In all, 5.3 percent of women had one elevated serum level, 3.3 percent were referred for sonography and 1.5 percent for amniocentesis. There were 12 cases of open neural tube defects (1.1 per 1,000); all of the mothers had one elevated serum αfetoprotein level: nine (75 percent) completed the protocol and the neural tube defects were correctly identified. No normal pregnancies were terminated. The risk of an open neural tube defect occurring was about 1 in 50 after the first abnormal serum level and 1 in 15 at amniocentesis. We found significantly increased risk for fetal death and low birth weight after one elevated serum α-fetoprotein level, though the likelihood of a normal pregnancy outcome was about 80 percent. Maternal serum screening was also useful in identifying twin pregnancies and correcting underestimated gestational dates. PMID:6191442

  13. Will Increasing Folic Acid in Fortified Grain Products Further Reduce Neural Tube Defects without Causing Harm?: Consideration of the Evidence

    Science.gov (United States)

    Will Increasing Folic Acid in Fortified Grain Products Further Reduce Neural Tube Defects without Causing Harm?: Consideration of the Evidence. In the January issue of this journal, Johnston (1) includes our group’s recent analysis of data from the 1999-2002 National Health and Nutrition Examination...

  14. Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid

    Science.gov (United States)

    The objective of this study was to evaluate the beneficial effects of different levels of folic acid administration on the prevalence of neural tube defects, with a concurrent assessment of other potential benefits or adverse effects. The evaluation was based on a systematic review of the published ...

  15. Increased sphingoid base-1-phosphates and failure of neural tube closure after exposure to fumonisin or FTY720

    Science.gov (United States)

    Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of corn. Ingestion of FB1-contaminated food is associated with increased risk for neural tube defects (NTDs). FB1 induces NTDs in inbred LM/Bc mice. FB1 inhibits ceramide synthase in de novo sphingolipid biosynthesis, resultin...

  16. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects

    NARCIS (Netherlands)

    Korstanje, Ron; Desai, Jigar; Lazar, Gloria; King, Benjamin; Rollins, Jarod; Spurr, Melissa; Joseph, Jamie; Kadambi, Sindhuja; Li, Yang; Cherry, Allison; Matteson, Paul G.; Paigen, Beverly; Millonig, James H.

    2008-01-01

    Korstanje R, Desai J, Lazar G, King B, Rollins J, Spurr M, Joseph J, Kadambi S, Li Y, Cherry A, Matteson PG, Paigen B, Millonig JH. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects. Physiol Genomics 35: 296-30

  17. Use of Family History Information for Neural Tube Defect Prevention: Integration into State-Based Recurrence Prevention Programs

    Science.gov (United States)

    Green, Ridgely Fisk; Ehrhardt, Joan; Ruttenber, Margaret F.; Olney, Richard S.

    2011-01-01

    A family history of neural tube defects (NTDs) can increase the risk of a pregnancy affected by an NTD. Periconceptional folic acid use decreases this risk. Purpose: Our objective was to determine whether second-degree relatives of NTD-affected children showed differences in folic acid use compared with the general population and to provide them…

  18. Neural Tube Defect Induction by Fumonisin B1 in LM/Bc Mice Fed Folate Deficient or Folate Replete Diets

    Science.gov (United States)

    Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides and F. proliferatum. FB1 is found in corn-based foods and evidence suggests that it is a risk factor for neural tube defects (NTD). The mechanism(s) underlying NTD induction by FB1 in the sensitive LM/Bc mouse model is not well...

  19. Genetic interactions between planar cell polarity genes cause diverse neural tube defects in mice

    Directory of Open Access Journals (Sweden)

    Jennifer N. Murdoch

    2014-10-01

    Full Text Available Neural tube defects (NTDs are among the commonest and most severe forms of developmental defect, characterized by disruption of the early embryonic events of central nervous system formation. NTDs have long been known to exhibit a strong genetic dependence, yet the identity of the genetic determinants remains largely undiscovered. Initiation of neural tube closure is disrupted in mice homozygous for mutations in planar cell polarity (PCP pathway genes, providing a strong link between NTDs and PCP signaling. Recently, missense gene variants have been identified in PCP genes in humans with NTDs, although the range of phenotypes is greater than in the mouse mutants. In addition, the sequence variants detected in affected humans are heterozygous, and can often be detected in unaffected individuals. It has been suggested that interactions between multiple heterozygous gene mutations cause the NTDs in humans. To determine the phenotypes produced in double heterozygotes, we bred mice with all three pairwise combinations of Vangl2Lp, ScribCrc and Celsr1Crsh mutations, the most intensively studied PCP mutants. The majority of double-mutant embryos had open NTDs, with the range of phenotypes including anencephaly and spina bifida, therefore reflecting the defects observed in humans. Strikingly, even on a uniform genetic background, variability in the penetrance and severity of the mutant phenotypes was observed between the different double-heterozygote combinations. Phenotypically, Celsr1Crsh;Vangl2Lp;ScribCrc triply heterozygous mutants were no more severe than doubly heterozygous or singly homozygous mutants. We propose that some of the variation between double-mutant phenotypes could be attributed to the nature of the protein disruption in each allele: whereas ScribCrc is a null mutant and produces no Scrib protein, Celsr1Crsh and Vangl2Lp homozygotes both express mutant proteins, consistent with dominant effects. The variable outcomes of these genetic

  20. Genetic interactions between planar cell polarity genes cause diverse neural tube defects in mice.

    Science.gov (United States)

    Murdoch, Jennifer N; Damrau, Christine; Paudyal, Anju; Bogani, Debora; Wells, Sara; Greene, Nicholas D E; Stanier, Philip; Copp, Andrew J

    2014-10-01

    Neural tube defects (NTDs) are among the commonest and most severe forms of developmental defect, characterized by disruption of the early embryonic events of central nervous system formation. NTDs have long been known to exhibit a strong genetic dependence, yet the identity of the genetic determinants remains largely undiscovered. Initiation of neural tube closure is disrupted in mice homozygous for mutations in planar cell polarity (PCP) pathway genes, providing a strong link between NTDs and PCP signaling. Recently, missense gene variants have been identified in PCP genes in humans with NTDs, although the range of phenotypes is greater than in the mouse mutants. In addition, the sequence variants detected in affected humans are heterozygous, and can often be detected in unaffected individuals. It has been suggested that interactions between multiple heterozygous gene mutations cause the NTDs in humans. To determine the phenotypes produced in double heterozygotes, we bred mice with all three pairwise combinations of Vangl2(Lp), Scrib(Crc) and Celsr1(Crsh) mutations, the most intensively studied PCP mutants. The majority of double-mutant embryos had open NTDs, with the range of phenotypes including anencephaly and spina bifida, therefore reflecting the defects observed in humans. Strikingly, even on a uniform genetic background, variability in the penetrance and severity of the mutant phenotypes was observed between the different double-heterozygote combinations. Phenotypically, Celsr1(Crsh);Vangl2(Lp);Scrib(Crc) triply heterozygous mutants were no more severe than doubly heterozygous or singly homozygous mutants. We propose that some of the variation between double-mutant phenotypes could be attributed to the nature of the protein disruption in each allele: whereas Scrib(Crc) is a null mutant and produces no Scrib protein, Celsr1(Crsh) and Vangl2(Lp) homozygotes both express mutant proteins, consistent with dominant effects. The variable outcomes of these genetic

  1. Inositol for the prevention of neural tube defects: a pilot randomised controlled trial.

    Science.gov (United States)

    Greene, Nicholas D E; Leung, Kit-Yi; Gay, Victoria; Burren, Katie; Mills, Kevin; Chitty, Lyn S; Copp, Andrew J

    2016-03-28

    Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised.

  2. Awareness of folic acid for neural tube defect prevention among Israeli women.

    Science.gov (United States)

    Ringel, S; Lahat, E; Elizov, T; Greenberg, R; Arieli, S; Afriat, R; Berkovitch, M

    1999-07-01

    The failure of neural tube closure during early embryogenesis results in a range of neural tube defects (NTD), the most common of which is spina bifida. The role of folic acid in reducing the rate of NTD has been well-established. Three recent cases of infants with NTD inspired this investigative study into the level of awareness and knowledge of folic acid and its function in the prevention of NTD among Israeli women. Of 920 women interviewed, only 51 (5.5%) had heard of folic acid, and 27 (2.8%) were reported to have taken it. The source of information and the motivation for self-medication were also explored with regard to socioeconomic and health profile. Awareness of folic acid was significant among women aged 17-29 years (P = 0.005) and those aged 30-39 years (P = 0.009), and among semireligious and nonreligious women (P = 0.008 and 0.01, respectively). Among women who were aware of folic acid, only nonreligious women tended to take it. No correlation was found between folic acid intake and age, religiosity, nationality, number of pregnancies, and health status among women who were aware of folic acid intake. The poor level of awareness, evident in our study, demands that the medical community broadcast the benefit of folic acid. Furthermore, government health initiatives, such as the addition of folic acid to flour preparations, may effectively ensure its appropriate daily intake. These improved education and prevention programs may forcibly reduce the rate of NTD-affected pregnancies.

  3. Risk factors, organ weight deviation and associated anomalies in neural tube defects: A prospective fetal and perinatal autopsy series

    Directory of Open Access Journals (Sweden)

    Asaranti Kar

    2015-01-01

    Full Text Available Introduction: Neural tube defects (NTD are a group of serious birth defects occurring due to defective closure of neural tube during embryonic development. It comprises of anencephaly, encephalocele and spina bifida. We conducted this prospective fetal autopsy series to study the rate and distribution of NTD, analyze the reproductive factors and risk factors, note any associated anomalies and evaluate the organ weights and their deviation from normal. Materials and Methods: This was a prospective study done over a period of 6 years from August, 2007 to July, 2013. All cases of NTDs delivered as abortion, still born and live born were included. The reproductive and risk factors like age, parity, multiple births, previous miscarriage, obesity, diabetes mellitus, socioeconomic status and use of folic acid during pregnancy were collected.Autopsy was performed according to Virchow′s technique. Detail external and internal examination were carried out to detect any associated anomalies. Gross and microscopic examination of organs were done. Results: Out of 210 cases of fetal and perinatal autopsy done, 72 (34.28% had NTD constituting 49 cases of anencephaly, 16 spina bifida and 7 cases of encephalocele. The mothers in these cases predominantly were within 25-29 years (P = 0.02 and primy (P = 0.01. Female sex was more commonly affected than males (M:F = 25:47, P = 0.0005 There was no history of folate use in majority of cases. Organ weight deviations were >2 standard deviation low in most of the cases. Most common associated anomalies were adrenal hypoplasia and thymic hyperplasia. Conclusion: The authors have made an attempt to study NTD cases in respect to maternal reproductive and risk factors and their association with NTD along with the organ weight deviation and associated anomalies. This so far in our knowledge is an innovative study which was not found in literature even after extensive search.

  4. 神经管畸形动物模型的研究进展%A review on the neural tube defects animal model

    Institute of Scientific and Technical Information of China (English)

    王秀伟

    2011-01-01

    Neural tube defects (NTDs) is one of the common, high incidence, serious consequences birth defects. It is an important problem to affect the quality of our country population. Now, the most content of the research are finished depending on animal model. Research on an neural tube defects animal model plays an important role in studying the development of pathogenesis, prevention and treatment. This article reviews the methods of NTDs induction and its mechanism from the two factors of physical and chemical.%神经管畸形(neural tube defects,NTDs)是一类常见的发病率高且后果严重的出生缺陷,为影响我国出生人口素质的重要问题.目前,其大部分研究内容依靠动物模型来完成.神经管畸形动物模型的建立对研究其发病机制及其防治起着重要作用.本文从物理和化学两方面因素对神经管畸形动物模型诱导方法及其机制作一综述.

  5. Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure

    Directory of Open Access Journals (Sweden)

    Erica M. McGreevy

    2015-01-01

    Full Text Available Neural tube closure is a critical developmental event that relies on actomyosin contractility to facilitate specific processes such as apical constriction, tissue bending, and directional cell rearrangements. These complicated processes require the coordinated activities of Rho-Kinase (Rock, to regulate cytoskeletal dynamics and actomyosin contractility, and the Planar Cell Polarity (PCP pathway, to direct the polarized cellular behaviors that drive convergent extension (CE movements. Here we investigate the role of Shroom3 as a direct linker between PCP and actomyosin contractility during mouse neural tube morphogenesis. In embryos, simultaneous depletion of Shroom3 and the PCP components Vangl2 or Wnt5a results in an increased liability to NTDs and CE failure. We further show that these pathways intersect at Dishevelled, as Shroom3 and Dishevelled 2 co-distribute and form a physical complex in cells. We observed that multiple components of the Shroom3 pathway are planar polarized along mediolateral cell junctions in the neural plate of E8.5 embryos in a Shroom3 and PCP-dependent manner. Finally, we demonstrate that Shroom3 mutant embryos exhibit defects in planar cell arrangement during neural tube closure, suggesting a role for Shroom3 activity in CE. These findings support a model in which the Shroom3 and PCP pathways interact to control CE and polarized bending of the neural plate and provide a clear illustration of the complex genetic basis of NTDs.

  6. Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure.

    Science.gov (United States)

    McGreevy, Erica M; Vijayraghavan, Deepthi; Davidson, Lance A; Hildebrand, Jeffrey D

    2015-01-16

    Neural tube closure is a critical developmental event that relies on actomyosin contractility to facilitate specific processes such as apical constriction, tissue bending, and directional cell rearrangements. These complicated processes require the coordinated activities of Rho-Kinase (Rock), to regulate cytoskeletal dynamics and actomyosin contractility, and the Planar Cell Polarity (PCP) pathway, to direct the polarized cellular behaviors that drive convergent extension (CE) movements. Here we investigate the role of Shroom3 as a direct linker between PCP and actomyosin contractility during mouse neural tube morphogenesis. In embryos, simultaneous depletion of Shroom3 and the PCP components Vangl2 or Wnt5a results in an increased liability to NTDs and CE failure. We further show that these pathways intersect at Dishevelled, as Shroom3 and Dishevelled 2 co-distribute and form a physical complex in cells. We observed that multiple components of the Shroom3 pathway are planar polarized along mediolateral cell junctions in the neural plate of E8.5 embryos in a Shroom3 and PCP-dependent manner. Finally, we demonstrate that Shroom3 mutant embryos exhibit defects in planar cell arrangement during neural tube closure, suggesting a role for Shroom3 activity in CE. These findings support a model in which the Shroom3 and PCP pathways interact to control CE and polarized bending of the neural plate and provide a clear illustration of the complex genetic basis of NTDs.

  7. Neural differentiation and synaptogenesis in retinal development.

    Science.gov (United States)

    Fan, Wen-Juan; Li, Xue; Yao, Huan-Ling; Deng, Jie-Xin; Liu, Hong-Liang; Cui, Zhan-Jun; Wang, Qiang; Wu, Ping; Deng, Jin-Bo

    2016-02-01

    To investigate the pattern of neural differentiation and synaptogenesis in the mouse retina, immunolabeling, BrdU assay and transmission electron microscopy were used. We show that the neuroblastic cell layer is the germinal zone for neural differentiation and retinal lamination. Ganglion cells differentiated initially at embryonic day 13 (E13), and at E18 horizontal cells appeared in the neuroblastic cell layer. Neural stem cells in the outer neuroblastic cell layer differentiated into photoreceptor cells as early as postnatal day 0 (P0), and neural stem cells in the inner neuroblastic cell layer differentiated into bipolar cells at P7. Synapses in the retina were mainly located in the outer and inner plexiform layers. At P7, synaptophysin immunostaining appeared in presynaptic terminals in the outer and inner plexiform layers with button-like structures. After P14, presynaptic buttons were concentrated in outer and inner plexiform layers with strong staining. These data indicate that neural differentiation and synaptogenesis in the retina play important roles in the formation of retinal neural circuitry. Our study showed that the period before P14, especially between P0 and P14, represents a critical period during retinal development. Mouse eye opening occurs during that period, suggesting that cell differentiation and synaptic formation lead to the attainment of visual function.

  8. Early adversity, neural development, and inflammation.

    Science.gov (United States)

    Chiang, Jessica J; Taylor, Shelley E; Bower, Julienne E

    2015-12-01

    Early adversity is a risk factor for poor mental and physical health. Although altered neural development is believed to be one pathway linking early adversity to psychopathology, it has rarely been considered a pathway linking early adversity to poor physical health. However, this is a viable pathway because the central nervous system is known to interact with the immune system via the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). In support of this pathway, early adversity has been linked to changes in neural development (particularly of the amygdala, hippocampus, and prefrontal cortex), HPA axis and ANS dysregulation, and higher levels of inflammation. Inflammation, in turn, can be detrimental to physical health when prolonged. In this review, we present these studies and consider how altered neural development may be a pathway by which early adversity increases inflammation and thus risk for adverse physical health outcomes.

  9. G-protein-coupled receptors and localized signaling in the primary cilium during ventral neural tube patterning.

    Science.gov (United States)

    Hwang, Sun-Hee; Mukhopadhyay, Saikat

    2015-01-01

    The primary cilium is critical in sonic hedgehog (Shh)-dependent ventral patterning of the vertebrate neural tube. Most mutants that cause disruption of the cilium result in decreased Shh signaling in the neural tube. In contrast, mutations in the intraflagellar complex A (IFT-A) and the tubby family protein, Tulp3, result in increased Shh signaling in the neural tube. Proteomic analysis of Tulp3-binding proteins first pointed to the role of the IFT-A complex in trafficking Tulp3 into the cilia. Tulp3 directs trafficking of rhodopsin family G-protein-coupled receptors (GPCRs) to the cilia, suggesting the role of a GPCR in mediating the paradoxical effects of the Tulp3/IFT-A complex in causing increased Shh signaling. Gpr161 has recently been identified as a Tulp3/IFT-A-regulated GPCR that localizes to the primary cilium. A null knock-out mouse model of Gpr161 phenocopies Tulp3 and IFT-A mutants, and causes increased Shh signaling throughout the neural tube. In the absence of Shh, the bifunctional Gli transcription factors are proteolytically processed into repressor forms in a protein kinase A (PKA) -dependent and cilium-dependent manner. Gpr161 activity results in increased cAMP levels in a Gαs -coupled manner, and determines processing of Gli3. Shh signaling also results in removal of Gpr161 from the cilia, suggesting that Gpr161 functions in a positive feedback loop in the Shh pathway. As PKA-null and Gαs mutant embryos also exhibit increased Shh signaling in the neural tube, Gpr161 is a strong candidate for a GPCR that regulates ciliary cAMP levels, and activates PKA in close proximity to the cilia.

  10. DEVELOPMENT OF ODS HEAT EXCHANGER TUBING

    Energy Technology Data Exchange (ETDEWEB)

    Mark A. Harper, Ph.D.

    2001-04-30

    Work has begun under three major tasks of this project. With respect to increasing the circumferential strength of a MA956 tube, approximately 60 MA956 rods have been extruded using a 20:1 extrusion ratio and extrusion temperatures of 1000, 1075, 1150, and 1200 C. Also, creep testing is underway for the purpose of determining the ''stress threshold'' curves for this alloy. Regarding joining of the alloy MA956, work has begun on the friction welding, magnetic impulse welding, explosive welding, and transient liquid phase bonding aspects of this project. And finally, material is being prepared for the laboratory fire-side high temperature corrosion tests, with potential gas and deposits for a typical Vision 21 plant being reviewed for final determination of these variables in the test program.

  11. Efeito da fortificação com ácido fólico na redução dos defeitos do tubo neural The effect of folic acid fortification on the reduction of neural tube defects

    Directory of Open Access Journals (Sweden)

    Leonor Maria Pacheco Santos

    2007-01-01

    Full Text Available Defeitos do tubo neural são malformações que ocorrem na fase inicial do desenvolvimento fetal, levando à anencefalia e espinha bífida; o ácido fólico é o mais importante fator de risco identificado até hoje. A prevalência relatada de defeitos do tubo neural coloca o Brasil no patamar dos países com as mais altas taxas no mundo. Inquéritos sobre consumo de folato entre gestantes brasileiras mostram ingestão altamente deficiente (Neural tube defects are congenital malformations that occur during initial fetal development, leading to anencephaly and spina bifida; folic acid deficiency is the most important risk factor identified to date. Brazil has one of the world's highest neural tube defect rates. Food consumption surveys among pregnant Brazilian women showed a high rate of inadequate folic acid intake (< 0.6mg/day. In 2004, the National Health Surveillance Agency (ANVISA mandated the fortification of corn meal and wheat flour with folic acid (0.15mg/100g. The National Family Budget Survey estimated the average amount of bread/flour products available in households as 106.1g/day (contributing with 0.16mg folic acid/day. However, while in the South of the country the supply was 144g/day, in the North and Central West it barely reached 70g/day. Folic acid food fortification is mandatory in some 40 countries, but only four have assessed this strategy. The existing studies have all shown a significant impact, ranging from 19 to 78%. Folic acid fortification is an undeniably important intervention for primary prevention, and neural tube defects can now be considered a preventable epidemic.

  12. Sulf1 influences the Shh morphogen gradient during the dorsal ventral patterning of the neural tube in Xenopus tropicalis.

    Science.gov (United States)

    Ramsbottom, Simon A; Maguire, Richard J; Fellgett, Simon W; Pownall, Mary Elizabeth

    2014-07-15

    Genetic studies have established that heparan sulphate proteoglycans (HSPGs) are required for signalling by key developmental regulators, including Hedgehog, Wnt/Wg, FGF, and BMP/Dpp. Post-synthetic remodelling of heparan sulphate (HS) by Sulf1 has been shown to modulate these same signalling pathways. Sulf1 codes for an N-acetylglucosamine 6-O-endosulfatase, an enzyme that specifically removes the 6-O sulphate group from glucosamine in highly sulfated regions of HS chains. One striking aspect of Sulf1 expression in all vertebrates is its co-localisation with that of Sonic hedgehog in the floor plate of the neural tube. We show here that Sulf1 is required for normal specification of neural progenitors in the ventral neural tube, a process known to require a gradient of Shh activity. We use single-cell injection of mRNA coding for GFP-tagged Shh in early Xenopus embryos and find that Sulf1 restricts ligand diffusion. Moreover, we find that the endogenous distribution of Shh protein in Sulf1 knockdown embryos is altered, where a less steep ventral to dorsal gradient forms in the absence of Sulf1, resulting in more a diffuse distribution of Shh. These data point to an important role for Sulf1 in the ventral neural tube, and suggests a mechanism whereby Sulf1 activity shapes the Shh morphogen gradient by promoting ventral accumulation of high levels of Shh protein.

  13. Folate deficiency-induced oxidative stress contributes to neuropathy in young and aged zebrafish--implication in neural tube defects and Alzheimer's diseases.

    Science.gov (United States)

    Kao, Tseng-Ting; Chu, Chia-Yi; Lee, Gang-Hui; Hsiao, Tsun-Hsien; Cheng, Nai-Wei; Chang, Nan-Shan; Chen, Bing-Hung; Fu, Tzu-Fun

    2014-11-01

    Folate is a nutrient essential for the development, function and regeneration of nervous systems. Folate deficiency has been linked to many neurological disorders including neural tube defects in fetus and Alzheimer's diseases in the elderly. However, the etiology underlying these folate deficiency-associated diseases is not completely understood. In this study, zebrafish transgenic lines with timing and duration-controllable folate deficiency were developed by ectopically overexpressing a recombinant EGFP-γ-glutamyl hydrolase (γGH). Impeded neural crest cell migration was observed in the transgenic embryos when folate deficiency was induced in early stages, leading to defective neural tube closure and hematopoiesis. Adding reduced folate or N-acetylcysteine reversed the phenotypic anomalies, supporting the causal link between the increased oxidative stress and the folate deficiency-induced abnormalities. When folate deficiency was induced in aged fish accumulation of beta-amyloid and phosphorylated Tau protein were found in the fish brain cryo-sections. Increased autophagy and accumulation of acidic autolysosome were apparent in folate deficient neuroblastoma cells, which were reversed by reduced folate or N-acetylcysteine supplementation. Decreased expression of cathepsin B, a lysosomal protease, was also observed in cells and tissue with folate deficiency. We concluded that folate deficiency-induced oxidative stress contributed to the folate deficiency-associated neuropathogenesis in both early and late stages of life.

  14. Grainyhead-like 2 downstream targets act to suppress epithelial-to-mesenchymal transition during neural tube closure.

    Science.gov (United States)

    Ray, Heather J; Niswander, Lee A

    2016-04-01

    The transcription factor grainyhead-like 2 (GRHL2) is expressed in non-neural ectoderm (NNE) and Grhl2 loss results in fully penetrant cranial neural tube defects (NTDs) in mice. GRHL2 activates expression of several epithelial genes; however, additional molecular targets and functional processes regulated by GRHL2 in the NNE remain to be determined, as well as the underlying cause of the NTDs in Grhl2 mutants. Here, we find that Grhl2 loss results in abnormal mesenchymal phenotypes in the NNE, including aberrant vimentin expression and increased cellular dynamics that affects the NNE and neural crest cells. The resulting loss of NNE integrity contributes to an inability of the cranial neural folds to move toward the midline and results in NTD. Further, we identified Esrp1, Sostdc1, Fermt1, Tmprss2 and Lamc2 as novel NNE-expressed genes that are downregulated in Grhl2 mutants. Our in vitro assays show that they act as suppressors of the epithelial-to-mesenchymal transition (EMT). Thus, GRHL2 promotes the epithelial nature of the NNE during the dynamic events of neural tube formation by both activating key epithelial genes and actively suppressing EMT through novel downstream EMT suppressors.

  15. Development of Polymer Resins using Neural Networks

    Directory of Open Access Journals (Sweden)

    Fabiano A. N. Fernandes

    2002-01-01

    Full Text Available The development of polymer resins can benefit from the application of neural networks, using its great ability to correlate inputs and outputs. In this work we have developed a procedure that uses neural networks to correlate the end-user properties of a polymer with the polymerization reactor's operational condition that will produce that desired polymer. This procedure is aimed at speeding up the development of new resins and help finding the appropriate operational conditions to produce a given polymer resin; reducing experimentation, pilot plant tests and therefore time and money spent on development. The procedure shown in this paper can predict the reactor's operational condition with an error lower than 5%.

  16. The use of folic acid for the prevention of neural tube defects and other congenital anomalies.

    Science.gov (United States)

    Wilson, R Douglas; Davies, Gregory; Désilets, Valérie; Reid, Gregory J; Summers, Anne; Wyatt, Philip; Young, David

    2003-11-01

    To provide information regarding the use of folic acid for the prevention of neural tube defects (NTDs) and other congenital anomalies, in order that physicians, midwives, nurses, and other health-care workers can assist in the education of women in the preconception phase of their health care. OPTION: Folic acid supplementation is problematic, since 50% of pregnancies are unplanned and the health status of women may not be optimal. Folic acid supplementation has been proven to decrease or minimize specific birth defects. A systematic review of the literature, including review and peer-reviewed articles, government publications, the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of March 1993, and statements from the American College of Obstetrics and Gynecology, was used to develop a new clinical practice guideline for the SOGC. Peer-review process within the committee structure. The benefit is reduced lethal and severe morbidity birth defects and the harm is minimal. The personal cost is of vitamin supplementation on a daily basis and eating a healthy diet. 1. Women in the reproductive age group should be advised about the benefits of folic acid supplementation during wellness visits (birth control renewal, Pap testing, yearly examination), especially if pregnancy is contemplated. (III-A) 2. Women should be advised to maintain a healthy nutritional diet, as recommended in Canada's Food Guide to Healthy Eating (good or excellent sources of folic acid: broccoli, spinach, peas, Brussels sprouts, corn, beans, lentils, oranges). (III-A) 3. Women who could become pregnant should be advised to take a multivitamin containing 0.4 mg to 1.0 mg of folic acid daily. (II-1A) 4. Women taking a multivitamin with folic acid supplement should be advised not to take more than 1 daily dose of vitamin supplement, as indicated on the product label. (II-2A) 5. Women in intermediate- to high-risk categories for NTDs (NTD-affected previous

  17. Developments in the flow of complex fluids in tubes

    CERN Document Server

    Siginer, Dennis A

    2015-01-01

    This book is dedicated to the tube flow of viscoelastic fluids and Newtonian single and multi-phase particle-laden fluids. This succinct volume collects the most recent analytical developments and experimental findings, in particular in predicting the secondary field, highlighting the historical developments which led to the progress made. This book brings a fresh and unique perspective and covers and interprets efforts to model laminar flow of viscoelastic fluids in tubes and laminar and turbulent flow of single and multi-phase particle-laden flow of linear fluids in light of the latest findings. This book also: Presents a thorough account of successes and failures in modeling and predicting tube flow of viscoelastic fluids and concentrated particle-laden flow of Newtonian fluids with specific explanations throughout Emphasizes the most up-to-date challenges in the field without requiring the reader to wade through detailed treatment of various theories Bridges the latest research results and established kno...

  18. Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects.

    Science.gov (United States)

    Bosoi, Ciprian M; Capra, Valeria; Allache, Redouane; Trinh, Vincent Quoc-Huy; De Marco, Patrizia; Merello, Elisa; Drapeau, Pierre; Bassuk, Alexander G; Kibar, Zoha

    2011-12-01

    The planar cell polarity (PCP) pathway controls the process of convergent extension (CE) during gastrulation and neural tube closure, and has been implicated in the pathogenesis of neural tube defects (NTDs) in animal models and human cohorts. In this study, we analyzed the role of one core PCP gene PRICKLE1 in these malformations. We screened this gene in 810 unrelated NTD patients and identified seven rare missense heterozygous mutations that were absent in all controls analyzed and predicted to be functionally deleterious using bioinformatics. Functional validation of five PRICKLE1 variants in a zebrafish model demonstrated that one variant, p.Arg682Cys, antagonized the CE phenotype induced by the wild-type zebrafish prickle1a (zpk1a) in a dominant fashion. Our study demonstrates that PRICKLE1 could act as a predisposing factor to human NTDs and further expands our knowledge of the role of PCP genes in the pathogenesis of these malformations.

  19. Folate Deficiency and Folic Acid Supplementation: The Prevention of Neural-Tube Defects and Congenital Heart Defects

    Directory of Open Access Journals (Sweden)

    Andrew E. Czeizel

    2013-11-01

    Full Text Available Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled trials indicated that periconceptional folic acid (FA-containing multivitamin supplementation prevented the major proportion (about 90% of neural-tube defects (NTD as well as a certain proportion (about 40% of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i dietary intake; (ii periconceptional supplementation; and (iii flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin’s statement: “An ounce of prevention is better than a pound of care”.

  20. Orally administered melatonin prevents lipopolysaccharide-induced neural tube defects in mice.

    Directory of Open Access Journals (Sweden)

    Lin Fu

    Full Text Available Lipopolysaccharide (LPS has been associated with adverse pregnant outcomes, including fetal demise, intra-uterine growth restriction (IUGR, neural tube defects (NTDs and preterm delivery in rodent animals. Previous studies demonstrated that melatonin protected against LPS-induced fetal demise, IUGR and preterm delivery. The aim of the present study was to investigate the effects of melatonin on LPS-induced NTDs. All pregnant mice except controls were intraperitoneally injected with LPS (25 µg/kg daily from gestational day (GD8 to GD12. Some pregnant mice were orally administered with melatonin (MT, 50 mg/kg before each LPS injection. A five-day LPS injection resulted in 27.5% of fetuses with anencephaly, exencephaly or encephalomeningocele. Additional experiment showed that maternal LPS exposure significantly down-regulated placental proton-coupled folate transporter (pcft and disturbed folate transport from maternal circulation through the placentas into the fetus. Interestingly, melatonin significantly attenuated LPS-induced down-regulation of placental pcft. Moreover, melatonin markedly improved the transport of folate from maternal circulation through the placentas into the fetus. Correspondingly, orally administered melatonin reduced the incidence of LPS-induced anencephaly, exencephaly or encephalomeningocele. Taken together, these results suggest that orally administered melatonin prevents LPS-induced NTDs through alleviating LPS-induced disturbance of folate transport from maternal circulation through the placenta into the fetus.

  1. Identifying environmental risk factors for human neural tube defects before and after folic acid supplementation

    Directory of Open Access Journals (Sweden)

    Li Xinhu

    2009-10-01

    Full Text Available Abstract Background Birth defects are a major cause of infant mortality and disability in many parts of the world. Neural tube defects (NTDs are one of the most common types of birth defects. In 2001, the Chinese population and family planning commission initiated a national intervention program for the prevention of birth defects. A key step in the program was the introduction of folic acid supplementation. Of interest in the present study was to determine whether folic acid supplementation has the same protective effect on NTDs under various geographical and socioeconomic conditions within the Chinese population and the nature in which the influence of environmental factors varied after folic acid supplementation. Methods In this study, Heshun was selected as the region of interest as a surrogate for helping to answer some of the questions raised in this study on the impact of the intervention program. Spatial filtering in combination with GIS software was used to detect annual potential clusters from 1998 to 2005 in Heshun, and Kruskal-wallis test and multivariate regression were applied to identify the environmental risk factors for NTDs among various regions. Results In 1998, a significant (p Conclusion This suggests that the government needs to adapt the intervention measures according to local conditions. More attention needs to be paid to the poor and to people living in areas near coal mines.

  2. Folic acid supplement use in the prevention of neural tube defects.

    Science.gov (United States)

    Delany, C; McDonnell, R; Robson, M; Corcoran, S; Fitzpatrick, C; De La Harpe, D

    2011-01-01

    In 2008, planned folic acid fortification for the prevention of Neural Tube Defects (NTD) was postponed. Concurrently, the economic recession may have affected dietary folic acid intake, placing increased emphasis on supplement use. This study examined folic acid supplement use in 2009. A cross-sectional survey of 300 ante-natal women was undertaken to assess folic acid knowledge and use. Associations between demographic, obstetric variables and folic acid knowledge and use were examined. A majority, 284/297 (96%), had heard of folic acid, and 178/297 (60%) knew that it could prevent NTD. Most, 270/297 (91%) had taken it during their pregnancy, but only 107/297 (36%) had used it periconceptionally. Being older, married, planned pregnancy and better socioeconomic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from economic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from earlier years. Continuous promotion efforts are necessary. Close monitoring of folic acid intake and NTD rates is essential, particularly in the absence of fortification.

  3. Folic acid and neural tube defects: are Jordanian pregnant women aware?

    Science.gov (United States)

    Alebous, H D; Ma'aita, M E; Alkhazaleh, F A

    2014-01-01

    To assess Jordanian pregnant women's awareness of folic acid and its contribution to neural tube defects (NTDs) prevention and to their folic acid intake. One thousand pregnant women were interviewed about their knowledge of folic acid for NTDs prevention and their folic acid intake using a questionnaire. Of 1,000 women surveyed, 93.4% reported hearing of folic acid and 30.3% of NTDs. Only 16.2% knew that folic acid can reduce NTDs risk; 42.0% of those aware of folic acid believed it should be taken periconceptionally but only 16.9% did so. The most common information sources on folic acid were physicians (82.8%). Whereas a large percentage of pregnant Jordanian women were aware of folic acid, only a small proportion are aware that it prevents NTDs and should be taken periconceptionally. Also, there was a gap between awareness, knowledge, and intake of folic acid. Awareness and knowledge of NTDs was less prevalent among Jordanian women. Despite the efforts that have been undertaken, further effort is required to educate Jordanian women about folic acid contribution to NTDs prevention.

  4. Folic acid supplementation during pregnancy protects against lipopolysaccharide-induced neural tube defects in mice.

    Science.gov (United States)

    Zhao, Mei; Chen, Yuan-Hua; Chen, Xue; Dong, Xu-Ting; Zhou, Jun; Wang, Hua; Wu, Shu-Xian; Zhang, Cheng; Xu, De-Xiang

    2014-01-13

    Folic acid is a water-soluble B-complex vitamin. Increasing evidence demonstrates that physiological supply of folic acid during pregnancy prevents folic acid deficiency-related neural tube defects (NTDs). Previous studies showed that maternal lipopolysaccharide (LPS) exposure caused NTDs in rodents. The aim of this study was to investigate the effects of high-dose folic acid supplementation during pregnancy on LPS-induced NTDs. Pregnant mice were intraperitoneally injected with LPS (20 μg/kg/d) from gestational day (GD) 8 to GD12. As expected, a five-day LPS injection resulted in 19.96% of fetuses with NTDs. Interestingly, supplementation with folic acid (3mg/kg/d) during pregnancy significantly alleviated LPS-induced NTDs. Additionally, folic acid significantly attenuated LPS-induced fetal growth restriction and skeletal malformations. Additional experiment showed that folic acid attenuated LPS-induced glutathione (GSH) depletion in maternal liver and placentas. Moreover, folic acid significantly attenuated LPS-induced expression of placental MyD88. Additionally, folic acid inhibited LPS-induced c-Jun NH2-terminal kinase (JNK) phosphorylation and nuclear factor kappa B (NF-κB) activation in placentas. Correspondingly, folic acid significantly attenuated LPS-induced tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in placentas, maternal serum and amniotic fluid. In conclusion, supplementation with high-dose folic acid during pregnancy protects against LPS-induced NTDs through its anti-inflammatory and anti-oxidative effects.

  5. Methylmalonic Acid in Amniotic Fluid and Maternal Urine as a Marker for Neural Tube Defects

    Institute of Scientific and Technical Information of China (English)

    罗小平; 张炼; 魏虹; 刘皖君; 王慕逖; 宁琴

    2004-01-01

    To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatographymass spectrometry with stable isotope of MMA as an internal standard. Amniotic fluid and maternal urine MMA concentration, maternal serum folate, red blood cell folate and vitamin B12 levels were measured in the middle term of NTD-affected and normal pregnancies. Amniotic fluid and maternal urine MMA concentrations in the middle term of NTD affected pregnancies (1.4 ± 0.9 μmol/L, and 22.1 ± 12.6 nmol/μmol creatinine) were significantly higher than that of normal pregnancies (1.0±0.4μ mol/L, and 2.5± 1.1 nmol/μmol creatinine). There was no significant difference between normal and NTD pregnancies for serum folate, red blood cell folate and vitamin B12 levels.The results suggested that MMAs in amniotic fluid and maternal urine are sensitive markers for early diagnosis of NTD. Vitamin B12 is an active cofactor involved in the remethylation of homocycteine and its deficiency is an independent risk factor for NTD. MMA is a specific and sensitive marker for intracellular vitamin B12 deficiency. This study suggests that it is necessary to monitor the vitamin B12 deficiency and advocates vitamin B12 supplementation with folate prevention program.

  6. Folic acid for the prevention of neural tube defects: the Danish experience.

    Science.gov (United States)

    Olsen, Sjurdur F; Knudsen, Vibeke Kildegaard

    2008-06-01

    Evidence from controlled trials suggests that ingestion of 0.4 mg of folic acid per day in the periconceptional period is effective in preventing neural tube defects (NTD). For this reason, most countries recommend that women planning pregnancy take folic acid supplements in the periconceptional period, and some countries even fortify stable foods with folic acid. Denmark exemplifies a country with a relatively conservative attitude with respect to taking action in these matters. In 1999, a national information campaign was launched that recommended women planning pregnancy take 0.4 mg of folic acid periconceptionally, but with the moderation that women who eat a healthy diet do not need to take folic acid supplement. The campaign was repeated during 2001. The results of the latter campaign were evaluated by using data from a national survey among pregnant women conducted simultaneously with the campaign by the Danish National Birth Cohort. An increase in the proportion of folic acid users took place concomitantly with the launching of the information events, but the increase was limited. Among women who did not plan their pregnancy, a small proportion had taken folic acid supplements periconceptionally, and this proportion did not change concomitantly with the campaign. Young age and low education were factors associated with low likelihood of taking folic acid. It seems that different and more efficient actions are needed if a more substantial proportion of Danish women and their fetuses are going to benefit from the knowledge that folic acid supplementation in the periconceptional period can prevent NTD.

  7. Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VII

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-09-01

    Full Text Available Neural tube defects (NTDs may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome, Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher-Zweymüller syndrome, parietal foramina (cranium bifidum, Apert syndrome, craniomicromelic syndrome, XX-agonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

  8. Prevention of valproic acid-induced neural tube defects by sildenafil citrate.

    Science.gov (United States)

    Tiboni, Gian Mario; Ponzano, Adalisa

    2015-08-15

    This study was undertaken to test the effects of sildenafil citrate (SC), a type 5 phosphodiesterase inhibitor, on valproic acid (VPA)-induced teratogenesis. On gestation day (GD) 8, ICR (CD-1) mice were treated by gastric intubation with SC at 0 (vehicle), 1.0, 2.5, 5.0 or 10mg/kg. One hour later, animals received a teratogenic dose of VPA (600mg/kg) or vehicle. Developmental endpoints were evaluated near the end of gestation. Twenty-eighth percent of fetuses exposed to VPA had neural tube defects (exencephaly). Pretreatment with SC at 2.5, 5.0 or 10mg/kg significantly reduced the rate of VPA-induced exencephaly to 15.9%, 13.7%, and 10.0%, respectively. Axial skeletal defects were observed in 75.8% of VPA-exposed fetuses. Pre-treatment with SC at 10mg/kg, but not at lower doses, significantly decreased the rate of skeletally affected fetuses to 61.6%. These results show that SC, which prolongs nitric oxide (NO) signaling action protects from VPA-induced teratogenesis.

  9. Clinical spectrum of neural tube defects with special reference to karyotyping study

    Directory of Open Access Journals (Sweden)

    Vijayendra Kumar

    2012-01-01

    Full Text Available Background: Neural tube defects are common congenital malformations of the central nervous system. Despite years of intensive epidemiological, clinical, and experimental research, the exact etiology of NTD remains rather complex and poorly understood. The present study attempted to look into the association of occurrence of NTD with reference to folic acid levels, along with karyotyping status. Materials and Methods: Detailed history was taken with emphasis on age of the baby and mother, parity, antenatal folic acid intake. Five milliliters of blood was drawn from all the babies and their mothers and divided equally in preheparinized vials (for karyotyping and plain vials (for folic acid estimation. The total duration was 2 years. Results: The total number (n in the study group was 75. The folic acid level was less in affected babies and their mother when compared to matched controls. Chromosomal defect was observed in nine of the 75 patients. Karyotyping defects were higher in children born to mothers of the age group 31-40 years and when their birth order was second. Conclusion: Folic acid supplementation needs to be continued to prevent the occurrence of NTD, and the perinatal identification of NTD should alert one to the possibility of chromosomal abnormalities and prompt a thorough cytogenetic investigation and genetic counseling.

  10. Neural tube defects in Malaysia: data from the Malaysian National Neonatal Registry.

    Science.gov (United States)

    Boo, Nem-Yun; Cheah, Irene G S; Thong, Meow-Keong

    2013-10-01

    This study aimed to determine the prevalence and early outcome of neural tube defects (NTDs) in Malaysia. This prospective study included all neonates with NTDs (spina bifida, anencephaly, encephalocoele) born in 2009 in 32 Malaysian hospitals in the Malaysian National Neonatal Network. The prevalence of NTDs was 0.42 per 1000 live births, being highest among the indigenous people of Sarawak (1.09 per 1000 live births) and lowest among Malaysians of Chinese descent (0.09 per 1000 live births). The most common type of NTDs was anencephaly (0.19 per 1000 live births), followed by spina bifida (0.11 per 1000 live births) and encephalocoele (0.07 per 1000 live births). Majority of the infants with anencephaly (94.5%, n = 51), 45.8% (n = 11) with encephalocoele and 9.5% (n = 4) with spina bifida died. The median duration of hospital stay was 4 (range: 0-161) days. NTDs were common in Malaysia. Mortality was high. Long-term monitoring of NTD prevalence following folic fortification of food is recommended.

  11. Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (III

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-06-01

    Full Text Available Fetuses with neural tube defects (NTDs may be associated with syndromes, disorders, and maternal and fetal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal and fetal risk factors associated with NTDs, such as omphalocele, OEIS (omphalocele-exstrophy-imperforate anus-spinal defects complex, pentalogy of Cantrell, amniotic band sequence, limb-body wall complex, Meckel syndrome, Joubert syndrome, skeletal dysplasia, diabetic embryopathy, and single nucleotide polymorphisms in genes of glucose metabolism. NTDs associated with syndromes, disorders, and maternal and fetal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multi facto rial NTDs. Perinatal identification of NTDs should alert the clinician to the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling. [Taiwan J Obstet Cynecol 2008;47(2:131-140

  12. Reduction of birth prevalence rates of neural tube defects after folic acid fortification in Chile.

    Science.gov (United States)

    López-Camelo, Jorge S; Orioli, Iêda M; da Graça Dutra, Maria; Nazer-Herrera, Julio; Rivera, Nelson; Ojeda, María Elena; Canessa, Aurora; Wettig, Elisabeth; Fontannaz, Ana María; Mellado, Cecília; Castilla, Eduardo E

    2005-06-01

    To verify whether the decreasing neural tube defects birth prevalence rates in Chile are due to folic acid fortification or to pre-existing decreasing trends, we performed a population survey using a network of Estudio Colaborativo Latino Americano de Malformaciones Congenitas (ECLAMC, Latin American Collaborative Study of Congenital Malformations) maternity hospitals in Chile, between the years 1982 and 2002. Within each maternity hospital, birth prevalence rates of spina bifida and anencephaly were calculated from two pre-fortification periods (1982-1989 and 1990-2000), and from one fortified period (2001-2002). There was no historical trend for spina bifida birth prevalence rates before folic acid fortification, and there was a 51% (minimum 27%, maximum 66%) decrease in the birth prevalence rates of this anomaly in the fortified period. The relative risks of spina bifida were homogeneous among hospitals in the two period comparisons. There was no historical trend for the birth prevalence of anencephaly comparing the two pre-fortified periods, but the relative risks were heterogeneous among hospitals in this comparison. There was a 42% (minimum 10%, maximum 63%) decrease in the birth prevalence rate of anencephaly in the fortified period as compared with the immediately pre-fortified period, with homogeneous relative risks among hospitals. Within the methodological constraints of this study we conclude that the birth prevalence rates for both spina bifida and anencephaly decreased as a result of folic acid fortification, without interference of decreasing secular trends.

  13. Folic acid supplements to prevent neural tube defects: trends in East of Ireland 1996-2002.

    Science.gov (United States)

    Ward, M; Hutton, J; Mc Donnell, R; Bachir, N; Scallan, E; O'Leary, M; Hoey, J; Doyle, A; Delany, V; Sayers, G

    2004-10-01

    Promotion of folic acid to prevent neural Tube Defects (NTD) has been ongoing for ten years in Ireland, without a concomitant reduction in the total birth prevalence of NTD. The effectiveness of folic acid promotion as the sole means of primary prevention of NTD is therefore questionable. We examined trends in folic acid knowledge and peri-conceptional use from 1996-2002 with the aim of assessing the value of this approach. From 1996-2002, 300 women attending ante-natal clinics in Dublin hospitals annually were surveyed regarding their knowledge and use of folic acid. During the period the proportion who had heard of folic acid rose from 54% to 94% between 1996 and 2002 (c2 test for trend: pfolic acid can prevent NTD also rose from 21% to 66% (c2 test for trend: pfolic acid during pregnancy increased from 14% to 83% from 1996 to 2002 (c2 test for trend: pawareness of folic acid and its relation to NTD, which is not matched by peri-conceptional uptake. The main barrier to peri-conceptional uptake is the lack of pregnancy planning. To date promotional campaigns appear to have been ineffective in reducing the prevalence of NTD in Ireland. Consequently, fortification of staple foodstuffs is the only practical and reliable means of primary prevention of NTD.

  14. Neural tube defects in the Republic of Ireland in 2009-11.

    LENUS (Irish Health Repository)

    McDonnell, R

    2014-03-18

    Neural tube defects (NTDs) are associated with deficient maternal folic acid peri-conceptionally. In Ireland, there is no mandatory folic acid food fortification, partly due to declining NTD rates in recent years. The aim of this study was to ascertain the incident rate of NTD during the period 2009-11 and describe epidemiologically NTD in Ireland.METHODSCases were ascertained through multiple sources, including three regional congenital anomaly registers, all maternity hospitals nationally and paediatric hospitals providing care for children with spina bifida in the Republic of Ireland during the period 2009-11.RESULTSFrom 225 998 total births, 236 NTDs were identified, giving an incidence of 1.04\\/1 000 births, increasing from 0.92\\/1 000 in 2009 to 1.17\\/1 000 in 2011. Of all cases, 45% (n = 106) had anencephaly, 49% (n = 115) had spina bifida and 6% (n = 15) had an encephalocoele; 78% (n = 184) were liveborn or stillborn and 22% (n = 52) were terminations abroad. Peri-conceptional folic acid supplement intake was 13.7% among the 52.5% (n = 124) of cases whose folic acid supplement intake was known.CONCLUSIONThe incidence of NTDs in the Republic of Ireland appears to be increasing. Renewed public health interventions, including mandatory folic acid food fortification, must be considered to reduce the incidence of NTD.

  15. Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review

    Directory of Open Access Journals (Sweden)

    Kelei Li

    2016-11-01

    Full Text Available Neural tube defects (NTDs are a group of severe congenital malformations, induced by the combined effects of genes and the environment. The most valuable finding so far has been the protective effect of folic acid supplementation against NTDs. However, many women do not take folic acid supplements until they are pregnant, which is too late to prevent NTDs effectively. Long-term intake of folic acid–fortified food is a good choice to solve this problem, and mandatory folic acid fortification should be further promoted, especially in Europe, Asia and Africa. Vitamin B2, vitamin B-6, vitamin B-12, choline, betaine and n-3 polyunsaturated fatty acids (PUFAs can also reduce the NTD risk by interacting with the one-carbon metabolism pathway. This suggest that multivitamin B combined with choline, betaine and n-3 PUFAs supplementation may have a better protective effect against NTDs than folic acid alone. Genetic polymorphisms involved in one-carbon metabolism are associated with NTD risk, and gene screening for women of childbearing age prior to pregnancy may help prevent NTDs induced by the risk allele. In addition, the consumption of alcohol, tea and coffee, and low intakes of fruit and vegetable are also associated with the increased risk of NTDs, and should be avoided by women of childbearing age.

  16. Folic acid supplement use in the prevention of neural tube defects.

    LENUS (Irish Health Repository)

    Delany, C

    2011-01-01

    In 2008, planned folic acid fortification for the prevention of Neural Tube Defects (NTD) was postponed. Concurrently, the economic recession may have affected dietary folic acid intake, placing increased emphasis on supplement use. This study examined folic acid supplement use in 2009. A cross-sectional survey of 300 ante-natal women was undertaken to assess folic acid knowledge and use. Associations between demographic, obstetric variables and folic acid knowledge and use were examined. A majority, 284\\/297 (96%), had heard of folic acid, and 178\\/297 (60%) knew that it could prevent NTD. Most, 270\\/297 (91%) had taken it during their pregnancy, but only 107\\/297 (36%) had used it periconceptionally. Being older, married, planned pregnancy and better socioeconomic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from economic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from earlier years. Continuous promotion efforts are necessary. Close monitoring of folic acid intake and NTD rates is essential, particularly in the absence of fortification.

  17. Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans.

    Directory of Open Access Journals (Sweden)

    Noa Safra

    Full Text Available Neural tube defects (NTDs is a general term for central nervous system malformations secondary to a failure of closure or development of the neural tube. The resulting pathologies may involve the brain, spinal cord and/or vertebral column, in addition to associated structures such as soft tissue or skin. The condition is reported among the more common birth defects in humans, leading to significant infant morbidity and mortality. The etiology remains poorly understood but genetic, nutritional, environmental factors, or a combination of these, are known to play a role in the development of NTDs. The variable conditions associated with NTDs occur naturally in dogs, and have been previously reported in the Weimaraner breed. Taking advantage of the strong linkage-disequilibrium within dog breeds we performed genome-wide association analysis and mapped a genomic region for spinal dysraphism, a presumed NTD, using 4 affected and 96 unaffected Weimaraners. The associated region on canine chromosome 8 (pgenome  =3.0 × 10(-5, after 100,000 permutations, encodes 18 genes, including NKX2-8, a homeobox gene which is expressed in the developing neural tube. Sequencing NKX2-8 in affected Weimaraners revealed a G to AA frameshift mutation within exon 2 of the gene, resulting in a premature stop codon that is predicted to produce a truncated protein. The exons of NKX2-8 were sequenced in human patients with spina bifida and rare variants (rs61755040 and rs10135525 were found to be significantly over-represented (p=0.036. This is the first documentation of a potential role for NKX2-8 in the etiology of NTDs, made possible by investigating the molecular basis of naturally occurring mutations in dogs.

  18. Valproic acid increases conservative homologous recombination frequency and reactive oxygen species formation: a potential mechanism for valproic acid-induced neural tube defects.

    Science.gov (United States)

    Defoort, Ericka N; Kim, Perry M; Winn, Louise M

    2006-04-01

    Valproic acid, a commonly used antiepileptic agent, is associated with a 1 to 2% incidence of neural tube defects when taken during pregnancy; however, the molecular mechanism by which this occurs has not been elucidated. Previous research suggests that valproic acid exposure leads to an increase in reactive oxygen species (ROS). DNA damage due to ROS can result in DNA double-strand breaks, which can be repaired through homologous recombination (HR), a process that is not error-free and can result in detrimental genetic changes. Because the developing embryo requires tight regulation of gene expression to develop properly, we propose that the loss or dysfunction of genes involved in embryonic development through aberrant HR may ultimately cause neural tube defects. To determine whether valproic acid induces HR, Chinese hamster ovary 3-6 cells, containing a neomycin direct repeat recombination substrate, were exposed to valproic acid for 4 or 24 h. A significant increase in HR after exposure to valproic acid (5 and 10 mM) for 24 h was observed, which seems to occur through a conservative HR mechanism. We also demonstrated that exposure to valproic acid (5 and 10 mM) significantly increased intracellular ROS levels, which were attenuated by preincubation with polyethylene glycol-conjugated (PEG)-catalase. A significant change in the ratio of 8-hydroxy-2'-deoxyguanosine/2'-de-oxyguanosine, a measure of DNA oxidation, was not observed after valproic acid exposure; however, preincubation with PEG-catalase significantly blocked the increase in HR. These data demonstrate that valproic acid increases HR frequency and provides a possible mechanism for valproic acid-induced neural tube defects.

  19. Food Fortification and Decline in the Prevalence of Neural Tube Defects: Does Public Intervention Reduce the Socioeconomic Gap in Prevalence?

    OpenAIRE

    Astrid Guttmann; Moore, Aideen M.; Rahim Moineddin; Mohammad M. Agha; Glazier, Richard H

    2013-01-01

    Objective: A significant decline in the prevalence of neural tube defects (NTD) through food fortification has been reported. Questions remain, however, about the effectiveness of this intervention in reducing the gap in prevalence across socioeconomic status (SES). Study Design: Using health number and through record linkage, children born in Ontario hospitals between 1994 and 2009 were followed for the diagnosis of congenital anomalies. SES quintiles were assigned to each child using census...

  20. Maternal Consumption of Non-Staple Food in the First Trimester and Risk of Neural Tube Defects in Offspring

    OpenAIRE

    Meng Wang; Zhi-Ping Wang; Li-Jie Gao; Hui Yang; Zhong-Tang Zhao

    2015-01-01

    To study the associations between maternal consumption of non-staple food in the first trimester and risk of neural tube defects (NTDs) in offspring. Data collected from a hospital-based case-control study conducted between 2006 and 2008 in Shandong/Shanxi provinces including 459 mothers with NTDs-affected births and 459 mothers without NTDs-affected births. Logistic regression models were used to examine the associations between maternal consumption of non-staple food in the first trimester...

  1. Folates for reduction of risk of neural tube defects: using oral contraceptives as a source of folate

    OpenAIRE

    Nelson AL

    2011-01-01

    Anita L Nelson Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Harbor UCLA Medical Center, Torrance, CA, USA Abstract: The evidence that folates reduce the risk of neural tube defects (NTDs) is so compelling that supplementation has been recommended by every relevant authority. The Cochrane Database of Systematic Reviews has determined that folate supplementation should be rated as a Grade 1 recommendation. United States Preventive Health Services Task Force, the US Food ...

  2. Multiple neural tube defects: a rare combination of limited dorsal myeloschisis, diplomyelia with dorsal bony spur, sacral meningocoele, syringohydromyelia, and tethered cord.

    Science.gov (United States)

    Shashank R, Ramdurg; Shubhi, Dubey; Vishal, Kadeli

    2017-04-01

    Multiple neural tube defects are relatively rare. They account for less than 1% reported neural tube defects. Cases of limited dorsal myeloschisis (LDM) and diplomyelia (two cords in single sac without intervening bony or fibrous septae) with dorsal bony spur are also a rare event. Here, the authors report a rare case of neonate with thoracic LDM, diplomyelia with dorsal bony spur, sacral meningocoele with syringohydromyelia, and low-lying tethered cord. The child also had a ventricular septal defect (VSD) and bilateral rocker bottom feet. Various environmental factors and genetic mutations in transmembrane proteins have been studied in animal models explaining the origin of neural tube defects. To the best of author's knowledge, this is the first case of varied multiple neural tube defects with diplomyelia reported in world literature.

  3. Continuation of Studies on Development of ODS Heat Exchanger Tubing

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence Brown; David Workman; Bimal Kad; Gaylord Smith; Archie Robertson; Ian Wright

    2008-04-15

    The Department of Energy (DOE), National Energy Technology Center (NETL), has initiated a strategic plan for the development of advanced technologies needed to design and build fossil fuel plants with very high efficiency and environmental performance. These plants, referred to as 'Vision 21' and FutureGen programs by DOE, will produce electricity, chemicals, fuels, or a combination of these products, and possibly secondary products such as steam/heat for industrial use. MA956 is a prime candidate material being considered for a high temperature heat exchanger in the 'Vision 21' and FutureGen programs. This material is an oxide dispersion strengthened (ODS) alloy; however, there are some gaps in the data required to commit to the use of these alloys in a full-size plant. To fill the technology gaps for commercial production and use of the material for 'Advanced Power Generation Systems' this project has performed development activity to significant increase in circumferential strength of MA956 as compared to currently available material, investigated bonding technologies for bonding tube-to-tube joints through joining development, and performed tensile, creep and fire-side corrosion tests to validate the use and fabrication processes of MA956 to heat exchanger tubing applications. Development activities within this projected has demonstrated increased circumferential strength of MA956 tubes through flow form processing. Of the six fabrication technologies for bonding tube-to-tube joints, inertia friction welding (IFW) and flash butt welding (FBW) were identified as processes for joining MA956 tubes. Tensile, creep, and fire-side corrosion test data were generated for both base metal and weld joints. The data can be used for design of future systems employing MA956. Based upon the positive development activities, two test probes were designed and fabricated for field exposure testing at 1204 C ({approx}2200 F) flue gas. The probes

  4. Duplex tube steam reformer development program

    Energy Technology Data Exchange (ETDEWEB)

    Lewe, C K; Nieto, J M; Papadopoulos, A

    1978-09-01

    Work done in partial fulfillment of Task 7 of the Duplex Steam Reformer Development Program is described. The DSR concept acts as a double barrier between a process heat high temperature reactor plant (PNP) and a closed loop chemical heat pipe (CHP) for the long distance transport of chemical energy to a remote industrial user. The current state of the DSR design is described as well as related systems and equipment. The PNP concept presented is based upon work currently underway in the Federal Republic of Germany.

  5. Zebrafish arl6ip1 is required for neural crest development during embryogenesis.

    Directory of Open Access Journals (Sweden)

    Chi-Tang Tu

    Full Text Available BACKGROUND: Although the embryonic expression pattern of ADP ribosylation factor-like 6 interacting protein 1 (Arl6ip1 has been reported, its function in neural crest development is unclear. METHODS/PRINCIPAL FINDINGS: We found that knockdown of Arl6ip1 caused defective embryonic neural crest derivatives that were particularly severe in craniofacial cartilages. Expressions of the ectodermal patterning factors msxb, dlx3b, and pax3 were normal, but the expressions of the neural crest specifier genes foxd3, snai1b, and sox10 were greatly reduced. These findings suggest that arl6ip1 is essential for specification of neural crest derivatives, but not neural crest induction. Furthermore, we revealed that the streams of crestin- and sox10-expressing neural crest cells, which migrate ventrally from neural tube into trunk, were disrupted in arl6ip1 morphants. This migration defect was not only in the trunk neural crest, but also in the enteric tract where the vagal-derived neural crest cells failed to populate the enteric nervous system. We found that this migration defect was induced by dampened Shh signaling, which may have resulted from defective cilia. These data further suggested that arl6ip1 is required for neural crest migration. Finally, by double-staining of TUNEL and crestin, we confirmed that the loss of neural crest cells could not be attributed to apoptosis. CONCLUSIONS/SIGNIFICANCE: Therefore, we concluded that arl6ip1 is required for neural crest migration and sublineage specification.

  6. Development of CANDU pressure tube integrity evaluation system

    Energy Technology Data Exchange (ETDEWEB)

    Kwac, S. L.; Kim, Y. J. [Sungkyunkwan Univ., Seoul (Korea, Republic of); Lee, J. S. [Kyonggi Univ., Suwon (Korea, Republic of); Park, Y. W. [KINS, Taejon (Korea, Republic of)

    1999-05-01

    The pressure tube is a major component of the CANDU reactor, which supports nuclear fuel bundle and it's containment vessel. If a flaw or contact with their calandria tubes is found during the periodic inspection, the integrity evaluation must be carried out, and the safety requirements must be satisfied for continued service. In order to perform the integrity evaluation, complicated and iterative calculation procedures are required. Besides, a lot of data and knowledge for the evaluation are required for the integrity evaluation process. For this reason, an integrity evaluation system was developed. The developed system was built on the basis of ASME Sec. XI and FFSG(Fitness For Service Guidelines for zirconium alloy pressure tubes in operating CANDU reactors) issued by the AECL. The evaluation procedure includes the crack growth calculation both by DHC and by fatigue. It also provides the prediction of fracture initiation, plastic collapse and leak-before-break(LBB), blister formation and blister growth. This system provides various databases including the 3-D finite element analysis results on pressure tubes, inspection data and design specifications. In order to verify the developed system, several case studies have been performed and the results were compared with those from AECL. A good agreement was observed between those two results.

  7. Development of programmable artificial neural networks

    Science.gov (United States)

    Meade, Andrew J.

    1993-01-01

    Conventionally programmed digital computers can process numbers with great speed and precision, but do not easily recognize patterns or imprecise or contradictory data. Instead of being programmed in the conventional sense, artificial neural networks are capable of self-learning through exposure to repeated examples. However, the training of an ANN can be a time consuming and unpredictable process. A general method is being developed to mate the adaptability of the ANN with the speed and precision of the digital computer. This method was successful in building feedforward networks that can approximate functions and their partial derivatives from examples in a single iteration. The general method also allows the formation of feedforward networks that can approximate the solution to nonlinear ordinary and partial differential equations to desired accuracy without the need of examples. It is believed that continued research will produce artificial neural networks that can be used with confidence in practical scientific computing and engineering applications.

  8. Eddy Current Signature Classification of Steam Generator Tube Defects Using A Learning Vector Quantization Neural Network

    Energy Technology Data Exchange (ETDEWEB)

    Gabe V. Garcia

    2005-01-03

    A major cause of failure in nuclear steam generators is degradation of their tubes. Although seven primary defect categories exist, one of the principal causes of tube failure is intergranular attack/stress corrosion cracking (IGA/SCC). This type of defect usually begins on the secondary side surface of the tubes and propagates both inwards and laterally. In many cases this defect is found at or near the tube support plates.

  9. A newly developed open-end intracranial hematoma drainage tube

    Institute of Scientific and Technical Information of China (English)

    Chao He; Nongnaphat Wanussakul; Dong Yang; Tianya Wu; Ming Zhao

    2016-01-01

    Methods:The newly developed device consists of two parts:the plunger and barrel. On one side, the barrel is bullet shaped with an opening tip. The plunger is located in the middle cavity of the tube barrel and extended out at the open-end. It was designed for strengthening the tube barrel and for convenience in performing the drainage procedure. It can be used by inserting the drainage tube into the lesion and pulling out the plunger, whereby blood will forcefully rise up inside the barrel, providing a satisfactory outcome. It is made for effusion drainage purposes. During the procedure, the drainage tip is placed at the deepest part of the intracranial hematoma to completely drain the blood. Moreover, the plunger fits tightly in the tube, preventing leakage during the operation. With the use of the device, brain can be separated. In addition, the device can help reduce the risk of cerebral damage because of the small operating area. The barrel sidewall has matching opening holes bilaterally and equally for exchanging substances between the inner and outer parts. The overlapping ratio in each horizontal pair is around 1/3–1/2. Each pair on the opposite side will form a different pressure. Thus, the opening holes will not easily get blocked with blood clot. Results: Blood and accumulated liquid from the deepest part of the intracranial hematoma can be directly drawn through the drainage tube without damaging a large area. The tube does not get blocked easily and allows for complete removal of the hematoma. Conclusions:The device is asuitable instrument for clinical application.

  10. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region.

    Science.gov (United States)

    Wang, Haochen; De Steur, Hans; Chen, Gong; Zhang, Xiaotian; Pei, Lijun; Gellynck, Xavier; Zheng, Xiaoying

    2016-03-09

    Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207-0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China.

  11. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region

    Directory of Open Access Journals (Sweden)

    Haochen Wang

    2016-03-01

    Full Text Available Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages and a control group received ordinary flour (three villages. NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207–0473, p < 0.001. In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory folic acid fortification in China.

  12. [Folic acid reduces the risk of neural tube defects: awareness and folate intake among pregnant women in 2006].

    Science.gov (United States)

    Kondo, Atsuo; Shimosuga, Yoichi; Oguchi, Hidenori; Shibata, Kanemitsu; Kurauchi, Osamu; Ichiko, Satoshi; Inoue, Hiromi; Tada, Katsuhiko; Yamada, Manshou; Kaseki, Nariaki; Narita, Osamu; Kusanishi, Hiroshi; Yamada, Yoshitaka; Yamamoto, Shin-Ichi; Ooura, Kuniaki; Takemura, Masahiko; Watanabe, Takanori; Ishihara, Osamu; Takeda, Akihiro; Watanabe, Junichiro; Wakita, Katsuji; Itoh, Kunihiko; Katoh, Sentoyo; Koyama, Masayasu; Oota, Shunji; Ninomiya, Keiu; Matsuzawa, Katsuji; Hujishima, Yoshiko; Ishida, Shoutarou; Okai, Ikuyo; Hayakawa, Chisa; Gotoh, Tohru

    2008-08-01

    Folic acid plays an important role in proliferating cells and tissues of the fetus. A randomized control trial demonstrated in 1991 that 4 mg of folic acid supplements successfully prevented 72% of recurrence of neural tube defects (NTDs) in women who had had afflicted pregnancy. In 2000, the Japanese Government recommended women of childbearing age to take 400 microgram of folate supplements per day from 4 weeks prior to and 12 weeks after conception. A questionnaire study was performed in pregnant women by post on their awareness of the role folic acid plays, their life style, and folate intake by dietary consumption. Thirty-five percent of 1,251 pregnant women were aware of the important role of folic acid in the critical stage of fetal development and 31% actually took the supplement. Information on folic acid was obtained through mass media in 47% of the women, through the internet in 17%, through healthcare providers in 13% and so forth. The food record analysis revealed that the dietary intake of folic acid averaged 341 microg/day that was 60 microg less than what was recommended by the Government and that 33 of 86 women took the supplement. Overall, a half of pregnant women are required to take 400 microg folate supplement per day. It is to be stressed that primary prevention of NTDs by periconceptional intake of folic acid is a major public health opportunity and that prevention is more important than cure in the management of NTDs.

  13. Development of the LPT9510 1 W Concentric Pulse Tube

    Science.gov (United States)

    Mullié, J. C.; Bruins, P. C.; Benschop, T.; Charles, I.; Coynel, A.; Duband, L.

    2006-04-01

    In order to provide cryogenic cooling for applications that are extremely sensitive to mechanical vibration, Thales Cryogenics has been delivering U-shape pulse tube cryocoolers since 2001. The disadvantage of the U-shape design is that the available regenerator volume is too limited if the application puts constrains on the overall diameter of the cold finger, thus limiting the coolers efficiency. As presented at CEC/ICMC 2003, Thales Cryogenics and CEA/SBT have achieved very good results with a large concentric pulse tube delivering 4W @ 77K driven by a flexure bearing compressor. Furthermore, the same team, together with Air Liquide DTA, developed a very efficient 1W pulse tube cooler for the ESA MPTC project. Based on the experiences obtained with those programs, Thales Cryogenics and CEA/SBT have now developed a small concentric pulse tube that is driven by a flexure bearing compressor. The result is a very compact and reliable cooler, with an efficiency that is nearly doubled compared to the U-shape version with the same overall external diameter dimensions. This paper describes the trade-offs that have been considered in the design phase, and gives a detailed overview of the test results, the status of the qualification program and a comparison with a comparable Stirling cold finger.

  14. [Folic acid use by pregnant women in Israel for preventing neural tube defects].

    Science.gov (United States)

    Gil, Z; Aran, A; Friedman, O; Beni-Adani, L; Constantini, S

    2000-12-01

    Spina bifida and anencephaly are the most common, serious malformations in neural tube defects (NTD). Randomized trials in the last 2 decades have demonstrated that folic acid, 0.4 mg/d, reduces the incidence of NTD by more than 50%. We investigated the use of folic acid and multivitamins containing folic acid in childbearing women. Of 221 women interviewed, 67 (30%) regularly took pills containing 0.4 mg folic acid. Women with higher educational levels were more likely to take multivitamins with folic acid than were the less educated (p = 0.05). Of the women who took folic acid, only 5 (7.5%) used separate folic acid tablets, before and during their pregnancy. The rest used multivitamins containing folic acid. The 5 women who took folic acid separately were college-educated and nonreligious, and they took multivitamins in addition (p > 0.05). Of the women interviewed, 58 (26.2%) were Bedouin of the Negev. 24 (41.4%) of them took pills containing folic acid on a regular basis. This percentage is higher than that in the Jewish women in the study who took folic acid for prevention of NTD (17%; p = 0.038). Most of the women took folic acid after the first trimester. Only a minority took daily periconceptional folic acid. Multivitamins containing 0.4 mg of folic acid were more popular than folic acid tablets alone. This study emphasizes the need for continuing efforts to increase consumption of folic acid and awareness of its benefits among women of childbearing age.

  15. A study on the possible involvement of the PAX3 gene in human neural tube defects

    Energy Technology Data Exchange (ETDEWEB)

    Hol, F.A.; Hamel, B.C.J.; Geurds, M.P.A. [University Hospital Nijmegen (Netherlands)] [and others

    1994-09-01

    Neural tube defects (NTD) are congenital malformations of the central nervous system which are generally attributed to a combination of environmental and genetic factors. Recently, the molecular defect responsible for the phenotype of the Splotch mouse, a monogenic model system for NTD, was determined. A mutation disrupts the homeodomain of the gene for Pax3. In humans, mutations in the cognate gene for PAX3 can cause Waardenburg syndrome (WS), which is associated with NTD. Based on these findings, PAX3 can be regarded as a candidate gene for human NTD. To test this hypothesis we have screened the DNA of 39 familial and 70 sporadic NTD patients for mutations in the coding exons and flanking intron sequences of the PAX3 gene. SSC analysis revealed abnormal bands in exon 2, exon 5, exon 6 and exon 7 in different patients. A missense mutation was identified in exon 6 downstream from the homeodomain in several patients resulting in an amino acid substitution (Thr315Lys) in the protein. However, the same substitution was detected in unaffected controls suggesting no biological significance. Above shifts most likely represent polymorphisms that are irrelevant for NTD. A conspicuous SSC-band shift was observed in exon 5 of one familial patient with spina bifida. Sequencing revealed that the patient was heterozygous for a 5 bp deletion upstream of the homeodomain. The deletion causes a frameshift, which leads to premature termination of translation. Mild characteristics of WS were detected in several members of the family including the index patient. DNA analysis showed co-segregation of the mutation with these symptoms. Although PAX3 mutations can increase the penetrance of NTD in families with WS, our results show that their presence is not sufficient to cause NTD.

  16. Economic burden of neural tube defects and impact of prevention with folic acid: a literature review.

    Science.gov (United States)

    Yi, Yunni; Lindemann, Marion; Colligs, Antje; Snowball, Claire

    2011-11-01

    Neural tube defects (NTDs) are the second most common group of serious birth defects. Although folic acid has been shown to reduce effectively the risk of NTDs and measures have been taken to increase the awareness, knowledge, and consumption of folic acid, the full potential of folic acid to reduce the risk of NTDs has not been realized in most countries. To understand the economic burden of NTDs and the economic impact of preventing NTDs with folic acid, a systematic review was performed on relevant studies. A total of 14 cost of illness studies and 10 economic evaluations on prevention of NTDs with folic acid were identified. Consistent findings were reported across all of the cost of illness studies. The lifetime direct medical cost for patients with NTDs is significant, with the majority of cost being for inpatient care, for treatment at initial diagnosis in childhood, and for comorbidities in adult life. The lifetime indirect cost for patients with spina bifida is even greater due to increased morbidity and premature mortality. Caregiver time costs are also significant. The results from the economic evaluations demonstrate that folic acid fortification in food and preconception folic acid consumption are cost-effective ways to reduce the incidence and prevalence of NTDs. This review highlights the significant cost burden that NTDs pose to healthcare systems, various healthcare payers, and society and concludes that the benefits of prevention of NTDs with folic acid far outweigh the cost. Further intervention with folic acid is justified in countries where the full potential of folic acid to reduce the risk of NTDs has not been realized.

  17. [Folic acid and prevention of neural tube closure defects: the question is not solved yet].

    Science.gov (United States)

    Vidailhet, M; Bocquet, A; Bresson, J-L; Briend, A; Chouraqui, J-P; Dupont, C; Darmaun, D; Frelut, M-L; Ghisolfi, J; Girardet, J-P; Goulet, O; Putet, G; Rieu, D; Rigo, J; Turck, D

    2008-07-01

    Between 1981 and 1996, several interventional studies proved the efficacy of periconceptional folic acid supplementation in the prevention of neural tube closure defects (NTCD), first in women at risk (with a previous case of NTCD) and also in women of the general population in age to become pregnant. The poor observance of this supplementation led several countries (USA, Canada, Chile...) to decide mandatory folic acid fortification of cereals, which permitted a 30% (USA) to 46% (Canada) reduction in the incidence of NTCD. Moreover, this benefit was accompanied by a diminished incidence of several other malformations and of stroke and coronary accidents in elderly people. However, several papers drew attention to an increased risk of colorectal and breast cancer in relation with high blood folate levels and the use of folic acid supplements. A controlled interventional study showed a higher rate of recurrence of colic adenomas and a higher percentage of advanced adenomas in subjects receiving 1mg/day of folic acid. A recent study demonstrated an abrupt reversal of the downward trend in colorectal cancer 1 year after the beginning of cereal folic acid fortification in the USA and Canada. Two studies also reported impaired cognitive functions in elder persons with defective vitamin B(12) status. Taken in aggregate, these studies question the wisdom of a nationwide, mandatory, folic acid fortification of cereals. As of today, despite their limited preventive efficacy, a safe approach is to keep our current French recommendations and to increase the awareness of all caregivers, so as to improve the observance of these recommendations.

  18. Maternal periconceptional consumption of pickled vegetables and risk of neural tube defects in offspring

    Institute of Scientific and Technical Information of China (English)

    LI Zhi-wen; ZHANG Le; YE Rong-wei; LIU Jian-meng; PEI Li-jun; ZHENG Xiao-ying; REN Ai-guo

    2011-01-01

    Background Maternal exposure to nitrate, nitrite, and N-nitroso compounds from drinking water or diet has been associated with an increased risk of neural tube defects (NTDs) in some studies. Pickled vegetables contain relatively large amounts of nitrite and N-nitroso compounds. We examined the association between maternal periconceptional consumption of pickled vegetables and NTDs in Shanxi Province of northern China.Methods Data were derived from a population based case-control study of major external birth defects in four counties of Shanxi Province. Participants included 519 NTDs cases identified between 2003 and 2007 and 694 healthy controls.Exposure information was collected within 1 week after delivery. Multivariable non-conditioanal Logistic regression model was used to estimate the adjusted odds ratio (OR) controlling for potentialconfounding variables.Results The risk of NTDs was positively associated with the frequency of the consumptionof pickled vegetables by the mother. Compared with pickled vegetables consumption at <1 meal/week, the adjusted Off for consumption at 1-3, 4-6,and >6 meals/week were 1.3 (95% confidence interval (CI): 1.0, 1.8), 1.9 (1.1, 3.2), and 3.6 (1.9, 6.9), respectively. A protective effect was found for maternal meat consumption at ≥1 meal/week (adjusted OR: 0.6, 95% Cl: 0.4, 0.7) and egg or milk consumption at ≥1 meal/week (adjusted OR: 0.6, 95% Cl: 0.4, 0.8).Conclusion Maternal periconceptional consumption of pickled vegetables may increase the risk for NTDs in Shanxi Province.

  19. Folic acid supplements to prevent neural tube defects: trends in East of Ireland 1996-2002.

    LENUS (Irish Health Repository)

    Ward, M

    2004-10-01

    Promotion of folic acid to prevent neural Tube Defects (NTD) has been ongoing for ten years in Ireland, without a concomitant reduction in the total birth prevalence of NTD. The effectiveness of folic acid promotion as the sole means of primary prevention of NTD is therefore questionable. We examined trends in folic acid knowledge and peri-conceptional use from 1996-2002 with the aim of assessing the value of this approach. From 1996-2002, 300 women attending ante-natal clinics in Dublin hospitals annually were surveyed regarding their knowledge and use of folic acid. During the period the proportion who had heard of folic acid rose from 54% to 94% between 1996 and 2002 (c2 test for trend: p<0.001). Knowledge that folic acid can prevent NTD also rose from 21% to 66% (c2 test for trend: p<0.001). Although the proportion who took folic acid during pregnancy increased from 14% to 83% from 1996 to 2002 (c2 test for trend: p<0.001), peri-conceptional intake did not rise above 24% in any year. There is a high awareness of folic acid and its relation to NTD, which is not matched by peri-conceptional uptake. The main barrier to peri-conceptional uptake is the lack of pregnancy planning. To date promotional campaigns appear to have been ineffective in reducing the prevalence of NTD in Ireland. Consequently, fortification of staple foodstuffs is the only practical and reliable means of primary prevention of NTD.

  20. Development of a Through Tubing (Microhole) Artificial Lift System

    Energy Technology Data Exchange (ETDEWEB)

    Steve Bodden

    2006-09-30

    The goal of this project was to develop a small diameter pump system capable of being deployed through existing production tubing strings in oil/gas wells. The pump system would then pump water up an inner tubing string (likely coil tubing) and allow gas to flow in the annulus between the coil tubing and production tubing. Accomplishing this would allow wells that are currently loaded up (unable to flow at high enough rates to lift the fluid out of the wellbore) to continue to produce additional gas/oil reserves. The project was unable to complete a working test system due to unforeseen complexities in coupling the system components together in part due to the small diameter. Although several of the individual components were sourced and secured, coupling them together and getting electricity to the motor proved technically more difficult than expected. Thus, the project is no longer active due primarily to the complications realized in coupling the components and the difficulties in getting electricity to the submersible motor in a slimhole system. The other problem in finishing this project was the lack of financial resources. When the grant was first applied for it was expected that it would be awarded in early 2004. Since the grant was not actually awarded until the end of August 2004, GPS had basically run out of $$$ and the principle developer (Steve Bodden) had to find a full time job which began in late July 2004. When the grant was finally awarded in late August, it was still hoped that the project could proceed as a part time development but with less financial exposure to the partners in GPS. This became very problematic as it still had many technical obstacles to overcome to get it to the stage of prototype testing.

  1. Slit molecules prevent entrance of trunk neural crest cells in developing gut.

    Science.gov (United States)

    Zuhdi, Nora; Ortega, Blanca; Giovannone, Dion; Ra, Hannah; Reyes, Michelle; Asención, Viviana; McNicoll, Ian; Ma, Le; de Bellard, Maria Elena

    2015-04-01

    Neural crest cells emerge from the dorsal neural tube early in development and give rise to sensory and sympathetic ganglia, adrenal cells, teeth, melanocytes and especially enteric nervous system. Several inhibitory molecules have been shown to play important roles in neural crest migration, among them are the chemorepulsive Slit1-3. It was known that Slits chemorepellants are expressed at the entry to the gut, and thus could play a role in the differential ability of vagal but not trunk neural crest cells to invade the gut and form enteric ganglia. Especially since trunk neural crest cells express Robo receptor while vagal do not. Thus, although we know that Robo mediates migration along the dorsal pathway in neural crest cells, we do not know if it is responsible in preventing their entry into the gut. The goal of this study was to further corroborate a role for Slit molecules in keeping trunk neural crest cells away from the gut. We observed that when we silenced Robo receptor in trunk neural crest, the sympathoadrenal (somites 18-24) were capable of invading gut mesenchyme in larger proportion than more rostral counterparts. The more rostral trunk neural crest tended not to migrate beyond the ventral aorta, suggesting that there are other repulsive molecules keeping them away from the gut. Interestingly, we also found that when we silenced Robo in sacral neural crest they did not wait for the arrival of vagal crest but entered the gut and migrated rostrally, suggesting that Slit molecules are the ones responsible for keeping them waiting at the hindgut mesenchyme. These combined results confirm that Slit molecules are responsible for keeping the timeliness of colonization of the gut by neural crest cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Process Technology Development of Ni Electroplating in Steam Generator Tube

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joung Soo; Kim, H. P.; Lim, Y. S.; Kim, S. S.; Hwang, S. S.; Yi, Y. S.; Kim, D. J.; Jeong, M. K.

    2009-11-15

    Operating nuclear power steam generator tubing material, Alloy 600, having superior resistance to corrosion has many experiences of damage by various corrosion mechanisms during long term operation period. In this research project, a new Ni electroplating technology to be applied to repair the damaged steam generator tubes has been developed. In this technology development, the optimum conditions for variables affecting the Ni electroplating process, optimum process conditions for maximum adhesion forces at interface between were established. The various mechanical properties (RT and HT tensile, fatigue, creep, burst, etc.) and corrosion properties (general corrosion, pitting, crevice corrosion, stress corrosion cracking, boric acid corrosion, doped steam) of the Ni plated layers made at the established optimum conditions have been evaluated and confirmed to satisfy the specifications. In addition, a new ECT probe developed at KAERI enable to detect defects from magnetic materials was confirmed to be used for Ni electroplated Alloy 600 tubes at the field. For the application of this developed technology to operating plants, a mock-up electroplating system has been designed and manufactured, and set up at Doosan Heavy Industry Co. and also its performance test has been done. At same time, the anode probe has been modified and improved to be used with the established mock-up system without any problem

  3. An adverse outcome pathway framework for neural tube and axial defects mediated by modulation of retinoic acid homeostasis.

    Science.gov (United States)

    Tonk, Elisa C M; Pennings, Jeroen L A; Piersma, Aldert H

    2015-08-01

    Developmental toxicity can be caused through a multitude of mechanisms and can therefore not be captured through a single simple mechanistic paradigm. However, it may be possible to define a selected group of overarching mechanisms that might allow detection of the vast majority of developmental toxicants. Against this background, we have explored the usefulness of retinoic acid mediated regulation of neural tube and axial patterning as a general mechanism that, when perturbed, may result in manifestations of developmental toxicity that may cover a large part of malformations known to occur in experimental animals and in man. Through a literature survey, we have identified key genes in the regulation of retinoic acid homeostasis, as well as marker genes of neural tube and axial patterning, that may be used to detect developmental toxicants in in vitro systems. A retinoic acid-neural tube/axial patterning adverse outcome pathway (RA-NTA AOP) framework was designed. The framework was tested against existing data of flusilazole exposure in the rat whole embryo culture, the zebrafish embryotoxicity test, and the embryonic stem cell test. Flusilazole is known to interact with retinoic acid homeostasis, and induced common and unique NTA marker gene changes in the three test systems. Flusilazole-induced changes were similar in directionality to gene expression responses after retinoic acid exposure. It is suggested that the RA-NTA framework may provide a general tool to define mechanistic pathways and biomarkers of developmental toxicity that may be used in alternative in vitro assays for the detection of embryotoxic compounds.

  4. [Folic acid supplementation as prophylaxis of neural tube defect in the Lower Silesia region: fact or fiction?].

    Science.gov (United States)

    Bagłaj, Maciej; Wojtyłko, Anna

    2011-01-01

    To assess the efficacy of nationwide programme of prophylaxis of neural tube defects in the Lower Silesia region. A questionnaire study was conducted among all mothers of infants admitted between 2001 and 2010 to the Department of Pediatric Surgery and Urology in Wroclaw Medical Academy. The data regarding pregnancy and delivery, newborn's medical condition, family history, parental health, profession and education, and finally folic acid supplementation by mothers were analysed. Among 1278 newborn infants, in 148 children (11.6%) central nervous system (CNS) defects were diagnosed. Among 894 mothers (69.9%) who took part in the study, 159 of them (17.8%) confirmed taking folic acid before becoming pregnant. The rate of supplementation with folic acid showed a rising trend in the study period and increased from 7.1% in 2001 to 35.8% in 2010. Folic acid was taken more frequently by the women living in urban areas (24.2%) than by those living in rural regions (9.2%). With regard to the educational level, the highest rate of supplementation with folic acid was noted among the women with high education (37.8%). Forty-eight percent of mothers were informed about prevention of neural tube defects by their physician, while in 32% of them the family or media were the source of information. Mothers of 255 infants confirmed that they knew about prevention of congenital defects by vitamin intake, but they had not taken folic acid before pregnancy. 1. Realization of the programme of prevention of neural tube defects in Lower Silesia region is highly unsatisfactory. 2. The actions undertaken on the national and local level and aimed to popularize the knowledge about prevention of CNS defects among women are assessed to be ineffective in the Lower Silesia region and need urgent verification.

  5. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

    Directory of Open Access Journals (Sweden)

    Pangilinan Faith

    2012-08-01

    Full Text Available Abstract Background Neural tube defects (NTDs are common birth defects (~1 in 1000 pregnancies in the US and Europe that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T and MTHFD1 rs2236225 (R653Q have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk. Methods A tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents, including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects. Results Nearly 70 SNPs in 30 genes were found to be associated with NTDs at the p MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury and included the known NTD risk factor MTHFD1 R653Q (rs2236225. The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele. Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing. Conclusions To our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive

  6. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

    LENUS (Irish Health Repository)

    Pangilinan, Faith

    2012-08-02

    AbstractBackgroundNeural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate\\/B12 pathway genes contribute to NTD risk.MethodsA tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate\\/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects.ResultsNearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003–0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing.ConclusionsTo our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the

  7. Describing the Prevalence of Neural Tube Defects Worldwide: A Systematic Literature Review.

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    Ibrahim Zaganjor

    Full Text Available Folate-sensitive neural tube defects (NTDs are an important, preventable cause of morbidity and mortality worldwide. There is a need to describe the current global burden of NTDs and identify gaps in available NTD data.We conducted a systematic review and searched multiple databases for NTD prevalence estimates and abstracted data from peer-reviewed literature, birth defects surveillance registries, and reports published between January 1990 and July 2014 that had greater than 5,000 births and were not solely based on mortality data. We classified countries according to World Health Organization (WHO regions and World Bank income classifications. The initial search yielded 11,614 results; after systematic review we identified 160 full text manuscripts and reports that met the inclusion criteria. Data came from 75 countries. Coverage by WHO region varied in completeness (i.e., % of countries reporting as follows: African (17%, Eastern Mediterranean (57%, European (49%, Americas (43%, South-East Asian (36%, and Western Pacific (33%. The reported NTD prevalence ranges and medians for each region were: African (5.2-75.4; 11.7 per 10,000 births, Eastern Mediterranean (2.1-124.1; 21.9 per 10,000 births, European (1.3-35.9; 9.0 per 10,000 births, Americas (3.3-27.9; 11.5 per 10,000 births, South-East Asian (1.9-66.2; 15.8 per 10,000 births, and Western Pacific (0.3-199.4; 6.9 per 10,000 births. The presence of a registry or surveillance system for NTDs increased with country income level: low income (0%, lower-middle income (25%, upper-middle income (70%, and high income (91%.Many WHO member states (120/194 did not have any data on NTD prevalence. Where data are collected, prevalence estimates vary widely. These findings highlight the need for greater NTD surveillance efforts, especially in lower-income countries. NTDs are an important public health problem that can be prevented with folic acid supplementation and fortification of staple foods.

  8. Detection of copy number variants reveals association of cilia genes with neural tube defects.

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    Xiaoli Chen

    Full Text Available BACKGROUND: Neural tube defects (NTDs are one of the most common birth defects caused by a combination of genetic and environmental factors. Currently, little is known about the genetic basis of NTDs although up to 70% of human NTDs were reported to be attributed to genetic factors. Here we performed genome-wide copy number variants (CNVs detection in a cohort of Chinese NTD patients in order to exam the potential role of CNVs in the pathogenesis of NTDs. METHODS: The genomic DNA from eighty-five NTD cases and seventy-five matched normal controls were subjected for whole genome CNVs analysis. Non-DGV (the Database of Genomic Variants CNVs from each group were further analyzed for their associations with NTDs. Gene content in non-DGV CNVs as well as participating pathways were examined. RESULTS: Fifty-five and twenty-six non-DGV CNVs were detected in cases and controls respectively. Among them, forty and nineteen CNVs involve genes (genic CNV. Significantly more non-DGV CNVs and non-DGV genic CNVs were detected in NTD patients than in control (41.2% vs. 25.3%, p<0.05 and 37.6% vs. 20%, p<0.05. Non-DGV genic CNVs are associated with a 2.65-fold increased risk for NTDs (95% CI: 1.24-5.87. Interestingly, there are 41 cilia genes involved in non-DGV CNVs from NTD patients which is significantly enriched in cases compared with that in controls (24.7% vs. 9.3%, p<0.05, corresponding with a 3.19-fold increased risk for NTDs (95% CI: 1.27-8.01. Pathway analyses further suggested that two ciliogenesis pathways, tight junction and protein kinase A signaling, are top canonical pathways implicated in NTD-specific CNVs, and these two novel pathways interact with known NTD pathways. CONCLUSIONS: Evidence from the genome-wide CNV study suggests that genic CNVs, particularly ciliogenic CNVs are associated with NTDs and two ciliogenesis pathways, tight junction and protein kinase A signaling, are potential pathways involved in NTD pathogenesis.

  9. Incidence of open neural tube defects in Nova Scotia after folic acid fortification

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    Persad, Vidia L.; Hof, Michiel; Dubé, Johanne M.; Zimmer, Pamela

    2002-01-01

    Background With the goal of preventing open neural tube defects (NTDs), recommendations for folic acid supplementation before conception were introduced in Canada in 1994, and by November 1998 Canadian grain products were being fortified with folic acid. We wished to determine whether the annual incidence of open NTDs in Nova Scotia, including those in stillbirths and terminated pregnancies, changed after the introduction of either folic acid supplementation or fortification. Methods For the 10-year period from Jan. 1, 1991, to Dec. 31, 2000, we retrospectively extracted the total number of births in Nova Scotia and the number of live births and stillbirths with open NTDs from the Nova Scotia Atlee Perinatal Database as well as the number of terminated pregnancies affected by NTDs from the Fetal Anomaly Database. We determined the total annual incidence of all open NTDs, and of the subgroups spina bifida and anencephaly, per 1000 births in the province during the periods before (1991–1994) and after (1995–1998) folic acid supplementation initiatives were begun but before folic acid fortification of grain products was implemented, and during the periods before (1991–1997) and after (1998–2000) fortification. Results In the period after supplementation initiatives were begun but before fortification was implemented, the incidence of open NTDs did not change significantly: the mean annual rate was 2.55 per 1000 births during 1991–1994 and 2.61 per 1000 births during 1995–1997 (relative risk [RR] 1.02, 95% confidence interval [CI] 0.77–1.35). After the fortification was implemented the incidence of open NTDs decreased by more than 50%: the mean annual rate was 2.58 per 1000 births during 1991–1997 and 1.17 per 1000 births during 1998–2000 (relative risk 0.46, 95% CI 0.32–0.66). Interpretation The recommendations for folic acid supplementation alone did not appear to succeed in reducing the incidence of open NTDs in Nova Scotia, whereas the

  10. Development of nanowire arrays for neural probe

    Science.gov (United States)

    Abraham, Jose K.; Xie, Jining; Varadan, Vijay K.

    2005-05-01

    It is already established that functional electrical stimulation is an effective way to restore many functions of the brain in disabled individuals. The electrical stimulation can be done by using an array of electrodes. Neural probes stimulate or sense the biopotentials mainly through the exposed metal sites. These sites should be smaller relative to the spatial potential distribution so that any potential averaging in the sensing area can be avoided. At the same time, the decrease in size of these sensing sites is limited due to the increase in impedance levels and the thermal noise while decreasing its size. It is known that current density in a planar electrode is not uniform and a higher current density can be observer around the perimeter of the electrodes. Electrical measurements conducted on many nanotubes and nanowires have already proved that it could be possible to use for current density applications and the drawbacks of the present design in neural probes can be overcome by incorporating many nanotechnology solutions. In this paper we present the design and development of nanowire arrays for the neural probe for the multisite contact which has the ability to collect and analyze isolated single unit activity. An array of vertically grown nanowires is used as contact site and many of such arrays can be used for stimulating as well as recording sites. The nanolevel interaction and wireless communication solution can extend to applications involving the treatment of many neurological disorders including Parkinson"s disease, Alzheimer"s disease, spinal injuries and the treatment of blindness and paralyzed patients with minimal or no invasive surgical procedures.

  11. Prediction of Heat Transfer Rates for Shell-and-Tube Heat Exchangers by Artificial Neural Networks Approach

    Institute of Scientific and Technical Information of China (English)

    Qiuwang WANG; Gongnan XIE; Ming ZENG; Laiqin LUO

    2006-01-01

    This work used artificial neural network (ANN) to predict the heat transfer rates of shell-and-tube heat exchangers with segmental baffles or continuous helical baffles, based on limited experimental data. The Back Propagation (BP) algorithm was used in training the networks. Different network configurations were also studied. The deviation between the predicted results and experimental data was less than 2%. Comparison with correlation for prediction shows ANN superiority. It is recommended that ANN can be easily used to predict the performances of thermal systems in engineering applications, especially to model heat exchangers for heat transfer analysis.

  12. Neurons derive from the more apical daughter in asymmetric divisions in the zebrafish neural tube.

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    Alexandre, Paula; Reugels, Alexander M; Barker, David; Blanc, Eric; Clarke, Jonathan D W

    2010-06-01

    In the developing CNS, asymmetric cell division is critical for maintaining the balanced production of differentiating neurons while renewing the population of neural progenitors. In invertebrates, this process depends on asymmetric inheritance of fate determinants during progenitor divisions. A similar mechanism is widely believed to underlie asymmetrically fated divisions in vertebrates, but compelling evidence for this is missing. We used live imaging of individual progenitors in the intact zebrafish embryo CNS to test this hypothesis. We found that asymmetric inheritance of a subcellular domain is strongly correlated with asymmetric daughter fates and our results reveal an unexpected feature of this process. The daughter cell destined to become a neuron was derived from the more apical of the two daughters, whereas the more basal daughter inherited the basal process and replenished the apical progenitor pool.

  13. Chemical milling of Zircaloy tubing to produce integral OD spiral finned tubes (AWBA development program)

    Energy Technology Data Exchange (ETDEWEB)

    Horwood, W.A.

    1982-02-01

    A detailed process description is provided for producing integral spiral fins on the outside surface of Zircaloy nuclear fuel cladding tubes by masking with pressure sensitive tape strips and then chemical milling (pickling) the tube wall between the tape strips to leave the fins in relief. Fins up to 0.020 inch high by 0.05 to 0.12 inch wide were consistently produced on tubes having wall thickness of 0.008 inch or greater after fin pickling. Wall thickness uniformity was excellent. Information is provided on tube surface preparation to maximize tape mask adhesion time during pickling, acid chemistry control to prevent local tube wall thinning near the fin, and pickling techniques to promote uniform material removal. Simple fixture designs are described for quickly and conveniently applying the tape strips to the tube wall in an accurate spiral. 13 figures, 4 tables.

  14. Advances in Etiology of Neural Tube Defects%神经管缺陷的病因学研究进展

    Institute of Scientific and Technical Information of China (English)

    谢远杰; 赵国军; 莫中成; 龙治峰

    2009-01-01

    Neural tube defects (NTDs) are a group of complex congenital defects of the CNS, commonly including anencephaly, spina bifida and encephaloceles which arise from the malformations of neural tube closure during the process of neurulation. Both environmental and genetic factors are involved in the etiology of NTDs, and many of them have been identified as risk factors of neural tube defects. Despite exhaustive research efforts, little is known about the actual genetic mechanisms governing the primary events involved in neural tube defects. We will review these factors in details.%脊柱裂、无脑儿和脑膜脑膨出通常被统称为神经管缺陷(neural tube defects,NTDs),是在神经胚形成过程中由于神经管闭合异常导致的中枢神经系统先天性疾病.其病因极其复杂,目前认为与神经管发育有关的基因异常和诸多环境因素均能导致NTDs,尽管很多学者对NTDs的病因做了大量的研究,但目前对于导致人NTDs的关键病因仍知之甚少.本文就目前研究最多的与神经管缺陷有关的基因和环境因素作一综述.

  15. Design, development and testing twin pulse tube cryocooler

    Science.gov (United States)

    Gour, Abhay Singh; Sagar, Pankaj; Karunanithi, R.

    2017-09-01

    The design and development of Twin Pulse Tube Cryocooler (TPTC) is presented. Both the coolers are driven by a single Linear Moving Magnet Synchronous Motor (LMMSM) with piston heads at both ends of the mover shaft. Magnetostatic analysis for flux line distribution was carried-out during design and development of LMMSM based pressure wave generator. Based on the performance of PWG, design of TPTC was carried out using Sage and Computational Fluid Dynamics (CFD) analysis. Detailed design, fabrication and testing of LMMSM, TPTC and their integration tests are presented in this paper.

  16. Folato, vitamina B12 e ferritina sérica e defeitos do tubo neural Folate, vitamin B12, serum ferritin and defects of the neural tube

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    Gizele Thame

    1998-09-01

    Full Text Available Objetivo: verificar os níveis de folatos, vitamina B12 e ferritina em pacientes cujos fetos apresentaram defeitos de tubo neural (DTN. O folato sangüíneo e a vitamina B12 atuam como cofatores para as enzimas envolvidas na biossíntese do DNA. A interrupção deste processo pode impedir o fechamento do tubo neural. A suplementação vitamínica contendo folato pode reduzir as taxas de ocorrência de defeitos de tubo neural, embora exista a preocupação de que esta prevenção possa mascarar a deficiência de vitamina B12. Métodos: dosagens de vitamina B12 e ferritina pelo método de enzimaimunoensaio com micropartículas e a dosagens de ácido fólico pelo método de captura iônica (IMx ABBOTT. Resultados: a porcentagem de gestantes com deficiência de vitamina B12 (níveis séricos Purpose: to determine folate, vitamin B12 and ferritin levels in patients whose fetuses presented neural-tube defects (NTD. Blood folate and vitamin B12 act as cofactors of enzymes involved in DNA biosynthesis. Interruption of this process may block neural-tube closing. Vitamin supplementation with folate may reduce occurrence rates and recurrence of NTD, although there is concern about the fact that this prevention may mask vitamin B12 deficiency. Methods: vitamin B12 and ferritin determinations by enzyme immunoassay with microparticles and folic acid determination using the ion capture method (IMx ABBOTT. Results: the percentage of pregnant women with vitamin B12 deficirncy (serum levels < 150 pg/ml was 11.8%. There was no case of folate deficiency (serum levels < 3.0 ng/ml and prevalence of pregnant women with iron store deficiency was 47.1% (serum levels < ng/mg. Conclusions: occording to the results obtained in this study (prevalence of 11.8% of vitamin B12 and 0% of folate deficient pregnant women we suggest that supplementation should be administered after serum vitamin B12 determination.

  17. Neural reuse in the organization and development of the brain.

    Science.gov (United States)

    Anderson, Michael L

    2016-03-01

    Neural reuse is the process by which neural elements originally developed for one purpose are put to many different subsequent uses. In this brief review I will outline the role of neural reuse in the development of the brain. Special attention will be paid to elucidating and differentiating between two different mechanisms of neurocognitive development: Hebbian plasticity, the importance of which is already well known, and a neural search mechanism that supports the establishment of new functional partnerships in the brain. I describe how these two mechanisms work in concert throughout development to produce the functional architecture we observe in the adult brain; outline the evidence for the importance of neural reuse; offer suggestions for some clinical implications of neural reuse; and point to future research directions.

  18. Roles of planar cell polarity pathways in the development of neutral tube defects

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    Hua Yimin

    2011-08-01

    Full Text Available Abstract Neural tube defects (NTDs are the second most common birth defect in humans. Despite many advances in the understanding of NTDs and the identification of many genes related to NTDs, the fundamental etiology for the majority of cases of NTDs remains unclear. Planar cell polarity (PCP signaling pathway, which is important for polarized cell movement (such as cell migration and organ morphogenesis through the activation of cytoskeletal pathways, has been shown to play multiple roles during neural tube closure. The disrupted function of PCP pathway is connected with some NTDs. Here, we summarize our current understanding of how PCP factors affect the pathogenesis of NTDs.

  19. Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.

    Science.gov (United States)

    Bauters, Marijke; Frints, Suzanna G; Van Esch, Hilde; Spruijt, Liesbeth; Baldewijns, Marcella M; de Die-Smulders, Christine E M; Fryns, Jean-Pierre; Marynen, Peter; Froyen, Guy

    2014-08-01

    Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects.

  20. Syndromes and disorders associated with omphalocele (III): single gene disorders, neural tube defects, diaphragmatic defects and others.

    Science.gov (United States)

    Chen, Chih-Ping

    2007-06-01

    Omphalocele can be associated with single gene disorders, neural tube defects, diaphragmatic defects, fetal valproate syndrome, and syndromes of unknown etiology. This article provides a comprehensive review of omphalocele-related disorders: otopalatodigital syndrome type II; Melnick-Needles syndrome; Rieger syndrome; neural tube defects; Meckel syndrome; Shprintzen-Goldberg omphalocele syndrome; lethal omphalocele-cleft palate syndrome; cerebro-costo-mandibular syndrome; fetal valproate syndrome; Marshall-Smith syndrome; fibrochondrogenesis; hydrolethalus syndrome; Fryns syndrome; omphalocele, diaphragmatic defects, radial anomalies and various internal malformations; diaphragmatic defects, limb deficiencies and ossification defects of skull; Donnai-Barrow syndrome; CHARGE syndrome; Goltz syndrome; Carpenter syndrome; Toriello-Carey syndrome; familial omphalocele; Cornelia de Lange syndrome; C syndrome; Elejalde syndrome; Malpuech syndrome; cervical ribs, Sprengel anomaly, anal atresia and urethral obstruction; hydrocephalus with associated malformations; Kennerknecht syndrome; lymphedema, atrial septal defect and facial changes; and craniosynostosismental retardation syndrome of Lin and Gettig. Perinatal identification of omphalocele should alert one to the possibility of omphalocele-related disorders and familial inheritance and prompt a thorough genetic counseling for these disorders.

  1. Knowledge and practice of urban Iranian pregnant women towards folic acid intake for neural tube defect prevention.

    Science.gov (United States)

    Nosrat, Sepideh Bakhshande; Sedehi, Maliheh; Golalipour, Mohammad Jafar

    2012-08-01

    To assess the knowledge and practice of urban Iranian pregnant women regarding periconceptional folic acid intake for neural tube defect (NTD) prevention. The population-based study was done on 676 primiparous women in an urban area in Golestan province in northern Iran from June to November, 2008. A questionnaire was completed by the subjects regarding their knowledge of folic acid. Questionnaires were administered to women who were seeking routine antenatal care at health centres, private gynaecological clinic and the Dezyani Gynaecologic and Obstetric Hospital. Questions covered knowledge and use of folic acid supplements and demographic and socioeconomic characteristics. Out of the 676 women surveyed, 96.2% reported that they heard of folate. Of these, only 27.6% knew that folate was something important in the prevention of neural tube defects. Overall, 20.12% of the total women took folic acid during periconceptional period. The most common information sources on folate were healthcare service (54.5%). Besides, 37.6% of the subjects who heard about folate were aware that green leafy vegetables were fortified with folic acid. In univariate analysis, knowledge and intake of folic acid was not associated with education and the age of women. A healthcare plan for intervention to increase the knowledge and intake of folic acid by pregnant women during the protective period is required.

  2. Molecular genetics and pathogenic mechanisms for the severe ciliopathies: insights into neurodevelopment and pathogenesis of neural tube defects.

    Science.gov (United States)

    Logan, Clare V; Abdel-Hamed, Zakia; Johnson, Colin A

    2011-02-01

    Meckel-Gruber syndrome (MKS) is a severe autosomal recessively inherited disorder characterized by developmental defects of the central nervous system that comprise neural tube defects that most commonly present as occipital encephalocele. MKS is considered to be the most common syndromic form of neural tube defect. MKS is genetically heterogeneous with six known disease genes: MKS1, MKS2/TMEM216, MKS3/TMEM67, RPGRIP1L, CEP290, and CC2D2A with the encoded proteins all implicated in the correct function of primary cilia. Primary cilia are microtubule-based organelles that project from the apical surface of most epithelial cell types. Recent progress has implicated the involvement of cilia in the Wnt and Shh signaling pathways and has led to an understanding of their role in normal mammalian neurodevelopment. The aim of this review is to provide an overview of the molecular genetics of the human disorder, and to assess recent insights into the etiology and molecular cell biology of severe ciliopathies from mammalian animal models of MKS.

  3. [A correlation study on homocysteine metabolism in pregnant women and neural tube defects in urban and rural areas].

    Science.gov (United States)

    Zhan, S; Hu, Y; Li, L

    1997-07-01

    Serum levels of homocysteine, folic acid and vitamin B12 in pregnant women in urban and rural areas were compared to study the relationship between homocysteine metabolism and neural tube defects. Four hundred and eleven serum specimens were sampled randomly from a serum bank for women with early pregnancy in Beijing area, 195 from urban and 216 from rural. Their levels of homocysteine were determined by high performance liquid chromatography combined with electrochemical methods, and those of folic acid and vitamin B12 by radioimmunoassay. Results showed that level of homocysteine was significantly higher in rural pregnant women than that in urban, with 9.31 mumol/L and 5.73 mumol/L, respectively, level of vitamin B12 was lower in rural than that in urban women, with 210.09 pmol/L and 233.35 pmol/L, respectively, and level of folic acid was higher in rural than that in urban women, but no significant difference in deficiency of folic acid between rural and urban was found. The average ratio of folic acid to homocysteine and that of vitamin B12 to homocysteine were higher in rural than those in urban women. It suggests that abnormal metabolism of homocysteine usually correlates with high incidence of neural tube defects in rural area.

  4. Syndromes and Disorders Associated with Omphalocele (III: Single Gene Disorders, Neural Tube Defects, Diaphragmatic Defects and Others

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2007-06-01

    Full Text Available Omphalocele can be associated with single gene disorders, neural tube defects, diaphragmatic defects, fetal valproate syndrome, and syndromes of unknown etiology. This article provides a comprehensive review of omphalocele-related disorders: otopalatodigital syndrome type II; Melnick–Needles syndrome; Rieger syndrome; neural tube defects; Meckel syndrome; Shprintzen–Goldberg omphalocele syndrome; lethal omphalocele-cleft palate syndrome; cerebro-costo-mandibular syndrome; fetal valproate syndrome; Marshall–Smith syndrome; fibrochondrogenesis; hydrolethalus syndrome; Fryns syndrome; omphalocele, diaphragmatic defects, radial anomalies and various internal malformations; diaphragmatic defects, limb deficiencies and ossification defects of skull; Donnai–Barrow syndrome; CHARGE syndrome; Goltz syndrome; Carpenter syndrome; Toriello–Carey syndrome; familial omphalocele; Cornelia de Lange syndrome; C syndrome; Elejalde syndrome; Malpuech syndrome; cervical ribs, Sprengel anomaly, anal atresia and urethral obstruction; hydrocephalus with associated malformations; Kennerknecht syndrome; lymphedema, atrial septal defect and facial changes; and craniosynostosis- mental retardation syndrome of Lin and Gettig. Perinatal identification of omphalocele should alert one to the possibility of omphalocele-related disorders and familial inheritance and prompt a thorough genetic counseling for these disorders.

  5. Folates for reduction of risk of neural tube defects: using oral contraceptives as a source of folate

    Directory of Open Access Journals (Sweden)

    Nelson AL

    2011-11-01

    Full Text Available Anita L Nelson Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Harbor UCLA Medical Center, Torrance, CA, USA Abstract: The evidence that folates reduce the risk of neural tube defects (NTDs is so compelling that supplementation has been recommended by every relevant authority. The Cochrane Database of Systematic Reviews has determined that folate supplementation should be rated as a Grade 1 recommendation. United States Preventive Health Services Task Force, the US Food and Drug Administration (FDA, and the Centers for Disease Control and Prevention (CDC have all produced clear guidelines for such supplementation. Unfortunately, despite food fortification and targeted public health campaigns promoting folic acid supplementation, periconceptional utilization of folic acid supplements has decreased in the US in recent years. Worldwide, over 300,000 newborns are affected with NTDs every year. NTDs account for 10% of all neonatal mortality. This article will review the risk factors for NTDs and the evidence supporting folate supplementation. It will also describe the remaining problems and outline current ideas to solve them. Finally, new evidence of the effectiveness of adding metafolin to drospirenone-containing oral contraceptives in raising serum and red blood cell folate levels, the rationale for making such an addition, and an estimate of the magnitude of the contribution use of such pills might have on reducing NTDs will be discussed. Keywords: neural tube defects, folate, metafolin, oral contraceptives

  6. Folic acid in the prevention of neural tube defects: awareness among laywomen and healthcare providers in Japan.

    Science.gov (United States)

    Kondo, Atsuo; Yamamoto, Shin-ichi; Inoue, Hiromi; Watanabe, Junichiro; Tada, Katsuhiko; Yoshimoto, Nobuko

    2009-09-01

    It is known that neural tube defects are folic acid preventable congenital anomalies. We investigated to what extent this information was disseminated among laywomen and healthcare providers. Questionnaire studies were conducted twice, in 2002 and 2007, for four groups of laywomen and seven groups of healthcare providers in Japan regarding awareness, folic acid supplements and healthy diets. Awareness among laywomen was less than 20%, except for families who had experience with spina bifida in 2002, and 5 years later only pregnant women showed a significant increase in awareness. Awareness among healthcare providers varied from 12 to 76%, depending on their profession, and this proportion increased in five of the seven groups in 2007. The majority of laywomen obtained their information from mass media, while the majority of healthcare providers received information through media for professionals. Laywomen who used folate supplements and healthcare providers who recommended them were initially fewer than 25 and 37%, respectively. Five years later, however, pregnant women who used folic acid supplements increased from 9.1 to 43.1%. As awareness among non-pregnant laywomen and some healthcare providers is considerably low, information should be presented repeatedly to these groups. The difficulty in getting women to consume folic acid supplements is an argument for the government to require folic acid fortification of grains so that the prevention of neural tube defects can be maximized.

  7. Brain tissue aspiration neural tube defect Aspiração de tecido cerebral em casos de defeitos de fechamento do tubo neural

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    Luiz Cesar Peres

    2005-09-01

    Full Text Available The study aimed to find out how frequent is brain tissue aspiration and if brain tissue heterotopia could be found in the lung of human neural tube defect cases. Histological sections of each lobe of both lungs of 22 fetuses and newborn with neural tube defect were immunostained for glial fibrillary acidic protein (GFAP. There were 15 (68.2% females and 7 (31.8% males. Age ranged from 18 to 40 weeks of gestation (mean= 31.8. Ten (45.5% were stillborn, the same newborn, and 2 (9.1% were abortuses. Diagnosis were: craniorrhachischisis (9 cases, 40.9%, anencephaly (8 cases, 36,4%, ruptured occipital encephalocele and rachischisis (2 cases, 9.1% each, and early amniotic band disruption sequence (1 case, 4.5%. Only one case (4.5% exhibited GFAP positive cells inside bronchioles and alveoli admixed to epithelial amniotic squames. No heterotopic tissue was observed in the lung interstitium. We concluded that aspiration of brain tissue from the amniotic fluid in neural tube defect cases may happen but it is infrequent and heterotopia was not observed.O objetivo do estudo foi identificar qual a freqüência de aspiração de tecido cerebral e a existência de heterotopia nos pulmões de casos humanos de defeito de fechamento do tubo neural através da reação imuno-histoquímica para proteína fibrilar glial ácida (GFAP em cortes histológicos de todos os lobos de ambos os pulmões de 22 casos de fetos e neonatos com defeito de fechamento do tubo neural. Havia 15 casos femininos (68,2% e 7 masculinos (31,8%, com idade gestacional variando de 18 a 40 semanas (média= 31,8, sendo natimortos e neomortos 10 (45,5% cada e 2 (9,1% abortos. Os diagnósticos foram: Craniorraquisquise (9 casos, 40,9%, anencefalia (8 casos, 36,4%, encefalocele occipital rota e raquisquise (2 casos, 9,1% e 1 (4,5%caso de seqüência de disruptura amniótica precoce. Somente 1 caso (4,5% apresentou células positivas dentro de bronquíolos e alvéolos em meio a células epiteliais

  8. Single nucleotide polymorphisms of the maternal Msx2 gene and their association with fetal neural tube defects in Han ethnic group in Shanxi Province, China

    Institute of Scientific and Technical Information of China (English)

    GUO Li; ZHAO Hong; PEI Yu-heng; HE Quan-ren; LI Wan-I; ZHANG Ting; ZHENG Xiao-ying; ZHOU Ran; XIE Jun

    2011-01-01

    Background Neural tube defects are the most common human birth defects. The causes are multifactorial with complex genetic and environmental factors, although the exact genetic causes are unknown. This research was conducted to study the frequency of Msx2 gene polymorphisms in 59 women with a history of pregnancy with a neural tube defect and in 73 healthy controls. We aimed to determine the effect of this genetic polymorphism on the incidence of neural tube defects in the Han Chinese population.Methods We studied 59 mothers with at least one previous child with a neural tube defect (the case group) and 73case-control subjects during the same period, from Shanxi Province, China. We analyzed the genotypic distributions and allele frequencies of Msx2 C386T poiymorphisms in DNA samples from the case and control groups. A three-dimensional protein model was predicted using Swiss-Pdb Viewer software version 4.0. Disease association was analyzed using chi-square tests.Results Significant differences were observed in the genotypes and allele frequencies of the Msx2 C386T allele between the case and control groups (CT: 32% vs. 15%, P=0.0073 and TT 15% vs. 4%, P=0.013, respectively). Logistic regression analysis showed that the C386T mutation is a potential risk factor for neural tube defects (P <0.05; OR: 3.466;95%CI: 1.831-6.560). Three-dimensional structure prediction revealed that the Msx2 C386T mutation results in a threonine substitution for methionine at position 129 of exon 2, which might lead to structural mutations or dysfunctions in the protein encoded by Msx2.Conclusion Maternal Msx2 C386T gene polymorphisms were associated with fetal neural tube defects in Han Chinese women in Shanxi Province.

  9. GMDH-type neural network modeling and genetic algorithm-based multi-objective optimization of thermal and friction characteristics in heat exchanger tubes with wire-rod bundles

    Science.gov (United States)

    Rahimi, Masoud; Beigzadeh, Reza; Parvizi, Mehdi; Eiamsa-ard, Smith

    2016-08-01

    The group method of data handling (GMDH) technique was used to predict heat transfer and friction characteristics in heat exchanger tubes equipped with wire-rod bundles. Nusselt number and friction factor were determined as functions of wire-rod bundle geometric parameters and Reynolds number. The performance of the developed GMDH-type neural networks was found to be superior in comparison with the proposed empirical correlations. For optimization, the genetic algorithm-based multi-objective optimization was applied.

  10. Development and quality assessments of commercial heat production of ATF FeCrAl tubes

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-09-01

    Development and quality assessment of the 2nd generation ATF FeCrAl tube production with commercial manufacturers were conducted. The manufacturing partners include Sophisticated Alloys, Inc. (SAI), Butler, PA for FeCrAl alloy casting via vacuum induction melting, Oak Ridge National Laboratory (ORNL) for extrusion process to prepare the master bars/tubes to be tube-drawn, and Rhenium Alloys, Inc. (RAI), North Ridgeville, OH, for tube-drawing process. The masters bars have also been provided to Los Alamos National Laboratory (LANL) who works with Century Tubes, Inc., (CTI), San Diego, CA, as parallel tube production effort under the current program.

  11. Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi [Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland); Alhonen, Leena [Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Kuopio (Finland); School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio (Finland); Salonurmi, Tuire; Savolainen, Markku J. [Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland)

    2014-03-28

    Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this

  12. Tube Maps for Effective Geoscience Career Planning and Development

    Science.gov (United States)

    Keane, C. M.; Wilson, C. E.; Houlton, H. R.

    2013-12-01

    One of the greatest challenges faced by students and new graduates is the advice that they must take charge of their own career planning. This is ironic as new graduates are least prepared to understand the full spectrum of options and the potential pathways to meeting their personal goals. We will examine the rationale, tools, and utility of an approach aimed at assisting individuals in career planning nicknamed a "tube map." In particular, this approach has been used in support of geoscientist recruitment and career planning in major European energy companies. By utilizing information on the occupational sequences of geoscience professionals within an organization or a community, a student or new hire can quickly understand the proven pathways towards their eventual career goals. The tube map visualizes the career pathways of individuals in the form of a subway map, with specific occupations represented as "stations" and pathway interconnections represented as "transfers." The major application of this approach in the energy sector was to demonstrate both the logical career pathways to either senior management or senior technical positions, as well as present the reality that time must be invested in "lower level" jobs, thereby nullifying a persistent overinflated sense of the speed of upward mobility. To this end, we have run a similar occupational analysis on several geoscience employers, including one with somewhat non-traditional geoscience positions and another that would be considered a very traditional employer. We will examine the similarities and differences between the resulting 'tube maps,' critique the tools used to create the maps, and assess the utility of the product in career development planning for geoscience students and new hires.

  13. Development of a neutron guide tube production technique at KAERI

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang-Jin [Korea Atomic Energy Reserch Institute, 150 Deokjin-dong, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Seung, Baek-Soek [Korea Atomic Energy Reserch Institute, 150 Deokjin-dong, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Lee, Chang-Hee [Korea Atomic Energy Reserch Institute, 150 Deokjin-dong, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Hark-Rho [Korea Atomic Energy Reserch Institute, 150 Deokjin-dong, Yuseong-gu, Daejeon 305-353 (Korea, Republic of)

    2006-11-15

    In this paper, we present KAERI's technical development status for a neutron guide tube fabrication. To achieve a high uniformity, very low roughness and perfect interface during the layer growth process, a sputtering machine was developed whereby various deposition parameters can be controlled. The Ni mirrors fabricated with this coating equipment show a neutron reflectivity of 97% at the critical angle and the Ni/Ti-supermirrors show (M=2) 84%. For a substrate alignment and assembly for the guide elements, a non-contact measurement apparatus equipped with optical microscopes was developed instead of using a 3-axis measuring machine. By employing this optical equipment, it was possible to assemble a neutron guide with an accuracy in the lateral direction of 0.005 mm and in the vertical direction of 0.01 mm.

  14. Prenatal screening, diagnosis, and pregnancy management of fetal neural tube defects.

    Science.gov (United States)

    Wilson, R Douglas; Wilson, R Douglas; Audibert, Francois; Brock, Jo-Ann; Campagnolo, Carla; Carroll, June; Cartier, Lola; Chitayat, David; Gagnon, Alain; Johnson, Jo-Ann; Langlois, Sylvie; MacDonald, W Kim; Murphy-Kaulbeck, Lynn; Okun, Nanette; Pastuck, Melanie; Popa, Vanessa

    2014-10-01

    Objectif : Fournir, aux professionnels de la santé des domaines de l’obstétrique et de la génétique, des lignes directrices et des recommandations en ce qui a trait au dépistage / diagnostic prénatal et à la prise en charge obstétricale du dysraphisme spinal ouvert / fermé (DSOF) chez le fœtus. Options : La présente analyse englobe les techniques de dépistage / diagnostic prénatal qui sont actuellement utilisées aux fins de la détection du DSOF, y compris le dépistage des concentrations sériques en alphafoetoprotéines chez la mère, l’échographie, l’imagerie par résonance magnétique visant le fœtus et l’amniocentèse. Issues : Améliorer le dépistage / diagnostic prénatal et la prise en charge obstétricale du DSOF, tout en prenant en considération les soins offerts à la patiente, l’efficacité, les coûts et les interventions de soins. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans PubMed ou MEDLINE, CINAHL et The Cochrane Library en novembre 2013 au moyen d’un vocabulaire contrôlé et de mots clés appropriés (p. ex. « prenatal screening », « congenital anomalies », « neural tube defects », « alpha-fetoprotein », « ultrasound scan », « magnetic resonance imaging »). Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles publiés en anglais entre 1977 et 2012. Les recherches ont été mises à jour de façon régulière et ont été intégrées à la directive clinique jusqu’au 30 novembre 2013. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d’organismes s’intéressant à l’évaluation des technologies dans le domaine de la santé et d’organismes connexes, dans des collections de directives cliniques, dans des registres d

  15. Advances in Artificial Neural Networks - Methodological Development and Application

    Science.gov (United States)

    Artificial neural networks as a major soft-computing technology have been extensively studied and applied during the last three decades. Research on backpropagation training algorithms for multilayer perceptron networks has spurred development of other neural network training algorithms for other ne...

  16. A Single-Center Experience of CNS Anomalies or Neural Tube Defects in Patients With Jarcho-Levin Syndrome.

    Science.gov (United States)

    Demir, Nihat; Peker, Erdal; Gülşen, İsmail; Ağengin, Kemal; Kaba, Sultan; Tuncer, Oğuz

    2016-03-01

    Jarcho-Levin syndrome (JLS) is a genetic disorder characterized by distinct malformations of the ribs and vertebrae, and/or other associated abnormalities such as neural tube defect, Arnold-Chiari malformation, renal and urinary abnormalities, hydrocephalus, congenital cardiac abnormalities, and extremity malformations. The study included 12 cases at 37-42 weeks of gestation and diagnosed to have had Jarcho-Levin syndrome, Arnold-Chiari malformation, and meningmyelocele. All cases of Jarcho-Levin syndrome had Arnold-Chiari type 2 malformation; there was corpus callosum dysgenesis in 6, lumbosacral meningmyelocele in 6, lumbal meningmyelocele in 3, thoracal meningmyelocele in 3, and holoprosencephaly in 1 of the cases. With this article, the authors underline the neurologic abnormalities accompanying Jarcho-Levin syndrome and that each of these abnormalities is a component of Jarcho-Levin syndrome.

  17. Development of high capacity Stirling type pulse tube cryocooler

    Energy Technology Data Exchange (ETDEWEB)

    Imura, J. [College of Science and Technology, Nihon University, 7-24-1, Narashinodai, Funabashi-shi, Chiba 274-8501 (Japan)], E-mail: junnosuke_imura@yahoo.co.jp; Shinoki, S.; Sato, T.; Iwata, N.; Yamamoto, H.; Yasohama, K. [College of Science and Technology, Nihon University, 7-24-1, Narashinodai, Funabashi-shi, Chiba 274-8501 (Japan); Ohashi, Y.; Nomachi, H.; Okumura, N. [Aisin Seiki Co., Ltd., 2-1, Asahi-machi, Kariya, Aichi 448-8650 (Japan); Nagaya, S.; Tamada, T.; Hirano, N. [Chubu Electric Power Co., Inc., 1, Toshin-cho, Higashi-ku, Nagoya-shi, Aichi 261-8680 (Japan)

    2007-10-01

    We have been developing a Stirling type pulse tube cryocooler, aiming for a cooling capacity of 200 W at 80 K for a superconducting magnetic energy storage system. In this work, we adopted stainless steel meshes for the regenerator of the cryocooler, and studied the influences of the mesh number on the cooling capacity. The prepared mesh numbers were 150, 200, 250, 350 and 400. Using 250 mesh, and at a frequency of 45 Hz and power consumption of 3.1 kW, the achievable lowest temperature and cooling capacity at 80 K was 46.2 K and 123 W, respectively. Furthermore, in order to optimize the performance, some regenerators were made by stacking several kinds of meshes with different stacking orders. Using these regenerators, we have obtained a high cooling capacity of 169 W at 80 K with power consumption of 4 kW.

  18. Development of high capacity Stirling type pulse tube cryocooler

    Science.gov (United States)

    Imura, J.; Shinoki, S.; Sato, T.; Iwata, N.; Yamamoto, H.; Yasohama, K.; Ohashi, Y.; Nomachi, H.; Okumura, N.; Nagaya, S.; Tamada, T.; Hirano, N.

    2007-10-01

    We have been developing a Stirling type pulse tube cryocooler, aiming for a cooling capacity of 200 W at 80 K for a superconducting magnetic energy storage system. In this work, we adopted stainless steel meshes for the regenerator of the cryocooler, and studied the influences of the mesh number on the cooling capacity. The prepared mesh numbers were #150, 200, 250, 350 and 400. Using #250 mesh, and at a frequency of 45 Hz and power consumption of 3.1 kW, the achievable lowest temperature and cooling capacity at 80 K was 46.2 K and 123 W, respectively. Furthermore, in order to optimize the performance, some regenerators were made by stacking several kinds of meshes with different stacking orders. Using these regenerators, we have obtained a high cooling capacity of 169 W at 80 K with power consumption of 4 kW.

  19. HETEROGENEITY OF NEURAL-TUBE DEFECTS IN EUROPE - THE SIGNIFICANCE OF SITE OF DEFECT AND PRESENCE OF OTHER MAJOR ANOMALIES IN RELATION TO GEOGRAPHIC DIFFERENCES IN PREVALENCE

    NARCIS (Netherlands)

    DOLK, H; DEWALS, P; GILLEROT, Y; LECHAT, MF; AYME, S; CORNEL, M; CUSCHIERI, A; GARNE, E; GOUJARD, J; LAURENCE, KM; LILLIS, D; LYS, F; NEVIN, N; OWENS, J; RADIC, A; STOLL, C; STONE, D; TENKATE, L

    1991-01-01

    In the period 1980-1987, neural tube defects were two to three times more prevalent in populations covered by EUROCAT registries in the United Kingdom and Ireland (UKI) than in Continental Europe and Malta (CEM). 1864 NTD cases in a total population of 580,000 births in UKI and 455 cases in a popula

  20. Increased nuclear sphingoid base-1-phosphates and HDAC inhibition after fumonisin and FTY720-treatment: the link between epigenomic modifications and neural tube defects?

    Science.gov (United States)

    Introduction: Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of corn. Ingestion of FB1-contaminated food during early pregnancy is associated with increased risk for neural tube defects (NTDs). FB1 inhibits the enzyme ceramide synthase in de novo sphingolipid biosynthes...

  1. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms resulting in suboptimal oocyte maturation: a discussion of folate status, neural tube defects, schizophrenia, and vasculopathy.

    NARCIS (Netherlands)

    Jongbloet, P.H.; Verbeek, A.L.M.; Heijer, M. den; Roeleveld, N.

    2008-01-01

    ABSTRACT: Several conditions apparent at birth, e.g., neural tube defects (NTDs) and cardiac anomalies, are associated with polymorphisms in folate-related genes, such as the 677C --> T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Similar associations have been established f

  2. The unique axon trajectory of the accessory nerve is determined by intrinsic properties of the neural tube in the avian embryo.

    Science.gov (United States)

    Bai, Zhongtian; Pu, Qin; Haque, Ziaul; Wang, Jianlin; Huang, Ruijin

    2016-05-01

    The accessory nerve is a cranial nerve, composed of only motor axons, which control neck muscles. Its axons ascend many segments along the lateral surface of the cervical spinal cord and hindbrain. At the level of the first somite, they pass ventrally through the somitic mesoderm into the periphery. The factors governing the unique root trajectory are unknown. Ablation experiments at the accessory nerve outlet points have shown that somites do not regulate the trajectory of the accessory nerve fibres. Factors from the neural tube that may control the longitudinal pathfinding of the accessory nerve fibres were tested by heterotopic transplantations of an occipital neural tube to the cervical and thoracic level. These transplantations resulted in a typical accessory nerve trajectory in the cervical and thoracic spinal cord. In contrast, cervical neural tube grafts were unable to give rise to the typical accessory nerve root pattern when transplanted to occipital level. Our results show that the formation of the unique axon root pattern of the accessory nerve is an intrinsic property of the neural tube.

  3. Maternal Folate and Vitamin B12 Status and Neural Tube Defects in Northern Iran: A Case Control Study

    Directory of Open Access Journals (Sweden)

    Mohammad-Jafar Golalipour

    2010-06-01

    Full Text Available Objective: This study was conducted to determine the serum level of folic acid and vitamin B12 in neural tube defects pregnancies (NTD and healthy controls in Northern Iran.Methods: This case-control study was performed on women with neural tube defects pregnancies and controls with unaffected pregnancies in Northern Iran during 2006. Twenty three pregnant women whose pregnancies were diagnosed as NTD by a second-trimester ultrasonographic examination were recruited as cases. The control group (n=23 consisted of women who were selected among socio-economic status (SES matched women who had a normal targeted ultrasound during the second trimester with documented normal fet al outcome. Fetal NTD was suspected with targeted second-trimester ultrasound during the 16th week of gestation and confirmed with high maternal serum α-fetoprotein levels. Folate, vitamin B12, homocysteine and alpha fetoprotein were evaluated after target ultrasonography.Findings: Serum alpha fetoprotein level (mean ± SD in cases and controls was 120.2±64.1 and 50±33.5 iu/ml, respectively (P<0.05. The mean ± SD folate in cases and controls was 8.4±4.2 versus 9.3±4.2 ng/ml, respectively. This difference was not significant. Folate deficiency was found in 30.4% of the cases and 13% of the controls (OR = 2.9, 95%: 0.54-19.8. Vitamin B12 deficiency was found in 13 % of cases and 17.7% of the controls (OR=0.7, 95%: 0.1-4.9.Conclusion: This study showed that the probability of having a newborn with NTDs in maternal folate deficiency is three times higher than with normal folate in Northern Iran.

  4. Maternal Folate and Vitamin B12 Status and Neural Tube Defects in Northern Iran: A Case Control Study

    Science.gov (United States)

    Mobasheri, Elahm; Keshtkar, Abbasali; Golalipour, Mohammad-Jafar

    2010-01-01

    Objective This study was conducted to determine the serum level of folic acid and vitamin B12 in neural tube defects pregnancies (NTD) and healthy controls in Northern Iran. Methods This case-control study was performed on women with neural tube defects pregnancies and controls with unaffected pregnancies in Northern Iran during 2006. Twenty three pregnant women whose pregnancies were diagnosed as NTD by a second-trimester ultrasonographic examination were recruited as cases. The control group (n=23) consisted of women who were selected among socio-economic status (SES) matched women who had a normal targeted ultrasound during the second trimester with documented normal fet al outcome. Fetal NTD was suspected with targeted second-trimester ultrasound during the 16th week of gestation and confirmed with high maternal serum α-fetoprotein levels. Folate, vitamin B12, homocysteine and alpha fetoprotein were evaluated after target ultrasonography. Findings Serum alpha fetoprotein level (mean±SD) in cases and controls was 120.2±64.1 and 50±33.5 iu/ml, respectively (P<0.05). The mean±SD folate in cases and controls was 8.4±4.2 versus 9.3±4.2 ng/ml, respectively. This difference was not significant. Folate deficiency was found in 30.4% of the cases and 13% of the controls (OR=2.9, 95%: 0.54–19.8). Vitamin B12 deficiency was found in 13% of cases and 17.7% of the controls (OR=0.7, 95%: 0.1-4.9). Conclusion This study showed that the probability of having a newborn with NTDs in maternal folate deficiency is three times higher than with normal folate in Northern Iran. PMID:23056699

  5. The preventive effects of taurine on neural tube defects through the Wnt/PCP-Jnk-dependent pathway.

    Science.gov (United States)

    Zhang, Qinghua; Liu, Yang; Wang, Hui; Ma, Li; Xia, Hechun; Niu, Jianguo; Sun, Tao; Zhang, Li

    2017-07-17

    The aim of this study was to clarify the protective role of taurine in neuronal apoptosis and the role of the Wnt/PCP-Jnk pathway in mediating the preventive effects of taurine on neural tube defects (NTDs). HT-22 cells (a hippocampal neuron cell line) were divided into a control group, a glutamate-induced apoptosis group, and glutamate (4.0 mmol/L) plus low-dose taurine (L; 0.5 mmol/L) and high-dose taurine (H; 2.0 mmol/L) groups. The MTT assay was used to monitor cell proliferation and cell survival. Immunofluorescence and Western blot analyses were used to determine caspase 9 expression. Retinoic acid (RA) induced embryonic NTDs in Kunming mice, thus establishing an NTD model. Pregnant mice were divided into a control group, an RA (30 mg/kg body weight) group, and an RA (30 mg/kg body weight) plus taurine (free drinking of 2 g/L solution) group. Immunohistochemistry and Western blot analyses were used to detect the expression of Dvl, RhoA and phosphorylated (p)-Jnk/Jnk in the embryonic neural tubes. In HT-22 cells, the apoptosis rate was significantly higher and caspase 9 activation was also significantly increased in the glutamate-induced apoptosis group compared to the L and H taurine groups. In the NTD model, the expression levels of Dvl, RhoA, and p-Jnk were significantly higher in the RA group than in the control group, whereas they were significantly reduced in the RA + taurine group. This study suggests that taurine has positive effects on neuronal protection and NTD prevention. Moreover, the Wnt/PCP-Jnk-dependent pathway plays an important role in taurine-mediated prevention of NTDs.

  6. MR-based morphometry of the posterior fossa in fetuses with neural tube defects of the spine.

    Directory of Open Access Journals (Sweden)

    Ramona Woitek

    Full Text Available OBJECTIVES: In cases of "spina bifida," a detailed prenatal imaging assessment of the exact morphology of neural tube defects (NTD is often limited. Due to the diverse clinical prognosis and prenatal treatment options, imaging parameters that support the prenatal differentiation between open and closed neural tube defects (ONTDs and CNTDs are required. This fetal MR study aims to evaluate the clivus-supraocciput angle (CSA and the maximum transverse diameter of the posterior fossa (TDPF as morphometric parameters to aid in the reliable diagnosis of either ONTDs or CNTDs. METHODS: The TDPF and the CSA of 238 fetuses (20-37 GW, mean: 28.36 GW with a normal central nervous system, 44 with ONTDS, and 13 with CNTDs (18-37 GW, mean: 24.3 GW were retrospectively measured using T2-weighted 1.5 Tesla MR -sequences. RESULTS: Normal fetuses showed a significant increase in the TDPF (r = .956; p<.001 and CSA (r = .714; p<.001 with gestational age. In ONTDs the CSA was significantly smaller (p<.001 than in normal controls and CNTDs, whereas in CNTDs the CSA was not significantly smaller than in controls (p = .160. In both ONTDs and in CNTDs the TDPF was significantly different from controls (p<.001. CONCLUSIONS: The skull base morphology in fetuses with ONTDs differs significantly from cases with CNTDs and normal controls. This is the first study to show that the CSA changes during gestation and that it is a reliable imaging biomarker to distinguish between ONTDs and CNTDs, independent of the morphology of the spinal defect.

  7. MR-based morphometry of the posterior fossa in fetuses with neural tube defects of the spine.

    Science.gov (United States)

    Woitek, Ramona; Dvorak, Anton; Weber, Michael; Seidl, Rainer; Bettelheim, Dieter; Schöpf, Veronika; Amann, Gabriele; Brugger, Peter C; Furtner, Julia; Asenbaum, Ulrika; Prayer, Daniela; Kasprian, Gregor

    2014-01-01

    In cases of "spina bifida," a detailed prenatal imaging assessment of the exact morphology of neural tube defects (NTD) is often limited. Due to the diverse clinical prognosis and prenatal treatment options, imaging parameters that support the prenatal differentiation between open and closed neural tube defects (ONTDs and CNTDs) are required. This fetal MR study aims to evaluate the clivus-supraocciput angle (CSA) and the maximum transverse diameter of the posterior fossa (TDPF) as morphometric parameters to aid in the reliable diagnosis of either ONTDs or CNTDs. The TDPF and the CSA of 238 fetuses (20-37 GW, mean: 28.36 GW) with a normal central nervous system, 44 with ONTDS, and 13 with CNTDs (18-37 GW, mean: 24.3 GW) were retrospectively measured using T2-weighted 1.5 Tesla MR -sequences. Normal fetuses showed a significant increase in the TDPF (r = .956; p<.001) and CSA (r = .714; p<.001) with gestational age. In ONTDs the CSA was significantly smaller (p<.001) than in normal controls and CNTDs, whereas in CNTDs the CSA was not significantly smaller than in controls (p = .160). In both ONTDs and in CNTDs the TDPF was significantly different from controls (p<.001). The skull base morphology in fetuses with ONTDs differs significantly from cases with CNTDs and normal controls. This is the first study to show that the CSA changes during gestation and that it is a reliable imaging biomarker to distinguish between ONTDs and CNTDs, independent of the morphology of the spinal defect.

  8. MR-Based Morphometry of the Posterior Fossa in Fetuses with Neural Tube Defects of the Spine

    Science.gov (United States)

    Woitek, Ramona; Dvorak, Anton; Weber, Michael; Seidl, Rainer; Bettelheim, Dieter; Schöpf, Veronika; Amann, Gabriele; Brugger, Peter C.; Furtner, Julia; Asenbaum, Ulrika; Prayer, Daniela; Kasprian, Gregor

    2014-01-01

    Objectives In cases of “spina bifida,” a detailed prenatal imaging assessment of the exact morphology of neural tube defects (NTD) is often limited. Due to the diverse clinical prognosis and prenatal treatment options, imaging parameters that support the prenatal differentiation between open and closed neural tube defects (ONTDs and CNTDs) are required. This fetal MR study aims to evaluate the clivus-supraocciput angle (CSA) and the maximum transverse diameter of the posterior fossa (TDPF) as morphometric parameters to aid in the reliable diagnosis of either ONTDs or CNTDs. Methods The TDPF and the CSA of 238 fetuses (20–37 GW, mean: 28.36 GW) with a normal central nervous system, 44 with ONTDS, and 13 with CNTDs (18–37 GW, mean: 24.3 GW) were retrospectively measured using T2-weighted 1.5 Tesla MR -sequences. Results Normal fetuses showed a significant increase in the TDPF (r = .956; p<.001) and CSA (r = .714; p<.001) with gestational age. In ONTDs the CSA was significantly smaller (p<.001) than in normal controls and CNTDs, whereas in CNTDs the CSA was not significantly smaller than in controls (p = .160). In both ONTDs and in CNTDs the TDPF was significantly different from controls (p<.001). Conclusions The skull base morphology in fetuses with ONTDs differs significantly from cases with CNTDs and normal controls. This is the first study to show that the CSA changes during gestation and that it is a reliable imaging biomarker to distinguish between ONTDs and CNTDs, independent of the morphology of the spinal defect. PMID:25393279

  9. Nutritional and genetic determinants of vitamin B and homocysteine metabolisms in neural tube defects: a multicenter case-control study.

    Science.gov (United States)

    Candito, Mirande; Rivet, Romain; Herbeth, Bernard; Boisson, Catherine; Rudigoz, René-Charles; Luton, Dominique; Journel, Hubert; Oury, Jean-François; Roux, François; Saura, Robert; Vernhet, Isabelle; Gaucherand, Pascal; Muller, Françoise; Guidicelli, Béatrice; Heckenroth, Hélène; Poulain, Patrice; Blayau, Martine; Francannet, Christine; Roszyk, Laurence; Brustié, Cécile; Staccini, Pascal; Gérard, Philippe; Fillion-Emery, Nathalie; Guéant-Rodriguez, Rosa-Maria; Van Obberghen, Emmanuel; Guéant, Jean-Louis

    2008-05-01

    Neural tube defects (NTDs) are severe congenital malformations due to failure of neural tube formation in early pregnancy. The proof that folic acid prevents NTDs raises the question of whether other parts of homocysteine (Hcy) metabolism may affect rates of NTDs. This French case-control study covered: 77 women aged 17-42 years sampled prior to elective abortion for a severe NTDs (cases) and 61 women aged 20-43 years with a normal pregnancy. Plasma and erythrocyte folate, plasma B6, B12 and Hcy were tested as five polymorphisms MTHFR 677 C --> T, MTHFR 1298 A --> C, MTR 2756 A --> G, MTTR 66 A --> G and TCN2 776 C --> G. Cases had significantly lower erythrocyte folate, plasma folate, B12 and B6 concentrations than the controls, and higher Hcy concentration. The odds ratio was 2.15 (95% CI: 1.00-4.59) for women with the MTRR 66 A --> G allele and it was decreased for mothers carrying the MTHFR 1298 A --> C allele. In multivariate analysis, only the erythrocyte folate concentration (P = 0.005) and plasma B6 concentration (P = 0.020) were predictors. Red cell folate is the main determinant of NTDs in France. Folic acid supplement or flour fortification would prevent most cases. Increased consumption of vitamins B12 and B6 could contribute to the prevention of NTDs. Genetic polymorphisms played only a small role. Until folic acid fortification becomes mandatory, all women of reproductive age should consume folic acid in a multivitamin that also contains B12 and B6.

  10. Xenopus reduced folate carrier regulates neural crest development epigenetically.

    Directory of Open Access Journals (Sweden)

    Jiejing Li

    Full Text Available Folic acid deficiency during pregnancy causes birth neurocristopathic malformations resulting from aberrant development of neural crest cells. The Reduced folate carrier (RFC is a membrane-bound receptor for facilitating transfer of reduced folate into the cells. RFC knockout mice are embryonic lethal and develop multiple malformations, including neurocristopathies. Here we show that XRFC is specifically expressed in neural crest tissues in Xenopus embryos and knockdown of XRFC by specific morpholino results in severe neurocristopathies. Inhibition of RFC blocked the expression of a series of neural crest marker genes while overexpression of RFC or injection of 5-methyltetrahydrofolate expanded the neural crest territories. In animal cap assays, knockdown of RFC dramatically reduced the mono- and trimethyl-Histone3-K4 levels and co-injection of the lysine methyltransferase hMLL1 largely rescued the XRFC morpholino phenotype. Our data revealed that the RFC mediated folate metabolic pathway likely potentiates neural crest gene expression through epigenetic modifications.

  11. Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage

    Directory of Open Access Journals (Sweden)

    Paige Snider

    2007-01-01

    Full Text Available Although it is well established that transgenic manipulation of mammalian neural crest-related gene expression and microsurgical removal of premigratory chicken and Xenopus embryonic cardiac neural crest progenitors results in a wide spectrum of both structural and functional congenital heart defects, the actual functional mechanism of the cardiac neural crest cells within the heart is poorly understood. Neural crest cell migration and appropriate colonization of the pharyngeal arches and outflow tract septum is thought to be highly dependent on genes that regulate cell-autonomous polarized movement (i.e., gap junctions, cadherins, and noncanonical Wnt1 pathway regulators. Once the migratory cardiac neural crest subpopulation finally reaches the heart, they have traditionally been thought to participate in septation of the common outflow tract into separate aortic and pulmonary arteries. However, several studies have suggested these colonizing neural crest cells may also play additional unexpected roles during cardiovascular development and may even contribute to a crest-derived stem cell population. Studies in both mice and chick suggest they can also enter the heart from the venous inflow as well as the usual arterial outflow region, and may contribute to the adult semilunar and atrioventricular valves as well as part of the cardiac conduction system. Furthermore, although they are not usually thought to give rise to the cardiomyocyte lineage, neural crest cells in the zebrafish (Danio rerio can contribute to the myocardium and may have different functions in a species-dependent context. Intriguingly, both ablation of chick and Xenopus premigratory neural crest cells, and a transgenic deletion of mouse neural crest cell migration or disruption of the normal mammalian neural crest gene expression profiles, disrupts ventral myocardial function and/or cardiomyocyte proliferation. Combined, this suggests that either the cardiac neural crest

  12. Development of a Numerical Model for an Expanding Tube with Linear Explosive Using AUTODYN

    Directory of Open Access Journals (Sweden)

    Mijin Choi

    2014-01-01

    Full Text Available Pyrotechnic devices have been employed in satellite launch vehicle missions, generally for the separation of structural subsystems such as stage and satellite separation. Expanding tubes are linear explosives enclosed by an oval steel tube and have been widely used for pyrotechnic joint separation systems. A numerical model is proposed for the prediction of the proper load of an expanding tube using a nonlinear dynamic analysis code, AUTODYN 2D and 3D. To compute a proper core load, numerical models of the open-ended steel tube and mild detonating tube encasing a high explosive were developed and compared with experimental results. 2D and 3D computational results showed good correlation with ballistic test results. The model will provide more flexibility in expanding tube design, leading to economic benefits in the overall expanding tube development procedure.

  13. Revised lineage of larval photoreceptor cells in Ciona reveals archetypal collaboration between neural tube and neural crest in sensory organ formation.

    Science.gov (United States)

    Oonuma, Kouhei; Tanaka, Moeko; Nishitsuji, Koki; Kato, Yumiko; Shimai, Kotaro; Kusakabe, Takehiro G

    2016-12-01

    The Ciona intestinalis larva has two distinct photoreceptor organs, a conventional pigmented ocellus and a nonpigmented ocellus, that are asymmetrically situated in the brain. The ciliary photoreceptor cells of these ocelli resemble visual cells of the vertebrate retina. Precise elucidation of the lineage of the photoreceptor cells will be key to understanding the developmental mechanisms of these cells as well as the evolutionary relationships between the photoreceptor organs of ascidians and vertebrates. Photoreceptor cells of the pigmented ocellus have been thought to develop from anterior animal (a-lineage) blastomeres, whereas the developmental origin of the nonpigmented ocellus has not been determined. Here, we show that the photoreceptor cells of both ocelli develop from the right anterior vegetal hemisphere: those of the pigmented ocellus from the right A9.14 cell and those of the nonpigmented ocellus from the right A9.16 cell. The pigmented ocellus is formed by a combination of two lineages of cells with distinct embryonic origins: the photoreceptor cells originate from a medial portion of the A-lineage neural plate, while the pigment cell originates from the lateral edge of the a-lineage neural plate. In light of the recently proposed close evolutionary relationship between the ocellus pigment cell of ascidians and the cephalic neural crest of vertebrates, the ascidian ocellus may represent a prototypic contribution of the neural crest to a cranial sensory organ.

  14. Estimated Outlet Temperatures in Shell-and-Tube Heat Exchanger Using Artificial Neural Network Approach Based on Practical Data

    Directory of Open Access Journals (Sweden)

    Hisham Hassan Jasim

    2013-01-01

    Full Text Available The objective of this study is to apply Artificial Neural Network for heat transfer analysis of shell-and-tube heat exchangers widely used in power plants and refineries. Practical data was obtained by using industrial heat exchanger operating in power generation department of Dura refinery. The commonly used Back Propagation (BP algorithm was used to train and test networks by divided the data to three samples (training, validation and testing data to give more approach data with actual case. Inputs of the neural network include inlet water temperature, inlet air temperature and mass flow rate of air. Two outputs (exit water temperature to cooling tower and exit air temperature to second stage of air compressor were taken in ANN.150 sets of data were generated in different days by the reference heat exchanger model to training the network. Regression between desired target and prediction ANN output for training , validation, testing and all samples show reasonably values are equal to one (R=1 . 50 sets of data were generated to test the network and compare between desired and predicated exit temperature (water temp. and air temp. show a good agreement ( .

  15. Development of a dual mode satellite traveling wave tube 11GHz, 12W/6W

    Science.gov (United States)

    Deml, L.

    1981-02-01

    A high power 11GHz dual mode traveling wave tube (TWT) was developed for use in communication satellites. The tube is based on the technology of previous space-qualified tubes (TL12006, TL12022, and TL12025). The tube operates at 12 or 6W, separated by 3dB, without a dramatic efficiency loss in the low power mode. Gain, efficiency and nonlinear distortion criteria are all met, by channel tuning the tube within the operating band (from 10.9 to 11.8 GHz). The channel bandwidth is 100MHz.

  16. Development of a 3D Electromagnetic Model for Eddy Current Tubing Inspection: Application to Steam Generator Tubing

    Science.gov (United States)

    Pichenot, G.; Prémel, D.; Sollier, T.; Maillot, V.

    2004-02-01

    In nuclear plants, the inspection of heat exchanger tubes is usually carried out by using eddy current nondestructive testing. A numerical model, based on a volume integral approach using the Green's dyadic formalism, has been developed, with support from the French Institute for Radiological Protection and Nuclear Safety, to predict the response of an eddy current bobbin coil to 3D flaws located in the tube's wall. With an aim of integrating this model into the NDE multi techniques platform CIVA, it has been validated with experimental data for 2D and 3D flaws.

  17. 3D reconstitution of the patterned neural tube from embryonic stem cells.

    Science.gov (United States)

    Meinhardt, Andrea; Eberle, Dominic; Tazaki, Akira; Ranga, Adrian; Niesche, Marco; Wilsch-Bräuninger, Michaela; Stec, Agnieszka; Schackert, Gabriele; Lutolf, Matthias; Tanaka, Elly M

    2014-12-09

    Inducing organogenesis in 3D culture is an important aspect of stem cell research. Anterior neural structures have been produced from large embryonic stem cell (ESC) aggregates, but the steps involved in patterning such complex structures have been ill defined, as embryoid bodies typically contained many cell types. Here we show that single mouse ESCs directly embedded in Matrigel or defined synthetic matrices under neural induction conditions can clonally form neuroepithelial cysts containing a single lumen in 3D. Untreated cysts were uniformly dorsal and could be ventralized to floor plate (FP). Retinoic acid posteriorized cysts to cervical levels and induced localize FP formation yielding full patterning along the dorsal/ventral (DV) axis. Correct spatial organization of motor neurons, interneurons, and dorsal interneurons along the DV axis was observed. This system serves as a valuable tool for studying morphogen action in 3D and as a source of patterned spinal cord tissue.

  18. Maternal Antenatal Bereavement and Neural Tube Defect in Live-Born Offspring

    DEFF Research Database (Denmark)

    Ingstrup, Katja Glejsted; Wu, Chun Sen; Olsen, Jørn

    2016-01-01

    BACKGROUND: Maternal emotional stress during pregnancy has previously been associated with congenital neural malformations, but most studies are based on data collected retrospectively. The objective of our study was to investigate associations between antenatal maternal bereavement due to death...... was seen (OR = 0.84; 95% confidence interval: 0.52-1.33). CONCLUSION: Overall maternal bereavement in the antenatal period was not related to NTDs in liveborn offspring....

  19. Neural crest stem cell population in craniomaxillofacial development and tissue repair

    Directory of Open Access Journals (Sweden)

    M La Noce

    2014-10-01

    Full Text Available Neural crest cells, delaminating from the neural tube during migration, undergo an epithelial-mesenchymal transition and differentiate into several cell types strongly reinforcing the mesoderm of the craniofacial body area – giving rise to bone, cartilage and other tissues and cells of this human body area. Recent studies on craniomaxillofacial neural crest-derived cells have provided evidence for the tremendous plasticity of these cells. Actually, neural crest cells can respond and adapt to the environment in which they migrate and the cranial mesoderm plays an important role toward patterning the identity of the migrating neural crest cells. In our experience, neural crest-derived stem cells, such as dental pulp stem cells, can actively proliferate, repair bone and give rise to other tissues and cytotypes, including blood vessels, smooth muscle, adipocytes and melanocytes, highlighting that their use in tissue engineering is successful. In this review, we provide an overview of the main pathways involved in neural crest formation, delamination, migration and differentiation; and, in particular, we concentrate our attention on the translatability of the latest scientific progress. Here we try to suggest new ideas and strategies that are needed to fully develop the clinical use of these cells. This effort should involve both researchers/clinicians and improvements in good manufacturing practice procedures. It is important to address studies towards clinical application or take into consideration that studies must have an effective therapeutic prospect for humans. New approaches and ideas must be concentrated also toward stem cell recruitment and activation within the human body, overcoming the classical grafting.

  20. Role of neural network models for developing speech systems

    Indian Academy of Sciences (India)

    K Sreenivasa Rao

    2011-10-01

    This paper discusses the application of neural networks for developing different speech systems. Prosodic parameters of speech at syllable level depend on positional, contextual and phonological features of the syllables. In this paper, neural networks are explored to model the prosodic parameters of the syllables from their positional, contextual and phonological features. The prosodic parameters considered in this work are duration and sequence of pitch $(F_0)$ values of the syllables. These prosody models are further examined for applications such as text to speech synthesis, speech recognition, speaker recognition and language identification. Neural network models in voice conversion system are explored for capturing the mapping functions between source and target speakers at source, system and prosodic levels. We have also used neural network models for characterizing the emotions present in speech. For identification of dialects in Hindi, neural network models are used to capture the dialect specific information from spectral and prosodic features of speech.

  1. Development of an Integrity Assessment Procedure for CANDU Pressure Tubes

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Han Sub [Korea Electric Power Research Institute, Daejeon (Korea, Republic of)

    2010-10-15

    The pressure tubes used in a CANDU reactor are made from Zr-2.5Nb. During service the pressure tubes operate at temperatures between about 150 and 310 .deg. C, and with variable coolant pressures up to 11MPa corresponding to hoop stress of up to 130MPa. The maximum flux of fast neutrons (E>1MeV) from the fuel is about 4X10{sup 17}nm{sup -2}{sub s}{sup -1}. The pressure tubes are exposed to very severe degradation environment. The aging degradation of the pressure tubes are summarized as below. - Geometric deformation; axial elongation, diametric creep, and wall thinning. - Deuterium uptake; some fraction of the deuterium generated by the corrosion of pressure tubes is absorbed into the pressure tubes. Total equivalent hydrogen content in the pressure tube is the sum of the initial hydrogen content before operation and the deuterium uptake during operation. High concentration of hydrogen inside the pressure tubes makes the metal susceptible to Delayed Hydride Cracking. The DHC is a degradation mechanism of prime importance for CANDU pressure tubes. Mechanical properties, in particular fracture toughness, are deteriorated by high concentration of dissolved hydrogen. - Flaws; volumetric flaws are generated during operation. Wear scars by debris fretting, and bearing pad fretting are common. These volumetric flaws can be a site of crack initiation by fatigue or DHC. Cracks can propagate by DHC or fatigue crack propagation if conditions are met. - Material properties degradation; mechanical properties are affected by neutron irradiation. Yield strength and tensile strength are increased, and fracture toughness is deteriorated. The susceptibility to DHC is also affected. The integrity assessment of the pressure tube is a procedure to determine if the risk of pressure tube failure is controlled to maintain acceptably low. CSA N285.4 and 285.8 are two important guidelines regarding the integrity of pressure tubes. N285.4 is to guide in-service inspection, and N285

  2. Mortalidad por defectos del tubo neural en México, 1980-1997 Mortality due to neural tube defects in Mexico, 1980-1997

    Directory of Open Access Journals (Sweden)

    José A Ramírez-Espitia

    2003-10-01

    Full Text Available OBJETIVO: Describir la mortalidad en México por defectos del tubo neural, durante el periodo 1980-1997. MATERIAL Y MÉTODOS: Las tasas anuales de mortalidad estatales y nacionales, por defectos del tubo neural, se calcularon por 10 000 nacidos vivos. La tendencia temporal fue evaluada por el porcentaje de cambio anual obtenido mediante un modelo de regresión de Poisson. Se calculó la razón de mortalidad, tomando la media nacional como referencia. Las tasas y las razones se representaron gráficamente en mapas. RESULTADOS: Durante el periodo la tasa bruta de mortalidad por defectos del tubo neural fue de 5.8 por 10 000 nacidos vivos. La anencefalia fue el tipo de defecto más frecuente (37.7%, seguida de la espina bífida sin hidrocefalia (31.6%. La tendencia nacional de la mortalidad por defectos del tubo neural fue ascendente entre 1980 y 1990 (porcentaje de cambio anual 7.5 IC 95% 6.5, 8.6 y descendente entre 1990-1997 (porcentaje de cambio anual -2.3 IC 95% -3.6, -0.9. CONCLUSIONES: Las altas tasas de mortalidad por defectos del tubo neural fueron debidas principalmente a la elevada frecuencia de las anencefalias. El incremento observado parece no ser sólo atribuible a cuestiones puramente diagnósticas o de mejora en los registros. La influencia de factores asociados a estos defectos, como determinados polimorfismos genéticos, la deficiencia de ácido fólico, la obesidad materna, la exposición laboral a plaguicidas y la pobreza deberán evaluarse mediante estudios específicos.OBJECTIVE: To describe the mortality due to neural tube defects (NTD in Mexico for the 1980-1997 period. MATERIAL AND METHODS: The annual NTD mortality rates per 10000 liveborn infants were calculated by state and for the country. The time trend was evaluated with the annual percent change (APC obtained using a Poisson regression model. The NTD mortality ratio was calculated using the average national rate as reference. NTD mortality rates and ratios were

  3. Disostose espôndilo-costal associada a defeitos de fechamento do tubo neural Spondylocostal dysostosis associated with neural tube defects

    Directory of Open Access Journals (Sweden)

    Rafael Fabiano M. Rosa

    2009-09-01

    Full Text Available OBJETIVO: Salientar a relação dos defeitos de fechamento do tubo neural com a disostose espôndilo-costal (DEC por meio da descrição de três pacientes. DESCRIÇÃO DOS CASOS: Paciente 1: menina branca, 22 meses, nascida com mielomeningocele lombar. Na avaliação, apresentava hipotonia, baixa estatura, dolicocefalia, fendas palpebrais oblíquas para cima, pregas epicânticas e tronco curto com tórax assimétrico. A avaliação radiográfica revelou hemivértebras múltiplas, vértebras em borboleta e fusão e ausência de algumas costelas. Paciente 2: menina branca, 22 meses, com moderado atraso do desenvolvimento neuropsicomotor, baixa estatura, olhos profundos, pregas epicânticas, pescoço e tronco curtos com assimetria do tórax, abdome protruso, hemangioma plano na altura da transição lombossacra e fosseta sacral profunda no dorso. A avaliação radiográfica identificou hemivértebras, fusão incompleta de vértebras e vértebras em borboleta, malformações de costelas e espinha bífida oculta em L5/S1. Paciente 3: menina branca, 9 dias de vida, com fendas palpebrais oblíquas para cima, ponte nasal alargada, orelhas baixo implantadas e rotadas posteriormente, tronco curto, tórax assimétrico e meningocele tóraco-lombar. A avaliação radiográfica evidenciou hemivértebras, malformação e ausência de algumas costelas e agenesia diafragmática à esquerda. A tomografia computadorizada de encéfalo mostrou estenose de aqueduto. COMENTÁRIOS: Vários defeitos de fechamento do tubo neural, de espinha bífida oculta a grandes mielomeningoceles, são observados em pacientes com DEC, indicando que tais pacientes devem ser cuidadosamente avaliados quanto à possível presença desses defeitos.OBJECTIVE: To highlight the relationship between neural tube defects and spondylocostal dysostosis (SCD through the description of three patients. CASES DESCRIPTION: Patient 1: white girl, 22 months old, born with a lumbar meningomyelocele. At

  4. Dificultades en los métodos de estudio de exposiciones ambientales y defectos del tubo neural Methodological challenges to assess environmental exposures related to neural tube defects

    Directory of Open Access Journals (Sweden)

    Víctor Hugo Borja-Aburto

    1999-11-01

    susceptibilidad genética.Objective. To discuss the attitudes in the assessment of environmental exposures as risk factors associated with neural tube defects, and to present the main risk factors studied to date. Results. Environmental exposures have been suggested to have a roll in the genesis of birth defects. However, studies conducted in human populations have found difficulties in the design and conduction to show such an association for neural tube defects (anencephaly, espina bifida and encefalocele because of problems raised from: a the frequency measures used to compare time trends and communities, b the classification of heterogeneous malformations, c the inclusion of maternal, paternal and fetal factors as an integrated process and, d the assessment of environmental exposures. Conclusions. Hypothetically both maternal and paternal environmental exposures can produce damage before and after conception by direct action on the embryo and the fetus-placenta complex. Therefore, in the assessment of environmental exposures we need to take into account: a both paternal and maternal exposures; b the critical exposure period, three months before conception for paternal exposures and one month around the conceptional period for maternal exposures; c quantitatively evaluate environmental exposures when possible, avoiding a dichotomous classification; d the use of biological markers of exposure is highly recommended as well as markers of genetic susceptibility.

  5. Imidacloprid Exposure Suppresses Neural Crest Cells Generation during Early Chick Embryo Development.

    Science.gov (United States)

    Wang, Chao-Jie; Wang, Guang; Wang, Xiao-Yu; Liu, Meng; Chuai, Manli; Lee, Kenneth Ka Ho; He, Xiao-Song; Lu, Da-Xiang; Yang, Xuesong

    2016-06-15

    Imidacloprid is a neonicotinoid pesticide that is widely used in the control pests found on crops and fleas on pets. However, it is still unclear whether imidacloprid exposure could affect early embryo development-despite some studies having been conducted on the gametes. In this study, we demonstrated that imidacloprid exposure could lead to abnormal craniofacial osteogenesis in the developing chick embryo. Cranial neural crest cells (NCCs) are the progenitor cells of the chick cranial skull. We found that the imidacloprid exposure retards the development of gastrulating chick embryos. HNK-1, PAX7, and Ap-2α immunohistological stainings indicated that cranial NCCs generation was inhibited after imidacloprid exposure. Double immunofluorescent staining (Ap-2α and PHIS3 or PAX7 and c-Caspase3) revealed that imidacloprid exposure inhibited both NCC proliferation and apoptosis. In addition, it inhibited NCCs production by repressing Msx1 and BMP4 expression in the developing neural tube and by altering expression of EMT-related adhesion molecules (Cad6B, E-Cadherin, and N-cadherin) in the developing neural crests. We also determined that imidacloprid exposure suppressed cranial NCCs migration and their ability to differentiate. In sum, we have provided experimental evidence that imidacloprid exposure during embryogenesis disrupts NCCs development, which in turn causes defective cranial bone development.

  6. Zebrafish Thsd7a is a neural protein required for angiogenic patterning during development.

    Science.gov (United States)

    Wang, Chieh-Huei; Chen, I-Hui; Kuo, Meng-Wei; Su, Pei-Tsu; Lai, Zih-Yin; Wang, Chian-Huei; Huang, Wei-Chang; Hoffman, Jana; Kuo, Calvin J; You, May-Su; Chuang, Yung-Jen

    2011-06-01

    Angiogenesis is a highly organized process under the control of guidance cues that direct endothelial cell (EC) migration. Recently, many molecules that were initially described as regulators of neural guidance were subsequently shown to also direct EC migration. Here, we report a novel protein, thrombospondin type I domain containing 7A (Thsd7a), that is a neural molecule required for directed EC migration during embryonic angiogenesis in zebrafish. Thsd7a is a vertebrate conserved protein. Zebrafish thsd7a transcript was detected along the ventral edge of the neural tube in the developing zebrafish embryos, correlating with the growth path of angiogenic intersegmental vessels (ISVs). Morpholino-knockdown of Thsd7a caused a lateral deviation of angiogenic ECs below the thsd7a-expressing sites, resulting in aberrant ISV patterning. Collectively, our study shows that zebrafish Thsd7a is a neural protein required for ISV angiogenesis, and suggests an important role of Thsd7a in the neurovascular interaction during zebrafish development.

  7. Advances in Artificial Neural Networks – Methodological Development and Application

    Directory of Open Access Journals (Sweden)

    Yanbo Huang

    2009-08-01

    Full Text Available Artificial neural networks as a major soft-computing technology have been extensively studied and applied during the last three decades. Research on backpropagation training algorithms for multilayer perceptron networks has spurred development of other neural network training algorithms for other networks such as radial basis function, recurrent network, feedback network, and unsupervised Kohonen self-organizing network. These networks, especially the multilayer perceptron network with a backpropagation training algorithm, have gained recognition in research and applications in various scientific and engineering areas. In order to accelerate the training process and overcome data over-fitting, research has been conducted to improve the backpropagation algorithm. Further, artificial neural networks have been integrated with other advanced methods such as fuzzy logic and wavelet analysis, to enhance the ability of data interpretation and modeling and to avoid subjectivity in the operation of the training algorithm. In recent years, support vector machines have emerged as a set of high-performance supervised generalized linear classifiers in parallel with artificial neural networks. A review on development history of artificial neural networks is presented and the standard architectures and algorithms of artificial neural networks are described. Furthermore, advanced artificial neural networks will be introduced with support vector machines, and limitations of ANNs will be identified. The future of artificial neural network development in tandem with support vector machines will be discussed in conjunction with further applications to food science and engineering, soil and water relationship for crop management, and decision support for precision agriculture. Along with the network structures and training algorithms, the applications of artificial neural networks will be reviewed as well, especially in the fields of agricultural and biological

  8. Research Team for Neural Development and Plasticity

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    The brain consists of billions of nerve cells, called neurons, which make specific connections (called synapses) among them to form many neural circuits to perform various brain functions, including processing, storage, and retrieval of information. Each neuron is a polarized cell. It sends out many highly arborized dendrites on one end for receiving input signals and a single long axon oll the other end for delivery of output signals to distant target neurons.

  9. Differentiation Induction of Mouse Neural Stem Cells in Hydrogel Tubular Microenvironments with Controlled Tube Dimensions.

    Science.gov (United States)

    Onoe, Hiroaki; Kato-Negishi, Midori; Itou, Akane; Takeuchi, Shoji

    2016-05-01

    In this paper, a tubular 3D microenvironment created in a calcium alginate hydrogel microtube with respect to the effect of scaffold dimensions on the differentiation of mouse neuronal stem cells (mNSCs) is evaluated. Five types of hydrogel microtubes with different core diameters (≈65-200 μm) and shell thicknesses (≈30-110 μm) are fabricated by using a double coaxial microfluidic device, and differentiation of encapsulated mNSCs is induced by changing the growth medium to the differentiation medium. The influence of the microtube geometries is examined by using quantitative real-time polymerase chain reaction and fluorescent immunocytochemistry. The analyses reveal that differences in microtube thickness within 30-110 μm affected the relative Tuj1 expression but do not affect the morphology of encapsulated mNSCs. The diameters of cores influence both the relative Tuj1 expression and morphology of the differentiated neurons. It is found that the tubular microenvironment with a core diameter of less than ≈100 μm contributes to forming highly viable and aligned neural tissue. The tubular microenvironment can provide an effective method for constructing microfiber-shaped neural tissues with geometrically controlled differentiation induction.

  10. Fetal neural tube stem cells from Pax3 mutant mice proliferate, differentiate, and form synaptic connections when stimulated with folic acid.

    Science.gov (United States)

    Ichi, Shunsuke; Nakazaki, Hiromichi; Boshnjaku, Vanda; Singh, Ravneet Monny; Mania-Farnell, Barbara; Xi, Guifa; McLone, David G; Tomita, Tadanori; Mayanil, Chandra Shekhar K

    2012-01-20

    Although maternal intake of folic acid (FA) prevents neural tube defects in 70% of the population, the exact mechanism of prevention has not been elucidated. We hypothesized that FA affects neural stem cell (NSC) proliferation and differentiation. This hypothesis was examined in a folate-responsive spina bifida mouse model, Splotch (Sp(-/-)), which has a homozygous loss-of-function mutation in the Pax3 gene. Neurospheres were generated with NSCs from the lower lumbar neural tube of E10.5 wild-type (WT) and Sp(-/-) embryos, in the presence and absence of FA. In the absence of FA, the number of neurospheres generated from Sp(-/-) embryos compared with WT was minimal (Pcell differentiation, FA-stimulated Sp(-/-) neurospheres were allowed to differentiate in the continued presence or absence of FA. Neurospheres from both conditions expressed multi-potent stem cell characteristics and the same differentiation potential as WT. Further, multiple neurospheres from both WT and FA-stimulated Sp(-/-) cell cultures formed extensive synaptic connections. On the whole, FA-mediated rescue of neural tube defects in Sp(-/-) embryos promotes NSC proliferation at an early embryonic stage. FA-stimulated Sp(-/-) neurospheres differentiate and form synaptic connections, comparable to WT.

  11. Ectopic Myf5 or MyoD prevents the neuronal differentiation program in addition to inducing skeletal muscle differentiation, in the chick neural tube.

    Science.gov (United States)

    Delfini, Marie-Claire; Duprez, Delphine

    2004-02-01

    Forced expression of the bHLH myogenic factors, Myf5 and MyoD, in various mammalian cell lines induces the full program of myogenic differentiation. However, this property has not been extensively explored in vivo. We have taken advantage of the chick model to investigate the effect of electroporation of the mouse Myf5 and MyoD genes in the embryonic neural tube. We found that misexpression of either mouse Myf5 or MyoD in the chick neural tube leads to ectopic skeletal muscle differentiation, assayed by the expression of the myosin heavy chains in the neural tube and neural crest derivatives. We also showed that the endogenous neuronal differentiation program is inhibited under the influence of either ectopic mouse Myf5 or MyoD. We used this new system to analyse, in vivo, the transcriptional regulation between the myogenic factors. We found that MyoD and Myogenin expression can be activated by ectopic mouse Myf5 or MyoD, while Myf5 expression cannot be activated either by mouse MyoD or by itself. We also analysed the transcriptional regulation between the myogenic factors and the different genes involved in myogenesis, such as Mef2c, Pax3, Paraxis, Six1, Mox1, Mox2 and FgfR4. We established the existence of an unexpected regulatory loop between MyoD and FgfR4. The consequences for myogenesis are discussed.

  12. Development of delayed hydride cracking resistant-pressure tube

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Suk; Kwon, Sang Chul; Kim, S. S.; Yim, K. S

    2000-10-01

    For the first time, we demonstrate that the pattern of nucleation and growth of a DHC crack is governed by the precipitation of hydrides so that the DHC velocity and K{sub IH} are determined by an angle of the cracking plane and the hydride habit plane 10.7. Since texture controls the distribution of the 10.7 habit plane in Zr-2.5Nb pressure tube, we draw a conclusion that a textural change in Zr-2.5Nb tube from a strong tangential texture to the radial texture shall increase the threshold stress intensity factor, K{sub IH}, and decrease the delayed hydride cracking velocity. This conclusion is also verified by a complimentary experiment showing a linear dependence of DHCV and K{sub IH} with an increase in the basal component in the cracking plane. On the basis of the study on the DHC mechanism and the effect of manufacturing processes on the properties of Zr-2.5Nb tube, we have established a manufacturing procedure to make pressure tubes with improved DHC resistance. The main features of the established manufacturing process consist in the two step-cold pilgering process and the intermediate heat treatment in the {alpha} + {beta} phase for Zr-2.5Nb alloy and in the {alpha} phase for Zr-1Nb-1.2Sn-0.4Fe alloy. The manufacturing of DHC resistant-pressure tubes of Zr-2.5Nb and Zr-1N-1.2Sn-0.4Fe was made in the ChMP zirconium plant in Russia under a joint research with Drs. Nikulina and Markelov in VNIINM (Russia). Zr-2.5Nb pressure tube made with the established manufacturing process has met all the specification requirements put by KAERI. Chracterization tests have been jointly conducted by VNIINM and KAERI. As expected, the Zr-2.5Nb tube made with the established procedure has improved DHC resistance compared to that of CANDU Zr-2.5Nb pressure tube used currently. The measured DHC velocity of the Zr-2.5Nb tube meets the target value (DHCV <5x10{sup -8} m/s) and its other properties also were equivalent to those of the CANDU Zr-2.5Nb tube used currently. The Zr-1Nb-1

  13. Electrospun Biocomposite Polycaprolactone/Collagen Tubes as Scaffolds for Neural Stem Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Joanne M. Hackett

    2010-06-01

    Full Text Available Studies using cellular therapies, scaffolds, and tubular structured implants have been carried out with the goal to restore functional recovery after spinal cord injury (SCI. None of these therapeutic strategies, by themselves, have been shown to be sufficient to achieve complete restoration of function. To reverse the devastating effects of SCI, an interdisciplinary approach that combines materials science and engineering, stem cell biology, and neurosurgery is being carried out. We are currently investigating a scaffold that has the ability to deliver growth factors for the proliferation and differentiation of endogenous stem cells. Neural stem cells (NSCs derived from mice are being used to assess the efficacy of the release of growth factors from the scaffold in vitro. The fabrication of the tubular implant allows a porous scaffold to be formed, which aids in the release of growth factors added to the scaffold.

  14. The causes of neural tube defect:evidence-based research%神经管缺陷发生原因的循证医学研究

    Institute of Scientific and Technical Information of China (English)

    谷茜; 刘佳琦; 何达; 葛智馨; 陈英耀; 厉传琳

    2011-01-01

    目的:通过系统性综述的方法,分析神经管缺陷(NTDs)的病因.方法:检索国内外文献数据库,检索时间从建库~2009年12月,纳入神经管缺陷病因学的系统性综述/Meta分析和随机对照试验,中文文献研究设计等级为病例-对照研究.结果:共纳入系统性综述/Meta分析9篇,随机对照试验2篇,病例-对照研究7篇.现有证据显示,遗传方面,MTHFR基因677位点TT基因型是非拉丁裔欧洲人群子代NTDs发生的危险因素;与HCY(同型半胱氨酸)代谢途径有关的酶或基因突变可引起NTDs发生概率增加,具有家族史及NTDs生产史其子代NTDs发病率较高.环境暴露方面,孕妇高热、父亲接触有机溶剂和使用抗癫痫药物(卡马西平和丙戊酸)是NTDs发生的危险因素,现有证据不支持紫外线照射和使用克罗米酚柠檬酸盐影响子代NTDs的发病风险的假设.生活行为方面,孕妇超重或肥胖、多次孕产史是NTDs发生的危险因素,使用IVF辅助生殖技术对NTDs发病的影响仍存在争议.结论:NTDs病因复杂,具有较高证据等级的病因学研究不多,病因仍有待探索.目前在孕早期补充叶酸是被广泛推荐使用的有效干预措施.%Objective: To analyze the causes of neural tube defect by systematic review. Methods: The international and national databases (from establishment to December 2009) were searched, all systematic reviews/Meta analysis and randomized controlled trials researches about the etiology of neural tube defect were included, case - control studies were also supplemented in Chinese literatures. Results: 9 systematic reviews/ Meta analysis researches, 2 randomized controlled trials and 7 case -control studies in Chinese were included. The current evidence suggested that TT genotype in 677 locus of MTHFR gene was a risk factor of neural tube defect of non - Latin European descents from the genetic point of view; the enzymatic mutation and gene mutation related to

  15. Dimensions of early experience and neural development: deprivation and threat.

    Science.gov (United States)

    Sheridan, Margaret A; McLaughlin, Katie A

    2014-11-01

    Over the past decade, a growing area of research has focused on adverse childhood experiences (ACEs) and their impacts on neural and developmental outcomes. Work in the field to-date has generally conceptualized ACEs in terms of exposure to stress while overlooking the underlying dimensions of environmental experience that may distinctly impact neural development. Here, we propose a novel framework that differentiates between deprivation (absence of expected cognitive and social input) and threat (presence of a threat to one's physical integrity). We draw support for the neural basis of this distinction from studies on fear learning and sensory deprivation in animals to highlight potential mechanisms through which experiences of threat and deprivation could affect neural structure and function in humans.

  16. Epidemiologic study of neural tube defects in Los Angeles County. I. Prevalence at birth based on multiple sources of case ascertainment

    Energy Technology Data Exchange (ETDEWEB)

    Sever, L.E. (Pacific Northwest Lab., Richland, WA); Sanders, M.; Monsen, R.

    1982-01-01

    Epidemiologic studies of the neural tube defects (NTDs), anencephalus and spina bifida, have for the most part been based on single sources of case ascertainment in past studies. The present investigation attempts total ascertainment of NTD cases in the newborn population of Los Angeles County residents for the period 1966 to 1972. Design of the study, sources of data, and estimates of prevalence rates based on single and multiple sources of case ascertainment are here discussed. Anencephalus cases totaled 448, spina bifida 442, and encephalocele 72, giving prevalence rates of 0.52, 0.51, and 0.08 per 1000 total births, respectively, for these neural tube defects - rates considered to be low. The Los Angeles County prevalence rates are compared with those of other recent North American studies and support is provided for earlier suggestions of low rates on the West Coast.

  17. Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines.

    Science.gov (United States)

    Cordero, Amy M; Crider, Krista S; Rogers, Lisa M; Cannon, Michael J; Berry, R J

    2015-04-24

    Neural tube defects (NTDs) such as spina bifida, anencephaly, and encephalocele are serious birth defects of the brain and spine that occur during the first month of pregnancy when the neural tube fails to close completely. Randomized controlled trials and observational studies have shown that adequate daily consumption of folic acid before and during early pregnancy considerably reduces the risk for NTDs. The U.S. Public Health Service recommends that women capable of becoming pregnant consume 400 µg of folic acid daily for NTD prevention. Furthermore, fortification of staple foods (e.g., wheat flour) with folic acid has decreased folate-sensitive NTD prevalence in multiple settings and is a highly cost-effective intervention.

  18. Mutations in the COPII vesicle component gene SEC24B are associated with human neural tube defects.

    Science.gov (United States)

    Yang, Xue-Yan; Zhou, Xiang-Yu; Wang, Qing Qing; Li, Hong; Chen, Ying; Lei, Yun-Ping; Ma, Xiao-Hang; Kong, Pan; Shi, Yan; Jin, Li; Zhang, Ting; Wang, Hong-Yan

    2013-08-01

    Neural tube defects (NTDs) are severe birth malformations that affect one in 1,000 live births. Recently, mutations in the planar cell polarity (PCP) pathway genes had been implicated in the pathogenesis of NTDs in both the mouse model and in human cohorts. Mouse models indicate that the homozygous disruption of Sec24b, which mediates the ER-to-Golgi transportation of the core PCP gene Vangl2 as a component of the COPII vesicle, will result in craniorachischisis. In this study, we found four rare missense heterozygous SEC24B mutations (p.Phe227Ser, p.Phe682Leu, p.Arg1248Gln, and p.Ala1251Gly) in NTDs cases that were absent in all controls. Among them, p.Phe227Ser and p.Phe682Leu affected its protein stability and physical interaction with VANGL2. Three variants (p.Phe227Ser, p.Arg1248Gln, and p.Ala1251Gly) were demonstrated to affect VANGL2 subcellular localization in cultured cells. Further functional analysis in the zebrafish including overexpression and dosage-dependent rescue study suggested that these four mutations all displayed loss-of-function effects compared with wild-type SEC24B. Our study demonstrated that functional mutations in SEC24B might contribute to the etiology of a subset of human NTDs and further expanded our knowledge of the role of PCP pathway-related genes in the pathogenesis of human NTDs.

  19. Impact of an online educational program on pharmacy students' knowledge of folic acid and neural tube defects.

    Science.gov (United States)

    Bykhovsky, Margarita; Meier, Mary Frances K; Mager, Natalie A DiPietro

    2014-10-01

    Pharmacy students must receive adequate training regarding folic acid for the prevention of neural tube defects (NTDs). Pharmacy students' knowledge should be evaluated and effective methods utilized to improve it, if needed. The objective of this study was to assess baseline knowledge among third-year students in a 0-6 Doctor of Pharmacy program and to evaluate the impact of an online educational video. Baseline knowledge was assessed by a pretest adapted with permission from the March of Dimes (MOD). Students watched a 30-minute MOD video and completed a posttest. Nine months later, students completed a longitudinal posttest. Analysis of variance was used to assess differences in the percentage of correct responses to each question. A total of 133 (90.5%) students completed the educational program and 105 (78.9%) completed the longitudinal test. Statistically significant improvements in knowledge from baseline were seen for 9 of 10 questions on the posttest and for 6 of 10 questions on the longitudinal test. Online videos are tools to teach pharmacy students key information regarding folic acid and NTD; however, material should be reinforced in experiential education as well. Counseling women of childbearing potential about folic acid fulfills an important public health need. © The Author(s) 2014.

  20. Awareness and intake of folic acid for the prevention of neural tube defects among Lebanese women of childbearing age.

    Science.gov (United States)

    Nasr Hage, Claudine; Jalloul, Maya; Sabbah, Mohamad; Adib, Salim M

    2012-01-01

    Since the early 1990s, international recommendations have promoted folic acid supplementation during the periconception period as an effective way of preventing neural tube defects (NTDs). However, the adoption of this recommendation remains insufficient. To assess the awareness and actual intake of folic acid among married Lebanese women aged 18-45 years, a cross-sectional study was conducted among 600 women selected from all five administrative districts in Lebanon, using a multistage cluster sampling procedure. An anonymous questionnaire was completed which covered measures of knowledge and use of folate supplements, as well as demographic, socioeconomic and obstetrical factors. Sixty percent of surveyed women (60%; n = 360) had heard about folic acid. Doctors were the most frequent source of information (61.1%) but only 24.7% of women have been told of the correct period during which folic acid supplementation was useful. Overall, only 6.2% had taken folic acid tablets during the adequate period. Younger age, higher education level and stability/sufficiency of income appeared to be significant predictors of awareness among Lebanese women. Actual folic acid intake was significantly associated with younger age, higher number of pregnancies, planning the last pregnancy and having had that last one after 1990. In Lebanon, the level of folic acid awareness and adequate intake remain relatively low. Several approaches should be used to promote folic acid intake including awareness campaigns, and routine counseling by primary health care physicians on folic acid during preconception visits.

  1. Prevalence of neural tube defects and folic acid knowledge and consumption--Puerto Rico, 1996-2006.

    Science.gov (United States)

    2008-01-11

    Birth defects are one of the leading causes of infant mortality in both the mainland United States and Puerto Rico. Neural tube defects (NTDs) are serious birth defects of the spine and brain; two of the most common NTDs are spina bifida and anencephaly. In the United States, NTD prevalence is higher among Hispanic women than among non-Hispanic white or non-Hispanic black women. In Puerto Rico, where most residents are Hispanic, the prevalence of NTDs (8.68 per 10,000 live births) is higher than in the mainland United States (5.59). Consumption of folic acid before and during early pregnancy can prevent NTDs. To assess trends in NTD prevalence and prevalence of knowledge and consumption of folic acid supplements in Puerto Rico, data were analyzed from the Birth Defects Surveillance System (BDSS) for 1996-2005 and the Behavioral Risk Factor Surveillance System (BRFSS) for 1997-2006. This report describes the results of those analyses, which indicated that prevalence of folic acid knowledge and consumption among women of childbearing age increased from 1997 to 2003 but decreased from 2003 to 2006. During similar periods, NTD prevalence declined from 1996 to 2003 but did not change significantly from 2003 to 2005. To resume the decline in prevalence of NTDs, additional measures might be needed to increase folic acid supplement use among Puerto Rican women of childbearing age.

  2. [Attitudes of pregnant Japanese women and folic acid intake for the prevention of neural tube defects: a nationwide Internet survey].

    Science.gov (United States)

    Sato, Yoko; Nakanishi, Tomoko; Chiba, Tsuyoshi; Umegaki, Keizo

    2014-01-01

    Folic acid intake is recommended for pregnant women because it significantly reduces the risk of neural tube defects (NTD) in the fetus. However, the risk of NTD remains medium in Japan. In this study, the attitudes of pregnant Japanese women and factors related to folic acid intake for the prevention of NTD were evaluated using a nationwide survey. An Internet-based questionnaire was conducted on 2,367 pregnant Japanese women who were registrants of a Japanese social research company in January 2012; 1,236 of these women responded. In the questionnaires, the knowledge regarding the folate intake (i.e., name of folic acid, the risk of NTD, recommended doses, and timing), actual intake of folic acid, demographic factors (i.e., age, geographical area, gestational age, and birth order), and intake of dietary supplements were surveyed. Eighty-five percent of respondents consumed folate, which was mostly obtained through dietary folic acid supplements during the first month of pregnancy or after. Factors associated with loss of folic acid intake until 3 months of pregnancy included lack of knowledge, failure to consume dietary supplements, younger age, and multigravida. Many pregnant women in Japan consumed folic acid. However, most of them started supplementation after pregnancy recognition, which is too late to reduce the risk of NTD. Alternative strategies to increase the efficacy of folic acid intake, such as recommending folic acid-enriched foods, promoting folic acid fortification efforts, and providing access to practical information, are necessary.

  3. Bayesian mapping of neural tube defects prevalence in Heshun County, Shanxi Province, China during 1998~2001

    Institute of Scientific and Technical Information of China (English)

    CHI Wen-xue; WANG Jin-feng; LI Xin-hu; ZHENG Xiao-ying; LIAO Yi-lan

    2007-01-01

    Objective: To estimate the prevalence rates of neural tube defects (NTDs) in Heshun County, Shanxi Province, China by Bayesian smoothing technique. Methods: A total of 80 infants in the study area who were diagnosed with NTDs were analyzed. Two mapping techniques were then used. Firstly, the GIS software ArcGIS was used to map the crude prevalence rates. Secondly,the data were smoothed by the method of empirical Bayes estimation. Results: The classical statistical approach produced an extremely dishomogeneous map, while the Bayesian map was much smoother and more interpretable. The maps produced by the Bayesian technique indicate the tendency of villages in the southeastern region to produce higher prevalence or risk values. Conclusions: The Bayesian smoothing technique addresses the issue of heterogeneity in the population at risk and it is therefore recommended for use in explorative mapping of birth defects. This approach provides procedures to identify spatial health risk levels and assists in generating hypothesis that will be investigated in further detail.

  4. Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages.

    Science.gov (United States)

    Jaber, Lutfi; Karim, Igbaria A; Jawdat, Abu Moch; Fausi, Mawasi; Merlob, Paul

    2004-01-01

    Neural tube defects (NTDs) are severe congenital malformations and can be fatal. Intake of 0.4 mg folic in the periconceptional period reduces the risk of NTD by 50-70%. Consanguinity in the Arab population in Israel is a prevalent custom. The aim of this study was to assess the level of awareness regarding folic acid and its effect in the prevention of NTD among Arab Israeli women of childbearing age. We conducted a cross-sectional study. Of the 653 women (18-45 years) who were randomly selected for interview while visiting their family physician or well-baby clinic, 624 women completed the questionnaire. Fifty-three percent (n = 333) of the respondents had heard of folic acid; 14% (n = 89) were familiar with the protective effect of NTD and 3% (n = 18) had taken folic acid in the first months of pregnancy whereas none of them had used it in the preconception period. Highly educated women, women with one or two children, paramedics, and women of high socioeconomic status were more knowledgeable about the protective effects of folic acid (P awareness of this population to the protective effect of folic acid. Daily supplementation and fertification of food with folic acid should be considered as the best way to improve the balance of folic acid in women of childbearing age of this special population (high prevalence of consanguinity).

  5. Folic acid and prevention of neural tube defects in 2000 improved awareness--low peri-conceptional uptake.

    Science.gov (United States)

    Oleary, M; Donnell, R M; Johnson, H

    2001-06-01

    Eight years have passed since recommendations were made by the Irish Department of Health on the importance of folic acid in the prevention of neural tube defects (NTD). There is currently no mandatory fortification of foodstuffs with folic acid in Ireland, with reliance placed on campaigns promoting increased dietary folate intake and supplements. We assessed knowledge and use of folic acid among 300 women attending ante-natal clinics in Dublin maternity hospitals in the year 2000 using an interviewer administered questionnaire. Qualitative information was obtained through means of a focus group. Ninety two percent of respondents had heard of folic acid and 67% knew it could prevent NTD. Thirty per cent were advised to take it peri-conceptionally but overall only 18% did so; 39% of women had planned their pregnancy. The focus group indicated that folic acid was not 'visible' enough and that fortification of food was more realistic. This study shows that improved folic acid awareness has not been accompanied by corresponding peri-conceptional uptake in 2000. Folic acid promotional campaigns should be continuous and targeted. Mandatory food fortification should be strongly considered.

  6. Development of Preliminary HT9 Cladding Tube for Sodium-cooled Fast Reactor (SFR)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jun Hwan; Baek, Jong Hyuk; Heo, Hyeong Min; Park, Sang Gyu; Kim, Sung Ho; Lee, Chan Bock [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-05-15

    To achieve manufacturing technology of the fuel cladding tube in order to keep pace with the predetermined schedule in developing SFR fuel, KAERI has launched in developing fuel cladding tube in cooperation with a domestic steelmaking company. After fabricating medium-sized 1.1 ton HT9 ingot, followed by the multiple processes of hot and cold working, preliminary samples of HT9 seamless cladding tube having 7.4mm in outer diameter, 0.56mm in thickness, and 3m in length were fabricated. The objective of this study is to summarize the brief development status of the HT9 cladding tubes. Mechanical properties like axial tension, biaxial burst, pressurized creep and sodium compatibility of the cladding tubes were carried out to set up the performance evaluation technology to test the prototype FMS cladding tube which is going to be manufactured in next stage. As a part of developing fuel cladding for the Sodium-cooled Fast Reactor (SFR), preliminary HT9 cladding tube was fabricated in cooperation with a domestic steelmaking company. Microstructure as well as mechanical tests like axial tensile test, biaxial burst test, and pressurized creep test of the fuel cladding were carried out. Performance of the domestic HT9 tube was revealed to be similar in the previously fabricated foreign HT9 tube. Further prototype FMS cladding tube is going to be manufactured in next year based on this experience. Various test items like mechanical test, sodium compatibility test, microstructural analysis, basic property, cladding performance under transient situation, and performance under ion and neutron irradiation are going be performed in the future to set up the relevant technology for the licensing of the SFR cladding tube.

  7. Assessing the prevalence of spina bifida and encephalocele in a Kenyan hospital from 2005-2010: implications for a neural tube defects surveillance system.

    Science.gov (United States)

    Githuku, Jane N; Azofeifa, Alejandro; Valencia, Diana; Ao, Trong; Hamner, Heather; Amwayi, Samuel; Gura, Zeinab; Omolo, Jared; Albright, Leland; Guo, Jing; Arvelo, Wences

    2014-01-01

    Neural tube defects such as anencephaly, spina bifida, and encephalocele are congenital anomalies of the central nervous system. Data on the prevalence of neural tube defects in Kenya are limited. This study characterizes and estimates the prevalence of spina bifida and encephalocele reported in a referral hospital in Kenya from 2005-2010. Cases were defined as a diagnosis of spina bifida or encephalocele. Prevalence was calculated as the number of cases by year and province of residence divided by the total number of live-births per province. From a total of 6,041 surgical records; 1,184 (93%) had reported diagnosis of spina bifida and 88 (7%) of encephalocele. Estimated prevalence of spina bifida and encephalocele from 2005-2010 was 3.3 [95% Confidence Interval (CI): 3.1-3.5] cases per 10,000 live-births. The highest prevalence of cases were reported in 2007 with 4.4 (95% CI: 3.9-5.0) cases per 10,000 live-births. Rift Valley province had the highest prevalence of spina bifida and encephalocele at 6.9 (95% CI: 6.3-7.5) cases per 10,000 live-births from 2005-2010. Prevalence of spina bifida and encephalocele is likely underestimated, as only patients seeking care at the hospital were included. Variations in regional prevalence could be due to referral patterns and healthcare access. Implementation of a neural tube defects surveillance system would provide a more thorough assessment of the burden of neural tube defects in Kenya.

  8. Assessing the prevalence of spina bifida and encephalocele in a Kenyan hospital from 2005–2010: implications for a neural tube defects surveillance system

    Science.gov (United States)

    Githuku, Jane N; Azofeifa, Alejandro; Valencia, Diana; Ao, Trong; Hamner, Heather; Amwayi, Samuel; Gura, Zeinab; Omolo, Jared; Albright, Leland; Guo, Jing; Arvelo, Wences

    2014-01-01

    Introduction Neural tube defects such as anencephaly, spina bifida, and encephalocele are congenital anomalies of the central nervous system. Data on the prevalence of neural tube defects in Kenya are limited. This study characterizes and estimates the prevalence of spina bifida and encephalocele reported in a referral hospital in Kenya from 2005-2010. Methods Cases were defined as a diagnosis of spina bifida or encephalocele. Prevalence was calculated as the number of cases by year and province of residence divided by the total number of live-births per province. Results From a total of 6,041 surgical records; 1,184 (93%) had reported diagnosis of spina bifida and 88 (7%) of encephalocele. Estimated prevalence of spina bifida and encephalocele from 2005-2010 was 3.3 [95% Confidence Interval (CI): 3.1-3.5] cases per 10,000 live-births. The highest prevalence of cases were reported in 2007 with 4.4 (95% CI: 3.9-5.0) cases per 10,000 live-births. Rift Valley province had the highest prevalence of spina bifida and encephalocele at 6.9 (95% CI: 6.3-7.5) cases per 10,000 live-births from 2005-2010. Conclusion Prevalence of spina bifida and encephalocele is likely underestimated, as only patients seeking care at the hospital were included. Variations in regional prevalence could be due to referral patterns and healthcare access. Implementation of a neural tube defects surveillance system would provide a more thorough assessment of the burden of neural tube defects in Kenya. PMID:26113894

  9. Knowledge and peri-conceptional use of folic acid in ethnic communities in the UK for the prevention of Neural Tube Defects

    OpenAIRE

    Peake, J; Copp, AJ; Shawe, J

    2013-01-01

    BACKGROUND: It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.). METHODS: A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced source...

  10. Time trends in the prevalence and epidemiological characteristics of neural tube defects in Liaoning Province, China, 2006-2015: A population-based study.

    Science.gov (United States)

    Zhang, Tie-Ning; Gong, Ting-Ting; Chen, Yan-Ling; Wu, Qi-Jun; Zhang, Yuan; Jiang, Cheng-Zhi; Li, Jing; Li, Li-Li; Zhou, Chen; Huang, Yan-Hong

    2017-02-03

    To evaluate the time trends in the prevalence of neural tube defects and all their subtypes as well as to identify the epidemiological characteristics of these malformations documented in the Liaoning Province of northeast China from 2006 to 2015. This was a population-based observational study using data from 3,248,954 live births as well as from 6217 cases of neural tube defects, 1,600 cases of anencephaly, 2,029 cases of spina bifida, 404 cases of encephalocele, and 3,008 cases of congenital hydrocephalus from 14 cities in Liaoning Province from 2006 to 2015. All analyses were conducted using SPSS software. During the observational period, the prevalence of neural tube defects, anencephaly, spina bifida, encephalocele, and congenital hydrocephalus was 19.1, 4.9, 6.2, 1.2, and 9.3 per 10,000 live births, respectively. Significantly decreasing trends were observed in the prevalence of all these malformations except for encephalocele. Notably, relatively higher prevalence rates were found in isolated compared with non-isolated malformations, with significant differences in selected characteristics (e.g., prognosis status, gestational age, and birth weight) between isolated and non-isolated cases of these malformations. The prevalence of neural tube defects showed a downward trend in Liaoning Province from 2006 to 2015. However, more attention should be focused on non-isolated cases in the future because of the severe clinical manifestations. Future prevention efforts should be strengthened to reduce the risk of these malformations, especially the non-isolated subtype, in areas with high prevalence.

  11. 反式维甲酸诱导显性脊柱裂胎鼠骶尾部神经前体细胞凋亡和增殖的变化规律研究%Disturbed apoptosis and cell proliferation in developing neuroepithelium of lumbo-sacral neural tubes in retinoic acid-induced spina biifda aperta in rat

    Institute of Scientific and Technical Information of China (English)

    魏晓伟; 袁正伟

    2015-01-01

    目的观察大鼠胚胎脊柱裂发生早期,细胞凋亡与细胞增殖的变化规律。方法孕鼠随机分为对照组和实验组。胚胎10天时,实验组1次性经胃管注入致畸量反式维甲酸诱导产生脊柱裂动物模型,对照组胃饲等量溶剂,分别在妊娠11、12、13天(E11, E12, E13)时剖宫取胚胎,一部分胚胎固定后进行全胚胎TUNEL染色观察其整体凋亡情况;另一部分胚胎常规制作石蜡切片,采用TUNEL切片染色和免疫荧光染色技术,检测胚胎脊部神经管组织中细胞凋亡和细胞增殖的变化。结果与对照组相比,细胞凋亡于多个发育部位明显增多,集中表现在颅面原基、颅部神经管的背外侧、骶尾部神经管的背部中线。免疫荧光染色显示,与对照组相比,脊柱裂组胚胎畸形发生部位的神经前体细胞的凋亡率升高[E11(2.02±0.52)%与(0.57±0.23)%, E12(3.56±0.33)%与(0.93±0.14)%,E13(3.76±0.37)%与(1.24±0.21)%,P<0.001]。而细胞增殖降低[E11(65.17±2.30)%与(81.76±2.17)%, E12(63.97±3.03)%与(76.98±5.14)%,E13(56.86±2.80)%与(73.43±1.99)%,P <0.001]。结论反式维甲酸诱导的大鼠脊柱裂胚胎骶尾部神经管中神经前体细胞凋亡增多,而细胞增殖减少,这可能是脊柱裂胚胎神经元发育异常的主要原因之一。%Objective To investigate the cell apoptosis in the whole embryosand proliferation of neural progenitor cells in the spinal neural tube during neurulation in all-trans retinoic acid (atRA)-induced spina biifda in fetal rats.MethodSpina biifda was induced by atRA in fetal rats. Cell apoptosis and cell proliferation were assessed using TUNEL labeling technique on both whole-mount and serially sectioned embryos and mitotic markers (Ki67) assay, respectively.ResultsAn excess of apoptosis in the neuroepithelium of embryos with spina bifida was found, which became more marked as embryos

  12. Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse.

    Science.gov (United States)

    Curtin, John A; Quint, Elizabeth; Tsipouri, Vicky; Arkell, Ruth M; Cattanach, Bruce; Copp, Andrew J; Henderson, Deborah J; Spurr, Nigel; Stanier, Philip; Fisher, Elizabeth M; Nolan, Patrick M; Steel, Karen P; Brown, Steve D M; Gray, Ian C; Murdoch, Jennifer N

    2003-07-01

    We identified two novel mouse mutants with abnormal head-shaking behavior and neural tube defects during the course of independent ENU mutagenesis experiments. The heterozygous and homozygous mutants exhibit defects in the orientation of sensory hair cells in the organ of Corti, indicating a defect in planar cell polarity. The homozygous mutants exhibit severe neural tube defects as a result of failure to initiate neural tube closure. We show that these mutants, spin cycle and crash, carry independent missense mutations within the coding region of Celsr1, encoding a large protocadherin molecule [1]. Celsr1 is one of three mammalian homologs of Drosophila flamingo/starry night, which is essential for the planar cell polarity pathway in Drosophila together with frizzled, dishevelled, prickle, strabismus/van gogh, and rhoA. The identification of mouse mutants of Celsr1 provides the first evidence for the function of the Celsr family in planar cell polarity in mammals and further supports the involvement of a planar cell polarity pathway in vertebrate neurulation.

  13. Zebrafish Zic2a and Zic2b regulate neural crest and craniofacial development.

    Science.gov (United States)

    Teslaa, Jessica J; Keller, Abigail N; Nyholm, Molly K; Grinblat, Yevgenya

    2013-08-01

    Holoprosencephaly (HPE), the most common malformation of the human forebrain, is associated with defects of the craniofacial skeleton. ZIC2, a zinc-finger transcription factor, is strongly linked to HPE and to a characteristic set of dysmorphic facial features in humans. We have previously identified important functions for zebrafish Zic2 in the developing forebrain. Here, we demonstrate that ZIC2 orthologs zic2a and zic2b also regulate the forming zebrafish craniofacial skeleton, including the jaw and neurocranial cartilages, and use the zebrafish to study Zic2-regulated processes that may contribute to the complex etiology of HPE. Using temporally controlled Zic2a overexpression, we show that the developing craniofacial cartilages are sensitive to Zic2 elevation prior to 24hpf. This window of sensitivity overlaps the critical expansion and migration of the neural crest (NC) cells, which migrate from the developing neural tube to populate vertebrate craniofacial structures. We demonstrate that zic2b influences the induction of NC at the neural plate border, while both zic2a and zic2b regulate NC migratory onset and strongly contribute to chromatophore development. Both Zic2 depletion and early ectopic Zic2 expression cause moderate, incompletely penetrant mispatterning of the NC-derived jaw precursors at 24hpf, yet by 2dpf these changes in Zic2 expression result in profoundly mispatterned chondrogenic condensations. We attribute this discrepancy to an additional role for Zic2a and Zic2b in patterning the forebrain primordium, an important signaling source during craniofacial development. This hypothesis is supported by evidence that transplanted Zic2-deficient cells can contribute to craniofacial cartilages in a wild-type background. Collectively, these data suggest that zebrafish Zic2 plays a dual role during craniofacial development, contributing to two disparate aspects of craniofacial morphogenesis: (1) neural crest induction and migration, and (2) early

  14. Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study.

    Science.gov (United States)

    Cadenas-Benitez, N M; Yanes-Sosa, F; Gonzalez-Meneses, A; Cerrillos, L; Acosta, D; Praena-Fernandez, J M; Neth, O; Gomez de Terreros, I; Ybot-González, P

    2014-03-26

    Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

  15. Current Status on the Development of a Double Wall Tube Steam Generator

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Ho Yun; Choi, Byoung Hae; Kim, Jong Man; Kim, Byung Ho

    2007-12-15

    A fast reactor, which uses sodium as a coolant, has a lot of merits as a next generation nuclear reactor. However, the possibility of a sodium-water reaction occurrence hinders the commercialization of this reactor. As one way to improve the reliability of a steam generator, a double-wall tube steam generator is being developed in GEN-4 program. In this report, the current state of the technical developments for a double-wall tube steam generator are reviewed and a future plan for the development of a double-wall tube steam generator is established. The current focuses of this research are an improvement of the heat transfer capability for a double-wall tube and the development of a proper leak detection method for the failure of a double-wall tube during a reactor operation. The ideal goal is an on-line leak detection of a double wall tube to prevent the sodium-water reaction. However, such a method is not developed as yet. An alternative method is being used to improve the reliability of a steam generator by performing a non-destructive test of a double wall tube during the refueling period of a reactor. In this method a straight double wall tube is employed to perform this test easily, but has a difficulty regarding an absorption of a thermal expansion of the used materials. If an on-line leak detection method is developed, the demerits of a straight double-wall tube are avoided by using a helical type double-wall tube, and the probability of a sodium-water reaction can be reduced to a level less than the design-based accident.

  16. Development of valve-less tube-type micropump with PZT actuator

    Science.gov (United States)

    Tsuchiya, Kazuyoshi; Morishima, Akifumi; Takamata, Atsushi; Uetsuji, Yasutomo; Nakamachi, Eiji

    2008-12-01

    The medical devices such as a micropump to extract blood through a tube have a structure which needle and pump part are mutually separated. Therefore, it is not easy to make smaller than the conventional pump. In this research, we aim to develop the pump combined with a tube as a final purpose. In this study, ring type PZT elements are mounted on the surface of the silicone tube, and the stationary waves are generated in the tube by the vibration of those PZT on the tube verified by changing the AC voltage. The waves generated by the collision of large and small stationary waves are synthesized, and then the wave becomes a progressive wave with an elliptic motion in the tube. The flow function demonstrated by the tube type micropump was evaluated and the flow velocities were increased 2.78% and decreased 1.79%. On the other hand, we have a technique to produce a titanium microtube by using RF magnetron sputtering deposition technique. A Titanium micro tube with the size of a female mosquito's labium (60µm external and 25μm internal diameter) was produced by the sputter deposition method. In order to deposit PZT thin film on the titanium micro tube, the thin film process is used. The thin film deposition conditions of the PZT thin film are investigated and the characteristic of the PZT thin films are evaluated.

  17. Chromophore-assisted laser inactivation in neural development

    Institute of Scientific and Technical Information of China (English)

    Wei Li; Nico Stuurman; Guangshuo Ou

    2012-01-01

    Chromophore-assisted laser inactivation (CALI) is a technique that uses photochemically-generated reactive oxygen species to acutely inactivate target proteins in living cells.Neural development includes highly dynamic cellular processes such as asymmetric cell division,migration,axon and dendrite outgrowth and synaptogenesis.Although many key molecules of neural development have been identified since the past decades,their spatiotemporal contributions to these cellular events are not well understood.CALI provides an appealing tool for elucidating the precise functions of these molecules during neural development.In this review,we summarize the principles of CALI,a recent microscopic setup to perform CALI experiments,and the application of CALI to the study of growth-cone motility and neuroblast asymmetric division.

  18. Meis3 is required for neural crest invasion of the gut during zebrafish enteric nervous system development.

    Science.gov (United States)

    Uribe, Rosa A; Bronner, Marianne E

    2015-11-01

    During development, vagal neural crest cells fated to contribute to the enteric nervous system migrate ventrally away from the neural tube toward and along the primitive gut. The molecular mechanisms that regulate their early migration en route to and entry into the gut remain elusive. Here we show that the transcription factor meis3 is expressed along vagal neural crest pathways. Meis3 loss of function results in a reduction in migration efficiency, cell number, and the mitotic activity of neural crest cells in the vicinity of the gut but has no effect on neural crest or gut specification. Later, during enteric nervous system differentiation, Meis3-depleted embryos exhibit colonic aganglionosis, a disorder in which the hindgut is devoid of neurons. Accordingly, the expression of Shh pathway components, previously shown to have a role in the etiology of Hirschsprung's disease, was misregulated within the gut after loss of Meis3. Taken together, these findings support a model in which Meis3 is required for neural crest proliferation, migration into, and colonization of the gut such that its loss leads to severe defects in enteric nervous system development.

  19. An overview on development of neural network technology

    Science.gov (United States)

    Lin, Chun-Shin

    1993-01-01

    The study has been to obtain a bird's-eye view of the current neural network technology and the neural network research activities in NASA. The purpose was two fold. One was to provide a reference document for NASA researchers who want to apply neural network techniques to solve their problems. Another one was to report out survey results regarding NASA research activities and provide a view on what NASA is doing, what potential difficulty exists and what NASA can/should do. In a ten week study period, we interviewed ten neural network researchers in the Langley Research Center and sent out 36 survey forms to researchers at the Johnson Space Center, Lewis Research Center, Ames Research Center and Jet Propulsion Laboratory. We also sent out 60 similar forms to educators and corporation researchers to collect general opinions regarding this field. Twenty-eight survey forms, 11 from NASA researchers and 17 from outside, were returned. Survey results were reported in our final report. In the final report, we first provided an overview on the neural network technology. We reviewed ten neural network structures, discussed the applications in five major areas, and compared the analog, digital and hybrid electronic implementation of neural networks. In the second part, we summarized known NASA neural network research studies and reported the results of the questionnaire survey. Survey results show that most studies are still in the development and feasibility study stage. We compared the techniques, application areas, researchers' opinions on this technology, and many aspects between NASA and non-NASA groups. We also summarized their opinions on difficulties encountered. Applications are considered the top research priority by most researchers. Hardware development and learning algorithm improvement are the next. The lack of financial and management support is among the difficulties in research study. All researchers agree that the use of neural networks could result in

  20. Roles of Hoxb5 in the development of vagal and trunk neural crest cells.

    Science.gov (United States)

    Kam, Mandy K M; Lui, Vincent C H

    2015-02-01

    Neural crest cells (NC) are a group of multipotent stem cells uniquely present in vertebrates. They are destined to form various organs according to their anterior-posterior (A-P) levels of origin in the neural tube (NT). They develop into a wide spectrum of cell lineages under the influence of signaling cascades, neural plate border genes and NC specifier genes. Although this complex gene regulatory network (GRN) specifies the fate of NC and the combinatory action of Hox genes executed at the time of NC induction governs the patterning of NC for the formation of specific structures along the A-P axis, not much information on how GRN and Hox genes directly interact and orchestrate is available. This review summarizes recent findings on the multiple roles of Hoxb5 on the survival and cell lineage differentiation of vagal and trunk NC cells during early development, by direct transcriptional regulation of NC specifier genes (Sox9 and Foxd3) of the GRN. We will also review findings on the transcriptional regulation of Ret by Hoxb5 in the population of the vagal NC that are committed to the enteric neuron and glia lineages. Functional redundancy between Hox proteins (Hoxa5 and Hoxc5) from the same paralogue group as Hoxb5, and the cooperative effects of Hox cofactors, collaborators and transcription factors in the Hoxb5 transcriptional regulation of target genes will also be discussed. © 2015 Japanese Society of Developmental Biologists.

  1. Development of an X-ray tube for irradiation experiments using a field emission electron gun

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Hidetoshi, E-mail: katou-h@aist.go.jp [Research Institute for Measurement and Analytical Instrumentation (RIMA), National Metrology Institute of Japan (NMIJ), National Institute of Advanced Industrial Science and Technology - AIST, Tsukuba-Central 2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568 (Japan); O' Rourke, Brian E.; Suzuki, Ryoichi [Research Institute for Measurement and Analytical Instrumentation (RIMA), National Metrology Institute of Japan (NMIJ), National Institute of Advanced Industrial Science and Technology - AIST, Tsukuba-Central 2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568 (Japan); Wang, Jiayu; Ooi, Takashi; Nakajima, Hidetoshi [Pureron Japan Co., Ltd., 1-37 Yoshima Industrial Park, Iwaki, Fukushima, 970-1144 (Japan)

    2016-01-21

    A new X-ray tube using a ring-shaped emitter as a field emission electron source has been developed. By using a ring shaped cathode, X-rays can be extracted along the axial direction through the central hole. This cylindrically symmetrical design allows for the tube to be arranged in the axial direction with the high voltage target at one end and the X-ray beam at the other. The newly developed X-ray tube can operate at a tube voltage of more than 100 kV and at a tube current of more than 4 mA, and can be used for irradiation experiments with an irradiation dose range from mGy up to kGy. The X-ray tube can be used immediately after turning on (i.e. there is no stand-by time). In the experimental model, we demonstrated stable electron emission at a tube voltage of 100 kV and at a tube current of 4 mA during a 560 h continuous test.

  2. Development of target-tracking algorithms using neural network

    Energy Technology Data Exchange (ETDEWEB)

    Park, Dong Sun; Lee, Joon Whaoan; Yoon, Sook; Baek, Seong Hyun; Lee, Myung Jae [Chonbuk National University, Chonjoo (Korea)

    1998-04-01

    The utilization of remote-control robot system in atomic power plants or nuclear-related facilities grows rapidly, to protect workers form high radiation environments. Such applications require complete stability of the robot system, so that precisely tracking the robot is essential for the whole system. This research is to accomplish the goal by developing appropriate algorithms for remote-control robot systems. A neural network tracking system is designed and experimented to trace a robot Endpoint. This model is aimed to utilized the excellent capabilities of neural networks; nonlinear mapping between inputs and outputs, learning capability, and generalization capability. The neural tracker consists of two networks for position detection and prediction. Tracking algorithms are developed and experimented for the two models. Results of the experiments show that both models are promising as real-time target-tracking systems for remote-control robot systems. (author). 10 refs., 47 figs.

  3. Development and characterization of an open-ended shock tube for the study of blast mtbi.

    Science.gov (United States)

    Shah Ms, Alok S; Stemper Phd, Brian D; Pintar Phd, Frank A

    2012-01-01

    Shock tubes can be used to study traumatic brain injuries due to blast waves in a laboratory setting without the use of explosives. A literature review shows that several shock tubes used in these type of studies are large in size and have a high cost of conducting tests and maintaining the device. The purpose of this study was to design and characterize small shock tubes to simulate open field blast waves, which can be used in a laboratory with limited space and has low cost of operation. In addition, the shock tube can be used to induce localized blast in a small region to study the injury mechanisms in the desired region. Furthermore, the animal is placed outside of the shock tube, which provides the ability to expose the animal to a pure primary blast wave. A helium-driven shock tube with driven length of 3.04 m and driver length of 0.30 m was used in the present study. Transducers were placed at multiple locations and distances to characterize the blast wave outside the shock tube. The versatile design of the shock tube can generate a wide range of peak overpressure, rise times and durations. The shock tube was able to generate peak overpressure ranging from 25 kPa to 508 kPa and positive durations ranging from 97 µs to 797 µs. The literature review also showed several studies where the data were collected and analyzed improperly. The under-sampling or improper filtering can significantly affect the data. Additionally, the orientation of the transducer with respect to the shock wave can also affect the recorded peak overpressure. This paper reports various peak overpressures, durations and rise-times that can be developed with a small open-ended shock tube and the methodology to properly collect and analyze blast wave data generated by the shock tube.

  4. Epigenetic alterations in folate transport genes in placental tissue from fetuses with neural tube defects and in leukocytes from subjects with hyperhomocysteinemia

    Science.gov (United States)

    Farkas, Sanja A.; Böttiger, Anna K.; Isaksson, Helena S.; Finnell, Richard H.; Ren, Aiguo; Nilsson, Torbjörn K.; Nilsson, Torbjörn K.

    2013-01-01

    The objectives of this study were to identify tissue-specific differentially methylated regions (T-DMR’s) in the folate transport genes in placental tissue compared with leukocytes, and from placental tissues obtained from normal infants or with neural tube defects (NTDs). Using pyrosequencing, we developed methylation assays for the CpG islands (CGIs) and the CGI shore regions of the folate receptor α (FOLR1), proton-coupled folate transporter (PCFT) and reduced folate carrier 1 (RFC1) genes. The T-DMRs differed in location for each gene and the difference in methylation ranged between 2 and 54%. A higher T-DMR methylated fraction was associated with a lower mRNA level of the FOLR1 and RFC1 genes. Methylation fractions differed according to RFC1 80G > A genotype in the NTD cases and in leukocytes from subjects with high total plasma homocysteine (tHcy). There were no differences in methylated fraction of folate transporter genes between NTD cases and controls. We suggest that T-DMRs participate in the regulation of expression of the FOLR1 and RFC1 genes, that the RFC1 80G > A polymorphism exerts a gene-nutrition interaction on DNA methylation in the RFC1 gene, and that this interaction appears to be most prominent in NTD-affected births and in subjects with high tHcy concentrations. PMID:23417011

  5. [Awareness and knowledge of the use of folic acid in the prevention of neural tube defects: a survey of women living in Santiago, Chile].

    Science.gov (United States)

    Pardo V, Rosa A; Lay-Son R, Guillermo; Aranda Ch, Waldo; Dib M, Martín; Espina M, Pablo; Muñoz K, María J; Muñoz B, Pilar; Navarrete C, María F; Ojeda M, Natalia V; Parra, Jorge; Rebolledo D, Cristian A; Recabal G, Pedro; Tenhamm T, Tamara

    2007-12-01

    Wheat flour in Chile is fortified with folie acid and pregnant women are also supplemented with the vitamin, but the population level of knowledge or awareness about this vitamin and its use by pregnant women is unknown. To assess the level of knowledge that postpartum women from Santiago de Chile have about folic acid. A questionnaire about folic acid and its effects on the prevention of neural tube defects was developed adapting questionnaires designed abroad. It was applied by medical students to puerperal women, hospitalized in public hospitals. The questionnaire was applied to 342 women aged 26 +/- 7 years. Sixty one percent were housewives and 55% completed high school education. Forty seven percent of these women had heard about folic acid, 9.6% knew that it was able to prevent congenital defects and only one received an adequate supplementation during pregnancy. Women aged 25 to 34 years and those with an adequate medical care during pregnancy had a significantly better knowledge about folic acid and its role in the prevention of congenital anomalies. The more common means to receive information about folic acid were midwives (34%), mass media (28%) and doctors (20%). Two hundred eleven women (62%) agreed to take folic acid in a future gestation and 58% preferred to do so using fortified foods. Post partum women from Santiago have a poor knowledge about the relevance of folic acid supplementation.

  6. Genetic effects on variation in red-blood-cell folate in adults: Implications for the familial aggregation of neural tube defects

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, L.E. [Children`s Hospital of Philadelphia, PA (United States); Duffy, P.; Bellingham, G. [Prince Charles Hospital, Brisbane (Australia)] [and others

    1997-02-01

    Recent studies have implicated folic acid as an important determinant of normal human growth, development, and function. Insufficient folate levels appear to be a risk factor for neural tube defects (NTD), as well as for several chronic diseases of adulthood. However, relatively little is known about the factors that influence folate status in the general population. To estimate the relative contribution of genetic and nongenetic factors to variation in folate, we have evaluated red blood cell (RBC) folate levels in 440 pairs of MZ twins and in 331 pairs of DZ twins. The data were best described by a model in which 46% of the variance in RBC folate was attributable to additive genetic effects, 16% of the variance was due to measured phenotypic covariates, and 38% of the variance was due to random environmental effects. Moreover, the correlations for RBC folate in MZ co-twins (r = .46) and in repeat measures from the same individual (r = .51) were very similar, indicating that virtually all repeatable variation in RBC folate is attributable to genetic factors. On the basis of these results, it would seem reasonable to initiate a search for the specific genes that influence RBC folate levels in the general population. Such genes ultimately may be used to identify individuals at increased risk for NTD and other folate-related diseases. 23 refs., 1 tab.

  7. Tissue-Specific Methylation of Long Interspersed Nucleotide Element-1 of Homo Sapiens (L1Hs) During Human Embryogenesis and Roles in Neural Tube Defects.

    Science.gov (United States)

    Wang, L; Chang, S; Guan, J; Shangguan, S; Lu, X; Wang, Z; Wu, L; Zou, J; Zhao, H; Bao, Y; Qiu, Z; Niu, B; Zhang, T

    2015-01-01

    Epigenetic regulation of long interspersed nucleotide element-1 (LINE-1) retrotransposition events plays crucial roles during early development. Previously we showed that LINE-1 hypomethylation in neuronal tissues is associated with pathogenesis of neural tube defect (NTD). Herein, we further evaluated LINE-1 Homo sapiens (L1Hs) methylation in tissues derived from three germ layers of stillborn NTD fetuses, to define patterns of tissue specific methylation and site-specific hypomethylation at CpG sites within an L1Hs promoter region. Stable, tissue-specific L1Hs methylation patterns throughout three germ layer lineages of the fetus, placenta, and maternal peripheral blood were observed. Samples from maternal peripheral blood exhibited the highest level of L1Hs methylation (64.95%) and that from placenta showed the lowest (26.82%). Between samples from NTDs and controls, decrease in L1Hs methylation was only significant in NTD-affected brain tissue at 7.35%, especially in females (8.98%). L1Hs hypomethylation in NTDs was also associated with a significant increase in expression level of an L1Hs-encoded transcript in females (r = -0.846, p = 0.004). This could be due to genomic DNA instability and alternation in chromatins accessibility resulted from abnormal L1Hs hypomethylation, as showed in this study with HCT-15 cells treated with methylation inhibitor 5-Aza.

  8. Some recent developments in the theory of acoustic transmission in tube bundles

    Science.gov (United States)

    Heckl, Maria A.; Mulholland, L. S.

    1995-01-01

    A comprehensive theoretical model for acoustic transmission in a tube bundle is presented. The tube bundle is considered as a series of diffraction gratings. Each grating consists of periodically spaced cylindrical tubes which obey the equations of motion of a cylindrical shell. Fluid loading is included. The model can be used for numerical simulations to calculate the sound field at any point in a tube bundle. Various phenomena can be predicted which are of interest for the development of acoustic diagnostics in heat exchangers. These include diffraction of a plane incident wave into several directions, the occurrence of passing and stopping bands in the transmission spectrum, features specific to oblique waves and the effect of dissipative losses. Tube bundles with baffle plates are also examined. The validity of the theoretical model is confirmed by comparison with experimental results.

  9. The posterior neural plate in axolotl gives rise to neural tube or turns anteriorly to form somites of the tail and posterior trunk.

    Science.gov (United States)

    Taniguchi, Yuka; Kurth, Thomas; Weiche, Susanne; Reichelt, Saskia; Tazaki, Akira; Perike, Srikanth; Kappert, Verena; Epperlein, Hans-Henning

    2017-02-15

    Classical grafting experiments in the Mexican axolotl had shown that the posterior neural plate of the neurula is no specified neuroectoderm but gives rise to somites of the tail and posterior trunk. The bipotentiality of this region with neuromesodermal progenitor cell populations was revealed more recently also in zebrafish, chick, and mouse. We reinvestigated the potency of the posterior plate in axolotl using grafts from transgenic embryos, immunohistochemistry, and in situ hybridization. The posterior plate is brachyury-positive except for its more anterior parts which express sox2. Between anterior and posterior regions of the posterior plate a small domain with sox2+ and bra+ cells exists. Lineage analysis of grafted GFP-labeled posterior plate tissue revealed that posterior GFP+ cells move from dorsal to ventral, form the posterior wall, turn anterior bilaterally, and join the gastrulated paraxial presomitic mesoderm. More anterior sox2+/GFP+ cells, however, are integrated into the developing spinal cord. Tail notochord is formed from axial mesoderm involuted already during gastrulation. Thus the posterior neural plate is a postgastrula source of paraxial mesoderm, which performs an anterior turn, a novel morphogenetic movement. More anterior plate cells, in contrast, do not turn anteriorly but become specified to form tail spinal cord. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Dieting to lose weight and occurrence of neural tube defects in offspring of Mexican-American women.

    Science.gov (United States)

    Suarez, Lucina; Felkner, Marilyn; Brender, Jean D; Canfield, Mark A

    2012-05-01

    Lowered maternal weight gain and reduction in early pregnancy have been associated with risk of neural tube defects (NTDs) in offspring. We examined the association of self-reported maternal dieting behaviors on the occurrence of NTDs. We conducted a population based case-control study among Mexican-American women who were residents of the 14 Texas counties bordering Mexico. Case women had an NTD-affected pregnancy identified at birth or prenatally and had deliveries during the years 1995-2000. Control women were those who delivered live born infants without an apparent congenital malformation, randomly selected and frequency-matched to cases by year and facility. One hundred eighty-four case women and 225 control women were asked in person about the use of nutritional supplements, dieting to lose weight, and type of weight reduction supplements used during the 3 months before conception. Women who reported being on a diet to lose weight during the 3 months before conception had an NTD odds ratio (OR) of 1.9 (95% confidence interval (CI) = 1.1, 3.3) compared with those not reporting being on a diet. Neither consuming vitamin drinks (OR = 1.2) nor using diet pills (OR = 1.6) during the 3 months before conception had ORs that were different from the null, when compared to women not reporting those behaviors. The risk effect for dieting did not differ markedly among normal or underweight (OR = 2.0, 95% CI = 0.7, 5.6), overweight (OR = 1.9, 95% CI = 0.7, 5.0), or obese women (OR = 1.5, 95% CI = 0.6, 4.0). No effect was seen among dieting women who were consuming at least 1.0 mg/day of folate (OR = 1.1, CI = 0.3, 4.5). Maternal dieting prior to conception may increase the risk of NTDs in offspring.

  11. Diabetes and obesity-related genes and the risk of neural tube defects in the national birth defects prevention study.

    Science.gov (United States)

    Lupo, Philip J; Canfield, Mark A; Chapa, Claudia; Lu, Wei; Agopian, A J; Mitchell, Laura E; Shaw, Gary M; Waller, D Kim; Olshan, Andrew F; Finnell, Richard H; Zhu, Huiping

    2012-12-15

    Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999-2007. Log-linear models were used to evaluate maternal and offspring genetic effects. After application of the false discovery rate, there were 5 significant maternal genetic effects. The less common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI): 0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR = 0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)). Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among obese women. These findings indicate that maternal genetic variants associated with glucose homeostasis may modify the risk of having an NTD-affected pregnancy.

  12. A GCH1 haplotype and risk of neural tube defects in the National Birth Defects Prevention Study.

    Science.gov (United States)

    Lupo, Philip J; Chapa, Claudia; Nousome, Darryl; Duhon, Cody; Canfield, Mark A; Shaw, Gary M; Finnell, Richard H; Zhu, Huiping

    2012-11-01

    Tetrahydrobiopterin (BH(4)) is an essential cofactor and an important cellular antioxidant. BH(4) deficiency has been associated with diseases whose etiologies stem from excessive oxidative stress. GTP cyclohydrolase I (GCH1) catalyzes the first and rate-limiting step of de novo BH(4) synthesis. A 3-SNP haplotype in GCH1 (rs8007267, rs3783641, and rs10483639) is known to modulate GCH1 gene expression levels and has been suggested as a major determinant of plasma BH(4) bioavailability. As plasma BH(4) bioavailability has been suggested as a mechanism of neural tube defect (NTD) teratogenesis, we evaluated the association between this GCH1 haplotype and the risk of NTDs. Samples were obtained from 760 NTD case-parent triads included in the National Birth Defects Prevention Study (NBDPS). The three SNPs were genotyped using TaqMan® SNP assays. An extension of the log-linear model was used to assess the association between NTDs and both offspring and maternal haplotypes. Offspring carrying two copies of haplotype C-T-C had a significantly increased NTD risk (risk ratio [RR]=3.40, 95% confidence interval [CI]: 1.02-11.50), after adjusting for the effect of the maternal haplotype. Additionally, mothers carrying two copies of haplotype C-T-C had a significantly increased risk of having an NTD-affected offspring (RR=3.46, 95% CI: 1.05-11.00), after adjusting for the effect of the offspring haplotype. These results suggest offspring and maternal variation in the GCH1 gene and altered BH(4) biosynthesis may contribute to NTD risk.

  13. [C677T polymorphism of the methylentetrahydrofolate reductase gene in mothers of children affected with neural tube defects].

    Science.gov (United States)

    Morales de Machín, Alisandra; Méndez, Karile; Solís, Ernesto; Borjas de Borjas, Lisbeth; Bracho, Ana; Hernández, María Luisa; Negrón, Aimara; Delgado, Wilmer; Sánchez, Yanira

    2015-09-01

    Neural tube defects (NTD) are the most common congenital anomalies of the central nervous system, with a multifactorial pattern of inheritance, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene 677C>T polymorphism has been implicated as a risk factor for NTD. The main objective of this research was to investigate the association of the 677C>T polymorphism of the MTHFR gene as a genetic risk factor for NTD. Molecular analysis was performed in DNA samples from 52 mothers with antecedent of NTD offspring and from 119 healthy control mothers. Using the Polymerase Chain Reaction, a 198 bases pairs fragment was digested with the restriction enzyme Hinfi. 677T MTHFR allele frequencies for the problem and the control groups were 51.92% and 34.45%, respectively, and 677C MTHFR allele frequencies were 48.08% and 65.55%, respectively. There were significant differences in allele (p: 0.002) and genotype (p: 0.007) frequencies between these two groups. The odds ratio (OR) to the TT genotype vs. the CC genotype was estimated as OR: 4.9 [95% CI: 1,347-6.416] p: 0.002; CT+TT vs. CC: OR: 2.9 [95% CI: 1.347-6.416] p: 0.005; TT vs. CT+CC: OR: 2.675 [95% CI: 1,111-6.441] p: 0.024. The data presented in this study support the relationship between MTHFR 677C>T polymorphism and risk in mothers with antecedent of NTD offspring.

  14. Diabetes and Obesity-Related Genes and the Risk of Neural Tube Defects in the National Birth Defects Prevention Study

    Science.gov (United States)

    Lupo, Philip J.; Canfield, Mark A.; Chapa, Claudia; Lu, Wei; Agopian, A. J.; Mitchell, Laura E.; Shaw, Gary M.; Waller, D. Kim; Olshan, Andrew F.; Finnell, Richard H.; Zhu, Huiping

    2012-01-01

    Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999–2007. Log-linear models were used to evaluate maternal and offspring genetic effects. After application of the false discovery rate, there were 5 significant maternal genetic effects. The less common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI): 0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR = 0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)). Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among obese women. These findings indicate that maternal genetic variants associated with glucose homeostasis may modify the risk of having an NTD-affected pregnancy. PMID:23132673

  15. Levels of Folate Receptor Autoantibodies in Maternal and Cord Blood and Risk of Neural Tube Defects in a Chinese population

    Science.gov (United States)

    Yang, Na; Wang, Linlin; Finnell, Richard H.; Li, Zhiwen; Jin, Lei; Zhang, Le; Cabrera, Robert M.; Ye, Rongwei; Ren, Aiguo

    2016-01-01

    Background After years of periconceptional folic acid supplementation, the prevalence of neural tube defects (NTDs) remains stable following the remarkable reduction observed immediately after the fortification practice. There is accumulating evidence that folate receptor (FR) autoimmunity may play a role in the etiology of folate-sensitive NTDs. Methods From 2011 to 2013, 118 NTD cases and 242 healthy controls were recruited from a population-based birth defects surveillance system in Northern China. Enzyme-linked immunosorbent assay was used to measure FR autoantibodies in maternal and cord blood. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). Results Plasma FR autoantibodies levels were significantly elevated in mothers of infants with NTDs compared with mothers of healthy controls. Using the lowest tertile as the referent group, 2.20-fold (95% CI, 0.71–6.80) and 5.53-fold increased odds (95% CI, 1.90–16.08) of NTDs were observed for the second and third tertile of immunoglobulin G (IgG), respectively, and the odds of NTDs for each successive tertile of IgM was 0.98 (95% CI, 0.35–2.75) and 3.49 (95% CI, 1.45–8.39), respectively. A dose–response relationship was found between FR autoantibodies levels and risk of NTDs (P < 0.001 for IgG, P = 0.002 for IgM). The same pattern was observed in both subtypes of spina bifida and anencephaly. No significant difference in levels of cord blood FR autoantibodies was observed. Conclusion Higher levels of FR autoimmunity in maternal plasma are associated with elevated risk of NTDs in a dose–response manner. PMID:27166990

  16. Maternal consumption of non-staple food in the first trimester and risk of neural tube defects in offspring.

    Science.gov (United States)

    Wang, Meng; Wang, Zhi-Ping; Gao, Li-Jie; Yang, Hui; Zhao, Zhong-Tang

    2015-04-24

    To study the associations between maternal consumption of non-staple food in the first trimester and risk of neural tube defects (NTDs) in offspring. Data collected from a hospital-based case-control study conducted between 2006 and 2008 in Shandong/Shanxi provinces including 459 mothers with NTDs-affected births and 459 mothers without NTDs-affected births. Logistic regression models were used to examine the associations between maternal consumption of non-staple food in the first trimester and risk of NTDs in offspring. The effects were evaluated by odds ratio (OR) and 95% confidence intervals (95% CIs) with SAS9.1.3.software. Maternal consumption of milk, fresh fruits and nuts in the first trimester were protective factors for total NTDs. Compared with consumption frequency of ˂1 meal/week, the ORs for milk consumption frequency of 1-2, 3-6, ≥7 meals/week were 0.50 (95% CI: 0.28-0.88), 0.56 (0.32-0.99), and 0.59 (0.38-0.90), respectively; the ORs for fresh fruits consumption frequency of 1-2, 3-6, ≥7 meals/week were 0.29 (95% CI: 0.12-0.72), 0.22 (0.09-0.53), and 0.32 (0.14-0.71), respectively; the ORs for nuts consumption frequency of 1-2, 3-6, ≥7 meals/week were 0.60 (95% CI: 0.38-0.94), 0.49 (0.31-0.79), and 0.63 (0.36-1.08), respectively. Different effects of above factors on NTDs were found for subtypes of anencephaly and spina bifida. Maternal non-staple food consumption of milk, fresh fruits and nuts in the first trimester was associated with reducing NTDs risk in offspring.

  17. Association between MTHFD1 G1958A polymorphism and neural tube defects susceptibility: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jianxin Jiang

    Full Text Available OBJECTIVES: The methylenetetrahydrofolate dehydrogenase (MTHFD1 gene, as one of the key genes involved in the folate pathway, has been reported to play a critical role in the pathogenesis of neural tube defects (NTDs. However, the results of published studies are contradictory and inconclusive. Thus, this meta-analysis aimed to evaluate the effect of the common polymorphism in the MTHFD1 gene, the G1958A (R653Q, dbSNP ID: rs2236225 variant, on the risk of NTDs in all eligible studies. METHODS: Relevant literature published before January 3, 2014 was retrieved from the MEDLINE, EMBASE, Cochrane Library, and CBM databases. Pooled crude odds ratios (ORs and their corresponding 95% confidence intervals (CIs were calculated to evaluate the association between the MTHFD1 G1958A polymorphism and NTDs risk. RESULTS: We performed a meta-analysis of nine studies with a total of 4,302 NTDs patients and 4,238 healthy controls. Our results demonstrated a significant correlation between the MTHFD1 G1958A polymorphism and NTDs in an overall meta-analysis. For family-based studies, the study subjects were classified as NTD cases, mothers with NTDs offspring, and fathers with NTDs offspring. We found no association between any of the fathers' genotypes and NTDs, whereas there was a clear excess of the 1958A allele in the mothers of children with NTDs compared with controls individuals. CONCLUSIONS: In summary, our meta-analysis strongly suggests that the MTHFD1 G1958A polymorphism might be associated with maternal risk for NTDs in Caucasian populations. However, the evidence of this association should be interpreted with caution due to the selective nature of publication of genetic association studies.

  18. [Folate and iron in fertile age women from a Venezuelan community affected by incidence of neural tube defects].

    Science.gov (United States)

    Mariela, Montilva; Jham, Papale; Nieves, García-Casal María; Yelitza, Berné; Yudith, Ontiveros; Lourdes, Durán

    2010-06-01

    The objective of this transversal study was to determine folate and iron nutritional status of women in fertile age from Municipio Jiménez, Lara State, Venezuela. The sampling was probabilistic by conglomerates from the urban and rural areas, selecting 15 conglomerates from which women between 12 and 45 years (269), were studied. After signing informed consent, participating were interviewed for personal data, antecedents related to folate and iron, socioeconomic data (Graffar-Mendez Castellano method and unsatisfied basic needs). In blood sample was determined Hemoglobin, and Erythrocytic Folate (FE). Serum was obtained to determine Ferritin and Serum Folate (FS). 53.53% of the sample presented low FS levels, 10.78% were FS deficient. Severe FE deficiency was present in 80.7% of the cases, moderate deficiency affected 5.9%. For both tests, median was higher for women in treatment with Acido Fólico or pregnant (p = 0.000), median for FE was higher for adults (p = 0.001) and in non poor women (p = 0.011). There were no significant differences for coffee, alcohol, anticonceptive consumption, urban or rural resident or socioeconomic strata. The prevalence of anemia was 11.2% being significantly more frequent in adults than in adolescents (p = 0.029) and in urban women (p = 0.042). Low ferritin were found in 37.3% of the sample, the effect of different variables was not statistically significant. In conclusion, there is a high prevalence of iron and folate deficiencies in women of fertile age from Municipio Jiménez, which could constitute a conditioning factor for the appearance of neural tube defects.

  19. Folic acid fortification and prevalences of neural tube defects, orofacial clefts, and gastroschisis in California, 1989 to 2010.

    Science.gov (United States)

    Yang, Wei; Carmichael, Suzan L; Shaw, Gary M

    2016-12-01

    We examined whether prevalences of neural tube defects (NTDs), orofacial clefts, and gastroschisis changed more rapidly after than before folic acid fortification in California. This population-based study used vital statistics and birth defects registry data. The study population included all live births and stillbirths delivered in central California counties from 1989 to 2010. Cases included deliveries with NTDs, orofacial clefts, and gastroschisis. Weighted least squares regression was used to estimate slopes during prefortification (before 1997) and postfortification (after 1998), respectively. The difference of the two slopes with the 95% confidence interval (CI) was calculated. For all NTDs combined, slopes indicated that NTD prevalence was decreasing by 8.7 (slope: -8.7; 95% CI, -13.5--3.9) cases per 100,000 deliveries per year before fortification and by 1.7 (slope: -1.7; 95% CI, -3.7-0.3) after fortification; thus the decline had slowed by 7.0 (95% CI, 2.7-11.3) cases per 100,000 deliveries per year. For orofacial clefts, slopes for cleft lip with/without palate as well as for cleft palate alone indicated that the postfortification slope was lower than the prefortification slope suggesting a more accelerated decrease in the postfortification time period. For gastroschisis, the slope after fortification was lower compared with prefortification, indicating a less accelerated prevalence increase in the postfortification time period. Stratification by race/ethnicity did not substantially alter results. We observed a slower decline in prevalence of NTDs, an emergence of a decline in orofacial clefts, and a slower increase in gastroschisis, during the postfortification period in central California, relative to the prefortification period. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1032-1041, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Cloning of zebrafish nkx6.2 and a comprehensive analysis of the conserved transcriptional response to Hedgehog/Gli signaling in the zebrafish neural tube.

    Science.gov (United States)

    Guner, Burcu; Karlstrom, Rolf O

    2007-04-01

    Sonic Hedgehog (Shh) signaling helps pattern the vertebrate neural tube, in part by regulating the dorsal/ventral expression of a number of homeodomain containing transcription factors. These Hh responsive genes have been divided into two classes, with Class II genes being activated by Hh signaling and Class I genes being repressed by Hh signaling. While the transcriptional response to varying Hh levels is well defined in chick and mouse, it is only partially described in zebrafish, despite the fact that zebrafish has emerged as a powerful genetic system for the study of neural patterning. To better characterize the Hh response in the zebrafish neural tube, we cloned the zebrafish Class II Hh target genes nkx2.9 and nkx6.2. We then analyzed the expression of a number of Class I and Class II Hh responsive genes in wild type, Hh mutant, and Hh over-expressing zebrafish embryos. We show that expression of Class I and Class II genes is highly conserved in the vertebrate neural tube. Further, ventral-most Class II gene expression was completely lost in all Hh pathway mutants analyzed, indicating high levels of Hh signaling are blocked in all of these mutants. In contrast, more dorsally expressed genes were variably affected in different Hh pathway mutants, indicating mid-levels of Hh signaling are differentially affected. This comprehensive expression study provides an important tool for the characterization of Hh signaling in zebrafish and provides a sensitive assay for determining the degree to which newly identified zebrafish mutants affect Hh signaling.

  1. Developing neural stem cell-based treatments for neurodegenerative diseases

    OpenAIRE

    Byrne, James A.

    2014-01-01

    Owing to the aging of the population, our society now faces an impending wave of age-related neurodegenerative pathologies, the most significant of which is Alzheimer’s disease. Currently, no effective therapies for Alzheimer’s disease have been developed. However, recent advances in the fields of neural stem cells and human induced pluripotent stem cells now provide us with the first real hope for a cure. The recent discovery by Blurton-Jones and colleagues that neural stem cells can effecti...

  2. Development of Fast Response SME TiNi Foam Torque Tubes Project

    Data.gov (United States)

    National Aeronautics and Space Administration — In Phase I, Shape Change Technologies had developed a process to manufacture net shape TiNi foam torque tubes that demonstrated the shape memory effect. The torque...

  3. A Constructive Neural-Network Approach to Modeling Psychological Development

    Science.gov (United States)

    Shultz, Thomas R.

    2012-01-01

    This article reviews a particular computational modeling approach to the study of psychological development--that of constructive neural networks. This approach is applied to a variety of developmental domains and issues, including Piagetian tasks, shift learning, language acquisition, number comparison, habituation of visual attention, concept…

  4. A Constructive Neural-Network Approach to Modeling Psychological Development

    Science.gov (United States)

    Shultz, Thomas R.

    2012-01-01

    This article reviews a particular computational modeling approach to the study of psychological development--that of constructive neural networks. This approach is applied to a variety of developmental domains and issues, including Piagetian tasks, shift learning, language acquisition, number comparison, habituation of visual attention, concept…

  5. Frecuencia de los defectos del tubo neural en Asturias: impacto del diagnóstico prenatal Prevalence of neural tube defects in Asturias (Spain: impact of prenatal diagnosis

    Directory of Open Access Journals (Sweden)

    Enrique García López

    2009-12-01

    Full Text Available Objetivo Describir la frecuencia de defectos del tubo neural (DTN -anencefalia, espina bífida y encefalocele-en Asturias, su evolución temporal y el impacto del diagnóstico prenatal. Métodos: Se estudiaron los casos de DTN en nacidos y abortos inducidos durante el período 1990-2004, utilizando la base de datos del Registro de Defectos Congénitos de Asturias, de base poblacional. Se calcularon las tasas de prevalencia total y al nacimiento. Resultados: La prevalencia total de DTN fue de 12,2 casos por 10.000 nacidos (5,9 anencefalias, 5,0 espinas bífidas y 1,3 encefaloceles y mostró una tendencia ligeramente descendente, con un descenso significativo de la espina bífida, mientras que las cifras de anencefalia y encefalocele se mantuvieron estables. Finalizaron en aborto inducido tras el diagnóstico prenatal el 88% de los casos (anencefalia 96,7%; espina bífida 80%; encefalocele 84,6%, lo que determinó una prevalencia al nacimiento muy baja (1,4 DTN por 10.000 nacidos. Conclusiones: En Asturias, en los últimos 15 años se ha producido un descenso selectivo en la prevalencia total de espina bífida de causa no aclarada. La prevención secundaria, mediante los programas de diagnóstico prenatal y la consiguiente interrupción del embarazo, fue el motivo del marcado descenso de la frecuencia en los nacidos; la simple recomendación de suplementación periconcepcional con ácido fólico no parece haber logrado el efecto buscado.Objective: To describe the frequency and prevalence trend for neural tube defects (NTD (anencephaly, spina bifida and encephalocele in Asturias (Spain, as well as the impact of prenatal diagnosis programs. Methods: All cases of NTD in births and induced abortions were studied, using data from the Registry of Congenital Defects of Asturias for 1990-2004. Total and birth prevalence rates were calculated. Results: The prevalence of NTD for 1990-2004 was 12.2 per 10,000 births (5.9 anencephaly, 5.0 spina bifida and 1

  6. Matrix metalloproteinases in neural development: a phylogenetically diverse perspective

    Science.gov (United States)

    Small, Christopher D.; Crawford, Bryan D.

    2016-01-01

    The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases originally characterized as secreted proteases responsible for degrading extracellular matrix proteins. Their canonical role in matrix remodelling is of significant importance in neural development and regeneration, but emerging roles for MMPs, especially in signal transduction pathways, are also of obvious importance in a neural context. Misregulation of MMP activity is a hallmark of many neuropathologies, and members of every branch of the MMP family have been implicated in aspects of neural development and disease. However, while extraordinary research efforts have been made to elucidate the molecular mechanisms involving MMPs, methodological constraints and complexities of the research models have impeded progress. Here we discuss the current state of our understanding of the roles of MMPs in neural development using recent examples and advocate a phylogenetically diverse approach to MMP research as a means to both circumvent the challenges associated with specific model organisms, and to provide a broader evolutionary context from which to synthesize an understanding of the underlying biology. PMID:27127457

  7. Matrix metalloproteinases in neural development:a phylogenetically diverse perspective

    Institute of Scientific and Technical Information of China (English)

    Christopher D. Small; Bryan D. Crawford

    2016-01-01

    The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases originally charac-terized as secreted proteases responsible for degrading extracellular matrix proteins. Their canonical role in matrix remodelling is of signiifcant importance in neural development and regeneration, but emerging roles for MMPs, especially in signal transduction pathways, are also of obvious importance in a neural con-text. Misregulation of MMP activity is a hallmark of many neuropathologies, and members of every branch of the MMP family have been implicated in aspects of neural development and disease. However, while extraordinary research efforts have been made to elucidate the molecular mechanisms involving MMPs, methodological constraints and complexities of the research models have impeded progress. Here we discuss the current state of our understanding of the roles of MMPs in neural development using recent ex-amples and advocate a phylogenetically diverse approach to MMP research as a means to both circumvent the challenges associated with speciifc model organisms, and to provide a broader evolutionary context from which to synthesize an understanding of the underlying biology.

  8. Development of a light weighted mobile robot for SG tube inspection in NPP

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Yong Chil; Jeong, Kyung Min; Shin, Hochul; Gweng, Jung Ju; Lee, Sung Uk; Jeong, Seung Ho; Choi, Young Soo; Kim, Seung Ho [KAERI, Daejeon (Korea, Republic of); Shin, Chun Sup; Park, Ki Tae [Korea Plant Service and Engineering, Busan (Korea, Republic of)

    2012-10-15

    Steam generators (SG) are among the most critical components of pressurized water Nuclear Power Plants (NPP). SG tubes must provide a reliable pressure boundary between the primary and secondary cooling water, because any leakage from tube defects could result in the release of radioactivity to the environment. Thus degradations of steam generators tubes should be monitored and inspected periodically under nuclear regulation. In service inspections of SG tubes are carried out using eddy current test (ECT) and the defected tubes are usually plugged. Because the radioactivity in the internal SG chambers limits free access of human workers, remote manipulators are required. In South Korea, Manipulators such as the Zet ec SM series and the Westinghouse ROSA series have bee used. Such manipulators are rigidly mounted to man ways or tube sheets of SG. Confusions of the inspected tubes may occur from deflection of the manipulators. To reduce the deflections of the manipulators for covering the large working areas of tube sheets, sufficient rigidity is required and that leads to an increase of the weight. Such weight increase results in some difficulties for handling and more radiation exposure of human workers. Recently light weighed mobile robots have been introduced by Westinghouse and Zet ec. The robots can move keeping in contact with the tube sheets using devices which are commonly called cam locks. They are easier to handle and provide no confusion for the position of the inspected tubes. But when the clamping forces are loosed accidentally, they can be fall down and light repair works can be performed. This paper provides the design results for a lightweight mobile robot which is being developed in cooperation of our institutes.

  9. Development of ultrasonic heat transfer tube thickness measurement apparatus. Contract research

    Energy Technology Data Exchange (ETDEWEB)

    Ohba, Toshihiro; Katoh, Chiaki; Yanagihara, Takao [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Suetugu, Hidehiko; Yano, Masaya [Sumitomo Chemical Co., Ltd., Tokyo (Japan)

    2003-01-01

    The demonstration test for evaluating reliability of the acid recovery evaporator at Rokkasho Reprocessing Plant has been carried out at JAERI. For the nondestructive measurement of the thickness of heat transfer tubes of the acid recovery evaporator in corrosion test, we have developed thickness measurement apparatus for heat transfer tubes by ultrasonic immersion method with high resolution. The ultrasonic prove in a heat transfer tube can be moved vertically and radially. The results obtained by this apparatus coincident well with those obtained by a destructive method using an optical microscope. (author)

  10. Development of ultrasonic heat transfer tube thickness measurement apparatus. Contract research

    Energy Technology Data Exchange (ETDEWEB)

    Ohba, Toshihiro; Katoh, Chiaki; Yanagihara, Takao [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Suetugu, Hidehiko; Yano, Masaya [Sumitomo Chemical Co., Ltd., Tokyo (Japan)

    2003-01-01

    The demonstration test for evaluating reliability of the acid recovery evaporator at Rokkasho Reprocessing Plant has been carried out at JAERI. For the nondestructive measurement of the thickness of heat transfer tubes of the acid recovery evaporator in corrosion test, we have developed thickness measurement apparatus for heat transfer tubes by ultrasonic immersion method with high resolution. The ultrasonic prove in a heat transfer tube can be moved vertically and radially. The results obtained by this apparatus coincident well with those obtained by a destructive method using an optical microscope. (author)

  11. Defeitos de fechamento do tubo neural e fatores associados em recém-nascidos vivos e natimortos Neural tube defects and associated factors among liveborn and stillborn infants

    Directory of Open Access Journals (Sweden)

    Marcos J.B. Aguiar

    2003-04-01

    evaluate the prevalence and factors associated to neural tube defects in liveborn and stillborn infants delivered at the Hospital das Clínicas, UFMG, from January 8, 1999 to July 31, 2000. METHODS: this is a descriptive study, based on a database, according to the Latin-American Collaborative Study of Congenital Malformation (ECLAMC rules. Reports on liveborn and stillborn infants with congenital anomalies were prepared including information about morphological description, necropsy results, complementary exams, family, social and pregnancy histories and other clinical data. Each malformed liveborn infant originated a control of the same sex, without malformations. The liveborn and stillborn infants with neural tube defects delivered during that period were classified according to their defect and the presence or absence of associated defects. The liveborn and stillborn infants with neural tube defects were compared to newborns without neural tube defects according to their weight and sex and their mother's age and parity. Epi-Info 6.0 Program was used for the statistical analysis of the results. RESULTS: the prevalence of neural tube defects was 4.73 to 1,000 deliveries (89:18,807; it was significantly higher among stillborn infants (23.7:1,000 than among liveborn infants (4.16:1,000, p < 0.001. Neural tube defects were more often found among low weight liveborn infants (< 2,500 g, p < 0.001 and less frequently among women who had had more than three gestations, p = 0.007. No association was found regarding newborn's sex or maternal age. There was no association with newborn's sex and weight, maternal parity or age among stillborn infants. The most common neural tube defects were myelomeningocele (47.2%, anencephaly (26.9% and encephalocele (16.9%. The defects were found as isolated anomalies in 71.1% of the liveborn and 38.5% of the stillborn infants; they were part of a syndrome in 9.2% (liveborn and 7.7% (stillborn. CONCLUSIONS: the neural tube defect prevalence found

  12. Frecuencia y algunos factores de riesgo de mortalidad en el estado de Hidalgo, México, por defectos de cierre del tubo neural Mortality due to neural tube defects and risk factors in Hidalgo, Mexico

    Directory of Open Access Journals (Sweden)

    Sergio Muñoz-Juárez

    2002-09-01

    Full Text Available Objetivo. Calcular el riesgo de muerte fetal secundaria a defectos del cierre del tubo neural y estimar factores asociados con este tipo de muertes en el estado de Hidalgo. Material y métodos. La información analizada en el año 2000 fue obtenida de los certificados de muerte fetal del periodo 1990-1995 en el estado de Hidalgo. Se utilizó un diseño de mortalidad proporcional, considerado como una variante del diseño de casos y controles. Los casos fueron aquellas muertes fetales secundarias a defectos del tubo neural y los controles las muertes fetales por otros motivos. Se utilizó ji cuadrada de Pearson para estimar las diferencias entre los casos y controles. Para el riesgo crudo de morir por defectos de cierre del tubo neural se empleó la razón de momios, y para el riesgo ajustado se usó la regresión logística no condicional. Resultados. Se analizaron 3 673 certificados de muerte fetal, identificándose 8.06% de muertes por defectos del tubo neural; el resto lo constituyeron muertes por otras causas. Se encontró como variables asociadas con la muerte fetal por defectos del tubo neural a los fetos que pesaron menos de 2 500 gramos (RM 5.0, IC 95% 3.6, 6.7, a los productos del sexo femenino (RM 1.7, IC 95% 1.3, 2.3 y a las muertes ocurridas en el periodo fetal tardío (RM 5.5 IC 95% 3.8, 8.1. Conclusiones. Los resultados indican que el riesgo de muerte fetal debida a defectos del tubo neural es mayor en productos de bajo peso, en los del sexo femenino y los que ocurren en el periodo fetal tardío.Objective. To calculate the risk of fetal death due to neural tube defects and estimate associated factors in the state of Hidalgo, Mexico. Material and Methods. Data were abstracted from death certificates registered during 1990-1995 in the state of Hidalgo, Mexico. The design was a proportional mortality study, which is considered as a variant of the case control design. Cases were deaths with any type of neural tube defect, and controls

  13. Neural Development in tsc2-Deficient Zebrafish

    Science.gov (United States)

    2011-10-01

    is an important model system for the study of brain malformations as well as the pathogenesis of epilepsy and autism . Advances in these fields require...mTOR signaling pathway, current therapies remain ineffective with many patients suffering from intractable epilepsy as well as autism , developmental...development of multiple organs as well as during disease pathogenesis . The use of zebrafish as our model organism here will greatly facilitate experiments

  14. Development and characterisation of new high-rate muon drift tube detectors

    Energy Technology Data Exchange (ETDEWEB)

    Bittner, Bernhard

    2012-07-25

    With the increase of the LHC luminosity above the design value and the higher background counting rates, detectors in the ATLAS muon spectrometer have to be replaced because the limits of the radiation tolerance will be exceeded. Therefore drift tube chambers with 15 mm tube diameter were developed. The required construction accuracy was verified and the limits of the resolution and efficiency were determined in a muon beam and under gamma irradiation and compared to model expectations.

  15. Development of lava tubes in the light of observations at Mauna Ulu, Kilauea Volcano, Hawaii

    Science.gov (United States)

    Peterson, D.W.; Holcomb, R.T.; Tilling, R.I.; Christiansen, R.L.

    1994-01-01

    During the 1969-1974 Mauna Ulu eruption on Kilauea's upper east rift zone, lava tubes were observed to develop by four principal processes: (1) flat, rooted crusts grew across streams within confined channels; (2) overflows and spatter accreted to levees to build arched roofs across streams; (3) plates of solidified crust floating downstream coalesced to form a roof; and (4) pahoehoe lobes progressively extended, fed by networks of distributaries beneath a solidified crust. Still another tube-forming process operated when pahoehoe entered the ocean; large waves would abruptly chill a crust across the entire surface of a molten stream crossing through the surf zone. These littoral lava tubes formed abruptly, in contrast to subaerial tubes, which formed gradually. All tube-forming processes were favored by low to moderate volume-rates of flow for sustained periods of time. Tubes thereby became ubiquitous within the pahoehoe flows and distributed a very large proportionof the lava that was produced during this prolonged eruption. Tubes transport lava efficiently. Once formed, the roofs of tubes insulate the active streams within, allowing the lava to retain its fluidity for a longer time than if exposed directly to ambient air temperature. Thus the flows can travel greater distances and spread over wider areas. Even though supply rates during most of 1970-1974 were moderate, ranging from 1 to 5 m3/s, large tube systems conducted lava as far as the coast, 12-13 km distant, where they fed extensive pahoehoe fields on the coastal flats. Some flows entered the sea to build lava deltas and add new land to the island. The largest and most efficient tubes developed during periods of sustained extrusion, when new lava was being supplied at nearly constant rates. Tubes can play a major role in building volcanic edifices with gentle slopes because they can deliver a substantial fraction of lava erupted at low to moderate rates to sites far down the flank of a volcano. We

  16. Computational Investigation on Fully Developed Periodic Laminar Flow Structure in Baffled Circular Tube with Various BR

    Directory of Open Access Journals (Sweden)

    Withada Jedsadaratanachai

    2014-01-01

    Full Text Available This paper presents a 3D numerical analysis of fully developed periodic laminar flow in a circular tube fitted with 45° inclined baffles with inline arrangement. The computations are based on a finite volume method, and the SIMPLE algorithm has been implemented. The characteristics of fluid flow are presented for Reynolds number, Re = 100–1000, based on the hydraulic diameter (D of the tube. The angled baffles were repeatedly inserted at the middle of the test tube with inline arrangement to generate vortex flows over the tested tube. Effects of different Reynolds numbers and blockage ratios (b/D, BR with a single pitch ratio of 1 on flow structure in the tested tube were emphasized. The flows in baffled tube show periodic flow at x/D ≈ 2-3, and become a fully developed periodic flow profiles at x/D ≈ 6-7, depending on Re, BR and transverse plane positions. The computational results reveal that the higher of BR and closer position of turbulators, the faster of fully developed periodic flow profiles.

  17. Development of a compact laminar flow heat exchanger with stainless steel micro-tubes

    Science.gov (United States)

    Saji, N.; Nagai, S.; Tsuchiya, K.; Asakura, H.; Obata, M.

    2001-05-01

    The present paper describes the design concept and manufacturing of a new compact laminar flow heat exchanger with stainless-steel micro-tubes for helium refrigerators. In the temperature range of less than 20 K, aluminum plate fin type heat exchangers exhibit a remarkable fall of performance characteristics as a compact heat exchanger. We presented in a previous paper that some compact heat exchangers with good performance in the temperature range of less than 4 K are required for a subcooled He II refrigerator cycle to be worked with 3He turbo-compressors (F. Doty, et al., A new look at the closed brayton cycle, Proceedings, IECEC-90 Reno, NV, 1991, p. 116). For this requirement, we developed a micro-tube strip counter flow type heat exchanger, which consists of 12 elements with a total of 4800 stainless steel micro-tubes. Each element is formed with 400 tubes and a newly developed vacuum brazing method was applied for the bonding to the side plate. Each tube has an inner diameter of 0.5 mm, an outer diameter of 0.7 mm and is 310 mm long. We developed a cladding plate with two layers of gold brazing sheet sandwiched inside. In aerodynamic and thermal design of the element, the laminar flow conditions were adopted for the flows of inner and outer tubes to keep a high heat transfer rate and a low pressure loss.

  18. Genetic background influences embryonic lethality and the occurrence of neural tube defects in Men1 null mice: relevance to genetic modifiers.

    Science.gov (United States)

    Lemos, Manuel C; Harding, Brian; Reed, Anita A C; Jeyabalan, Jeshmi; Walls, Gerard V; Bowl, Michael R; Sharpe, James; Wedden, Sarah; Moss, Julie E; Ross, Allyson; Davidson, Duncan; Thakker, Rajesh V

    2009-10-01

    Germline mutations of the multiple endocrine neoplasia type 1 (MEN1) gene cause parathyroid, pancreatic and pituitary tumours in man. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP) and the same MEN1 mutations, in different families, can cause either FIHP or MEN1. This suggests a role for genetic background and modifier genes in altering the expression of a mutation. We investigated the effects of genetic background on the phenotype of embryonic lethality that occurs in a mouse model for MEN1. Men1(+/-) mice were backcrossed to generate C57BL/6 and 129S6/SvEv incipient congenic strains, and used to obtain homozygous Men1(-/-) mice. No viable Men1(-/-) mice were obtained. The analysis of 411 live embryos obtained at 9.5-16.5 days post-coitum (dpc) revealed that significant deviations from the expected Mendelian 1:2:1 genotype ratio were first observed at 12.5 and 14.5 dpc in the 129S6/SvEv and C57BL/6 strains respectively (P<0.05). Moreover, live Men1(-/-) embryos were absent by 13.5 and 15.5 dpc in the 129S6/SvEv and C57BL/6 strains respectively thereby indicating an earlier lethality by 2 days in the 129S6/SvEv strain (P<0.01). Men1(-/-) embryos had macroscopic haemorrhages, and histology and optical projection tomography revealed them to have internal haemorrhages, myocardial hypotrophy, pericardial effusion, hepatic abnormalities and neural tube defects. The neural tube defects occurred exclusively in 129S6/SvEv embryos (21 vs 0%, P<0.01). Thus, our findings demonstrate the importance of genetic background in influencing the phenotypes of embryonic lethality and neural tube defects in Men1(-/-) mice, and implicate a role for genetic modifiers.

  19. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects

    Directory of Open Access Journals (Sweden)

    Lam Angeline

    2004-09-01

    Full Text Available Abstract Background Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD. In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. Methods This study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I Determination of rates of NTDs; II Dietary assessment; III Blood analysis; IV Assessment of knowledge and use of folic acid supplements. Results The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991–93 and 1994–97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76–1.34. The rates of NTDs fell by 78% (95% CI 65%–86% after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35. The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B12 deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B12 deficiency. The proportion of women aged 19–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. Conclusions Based on these findings, mandatory food fortification in Canada should continue at the

  20. Maternal Consumption of Non-Staple Food in the First Trimester and Risk of Neural Tube Defects in Offspring

    Directory of Open Access Journals (Sweden)

    Meng Wang

    2015-04-01

    Full Text Available To study the associations between maternal consumption of non-staple food in the first trimester and risk of neural tube defects (NTDs in offspring. Data collected from a hospital-based case-control study conducted between 2006 and 2008 in Shandong/Shanxi provinces including 459 mothers with NTDs-affected births and 459 mothers without NTDs-affected births. Logistic regression models were used to examine the associations between maternal consumption of non-staple food in the first trimester and risk of NTDs in offspring. The effects were evaluated by odds ratio (OR and 95% confidence intervals (95% CIs with SAS9.1.3.software. Maternal consumption of milk, fresh fruits and nuts in the first trimester were protective factors for total NTDs. Compared with consumption frequency of ˂1 meal/week, the ORs for milk consumption frequency of 1–2, 3–6, ≥7 meals/week were 0.50 (95% CI: 0.28–0.88, 0.56 (0.32–0.99, and 0.59 (0.38–0.90, respectively; the ORs for fresh fruits consumption frequency of 1–2, 3–6, ≥7 meals/week were 0.29 (95% CI: 0.12–0.72, 0.22 (0.09–0.53, and 0.32 (0.14–0.71, respectively; the ORs for nuts consumption frequency of 1–2, 3–6, ≥7 meals/week were 0.60 (95% CI: 0.38–0.94, 0.49 (0.31–0.79, and 0.63 (0.36–1.08, respectively. Different effects of above factors on NTDs were found for subtypes of anencephaly and spina bifida. Maternal non-staple food consumption of milk, fresh fruits and nuts in the first trimester was associated with reducing NTDs risk in offspring.

  1. Survey of prenatal screening policies in Europe for structural malformations and chromosome anomalies, and their impact on detection and termination rates for neural tube defects and Down's syndrome

    DEFF Research Database (Denmark)

    Boyd, P A; Devigan, C; Khoshnood, B

    2008-01-01

    screening policies in 18 countries and 1.13 million births in 12 countries in 2002-04. METHODS: (i) Questionnaire on national screening policies and termination of pregnancy for fetal anomaly (TOPFA) laws in 2004. (ii) Analysis of data on prenatal detection and termination for Down's syndrome and neural...... tube defects (NTDs) using the EUROCAT database. MAIN OUTCOME MEASURES: Existence of national prenatal screening policies, legal gestation limit for TOPFA, prenatal detection and termination rates for Down's syndrome and NTD. RESULTS: Ten of the 18 countries had a national country-wide policy for Down...

  2. Development of a Large-capacity, Stirling-type, Pulse-tube Refrigerator

    Science.gov (United States)

    Potratz, S. A.; Nellis, G. F.; Maddocks, J. R.; Kashani, A.; Helvensteijn, B. P. M.; Rhoads, G. L.; Flake, B.

    2006-04-01

    This paper describes progress towards the development of a large-capacity, single-stage, Stirling-type, pulse-tube refrigerator (PTR) for high temperature superconducting power applications. Specifically, the design and fabrication of an experimental PTR is described followed by a series of design modifications which have focused on optimization of the flow transition components the hot and cold ends of the pulse-tube. Computational fluid dynamic models are described and have been used to guide the design modifications. The impact of each modification on cooler performance is discussed. The cooler is instrumented with piston displacement sensors, high-frequency pressure sensors, and thermocouples along the regenerator wall, within the cold heat exchanger gas volume, and along the pulse-tube wall. These sensors provide some characterization of the flow distribution in the regenerator and pulse-tube.

  3. Dynamic neck development in a polymer tube under internal pressure loading

    DEFF Research Database (Denmark)

    Lindgreen, Britta; Tvergaard, Viggo; Needleman, Alan

    2008-01-01

    and a short wave length imperfection. After some thinning down at the necks, the mode of deformation switches to neck propagation along the circumference of the tube. A case is shown in which the necks have propagated along the entire tube wall, so that network locking in the polymer results in high stiffness......The initiation and growth of necks in polymer tubes subjected to rapidly increasing internal pressure is analyzed numerically. Plane strain conditions are assumed to prevail in the axial direction. The polymer is characterized by a finite strain elastic-viscoplastic constitutive relation...... and the calculations are carried out using a dynamic finite element program. Numerical results for neck development are illustrated and discussed for tubes of various thicknesses. The sensitivity to the wave number of the thickness imperfections is studied with a focus on comparing a long wave length imperfection...

  4. Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone.

    Science.gov (United States)

    van de Ven, Cesca; Bialecka, Monika; Neijts, Roel; Young, Teddy; Rowland, Jennifer E; Stringer, Emma J; Van Rooijen, Carina; Meijlink, Frits; Nóvoa, Ana; Freund, Jean-Noel; Mallo, Moises; Beck, Felix; Deschamps, Jacqueline

    2011-08-01

    Decrease in Cdx dosage in an allelic series of mouse Cdx mutants leads to progressively more severe posterior vertebral defects. These defects are corrected by posterior gain of function of the Wnt effector Lef1. Precocious expression of Hox paralogous 13 genes also induces vertebral axis truncation by antagonizing Cdx function. We report here that the phenotypic similarity also applies to patterning of the caudal neural tube and uro-rectal tracts in Cdx and Wnt3a mutants, and in embryos precociously expressing Hox13 genes. Cdx2 inactivation after placentation leads to posterior defects, including incomplete uro-rectal septation. Compound mutants carrying one active Cdx2 allele in the Cdx4-null background (Cdx2/4), transgenic embryos precociously expressing Hox13 genes and a novel Wnt3a hypomorph mutant all manifest a comparable phenotype with similar uro-rectal defects. Phenotype and transcriptome analysis in early Cdx mutants, genetic rescue experiments and gene expression studies lead us to propose that Cdx transcription factors act via Wnt signaling during the laying down of uro-rectal mesoderm, and that they are operative in an early phase of these events, at the site of tissue progenitors in the posterior growth zone of the embryo. Cdx and Wnt mutations and premature Hox13 expression also cause similar neural dysmorphology, including ectopic neural structures that sometimes lead to neural tube splitting at caudal axial levels. These findings involve the Cdx genes, canonical Wnt signaling and the temporal control of posterior Hox gene expression in posterior morphogenesis in the different embryonic germ layers. They shed a new light on the etiology of the caudal dysplasia or caudal regression range of human congenital defects.

  5. Use of Natural Neural Scaffolds Consisting of Engineered Vascular Endothelial Growth Factor Immobilized on Ordered Collagen Fibers Filled in a Collagen Tube for Peripheral Nerve Regeneration in Rats

    Directory of Open Access Journals (Sweden)

    Fukai Ma

    2014-10-01

    Full Text Available The search for effective strategies for peripheral nerve regeneration has attracted much attention in recent years. In this study, ordered collagen fibers were used as intraluminal fibers after nerve injury in rats. Vascular endothelial growth factor (VEGF plays an important role in nerve regeneration, but its very fast initial burst of activity within a short time has largely limited its clinical use. For the stable binding of VEGF to ordered collagen fibers, we fused a collagen-binding domain (CBD to VEGF through recombinant DNA technology. Then, we filled the ordered collagen fibers-CBD-VEGF targeting delivery system in a collagen tube to construct natural neural scaffolds, which were then used to bridge transected nerve stumps in a rat sciatic nerve transection model. After transplantation, the natural neural scaffolds showed minimal foreign body reactions and good integration into the host tissue. Oriented collagen fibers in the collagen tube could guide regenerating axons in an oriented manner to the distal, degenerating nerve segment, maximizing the chance of target reinnervation. Functional and histological analyses indicated that the recovery of nerve function in the natural neural scaffolds-treated group was superior to the other grafted groups. The guiding of oriented axonal regeneration and effective delivery systems surmounting the otherwise rapid and short-lived diffusion of growth factors in body fluids are two important strategies in promoting peripheral nerve regeneration. The natural neural scaffolds described take advantage of these two aspects and may produce synergistic effects. These properties qualified the artificial nerve conduits as a putative candidate system for the fabrication of peripheral nerve reconstruction devices.

  6. Use of natural neural scaffolds consisting of engineered vascular endothelial growth factor immobilized on ordered collagen fibers filled in a collagen tube for peripheral nerve regeneration in rats.

    Science.gov (United States)

    Ma, Fukai; Xiao, Zhifeng; Meng, Danqing; Hou, Xianglin; Zhu, Jianhong; Dai, Jianwu; Xu, Ruxiang

    2014-10-15

    The search for effective strategies for peripheral nerve regeneration has attracted much attention in recent years. In this study, ordered collagen fibers were used as intraluminal fibers after nerve injury in rats. Vascular endothelial growth factor (VEGF) plays an important role in nerve regeneration, but its very fast initial burst of activity within a short time has largely limited its clinical use. For the stable binding of VEGF to ordered collagen fibers, we fused a collagen-binding domain (CBD) to VEGF through recombinant DNA technology. Then, we filled the ordered collagen fibers-CBD-VEGF targeting delivery system in a collagen tube to construct natural neural scaffolds, which were then used to bridge transected nerve stumps in a rat sciatic nerve transection model. After transplantation, the natural neural scaffolds showed minimal foreign body reactions and good integration into the host tissue. Oriented collagen fibers in the collagen tube could guide regenerating axons in an oriented manner to the distal, degenerating nerve segment, maximizing the chance of target reinnervation. Functional and histological analyses indicated that the recovery of nerve function in the natural neural scaffolds-treated group was superior to the other grafted groups. The guiding of oriented axonal regeneration and effective delivery systems surmounting the otherwise rapid and short-lived diffusion of growth factors in body fluids are two important strategies in promoting peripheral nerve regeneration. The natural neural scaffolds described take advantage of these two aspects and may produce synergistic effects. These properties qualified the artificial nerve conduits as a putative candidate system for the fabrication of peripheral nerve reconstruction devices.

  7. Technique Developed for Optimizing Traveling-Wave Tubes

    Science.gov (United States)

    Wilson, Jeffrey D.

    1999-01-01

    A traveling-wave tube (TWT) is an electron beam device that is used to amplify electromagnetic communication waves at radio and microwave frequencies. TWT s are critical components in deep-space probes, geosynchronous communication satellites, and high-power radar systems. Power efficiency is of paramount importance for TWT s employed in deep-space probes and communications satellites. Consequently, increasing the power efficiency of TWT s has been the primary goal of the TWT group at the NASA Lewis Research Center over the last 25 years. An in-house effort produced a technique (ref. 1) to design TWT's for optimized power efficiency. This technique is based on simulated annealing, which has an advantage over conventional optimization techniques in that it enables the best possible solution to be obtained (ref. 2). A simulated annealing algorithm was created and integrated into the NASA TWT computer model (ref. 3). The new technique almost doubled the computed conversion power efficiency of a TWT from 7.1 to 13.5 percent (ref. 1).

  8. Development during adolescence of the neural processing of social emotion

    OpenAIRE

    Burnett, Stephanie; Bird, Geoffrey; Moll, Jorge; Frith, Chris; Blakemore, Sarah-Jayne

    2009-01-01

    In this fMRI study, we investigated the development between adolescence and adulthood of the neural processing of social emotions. Unlike basic emotions (such as disgust and fear), social emotions (such as guilt and embarrassment) require the representation of another’s mental states. Nineteen adolescents (10–18 years) and 10 adults (22–32 years) were scanned while thinking about scenarios featuring either social or basic emotions. In both age groups, the anterior rostral medial prefrontal co...

  9. Involvement of XZFP36L1,an RNA-binding protein,in Xenopus neural development%Involvement of XZFP36L1, an RNA-binding protein,in Xenopus neural development

    Institute of Scientific and Technical Information of China (English)

    Yingjie XIA; Shuhua ZHAO; Bingyu MAO

    2012-01-01

    Xenopus ZFP36L1 (zinc finger protein 36,C3H type-like 1) belongs to the ZFP36 family of RNA-binding proteins,which contains two characteristic tandem CCCH-type zinc-finger domains.The ZFP36 proteins can bind AU-rich elements in 3' untranslated regions of target mRNAs and promote their turnover.However,the expression and role of ZFP36 genes during neural development in Xenopus embryos remains largely tmknown.The present study showed that Xenopus ZFP36L1 was expressed at the dorsal part of the forebrain,forebrain-midbrain boundary,and midbrain-hindbrain boundary from late neurula stages to tadpole stages of embryonic development.Overexpression of XZFP36L1 in Xenopus embryos inhibited neural induction and differentiation,leading to severe neural tube defects.The function of XZP36L1 requires both its zinc finger and C terminal domains,which also affect its subcellular localization.These results suggest that XZFP36L1 is likely involved in neural development in Xenopus and might play an important role in post-transcriptional regulation.

  10. Yap and Taz play a crucial role in neural crest-derived craniofacial development.

    Science.gov (United States)

    Wang, Jun; Xiao, Yang; Hsu, Chih-Wei; Martinez-Traverso, Idaliz M; Zhang, Min; Bai, Yan; Ishii, Mamoru; Maxson, Robert E; Olson, Eric N; Dickinson, Mary E; Wythe, Joshua D; Martin, James F

    2016-02-01

    The role of the Hippo signaling pathway in cranial neural crest (CNC) development is poorly understood. We used the Wnt1(Cre) and Wnt1(Cre2SOR) drivers to conditionally ablate both Yap and Taz in the CNC of mice. When using either Cre driver, Yap and Taz deficiency in the CNC resulted in enlarged, hemorrhaging branchial arch blood vessels and hydrocephalus. However, Wnt1(Cre2SOR) mutants had an open cranial neural tube phenotype that was not evident in Wnt1(Cre) mutants. In O9-1 CNC cells, the loss of Yap impaired smooth muscle cell differentiation. RNA-sequencing data indicated that Yap and Taz regulate genes encoding Fox transcription factors, specifically Foxc1. Proliferation was reduced in the branchial arch mesenchyme of Yap and Taz CNC conditional knockout (CKO) embryos. Moreover, Yap and Taz CKO embryos had cerebellar aplasia similar to Dandy-Walker spectrum malformations observed in human patients and mouse embryos with mutations in Foxc1. In embryos and O9-1 cells deficient for Yap and Taz, Foxc1 expression was significantly reduced. Analysis of Foxc1 regulatory regions revealed a conserved recognition element for the Yap and Taz DNA binding co-factor Tead. ChIP-PCR experiments supported the conclusion that Foxc1 is directly regulated by the Yap-Tead complex. Our findings uncover important roles for Yap and Taz in CNC diversification and development. © 2016. Published by The Company of Biologists Ltd.

  11. Developing neural stem cell-based treatments for neurodegenerative diseases.

    Science.gov (United States)

    Byrne, James A

    2014-05-30

    Owing to the aging of the population, our society now faces an impending wave of age-related neurodegenerative pathologies, the most significant of which is Alzheimer's disease. Currently, no effective therapies for Alzheimer's disease have been developed. However, recent advances in the fields of neural stem cells and human induced pluripotent stem cells now provide us with the first real hope for a cure. The recent discovery by Blurton-Jones and colleagues that neural stem cells can effectively deliver disease-modifying therapeutic proteins throughout the brains of our best rodent models of Alzheimer's disease, combined with recent advances in human nuclear reprogramming, stem cell research, and highly customized genetic engineering, may represent a potentially revolutionary personalized cellular therapeutic approach capable of effectively curing, ameliorating, and/or slowing the progression of Alzheimer's disease.

  12. Asociación inversa entre asma y defectos del tubo neural: estudio ecológico binacional Inverse association between asthma and neural tube defects: a binational ecological study

    Directory of Open Access Journals (Sweden)

    Mario H Vargas

    2012-08-01

    Full Text Available OBJETIVO: Los donadores de metilo como el ácido fólico previenen defectos del tubo neural (DTN, pero estudios recientes sugieren que también favorecen el desarrollo de asma. En este trabajo exploramos una posible asociación ecológica entre DTN y asma. MATERIAL Y MÉTODOS: Se consultaron bases de datos de México y EUA para obtener información sobre distribución geográfica (por estado y tendencia temporal (por año de DTN y asma. RESULTADOS: Los estados con menor frecuencia de DTN tuvieron mayor frecuencia de asma, tanto en México (rS=-0.48, p=0.005 como en EUA (rS=-0.39, p=0.005. Las tendencias temporales también mostraron correlación inversa en México (1997-2007, rS=-0.73, p=0.01 y EUA (1979-1998, rS=-0.91, pOBJECTIVE: Dietary intake of methyl donors such as folic acid prevents neural tube defects (NTD, but recent studies showed that it might also favor the development of asthma. In this work a possible ecological association between NTD and asthma was explored. MATERIAL AND METHODS: Data bases from Mexico and the United States (US were reviewed to obtain information about geographical distribution (by state and temporal trends (by year of NTD and asthma. RESULTS: Those states with the lowest frequency of NTD had the highest frequency of asthma, both in Mexico (rS=-0.48, p=0.005 and US (rS=-0.39, p=0.005. Temporal trends also showed an inverse correlation in Mexico (1997-2007, rS=-0.73, p=0.01 and US (1979-1998, rS=-0.91, p<0.001. CONCLUSIONS: In both countries the frequency of asthma inversely correlated with the frequency of NTD, both in geographical distribution and annual trends, giving support to the possibility that methyl donors intake in diet or supplements is influencing the asthma frequency.

  13. Prevalence of cystathionine beta synthase gene mutation 852Ins68 as a possible risk for neural tube defects in eastern India.

    Science.gov (United States)

    Saxena, A K; Gupta, J; Pandey, S; Gangopadhaya, A N; Pandey, L K

    2011-10-07

    Cystathionine beta synthase gene (CβS) catalyzes the condensation of homocysteine with serine, forming cystathionine by the transsulfuration pathway. Disruption of CβS enzyme activity due to defective folic acid metabolism increases the risk factor for neural tube defects. We evaluated the CβS gene mutation in 25 children with neural tube defects (NTDs), including lumbosacral and thoracic myelomeningocele and open NTDs and mothers of cases, along with 25 healthy children and their mothers, serving as controls. Genomic DNA was isolated to assess the polymorphism of 852Ins68 in the CβS gene using PCR-RFLP analysis and nucleotide sequencing techniques. The 68-bp insertion was observed in one of the 25 NTD cases (lumbosacral myelomeningocele), and in two of the mothers of NTD cases. Statistical analysis was carried out using the Fischer exact probability test, which showed a lack of significance (P > 0.05), but the odds ratio of 2.08 with 95% confidence interval of 0.17-24.6 in NTDs mother was quite high because of the small sample size. However, the study was further extended to find out the involvement of specific nucleotide sequences, which again confirmed the 852Ins68 insertion and replacement of nucleotides (TCCAT to GGGG) in lumbosacral myelomeningocele (due to other category of NTDs), suggesting that it could be an independent risk factor for birth defects, including NTDs.

  14. Neural tube derived Wnt signals cooperate with FGF signaling in the formation and differentiation of the trigeminal placodes

    Directory of Open Access Journals (Sweden)

    Graham Anthony

    2008-12-01

    Full Text Available Abstract Background Neurogenic placodes are focal thickenings of the embryonic ectoderm that form in the vertebrate head. It is within these structures that the precursors of the majority of the sensory neurons of the cranial ganglia are specified. The trigeminal placodes, the ophthalmic and maxillomandibular, form close to the midbrain-hindbrain boundary and many lines of evidence have shown that signals emanating from this level of the neuraxis are important for the development of the ophthalmic placode. Results Here, we provide the first evidence that both the ophthalmic and maxillomandibular placodes form under the influence of isthmic Wnt and FGF signals. Activated Wnt signals direct development of the Pax3 expressing ophthalmic placodal field and induce premature differentiation of both the ophthalmic and the maxillomandibular placodes. Similarly, overexpression of Fgf8 directs premature differentiation of the trigeminal placodes. Wnt signals require FGF receptor activity to initiate Pax3 expression and, subsequently, the expression of neural markers, such as Brn3a, within the cranial ectoderm. Furthermore, fibroblast growth factor signaling via the mitogen activated protein kinase pathway is required to maintain early neuronal differentiation within the trigeminal placodes. Conclusion We demonstrate the identity of inductive signals that are necessary for trigeminal ganglion formation. This is the first report that describes how isthmic derived Wnt signals act in concert with fibroblast growth factor signaling. Together, both are necessary and sufficient for the establishment and differentiation of the ophthalmic and maxillomandibular placodes and, consequently, the trigeminal ganglion.

  15. Tube Defects in Women of Childbearing Age in the Supplementary Folic Acid to Prevent Fetal Neural%育龄妇女增补叶酸预防胎儿神经管缺陷分析干预

    Institute of Scientific and Technical Information of China (English)