Science.gov

Sample records for background neural tube

  1. Neural Tube Defects

    MedlinePlus

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

  2. Neural tube defects.

    PubMed

    Greene, Nicholas D E; Copp, Andrew J

    2014-01-01

    Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies. PMID:25032496

  3. Genetic background influences embryonic lethality and the occurrence of neural tube defects in Men1 null mice: relevance to genetic modifiers.

    PubMed

    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. PMID:19587266

  4. Genetics of neural tube defects.

    PubMed

    Gelineau-van Waes, J; Finnell, R H

    2001-09-01

    Neural tube defects (NTDs) are common congenital malformations that occur when the embryonic neural tube fails to close properly during early development. Although multifactorial in origin, NTDs appear to have a strong genetic component. Mouse NTD mutants provide useful models for the study of candidate genes involved in neural tube development and closure. Because maternal nutrition, specifically folate supplementation, is a significant modulator of NTD risk, genes involved in folate transport and metabolism are a focus of investigation. In addition, transcription factors, as well as genes involved in mitosis, actin regulation, and methylation appear to be implicated in the causes of NTDs. The heterogeneity of function of candidate genes suggests that alterations in multiple developmental pathways may lead to the same clinical malformation. PMID:11575845

  5. Screening for Open Neural Tube Defects.

    PubMed

    Krantz, David A; Hallahan, Terrence W; Carmichael, Jonathan B

    2016-06-01

    Biochemical prenatal screening was initiated with the use of maternal serum alpha fetoprotein to screen for open neural tube defects. Screening now includes multiple marker and sequential screening protocols involving serum and ultrasound markers to screen for aneuploidy. Recently cell-free DNA screening for aneuploidy has been initiated, but does not screen for neural tube defects. Although ultrasound is highly effective in identifying neural tube defects in high-risk populations, in decentralized health systems maternal serum screening still plays a significant role. Abnormal maternal serum alpha fetoprotein alone or in combination with other markers may indicate adverse pregnancy outcome in the absence of open neural tube defects. PMID:27235920

  6. Opioid Use and Neural Tube Defects

    MedlinePlus

    ... this page: About CDC.gov . Articles Key Findings: Opioid Use and Neural Tube Defects Recommend on Facebook ... new study that looked at the use of opioids during pregnancy and their relationship to having a ...

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

    PubMed

    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. PMID:24902834

  8. Neural Tube Defects, Folic Acid and Methylation

    PubMed Central

    Imbard, Apolline; Benoist, Jean-François; Blom, Henk J.

    2013-01-01

    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. PMID:24048206

  9. Mouse models for neural tube closure defects.

    PubMed

    Juriloff, D M; Harris, M J

    2000-04-12

    Neural tube closure defects (NTDs), in particular anencephaly and spina bifida, are common human birth defects (1 in 1000), their genetics is complex and their risk is reduced by periconceptional maternal folic acid supplementation. There are > 60 mouse mutants and strains with NTDs, many reported within the past 2 years. Not only are NTD mutations at loci widely heterogeneous in function, but also most of the mutants demonstrate variable low penetrance and some show complex inheritance patterns (e.g. SELH/Bc, Abl / Arg, Mena / Profilin1 ). In most of these mouse models, the NTDs are exencephaly (equivalent to anencephaly) or spina bifida or both, reflecting failure of neural fold elevation in well defined, mechanistically distinct elevation zones. NTD risk is reduced in various models by different maternal nutrient supplements, including folic acid ( Pax3, Cart1, Cd mutants), inositol ( ct ) and methionine ( Axd ). Lack of de novo methylation in embryos ( Dnmt3b -null) leads to NTD risk, and we suggest a potential link between methylation and the observed female excess among cranial NTDs in several models. Some surprising NTD mutants ( Gadd45a, Terc, Trp53 ) suggest that genes with a basic mitotic function also have a function specific to neural fold elevation. The genes mutated in several mouse NTD models involve actin regulation ( Abl/Arg, Macs, Mena/Profilin1, Mlp, Shrm, Vcl ), support the postulated key role of actin in neural fold elevation, and may be a good candidate pathway to search for human NTD genes. PMID:10767323

  10. Genetic, Epigenetic, and Environmental Contributions to Neural Tube Closure

    PubMed Central

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

    2015-01-01

    The formation of the embryonic brain and spinal cord begins as the neural plate bends to form the neural folds, which meet and fuse 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. PMID:25292356

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

    PubMed Central

    Aquilina-Beck, Allisan; Ilagan, Kristine; Liu, Qin; Liang, Jennifer O

    2007-01-01

    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 TGF? 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. PMID:17996054

  12. Periconceptional folate and neural tube defect.

    PubMed

    Rush, D

    1994-02-01

    The US Public Health Service recommends that all women in the United States who might possibly become pregnant should consume 0.4 mg folic acid/d to lower the incidence of neural tube defect (NTD). This paper reviews the bases for this recommendation: controlled trials of periconceptional folate, observational studies of folate supplementation, studies relating dietary folate to NTD, a trial of dietary education aimed at lowering the rate of NTD, and studies of the relationship to NTD of serum and red blood cell folate concentrations. It remains unclear that trials to prevent recurrent NTD apply directly to occurrent NTD, and the minimum necessary dose of folate is unknown. Given the potential dangers of high levels of folate in the general diet, particularly the masking of the hematologic effects of vitamin B-12 deficiency in elderly persons, with the consequent possibility of vitamin B-12 deficiency presenting as severe, irreversible neurologic disease, it is suggested that, until the impact of increasing the general folate level of the diet is better understood, tablet supplementation of folate to women of child-bearing age is preferable as an interim measure to increased food fortification. PMID:8304289

  13. Neural Tube Defects: From a Proteomic Standpoint

    PubMed Central

    Puvirajesinghe, Tania M.; Borg, Jean-Paul

    2015-01-01

    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. PMID:25789708

  14. Aneuploidy among prenatally detected neural tube defects

    SciTech Connect

    Hume, R.F. Jr.; Lampinen, J.; Martin, L.S.; Johnson, M.P.; Evans, M.I.

    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.

  15. Neural tube defects: from a proteomic standpoint.

    PubMed

    Puvirajesinghe, Tania M; Borg, Jean-Paul

    2015-01-01

    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. PMID:25789708

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

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How do health care providers diagnose neural tube defects? Skip sharing on ... AFP, as well as high levels of acetylcholinesterase; health care providers might conduct this test to confirm high ...

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

    PubMed

    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. PMID:23790957

  18. Morphogenesis: shroom in to close the neural tube.

    PubMed

    Martin, Paul

    2004-02-17

    A novel actin-binding protein, Shroom, localises to precisely those cells that will constrict during cranial neural tube closure and appears pivotal in regulating the apical constrictions that drive epithelial foldings in vertebrate embryos. PMID:15027465

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

    PubMed

    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. PMID:26959966

  20. Epithelial cell polarity genes are required for neural tube closure.

    PubMed

    Doudney, Kit; Stanier, Philip

    2005-05-15

    Human neural tube defects (NTD) are a heterogeneous group that exhibit complex inheritance, making it difficult to identify the underlying cause. Due to the uniform genetic background, inbred mouse strains are a more amenable target for genetic studies. We investigated the loop-tail (Lp) mouse as a model for the severe NTD, craniorachischisis. A homozygous point mutation was identified in the transmembrane protein Vangl2, which in Drosophila has been shown to function in the planar cell polarity (PCP) pathway. Morphological analysis of the Lp mice shows that the defect results from an abnormally broad floor plate, most likely through a failure in convergent extension. The elevated neural folds remain too far apart to contact, inhibiting neural tube closure. Recently, two other mouse mutants (crash and circletail) were described with a similar phenotype to Lp and were investigated as potentially new alleles. Mapping studies, however, showed that both mutants segregated to distinct loci. In the crash (Crsh) mouse, a mutation was identified in Celsr1, a seven pass transmembrane receptor that encodes a protein orthologous to Drosophila Flamingo. Like Vangl2, this gene also functions in the PCP pathway. While in circletail, a point mutation was identified introducing a premature stop codon into the apical-basal cell polarity gene scribble (Scrb1). We subsequently demonstrated a genetic interaction between all three genes, where double heterozygotes exhibit the same homozygous NTD phenotype. This strongly suggests both a candidate gene pathway and that interaction between independent recessive alleles may be a possible explanation for the complex inheritance in severe human NTD. PMID:15800847

  1. Apical Accumulation of Rho in the Neural Plate Is Important for Neural Plate Cell Shape Change and Neural Tube Formation

    PubMed Central

    Kinoshita, Nagatoki; Sasai, Noriaki; Misaki, Kazuyo

    2008-01-01

    Although Rho-GTPases are well-known regulators of cytoskeletal reorganization, their in vivo distribution and physiological functions have remained elusive. In this study, we found marked apical accumulation of Rho in developing chick embryos undergoing folding of the neural plate during neural tube formation, with similar accumulation of activated myosin II. The timing of accumulation and biochemical activation of both Rho and myosin II was coincident with the dynamics of neural tube formation. Inhibition of Rho disrupted its apical accumulation and led to defects in neural tube formation, with abnormal morphology of the neural plate. Continuous activation of Rho also altered neural tube formation. These results indicate that correct spatiotemporal regulation of Rho is essential for neural tube morphogenesis. Furthermore, we found that a key morphogenetic signaling pathway, the Wnt/PCP pathway, was implicated in the apical accumulation of Rho and regulation of cell shape in the neural plate, suggesting that this signal may be the spatiotemporal regulator of Rho in neural tube formation. PMID:18337466

  2. Epidemiology of neural tube defects in Utah, 1940-1979.

    PubMed

    Jorde, L B; Fineman, R M; Martin, R A

    1984-04-01

    The prevalence and distribution of 991 cases of neural tube defects who were born in Utah in 1940-1979 are analyzed. The average prevalence at birth is 1.00 per 1000 births (live and stillbirths), which is similar to other states in the western United States. A decline in prevalence is observed during the past 10 years, although there is not a long-term secular trend for the whole time period. Examination of hospital records shows that 17.9% of neural tube defects were not reported on birth or fetal death certificates. The male/female sex ratio is 0.67. No seasonality is found for spina bifida cases; however, a bimodal distribution, with a substantial deficit in May, is observed for anencephaly. A significant negative correlation is found between neural tube defect prevalence and the percentage of individuals in each Utah county who are members of the Mormon Church. No association is found between levels of fallout exposure in Utah and regional variation in neural tube defects, and time-space clustering analysis demonstrates no significant clusters of neural tube defects in Utah. PMID:6369963

  3. Periconceptional Folate Deficiency and Implications in Neural Tube Defects

    PubMed Central

    Safi, J.; Joyeux, L.; Chalouhi, G. E.

    2012-01-01

    Nutritional deficiencies are preventable etiological and epigenetic factors causing congenital abnormalities, first cause of infant mortality. Folate deficiency has a well-established teratogenic effect, leading to an increasing risk of neural tube defects. This paper highlights the most recent medical literature about folate deficiency, be it maternal or paternal. It then focuses on associated deficiencies as nutritional deficiencies are multiple and interrelated. Observational and interventional studies have all been consistent with a 50–70% protective effect of adequate women consumption of folates on neural tube defects. Since strategies to modify women's dietary habits and vitamin use have achieved little progress, scientific as well as political effort is mandatory in order to implement global preventive public health strategies aimed at improving the alimentation of women in reproductive age, especially folic acid supplementation. Even with the recent breakthrough of fetal surgery for myelomeningocele, the emphasis should still be on prevention as the best practice rather than treatment of neural tube defects. PMID:22900183

  4. Neural tube defects in Jamaica following Hurricane Gilbert.

    PubMed Central

    Duff, E M; Cooper, E S

    1994-01-01

    An increased incidence of obvious live-birth neural tube defects (i.e., spina bifida cystica and encephalocele) occurred in Jamaica 11 to 18 months after Hurricane Gilbert. The conceptions of the affected babies coincided with a rise in megaloblastic change in sickle cell patients, suggesting a wide-spread drop in dietary folate intake. A detailed history was taken from each of the 17 affected mothers (case subjects) and 51 unaffected mothers (matched control subjects). The case subjects reported a significantly lower mean intake of dietary folate in the periconceptional period (154 micrograms/day) than did the control subjects (254 micrograms/day). The temporary increase in neural tube defects was associated with a diet comparatively low in folate in the periconceptional period, suggesting the dietary level of folate that fails to protect against neural tube defects under natural conditions. PMID:8129070

  5. Fumonisins, Tortillas and Neural Tube Defects: Untangling a Complex Issue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisin mycotoxins are found in corn and corn-based foods. Fumonisin B1 (FB1), the most common, disrupts sphingolipid metabolism thereby causing species-specific diseases in animals that include cancer in rodents and (birth) neural tube defects (NTD) in LM/Bc mice. Fumonisins’ affect on human heal...

  6. Classification, clinical features, and genetics of neural tube defects

    PubMed Central

    Salih, Mustafa A.; Murshid, Waleed R.; Seidahmed, Mohammed Z.

    2014-01-01

    Neural tube defects (NTDs) constitute a major health burden (0.5-2/1000 pregnancies worldwide), and remain a preventable cause of still birth, neonatal, and infant death, or significant lifelong handicaps. The malformations result from failure of the neural folds to fuse in the midline, and form the neural tube between the third and the fourth week of embryonic development. This review article discusses their classification, clinical features, and genetics. Most NTDs are sporadic and both genetic, and non-genetic environmental factors are involved in its etiology. Consanguinity was suggested to contribute to the high incidence of NTDs in several countries, including Saudi Arabia. Syndromes, often associated with chromosomal anomalies, account for <10% of all NTDs; but a higher proportion (20%) has been documented in Saudi Arabia. Genetic predisposition constitutes the major underlying risk factor, with a strong implication of genes that regulate folate one-carbon metabolism and planar cell polarity. PMID:25551113

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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

  9. New Techniques for the Study of Neural Tube Defects

    PubMed Central

    Lei, Yunping; Finnell, Richard H

    2016-01-01

    Neural tube defects (NTDs) are among the most common complex congenital malformations observed in newborns. When the neural tube fails to close completely, severe malformations of the brain and/or spinal cord and subsequent neurologic impairment occurs. It is widely believed that nutritional, environmental and genetic interactions contribute to NTDs. It is well established that low folate levels during pregnancy increases a mother’s risk of having pregnancy complicated by an NTD, and providing periconceptional folate supplementation reduces this risk. The underlying genetic mechanisms of NTDs are still unclear. We review the many new approaches to better understand the etiology, especially the genetic etiology, underlying this family of birth defects. PMID:27066597

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

    PubMed

    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. PMID:21730342

  11. Etiology, pathogenesis and prevention of neural tube defects.

    PubMed

    Padmanabhan, Rengasamy

    2006-06-01

    Spina bifida, anencephaly, and encephalocele are commonly grouped together and termed neural tube defects (NTD). Failure of closure of the neural tube during development results in anencephaly or spina bifida aperta but encephaloceles are possibly post-closure defects. NTD are associated with a number of other central nervous system (CNS) and non-neural malformations. Racial, geographic and seasonal variations seem to affect their incidence. Etiology of NTD is unknown. Most of the non-syndromic NTD are of multifactorial origin. Recent in vitro and in vivo studies have highlighted the molecular mechanisms of neurulation in vertebrates but the morphologic development of human neural tube is poorly understood. A multisite closure theory, extrapolated directly from mouse experiments highlighted the clinical relevance of closure mechanisms to human NTD. Animal models, such as circle tail, curly tail, loop tail, shrm and numerous knockouts provide some insight into the mechanisms of NTD. Also available in the literature are a plethora of chemically induced preclosure and a few post-closure models of NTD, which highlight the fact that CNS malformations are of hetergeneitic nature. No Mendelian pattern of inheritance has been reported. Association with single gene defects, enhanced recurrence risk among siblings, and a higher frequency in twins than in singletons indicate the presence of a strong genetic contribution to the etiology of NTD. Non-availability of families with a significant number of NTD cases makes research into genetic causation of NTD difficult. Case reports and epidemiologic studies have implicated a number of chemicals, widely differing therapeutic drugs, environmental contaminants, pollutants, infectious agents, and solvents. Maternal hyperthermia, use of valproate by epileptic women during pregnancy, deficiency and excess of certain nutrients and chronic maternal diseases (e.g. diabetes mellitus) are reported to cause a manifold increase in the incidence of NTD. A host of suspected teratogens are also available in the literature. The UK and Hungarian studies showed that periconceptional supplementation of women with folate (FA) reduces significantly both the first occurrence and recurrence of NTD in the offspring. This led to mandatory periconceptional FA supplementation in a number of countries. Encouraged by the results of clinical studies, numerous laboratory investigations focused on the genes involved in the FA, vitamin B12 and homocysteine metabolism during neural tube development. As of today no clinical or experimental study has provided unequivocal evidence for a definitive role for any of these genes in the causation of NTD suggesting that a multitude of genes, growth factors and receptors interact in controlling neural tube development by yet unknown mechanisms. Future studies must address issues of gene-gene, gene-nutrient and gene-environment interactions in the pathogenesis of NTD. PMID:16732763

  12. Neural dynamic optimization for control systems. I. Background.

    PubMed

    Seong, C Y; Widrow, B

    2001-01-01

    The paper presents neural dynamic optimization (NDO) as a method of optimal feedback control for nonlinear multi-input-multi-output (MIMO) systems. The main feature of NDO is that it enables neural networks to approximate the optimal feedback solution whose existence dynamic programming (DP) justifies, thereby reducing the complexities of computation and storage problems of the classical methods such as DP. This paper mainly describes the background and motivations for the development of NDO, while the two other subsequent papers of this topic present the theory of NDO and demonstrate the method with several applications including control of autonomous vehicles and of a robot arm, respectively. PMID:18244815

  13. Maternal Periconceptional Occupational Pesticide Exposure and Neural Tube Defects

    PubMed Central

    Makelarski, Jennifer A.; Romitti, Paul A.; Rocheleau, Carissa M.; Burns, Trudy L.; Stewart, Patricia A.; Waters, Martha A.; Lawson, Christina C.; Bell, Erin M.; Lin, Shao; Shaw, Gary M.; Olney, Richard S.

    2015-01-01

    Background Adverse associations between maternal pesticide exposure and neural tube defects (NTDs) have been suggested but not consistently observed. This study used data from the multisite National Birth Defects Prevention Study to examine associations between maternal periconceptional (1 month preconception through 2 months postconception) occupational pesticide exposure and NTDs. Methods Mothers of 502 NTD cases and 2950 unaffected live-born control infants with estimated delivery dates from 1997 through 2002 were included. Duration, categorical intensity scores, and categorical frequency scores for pesticide classes (e.g., insecticides) were assigned using a modified, literature-based job-exposure matrix and maternal-reported occupational histories. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated based on fitted multivariable logistic regression models that described associations between maternal periconceptional occupational pesticide exposure and NTDs. The aORs were estimated for pesticide exposure (any [yes/no] and cumulative exposure [intensity × frequency × duration] to any pesticide class, each pesticide class, or combination of pesticide classes) and all NTD cases combined and NTD subtypes. Results Positive, but marginally significant or nonsignificant, aORs were observed for exposure to insecticides + herbicides for all NTD cases combined and for spina bifida alone. Similarly, positive aORs were observed for any exposure and cumulative exposure to insecticides + herbicides + fungicides and anencephaly alone and encephalocele alone. All other aORs were near unity. Conclusion Pesticide exposure associations varied by NTD subtype and pesticide class. Several aORs were increased, but not significantly. Future work should continue to examine associations between pesticide classes and NTD subtypes using a detailed occupational pesticide exposure assessment and examine pesticide exposures outside the workplace. PMID:25124525

  14. Epidemiology of the neural tube defects in Kashmir Valley

    PubMed Central

    Laharwal, Masood Ahmed; Sarmast, Arif Hussain; Ramzan, Altaf Umer; Wani, Abrar Ahad; Malik, Nayil Khursheed; Arif, Sajad Hussain; Rizvi, Masooma

    2016-01-01

    Background: Neural tube defects (NTDs) 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. Methods: A 2-year hospital-based prospective study was carried out from November 2013 to October 2015 to determine the incidence, types, demographics, risk factors, and other associated anamolies relevant to NTDs in Kashmir Valley. 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: Anterior-posterior (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. Kupwara district was having the highest incidence (1.047) and Srinagar district the lowest incidence of NTD's (0.197). 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 were 70 females (56%) and 55 males (44%), respectively, with a male: female ratio of 0.8:1 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. PMID:27127700

  15. Neural-tube defects in a prehistoric south-western Indian population.

    PubMed

    Devor, E J; Cordell, L S

    1981-01-01

    Concern with the frequency and patterning of the occurrence of midline neural-tube defects among contemporary human populations is widespread. These defects are, however, quite old and occur in unusually high numbers of prehistoric skeletons. A common explanation offered for such high incidence has been inbreeding among small, reproductively isolated populations. In a sample of 54 skeletons from the prehistoric south-western Indian site of Tijeras Pueblo in New Mexico, failure of neural-tube closure occurs in 10% of sacra recovered. While a more homogeneous genetic background and inbreeding may account for a portion of this elevated prevalence, the cause appears to lie with cultural-environmental factors. It is suggested that the aetiology of these conditions has become more complex in recent human history. PMID:7013648

  16. Antenatal Diagnosis of a Rare Neural Tube Defect: Sincipital Encephalocele

    PubMed Central

    Kehila, Mehdi; Ghades, Sana; Abouda, Hassine Saber; Masmoudi, Aida; Chanoufi, Mohamed Badis

    2015-01-01

    Context. Fetal sincipital encephalocele is one of the most serious congenital neural tube defects with a high risk of mortality and neonatal morbidity. Prenatal diagnosis of this malformation is important in fetal medicine. Case Report. We report a case of prenatal diagnosis of sincipital encephalocele using ultrasound and MRI imaging. The diagnosis was done at 25 weeks of gestation by identifying an anterior cephalic protrusion through a defect in the skull. Conclusion. Through this case, we discuss the differential diagnosis, management, and prognosis of such lesions. PMID:26294989

  17. Antenatal Diagnosis of a Rare Neural Tube Defect: Sincipital Encephalocele.

    PubMed

    Kehila, Mehdi; Ghades, Sana; Abouda, Hassine Saber; Masmoudi, Aida; Chanoufi, Mohamed Badis

    2015-01-01

    Context. Fetal sincipital encephalocele is one of the most serious congenital neural tube defects with a high risk of mortality and neonatal morbidity. Prenatal diagnosis of this malformation is important in fetal medicine. Case Report. We report a case of prenatal diagnosis of sincipital encephalocele using ultrasound and MRI imaging. The diagnosis was done at 25 weeks of gestation by identifying an anterior cephalic protrusion through a defect in the skull. Conclusion. Through this case, we discuss the differential diagnosis, management, and prognosis of such lesions. PMID:26294989

  18. Recent studies on neural tube defects in embryos of diabetic pregnancy: an overview.

    PubMed

    Dheen, S Thameem; Tay, Samuel S W; Boran, Jiang; Ting, Loh Wan; Kumar, S Dinesh; Fu, Jiang; Ling, Eng-Ang

    2009-01-01

    Maternal diabetes develops in 2-6% of total pregnancies, depending on geographical and ethnic background. About 10% of fetuses from diabetic pregnancy display congenital malformations in various organ systems including cardiovascular, gastrointestinal, genitourinary and neurological systems, among which the neural tube defects (NTDs) such as anencephaly, holoprosencephaly and syntelencephaly were more frequently demonstrated. Recent studies by the Diabetes Control and Complications Trial Research Group show that tight glycemic control early in pregnancy decreases the progression of a number of diabetic complications. However, it appears that the pre-existing tissue damage cannot be reversed even after normoglycemic levels are achieved during pregnancy. In recent years, considerable efforts have been made to investigate the etiology of birth defects among infants of diabetic mothers. It has been shown that diabetes-induced fetal abnormalities are accompanied by some metabolic disturbances including elevated superoxide dismutase (SOD) activity, reduced levels of myoinositol and arachidonic acid and inhibition of the pentose phosphate shunt pathway. Moreover, the frequency of fetal malformations in diabetic pregnancy has been reported to be markedly reduced by dietary supplements of antioxidants such as vitamin E, vitamin C and butylated hy- droxytoluene, suggesting that oxidative stress is involved in the etiology of fetal dysmorphogenesis. Furthermore, several experimental studies have shown that NTDs in embryos of diabetic mice are associated with altered expression of genes, which control development of the neural tube. In this review, recent findings of possible molecular mechanisms which cause morphological changes during neural tube development in embryos of diabetic pregnancy are discussed. PMID:19519395

  19. Associated anomalies with neural tube defects in fetal autopsies.

    PubMed

    Toru, Havva Serap; Sanhal, Cem Yasar; Uzun, Özlem Ceren; Ocak, Guzide Ayse; Mendilcioğlu, İnanç; Karaveli, Fatma Şeyda

    2016-03-01

    Neural tube defects (NTD), the consequences of aberrant neural tube closure during embryogenesis, have been mostly investigated in terms of their high prevalence, rate of mortalities and serious morbidities. A proper prenatal outcome counseling of couples coming across a fetal anomaly necessitates the detection and categorization of the primer abnormality, all the co-existing malformations. The aim of this work is to study the incidence and relevance of associated malformations in order to offer a complete pathology report with a true diagnosis. In this study, among 542 fetal autopsy 62 (%11.4) cases with NTD was recorded by the Akdeniz University Pathology Department between January 2006 and June 2012. Twenty (32.4%) NTD cases were associated with anomaly. Twelve cases of associated groups consisted of a congenital syndrome/association, spondylothoracic dysplasia, amniotic band syndrome, Meckel-Gruber syndrome, schisis association. The frequency of associated NTD was 32%, this result was higher than previous reports. NTDs have a significant genetic component to their etiology that interacts with environmental risk factors, which might pose Turkey to be a country with high prevalence of NTD. We want to emphasize that intensive screening, documentation of co-existent abnormalities of NTD, should be conducted in order to exhibit certain diagnosis, to perform proper prenatal genetic counseling of parents for on-going/future pregnancies. PMID:25800566

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

    SciTech Connect

    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{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 development by tightly coordinating cell proliferation and differentiation during neurulation. - Highlights: ► The role of Slit/Robo1 signaling was investigated with chick and mouse models. ► Disturbance of Slit/Robo1 signaling resulted in neural tube defects. ► Slit/Robo1 signaling regulated the proliferation of neural tube cells. ► Slit/Robo1 signaling modulated the differentiation of neural tube cells. ► Slit/Robo1 signaling balanced the proliferation and differentiation of neural tube.

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

    PubMed

    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. Developmental Dynamics 245:197-208, 2016. © 2015 Wiley Periodicals, Inc. PMID:26177834

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

    PubMed

    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. PMID:26349489

  3. Neural tube defects and abnormal brain development in F52-deficient mice.

    PubMed Central

    Wu, M; Chen, D F; Sasaoka, T; Tonegawa, S

    1996-01-01

    F52 is a myristoylated, alanine-rich substrate for protein kinase C. We have generated F52-deficient mice by the gene targeting technique. These mutant mice manifest severe neural tube defects that are not associated with other complex malformations, a phenotype reminiscent of common human neural tube defects. The neural tube defects observed include both exencephaly and spina bifida, and the phenotype exhibits partial penetrance with about 60% of homozygous embryos developing neural tube defects. Exencephaly is the prominent type of defect and leads to high prenatal lethality. Neural tube defects are observed in a smaller percentage of heterozygous embryos (about 10%). Abnormal brain development and tail formation occur in homozygous mutants and are likely to be secondary to the neural tube defects. Disruption of F52 in mice therefore identifies a gene whose mutation results in isolated neural tube defects and may provide an animal model for common human neural tube defects. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8700893

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

    MedlinePlus

    ... by or are at risk for neural tube defects? Skip sharing on social media links Share this: Page Content In the United States, about 1,500 infants are born each year with spina bifida. 1 The other types of neural tube defects are less common. About 340 infants are born ...

  5. Birth Prevalence of Neural Tube Defects and Orofacial Clefts in India: A Systematic Review and Meta-Analysis

    PubMed Central

    Allagh, Komal Preet; Shamanna, B. R.; Murthy, Gudlavalleti V. S.; Ness, Andy R.; Doyle, Pat; Neogi, Sutapa B.; Pant, Hira B.

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:25768737

  6. Epidemiology, prenatal management, and prevention of neural tube defects

    PubMed Central

    Salih, Mustafa A.; Murshid, Waleed R.; Seidahmed, Mohammed Z.

    2014-01-01

    This review article discusses the epidemiology, risk factors, prenatal screening, diagnosis, prevention potentials, and epidemiologic impact of neural tube defects (NTDs). The average incidence of NTDs is 1/1000 births, with a marked geographic variation. In the developed countries, the incidence of NTDs has fallen over recent decades. However, it still remains high in the less-developed countries in Latin America, Africa, the Middle East, Asia, and the Far East (>1 to 11/1000 births). Recognized NTDs risks include maternal diabetes, obesity, lower socioeconomic status, hyperthermia, and exposure to certain teratogens during the periconceptional period. Periconceptional folic acid supplementation decreased the prevalence of NTDs by 50-70%, and an obligatory folic acid fortification of food was adopted in several countries to reach women with unplanned pregnancies and those facing social deprivation. Prevention of NTDs can be accelerated if more, especially low income countries, adopted fortification of the staple food in their communities. PMID:25551106

  7. Folic Acid for the Prevention of Infant Neural Tube Defects: U.S. Preventive Services Task Force Recommendation

    MedlinePlus

    ... Infant Neural Tube Defects: U.S. Preventive Services Task Force Recommendation Summaries for Patients are a service provided ... of Neural Tube Defects: U.S. Preventive Services Task Force Recommen- dation Statement” and “Folic Acid Supplementation for ...

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

    PubMed Central

    Ramírez-Altamirano, María de Jesús; Fenton-Navarro, Patricia; Sivet-Chiñas, Elvira; Harp-Iturribarria, Flor de María; Martínez-Cruz, Ruth; Cruz, Pedro Hernández; Cruz, Margarito Martínez; Pérez-Campos, Eduardo

    2012-01-01

    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. PMID:23400307

  9. Neural tube defects: an experimental model in the foetal rat.

    PubMed

    Diez-Pardo, J A; Mariño, J M; Baoquan, Q; Delgado-Baeza, E; Fernáneez, A; Morales, M C; Tovar, J A

    1995-08-01

    We report on our experience in the experimental induction of Neural Tube Defects (NTD) in the foetal rat by maternal administration of retinoic acid. The teratogen diluted in olive oil was administered in a single intragastric dose (125 mg/kg body weight) to pregnant rats (n = 31) on the 10th day of gestation. Pure olive oil was given to control rats (n = 9). The foetuses were recovered by caesarian section on the 20th day and prepared for morphological investigation. We have studied 201 experimental and 82 control animals. There were NTD in 36.3% of experimental foetuses and none in the control ones. Sacral dysraphism was the most frequent defect but we also observed Arnold Chiari malformations and crowding of the bony limits by an enlarged neural axis. Other associated malformations found were: craneofacial (78.1%), caudal (80%), anorectal (31.4%), and limb defects (89.5%). This simple and inexpensive model may allow us to gain a better knowledge of the biology in the foetus with NTD. PMID:7577855

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

    PubMed

    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. PMID:23935126

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

    PubMed Central

    Devine, Owen; Hao, Ling; Dowling, Nicole F; Li, Song; Molloy, Anne M; Li, Zhu; Zhu, Jianghui; Berry, Robert J

    2014-01-01

    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 (2003-05) to evaluate the effect of folic acid supplementation on blood folate concentration among Chinese women of reproductive age. Intervention Folic acid supplementation (400 μg/day). Main outcome measures Estimated RBC folate concentration at time of neural tube closure (day 28 of gestation) and risk of neural tube defects. Results Risk of neural tube defects was high at the lowest estimated RBC folate concentrations (for example, 25.4 (95% uncertainty interval 20.8 to 31.2) neural tube defects per 10 000 births at 500 nmol/L) and decreased as estimated RBC folate concentration increased. Risk of neural tube defects was substantially attenuated at estimated RBC folate concentrations above about 1000 nmol/L (for example, 6 neural tube defects per 10 000 births at 1180 (1050 to 1340) nmol/L). The modeled dose-response relation was consistent with the existing literature. In addition, neural tube defect risk estimates developed using the proposed model and population level RBC information were consistent with the prevalence of neural tube defects in the US population before and after food fortification with folic acid. Conclusions A threshold for “optimal” population RBC folate concentration for the prevention of neural tube defects could be defined (for example, approximately 1000 nmol/L). Population based RBC folate concentrations, as a biomarker for risk of neural tube defects, can be used to facilitate evaluation of prevention programs as well as to identify subpopulations at elevated risk for a neural tube defect affected pregnancy due to folate insufficiency. PMID:25073783

  12. USE OF A MURINE EMBRYONIC STEM CELL LINE THAT IS SENSITIVE TO HIGH GLUCOSE ENVIRONMENT TO MODEL NEURAL TUBE DEVELOPMENT IN DIABETIC PREGNANCY

    PubMed Central

    Sanders, Kaitlyn; Jung, Jin Hyuk; Loeken, Mary R.

    2014-01-01

    Background Neural tube defects (NTDs) are significantly increased by maternal diabetes. Embryonic stem cells (ESC) that can differentiate into neuroepithelium and can sense supraphysiological glucose concentrations would be very valuable to simulate the effects of maternal diabetes on molecular and cellular processes during neural tube formation. Methods LG-ESC, a recently established ESC line that expresses the glucose transporter, Scl2a2, and is sensitive to elevated glucose concentrations, were grown for up to 8 days in a 3-dimensional culture to form neural cysts (NC). We tested whether high glucose media inhibits expression of Pax3, a gene that is required for neural tube closure and whose expression is inhibited in embryos of diabetic mice, and inhibits formation of NC. Results Pax3 expression was detected after 4 days of culture and increased with time. Pax3 expression was inhibited by high glucose media, but not if cells had been cultured in low glucose media for the first 4 days of culture. Pax7, which is also expressed in dorsal neural tube, was not detected. Pax6, which is expressed in the ventral neural tube, was detected only after 8 days of culture, but was not inhibited by high glucose. High glucose media did not inhibit formation of NC. Conclusions LG-ESC can be used as a model of embryonic exposure to a diabetic environment during neural tube development. While high glucose exposure inhibits expression of a gene required for neural tube closure, it may not inhibit all of the processes involved in formation of a neural tube-like structure. PMID:25124397

  13. Folate receptor gene variants and neural tube defect occurrence

    SciTech Connect

    Finnell, R.; Greer, K.; Lammer, E.

    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.

  14. Pathophysiology, prevention, and potential treatment of neural tube defects.

    PubMed

    Manning, S M; Jennings, R; Madsen, J R

    2000-01-01

    Neural tube defects (NTD) remain a major cause of morbidity in spite of the reduction in liveborn incidence with periconceptional folic acid. However, the etiology remains unknown. This article reviews studies that address causation and potential treatment of NTD in humans and in animal models that resemble aspects of the common human NTD. Studies of nutritional markers of vitamin B12 and folic acid support a defect in homocysteine metabolism; a thermolabile variant of methylene tetrahydrofolate reductase, an enzyme that remethylates homocysteine to methionine, correlates with a risk of NTD in some human populations. Numerous mouse mutant models of NTD exist, attesting to the ease of disruption of neurulation, and a genetic basis for this malformation. Of these models, the curly tail mouse mutant most closely resembles the common human NTD. Folic acid does not prevent NTD in this model; however inositol supplementation does result in a significant reduction in incidence. Recent advances in fetal surgery, and evidence from mechanically created myelomeningocele in large animals amenable to surgical intervention suggest that the handicaps associated with myelomeningocele and associated Chiari Type II malformation may be prevented by in utero NTD closure. Success will depend on preservation of neurological tissue until such intervention is possible. Further research in animal models at the genetic and cellular levels, together with technological surgical advances, provide hope that prevention of more NTD and the associated handicaps may be possible. MRDD Research Reviews 6:6-14, 2000. PMID:10899792

  15. [Territorial distribution of neural tube defects in Poland].

    PubMed

    Lech, M; Mazur, J; Sawi?ska, I

    1997-01-01

    Neural tube defects (ntd) remain unresolved therapeutic problems, even for contemporary health services. Prophylactic measures are the best methods for limitation of the problem. In many countries, the number of children born with ntd has been reduced significantly, even in 4-5 folds. Authors found that the situation in Poland remains stable since last 20 years. Epidemiological evaluation of the ntd morbidity in Poland is very difficult. There is no National Register of Inherited Defects. Authors observed and analysed mortality and hospitalisation due to ntd in Poland, in early ninetees, and compared these data with information originated from Regional (Wielkopolska) Inherited Defects Register. It was found that ntd mortality and hospitalisation in Wielkopolska was similar to average in Poland. It has been estimated that the rate of children born with ntd in Poland, in 1995 was 2.68 per 1000 live and stillbriths (in 1972-1974 was 2.04). Especially high rates of ntd's have been found in north-eastern part of Country. Incidence of ntd's was higher in rural, than in urban population of the Country. PMID:9333850

  16. Chromosomal abnormalities associated with neural tube defects (II): partial aneuploidy.

    PubMed

    Chen, Chih-Ping

    2007-12-01

    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 a comprehensive review of structural chromosomal abnormalities associated with NTDs, such as del(13q), r(13), dup(2p), del(2q), del(1p), del(1q), dup(1q), del(3p), dup(3p), del(3q), dup(3q), del(4p), dup(4p), del(4q), dup(4q), del(5p), del(6p), dup(6q), del(6q), dup(7p), del(7q), dup(8q), del(9p), del(10q), del(11q), dup(11q), dup(12p), dup(14q), del(14q), del(15q), dup(16q), del(18q), r(18), dup(20p), +i(20p), del(22q), del(Xp), and dup(Xq). 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. PMID:18182339

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

    PubMed Central

    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

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

    PubMed

    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; Waes, Janee Gelineau-van; Band, Vimla; Band, Hamid

    2016-01-01

    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. PMID:26884322

  19. Sall1, Sall2, and Sall4 Are Required for Neural Tube Closure in Mice

    PubMed Central

    Bhm, Johann; Buck, Anja; Borozdin, Wiktor; Mannan, Ashraf U.; Matysiak-Scholze, Uta; Adham, Ibrahim; Schulz-Schaeffer, Walter; Floss, Thomas; Wurst, Wolfgang; Kohlhase, Jrgen; Barrionuevo, Francisco

    2008-01-01

    Four homologs to the Drosophila homeotic gene spalt (sal) exist in both humans and mice (SALL1 to SALL4/Sall1 to Sall4, respectively). Mutations in both SALL1 and SALL4 result in the autosomal-dominant developmental disorders Townes-Brocks and Okihiro syndrome, respectively. In contrast, no human diseases have been associated with SALL2 to date, and Sall2-deficient mice have shown no apparent abnormal phenotype. We generated mice deficient in Sall2 and, contrary to previous reports, 11% of our Sall2-deficient mice showed background-specific neural tube defects, suggesting that Sall2 has a role in neurogenesis. To investigate whether Sall4 may compensate for the absence of Sall2, we generated compound Sall2 knockout/Sall4 genetrap mutant mice. In these mutants, the incidence of neural tube defects was significantly increased. Furthermore, we found a similar phenotype in compound Sall1/4 mutant mice, and in vitro studies showed that SALL1, SALL2, and SALL4 all co-localized in the nucleus. We therefore suggest a fundamental and redundant function of the Sall proteins in murine neurulation, with the heterozygous loss of a particular SALL protein also possibly compensated in humans during development. PMID:18818376

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

    PubMed Central

    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; Waes, Janee Gelineau-van; Band, Vimla; Band, Hamid

    2016-01-01

    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. PMID:26884322

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

    PubMed

    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. PMID:26434722

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

    PubMed

    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. PMID:26542009

  3. Genetic analysis of disheveled 2 and disheveled 3 in human neural tube defects.

    PubMed

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

    2013-03-01

    Neural tube defects are severe malformations affecting 1/1,000 live births. The planar cell polarity pathway controls the neural tube closure and has been implicated in the pathogenesis of neural tube defects both in animal models and human cohorts. In mouse disruption of Dvl2 alone (Dvl2 (-/-)) or Dvl2 and Dvl3 (Dvl2 (-/-); Dvl3 (+/-), Dvl2 (+/-); Dvl3 (-/-)) results in incomplete neurulation, suggesting a role for Disheveled in neural tube closure. Disheveled is a multifunctional protein that is involved in both the canonical Wnt signaling and the noncanonical planar cell polarity pathway. In this study, we analyzed the role of the human orthologs DVL2 and DVL3 in a cohort of 473 patients with neural tube defects. Rare variants were genotyped in 639 ethnically matched controls. We identified seven rare missense mutations that were absent in all controls analyzed. Two of these mutations, p.Tyr667Cys and p.Ala53Val, identified in DVL2 were predicted to be detrimental in silico. Significantly, a 1-bp insertion (c.1801_1802insG) in exon 15 of DVL2 predicted to lead to the truncation of the protein was identified in a patient with a complex form of caudal agenesis. In summary, we demonstrate a possible role for rare variants in DVL2 gene as risk factors for neural tube defects. PMID:22892949

  4. Isolation of Human Neural Stem Cells from the Amniotic Fluid with Diagnosed Neural Tube Defects.

    PubMed

    Chang, Yu-Jen; Su, Hong-Lin; Hsu, Lee-Feng; Huang, Po-Jui; Wang, Tzu-Hao; Cheng, Fu-Chou; Hsu, Li-Wen; Tsai, Ming-Song; Chen, Chih-Ping; Chang, Yao-Lung; Chao, An-Shine; Hwang, Shiaw-Min

    2015-08-01

    Human neural stem cells (NSCs) are particularly valuable for the study of neurogenesis process and have a therapeutic potential in treating neurodegenerative disorders. However, current progress in the use of human NSCs is limited due to the available NSC sources and the complicated isolation and culture techniques. In this study, we describe an efficient method to isolate and propagate human NSCs from the amniotic fluid with diagnosed neural tube defects (NTDs), specifically, anencephaly. These amniotic fluid-derived NSCs (AF-NSCs) formed neurospheres and underwent long-term expansion in vitro. In addition, these cells showed normal karyotypes and telomerase activity and expressed NSC-specific markers, including Nestin, Sox2, Musashi-1, and the ATP-binding cassette G2 (ABCG2). AF-NSCs displayed typical morphological patterns and expressed specific markers that were consistent with neurons, astrocytes, oligodendrocytes, and dopaminergic neurons after proper induction conditions. Furthermore, grafted AF-NSCs improved the physiological functions in a rat stroke model. The ability to isolate and bank human NSCs from this novel source provides a unique opportunity for translational studies of neurological disorders. PMID:25923707

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

    PubMed Central

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

    2016-01-01

    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 a major advance toward understanding how these tissue layers interact during axis extension with important implications in human disease. PMID:27144312

  6. Progressive Differentiation and Instructive Capacities of Amniotic Fluid and Cerebrospinal Fluid Proteomes following Neural Tube Closure.

    PubMed

    Chau, Kevin F; Springel, Mark W; Broadbelt, Kevin G; Park, Hye-Yeon; Topal, Salih; Lun, Melody P; Mullan, Hillary; Maynard, Thomas; Steen, Hanno; LaMantia, Anthony S; Lehtinen, Maria K

    2015-12-21

    After neural tube closure, amniotic fluid (AF) captured inside the neural tube forms the nascent cerebrospinal fluid (CSF). Neuroepithelial stem cells contact CSF-filled ventricles, proliferate, and differentiate to form the mammalian brain, while neurogenic placodes, which generate cranial sensory neurons, remain in contact with the AF. Using in vivo ultrasound imaging, we quantified the expansion of the embryonic ventricular-CSF space from its inception. We developed tools to obtain pure AF and nascent CSF, before and after neural tube closure, and to define how the AF and CSF proteomes diverge during mouse development. Using embryonic neural explants, we demonstrate that age-matched fluids promote Sox2-positive neurogenic identity in developing forebrain and olfactory epithelia. Nascent CSF also stimulates SOX2-positive self-renewal of forebrain progenitor cells, some of which is attributable to LIFR signaling. Our Resource should facilitate the investigation of fluid-tissue interactions during this highly vulnerable stage of early brain development. PMID:26702835

  7. Planar cell polarity links axes of spatial dynamics in neural-tube closure.

    PubMed

    Nishimura, Tamako; Honda, Hisao; Takeichi, Masatoshi

    2012-05-25

    Neural-tube closure is a critical step of embryogenesis, and its failure causes serious birth defects. Coordination of two morphogenetic processes--convergent extension and neural-plate apical constriction--ensures the complete closure of the neural tube. We now provide evidence that planar cell polarity (PCP) signaling directly links these two processes. In the bending neural plates, we find that a PCP-regulating cadherin, Celsr1, is concentrated in adherens junctions (AJs) oriented toward the mediolateral axes of the plates. At these AJs, Celsr1 cooperates with Dishevelled, DAAM1, and the PDZ-RhoGEF to upregulate Rho kinase, causing their actomyosin-dependent contraction in a planar-polarized manner. This planar-polarized contraction promotes simultaneous apical constriction and midline convergence of neuroepithelial cells. Together our findings demonstrate that PCP signals confer anisotropic contractility on the AJs, producing cellular forces that promote the polarized bending of the neural plate. PMID:22632972

  8. National Neural Tube Defects Prevention Program in China.

    PubMed

    Zhu, Li; Ling, Hao

    2008-06-01

    Neural tube defects (NTD) are among the most common and devastating birth defects. Annually, in China, between 80,000 and 100,000 pregnancies result in children born with NTD. Northern China has the highest known rate of NTD in the world. Birth defects are becoming the leading cause of infant mortality in the urban and developed areas in China. The results of studies conducted in the early 1990s and early 2000s showed significant geographic and seasonal variations of folate status among Chinese women of childbearing age, with lower serum and red blood cell folate levels in northern China. In the north, 32% to 35% of women had low plasma folate and low red blood cell folate, and folate levels were significantly lower in spring than in fall. Since 1993, Peking University Health Science Center (formerly Beijing Medical University), collaborating with the US Centers for Disease Control and Prevention (CDC), has conducted a large-scale study to evaluate a public health campaign in China among women preparing for marriage in order to determine the effectiveness of daily supplementation of 400 microg of folic acid alone in preventing NTD in both the north and the south of China. The results showed that among the fetuses or infants of the women who took periconceptional folic acid, the reduction in risk of NTD was 85% in the northern region and 40% in the southern region. Daily intake of 400 microg of folic acid may also reduce the risk of nonsyndromic orofacial clefts. We found no evidence that daily consumption of folic acid before and during early pregnancy influenced the risk of miscarriage or twinning. In 2001, the Chinese Ministry of Health and the Chinese Disabled Person Federation released a National Action Plan for Reducing Birth Defects and Disabilities in China for 2002-2010. The Action Plan aims to improve birth outcomes, to reduce infant mortality by reducing the risk of birth defects and disabilities, and to ensure that every baby is born healthy. PMID:18709893

  9. Modeling Anterior Development in Mice: Diet as Modulator of Risk for Neural Tube Defects

    PubMed Central

    Kappen, Claudia

    2014-01-01

    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. PMID:24124024

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

    PubMed

    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. PMID:24124024

  11. Is LMNB1 a Susceptibility Gene for Neural Tube Defects in Humans?

    PubMed Central

    Robinson, Alexis; Partridge, Darren; Malhas, Ashraf; De Castro, Sandra CP; Gustavsson, Peter; Thompson, Dominic N; Vaux, David J; Copp, Andrew J; Stanier, Philip; Bassuk, Alexander G; Greene, Nicholas DE

    2013-01-01

    BACKGROUND Lamins are intermediate filament proteins that form a major component of the nuclear lamina, a protein complex at the surface of the inner nuclear membrane. Numerous clinically diverse conditions, termed laminopathies, have been found to result from mutation of LMNA. In contrast, coding or loss of function mutations of LMNB1, encoding lamin B1, have not been identified in human disease. In mice, polymorphism in Lmnb1 has been shown to modify risk of neural tube defects (NTDs), malformations of the central nervous system that result from incomplete closure of the neural folds. METHODS Mutation analysis by DNA sequencing was performed on all exons of LMNB1 in 239 samples from patients with NTDs from the United Kingdom, Sweden, and United States. Possible functional effects of missense variants were analyzed by bioinformatics prediction and fluorescence in photobleaching. RESULTS In NTD patients, we identified two unique missense variants that were predicted to disrupt protein structure/function and represent putative contributory mutations. Fluorescence loss in photobleaching analysis showed that the A436T variant compromised stability of lamin B1 interaction within the lamina. CONCLUSION The genetic basis of human NTDs appears highly heterogenous with possible involvement of multiple predisposing genes. We hypothesize that rare variants of LMNB1 may contribute to susceptibility to NTDs. Birth Defects Research (Part A) 97:398–402, 2013. © 2013 Wiley Periodicals, Inc. PMID:23733478

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

    PubMed

    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 interactions are of direct relevance to human patients and emphasize the importance of performing comprehensive genetic screens in humans. PMID:25128525

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

    PubMed Central

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

    2014-01-01

    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 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 interactions are of direct relevance to human patients and emphasize the importance of performing comprehensive genetic screens in humans. PMID:25128525

  14. Spontaneous neural tube defects in splotch mice supplemented with selected micronutrients

    SciTech Connect

    Wlodarczyk, Bogdan J. . E-mail: bwlodarczyk@ibt.tamhsc.edu; Tang, Louisa S.; Triplett, Aleata; Aleman, Frank; Finnell, Richard H.

    2006-05-15

    Splotch (Sp/Sp) mice homozygous for a mutation in the Pax3 gene inevitably present with neural tube defects (NTDs), along with other associated congenital anomalies. The affected mutant embryos usually die by gestation days (E) 12-13. In the present study, the effect of modifier genes from a new genetic background (CXL-Sp) and periconceptional supplementation with selected micronutrients (folic acid, 5-formyltetrahydrofolate, 5-methyltetrahydrofolate, methionine, myoinositol, thiamine, thymidine, and {alpha}-tocopherol) was determined with respect to the incidence of NTDs. In order to explore how different exposure parameters (time, dose, and route of compound administration) modulate the beneficial effects of micronutrient supplementation, female mice received either short- or long-term nutrient supplements via enteral or parenteral routes. Embryos were collected on E12.5 and examined for the presence of anterior or posterior NTDs. Additionally, whole mount in situ hybridization studies were conducted in order to reveal/confirm normal expression patterns of the Pax3 gene during neurulation in the wild-type and Sp/Sp homozygous mutant mouse embryos utilized in this study. A strong Pax3 signal was demonstrated in CXL-Sp embryos during neural tube closure (E9.5 to E10.5). The intensity and spatial pattern of expression were similar to other Splotch mutant mice. Of all the micronutrients tested, only supplementation with folic acid or 5-methyltetrahydrofolate rescued the normal phenotype in Sp/Sp embryos. When the folate supplementation dose was increased to 200 mg/kg in the diet, the incidence of rescued splotch homozygotes reached 30%; however, this was accompanied by six-fold increased resorption rate.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26593875

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

    PubMed

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

    2015-01-01

    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. PMID:26593875

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

    PubMed Central

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

    2013-01-01

    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;Vangl2Lp 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 Vangl2Lp 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 Vangl2Lp/+ enhances the Sdc4-null phenotype. This could be mediated via heparan sulfate residues, as Vangl2Lp/+ embryos fail to initiate neural tube closure and develop craniorachischisis (usually seen only in Vangl2Lp/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. PMID:23760952

  18. Roles of planar cell polarity pathways in the development of neural [correction of neutral] tube defects.

    PubMed

    Wu, Gang; Huang, Xupei; Hua, Yimin; Mu, Dezhi

    2011-01-01

    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. PMID:21864354

  19. In toto live imaging of mouse morphogenesis and new insights into neural tube closure

    PubMed Central

    Massarwa, R’ada; Niswander, Lee

    2013-01-01

    In the field of developmental biology, live imaging is a powerful tool for studying, in real time, the dynamic behaviors of tissues and cells during organ formation. Mammals, which develop in utero, have presented a challenge for live imaging. Here, we offer a novel, prolonged and robust live imaging system for visualizing the development of a variety of embryonic tissues in the midgestation mouse embryo. We demonstrate the advantages of this imaging system by following the dynamics of neural tube closure during mouse embryogenesis and reveal extensive movements of the cranial neural tissue that are independent of neural fold zipping. PMID:23175632

  20. Folic acid supplementation for the prevention of neural tube defects. Should it be a priority for developing countries?

    PubMed

    Perez-escamilla, R

    1997-12-01

    Folic acid supplementation during pregnancy has been widely advocated for the prevention of neural tube defects in developing countries. The author of this letter, however, argues that such a strategy is unwarranted and a misuse of scarce resources. Folic acid deficiency is not the primary cause of neural tube defects and the incidence of this defect is similar in developed and developing countries. It has been estimated that folic acid fortification of cereal-based products--an exceedingly difficult, expensive intervention--would prevent only about 1000 neural tube defect cases per year. Moreover, additional folic acid can prevent neural tube defects only if consumed during the periconceptional period. Although women at risk of neural tube defect recurrence are advised to take 4 mg of folic acid per day when they plan to become pregnant, the recommendation for the vast majority of women in developing countries is increased consumption of beans, oranges, and green leafy vegetables. PMID:12293181

  1. Maternal fumonisin exposure as a risk factor for neural tube defects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisins are mycotoxins produced by the fungus F. verticillioides, a common contaminant of maize (corn) worldwide. Maternal consumption of fumonisin B1-contaminated maize during early pregnancy has recently been associated with increased risk for neural tube defects (NTDs) in human populations th...

  2. Periconceptional supplementation with folic acid. Does it prevent neural tube defects?

    PubMed

    Murphy, P A

    1992-01-01

    There has been considerable controversy in recent years concerning the benefit of periconceptional vitamin supplementation in the prevention of neural tube defects. Recent reports of a successful randomized clinical trial have prompted official recommendations for folic acid supplementation in women with a history of an affected pregnancy. Periconceptional supplementation of low-risk women remains controversial. PMID:1538265

  3. Fetotoxicity and neural tube defects in CD1 mice exposed to the mycotoxin Fumonisin B1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisins are mycotoxins that are produced by Fusarium verticillioides and that occur in corn and corn-based foods. Their effects on human health are unclear, however, epidemiological and experimental evidence suggests that they increase the risk of neural tube defects (NTDs) in populations routine...

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

    ERIC Educational Resources Information Center

    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

  5. Placental and neural tube defects after maternal fumonisin or FRY720 exposure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of maize. Increased neural tube defect (NTD) risk is observed in human populations that rely heavily on maize as a dietary staple. FB1 inhibition of ceramide synthase results in elevated sphingoid bases. FTY720 is a sphingoid ...

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

    ERIC Educational Resources Information Center

    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…

  7. Lipid mediators link cells progression with placental and neural tube defects after maternal fumonisin exposure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of maize. Increased risk for neural tube defects (NTDs) is observed in populations that rely on maize as a dietary staple. FB1 inhibits ceramide synthase, resulting in altered pools of biologically active sphingolipids. FB1...

  8. Gene-environment interactions in susceptibility to fumonisin-induced neural tube defects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of corn. In populations that rely on maize-based foods as a dietary staple, consumption of FB1-contaminated food during early pregnancy is associated with increased risk for neural tube defects (NTDs). Administration of FB1 ...

  9. Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background

    PubMed Central

    Ksiazek-Winiarek, Dominika Justyna; Szpakowski, Piotr; Glabinski, Andrzej

    2015-01-01

    Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets. PMID:26229689

  10. Gene transfer of lacZ into avian neural tube and neural crest cells by retroviral infection of grafted embryonic tissues.

    PubMed

    Stocker, K M; Brown, A M; Ciment, G

    1993-01-01

    We describe here a new method for transferring genes into cells of the neural tube and neural crest of early avian embryos in vivo. Using the marker gene lacZ as an example, we infected dissected neural tubes from Hamburger-Hamilton stage 12-13 quail embryos with a replication-defective retrovirus carrying lacZ during a 2 hr period of exposure to the virus in culture. Infected neural tubes were then grafted into uninfected host chicken embryos in ovo and, after continued development for several days, the chimeric embryos were processed for beta-galactosidase histochemistry to identify the progeny of infected cells. We show that virus-infected neural tubes grafted isotopically into the trunk region of host embryos gave rise to cells of both the spinal cord and neural crest. Infected neural crest cells localized within dorsal root ganglia, sympathetic ganglia, peripheral nerves, and within the skin, where they were likely to give rise to melanocytes. These data are consistent with those using other cell marking techniques applied to the neural crest, indicating that retrovirus infection in culture, grafting, and beta-galactosidase expression has a neutral effect on neural crest cell migration and localization. These results indicate the heterospecific grafting of early avian tissues infected with retroviruses carrying foreign genes may be an effective strategy for testing the biological role of various gene products during development. PMID:8380875

  11. Distinct Regulatory Mechanisms Act to Establish and Maintain Pax3 Expression in the Developing Neural Tube

    PubMed Central

    Moore, Steven; Ribes, Vanessa; Terriente, Javier; Wilkinson, David; Relaix, Frédéric; Briscoe, James

    2013-01-01

    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. PMID:24098141

  12. Scaling Pattern to Variations in Size during Development of the Vertebrate Neural Tube.

    PubMed

    Uygur, Aysu; Young, John; Huycke, Tyler R; Koska, Mervenaz; Briscoe, James; Tabin, Clifford J

    2016-04-18

    Anatomical proportions are robustly maintained in individuals that vary enormously in size, both within a species and between members of related taxa. However, the mechanisms underlying scaling are still poorly understood. We have examined this phenomenon in the context of the patterning of the ventral neural tube in response to a gradient of the morphogen Sonic hedgehog (SHH) in the chick and zebra finch, two species that differ in size during the time of neural tube patterning. We find that scaling is achieved, at least in part, by altering the sensitivity of the target cells to SHH and appears to be achieved by modulating the ratio of the repressive and activating transcriptional regulators, GLI2 and GLI3. This mechanism contrasts with previous experimental and theoretical analyses of morphogenic scaling that have focused on compensatory changes in the morphogen gradient itself. PMID:27093082

  13. Adding folate to the contraceptive pill: a new concept for the prevention of neural tube defects.

    PubMed

    Holzgreve, Wolfgang; Pietrzik, Klaus; Koletzko, Berthold; Eckmann-Scholz, Christel

    2012-09-01

    Although it is proven for a long time that folic acid supplementation in the periconceptional period can prevent neural tube defects (NTDs) effectively, all measures taken so far including food fortification and awareness campaigns so far had only limited success. Since more than 50% of the pregnant women in Europe get pregnant after they have used oral contraceptives (OCs) before, OCs are an ideal vehicle to increase not only the awareness for periconceptional folate application, but they can also help to bridge the gap between the recognition of a pregnancy and closure of the neural tube which is before day 26. In order to reach a truly protective folate level at the critical time period during pregnancy, now OCs are available which contain metafolin. The availability of this innovative type of OC will significantly reduce the number of NTDs. PMID:22272814

  14. Particulate acetylcholinesterase in amniotic fluid and its implications for neural tube defect screening.

    PubMed

    Webb, B; Richardson, S J; Garry, R; Atkins, J

    1981-09-01

    Acetylcholinesterase activity in mid-trimester amniotic fluid has been determined by a quantitative spectrophotometric method and a qualitative electrophoretic technique in a limited (76 samples) retrospective study. Differential centrifugation studies on amniotic fluid from normal pregnancies demonstrated the presence of particle-associated acetylcholinesterase sedimenting only at relatively high centrifugal forces. It is postulated that this particle-associated activity was a contributory factor to an observed false-positive incidence of 6.6% when quantitative acetylcholinesterase measurement was used to discriminate between normal pregnancies and those associated with neural tube defects. Discrimination on the basis of electrophoretic analysis of acetylcholinesterase resulted in no misclassification of pregnancies. Particulate acetylcholinesterase would not be expected to influence the interpretation of the electrophoretic pattern due to its size-related exclusion from gel pores. The implication of these observations in the accurate prenatal diagnosis of neural tube defects is discussed. PMID:7305259

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

    PubMed Central

    Ren, Ai-Guo

    2015-01-01

    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 28th 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. PMID:26261765

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

    PubMed

    Ren, Ai-Guo

    2015-08-01

    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. PMID:26261765

  17. An association study between SUFU gene polymorphisms and neural tube defects.

    PubMed

    Lu, Xiaolin; Wang, Zhen; Wang, Jianhua; Shangguan, Shaofang; Bao, Yihua; Lu, Ping; Wang, Li

    2014-06-01

    Neural tube defects (NTDs) in mammals are rooted in aberrant neural tube closure during early embryogenesis, which is caused by multiple environmental and genetic factors. The Sonic Hedgehog pathway is involved in the induction of the floor plate and participates in formation of the neural tube. Mutation of the suppressor of fused gene (SUFU), an essential repressor of Sonic Hedgehog signaling pathway, can result in NTDs. A case-control study was designed to compare the frequencies of the polymorphism at four sites in the SUFU gene in control and NTDs group, as well as in subtype groups, including anencephaly, spina bifida and encephalocele. We also explored the association between polymorphism and NTDs risk in a high prevalence population in China. Rs10786691, but not the other three SNPs, had an association between polymorphisms and NTDs. The heterozygous AG allele of rs10786691 was significantly related with NTDs and encephalocele (OR = 1.60, 95% CI: 1.04-2.48, p = 0.034; OR = 2.83, 95% CI: 1.07-7.47, p = 0.036). In female but not male fetuses, the AG genotype of rs10786691 increased the risk of NTDs (OR = 1.88, 95% CI: 1.03-3.41, p = 0.040). The SUFU rs10786691 A>G polymorphism may be a potential risk factor for NTDs and encephalocele in this high-risk population, but the association between the polymorphism and NTDs was probably influenced by gender. PMID:24070372

  18. Genomic DNA Hypomethylation Is Associated with Neural Tube Defects Induced by Methotrexate Inhibition of Folate Metabolism

    PubMed Central

    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. PMID:25822193

  19. [The effect of folic acid fortification on the reduction of neural tube defects].

    PubMed

    Santos, Leonor Maria Pacheco; Pereira, Michelle Zanon

    2007-01-01

    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 (< 0.6 mg/day). In 2004, the National Health Surveillance Agency (ANVISA) mandated the fortification of corn meal and wheat flour with folic acid (0.15 mg/100g). The National Family Budget Survey estimated the average amount of bread/flour products available in households as 106.1g/day (contributing with 0.16 mg folic acid/day). However, while in the South of the country the supply was 144 g/day, in the North and Central West it barely reached 70 g/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. PMID:17187100

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

    PubMed

    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 (<400 g/day, ?400 g/day), with a slightly higher risk in the ?400-g/day stratum. Our findings support previously reported positive associations between neural tube defects and periconceptional exposure to NSDs containing a secondary or tertiary amine or amide. PMID:26424074

  1. Mini-review: toward understanding mechanisms of genetic neural tube defects in mice.

    PubMed

    Harris, M J; Juriloff, D M

    1999-11-01

    We review the data from studies of mouse mutants that lend insight to the mechanisms that lead to neural tube defects (NTDs). Most of the 50 single-gene mutations that cause neural tube defects (NTDs) in mice also cause severe embryonic-lethal syndromes, in which exencephaly is a nonspecific feature. In a few mutants (e.g., Trp53, Macs, Mlp or Sp), other defects may be present, but affected fetuses can survive to birth. Multifactorial genetic causes, as are present in the curly tail stock (15-20% spina bifida), or the SELH/Bc strain (15-20% exencephaly), lead to nonsyndromic NTDs. The mutations indicate that "spina bifida occulta," a dorsal gap in the vertebral arches over an intact neural tube, is usually genetically and developmentally unrelated to exencephaly or "spina bifida" (aperta). Almost all exencephaly or spina bifida aperta of genetic origin is caused by failure of neural fold elevation. The developmental mechanisms in genetic NTDs are considered in terms of distinct rostro-caudal zones along the neural folds that likely differ in mechanism of elevation. Failure of elevation leads to: split face (zone A), exencephaly (zone B), rachischisis (all of zone D), or spina bifida (caudal zone D). The developmental mechanisms leading to these genetic NTDs are heterogeneous, even within one zone. At the tissue level, the mutants show that the mechanism of failure of elevation can involve, e.g., (1) slow growth of adjacent tethered tissue (curly tail), (2) defective forebrain mesenchyme (Cart1 or twist), (3) defective basal lamina in surface ectoderm (Lama5), (4) excessive breadth of floorplate and notochord (Lp), (5) abnormal neuroepithelium (Apob, Sp, Tcfap2a), (6) morphological deformation of neural folds (jmj), (7) abnormal neuroepithelial and neural crest cell gap-junction communication (Gja1), or (8) incomplete compensation for a defective step in the elevation sequence (SELH/Bc). At the biochemical level, mutants suggest involvement of: (1) faulty regulation of apoptosis (Trp53 or p300), (2) premature differentiation (Hes1), (3) disruption of actin function (Macs or Mlp), (4) abnormal telomerase complex (Terc), or (5) faulty pyrimidine synthesis (Sp). The NTD preventative effect of maternal dietary supplementation is also heterogeneous, as demonstrated by: (1) methionine (Axd), (2) folic acid or thymidine (Sp), or (3) inositol (curly tail). The heterogeneity of mechanism of mouse NTDs suggests that human NTDs, including the common nonsyndromic anencephaly or spina bifida, may also reflect a variety of genetically caused defects in developmental mechanisms normally responsible for elevation of the neural folds. PMID:10525207

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

    PubMed Central

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

    2015-01-01

    Summary 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. PMID:26079577

  3. Arsenate-induced maternal glucose intolerance and neural tube defects in a mouse model

    SciTech Connect

    Hill, Denise S.; Wlodarczyk, Bogdan J.; Mitchell, Laura E.; Finnell, Richard H.

    2009-08-15

    Background: Epidemiological studies have linked environmental arsenic (As) exposure to increased type 2 diabetes risk. Periconceptional hyperglycemia is a significant risk factor for neural tube defects (NTDs), the second most common structural birth defect. A suspected teratogen, arsenic (As) induces NTDs in laboratory animals. Objectives: We investigated whether maternal glucose homeostasis disruption was responsible for arsenate-induced NTDs in a well-established dosing regimen used in studies of arsenic's teratogenicity in early neurodevelopment. Methods: We evaluated maternal intraperitoneal (IP) exposure to As 9.6 mg/kg (as sodium arsenate) in LM/Bc/Fnn mice for teratogenicity and disruption of maternal plasma glucose and insulin levels. Selected compounds (insulin pellet, sodium selenate (SS), N-acetyl cysteine (NAC), L-methionine (L-Met), N-tert-Butyl-{alpha}-phenylnitrone (PBN)) were investigated for their potential to mitigate arsenate's effects. Results: Arsenate caused significant glucose elevation during an IP glucose tolerance test (IPGTT). Insulin levels were not different between arsenate and control dams before (arsenate, 0.55 ng/dl; control, 0.48 ng/dl) or after glucose challenge (arsenate, 1.09 ng/dl; control, 0.81 ng/dl). HOMA-IR index was higher for arsenate (3.9) vs control (2.5) dams (p = 0.0260). Arsenate caused NTDs (100%, p < 0.0001). Insulin pellet and NAC were the most successful rescue agents, reducing NTD rates to 45% and 35%. Conclusions: IPGTT, insulin assay, and HOMA-IR results suggest a modest failure of glucose stimulated insulin secretion and insulin resistance characteristic of glucose intolerance. Insulin's success in preventing arsenate-induced NTDs provides evidence that these arsenate-induced NTDs are secondary to elevated maternal glucose. The NAC rescue, which did not restore maternal glucose or insulin levels, suggests oxidative disruption plays a role.

  4. ARSENATE-INDUCED MATERNAL GLUCOSE INTOLERANCE AND NEURAL TUBE DEFECTS IN A MOUSE MODEL

    PubMed Central

    Hill, Denise S.; Wlodarczyk, Bogdan J.; Mitchell, Laura E.; Finnell, Richard H.

    2009-01-01

    Background Epidemiological studies have linked environmental arsenic (As) exposure to increased type 2 diabetes risk. Periconceptional hyperglycemia is a significant risk factor for neural tube defects (NTDs), the second most common structural birth defect. A suspected teratogen, arsenic (As) induces NTDs in laboratory animals. Objectives We investigated whether maternal glucose homeostasis disruption was responsible for arsenate-induced NTDs in a well-established dosing regimen used in studies of arsenic’s teratogenicity in early neurodevelopment. Methods We evaluated maternal intraperitoneal (I.P.) exposure to As 9.6 mg/kg (as sodium arsenate) in LM/Bc/Fnn mice for teratogenicity and disruption of maternal plasma glucose and insulin levels. Selected compounds (insulin pellet, sodium selenate (SS), N-acetyl cysteine (NAC), L-methionine (L-Met), N-tert-Butyl-α-phenylnitrone (PBN)) were investigated for their potential to mitigate arsenate’s effects. Results Arsenate caused significant glucose elevation during an I.P. glucose tolerance test (IPGTT). Insulin levels were not different between arsenate and control dams before (arsenate, 0.55 ng/dl; control, 0.48 ng/dl) or after glucose challenge (arsenate, 1.09 ng/dl; control, 0.81 ng/dl). HOMA-IR index was higher for arsenate (3.9) vs control (2.5) dams (p=0.0260). Arsenate caused NTDs (100%, p<0.0001). Insulin pellet and NAC were the most successful rescue agents, reducing NTD rates to 45% and 35%. Conclusions IPGTT, insulin assay, and HOMA-IR results suggest a modest failure of glucose stimulated insulin secretion and insulin resistance characteristic of glucose intolerance. Insulin’s success in preventing arsenate-induced NTDs provides evidence that these arsenate-induced NTDs are secondary to elevated maternal glucose. The NAC rescue, which did not restore maternal glucose or insulin levels, suggests oxidative disruption plays a role. PMID:19446573

  5. Untargeted Metabolite Profiling of Murine Embryos to Reveal Metabolic Perturbations Associated with Neural Tube Closure Defects

    PubMed Central

    Hansler, Alex; Chen, Qiuying; Gray, Jason D.; Ross, M. Elizabeth; Finnell, Richard H.; Gross, Steven S.

    2014-01-01

    Background Neural tube closure defects (NTDs) are among the most common congenital malformation in human, typically presenting in liveborns as spina bifida. At least 240 gene mutations in mouse are known to increase the risk of NTD. There is a growing appreciation that environmental factors significantly contribute to NTD expression, and that NTDs likely arise from complex gene-environment interactions. Because maternal folic acid supplementation reduces human NTD risk in some populations by 60–70%, it is likely that NTD predisposition is often associated with a defect in folate-dependent one-carbon metabolism. A comprehensive, untargeted metabolic survey of NTD-associated changes in embryo metabolism would provide a valuable test of this assumption. We sought to establish a metabolic profiling platform that is capable of broadly assessing metabolic aberrations associated with NTD-promoting gene mutations in early-stage mouse embryos. Methods An LC/MS-based untargeted metabolite profiling platform was employed to broadly identify significant differences in small molecule levels (50 – 1,000 Da) in NTD-affected E9.5 mouse embryos (Lrp6−/−) vs. unaffected (Lrp6+/+) control embryos. Conclusion Results provide proof-of-principal feasibility for the broad survey of the metabolome of individual E9.5 mouse embryos and identification of metabolic changes associated with NTDs and gene mutations. Levels of 30 different metabolites were altered in association with Lrp6 gene deletion. Some metabolites link to folate-dependent one-carbon transfer reactions, as anticipated, while others await structure elucidation and pathway integration. Whole-Embryo Metabolomics offers the potential to identify metabolic changes in genetically determined NTD-prone embryos. PMID:25115437

  6. When folic acid fails: Insights from 20 years of neural tube defect surveillance in South Carolina.

    PubMed

    Bupp, Caleb P; Sarasua, Sara M; Dean, Jane H; Stevenson, Roger E

    2015-10-01

    Neural tube defects (NTDs) are the most common of the severe malformations of the brain and spinal cord. Increased maternal intake of folic acid (FA) during the periconceptional period is known to reduce NTD risk. Data from 1046 NTD cases in South Carolina were gathered over 20 years of surveillance. It was possible to determine maternal periconceptional FA use in 615 NTD-affected pregnancies. In 163 occurrent (26.9%) and two recurrent (22%) NTD cases, the mothers reported periconceptional FA use. These women were older and more likely to be white. Maternal periconceptional FA usage was reported in 40.4% of cases of spina bifida with other anomalies but in only 25.2% of isolated spina bifida cases (P = 0.02). This enrichment for associated anomalies was not noted among cases of anencephaly or of encephalocele. Among the 563 subsequent pregnancies to mothers with previous NTD-affected pregnancies, those taking FA had a 0.4% NTD recurrence rate, but the recurrence without FA was 8.5%. NTDs with other associated findings were less likely to be prevented by FA, suggesting there is a background NTD rate that cannot be further reduced by FA. Nonetheless, the majority (73.9%) of NTDs in pregnancies in which the mothers reported periconceptional FA use were isolated NTDs of usual types. Cases in which FA failed in prevention of NTDs provide potential areas for further study into the causation of NTDs. The measures and techniques implemented in South Carolina can serve as an effective and successful model for prevention of NTD occurrence and recurrence. PMID:26108864

  7. Dietary folate, but not choline, modifies neural tube defect risk in Shmt1 knockout mice12345

    PubMed Central

    Beaudin, Anna E; Abarinov, Elena V; Malysheva, Olga; Perry, Cheryll A; Caudill, Marie; Stover, Patrick J

    2012-01-01

    Background: Low dietary choline intake has been proposed to increase the risk of neural tube defects (NTDs) in human populations. Mice with reduced Shmt1 expression exhibit a higher frequency of NTDs when placed on a folate- and choline-deficient diet and may represent a model of human NTDs. The individual contribution of dietary folate and choline deficiency to NTD incidence in this mouse model is not known. Objective: To dissociate the effects of dietary folate and choline deficiency on Shmt1-related NTD sensitivity, we determined NTD incidence in embryos from Shmt1-null dams fed diets deficient in either folate or choline. Design: Shmt1+/+ and Shmt1−/− dams were maintained on a standard AIN93G diet (Dyets), an AIN93G diet lacking folate (FD), or an AIN93G diet lacking choline (CD). Virgin Shmt1+/+ and Shmt1−/− dams were crossed with Shmt1+/− males, and embryos were examined for the presence of NTDs at embryonic day (E) 11.5 or E12.5. Results: Exencephaly was observed only in Shmt1−/− embryos isolated from dams maintained on the FD diet (P = 0.004). Approximately 33% of Shmt1−/−embryos (n = 18) isolated from dams maintained on the FD diet exhibited exencephaly. NTDs were not observed in any embryos isolated from dams maintained on the CD (n = 100) or control (n = 152) diets or in any Shmt1+/+ (n = 78) or Shmt1+/− embryos (n = 182). Conclusion: Maternal folate deficiency alone is sufficient to induce NTDs in response to embryonic Shmt1 disruption. PMID:22134951

  8. Maternal vitamin levels in pregnancies affected by congenital malformations other than neural tube defects

    PubMed Central

    Sutton, Marie; Mills, James L.; Molloy, Anne M.; Troendle, James F.; Brody, Lawrence C.; Conley, Mary; Mc Donnell, Robert; Scott, John M.; Kirke, Peadar N.

    2012-01-01

    Background Periconceptional use of folic acid prevents most neural tube defects (NTDs). Whether folic acid and/or multivitamins can prevent other congenital anomalies is not clear. This study tested whether maternal blood levels of folate and vitamin B12 in pregnancies affected by congenital malformations excluding NTDs are lower when compared to non-affected pregnancies. Methods We measured pregnancy red cell folate (RCF), vitamin B12, and homocysteine (tHcy) concentrations in blood samples taken at the first antenatal clinic in Dublin maternity hospitals in 1986–1990 when vitamin supplementation was rare. The cases were mothers who delivered a baby with a congenital malformation other than NTD identified by the Dublin EUROCAT Registry; controls were a systematic sample of mothers of offspring without congenital malformations from the same hospitals in the same time period. Results The median maternal levels of RCF and tHcy did not differ significantly between cases and controls for any of the congenital malformation groups examined (RCF: all malformations 275.9 ug/L v controls 271.2; p=0.77; tHcy: all malformations 7.5 umol/L v controls 7.6; p=0.57). In an unadjusted analysis vitamin B12 was significantly higher in case-mothers whose babies had cleft palate only (p=0.006), musculoskeletal malformations (p=0.034) and midline defects (p=0.039) but not after adjustment for multiple testing. Conclusions Our data suggest that low maternal folate and B12 levels or high tHcy levels in early pregnancy are not associated with all congenital malformations excluding NTDs. Fortification with folic acid or B12 may not have a beneficial effect in the prevention of these anomalies. PMID:21591245

  9. Uncoupling Protein 2 Polymorphisms as Risk Factors for Neural Tube Defects

    PubMed Central

    Mitchell, Adam; Pangilinan, Faith; VanderMeer, Julie; Molloy, Anne M.; Troendle, James; Conley, Mary; Kirke, Peadar N.; Scott, John M.; Brody, Lawrence C.; Mills, James L.

    2008-01-01

    BACKGROUND: Both environmental and genetic factors are involved in the etiology of neural tube defects (NTDs). Inadequate folate intake and obesity are important environmental risk factors. Several folate-related genetic variants have been identified as risk factors; however, little is known about how genetic variants relate to the increased risk seen in obese women. Uncoupling Protein 2 (UCP2) is an attractive candidate to screen for NTD risk because of its possible role in obesity as well as energy metabolism, type-2 diabetes, and the regulation of reactive oxygen species. Interestingly, a previous study found that a common UCP2 compound homozygous genotype was associated with a threefold increase in NTD risk. METHODS: We evaluated three polymorphisms, −866G>A, A55V, and the 3′UTR 45bp insertion/deletion, as risk factors for NTDs in Irish NTD cases (N=169), their mothers (N=163), their fathers (N=167) and normal control subjects (N=332). RESULTS: Allele and genotype frequencies were not significantly different when comparing NTD mothers, NTD fathers, or affected children to controls. Additionally, the previously reported risk genotype (combined homozygosity of 55VV and 3′UTR 45bp deletion/deletion) was not present at a higher frequency in any NTD group when compared to controls. CONCLUSIONS: In our Irish study population, UCP2 polymorphisms do not influence NTD risk. Moreover, the prevalence of this allele in other populations was similar to the Irish prevalence but far lower than reported in the previous NTD study, suggesting that this previous finding of an association with NTDs might have been due to an unrepresentative study sample. PMID:19137581

  10. A spatial model to predict the incidence of neural tube defects

    PubMed Central

    2012-01-01

    Background Environmental exposure may play an important role in the incidences of neural tube defects (NTD) of birth defects. Their influence on NTD may likely be non-linear; few studies have considered spatial autocorrelation of residuals in the estimation of NTD risk. We aimed to develop a spatial model based on generalized additive model (GAM) plus cokriging to examine and model the expected incidences of NTD and make the inference of the incidence risk. Methods We developed a spatial model to predict the expected incidences of NTD at village level in Heshun County, Shanxi Province, China, a region with high NTD cases. GAM was used to establish linear and non-linear relationships between local covariates and the expected NTD incidences. We examined the following village-level covariates in the model: projected coordinates, soil types, lithodological classes, distance to watershed, rivers, faults and major roads, annual average fertilizer uses, fruit and vegetable production, gross domestic product, and the number of doctors. The residuals from GAM were assumed to be spatially auto-correlative and cokriged with regional residuals to improve the prediction. Our approach was compared with three other models, universal kriging, generalized linear regression and GAM. Cross validation was conducted for validation. Results Our model predicted the expected incidences of NTD well, with a good CV R2 of 0.80. Important predictive factors included the fertilizer uses, locations of the centroid of each village, the shortest distance to rivers and faults and lithological classes with significant spatial autocorrelation of residuals. Our model out-performed the other three methods by 16% or more in term of R2. Conclusions The variance explained by our model was approximately 80%. This modeling approach is useful for NTD epidemiological studies and intervention planning. PMID:23134640

  11. Lulu Regulates Shroom-Induced Apical Constriction during Neural Tube Closure

    PubMed Central

    Chu, Chih-Wen; Gerstenzang, Emma; Ossipova, Olga; Sokol, Sergei Y.

    2013-01-01

    Apical constriction is an essential cell behavior during neural tube closure, but its underlying mechanisms are not fully understood. Lulu, or EPB4.1l5, is a FERM domain protein that has been implicated in apical constriction and actomyosin contractility in mouse embryos and cultured cells. Interference with the function of Lulu in Xenopus embryos by a specific antisense morpholino oligonucleotide or a carboxy-terminal fragment of Lulu impaired apical constriction during neural plate hinge formation. This effect was likely due to lack of actomyosin contractility in superficial neuroectodermal cells. By contrast, overexpression of Lulu RNA in embryonic ectoderm cells triggered ectopic apico-basal elongation and apical constriction, accompanied by the apical recruitment of F-actin. Depletion of endogenous Lulu disrupted the localization and activity of Shroom3, a PDZ-containing actin-binding protein that has also been implicated in apical constriction. Furthermore, Lulu and Shroom3 RNAs cooperated in triggering ectopic apical constriction in embryonic ectoderm. Our findings reveal that Lulu is essential for Shroom3-dependent apical constriction during vertebrate neural tube closure. PMID:24282618

  12. Lulu regulates Shroom-induced apical constriction during neural tube closure.

    PubMed

    Chu, Chih-Wen; Gerstenzang, Emma; Ossipova, Olga; Sokol, Sergei Y

    2013-01-01

    Apical constriction is an essential cell behavior during neural tube closure, but its underlying mechanisms are not fully understood. Lulu, or EPB4.1l5, is a FERM domain protein that has been implicated in apical constriction and actomyosin contractility in mouse embryos and cultured cells. Interference with the function of Lulu in Xenopus embryos by a specific antisense morpholino oligonucleotide or a carboxy-terminal fragment of Lulu impaired apical constriction during neural plate hinge formation. This effect was likely due to lack of actomyosin contractility in superficial neuroectodermal cells. By contrast, overexpression of Lulu RNA in embryonic ectoderm cells triggered ectopic apico-basal elongation and apical constriction, accompanied by the apical recruitment of F-actin. Depletion of endogenous Lulu disrupted the localization and activity of Shroom3, a PDZ-containing actin-binding protein that has also been implicated in apical constriction. Furthermore, Lulu and Shroom3 RNAs cooperated in triggering ectopic apical constriction in embryonic ectoderm. Our findings reveal that Lulu is essential for Shroom3-dependent apical constriction during vertebrate neural tube closure. PMID:24282618

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

    NASA Astrophysics Data System (ADS)

    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.

  14. How to form and close the brain: insight into the mechanism of cranial neural tube closure in mammals.

    PubMed

    Yamaguchi, Yoshifumi; Miura, Masayuki

    2013-09-01

    The development of the embryonic brain critically depends on successfully completing cranial neural tube closure (NTC). Failure to properly close the neural tube results in significant and potentially lethal neural tube defects (NTDs). We believe these malformations are caused by disruptions in normal developmental programs such as those involved in neural plate morphogenesis and patterning, tissue fusion, and coordinated cell behaviors. Cranial NTDs include anencephaly and craniorachischisis, both lethal human birth defects. Newly emerging methods for molecular and cellular analysis offer a deeper understanding of not only the developmental NTC program itself but also mechanical and kinetic aspects of closure that may contribute to cranial NTDs. Clarifying the underlying mechanisms involved in NTC and how they relate to the onset of specific NTDs in various experimental models may help us develop novel intervention strategies to prevent NTDs. PMID:23242429

  15. Signal/background classification in a cosmic ray space experiment by a modular neural system

    NASA Astrophysics Data System (ADS)

    Bellotti, Roberto; Castellano, Marcello; De Marzo, Carlo N.; Satalino, Giuseppe

    1995-04-01

    In the cosmic ray space experiments, the separation of the signal from background is a hard task. Due to the well-known critical conditions that characterize this class of experiments, some changes of the detector performances can be observed during the data taking. As a consequence, differences between the test and real data are found as systematic errors in the classification phase. In this paper, a modular classification system based on neural networks is proposed for the signal/background discrimination task in cosmic ray space experiments, without a priori knowledge of the discriminating feature distributions. The system is composed by two neural modules. The first one is a self organizing map (SOM) that both clusters the real data space in suitable classes of similarity and builds a prototype for each of them; a skilled inspection of the prototypes defines the signal and background. The second one, a multi layer perceptron (MLP) with a single hidden layer, adapts the classification model based on training/test data to the real experimental conditions. The MLP synaptic weights adaptive formation takes into account the labelled real data set as defined in the first system-phase. The modular neural system has been applied in the context of TRAMP-Si experiment, performed on the NASA Balloon-Borne Magnet Facility, for the positron/proton discrimination.

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

    PubMed Central

    Fisk Green, Ridgely; Byrne, Julianne; Crider, Krista S.; Gallagher, Margaret; Koontz, Deborah; Berry, Robert J.

    2013-01-01

    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 19 bp 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 epigenetic mechanisms. PMID:24223580

  17. Neural tube malformations: complex segregation analysis and calculation of recurrence risks.

    PubMed Central

    Lalouel, J M; Morton, N E; Jackson, J

    1979-01-01

    Familial data on neural tube malformations in Great Britain were submitted to segregation analysis under the mixed model. Maternal and fetal factors cannot be discriminated in the absence of substantial bodies of data on spina bifida survivors who reproduce or on half-sibs. Early abortion studies would allow differential mortality in utero to be taken into account. After fitting the mixed and generalised single locus models, it is concluded that the multifactorial model can provisionally be used for calculation of recurrence risks. Pathogenic hypotheses implicating twinning seem to rest on little evidence. PMID:381662

  18. Descriptive epidemiology of neural tube defects, Rochester, New York, 1918-1938.

    PubMed

    Biggar, R J; Mortimer, E A; Haughie, G E

    1976-07-01

    This study examines the secular distribution of births, sex, and age at death of 330 cases of anencephaly and spina bifida and 62 cases of "monstrosity" recorded on City of Rochester death certificates between 1918 and 1938. The results show that death certificates may be used as a source of data (with inherent biases) and that persons diagnosed as monstrosity had similar epidemiologic characteristics to those diagnosed as anencephalic during this period. In Rochester the rise in prevalence at birth of neural tube defects was similar to, and occurred at approximately the same years as, the rises reported in Boston and Providence. PMID:779463

  19. Neural tube defects and their significance in clinical dentistry: a mini review.

    PubMed

    Garg, Anuradha; Utreja, Ashok; Singh, Satinder P; Angurana, Suresh K

    2013-02-01

    Neural tube defects are common congenital malformations that could be apparent at birth or manifested in later stages of life. Morbidity is high in anencephaly, whereas in spina bifida, there are neurological and motor disorders. These defects deserve paramount importance in clinical dentistry. Latex allergy, dental caries, difficulty in mouth opening, and sitting in a dental chair are common problems. There is a high risk of anaphylactic response during anaesthesia. There could be associated craniosynostosis causing maxillary deficiency, and malformed sella turcica might be seen. An association of the defects has been linked with orofacial clefts and Down syndrome. PMID:23255477

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

    PubMed

    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. PMID:25650704

  1. Sibs of probands with neural tube defects--a study in the Federal Republic of Germany.

    PubMed

    Koch, M; Fuhrmann, W

    1985-01-01

    Data for the risk of neural tube defects in sibs of affected children are needed for genetic counselling, for decision on prenatal studies, and for planning of preventive measures. Data have been reported from various populations but were lacking for Germany. This study presents data on the siblings of 240 index patients in the Western part of the Federal Republic of Germany. The prevalence among sibs of affected individuals was found to be 2.6%. This figure agrees well with reports from other countries in Continental Europe and the United States, and fits the expectation of lower recurrence risks in low incidence populations. PMID:3873392

  2. Optimal Combination of Neural Temporal Envelope and Fine Structure Cues to Explain Speech Identification in Background Noise

    PubMed Central

    Moon, Il Joon; Won, Jong Ho; Ives, D. Timothy; Nie, Kaibao; Heinz, Michael G.; Lorenzi, Christian; Rubinstein, Jay T.

    2014-01-01

    The dichotomy between acoustic temporal envelope (ENV) and fine structure (TFS) cues has stimulated numerous studies over the past decade to understand the relative role of acoustic ENV and TFS in human speech perception. Such acoustic temporal speech cues produce distinct neural discharge patterns at the level of the auditory nerve, yet little is known about the central neural mechanisms underlying the dichotomy in speech perception between neural ENV and TFS cues. We explored the question of how the peripheral auditory system encodes neural ENV and TFS cues in steady or fluctuating background noise, and how the central auditory system combines these forms of neural information for speech identification. We sought to address this question by (1) measuring sentence identification in background noise for human subjects as a function of the degree of available acoustic TFS information and (2) examining the optimal combination of neural ENV and TFS cues to explain human speech perception performance using computational models of the peripheral auditory system and central neural observers. Speech-identification performance by human subjects decreased as the acoustic TFS information was degraded in the speech signals. The model predictions best matched human performance when a greater emphasis was placed on neural ENV coding rather than neural TFS. However, neural TFS cues were necessary to account for the full effect of background-noise modulations on human speech-identification performance. PMID:25186758

  3. Modifier locus for exencephaly in Cecr2 mutant mice is syntenic to the 10q25.3 region associated with neural tube defects in humans.

    PubMed

    Davidson, Courtney E; Li, Qian; Churchill, Gary A; Osborne, Lucy R; McDermid, Heather E

    2007-10-22

    Neural tube defects (NTDs), the second most common birth defect in humans, are multifactorial with complex genetic and environmental causes, although the genetic factors are almost completely unknown. In mice, >100 single gene mutations cause NTDs; however, the penetrance in many of these single gene mutant lines is highly dependent on the genetic background. We previously reported that a homozygous Cecr2 mutation on a BALB/c background causes exencephaly at a frequency of 74% compared with 0% on an FVB/N background. We now report that a major genetic modifier on chromosome 19, mapped using whole genome linkage analysis, increases the relative risk of exencephaly by 3.74 times in homozygous BALB embryos vs. BALB/FVB heterozygotes. Scanning electron microscopy revealed that the modifier does not affect the location of neural tube closure site 2, a known murine susceptibility factor for exencephaly. Crossing the Sp (Splotch) mutation in the Pax3 gene onto the FVB/N background for two generations indicated that this resistant strain also decreases the penetrance of spina bifida. The chromosome 19 modifier region corresponds to a linkage region on human chromosome 10q25.3 mapped in a whole genome scan of human NTD families. Since the FVB/N genetic background affects susceptibility to both exencephaly and spina bifida, the human homolog of the chromosome 19 modifier locus may be a better candidate for human NTD susceptibility factors than genes that when mutated actually cause NTDs in mice. PMID:17623803

  4. Estimating the burden of neural tube defects in low– and middle–income countries

    PubMed Central

    Lo, Annie; Polšek, Dora; Sidhu, Simrita

    2014-01-01

    Background To provide an estimate for the burden of neural tube defects (NTD) in low– and middle–income countries (LMIC) and explore potential public health policies that may be implemented. Although effective interventions are available to prevent NTD, there is still considerable childhood morbidity and mortality present in LMIC. Methods A search of Medline, EMBASE, Global Health Library and PubMed identified 37 relevant studies that provided estimates of the burden of NTD in LMIC. Information on burden of total NTD and specific NTD types was separated according to the denominator into two groups: (i) estimates based on the number of live births only; and (ii) live births, stillbirths and terminations. The data was then extracted and analysed. Results The search retrieved NTD burden from 18 countries in 6 WHO regions. The overall burden calculated using the median from studies based on livebirths was 1.67/1000 (IQR = 0.98–3.49) for total NTD burden, 1.13/1000 (IQR = 0.75–1.73) for spina bifida, 0.25/1000 (IQR = 0.08–1.07) for anencephaly and 0.15/1000 (IQR = 0.08–0.23) for encephalocele. Corresponding estimates based on all pregnancies resulting in live births, still births and terminations were 2.55/1000 (IQR = 1.56–3.91) for total NTD burden, 1.04/1000 (IQR = 0.67–2.48) for spina bifida, 1.03/1000 (IQR = 0.67–1.60) for anencephaly and 0.21 (IQR = 0.16–0.28) for encephalocele. This translates into about 190 000neonates who are born each year with NTD in LMIC. Conclusion Limited available data on NTD in LMIC indicates the need for additional research that would improve the estimated burden of NTD and recommend suitable aid policies through maternal education on folic acid supplementation or food fortification. PMID:24976961

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

    PubMed Central

    Zaganjor, Ibrahim; Sekkarie, Ahlia; Tsang, Becky L.; Williams, Jennifer; Razzaghi, Hilda; Mulinare, Joseph; Sniezek, Joseph E.; Cannon, Michael J.; Rosenthal, Jorge

    2016-01-01

    Background 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. Methods and Findings 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%). Conclusions 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. PMID:27064786

  6. Mouse as a model for multifactorial inheritance of neural tube defects.

    PubMed

    Zohn, Irene E

    2012-06-01

    Neural tube defects (NTDs) such as spina bifida and anencephaly are some of the most common structural birth defects found in humans. These defects occur due to failures of neurulation, a process where the flat neural plate rolls into a tube. In spite of their prevalence, the causes of NTDs are poorly understood. The multifactorial threshold model best describes the pattern of inheritance of NTDs where multiple undefined gene variants interact with environmental factors to cause an NTD. To date, mouse models have implicated a multitude of genes as required for neurulation, providing a mechanistic understanding of the cellular and molecular pathways that control neurulation. However, the majority of these mouse models exhibit NTDs with a Mendelian pattern of inheritance. Still, many examples of multifactorial inheritance have been demonstrated in mouse models of NTDs. These include null and hypomorphic alleles of neurulation genes that interact in a complex fashion with other genetic mutations or environmental factors to cause NTDs. These models have implicated several genes and pathways for testing as candidates for the genetic basis of NTDs in humans, resulting in identification of putative pathogenic mutations in some patients. Mouse models also provide an experimental paradigm to gain a mechanistic understanding of the environmental factors that influence NTD occurrence, such as folic acid and maternal diabetes, and have led to the discovery of additional preventative nutritional supplements such as inositol. This review provides examples of how multifactorial inheritance of NTDs can be modeled in the mouse. PMID:22692891

  7. Incidence and Risk Factors of Neural Tube Defects in Kashan, Central Iran

    PubMed Central

    TALEBIAN, Ahmad; SOLTANI, Babak; SEHAT, Mojtaba; ZAHEDI, Abolfazl; NOORIAN, Akram; TALEBIAN, Motahhareh

    2015-01-01

    Objective Neural tube defects (NTDs) are the most common congenital defects of central nervous system due to neural tube closure deficit during the third and fourth weeks of gestational age. Our study was performed to detect the incidence and risk factors of NTDs in Kashan, center of Iran. Material & Methods This case-control study was done on all pregnancies with NTD affected neonates (n=91) and 209 pregnancies with normal neonates from February 2007 to December 2012 in three hospitals in Kashan, center of Iran. Annual and the mean incidence of NTDs were calculated. Risk factors including neonatal gender, maternal age, gravidity, maternal abortion history, maternal gestational diabetes (GDM), folic acid use, familial marriage, maternal body mass index (BMI), birth season and family history of NTDs were evaluated by interview with mothers. Univariate and multivariate logistic regression were used to analyze the risk factors. Results The mean incidence of NTDs was 2.33 per 1000 births. The multivariate analysis indicated that maternal history of abortion (OR: 4.9, CI: 1.9-12.8), and maternal obesity (OR: 5.4, CI: 1.3-21.8) were significantly associated with NTDs. Conclusion Maternal history of abortion and BMI were the major risk factors of NTDs. PMID:26401153

  8. Neural Tube Defects and Atypical Deletion on 22q11.2

    PubMed Central

    Leoni, Chiara; Stevenson, David A.; Geiersbach, Katherine B.; Paxton, Christian N.; Krock, Bryan L.; Mao, Rong; Rope, Alan F.

    2014-01-01

    The 22q11.2 deletion syndrome (22q11.2DS) is a common microdeletion disorder. Most of the patients show the common 3 Mb deletion but proximal 1.5 Mb deletion and unusual deletions located outside the common deleted region, have been detected particularly with the advance of comparative cytogenomic microarray technologies. The individuals reported in the literature with unusual deletions involving the 22q11 region, showed milder facial phenotypes, decreased incidence of cardiac anomalies and intellectual disability. We describe two sibs with an atypical 0.8 Mb microdeletion of chromosome 22q11 who both showed myelomeningocele and mild facial dysmorphisms. The association between neural tube defect and the clinical diagnosis of Di George anomaly/velocardiofacial syndrome is well documented in the literature, but not all cases had molecular studies to determine breakpoint regions. This report helps to narrow a potential critical region for neural tube defects associated with 22q11 deletions. PMID:25123577

  9. METHYLMERCURY INDUCED TOXICOGENOMIC RESPONSE IN C57 AND SWV MOUSE EMBRYOS UNDERGOING NEURAL TUBE CLOSURE

    PubMed Central

    Robinson, Joshua F.; Griffith, William C.; Yu, Xiaozhong; Hong, Sungwoo; Kim, Euvin; Faustman, Elaine M.

    2010-01-01

    Methylmercury (MeHg) is a developmental neurotoxicant and teratogen and is hypothesized to perturb a wide range of biological processes, like other metals including arsenic (As) and cadmium (Cd). Common inbred mouse strains including C57 (sensitive) and SWV (resistant) display differences in sensitivity to metals such as As and Cd when exposed during neurulation. In this study, we investigated the impact of MeHg on neurulation, assessing for potential differences in sensitivity and associated toxicogenomic response in C57 and SWV mouse embryos. Parallel with morphological assessments of neural tube closure, we evaluated quantitative differences in MeHg-induced alterations in expression between strains at the gene level and within gene-enriched biological processes. Specifically, we observed differing sensitivities to MeHg-induced impacts on neural tube closure between C57 and SWV embryos in a time-dependent manner. These observations correlated with greater impact on the expression of genes associated with development and environmental stress-related pathways in the C57 compared to the SWV. Additional developmental parameters (e.g. mortality, growth effects) evaluated showed mixed significant effects across the two strains and did not support observations of differential sensitivity to MeHg. This study provides potential insights into MeHg-induced mechanisms of developmental toxicity, alterations associated with increased MeHg sensitivity and common biological processes affected by metals in embryos undergoing neurulation. PMID:20493249

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

    PubMed

    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. PMID:24863049

  11. Neural tube defects--disorders of neurulation and related embryonic processes.

    PubMed

    Copp, Andrew J; Greene, Nicholas D E

    2013-01-01

    Neural tube defects (NTDs) are severe congenital malformations affecting 1 in every 1000 pregnancies. 'Open' NTDs result from failure of primary neurulation as seen in anencephaly, myelomeningocele (open spina bifida), and craniorachischisis. Degeneration of the persistently open neural tube in utero leads to loss of neurological function below the lesion level. 'Closed' NTDs are skin-covered disorders of spinal cord structure, ranging from asymptomatic spina bifida occulta to severe spinal cord tethering, and usually traceable to disruption of secondary neurulation. 'Herniation' NTDs are those in which meninges, with or without brain or spinal cord tissue, become exteriorized through a pathological opening in the skull or vertebral column (e.g., encephalocele and meningocele). NTDs have multifactorial etiology, with genes and environmental factors interacting to determine individual risk of malformation. While over 200 mutant genes cause open NTDs in mice, much less is known about the genetic causation of human NTDs. Recent evidence has implicated genes of the planar cell polarity signaling pathway in a proportion of cases. The embryonic development of NTDs is complex, with diverse cellular and molecular mechanisms operating at different levels of the body axis. Molecular regulatory events include the bone morphogenetic protein and Sonic hedgehog pathways which have been implicated in control of neural plate bending. Primary prevention of NTDs has been implemented clinically following the demonstration that folic acid (FA), when taken as a periconceptional supplement, can prevent many cases. Not all NTDs respond to FA, however, and adjunct therapies are required for prevention of this FA-resistant category. PMID:24009034

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

    PubMed

    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. PMID:26475080

  13. Restricted Pax3 Deletion within the Neural Tube Results in Congenital Hydrocephalus

    PubMed Central

    Zhou, Hong-Ming; Conway, Simon J.

    2016-01-01

    Congenital hydrocephalus is a common birth-defect whose developmental origins are poorly understood. Pax3-null mutants show defects in myogenesis, neural tube closure, neural crest morphogenesis, and heart development that, consequently, results in embryonic lethality. Here we demonstrate that conditional deletion of the mouse Pax3 transcription factor results in fully-penetrant congenital obstructive hydrocephalus. To identify the role of Pax3 during cranial development, we deleted Pax3 within the neuroepithelium (via Pax7−Cre), in the neural crest (via P0-Cre), and in both the neuroepithelium and the neural crest (via Wnt1-Cre). Only conditional mutants generated using Pax7−Cre or Wnt1-Cre developed early onset congenital hydrocephalus due to stenosis of the third ventricle, suggesting that loss of neuroepithelial Pax3 is sufficient to disturb third ventricle morphogenesis. Dilation of lateral ventricles occurs as early as E14.5, and lineage-mapping revealed that the neuroepithelial cells in the conditional mutants are present, but fail to undergo normal differentiation at the stenotic site. Concomitant with a narrowing of the mutant third ventricle, we detected ectopic apoptosis, reduced proliferation, and abnormal β-catenin localization. Furthermore, consistent with the overlapping expression pattern of Pax3 and Pax7 in early cranial neuroepithelium, we demonstrated a combinatorial role, as compound Pax3/Pax7 heterozygotes display partially-penetrant congenital hydrocephalus. These murine data provide an experimental paradigm underpinning clinical observations of the presence of PAX3 mutations in some hydrocephalic patients. PMID:26949601

  14. A neural mechanism for background information-gated learning based on axonal-dendritic overlaps.

    PubMed

    Mainetti, Matteo; Ascoli, Giorgio A

    2015-03-01

    Experiencing certain events triggers the acquisition of new memories. Although necessary, however, actual experience is not sufficient for memory formation. One-trial learning is also gated by knowledge of appropriate background information to make sense of the experienced occurrence. Strong neurobiological evidence suggests that long-term memory storage involves formation of new synapses. On the short time scale, this form of structural plasticity requires that the axon of the pre-synaptic neuron be physically proximal to the dendrite of the post-synaptic neuron. We surmise that such "axonal-dendritic overlap" (ADO) constitutes the neural correlate of background information-gated (BIG) learning. The hypothesis is based on a fundamental neuroanatomical constraint: an axon must pass close to the dendrites that are near other neurons it contacts. The topographic organization of the mammalian cortex ensures that nearby neurons encode related information. Using neural network simulations, we demonstrate that ADO is a suitable mechanism for BIG learning. We model knowledge as associations between terms, concepts or indivisible units of thought via directed graphs. The simplest instantiation encodes each concept by single neurons. Results are then generalized to cell assemblies. The proposed mechanism results in learning real associations better than spurious co-occurrences, providing definitive cognitive advantages. PMID:25767887

  15. A Neural Mechanism for Background Information-Gated Learning Based on Axonal-Dendritic Overlaps

    PubMed Central

    Mainetti, Matteo; Ascoli, Giorgio A.

    2015-01-01

    Experiencing certain events triggers the acquisition of new memories. Although necessary, however, actual experience is not sufficient for memory formation. One-trial learning is also gated by knowledge of appropriate background information to make sense of the experienced occurrence. Strong neurobiological evidence suggests that long-term memory storage involves formation of new synapses. On the short time scale, this form of structural plasticity requires that the axon of the pre-synaptic neuron be physically proximal to the dendrite of the post-synaptic neuron. We surmise that such “axonal-dendritic overlap” (ADO) constitutes the neural correlate of background information-gated (BIG) learning. The hypothesis is based on a fundamental neuroanatomical constraint: an axon must pass close to the dendrites that are near other neurons it contacts. The topographic organization of the mammalian cortex ensures that nearby neurons encode related information. Using neural network simulations, we demonstrate that ADO is a suitable mechanism for BIG learning. We model knowledge as associations between terms, concepts or indivisible units of thought via directed graphs. The simplest instantiation encodes each concept by single neurons. Results are then generalized to cell assemblies. The proposed mechanism results in learning real associations better than spurious co-occurrences, providing definitive cognitive advantages. PMID:25767887

  16. Integration of Signals along Orthogonal Axes of the Vertebrate Neural Tube Controls Progenitor Competence and Increases Cell Diversity

    PubMed Central

    Sasai, Noriaki; Kutejova, Eva; Briscoe, James

    2014-01-01

    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. PMID:25026549

  17. Neural tube defects, maternal cohorts, and age: a pointer to aetiology.

    PubMed Central

    Bound, J P; Francis, B J; Harvey, P W

    1991-01-01

    The effects of maternal year of birth and age on the declining prevalence of neural tube defects after 1972-3 were examined using 403 cases ascertained in a prospective study in the Fylde of Lancashire during 1957-89. Matched case-control data were analysed using conditional logistic regression analysis. The risk of an anencephalic baby was significantly greater for older mothers, but changes in the maternal age distribution in the population did not appear to be relevant to the recent decline in prevalence. Antenatal diagnosis and termination of pregnancy was the major cause. Mothers born before 1950 were at significantly greater risk of producing a baby with spina bifida or cranium bifidum. We suggest that abandonment of mercury as a therapeutic agent for infants in the early 1950s is a possible factor in the current decline of these malformations. PMID:1953007

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

    PubMed Central

    Yaliwal, Laxmi V.; Desai, Rathnamala M.

    2012-01-01

    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. PMID:22754237

  19. Recurrence risks for neural tube defects in a genetic counseling clinic population.

    PubMed Central

    Seller, M J

    1981-01-01

    The recurrence of neural tube defects (NTD) in the sib following the index case of all patients who consulted the South-East Thames Regional Health Authority Genetics Centre in the period 1972 to mid-1979 was calculated. A total of 1037 consecutive patients was studied, of whom 958 (93%) were traced. The overall recurrence was 3.44% (1 in 29). However, if the index case was the first affected child in the family, the recurrence in the next sib was 3.15% (1 in 32), and if it was the second affected child, the recurrence was 11.76% (1 in 9). These figures give an indication of the actual recurrence among the 'selected' population who consult a genetic advice centre, and are somewhat, but not significantly, different from figures for the general NTD population, which have been derived from studies of whole families. PMID:7277415

  20. Folic acid for the prevention of neural tube defects. American Academy of Pediatrics. Committee on Genetics.

    PubMed

    1999-08-01

    The American Academy of Pediatrics endorses the US Public Health Service (USPHS) recommendation that all women capable of becoming pregnant consume 400 microgram of folic acid daily to prevent neural tube defects (NTDs). Studies have demonstrated that periconceptional folic acid supplementation can prevent 50% or more of NTDs such as spina bifida and anencephaly. For women who have previously had an NTD-affected pregnancy, the Centers for Disease Control and Prevention (CDC) recommends increasing the intake of folic acid to 4000 microgram per day beginning at least 1 month before conception and continuing through the first trimester. Implementation of these recommendations is essential for the primary prevention of these serious and disabling birth defects. Because fewer than 1 in 3 women consume the amount of folic acid recommended by the USPHS, the Academy notes that the prevention of NTDs depends on an urgent and effective campaign to close this prevention gap. PMID:10429019

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

    PubMed

    van der Linden, Ivon J M; Afman, Lydia A; Heil, Sandra G; Blom, Henk J

    2006-05-01

    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 C677T single-nucleotide polymorphism (SNP) in the methylenetetrahydrofolate reductase (MTHFR) gene, and the observation that elevated plasma homocysteine levels are associated with NTD, research has focused on genetic variation in genes encoding for enzymes of folate metabolism and the closely-related homocysteine metabolism. In the present review relevant SNP in genes that code for enzymes involved in folate transport and uptake, the folate cycles and homocysteine metabolism are summarised and the importance of these SNP discussed in relation to NTD risk. PMID:16672082

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

    PubMed

    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. PMID:26627544

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

    PubMed Central

    Zhu, Xiaoqing; Li, Bo; Ai, Zongyong; Xiang, Zheng; Zhang, Kunshang; Qiu, Xiaoyan; Chen, Yongchang; Li, Yuemin; Rizak, Joshua D.; Niu, Yuyu; Hu, Xintian; Sun, Yi Eve; Ji, Weizhi; Li, Tianqing

    2015-01-01

    Summary 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. PMID:26584544

  4. The role of maternal reproductive history in the aetiology of neural tube defects.

    PubMed

    Bianca, S; Bianca, M; Bonaffini, F; Ettore, G

    2002-02-01

    The contribution of environmental factors to the aetiology of neural tube defects (NTD) has been stressed over recent years and many different risk factors have been proposed. We evaluated the reproductive history of 113 NTD cases to investigate the possible role of maternal age, gestational age, sex, parity and previous pregnancy. Our results show that parity and previous spontaneous abortion can be considered as risk factors for NTD and that an accurate evaluation of reproductive history can be useful for genetic counselling. The known benefits of periconceptional intervention in reducing the incidence of NTD in high risk populations, together with our results, means that mothers with a positive reproductive history for spontaneous abortion and for multiparity are ideal subjects for folic acid periconceptional management. PMID:11812184

  5. Folic Acid Supplementation and Pregnancy: More Than Just Neural Tube Defect Prevention

    PubMed Central

    Greenberg, James A; Bell, Stacey J; Guan, Yong; Yu, Yan-hong

    2011-01-01

    Folate (vitamin B9) is an essential nutrient that is required for DNA replication and as a substrate for a range of enzymatic reactions involved in amino acid synthesis and vitamin metabolism. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus. Folate deficiency has been associated with abnormalities in both mothers (anemia, peripheral neuropathy) and fetuses (congenital abnormalities). This article reviews the metabolism of folic acid, the appropriate use of folic acid supplementation in pregnancy, and the potential benefits of folic acid, as well as the possible supplementation of l-methylfolate for the prevention of pregnancy-related complications other than neural tube defects. PMID:22102928

  6. Gastric bypass: a risk factor for neural tube defects? Case report.

    PubMed

    Moliterno, Jennifer A; DiLuna, Michael L; Sood, Shreya; Roberts, Kurt E; Duncan, Charles C

    2008-05-01

    Gastric bypass surgery has become a safe and acceptable surgical weight loss treatment for individuals who suffer from morbid obesity. Patients who undergo this procedure are subject to vitamin deficiencies due to an iatrogenic malabsorptive state. Folate, a vitamin known for its role in the prevention of neural tube defects (NTDs), can be part of the deficiency spectrum resulting from this procedure. The authors describe the case of a woman who was nonadherent to multivitamin treatment after undergoing gastric bypass surgery. Her lack of understanding and appreciation of the relationship between gastric bypass surgery, folate deficiency, and NTDs may have contributed to her noncompliance with daily multivitamin consumption. As a result, her potential problems with folate absorption could have contributed to her subsequently giving birth to a child with a myelomeningocele. Thus, patient awareness and counseling along with aggressive vitamin supplementation among this particular population may help prevent the occurrence of NTDs after gastric bypass surgery. PMID:18447680

  7. A familial association between twinning and upper-neural tube defects.

    PubMed Central

    Garabedian, B. H.; Fraser, F. C.

    1994-01-01

    An increased twinning rate has been observed in the near relatives (sibs, parents, and aunts and uncles) of probands with neural tube defects (NTDs) occurring at the level of the 11th thoracic vertebra and above (upper NTDs). The twin rate was more than double that of the near relatives of probands with lower NTDs and of those of probands with Mendelian disorders (the controls). The excess twinning was same sex and can therefore consist of either MZ or same-sex DZ twins. Furthermore, upper-NTD families with twins had a higher NTD-sibling occurrence rate than did families without twins. These findings, if corroborated, may imply an etiology common to twinning and NTDs and can perhaps be applied in counseling NTD families. PMID:7977342

  8. Gene Regulatory Logic for Reading the Sonic Hedgehog Signaling Gradient in the Vertebrate Neural Tube

    PubMed Central

    Balaskas, Nikolaos; Ribeiro, Ana; Panovska, Jasmina; Dessaud, Eric; Sasai, Noriaki; Page, Karen M.; Briscoe, James; Ribes, Vanessa

    2012-01-01

    Summary Secreted signals, known as morphogens, provide the positional information that organizes gene expression and cellular differentiation in many developing tissues. In the vertebrate neural tube, Sonic Hedgehog (Shh) acts as a morphogen to control the pattern of neuronal subtype specification. Using an in vivo reporter of Shh signaling, mouse genetics, and systems modeling, we show that a spatially and temporally changing gradient of Shh signaling is interpreted by the regulatory logic of a downstream transcriptional network. The design of the network, which links three transcription factors to Shh signaling, is responsible for differential spatial and temporal gene expression. In addition, the network renders cells insensitive to fluctuations in signaling and confers hysteresis—memory of the signal. Our findings reveal that morphogen interpretation is an emergent property of the architecture of a transcriptional network that provides robustness and reliability to tissue patterning. PMID:22265416

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

    PubMed

    Zhu, Xiaoqing; Li, Bo; Ai, Zongyong; Xiang, Zheng; Zhang, Kunshang; Qiu, Xiaoyan; Chen, Yongchang; Li, Yuemin; Rizak, Joshua D; Niu, Yuyu; Hu, Xintian; Sun, Yi Eve; Ji, Weizhi; Li, Tianqing

    2016-02-01

    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. PMID:26584544

  10. Genetic association analyses of nitric oxide synthase genes and neural tube defects vary by phenotype.

    PubMed

    Soldano, Karen L; Garrett, Melanie E; Cope, Heidi L; Rusnak, J Michael; Ellis, Nathen J; Dunlap, Kaitlyn L; Speer, Marcy C; Gregory, Simon G; Ashley-Koch, Allison E

    2013-10-01

    Neural tube defects (NTDs) are caused by improper neural tube closure during the early stages of embryonic development. NTDs are hypothesized to have a complex genetic origin and numerous candidate genes have been proposed. The nitric oxide synthase 3 (NOS3) G594T polymorphism has been implicated in risk for spina bifida, and interactions between that single nucleotide polymorphism (SNP) and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have also been observed. To evaluate other genetic variation in the NO pathway in the development of NTDs, we examined all three NOS genes: NOS1, NOS2, and NOS3. Using 3109 Caucasian samples in 745 families, we evaluated association in the overall dataset and within specific phenotypic subsets. Haplotype tagging SNPs in the NOS genes were tested for genetic association with NTD subtypes, both for main effects as well as for the presence of interactions with the MTHFR C677T polymorphism. Nominal main effect associations were found with all subtypes, across all three NOS genes, and interactions were observed between SNPs in all three NOS genes and MTHFR C677T. Unlike the previous report, the most significant associations in our dataset were with cranial subtypes and the AG genotype of rs4795067 in NOS2 (p = 0.0014) and the interaction between the rs9658490 G allele in NOS1 and MTHFR 677TT genotype (p = 0.0014). Our data extend the previous findings by implicating a role for all three NOS genes, independently and through interactions with MTHFR, in risk not only for spina bifida, but all NTD subtypes. PMID:24323870

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

    PubMed

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

    2016-03-01

    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. PMID:26847388

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  15. Hydrolyzed fumonisin B1 (HFB1) did not induce neural tube defects in LM/Bc mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisins are mycotoxins produced by Fusarium verticillioides. They are found in corn-based foods and are toxic and carcinogenic to rodents. There is evidence suggesting that consumption of corn tortillas containing fumonisins contributed to an enigmatic cluster of neural tube defects (NTDs) in s...

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

    ERIC Educational Resources Information Center

    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…

  17. Fumonisin as a possible contributing factor to neural tube defects in populations consuming large amounts of maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisin B1 (FB) is an inhibitor of sphingolipid (SL) biosynthesis and folate transport and can induce neural tube defects (NTD) in mice. NTD incidence is high in countries where maize is a dietary staple and FB exposure is likely. In Guatemala the incidence of FB in maize has been well documented ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. GENE-NUTRIENT-ENVIRONMENT INTERACTIONS AS RISK FACTORS FOR BIRTH DEFECTS: FUMONISIN, FOLATE, GENETIC VARIATION AND NEURAL TUBE DEFECTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The second most common birth defect is neural tube defects (NTDs). In Guatemala, parts of China and Africa, NTD risk is estimated to be higher than that observed in the USA. The etiology of NTD in these areas is complex. Increased risk has been associated with genetic predisposition, dietary expo...

  20. Fumonisin B1 induced neural tube defects were not increased in LM/Bc mice fed folate-deficient diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides that is found in corn-based foods and is possibly 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 understood, however, there is evidenc...

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

    PubMed Central

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

    2015-01-01

    ABSTRACT 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. PMID:25596276

  2. Excess FoxG1 causes overgrowth of the neural tube.

    PubMed

    Ahlgren, Sara; Vogt, Peter; Bronner-Fraser, Marianne

    2003-12-01

    The winged helix transcription factor FoxG1 (Bf-1, qin) plays multiple roles in the development of the telencephalon, with different parts of the protein affecting either proliferation or differentiation. We examined the consequences of over-expression, via retroviral expression, of FoxG1 on the growth of different regions of the chicken brain. Excess expression of FoxG1 caused a thickening of the neuroepithelium, and ultimately large outgrowths of the telencephalon and mesencephalon. In contrast, the myelencephalon appeared unaffected, exhibiting normal apoptosis and growth characteristics. A DNA binding defective form of FoxG1 did not exhibit these abnormalities, suggesting that these effects are due to FoxG1's function as a transcriptional repressor. To examine the means by which excess FoxG1 caused overgrowth of the brain, we examined alterations in cell proliferation and death. No increase in proliferation was noted in any portion of the neural tube, rather a significant decrease in neuroepithelial apoptosis was seen. These results demonstrate a previously unrecognized role for winged helix factors in the regulation of neural cell apoptosis. PMID:14608667

  3. Neural Tube Defects in Costa Rica, 1987–2012: Origins and Development of Birth Defect Surveillance and Folic Acid Fortification

    PubMed Central

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

    2015-01-01

    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 < 0.05) decrease of 51 % in the prevalence of 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. PMID:24952876

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

    PubMed

    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 < 0.05) decrease of 51 % in the prevalence of 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. PMID:24952876

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

    PubMed

    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. PMID:24768893

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

    PubMed Central

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

    2015-01-01

    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. PMID:26209645

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

    PubMed Central

    ES, Patterson; LE, Waller; KL, Kroll

    2014-01-01

    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. PMID:24995796

  8. [Prevalence of neural tube defects and estimation of cases averted in the post-fortification period in Argentina].

    PubMed

    Bidondo, María P; Liascovich, Rosa; Barbero, Pablo; Groisman, Boris

    2015-12-01

    Periconceptional intake of folic acid has demonstrated to be effective to reduce the frequency of neural tube defects, and food fortification has been one of the strategies implemented to increase it. An update is herein presented on the reduced prevalence of neural tube defect cases in the post-fortification period in Argentina and an estimation of cases averted in the 2005-2013 period as a result of this intervention. When comparing the prevalence observed in the post-fortification period to that reported in the pre-fortification period, anencephaly and encephalocele decreased by 66%, and spina bifida, by 47%, which were significant reductions. The estimated number of cases averted was higher for anencephaly, followed by spina bifida; encephalocele showed the lowest number of cases averted given that the prevalence of this defect was smaller. The decrease observed in the prevalence supports findings from previous studies on the impact of fortification. PMID:26593794

  9. The natural history of neural tube defects in the setting of an Irish tertiary referral foetal medicine unit.

    PubMed

    Anglim, B; Mandiwanza, T; Miletin, J; Turner, M; Kennelly, M M

    2016-01-01

    Neural tube defects (NTDs) carry a heavy burden for affected individuals and their family. Physical and neurological outcome measures may help in counselling couples. The aim of this audit was to review all cases of NTDs seen at a tertiary referral foetal medicine unit. Cases were identified from obstetric, neonatal and neurosurgical records. Thirty-six cases of NTDs were identified. Of the 36, 25% (n = 9, one trisomy 18) opted for termination of pregnancy abroad. Of the remaining 27, 19% (n = 5) died in the antepartum period. 81% (n = 22) were liveborn with four neonatal deaths (one trisomy 18). Of 15 cases, 14 had neurosurgical repair within a median time of 3 days and 9 of these also had a ventriculoperitoneal shunt inserted. Antenatal ultrasound accurately diagnosed lesion level in the majority of cases. The survival rate for babies diagnosed with non-lethal neural tubes defects is high when multidisciplinary care is initiated early. PMID:26214050

  10. Periconceptional vitamin supplementation to prevent neural tube defects: how can we do it?

    PubMed

    Mills, J L; Conley, M R

    1995-07-01

    The discovery that folic acid can reduce neural tube defect rates offers a great opportunity for primary prevention. Unfortunately, women must receive the folic acid before or immediately after conception, before many know that they are pregnant. Thus, we are faced with a difficult choice: (1) ask all women at risk of getting pregnant to take supplements, or (2) fortify the food supply to ensure that all women at risk receive additional folic acid. Neither approach is ideal. Many women will not take vitamin supplements. Fortification at sufficiently high levels to provide all women with 400 micrograms of folic acid will expose other segments of the population to unacceptably high levels. Because many women of child-bearing age are unaware of the benefits of folic acid, a vigorous education campaign should begin immediately to encourage women at risk to take supplements. Adding 70 micrograms of folic acid per 100 g of grain could be justified easily because this amount is removed from grain in processing. If it is technically feasible, adding up to 140 micrograms is likely to be safe, and could prevent more NTDs. A major educational campaign and modest fortification of grain with folic acid may be the best practical solution. PMID:8549847

  11. [Uncertain effects of folic acid on disorders other than neural-tube defects].

    PubMed

    Verhoef, P; Katan, M B

    2006-07-01

    Periconceptional supplemention with folic acid prevents neural-tube defects in infants. However, contrary to expectations, clinical trials found no beneficial effect of folic acid on the recurrence of cardiovascular disease. Trial evidence on folic acid and cognitive decline or dementia is scarce, though observational studies suggest that high folate intake may prevent these disorders. In contrast, animal studies suggest that high doses of folic acid enhance the growth of existing tumours. However, recent clinical trials failed to show significant effects of folic acid on cancer incidence and mortality. There are also speculations that folic-acid fortification may increase the number of newborns with the thermolabile variant of methylene tetrahydrofolate reductase. There appears to be little evidence that folic-acid supplementation may mask vitamin-B12 deficiency. In view of these controversies, it is unlikely that The Netherlands will mandate folic-acid fortification of staple foods in the near future. Therefore, women who are planning a pregnancy should be urged to take folic-acid supplements. PMID:16875263

  12. Levels of Polycyclic Aromatic Hydrocarbons in Maternal Serum and Risk of Neural Tube Defects in Offspring

    PubMed Central

    2015-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants, and have been reported to be a risk factor for human neural tube defects (NTDs). We investigated the relationship between PAH concentrations in maternal serum and NTD risk in offspring using a case-control study design, and explored the link between PAH concentrations to household energy usage characteristics and life styles. One hundred and seventeen women who had NTD-affected pregnancies (cases) and 121 women who delivered healthy infants (controls) were recruited in Northern China. Maternal blood samples were collected at pregnancy termination or at delivery. Twenty-seven PAHs were measured by gas chromatography–mass spectrometry. The concentrations of 13 individual PAHs detected were significantly higher in the cases than in the controls. Clear dose–response relationships between concentrations of most individual PAHs and the risk of total NTDs or subtypes were observed, even when potential covariates were adjusted for. High-molecular-weight PAHs (H-PAHs) showed higher risk than low-molecular-weight PAHs (L-PAHs). No associations between PAH concentrations and indoor life styles and energy usage characteristics were observed. It was concluded that maternal exposure to PAHs was associated with an increased risk of NTDs, and H-PAHs overall posed a higher risk for NTDs than L-PAHs. PMID:25488567

  13. Metabonomic profiling of human placentas reveals different metabolic patterns among subtypes of neural tube defects.

    PubMed

    Chi, Yi; Pei, Lijun; Chen, Gong; Song, Xinming; Zhao, Aihua; Chen, Tianlu; Su, Mingming; Zhang, Yinan; Liu, Jianmeng; Ren, Aiguo; Zheng, Xiaoying; Xie, Guoxiang; Jia, Wei

    2014-02-01

    Neural tube defects (NTDs) are one of the most common types of birth defects with a complex etiology. We have previously profiled serum metabolites of pregnant women in Lvliang prefecture, Shanxi Province of China, which revealed distinct metabolic changes in pregnant women with NTDs outcome. Here we present a metabonomics study of human placentas of 144 pregnant women with normal pregnancy outcome and 115 pregnant women affected with NTDs recruited from four rural counties (Pingding, Xiyang, Taigu, and Zezhou) of Shanxi Province, the area with the highest prevalence worldwide. A panel of 19 metabolites related to one-carbon metabolism was also quantitatively determined. We observed obvious differences in global metabolic profiles and one-carbon metabolism among three subtypes of NTDs, anencephaly (Ane), spina bifida (SB), and Ane complicated with SB (Ane & SB) via mass-spectrometry-based metabonomics approach. Disturbed carbohydrate, amino acid, lipid, and nucleic acid metabolism were identified. Placental transport of amino acids might be depressed in Ane and Ane & SB group. Deficiency of choline contributes to Ane and Ane & SB pathogenesis via different metabolic pathways. The formation of NTDs seemed to be weakly related to folates. The metabonomic analysis reveals that the physiological and biochemical processes of the three subtypes of NTDs might be different and the subtype condition should be considered for the future investigation of NTDs. PMID:24397701

  14. Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice

    PubMed Central

    Pai, Yun Jin; Leung, Kit-Yi; Savery, Dawn; Hutchin, Tim; Prunty, Helen; Heales, Simon; Brosnan, Margaret E.; Brosnan, John T.; Copp, Andrew J.; Greene, Nicholas D.E.

    2015-01-01

    Glycine decarboxylase (GLDC) acts in the glycine cleavage system to decarboxylate glycine and transfer a one-carbon unit into folate one-carbon metabolism. GLDC mutations cause a rare recessive disease non-ketotic hyperglycinemia (NKH). Mutations have also been identified in patients with neural tube defects (NTDs); however, the relationship between NKH and NTDs is unclear. We show that reduced expression of Gldc in mice suppresses glycine cleavage system activity and causes two distinct disease phenotypes. Mutant embryos develop partially penetrant NTDs while surviving mice exhibit post-natal features of NKH including glycine accumulation, early lethality and hydrocephalus. In addition to elevated glycine, Gldc disruption also results in abnormal tissue folate profiles, with depletion of one-carbon-carrying folates, as well as growth retardation and reduced cellular proliferation. Formate treatment normalizes the folate profile, restores embryonic growth and prevents NTDs, suggesting that Gldc deficiency causes NTDs through limiting supply of one-carbon units from mitochondrial folate metabolism. PMID:25736695

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

    PubMed

    Fu, Lin; Yu, Zhen; Chen, Yuan-Hua; Xia, Mi-Zhen; Wang, Hua; Zhang, Cheng; Tao, Fang-Biao; Xu, De-Xiang

    2014-01-01

    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 (GD)8 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. PMID:25420102

  16. Association study of PARD3 gene polymorphisms with neural tube defects in a Chinese Han population.

    PubMed

    Gao, Yonghui; Chen, Xiaoli; Shangguan, Shaofang; Bao, Yihua; Lu, Xiaoli; Zou, Jizhen; Guo, Jin; Dai, Yaohua; Zhang, Ting

    2012-07-01

    Partitioning defective 3 homolog (PARD3) is an attractive candidate gene for screening neural tube defect (NTD) risk. To investigate the role of genetic variants in PARD3 on NTD risk, a case-control study was performed in a region of China with a high prevalence of NTDs. Total 53 single-nucleotide polymorphisms (SNPs) in PARD3 were genotyped in 224 fetuses with NTDs and in 253 normal fetuses. We found that 6 SNPs (rs2496720, rs2252655, rs3851068, rs118153230, rs10827337, and rs12218196) were statistically associated with NTDs (P < .05). After stratifying participants by NTD phenotypes, the significant association only existed in cases with anencephaly rather than spina bifida. Further haplotype analysis confirmed the association between PARD3 polymorphisms and NTD risk (global test P = 3.41e-008). Our results suggested that genetic variants in PARD3 were associated with susceptibility to NTDs in a Chinese Han population, and this association was affected by NTD phenotypes. PMID:22447895

  17. Neural tube opening and abnormal extraembryonic membrane development in SEC23A deficient mice

    PubMed Central

    Zhu, Min; Tao, Jiayi; Vasievich, Matthew P.; Wei, Wei; Zhu, Guojing; Khoriaty, Rami N.; Zhang, Bin

    2015-01-01

    COPII (coat protein complex-II) vesicles transport proteins from the endoplasmic reticulum (ER) to the Golgi. Higher eukaryotes have two or more paralogs of most COPII components. Here we characterize mice deficient for SEC23A and studied interactions of Sec23a null allele with the previously reported Sec23b null allele. SEC23A deficiency leads to mid-embryonic lethality associated with defective development of extraembryonic membranes and neural tube opening in midbrain. Secretion defects of multiple collagen types are observed in different connective tissues, suggesting that collagens are primarily transported in SEC23A-containing vesicles in these cells. Other extracellular matrix proteins, such as fibronectin, are not affected by SEC23A deficiency. Intracellular accumulation of unsecreted proteins leads to strong induction of the unfolded protein response in collagen-producing cells. No collagen secretion defects are observed in SEC23B deficient embryos. We report that E-cadherin is a cargo that accumulates in acini of SEC23B deficient pancreas and salivary glands. Compensatory increase of one paralog is observed in the absence of the second paralog. Haploinsufficiency of the remaining Sec23 paralog on top of homozygous inactivation of the first paralog leads to earlier lethality of embryos. Our results suggest that mammalian SEC23A and SEC23B transport overlapping yet distinct spectra of cargo in vivo. PMID:26494538

  18. Long Term Maintenance of Neural Tube Defects Prevention in a High Prevalence State

    PubMed Central

    Collins, Julianne S.; Atkinson, Kristy K.; Dean, Jane H.; Best, Robert G.; Stevenson, Roger E.

    2011-01-01

    Objective To assess the efficacy of folic acid (FA) supplementation and fortification in preventing neural tube defects (NTDs) in a high prevalence region of the US. Study design Active and passive surveillance methods were used to identify all fetuses/infants affected by an NTD in South Carolina. Prevalence rates were compared with FA intake to determine the effects of increased intake on NTD occurrence and recurrence. Results From 1992–2009, 916 NTD cases occurred in South Carolina with isolated defects comprising 79% of cases. The NTD rate decreased 58% during this period. There was one NTD-affected pregnancy among 418 subsequent pregnancies (0.2%) in mothers with previous NTD-affected pregnancies who consumed periconceptional FA supplements and four NTDs among 66 pregnancies (6.1%) in which the mother did not take FA supplements. Folic acid supplementation increased from 8% to 35% from 1992–2007 and knowledge of the protective benefits of FA increased from 8% to 65% in women of childbearing age. Conclusions Increased periconceptional intake of FA appeared to reduce NTDs in a high prevalence region. The rate of spina bifida and anencephaly in South Carolina is now essentially the same (0.69 cases per 1000 live births and fetal deaths) as the 1998–2005 US rate (0.69). PMID:21345450

  19. Role of arsenic as a reproductive toxin with particular attention to neural tube defects

    SciTech Connect

    Shalat, S.L.; Walker, D.B.; Finnell, R.H.

    1996-10-01

    Arsenic has been recognized as a human toxicant for over 2000 years. More recently it has been readily accepted as a human carcinogen. Animal research has demonstrated arsenic`s ability to have profound detrimental effects on the developing embryo in avian and mamalian species. This article comprehensively reviews the human and animal literature on the subject of the reproductive toxicity of arsenic. A variety of endpoints are considered, including spontaneous abortion, cardiovascular defects, and arsenic`s role in the causation of neural tube defects (NTDs). A summary of the literature that has examined the various postulated mechanisms by which arsenic may produce NTDs is also considered. In addition, a discussion of literature relative to the presence of arsenic in the general environment and in the workplace presented. This article reaches the conclusion that while further research is clearly needed, particularly on the potential toxicity of organic arsenical compounds, the current literature suggests it may be prudent and appropriate to treat inorganic arsenic as a probable human reproductive toxin. 132 refs.

  20. Live imaging of apoptosis in a novel transgenic mouse highlights its role in neural tube closure.

    PubMed

    Yamaguchi, Yoshifumi; Shinotsuka, Naomi; Nonomura, Keiko; Takemoto, Kiwamu; Kuida, Keisuke; Yosida, Hiroki; Miura, Masayuki

    2011-12-12

    Many cells die during development, tissue homeostasis, and disease. Dysregulation of apoptosis leads to cranial neural tube closure (NTC) defects like exencephaly, although the mechanism is unclear. Observing cells undergoing apoptosis in a living context could help elucidate their origin, behavior, and influence on surrounding tissues, but few tools are available for this purpose, especially in mammals. In this paper, we used insulator sequences to generate a transgenic mouse that stably expressed a genetically encoded fluorescence resonance energy transfer (FRET)-based fluorescent reporter for caspase activation and performed simultaneous time-lapse imaging of apoptosis and morphogenesis in living embryos. Live FRET imaging with a fast-scanning confocal microscope revealed that cells containing activated caspases showed typical and nontypical apoptotic behavior in a region-specific manner during NTC. Inhibiting caspase activation perturbed and delayed the smooth progression of cranial NTC, which might increase the risk of exencephaly. Our results suggest that caspase-mediated cell removal facilitates NTC completion within a limited developmental window. PMID:22162136

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

    PubMed

    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. PMID:25797655

  2. Maternal Coffee Consumption During Pregnancy and Neural Tube Defects in Offspring: A Meta-Analysis.

    PubMed

    Li, Zhao-Xia; Gao, Zhuang-Lei; Wang, Jin-Na; Guo, Qing-Hui

    2016-01-01

    Purpose To examine the association between maternal coffee consumption during pregnancy and the occurrence of neural tube defects (NTDs) in offspring. Methods PubMed, Springer Link and Elsevier databases were searched up to August, 2014. Case-control and cohort studies published on the association between maternal coffee consumption during pregnancy and the occurrence of NTDs in offspring were included. Meta-analysis was applied to calculate the pooled effect estimates and their 95% confidence intervals (CIs) using a random-effects model. Results A total of six case-control studies and one cohort study were included. The pooled effect estimate of maternal coffee consumption during pregnancy was 0.86 for total NTDs (95% CI: 0.51- 1.45) and 1.30 (95% CI: 0.67- 2.52) for NTDs subtype of spina bifida. Conclusions Our findings suggested that maternal coffee consumption during pregnancy was not significantly associated with the occurrence of total NTD or the spina bifida subtype of NTD. PMID:26720182

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

    PubMed

    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. PMID:24838524

  4. Folate-mediated one-carbon metabolism and neural tube defects: balancing genome synthesis and gene expression.

    PubMed

    Beaudin, Anna E; Stover, Patrick J

    2007-09-01

    Neural tube defects (NTDs) refer to a cluster of neurodevelopmental conditions associated with failure of neural tube closure during embryonic development. Worldwide prevalence of NTDs ranges from approximately 0.5 to 60 per 10,000 births, with regional and population-specific variation in prevalence. Numerous environmental and genetic influences contribute to NTD etiology; accumulating evidence from population-based studies has demonstrated that folate status is a significant determinant of NTD risk. Folate-mediated one-carbon metabolism (OCM) is essential for de novo nucleotide biosynthesis, methionine biosynthesis, and cellular methylation reactions. Periconceptional maternal supplementation with folic acid can prevent occurrence of NTDs in the general population by up to 70%; currently several countries fortify their food supply with folic acid for the prevention of NTDs. Despite the unambiguous impact of folate status on NTD risk, the mechanism by which folic acid protects against NTDs remains unknown. Identification of the mechanism by which folate status affects neural tube closure will assist in developing more efficacious and better targeted preventative measures. In this review, we summarize current research on the relationship between folate status and NTDs, with an emphasis on linking genetic variation, folate nutriture, and specific metabolic and/or genomic pathways that intersect to determine NTD outcomes. PMID:17963270

  5. The interaction between Shroom3 and Rho-kinase is required for neural tube morphogenesis in mice.

    PubMed

    Das, Debamitra; Zalewski, Jenna K; Mohan, Swarna; Plageman, Timothy F; VanDemark, Andrew P; Hildebrand, Jeffrey D

    2014-01-01

    Shroom3 is an actin-associated regulator of cell morphology that is required for neural tube closure, formation of the lens placode, and gut morphogenesis in mice and has been linked to chronic kidney disease and directional heart looping in humans. Numerous studies have shown that Shroom3 likely regulates these developmental processes by directly binding to Rho-kinase and facilitating the assembly of apically positioned contractile actomyosin networks. We have characterized the molecular basis for the neural tube defects caused by an ENU-induced mutation that results in an arginine-to-cysteine amino acid substitution at position 1838 of mouse Shroom3. We show that this substitution has no effect on Shroom3 expression or localization but ablates Rock binding and renders Shroom3 non-functional for the ability to regulate cell morphology. Our results indicate that Rock is the major downstream effector of Shroom3 in the process of neural tube morphogenesis. Based on sequence conservation and biochemical analysis, we predict that the Shroom-Rock interaction is highly conserved across animal evolution and represents a signaling module that is utilized in a variety of biological processes. PMID:25171888

  6. Mutations in genes encoding the glycine cleavage system predispose to neural tube defects in mice and humans.

    PubMed

    Narisawa, Ayumi; Komatsuzaki, Shoko; Kikuchi, Atsuo; Niihori, Tetsuya; Aoki, Yoko; Fujiwara, Kazuko; Tanemura, Mitsuyo; Hata, Akira; Suzuki, Yoichi; Relton, Caroline L; Grinham, James; Leung, Kit-Yi; Partridge, Darren; Robinson, Alexis; Stone, Victoria; Gustavsson, Peter; Stanier, Philip; Copp, Andrew J; Greene, Nicholas D E; Tominaga, Teiji; Matsubara, Yoichi; Kure, Shigeo

    2012-04-01

    Neural tube defects (NTDs), including spina bifida and anencephaly, are common birth defects of the central nervous system. The complex multigenic causation of human NTDs, together with the large number of possible candidate genes, has hampered efforts to delineate their molecular basis. Function of folate one-carbon metabolism (FOCM) has been implicated as a key determinant of susceptibility to NTDs. The glycine cleavage system (GCS) is a multi-enzyme component of mitochondrial folate metabolism, and GCS-encoding genes therefore represent candidates for involvement in NTDs. To investigate this possibility, we sequenced the coding regions of the GCS genes: AMT, GCSH and GLDC in NTD patients and controls. Two unique non-synonymous changes were identified in the AMT gene that were absent from controls. We also identified a splice acceptor site mutation and five different non-synonymous variants in GLDC, which were found to significantly impair enzymatic activity and represent putative causative mutations. In order to functionally test the requirement for GCS activity in neural tube closure, we generated mice that lack GCS activity, through mutation of AMT. Homozygous Amt(-/-) mice developed NTDs at high frequency. Although these NTDs were not preventable by supplemental folic acid, there was a partial rescue by methionine. Overall, our findings suggest that loss-of-function mutations in GCS genes predispose to NTDs in mice and humans. These data highlight the importance of adequate function of mitochondrial folate metabolism in neural tube closure. PMID:22171071

  7. The interaction between Shroom3 and Rho-kinase is required for neural tube morphogenesis in mice

    PubMed Central

    Das, Debamitra; Zalewski, Jenna K.; Mohan, Swarna; Plageman, Timothy F.; VanDemark, Andrew P.; Hildebrand, Jeffrey D.

    2014-01-01

    ABSTRACT Shroom3 is an actin-associated regulator of cell morphology that is required for neural tube closure, formation of the lens placode, and gut morphogenesis in mice and has been linked to chronic kidney disease and directional heart looping in humans. Numerous studies have shown that Shroom3 likely regulates these developmental processes by directly binding to Rho-kinase and facilitating the assembly of apically positioned contractile actomyosin networks. We have characterized the molecular basis for the neural tube defects caused by an ENU-induced mutation that results in an arginine-to-cysteine amino acid substitution at position 1838 of mouse Shroom3. We show that this substitution has no effect on Shroom3 expression or localization but ablates Rock binding and renders Shroom3 non-functional for the ability to regulate cell morphology. Our results indicate that Rock is the major downstream effector of Shroom3 in the process of neural tube morphogenesis. Based on sequence conservation and biochemical analysis, we predict that the Shroom-Rock interaction is highly conserved across animal evolution and represents a signaling module that is utilized in a variety of biological processes. PMID:25171888

  8. Sequential contraction and exchange of apical junctions drives zippering and neural tube closure in a simple chordate.

    PubMed

    Hashimoto, Hidehiko; Robin, Francois B; Sherrard, Kristin M; Munro, Edwin M

    2015-01-26

    Unidirectional zippering is a key step in neural tube closure that remains poorly understood. Here, we combine experimental and computational approaches to identify the mechanism for zippering in a basal chordate, Ciona intestinalis. We show that myosin II is activated sequentially from posterior to anterior along the neural/epidermal (Ne/Epi) boundary just ahead of the advancing zipper. This promotes rapid shortening of Ne/Epi junctions, driving the zipper forward and drawing the neural folds together. Cell contact rearrangements (Ne/Epi + Ne/Epi → Ne/Ne + Epi/Epi) just behind the zipper lower tissue resistance to zipper progression by allowing transiently stretched cells to detach and relax toward isodiametric shapes. Computer simulations show that measured differences in junction tension, timing of primary contractions, and delay before cell detachment are sufficient to explain the speed and direction of zipper progression and highlight key advantages of a sequential contraction mechanism for robust efficient zippering. PMID:25625209

  9. Statistical properties of cosmic-ray showers at ground level determined from photomultiplier-tube background registrations

    NASA Astrophysics Data System (ADS)

    Teich, Malvin C.; Campos, Richard A.; Saleh, Bahaa E. A.

    1987-11-01

    The fluctuations of cosmic-ray particles resulting from extensive air showers at ground level are well described by the two-parameter Poisson-driven Yule-Furry and negative-binomial counting probability distributions. The background signal from a single photomultiplier tube has been used to experimentally verify these results with remarkable precision, in spite of the simplicity of the underlying pure-birth stochastic process. Counting distributions from three different photomultiplier-tube detectors operated in the dark are presented, together with the theoretical predictions. Probability distributions of interevent times have also been obtained and these are found to be consistent with the observed clustering properties at the detector output. Our approach is expected to be of importance in quantum optics where cosmic-ray-shower particles can pose a significant limitation on the detection of squeezed light.

  10. Loss of mitogen-activated protein kinase kinase kinase 4 (MEKK4) results in enhanced apoptosis and defective neural tube development

    PubMed Central

    Chi, Hongbo; Sarkisian, Matthew R.; Rakic, Pasko; Flavell, Richard A.

    2005-01-01

    Neural tube defects (NTDs) are prevalent human birth defects. Mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK), are implicated in facilitating neural tube closure, yet upstream regulators remain to be identified. Here, we show that MAP kinase kinase kinase 4 (MEKK4) is strongly expressed in the developing neuroepithelium. Mice deficient in MEKK4 develop highly penetrant NTDs that cannot be rescued by supplementation with folic acid or inositol. Unlike most mouse models of NTDs, MEKK4 mutant embryos display genetically co-segregated exencephaly and spina bifida, recapitulating the phenotypes observed in human patients. To identify downstream targets of MEKK4 during neural tube development, we examined the activity of MAP kinase kinase 4 (MKK4), a signaling intermediate between MAP kinase kinase kinase and JNK/p38. We found a significant reduction in MKK4 activity in MEKK4-deficient neuroepithelium at sites of neural tube closure. MAPK pathways are key regulators of cell apoptosis and proliferation. Analyses of the neuroepithelium in MEKK4-deficient embryos showed massively elevated apoptosis before and during neural tube closure, suggesting an antiapoptotic role for MEKK4 during development. In contrast, proliferation of MEKK4-deficient neuroepithelial cells appeared to be largely unaffected. MEKK4 therefore plays a critical role in regulating MKK4 activity and apoptotic cell death during neural tube development. Disruption of this signaling pathway may be clinically relevant to folate-resistant human NTDs. PMID:15731347

  11. Does dietary folic acid supplementation in mouse NTD models affect neural tube development or gamete preference at fertilization?

    PubMed Central

    2014-01-01

    Background Neural tube defects (NTDs) are the second most common birth defect in humans. Dietary folic acid (FA) supplementation effectively and safely reduces the incidence of these often debilitating congenital anomalies. FA plays an established role in folate and homocysteine metabolism, but the means by which it suppresses occurrence of NTDs is not understood. In addition, many cases remain resistant to the beneficial effects of folic acid supplementation. To better understand the molecular, biochemical and developmental mechanisms by which FA exerts its effect on NTDs, characterized mouse models are needed that have a defined genetic basis and known response to dietary supplementation. Results We examined the effect of FA supplementation, at 5-fold the level in the control diet, on the NTD and vertebral phenotypes in Apob tm1Unc and Vangl2 Lp mice, hereafter referred to as Apob and Lp respectively. The FA supplemented diet did not reduce the incidence or severity of NTDs in Apob or Lp mutant homozygotes or the loop-tail phenotype in Lp mutant heterozygotes, suggesting that mice with these mutant alleles are resistant to FA supplementation. Folic acid supplementation also did not affect the rate of resorptions or the size of litters, but instead skewed the embryonic genotype distribution in favor of wild-type alleles. Conclusion Similar genotypic biases have been reported for several NTD models, but were interpreted as diet-induced increases in the incidence and severity of NTDs that led to increased embryonic lethality. Absence of differences in resorption rates and litter sizes argue against induced embryonic lethality. We suggest an alternative interpretation, namely that FA supplementation led to strongly skewed allelic inheritance, perhaps from disturbances in polyamine metabolism that biases fertilization in favor of wild-type gametes. PMID:25154628

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

    SciTech Connect

    Hol, F.A.; Hamel, B.C.J.; Geurds, M.P.A.

    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.

  13. Exposure to fumonisins and the occurrence of neural tube defects along the Texas-Mexico border.

    PubMed

    Missmer, Stacey A; Suarez, Lucina; Felkner, Marilyn; Wang, Elaine; Merrill, Alfred H; Rothman, Kenneth J; Hendricks, Katherine A

    2006-02-01

    Along the Texas-Mexico border, the prevalence of neural tube defects (NTDs) among Mexican-American women doubled during 1990-1991. The human outbreak began during the same crop year as epizootics attributed to exposure to fumonisin, a mycotoxin that often contaminates corn. Because Mexican Americans in Texas consume large quantities of corn, primarily in the form of tortillas, they may be exposed to high levels of fumonisins. We examined whether or not maternal exposure to fumonisins increases the risk of NTDs in offspring using a population-based case-control study. We estimated fumonisin exposure from a postpartum sphinganine:sphingosine (sa:so) ratio, a biomarker for fumonisin exposure measured in maternal serum, and from maternal recall of periconceptional corn tortilla intake. After adjusting for confounders, moderate (301-400) compared with low (< or = 100) consumption of tortillas during the first trimester was associated with increased odds ratios (ORs) of having an NTD-affected pregnancy (OR = 2.4; 95% confidence interval, 1.1-5.3). No increased risks were observed at intakes higher than 400 tortillas (OR = 0.8 for 401-800, OR = 1.0 for > 800). Based on the postpartum sa:so ratio, increasing levels of fumonisin exposure were associated with increasing ORs for NTD occurrences, except for the highest exposure category (sa:so > 0.35). Our findings suggest that fumonisin exposure increases the risk of NTD, proportionate to dose, up to a threshold level, at which point fetal death may be more likely to occur. These results also call for population studies that can more directly measure individual fumonisin intakes and assess effects on the developing embryo. PMID:16451860

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

    PubMed

    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. PMID:18709894

  15. SELDI-TOF-MS Proteomic Profiling of Serum, Urine, and Amniotic Fluid in Neural Tube Defects

    PubMed Central

    Liu, Zhenjiang; Yuan, Zhengwei; Zhao, Qun

    2014-01-01

    Neural tube defects (NTDs) are common birth defects, whose specific biomarkers are needed. The purpose of this pilot study is to determine whether protein profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS. ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78 urine samples and 76 amniotic fluid samples. The validity of classification tree was then challenged with a blind test set including another 20 NTD-mothers and 18 controls in serum samples, and another 19 NTD-mothers and 17 controls in urine samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples. Eight proteins detected in serum samples were up-regulated and four proteins were down-regulated in the NTD group. Four proteins detected in urine samples were up-regulated and one protein was down-regulated in the NTD group. Six proteins detected in amniotic fluid samples were up-regulated and one protein was down-regulated in the NTD group. The classification tree for serum samples separated NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity of 97% in the training set, and achieving a sensitivity of 90% and a specificity of 97% and a positive predictive value of 95% in the test set. The classification tree for urine samples separated NTDs from controls, achieving a sensitivity of 95% and a specificity of 94% in the training set, and achieving a sensitivity of 89% and a specificity of 82% and a positive predictive value of 85% in the test set. The classification tree for amniotic fluid samples separated NTDs from controls, achieving a sensitivity of 93% and a specificity of 89% in the training set, and achieving a sensitivity of 90% and a specificity of 88% and a positive predictive value of 90% in the test set. These suggest that SELDI-TOF-MS is an additional method for NTDs pregnancies detection. PMID:25054433

  16. Folic Acid Intake and Neural Tube Defects: Two Egyptian Centers Experience

    PubMed Central

    El-Shabrawi, Mortada H.; Kamal, Naglaa Mohamed; Elhusseini, Mona Abbas; Hussein, Laila; Abdallah, Enas Abdallah Ali; Ali, Yahia Zakaria Abdelalim; Azab, Ahmed Abelfattah; Salama, Mostafa Abdelazim; Kassab, Muna; Krawinkel, Michael

    2015-01-01

    Abstract Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex etiopathogenesis. Folic acid plays a pivotal role in their prevention. We aimed to identify the protective effect of folic acid intake against NTDs and its dependence on different socioeconomic and environmental factors in a cohort of mothers in Egypt. A cross-sectional study was carried over a period of 12 months on mothers who gave birth to babies with NTDs (group 1) and a control group with healthy offsprings (group 2). Both groups completed 2 questionnaires: food frequency questionnaire targeting the daily folate intake, and socioeconomic status and medical history questionnaire. Both groups of mothers received folate <800 μg/day, recommended for pregnant women. A strong association was detected between NTDs and urban residency with medium educated mothers, with negative consanguinity, who had folate intake < 400 μg daily, and who had their food long cooked. Each of these factors separately had a limited impact to cause NTDs, but when present together they did augment each other. Interestingly enough is the role of fava bean, cauliflower, spinach, and mango in predisposing of NTDs in the presence of the above-mentioned factors. The protective effect of folic acid intake against NTDs may depend on the synergism of different socioeconomic and environmental factors (which differ from country to another). In Egypt, females especially the medium-educated who live in urban areas should be well-informed with the value of folate intake in the periconceptional period. PMID:26376380

  17. Variants in maternal COMT and MTHFR genes and risk of neural tube defects in offspring.

    PubMed

    Liu, Jufen; Zhang, Yali; Jin, Lei; Li, Guoxing; Wang, Linlin; Bao, Yanping; Fu, Yunting; Li, Zhiwen; Zhang, Le; Ye, Rongwei; Ren, Aiguo

    2015-04-01

    Methylenetetrahydrofolate reductase (MTHFR) C677T and catechol-O-Methyltransferase (COMT) G158A are associated with a risk of neural tube defects (NTDs) in offspring. This study examined the effect of a MTHFR × COMT interaction on the risk of NTDs in a Chinese population with a high prevalence of NTDs. A total of 576 fetuses or newborns with NTDs and 594 controls were genotyped for MTHFRrs1801133, MTHFRrs1801131, and COMTrs4680 and COMTrs737865. Information on maternal sociodemographic characteristics, reproductive history, and related behavior was collected through face-to-face interviews. Possible interactions between genetic variants of MTHFR and COMT were examined. MTHFR C677T homozygous TT was associated with an elevated risk of total NTDs (odds ratio [OR] = 1.37, 95 % confidence interval [CI] = 0.93-2.03) and of anencephaly (OR = 1.67, 95 % CI = 0.98-2.84) compared with the CC genotype. There was a COMT rs737865 CC × MTHFR rs1801133 TT interaction for total NTDs (OR = 3.02, 95 % CI = 1.00-9.14) and for anencephaly (OR = 3.39, 95 % CI = 0.94-12.18). No interaction was found between COMT rs4680 AA/AG and MTHFR CT/TT genotypes for total NTDs or any subtype of NTD. The interaction of COMT rs737865 and MTHFR C677T was associated with an increased risk of NTDs, especially anencephaly, in a Chinese population with a high prevalence of NTDs. PMID:24990354

  18. Placental concentrations of manganese and the risk of fetal neural tube defects.

    PubMed

    Liu, Jufen; Jin, Lei; Zhang, Le; Li, Zhiwen; Wang, Linlin; Ye, Rongwei; Zhang, Yali; Ren, Aiguo

    2013-10-01

    Manganese (Mn) is an essential trace element required for normal growth, development, and cellular homeostasis, but excess Mn is toxic to the central nervous system. The present pilot study examined whether the level of Mn in the placenta was associated with the risk of fetal neural tube defects (NTDs). A case-control study was conducted. Cases were 80 fetuses or newborns with NTDs, and controls were 50 healthy, nonmalformed newborns. Placental Mn, zinc, copper, iron, and selenium were determined with inductively coupled plasma-mass spectrometry. The median Mn concentration was significantly higher in case placentas than in controls: cases, 131.60 ng/g (95% confidence interval [CI], 99.25-166.76); controls, 101.54 ng/g (95% CI, 80.14-119.79). Mn concentrations above the median were associated with a 4-fold (95% CI, 1.23-14.79) increased risk for any NTDs and a 7-fold (95% CI, 1.52-39.64) increased risk for spina bifida after other confounding factors were controlled. Elevated Mn levels were associated with an increased risk of anencephaly, although the adjusted odds ratio did not reach statistical significance. The association between higher Mn concentrations and risk of NTDs showed a clear dose-response relationship. Risk of NTDs increased to 1.51 (95% CI, 0.65-3.52) and 5.03 (95% CI, 1.89-13.33) for those whose placental Mn level was in the second and third tertiles, respectively, compared with the lowest tertile. Elevated placental concentrations of Mn may be associated with increased risks of NTDs in this population. PMID:23664920

  19. Quantitative assessment of maternal biomarkers related to one-carbon metabolism and neural tube defects

    PubMed Central

    Tang, Ke-Fu; Li, Yao-Long; Wang, Hong-Yan

    2015-01-01

    Periconceptional supplementation with folic acid reduces the occurrence of neural tube defects (NTDs). The association between maternal abnormalities in homocysteine metabolism (e.g., hyperhomocysteinaemia, folate deficiency and low vitamin B12) and the risk of NTDs-affected pregnancies has been widely evaluated in recent years, although the results are conflicting. To investigate this inconsistency, we performed a meta-analysis of 32 studies, involving 1,890 NTD-affected mothers and 3,995 control mothers, to develop an understanding of the relationship between maternal biomarkers related to one-carbon metabolism and NTD. A random-effects model was used to calculate the ratio of means (RoM) between the cases and controls, along with the 95% confidence intervals (CIs). A significant increase in homocysteine levels was observed in NTD-affected mothers compared with controls (RoM: 1.16, 95% CI: 1.09–1.23, P = 1.8 × 10−6). The pooled analysis also revealed that NTD-affected mothers had significantly lower levels of folate (RoM: 0.93, 95% CI: 0.88–0.97, P = 0.002), vitamin B12 (RoM: 0.91, 95% CI: 0.87–0.95, P = 3.6 × 10−5) and red blood cell folate (RoM: 0.92, 95% CI: 0.86–0.98, P = 0.01). Therefore, altered plasma levels of biomarkers related to one-carbon metabolism are associated with NTD-affected pregnancies. PMID:25728980

  20. Neural tube defects in Latin America and the impact of fortification: a literature review

    PubMed Central

    Rosenthal, Jorge; Casas, Jessica; Taren, Douglas; Alverson, Clinton J; Flores, Alina; Frias, Jaime

    2015-01-01

    Objective Data on the prevalence of birth defects and neural tube defects (NTD) in Latin America are limited. The present review summarizes NTD prevalence and time trends in Latin American countries and compares pre- and post-fortification periods to assess the impact of folic acid fortification in these countries. Design We carried out a literature review of studies and institutional reports published between 1990 and 2010 that contained information on NTD prevalence in Latin America. Results NTD prevalence in Latin American countries varied from 0.2 to 9.6 per 1000 live births and was influenced by methods of ascertainment. Time trends from Bogota, Costa Rica, Dominican Republic, Guatemala City, México and Puerto Rico showed average annual declines of 2.5% to 21.8%. Pre- and post-fortification comparisons were available for Argentina, Brazil, Chile, Costa Rica, Puerto Rico and México. The aggregate percentage decline in NTD prevalence ranged from 33% to 59%. Conclusions The present publication is the first to review data on time trends and the impact of folic acid fortification on NTD prevalence in Latin America. Reported NTD prevalence varied markedly by geographic region and in some areas of Latin America was among the lowest in the world, while in other areas it was among the highest. For countries with available information, time trends showed significant declines in NTD prevalence and these declines were greater in countries where folic acid fortification of staples reached the majority of the population at risk, such as Chile and Costa Rica. PMID:23464652

  1. Folic Acid Intake and Neural Tube Defects: Two Egyptian Centers Experience.

    PubMed

    El-Shabrawi, Mortada H; Kamal, Naglaa Mohamed; Elhusseini, Mona Abbas; Hussein, Laila; Abdallah, Enas Abdallah Ali; Ali, Yahia Zakaria Abdelalim; Azab, Ahmed Abelfattah; Salama, Mostafa Abdelazim; Kassab, Muna; Krawinkel, Michael

    2015-09-01

    Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex etiopathogenesis. Folic acid plays a pivotal role in their prevention. We aimed to identify the protective effect of folic acid intake against NTDs and its dependence on different socioeconomic and environmental factors in a cohort of mothers in Egypt. A cross-sectional study was carried over a period of 12 months on mothers who gave birth to babies with NTDs (group 1) and a control group with healthy offsprings (group 2). Both groups completed 2 questionnaires: food frequency questionnaire targeting the daily folate intake, and socioeconomic status and medical history questionnaire. Both groups of mothers received folate <800 μg/day, recommended for pregnant women. A strong association was detected between NTDs and urban residency with medium educated mothers, with negative consanguinity, who had folate intake < 400 μg daily, and who had their food long cooked. Each of these factors separately had a limited impact to cause NTDs, but when present together they did augment each other. Interestingly enough is the role of fava bean, cauliflower, spinach, and mango in predisposing of NTDs in the presence of the above-mentioned factors. The protective effect of folic acid intake against NTDs may depend on the synergism of different socioeconomic and environmental factors (which differ from country to another). In Egypt, females especially the medium-educated who live in urban areas should be well-informed with the value of folate intake in the periconceptional period. PMID:26376380

  2. Autoantibodies to folate receptor during pregnancy and neural tube defect risk

    PubMed Central

    Cabrera, Robert M.; Shaw, Gary M.; Ballard, Johnathan L.; Carmichael, Suzan L.; Yang, Wei; Lammer, Edward J.; Finnell, Richard H.

    2008-01-01

    Periconceptional folic acid can reduce the occurrence of neural tube defects (NTDs) by up to 70%, and autoantibodies for folate receptors (FRs) have been observed in serum from women with a pregnancy complicated by an NTD. This population-based cohort study has examined serum from pregnant mothers for autoantibodies to FRs, antibodies to bovine folate binding protein (FBP), and inhibition of folic acid binding to FR and FBP in association with NTD risk. The mid-gestational maternal serum specimens used for this study were collected during the 15th18th week of pregnancy. Samples were obtained from the California Birth Defects Monitoring Program; 29 mothers had a pregnancy complicated by spina bifida and 76 mothers had unaffected children. The presence of IgG and IgM antibodies to human FR, bovine FBP, and inhibition of folic acid binding to FR and FBP was determined. Higher activity of IgM to FBP in cases verses controls was observed (P=.04). Higher activity of IgM and IgG autoantibodies to FR was observed (P<0.001 and P=.04, respectively). Risk estimates at two standard deviations above average control antibody concentrations were OR=2.07 (CI=1.02, 4.06) for anti-FBPIgM, OR=2.15 (CI=1.02, 4.69) for anti-FRIgG and OR=3.19 (CI=1.47, 6.92) for anti-FR IgM. These data support the hypothesis that high titers of antibodies and blocking of folic acid binding to FRs by maternal serum should be regarded as risk factors for NTDs. PMID:18804286

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

    PubMed

    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. PMID:26453010

  4. Epidemiologic and genetic aspects of spina bifida and other neural tube defects

    PubMed Central

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

    2011-01-01

    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 health officials to design and implement policies to prevent NTD pregnancies, and (c) individuals to take precautions to reduce the chance of having an NTD-affected pregnancy. Despite extensive research, our knowledge of the genetic etiology of human NTDs is limited. Although more than 200 small animal models with NTDs exist, most of these models do not replicate the human disease phenotype. Over a hundred candidate genes have been examined for risk association to human SB. The candidate genes studied include those important in folic acid metabolism, glucose metabolism, retinoid metabolism, and apoptosis. Many genes that regulate transcription in early embryogenesis and maintain planar cell polarity have also been tested as candidates. Additionally, genes identified through mouse models of NTDs have been explored as candidates. We do not know how many genes in the human genome may confer risk for NTDs in human. Less than 20% of the studied candidate genes have been determined to confer even a minor effect on risk association. Many studies have provided conflicting conclusions due to limitations in study design that potentially affect the power of statistical analysis. Future directions such as genomewide association studies (GWAS) and whole exome or even whole genome sequencing are discussed as possible avenues to identify genes that affect risk for human NTDs. PMID:20419766

  5. Maternal exposure to arsenic, cadmium, lead, and mercury and neural tube defects in offspring

    SciTech Connect

    Brender, Jean D. . E-mail: jdbrender@aol.com; Suarez, Lucina; Felkner, Marilyn; Gilani, Zunera; Stinchcomb, David; Moody, Karen; Henry, Judy; Hendricks, Katherine

    2006-05-15

    Arsenic, cadmium, lead, and mercury are neurotoxins, and some studies suggest that these elements might also be teratogens. Using a case-control study design, we investigated the relation between exposure to these heavy metals and neural tube defects (NTDs) in offspring of Mexican-American women living in 1 of the 14 Texas counties bordering Mexico. A total of 184 case-women with NTD-affected pregnancies and 225 control-women with normal live births were interviewed about their environmental and occupational exposures during the periconceptional period. Biologic samples for blood lead and urinary arsenic, cadmium, and mercury were also obtained for a subset of these women. Overall, the median levels of these biomarkers for heavy metal exposure did not differ significantly (P>0.05) between case- and control-women. However, among women in the highest income group, case-women were nine times more likely (95% confidence interval (CI) 1.4-57) than control-women to have a urinary mercury >=5.62{mu}g/L. Case-women were 4.2 times more likely (95% CI 1.1-16) to report burning treated wood during the periconceptional period than control-women. Elevated odds ratios (ORs) were observed for maternal and paternal occupational exposures to arsenic and mercury, but the 95% CIs were consistent with unity. The 95% CIs of the ORs were also consistent with unity for higher levels of arsenic, cadmium, lead, and mercury in drinking water and among women who lived within 2 miles at the time of conception to industrial facilities with reported emissions of any of these heavy metals. Our findings suggest that maternal exposures to arsenic, cadmium, or lead are probably not significant risk factors for NTDs in offspring. However, the elevated urinary mercury levels found in this population and exposures to the combustion of treated wood may warrant further investigation.

  6. Midline craniofacial malformations with a lipomatous cephalocele are associated with insufficient closure of the neural tube in the tuft mouse

    PubMed Central

    Fong, Keith S. K.; Adachi, Dana A. T.; Chang, Shaun B.; Lozanoff, Scott

    2015-01-01

    Genetic variations affecting neural tube closure along the head result in malformations to the face and brain, posing a significant impact on health care costs and the quality of life. We have established a mouse line from a mutation that arose spontaneously in our wildtype colony that we called tuft. Tuft mice have heritable midline craniofacial defects featuring an anterior lipomatous cephalocele. Whole mount skeletal stains indicated that affected newborns had a broader interfrontal suture where the cephalocele emerged between the frontal bones. Mice with a cephalocele positioned near the rostrum also presented craniofacial malformations such as ocular hypertelorism and midfacial cleft of the nose. Gross and histological examination revealed that the lipomatous cephalocele originated as a fluid filled cyst no earlier than E14.5 while embryos with a midfacial cleft was evident during craniofacial development at E11.5. Histological sections of embryos with a midfacial cleft revealed the cephalic neuroectoderm remained proximal or fused to the frontonasal ectoderm about the closure site of the anterior neuropore, indicating a defect to neural tube closure. We found the neural folds along the rostrum of E9-10.5 embryos curled inward and failed to close as well as embryos with exencephaly and anencephaly at later stages. Whole mount in situ hybridization of anterior markers Fgf8 and Shh indicated closure of the rostral site was compromised in severe cases. We present a model demonstrating how anterior cranial cephaloceles are generated following a defect to neural tube closure and relevance to subsequent craniofacial morphogenesis in the tuft mouse. PMID:24931720

  7. Fumonisins disrupt sphingolipid metabolism, folate transport, and neural tube development in embryo culture and in vivo: a potential risk factor for human neural tube defects among populations consuming fumonisin-contaminated maize.

    PubMed

    Marasas, Walter F O; Riley, Ronald T; Hendricks, Katherine A; Stevens, Victoria L; Sadler, Thomas W; Gelineau-van Waes, Janee; Missmer, Stacey A; Cabrera, Julio; Torres, Olga; Gelderblom, Wentzel C A; Allegood, Jeremy; Martínez, Carolina; Maddox, Joyce; Miller, J David; Starr, Lois; Sullards, M Cameron; Roman, Ana Victoria; Voss, Kenneth A; Wang, Elaine; Merrill, Alfred H

    2004-04-01

    Fumonisins are a family of toxic and carcinogenic mycotoxins produced by Fusarium verticillioides (formerly Fusarium moniliforme), a common fungal contaminant of maize. Fumonisins inhibit ceramide synthase, causing accumulation of bioactive intermediates of sphingolipid metabolism (sphinganine and other sphingoid bases and derivatives) as well as depletion of complex sphingolipids, which interferes with the function of some membrane proteins, including the folate-binding protein (human folate receptor alpha). Fumonisin causes neural tube and craniofacial defects in mouse embryos in culture. Many of these effects are prevented by supplemental folic acid. Recent studies in LMBc mice found that fumonisin exposure in utero increases the frequency of developmental defects and administration of folate or a complex sphingolipid is preventive. High incidences of neural tube defects (NTD) occur in some regions of the world where substantial consumption of fumonisins has been documented or plausibly suggested (Guatemala, South Africa, and China); furthermore, a recent study of NTD in border counties of Texas found a significant association between NTD and consumption of tortillas during the first trimester. Hence, we propose that fumonisins are potential risk factors for NTD, craniofacial anomalies, and other birth defects arising from neural crest cells because of their apparent interference with folate utilization. PMID:15051815

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

    SciTech Connect

    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. Lamin b1 polymorphism influences morphology of the nuclear envelope, cell cycle progression, and risk of neural tube defects in mice.

    PubMed

    De Castro, Sandra C P; Malhas, Ashraf; Leung, Kit-Yi; Gustavsson, Peter; Vaux, David J; Copp, Andrew J; Greene, Nicholas D E

    2012-01-01

    Neural tube defects (NTDs), including spina bifida and anencephaly, are common birth defects whose complex multigenic causation has hampered efforts to delineate their molecular basis. The effect of putative modifier genes in determining NTD susceptibility may be investigated in mouse models, particularly those that display partial penetrance such as curly tail, a strain in which NTDs result from a hypomorphic allele of the grainyhead-like-3 gene. Through proteomic analysis, we found that the curly tail genetic background harbours a polymorphic variant of lamin B1, lacking one of a series of nine glutamic acid residues. Lamins are intermediate filament proteins of the nuclear lamina with multiple functions that influence nuclear structure, cell cycle properties, and transcriptional regulation. Fluorescence loss in photobleaching showed that the variant lamin B1 exhibited reduced stability in the nuclear lamina. Genetic analysis demonstrated that the variant also affects neural tube closure: the frequency of spina bifida and anencephaly was reduced three-fold when wild-type lamin B1 was bred into the curly tail strain background. Cultured fibroblasts expressing variant lamin B1 show significantly increased nuclear dysmorphology and diminished proliferative capacity, as well as premature senescence, associated with reduced expression of cyclins and Smc2, and increased expression of p16. The cellular basis of spinal NTDs in curly tail embryos involves a proliferation defect localised to the hindgut epithelium, and S-phase progression was diminished in the hindgut of embryos expressing variant lamin B1. These observations indicate a mechanistic link between altered lamin B1 function, exacerbation of the Grhl3-mediated cell proliferation defect, and enhanced susceptibility to NTDs. We conclude that lamin B1 is a modifier gene of major effect for NTDs resulting from loss of Grhl3 function, a role that is likely mediated via the key function of lamin B1 in maintaining integrity of the nuclear envelope and ensuring normal cell cycle progression. PMID:23166514

  10. Epidémiologie et facteurs de risque des anomalies de fermeture du tube neural: données marocaines

    PubMed Central

    Radouani, Mohammed Amine; Chahid, Naima; Benmiloud, Loubna; Elammari, Laila; Lahlou, Khalid; Barkat, Amina

    2015-01-01

    Introduction Les anomalies de fermeture du tube neural sont des défauts congénitaux de la formation du système nerveux central. L'incidence varie entre 3 et 40 cas pour 10000 dans le monde. Il existe des facteurs de risque de survenue de cette affection. La prévention reste un élément important dans la prise en charge. L'objectif de ceete étude est d’étudier les paramètres sociodémographiques, maternels, obstétricaux et néonatals des anomalies de fermeture du tube neural et analyser les facteurs de risque responsables dans notre contexte. Méthodes Etude prospective cas-témoin sur 4 ans. Ont été recrutés tous les cas portant une malformation du tube neural isolée ou associée à d'autres malformations. Les données maternelles, obstétricales et néonatales ont été enregistrées. L'analyse statistique était réalisée par le biais d'un logiciel de statistiques SPSS version 17.0 pour Windows. Résultats Soixante huit cas ont été inclus. Quatre-vingts cinq pour cent des malformations étaient isolées. L'anencéphalie était l'anomalie la plus retrouvée (67%). L’âge maternel moyen était 31,03±7,50 ans. La consanguinité parentale était notée dans 9 cas. Un niveau socio-économique bas et un non suivi des grossesses ont été rapportés dans 29% des cas. L’étude a retrouvé des antécédents de mort-nés et de morts néonatales dans 4% des cas. La consommation de Fenugrec était significativement associée aux malformations du tube neural et a été retrouvée dans 8 cas contre 1 cas dans le groupe sain. La voie haute d'accouchement était utilisée dans 29% des cas. L’âge gestationnel moyen était de 35,55±4,16 semaines d'aménorrhée. Il n'y avait pas de prédominance de sexe. On avait noté une relation significative entre les malformations du tube neural et l'avènement d'une asphyxie périnatale, 15 cas présentaient un apgar à 0 à la première minute et 12 cas un apgar inférieur à 7 à la cinquième minute. Conclusion Le bas niveau socio-économique, le non suivi des grossesses et la consommation maternelle de fenugrec en période gestationnelle étaient des facteurs prédictifs de développement d'anomalies du tube neural dans notre contexte. PMID:26664544

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

    PubMed Central

    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; β-difference > 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 < 0.0001) independent of the MTHFR 667C>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. PMID:25565354

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

    PubMed

    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; β-difference > 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 < 0.0001) independent of the MTHFR 667C>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. PMID:25565354

  13. Shroom, a PDZ domain-containing actin-binding protein, is required for neural tube morphogenesis in mice.

    PubMed

    Hildebrand, J D; Soriano, P

    1999-11-24

    Using gene trap mutagenesis, we have identified a mutation in mice that causes exencephaly, acrania, facial clefting, and spina bifida, all of which can be attributed to failed neural tube closure. This mutation is designated shroom (shrm) because the neural folds "mushroom" outward and do not converge at the dorsal midline. shrm encodes a PDZ domain protein that is involved at several levels in regulating aspects of cytoarchitecture. First, endogenous Shrm localizes to adherens junctions and the cytoskeleton. Second, ectopically expressed Shrm alters the subcellular distribution of F-actin. Third, Shrm directly binds F-actin. Finally, cytoskeletal polarity within the neuroepithelium is perturbed in mutant embryos. In concert, these observations suggest that Shrm is a critical determinant of the cellular architecture required for proper neurulation. PMID:10589677

  14. Maternal and infant gene-folate interactions and the risk of neural tube defects.

    PubMed

    Etheredge, Analee J; Finnell, Richard H; Carmichael, Suzan L; Lammer, Edward J; Zhu, Huiping; Mitchell, Laura E; Shaw, Gary M

    2012-10-01

    Neural tube defects (NTDs) are common, serious malformations with a complex etiology that suggests involvement of both genetic and environmental factors. The authors evaluated maternal or offspring folate-related gene variants and interactions between the gene variants and maternal intake of folates on the risk of NTDs in their offspring. A case-control study was conducted on mothers and/or their fetuses and infants who were born in California from 1999 to 2003 with an NTD (cases n = 222, including 24 mother-infant pairs) or without a major malformation (controls n = 454, including 186 mother-infant pairs). Maternal intake of folates was assessed by food frequency questionnaire and genotyping was performed on samples from mothers and infants. For mothers in the lowest folate-intake group, risk of NTDs in offspring was significantly decreased for maternal MTHFR SNPs rs1476413, rs1801131, and rs1801133 (odds ratio [OR] = 0.55, 80% confidence interval [CI]: 0.20, 1.48; OR = 0.58, 80% CI: 0.24, 1.43; OR = 0.69, 80% CI: 0.41, 1.17, respectively), and TYMS SNPs rs502396 and rs699517 (OR = 0.91, 80% CI: 0.53, 1.56; OR = 0.70, 80% CI: 0.38, 1.29). A gene-only effect was observed for maternal SHMT1 SNP rs669340 (OR = 0.69, 95% CI: 0.49, 0.96). When there was low maternal folate intake, risk of NTDs was significantly increased for infant MTHFD1 SNPs rs2236224, rs2236225, and rs11627387 (OR = 1.58, 80% CI: 0.99, 2.51; OR = 1.53, 80% CI: 0.95, 2.47; OR = 4.25, 80% CI: 2.33, 7.75, respectively) and SHMT1 SNP rs12939757 (OR = 2.01, 80% CI: 1.20, 3.37), but decreased for TYMS SNP rs2847153 (OR = 0.73, 80% CI: 0.37, 1.45). Although power to detect interaction effects was low for this birth defects association study, the gene-folate interactions observed in this study represent preliminary findings that will be useful for informing future studies on the complex etiology of NTDs. PMID:22903727

  15. Analysis of MTR and MTRR Polymorphisms for Neural Tube Defects Risk Association.

    PubMed

    Wang, Yongxin; Liu, Yuan; Ji, Wenyu; Qin, Hu; Wu, Hao; Xu, Danshu; Tukebai, Turtuohut; Wang, Zengliang

    2015-09-01

    Neural tube defects (NTDs) are the most common congenital defects of the central nervous system among neonates and the folate status during pregnancy was considered as the most important etiopathogenesis of NTDs. Besides, methionine synthase (MTR) gene and methionine synthase reductase (MTRR) gene were folate metabolism involved genes and had been investigated in several previous studies with inconsistent results. Hence, we aimed to explore the association of 4 selected single-nucleotide polymorphisms (SNPs) on MTRR/MTR gene and the susceptibility of NTDs in a Chinese population.Seven SNPs were selected from HapMap databases with Haploview 4.2 software. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to genotype the polymorphisms from blood samples of 165 NTDs patients and 280 healthy controls. The correlation between these SNPs and NTDs risk was tested by Student t test and Chi-square test by STATA 11.0 software. Furthermore, we performed a meta-analysis of relevant studies to investigate the association between the SNPs MTRR 66A>G and MTR 2756A>G and the susceptibility of NTDs.An increased risk of NTDs was verified to be significantly associated with MTRR 66A>G (G allele vs. A allele: OR = 1.36 (1.03-1.80), P = 0.028; GG + AG vs. AA: OR = 1.60 (1.05-2.43), P = 0.027) and MTR 2756A>G (G allele vs. A allele: OR = 1.45 (1.06-1.98), P = 0.021; GG + AG vs. AA: OR = 1.51 (1.02-2.23), P = 0.038) in our study. However, the other SNPs in our analysis showed no significant association with NTDs risk (all P > 0.05). Furthermore, the result of the meta-analysis supported the association between MTRR 66A>G and NTDs risk (G allele vs. A allele: OR = 1.32, 95% CI = 1.09-1.61, GG + GA vs. AA: OR = 1.49, 95% CI = 1.06-2.09, GG vs. AA: OR = 1.61, 95% CI = 1.04-2.49).Our study confirmed that the MTRR 66A>G and MTR 2756A>G were significantly associated with the increased NTDs risk in a Chinese population. The further meta-analysis enhance that MTRR 66A>G was connected with the susceptibility of NTDs widely. Further investigations based on more detailed stratification were recommended. PMID:26334892

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

    PubMed Central

    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 mandatory folic acid fortification of food does not exist? Methods This was a population based, observational study using data on 11 353 cases of NTD not associated with chromosomal anomalies, including 4162 cases of anencephaly and 5776 cases of spina bifida from 28 EUROCAT (European Surveillance of Congenital Anomalies) registries covering approximately 12.5 million births in 19 countries between 1991 and 2011. The main outcome measures were total and live birth prevalence of NTD, as well as anencephaly and spina bifida, with time trends analysed using random effects Poisson regression models to account for heterogeneities across registries and splines to model non-linear time trends. Summary answer and limitations Overall, the pooled total prevalence of NTD during the study period was 9.1 per 10 000 births. Prevalence of NTD fluctuated slightly but without an obvious downward trend, with the final estimate of the pooled total prevalence of NTD in 2011 similar to that in 1991. Estimates from Poisson models that took registry heterogeneities into account showed an annual increase of 4% (prevalence ratio 1.04, 95% confidence interval 1.01 to 1.07) in 1995-99 and a decrease of 3% per year in 1999-2003 (0.97, 0.95 to 0.99), with stable rates thereafter. The trend patterns for anencephaly and spina bifida were similar, but neither anomaly decreased substantially over time. The live birth prevalence of NTD generally decreased, especially for anencephaly. Registration problems or other data artefacts cannot be excluded as a partial explanation of the observed trends (or lack thereof) in the prevalence of NTD. What this study adds In the absence of mandatory fortification, the prevalence of NTD has not decreased in Europe despite longstanding recommendations aimed at promoting peri-conceptional folic acid supplementation and existence of voluntary folic acid fortification. Funding, competing interests, data sharing The study was funded by the European Public Health Commission, EUROCAT Joint Action 2011-2013. HD and ML received support from the European Commission DG Sanco during the conduct of this study. No additional data available. PMID:26601850

  17. Dual labeling of neural crest cells and blood vessels within chicken embryos using Chick(GFP) neural tube grafting and carbocyanine dye DiI injection.

    PubMed

    Delalande, Jean-Marie; Thapar, Nikhil; Burns, Alan J

    2015-01-01

    All developing organs need to be connected to both the nervous system (for sensory and motor control) as well as the vascular system (for gas exchange, fluid and nutrient supply). Consequently both the nervous and vascular systems develop alongside each other and share striking similarities in their branching architecture. Here we report embryonic manipulations that allow us to study the simultaneous development of neural crest-derived nervous tissue (in this case the enteric nervous system), and the vascular system. This is achieved by generating chicken chimeras via transplantation of discrete segments of the neural tube, and associated neural crest, combined with vascular DiI injection in the same embryo. Our method uses transgenic chick(GFP) embryos for intraspecies grafting, making the transplant technique more powerful than the classical quail-chick interspecies grafting protocol used with great effect since the 1970s. Chick(GFP)-chick intraspecies grafting facilitates imaging of transplanted cells and their projections in intact tissues, and eliminates any potential bias in cell development linked to species differences. This method takes full advantage of the ease of access of the avian embryo (compared with other vertebrate embryos) to study the co-development of the enteric nervous system and the vascular system. PMID:26065540

  18. Epigenetic Profiles in Children with a Neural Tube Defect; A Case-Control Study in Two Populations

    PubMed Central

    Stolk, Lisette; Bouwland-Both, Marieke I.; van Mill, Nina H.; Verbiest, Michael M. P. J.; Eilers, Paul H. C.; Zhu, Huiping; Suarez, Lucina; Uitterlinden, André G.; Steegers-Theunissen, Régine P. M.

    2013-01-01

    Folate deficiency is implicated in the causation of neural tube defects (NTDs). The preventive effect of periconceptional folic acid supplement use is partially explained by the treatment of a deranged folate-dependent one carbon metabolism, which provides methyl groups for DNA-methylation as an epigenetic mechanism. Here, we hypothesize that variations in DNA-methylation of genes implicated in the development of NTDs and embryonic growth are part of the underlying mechanism. In 48 children with a neural tube defect and 62 controls from a Dutch case-control study and 34 children with a neural tube defect and 78 controls from a Texan case-control study, we measured the DNA-methylation levels of imprinted candidate genes (IGF2-DMR, H19, KCNQ1OT1) and non-imprinted genes (the LEKR/CCNL gene region associated with birth weight, and MTHFR and VANGL1 associated with NTD). We used the MassARRAY EpiTYPER assay from Sequenom for the assessment of DNA-methylation. Linear mixed model analysis was used to estimate associations between DNA-methylation levels of the genes and a neural tube defect. In the Dutch study group, but not in the Texan study group we found a significant association between the risk of having an NTD and DNA methylation levels of MTHFR (absolute decrease in methylation of −0.33% in cases, P-value = 0.001), and LEKR/CCNL (absolute increase in methylation: 1.36% in cases, P-value = 0.048), and a borderline significant association for VANGL (absolute increase in methylation: 0.17% in cases, P-value = 0.063). Only the association between MTHFR and NTD-risk remained significant after multiple testing correction. The associations in the Dutch study were not replicated in the Texan study. We conclude that the associations between NTDs and the methylation of the MTHFR gene, and maybe VANGL and LEKKR/CNNL, are in line with previous studies showing polymorphisms in the same genes in association with NTDs and embryonic development, respectively. PMID:24223810

  19. Modifying a sealed tube zinc reduction method for preparation of AMS graphite targets: Reducing background and attaining high precision

    NASA Astrophysics Data System (ADS)

    Xu, Xiaomei; Trumbore, Susan E.; Zheng, Shuhui; Southon, John R.; McDuffee, Kelsey E.; Luttgen, Madelyn; Liu, Julia C.

    2007-06-01

    The sealed tube zinc reduction method for converting CO2 to graphite for AMS 14C measurements was originally developed for rapid production of graphite in biomedical tracer experiments. The method was usually thought to have low precision and a high background. We have modified the zinc reduction method originally outlined in Vogel [J.S. Vogel, Radiocarbon 34 (3) (1992) 344] by carefully controlling the amounts of reagents (zinc, titanium hydride and Co or Fe catalyst) and now routinely obtain a precision of 2-3‰ and a relatively low background of ∼50,000 14C years when analyzing for 14C at the Keck Carbon Cycle AMS facility at UC Irvine. Fractionation of carbon isotopes does occur during graphitization and depends on the graphitization yield, which can be affected by the amounts of reagents used and other conditions. The δ13C of our zinc-reduced graphite is usually lighter by 2-3‰ than the CO2 from which it is made, but this is corrected for in our system by simultaneous measurement of 13C/12C along with 14C/12C by the spectrometer. This method is suitable for 14C enriched samples, as well as natural abundance 14C samples, especially those with modern 14C contents. With improved precision and background, we believe that many disciplines can benefit from this technique because of its low cost and rapid production of graphite.

  20. Temporal and Spatial Analysis of Neural Tube Defects and Detection of Geographical Factors in Shanxi Province, China

    PubMed Central

    He, Lei; Wang, Jinfeng; Liu, Xin; Zhang, Ningxu; Xu, Bing

    2016-01-01

    Background Neural tube defects (NTDs) are congenital birth defects that occur in the central nervous system, and they have the highest incidence among all birth defects. Shanxi Province in China has the world’s highest rate of NTDs. Since the 1990s, China’s government has worked on many birth defect prevention programs to reduce the occurrence of NTDs, such as pregnancy planning, health education, genetic counseling, antenatal ultrasonography and serological screening. However, the rate of NTDs in Shanxi Province is still higher than the world’s average morbidity rate after intervention. In addition, Shanxi Province has abundant coal reserves, and is the largest coal production province in China. The objectives of this study are to determine the temporal and spatial variation of the NTD rate in rural areas of Shanxi Province, China, and identify geographical environmental factors that were associated with NTDs in the risk area. Methods In this study, Heshun County and Yuanping County in Shanxi Province, which have high incidence of NTDs, were selected as the study areas. Two paired sample T test was used to analyze the changes in the risk of NTDs from the time dimension. Ripley’s k function and spatial filtering were combined with geographic information system (GIS) software to study the changes in the risk of NTDs from the spatial dimension. In addition, geographical detectors were used to identify the risk geographical environmental factors of NTDs in the study areas, especially the areas close to the coal sites and main roads. Results In both Heshun County and Yuanping County, the incidence of NTDs was significantly (P<0.05) reduced after intervention. The results from spatial analysis showed that significant spatial heterogeneity existed in both counties. NTD clusters were still identified in areas close to coal sites and main roads after interventions. This study also revealed that the elevation, fault and soil types always had a larger influence on the incidence of NTDs in our study areas. In addition, distance to the river was a risk factor of NTDs in areas close to the coal sites and main roads. Conclusion The existing interventions may have played an important role to reduce the incidence of NTDs. However, there is still spatial heterogeneity in both counties after using the traditional intervention methods. The government needs to take more measures to strengthen the environmental restoration to prevent the occurrence of NTDs, especially those areas close to coal sites and main roads. The outcome of this research provides an important theoretical basis and technical support for the government to prevent the occurrence of NTDs. PMID:27100082

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

    PubMed Central

    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 915measuredsamples of water-in-glass evacuated tube solar water heaters. This artificial neural networks-based software program automatically obtained accurate heat collection rateand 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. PMID:26624613

  2. Rho-kinase-dependent actin turnover and actomyosin disassembly are necessary for mouse spinal neural tube closure

    PubMed Central

    Escuin, Sarah; Vernay, Bertrand; Savery, Dawn; Gurniak, Christine B.; Witke, Walter; Greene, Nicholas D. E.; Copp, Andrew J.

    2015-01-01

    ABSTRACT The cytoskeleton is widely considered essential for neurulation, yet the mouse spinal neural tube can close despite genetic and non-genetic disruption of the cytoskeleton. To investigate this apparent contradiction, we applied cytoskeletal inhibitors to mouse embryos in culture. Preventing actomyosin cross-linking, F-actin assembly or myosin II contractile activity did not disrupt spinal closure. In contrast, inhibiting Rho kinase (ROCK, for which there are two isoforms ROCK1 and ROCK2) or blocking F-actin disassembly prevented closure, with apical F-actin accumulation and adherens junction disturbance in the neuroepithelium. Cofilin-1-null embryos yielded a similar phenotype, supporting the hypothesis that there is a key role for actin turnover. Co-exposure to Blebbistatin rescued the neurulation defects caused by RhoA inhibition, whereas an inhibitor of myosin light chain kinase, ML-7, had no such effect. We conclude that regulation of RhoA, Rho kinase, LIM kinase and cofilin signalling is necessary for spinal neural tube closure through precise control of neuroepithelial actin turnover and actomyosin disassembly. In contrast, actomyosin assembly and myosin ATPase activity are not limiting for closure. PMID:26040287

  3. Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis.

    PubMed

    Robinson, Alexis; Escuin, Sarah; Doudney, Kit; Vekemans, Michel; Stevenson, Roger E; Greene, Nicholas D E; Copp, Andrew J; Stanier, Philip

    2012-02-01

    Craniorachischisis (CRN) is a severe neural tube defect (NTD) resulting from failure to initiate closure, leaving the hindbrain and spinal neural tube entirely open. Clues to the genetic basis of this condition come from several mouse models, which harbor mutations in core members of the planar cell polarity (PCP) signaling pathway. Previous studies of humans with CRN failed to identify mutations in the core PCP genes, VANGL1 and VANGL2. Here, we analyzed other key PCP genes: CELSR1, PRICKLE1, PTK7, and SCRIB, with the finding of eight potentially causative mutations in both CELSR1 and SCRIB. Functional effects of these unique or rare human variants were evaluated using known protein-protein interactions as well as subcellular protein localization. While protein interactions were not affected, variants from five of the 36 patients exhibited a profound alteration in subcellular protein localization, with diminution or abolition of trafficking to the plasma membrane. Comparable effects were seen in the crash and spin cycle mouse Celsr1 mutants, and the line-90 mouse Scrib mutant. We conclude that missense variants in CELSR1 and SCRIB may represent a cause of CRN in humans, as in mice, with defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism. PMID:22095531

  4. Updated estimates of neural tube defects prevented by mandatory folic Acid fortification - United States, 1995-2011.

    PubMed

    Williams, Jennifer; Mai, Cara T; Mulinare, Joe; Isenburg, Jennifer; Flood, Timothy J; Ethen, Mary; Frohnert, Barbara; Kirby, Russell S

    2015-01-16

    In 1992, the U.S. Public Health Service recommended that all women capable of becoming pregnant consume 400 µg of folic acid daily to prevent neural tube defects (NTDs). NTDs are major birth defects of the brain and spine that occur early in pregnancy as a result of improper closure of the embryonic neural tube, which can lead to death or varying degrees of disability. The two most common NTDs are anencephaly and spina bifida. Beginning in 1998, the United States mandated fortification of enriched cereal grain products with 140 µg of folic acid per 100 g. Immediately after mandatory fortification, the birth prevalence of NTD cases declined. Fortification was estimated to avert approximately 1,000 NTD-affected pregnancies annually. To provide updated estimates of the birth prevalence of NTDs in the period after introduction of mandatory folic acid fortification (i.e., the post-fortification period), data from 19 population-based birth defects surveillance programs in the United States, covering the years 1999-2011, were examined. After the initial decrease, NTD birth prevalence during the post-fortification period has remained relatively stable. The number of births occurring annually without NTDs that would otherwise have been affected is approximately 1,326 (95% confidence interval = 1,122-1,531). Mandatory folic acid fortification remains an effective public health intervention. There remain opportunities for prevention among women with lower folic acid intakes, especially among Hispanic women, to further reduce the prevalence of NTDs in the United States. PMID:25590678

  5. Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect, craniorachischisis

    PubMed Central

    Robinson, Alexis; Escuin, Sarah; Doudney, Kit; Vekemans, Michel; Stevenson, Roger E; Greene, Nicholas DE; Copp, Andrew J; Stanier, Philip

    2016-01-01

    Craniorachischisis is a severe neural tube defect (NTD) resulting from failure to initiate closure, leaving the hindbrain and spinal neural tube entirely open. Clues to the genetic basis of this condition come from several mouse models, which harbour mutations in core members of the planar cell polarity (PCP) signalling pathway. Previous studies of humans with craniorachischisis failed to identify mutations in the core PCP genes VANGL1 and VANGL2. Here we analysed other key PCP genes: CELSR1, PRICKLE1, PTK7 and SCRIB, with the finding of eight potentially causative mutations in both CELSR1 and SCRIB. Functional effects of these unique or rare human variants were evaluated using known protein-protein interactions as well as subcellular protein localisation. While protein interactions were not affected, variants from 5 of the 36 patients exhibited a profound alteration in subcellular protein localisation, with diminution or abolition of trafficking to the plasma membrane. Comparable effects were seen in the crash and spin cycle mouse Celsr1 mutants, and the line-90 mouse Scrib mutant. We conclude that missense variants in CELSR1 and SCRIB may represent a cause of craniorachischisis in humans, as in mice, with defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism. PMID:22095531

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

    PubMed

    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. PMID:17638618

  7. A case-control study to investigate the role of recent spontaneous abortion in the aetiology of neural tube defects.

    PubMed

    Kurinczuk, J J; Clarke, M

    1993-04-01

    Clarke et al. suggested that women who have had a spontaneous abortion are at an increased risk in their next pregnancy of producing an offspring with a neural tube defect (NTD). A matched case-control study was carried out to test the related hypothesis that a spontaneous abortion occurring in the 6-month period prior to the conception of a pregnancy (recent spontaneous abortion) is a risk factor for the development of an NTD in that pregnancy. The cases were 177 singleton pregnancies to non-primigravida Leicestershire women, which were affected by non-syndromal NTDs between 1976 and 1989. Two control pregnancies were matched with each case on intended place of delivery and date of maternal last normal menstrual period (LNMP). After adjusting for potential confounders, recent spontaneous abortion was found to be associated with a decreased relative risk of neural tube defect, odds ratio 0.46, 95% confidence interval 0.20, 1.07. The result provided little evidence in favour of the hypothesis, suggesting instead that prior spontaneous abortion has a protective effect in relation to subsequent NTD development rather than being a major risk factor in the aetiology of NTDs. PMID:8516190

  8. Analysis of MTR and MTRR Polymorphisms for Neural Tube Defects Risk Association

    PubMed Central

    Wang, Yongxin; Liu, Yuan; Ji, Wenyu; Qin, Hu; Wu, Hao; Xu, Danshu; Tukebai, Turtuohut; Wang, Zengliang

    2015-01-01

    Abstract Neural tube defects (NTDs) are the most common congenital defects of the central nervous system among neonates and the folate status during pregnancy was considered as the most important etiopathogenesis of NTDs. Besides, methionine synthase (MTR) gene and methionine synthase reductase (MTRR) gene were folate metabolism involved genes and had been investigated in several previous studies with inconsistent results. Hence, we aimed to explore the association of 4 selected single-nucleotide polymorphisms (SNPs) on MTRR/MTR gene and the susceptibility of NTDs in a Chinese population. Seven SNPs were selected from HapMap databases with Haploview 4.2 software. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to genotype the polymorphisms from blood samples of 165 NTDs patients and 280 healthy controls. The correlation between these SNPs and NTDs risk was tested by Student t test and Chi-square test by STATA 11.0 software. Furthermore, we performed a meta-analysis of relevant studies to investigate the association between the SNPs MTRR 66A>G and MTR 2756A>G and the susceptibility of NTDs. An increased risk of NTDs was verified to be significantly associated with MTRR 66A>G (G allele vs. A allele: OR = 1.36 (1.03–1.80), P = 0.028; GG + AG vs. AA: OR = 1.60 (1.05–2.43), P = 0.027) and MTR 2756A>G (G allele vs. A allele: OR = 1.45 (1.06–1.98), P = 0.021; GG + AG vs. AA: OR = 1.51 (1.02–2.23), P = 0.038) in our study. However, the other SNPs in our analysis showed no significant association with NTDs risk (all P > 0.05). Furthermore, the result of the meta-analysis supported the association between MTRR 66A>G and NTDs risk (G allele vs. A allele: OR = 1.32, 95% CI = 1.09–1.61, GG + GA vs. AA: OR = 1.49, 95% CI = 1.06–2.09, GG vs. AA: OR = 1.61, 95% CI = 1.04–2.49). Our study confirmed that the MTRR 66A>G and MTR 2756A>G were significantly associated with the increased NTDs risk in a Chinese population. The further meta-analysis enhance that MTRR 66A>G was connected with the susceptibility of NTDs widely. Further investigations based on more detailed stratification were recommended. PMID:26334892

  9. Prevention of neural tube defects by the fortification of flour with folic acid: a population-based retrospective study in Brazil

    PubMed Central

    Lecca, Roberto Carlos Reyes; Cortez-Escalante, Juan Jose; Sanchez, Mauro Niskier; Rodrigues, Humberto Gabriel

    2016-01-01

    Abstract Objective To determine if the fortification of wheat and maize flours with iron and folic acid – which became mandatory in Brazil from June 2004 – is effective in the prevention of neural tube defects. Methods Using data from national information systems on births in central, south-eastern and southern Brazil, we determined the prevalence of neural tube defects among live births and stillbirths in a pre-fortification period – i.e. 2001–2004 – and in a post-fortification period – i.e. 2005–2014. We distinguished between anencephaly, encephalocele, meningocele, myelomeningocele and other forms of spina bifida. Findings There were 8554 neural tube defects for 17 925 729 live births notified between 2001 and 2014. For the same period, 2673 neural tube defects were reported for 194 858 stillbirths. The overall prevalence of neural tube defects fell from 0.79 per 1000 pre-fortification to 0.55 per 1000 post-fortification (prevalence ratio, PR: 1.43; 95% confidence interval, CI: 1.38–1.50). For stillbirths, prevalence fell from 17.74 per 1000 stillbirths pre-fortification to 11.70 per 1000 stillbirths post-fortification. The corresponding values among live births were 0.57 and 0.44, respectively. Conclusion The introduction of the mandatory fortification of flour with iron and folic acid in Brazil was followed by a significant reduction in the prevalence of neural tube defects in our study area. PMID:26769993

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

    PubMed

    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. PMID:26989192

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

    PubMed

    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 sirtuin deacetylase 2 (SIRT2) and 6 (SIRT6) expression leading to histone acetylation and gene expression. SIRT down-regulation mediates the teratogenicity of diabetes leading to (NTD) formation. The study provides a mechanistic basis for the development of natural antioxidants and SIRT activators as therapeutics for diabetic embryopathy. PMID:26896748

  12. Detection of Foreign Matter in Transfusion Solution Based on Gaussian Background Modeling and an Optimized BP Neural Network

    PubMed Central

    Zhou, Fuqiang; Su, Zhen; Chai, Xinghua; Chen, Lipeng

    2014-01-01

    This paper proposes a new method to detect and identify foreign matter mixed in a plastic bottle filled with transfusion solution. A spin-stop mechanism and mixed illumination style are applied to obtain high contrast images between moving foreign matter and a static transfusion background. The Gaussian mixture model is used to model the complex background of the transfusion image and to extract moving objects. A set of features of moving objects are extracted and selected by the ReliefF algorithm, and optimal feature vectors are fed into the back propagation (BP) neural network to distinguish between foreign matter and bubbles. The mind evolutionary algorithm (MEA) is applied to optimize the connection weights and thresholds of the BP neural network to obtain a higher classification accuracy and faster convergence rate. Experimental results show that the proposed method can effectively detect visible foreign matter in 250-mL transfusion bottles. The misdetection rate and false alarm rate are low, and the detection accuracy and detection speed are satisfactory. PMID:25347581

  13. Self-organized criticality in a two-dimensional cellular automaton model of a magnetic flux tube with background flow

    NASA Astrophysics Data System (ADS)

    Dănilă, B.; Harko, T.; Mocanu, G.

    2015-11-01

    We investigate the transition to self-organized criticality in a two-dimensional model of a flux tube with a background flow. The magnetic induction equation, represented by a partial differential equation with a stochastic source term, is discretized and implemented on a two-dimensional cellular automaton. The energy released by the automaton during one relaxation event is the magnetic energy. As a result of the simulations, we obtain the time evolution of the energy release, of the system control parameter, of the event lifetime distribution and of the event size distribution, respectively, and we establish that a self-organized critical state is indeed reached by the system. Moreover, energetic initial impulses in the magnetohydrodynamic flow can lead to one-dimensional signatures in the magnetic two-dimensional system, once the self-organized critical regime is established. The applications of the model for the study of gamma-ray bursts (GRBs) is briefly considered, and it is shown that some astrophysical parameters of the bursts, like the light curves, the maximum released energy and the number of peaks in the light curve can be reproduced and explained, at least on a qualitative level, by working in a framework in which the systems settles in a self-organized critical state via magnetic reconnection processes in the magnetized GRB fireball.

  14. A Single-Center Experience of CNS Anomalies or Neural Tube Defects in Patients With Jarcho-Levin Syndrome.

    PubMed

    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. PMID:26239489

  15. Uptake and utilization of DL-5-[methyl-14C] tetrahydropteroylmonoglutamate by cultured cytotrophoblasts associated with neural tube defects.

    PubMed

    Habibzadeh, N; Schorah, C J; Seller, M J; Smithells, R W; Levene, M I

    1993-05-01

    A significant advance in the primary prevention of neural tube defects (NTD) is the recent finding that the periconceptional supplementation with folate has a 72% preventive effect against recurrence of NTD. However, failure of folate supplements to prevent all recurrences supports the multifactorial causation hypothesis, with inherited components exerting their influence, possibly through defects of storage, transport, or metabolism of folate. We have assessed the kinetics of DL-5-[methyl-14C]tetrahydropteroylmonoglutamate ([14C]MTHF) uptake and incorporation into the nucleic acid and protein pools by NTD-associated and control trophoblasts cultured in a medium lacking thymidine and other DNA precursors. We report a significant initial "lag" in the rate of incorporation of 14C label into the nucleic acid pool in NTD-associated trophoblasts. This we attribute to a defect in the de novo pathway of folate metabolism and its associated pathways, including the pathway for methionine synthesis, although the rate of incorporation of 14C label into the protein pool was not significantly different from that of the control cells. We discuss the possible pathways involved in the transfer of the label from the methyl group of [14C]MTHF to the nucleic acid pool, and argue that a slightly (but significantly) reduced rate of uptake into the NTD-associated cells is a reflection of the lag in incorporation into the nucleic acid pool. It is concluded that in the absence of thymidine, most of the NTD-associated trophoblasts require a longer period than controls to adjust to utilization of [14C]MTHF for synthesis of DNA, a period that could be crucial for completion of neural tube embryogenesis. We suggest that these findings could offer a way to a marker for risk of NTD. PMID:8475138

  16. Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice

    SciTech Connect

    Dawson, Jennifer E.; Raymond, Angela M.; Winn, Louise M. . E-mail: winnl@biology.queensu.ca

    2006-03-01

    In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-{kappa}B, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

  17. Raltitrexed's effect on the development of neural tube defects in mice is associated with DNA damage, apoptosis, and proliferation.

    PubMed

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

    2015-01-01

    The causal metabolic pathway and the underlying mechanism between folate deficiency and neural tube defects (NTDs) remain obscure. Thymidylate (dTMP) is catalyzed by thymidylate synthase (TS) using the folate-derived one-carbon unit as the sole methyl donor. This study aims to examine the role of dTMP biosynthesis in the development of neural tube in mice by inhibition of TS via a specific inhibitor, raltitrexed (RTX). Pregnant mice were intraperitoneally injected with various doses of RTX on gestational day 7.5, and embryos were examined for the presence of NTDs on gestational day 11.5. TS activity and changes of dUMP and dTMP levels were measured following RTX treatment at the optimal dose. DNA damage was determined by detection of phosphorylated replication protein A2 (RPA2) and ?-H2AX in embryos with NTDs induced by RTX. Besides, apoptosis and proliferation were also analyzed in RTX-treated embryos with NTDs. We found that NTDs were highly occurred by the treatment of RTX at the optimal dose of 11.5 mg/kg b/w. RTX treatment significantly inhibited TS activity. Meanwhile, dTMP was decreased associated with the accumulation of dUMP in RTX-treated embryos. Phosphorylated RPA2 and ?-H2AX were significantly increased in RTX-treated embryos with NTDs compared to control. More apoptosis and decreased proliferation were also found in embryos with NTDs induced by RTX. These results indicate that impairment of dTMP biosynthesis caused by RTX led to the development of NTDs in mice. DNA damage and imbalance between apoptosis and proliferation may be potential mechanisms. PMID:25245820

  18. Maternal Folate and Vitamin B12 Status and Neural Tube Defects in Northern Iran: A Case Control Study

    PubMed Central

    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 ?-fetoprotein levels. Folate, vitamin B12, homocysteine and alpha fetoprotein were evaluated after target ultrasonography. Findings Serum alpha fetoprotein level (meanSD) in cases and controls was 120.264.1 and 5033.5 iu/ml, respectively (P<0.05). The meanSD folate in cases and controls was 8.44.2 versus 9.34.2 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%: 0.5419.8). 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

  19. Consumption of folate deficient diet did not increase neural tube defects in LM/Bc mice exposed to fumonisin B1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides and F. proliferatum. It is found in corn and evidence suggests it is a possible risk factor for neural tube defects (NTD) in populations consuming large amounts of contaminated corn-based foods. The mechanism(s) underlying NTD i...

  20. The unique axon trajectory of the accessory nerve is determined by intrinsic properties of the neural tube in the avian embryo.

    PubMed

    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. PMID:26955910

  1. Elevated Nuclear and Cytoplasmic FTY720-Phosphate in Mouse Embryonic Fibroblasts Suggests the Potential for Multiple Mechanisms in FTY720-Induced Neural Tube Defects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    FTY720 (fingolimod) is an FDA-approved drug to treat relapsing remitting multiple sclerosis. FTY720 treatment in pregnant inbred LM/Bc mice results in approximately 60% of embryos having a neural tube defect (NTD). Sphingosine kinases (Sphk1, Sphk2) phosphorylate FTY720 in vivo to form the bioactive...

  2. Increased nuclear sphingoid base-1-phosphates and HDAC inhibition after fumonisin and FTY720-treatment: the link between epigenomic modifications and neural tube defects?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. 3D Reconstitution of the Patterned Neural Tube from Embryonic Stem Cells

    PubMed Central

    Meinhardt, Andrea; Eberle, Dominic; Tazaki, Akira; Ranga, Adrian; Niesche, Marco; Wilsch-Bruninger, Michaela; Stec, Agnieszka; Schackert, Gabriele; Lutolf, Matthias; Tanaka, EllyM.

    2014-01-01

    Summary 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. PMID:25454634

  4. Ectopic Myf5 or MyoD prevents the neuronal differentiation program in addition to inducing skeletal muscle differentiation, in the chick neural tube.

    PubMed

    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. PMID:14724123

  5. Fetal neural tube stem cells from Pax3 mutant mice proliferate, differentiate, and form synaptic connections when stimulated with folic acid.

    PubMed

    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 (P<0.05). Addition of FA to Sp(-/-) cultures increased the expression of a Pax3 downstream target, fgfr4, and rescued NSC proliferative potential, as demonstrated by a significant increase in neurosphere formation (P<0.01). To ascertain if FA affected cell 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. PMID:21521032

  6. A Study on The Incidence of Neural Tube Defects in A Tertiary Care Hospital Over A Period of Five Years

    PubMed Central

    Subramanian, Manickam; Rajilarajendran, Hannahsugirthabai; Ramanujam, Sailatha; Saktivel, Sathiya; Sivaanandam, Renuka

    2015-01-01

    Introduction Several congenital malformations affect developing fetuses, among which Neural tube defect (NTD) is most common. Folic acid supplementation brought decline in the incidence of NTDs. The present study aims at finding the incidence of NTDs in a tertiary care hospital and compares the results with the similar Indian studies published earlier. Materials and Methods The study was done at Chettinad Hospital & Research Institute (CHRI), Kelambakkam. The total number of deliveries was recorded for a period of five years from 2009 to 2013. Fetuses which were still born with neural defect were collected and observed in detail externally for the sex, type of NTD and other associated anomalies. Indian studies published between 1987 and 2014 reporting the incidence of NTDs among the births occurred were retrieved from the Internet and their various observations were used for comparison. Results The number of deliveries conducted between 2009 and 2013 at CHRI was 3220. Of these, babies born with NTDs were nine (5 males and 4 females). The incidence of fetuses with meroanencephaly, holoanencephaly, craniorachischisis, encephalocele and myelocele were 0.62, 0.62, 0.93, 0.31 and 0.31 per 1000 births respectively. Overall incidence of NTDs in the present study was 2.79/1000 births. Fetuses with NTDs also had the following anomalies – Club foot, cleft lip and palate and exomphalos. Conclusion Comparing the results with the previous studies it is clearly evident that the incidence of NTDs have significantly reduced from 11.42/1000 births to 2.79/1000 births. In most of the previous studies NTDs had a female preponderance whereas present study has a male preponderance.In older studies, spina bifida was the most common NTDs followed by anencephaly. But in the present study anencephaly was the common NTD than spina bifida. Incidence of NTDs has reduced due to various reasons like prenatal screening for fetal anomalies and folic acid supplementation. PMID:26393168

  7. Expression of the Celsr/flamingo homologue, c-fmi1, in the early avian embryo indicates a conserved role in neural tube closure and additional roles in asymmetry and somitogenesis.

    PubMed

    Formstone, Caroline J; Mason, Ivor

    2005-02-01

    Flamingo is one of a core group of proteins that regulate planar cell polarity of epithelial structures within the Drosophila embryo while their vertebrate counterparts have been implicated in the coordination of convergent extension movements during gastrulation and in neural tube closure, suggesting that planar polarity mechanisms also function in these processes. Failure of neural tube closure is one of the most common human birth defects, and a murine flamingo (fmi) homologue, Celsr1/fmi-1, was identified as the defective gene in two mouse mutants exhibiting failure of closure 1 of the neural tube. This failure resulted in craniorachischisis in which the neural tube is open from the midbrain posteriorly. The avian embryo provides a tractable system to study neural tube closure. We have identified a chick Celsr1/fmi-1 orthologue, c-fmi1 and provide the first study of expression of an avian flamingo gene. We show that expression is highly dynamic in the early embryo and that c-fmi1 transcripts become enriched within the avian neural epithelium at the initiation of neural tube closure, suggesting a conserved function for Flamingo proteins in this process. Our data also suggest a role for c-fmi1 in myotome development. PMID:15614764

  8. Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines.

    PubMed

    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. PMID:25905896

  9. Amniotic fluid levels of fibrin(ogen) degradation fragment E and alpha-fetoprotein in normal pregnancy and with fetal neural tube defect.

    PubMed

    Gordon, Y B; Ratky, S M; Leighton, P C; Kitau, M J; Chard, T

    1976-10-01

    Amniotic fluid levels of alpha-fetoprotein (AFP) and fibrin(ogen) degradation fragment E (FgE) were measured in 214 normal subjects and 27 pregnancies associated with an abnormal fetus (open neural tube defect or exomphalos). AFP levels showed no overlap between the normal and abnormal groups, thus confirming the reliability of the AFP assay in the detection of these abnormalities. FgE levels however showed considerable overlap and could not be used as a diagnostic parameter. Agarose gel chromatography of the amniotic fluid revealed the presence of large molecular weight FgE related antigen in open neural tube defect suggesting that leakage of proteins from exposed capillaries is responsible for the elevation of amniotic fluid protein levels. PMID:62585

  10. Amelioration of intracellular stress and reduction of neural tube defects in embryos of diabetic mice by phytochemical quercetin

    PubMed Central

    Cao, Lixue; Tan, Chengyu; Meng, Fantong; Liu, Peiyan; Reece, E. Albert; Zhao, Zhiyong

    2016-01-01

    Diabetes mellitus in early pregnancy causes birth defects, including neural tube defects (NTDs). Hyperglycemia increases production of nitric oxide (NO) through NO synthase 2 (Nos2) and reactive oxygen species (ROS), generating nitrosative and oxidative stress conditions in the embryo. The present study aimed to target nitrosative stress using a naturally occurring Nos2 inhibitor, quercetin, to prevent NTDs in the embryos of diabetic mice. Daily administration of quercetin to diabetic pregnant mice during the hyperglycemia-susceptible period of organogenesis significantly reduced NTDs and cell apoptosis in the embryos, compared with those of vehicle-treated diabetic pregnant mice. Using HPLC-coupled ESI-MS/MS, quercetin metabolites, including methylated and sulfonylated derivatives, were detected in the conceptuses. The methylated metabolite, 3-O-methylquercetin, was shown to reduce ROS level in embryonic stem cells cultured in high glucose. Quercetin treatment decreased the levels of Nos2 expression, protein nitrosylation, and protein nitration, alleviating nitrosative stress. Quercetin increased the expression of superoxide dismutase 1 and 2, and reduced the levels of oxidative stress markers. Expression of genes of redox regulating enzymes and DNA damage repair factors was upregulated. Our study demonstrates that quercetin ameliorates intracellular stresses, regulates gene expression, and reduces embryonic malformations in diabetic pregnancy. PMID:26887929

  11. Ectopic cross-talk between thyroid and retinoic acid signaling: A possible etiology for spinal neural tube defects.

    PubMed

    Li, Huili; Bai, Baoling; Zhang, Qin; Bao, Yihua; Guo, Jin; Chen, Shuyuan; Miao, Chunyue; Liu, Xiaozhen; Zhang, Ting

    2015-12-01

    Previous studies have highlighted the connections between neural tube defects (NTDs) and both thyroid hormones (TH) and vitamin A. However, whether the two hormonal signaling pathways interact in NTDs has remained unclear. We measured the expression levels of TH signaling genes in human fetuses with spinal NTDs associated with maternal hyperthyroidism as well as levels of retinoic acid (RA) signaling genes in mouse fetuses exposed to an overdose of RA using NanoString or real-time PCR on spinal cord tissues. Interactions between the two signaling pathways were detected by ChIP assays. The data revealed attenuated DIO2/DIO3 switching in fetuses with NTDs born to hyperthyroid mothers. The promoters of the RA signaling genes CRABP1 and RARB were ectopically occupied by increased RXRG and RXRB but displayed decreased levels of inhibitory histone modifications, suggesting that elevated TH signaling abnormally stimulates RA signaling genes. Conversely, in the mouse model, the observed decrease in Dio3 expression could be explained by increased levels of inhibitory histone modifications in the Dio3 promoter region, suggesting that overactive RA signaling may ectopically derepress TH signaling. This study thus raises in vivo a possible abnormal cross-promotion between two different hormonal signals through their common RXRs and the subsequent recruitment of histone modifications, prompting further investigation into their involvement in the etiology of spinal NTDs. PMID:26188161

  12. Supplementation With Vitamin D3 During Pregnancy Protects Against Lipopolysaccharide-Induced Neural Tube Defects Through Improving Placental Folate Transportation

    PubMed Central

    Chen, Yuan-Hua; Yu, Zhen; Fu, Lin; Xia, Mi-Zhen; Zhao, Mei; Wang, Hua; Zhang, Cheng; Hu, Yong-Fang; Tao, Fang-Biao; Xu, De-Xiang

    2015-01-01

    Several reports demonstrated that maternal lipopolysaccharide (LPS) exposure at middle gestational stage caused neural tube defects (NTDs). This study investigated the effects of supplementation with vitamin D3 (VitD3) during pregnancy on LPS-induced NTDs. Pregnant mice except controls were ip injected with LPS (25 μg/kg) daily from gestational day (GD)8 to GD12. In LPS+VitD3 group, pregnant mice were orally administered with VitD3 (25 μg/kg) before LPS injection. As expected, a 5-day LPS injection resulted in 62.5% (10/16) of dams and 20.3% of fetuses with NTDs. Additional experiment showed that a 5-day LPS injection downregulated placental proton-coupled folate transporter (pcft) and reduced folate carrier 1 (rfc1), 2 major folate transporters in placentas. Consistent with downregulation of placental folate transporters, folate transport from maternal circulation into embryos was disturbed in LPS-treated mice. Interestingly, VitD3 not only inhibited placental inflammation but also attenuated LPS-induced downregulation of placental folate transporters. Correspondingly, VitD3 markedly improved folate transport from maternal circulation into the embryos. Importantly, supplementation with VitD3 during pregnancy protected mice from LPS-induced NTDs. Taken together, these results suggest that supplementation with VitD3 during pregnancy prevents LPS-induced NTDs through inhibiting placental inflammation and improving folate transport from maternal circulation into the embryos. PMID:25673501

  13. Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages.

    PubMed

    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 < 0.001). Age and religion had no significant effect. An urgent need exists to improve the 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). PMID:15050876

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

    PubMed Central

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

    PubMed Central

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

    2016-01-01

    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. PMID:27005659

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

    PubMed

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

    2016-01-01

    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. PMID:27005659

  17. Amelioration of intracellular stress and reduction of neural tube defects in embryos of diabetic mice by phytochemical quercetin.

    PubMed

    Cao, Lixue; Tan, Chengyu; Meng, Fantong; Liu, Peiyan; Reece, E Albert; Zhao, Zhiyong

    2016-01-01

    Diabetes mellitus in early pregnancy causes birth defects, including neural tube defects (NTDs). Hyperglycemia increases production of nitric oxide (NO) through NO synthase 2 (Nos2) and reactive oxygen species (ROS), generating nitrosative and oxidative stress conditions in the embryo. The present study aimed to target nitrosative stress using a naturally occurring Nos2 inhibitor, quercetin, to prevent NTDs in the embryos of diabetic mice. Daily administration of quercetin to diabetic pregnant mice during the hyperglycemia-susceptible period of organogenesis significantly reduced NTDs and cell apoptosis in the embryos, compared with those of vehicle-treated diabetic pregnant mice. Using HPLC-coupled ESI-MS/MS, quercetin metabolites, including methylated and sulfonylated derivatives, were detected in the conceptuses. The methylated metabolite, 3-O-methylquercetin, was shown to reduce ROS level in embryonic stem cells cultured in high glucose. Quercetin treatment decreased the levels of Nos2 expression, protein nitrosylation, and protein nitration, alleviating nitrosative stress. Quercetin increased the expression of superoxide dismutase 1 and 2, and reduced the levels of oxidative stress markers. Expression of genes of redox regulating enzymes and DNA damage repair factors was upregulated. Our study demonstrates that quercetin ameliorates intracellular stresses, regulates gene expression, and reduces embryonic malformations in diabetic pregnancy. PMID:26887929

  18. [Differences in folic-acid policy and the prevalence of neural-tube defects in Europe; recommendations for food fortification in a EUROCAT report].

    PubMed

    Meijer, W M; de Walle, H E K

    2005-11-12

    The European Registration Of Congenital Anomalies and Twins (EUROCAT), a network of 40 European registries of congenital anomalies, has published a special report on the prevention of neural-tube defects by, periconceptional folic-acid supplementation in Europe. This report reviews the progress made in 17 European countries since i99I in terms of developing and implementing public health policies to raise periconceptional folate status. Data on the prevalence of neural-tube defects in 1980-2000 were also analysed. - At the beginning of 2002, 10 of the 17 countries had an official government recommendation that women planning a pregnancy should take folic-acid supplementation daily. Only 7 countries implemented official health-education initiatives. - Despite the various measures taken to date, the majority of women in all countries surveyed are not taking periconceptional folic-acid supplements. Even in the Netherlands, where the percentage of planned pregnancies is estimated at 85%, only 36% of women take folic-acid supplements during the advised period. - Overall, the number of neural-tube defects has not decreased in Europe. A slight decrease was seen in those countries with an official policy regarding periconceptional folic-acid supplementation. - It is clear from the report that more effective prevention of neuraltube defects could be achieved with folic-acid fortification of staple foods; this approach has led to a reduction in the prevalence of neuraltube defects in the US and Canada. This approach can also prevent the majority of neural-tube defects in unplanned pregnancies and reduce the socioeconomic differences in prevalence. PMID:16320666

  19. Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse.

    PubMed

    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. PMID:12842012

  20. Amniotic fluid analysis in prenatal diagnosis of neural tube defects: a comparison between six biochemical tests supplementary to the measurement of amniotic fluid alpha-fetoprotein.

    PubMed

    Toftager-Larsen, K; Wandrup, J; Nørgaard-Pedersen, B

    1984-11-01

    Concanavalin A (con A) and lens culinaris agglutinin (LCA) microheterogeneity pattern of AFP (crossed affinity immunoelectrophoresis), alpha-2-macroglobulin and synaptic membrane protein D-2 (rocket immunoelectrophoresis) and qualitative (polyacrylamide gel electrophoresis) and quantitative (enzyme kinetic reaction rate) acetylcholinesterase were analysed in 87 consequtive samples from normal pregnancies and 37 abnormal samples (fetal neural tube defect or abdominal wall defect). Very few false positive results were obtained in normal pregnancies with any of the tests. In all cases of neural tube defects the correct result was obtained with qualitative acetylcholinesterase analysis, whereas only 2/3 of the abdominal wall defects were correctly predicted. Testing with con A or LCA was less optimal in neural tube defects, whereas all abdominal wall defects could be predicted correctly. Acetylcholinesterase in the quantitative test and protein D-2 did not decrease the rate of false results. Determination of the alpha-2-macroglobulin concentration performed well in the present study, but is not recommended because of the very high susceptibility to contamination of amniotic fluid with fetal or maternal blood. PMID:6209039

  1. Genetic diversity of stem cells and their functional impact on the development of neural tube defects in Eastern population of India.

    PubMed

    Saxena, A K; Pandey, S; Pandey, L K

    2013-01-01

    Anencephaly and myelomeningocele are the 2 most common forms of neural tube defects (NTDs). During embryogenesis large numbers of extrinsic and intrinsic factors are responsible for the closing of the neural tube. "Stem cells" maintain the pluripotency during differentiation of 3 germ layers, including the neural ectoderm. We examined the role of Oct4, Nanog3, and Sox2 genes in the etiopathology of NTDs in an eastern Indian population using PCR-based DNA analysis. The highest frequency (16%) of complete loss of the Sox2 gene was found in NTDs. The highest frequency (48%) of overexpression (upregulation) was found for Nanog3, while 40% was observed for Oct4 and Sox2. The odds ratio for cases versus controls was from 0.132 at 95% confidence interval = 0.005-1.298 for Nanog3 to 2.316 (0.424-13.812) for Oct4. The highest frequency (77%) of overexpression for Nanog3 and Sox2 was observed in encephalocele and anencephalic patients, while in the comparison of regional variation, i.e., cephalic to caudal regions of NTDs, the highest frequency of downregulation (regression) of Nanog3 and Sox2 was found in lumbosacral myelomeningocele patients. However, cervical myelomeningocele patients had the highest frequency of overexpression in all 3 genes, suggesting that the mutational spectra of stem cells influence the cells of the neural crest in NTDs. PMID:23979878

  2. Association of the Maternal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects in Offsprings: Evidence from 25 Case-Control Studies

    PubMed Central

    Zou, Peng; Ji, Guixiang; Gu, Aihua; Zhao, Peng

    2012-01-01

    Background Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA methylation, DNA synthesis, and DNA repair. In addition, it is a possible risk factor in neural tube defects (NTDs). The association of the C677T polymorphism in the MTHFR gene and NTD susceptibility has been widely demonstrated, but the results remain inconclusive. In this study, we performed a meta-analysis with 2429 cases and 3570 controls to investigate the effect of the MTHFR C677T polymorphism on NTDs. Methods An electronic search of PubMed and Embase database for papers on the MTHFR C677T polymorphism and NTD risk was performed. All data were analysed with STATA (version 11). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were performed in our meta-analysis. Results A significant association between the MTHFR C677T polymorphism and NTD susceptibility was revealed in our meta-analysis ( TT versus CC: OR ?=?2.022, 95% CI: 1.508, 2.712; CT+TT versus CC: OR ?=?1.303, 95% CI: 1.089, 1.558; TT versus CC+CT: OR ?=?1.716, 95% CI: 1.448, 2.033; 2TT+CT versus 2CC+CT: OR ?=?1.330, 95% CI: 1.160, 1.525). Moreover, an increased NTD risk was found after stratification of the MTHFR C677T variant data by ethnicity and source of controls. Conclusion The results suggested the maternal MTHFR C677T polymorphism is a genetic risk factor for NTDs. Further functional studies to investigate folate-related gene polymorphisms, periconceptional multivitamin supplements, complex interactions, and the development of NTDs are warranted. PMID:23056169

  3. Patterns of folic acid use in pregnant Saudi women and prevalence of neural tube defects — Results from a nested case–control study☆

    PubMed Central

    Al Rakaf, Maha S.; Kurdi, Ahmed M.; Ammari, Amer N.; Al Hashem, Amal M.; Shoukri, Mohamed M.; Garne, Ester; Majeed-Saidan, Muhammad Ali

    2015-01-01

    Background Although the role of folic acid (FA) in preventing neural tube defects (NTDs) is well documented, its optimal intake in pregnant women is still low in many countries. Here, we prospectively studied the prevalence of NTDs in the newborns and the patterns of FA intake in pregnant Saudi mothers. Methods This case–control study was nested within a 3-year project (July 2010 to June 2013) to study the patterns of birth defects in the offspring of Saudi women who received their antenatal care and delivered at Prince Sultan Military Medical City, Riyadh—Saudi Arabia. Enrolled mothers were divided into 4 groups: group 1 (FA taken before pregnancy and continued regularly after conception), group 2 (FA taken post-conception), group 3 (no FA intake), and group 4 (did not remember or were unsure of taking FA). Control mothers were randomly selected from those with normal first obstetrical ultrasound scan at 18–22 weeks of gestation. Results The cohort included 30,531 mothers giving birth to 28,646 infants. We studied 1179 mothers of babies with birth defects (BDs) and 1262 control mothers. There were 237 (9.7%) mothers in-group 1; 2001 (82%) in-group 2; 154 (6.3%) in-group 3; and 49 (2%) in-group 4. There were 49 babies with NTDs, a prevalence of 1.7/1000 total births. Among the studied mothers 2274 (93%) took FA either full or partial course. Conclusion The high prevalence of NTDs and the low optimal FA intake highlight the need for a strict implementation of staple food fortification and health education program for Saudi women. PMID:26844119

  4. "Polymorphisms in folate metabolism genes as maternal risk factor for neural tube defects: an updated meta-analysis".

    PubMed

    Yadav, Upendra; Kumar, Pradeep; Yadav, Sushil Kumar; Mishra, Om Prakash; Rai, Vandana

    2015-02-01

    Epidemiological studies have evaluated the association between maternal methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms and risk of neural tube defects (NTDs) in offspring. However, the results from the published studies on the association between these three polymorphisms and NTD risk are conflicting. To derive a clearer picture of association between these three maternal polymorphisms and risk of NTD, we performed meta-analysis. A comprehensive search was conducted to identify all case-control studies of maternal MTHFR and MTRR polymorphisms and NTD risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that maternal MTHFR C677T polymorphism (OR(TvsC) =1.20; 95% CI = 1.13-1.28) and MTRR A66G polymorphism (OR(GvsA) = 1.21; 95% CI = 0.98-1.49) were risk factors for producing offspring with NTD but maternal MTHFR A1298C polymorphism (OR(CvsA) = 0.91; 95% CI = 0.78-1.07) was not associated with NTD risk. However, in stratified analysis by geographical regions, we found that the maternal C677T polymorphism was significantly associated with the risk of NTD in Asian (OR(TvsC) = 1.43; 95% CI: 1.05-1.94), European (OR(TvsC) = 1.13; 95% CI: 1.04-1.24) and American (OR(TvsC) = 1.26; 95% CI: 1.13-1.41) populations. In conclusion, present meta-analysis supports that the maternal MTHFR C677T and MTRR A66G are polymorphisms contributory to risk for NTD. PMID:25005003

  5. Association between MTHFD1 G1958A Polymorphism and Neural Tube Defects Susceptibility: A Meta-Analysis

    PubMed Central

    Jiang, Jianxin; Zhang, Yanfei; Wei, Liang; Sun, Zhiyang; Liu, Zhongmin

    2014-01-01

    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. PMID:24977710

  6. A randomised trial of low dose folic acid to prevent neural tube defects. The Irish Vitamin Study Group.

    PubMed

    Kirke, P N; Daly, L E; Elwood, J H

    1992-12-01

    A randomised trial was initiated in Ireland in 1981 to determine if periconceptional supplementation with either folic acid alone or a multivitamin preparation alone could reduce the recurrence risk of neural tube defects (NTDs) in women with a previously affected pregnancy from 5.0% to 1.0% or less. The trial was concluded before the initial target number of study subjects was reached and without a clear treatment effect being observed. A total of 354 women were randomised to receive one of three treatments: folic acid, multivitamins without folic acid, and folic acid plus multivitamins. At the end of the trial 257 women had had a first trial pregnancy outcome (261 infants/fetuses) where the presence or absence of NTDs was ascertainable. There was one NTD recurrence in the 89 infants/fetuses of women in the multivitamin group and no recurrence in the 172 infants/fetuses of women in the folic acid groups, a non-significant difference. Otherwise eligible women who were pregnant when first contacted constituted a non-randomised control group; there were three recurrences among the 103 infants in this group. The difference in the recurrence rate between the folic acid groups and the non-randomised controls was statistically significant but we have reservations about the validity of this comparison. Although our findings do not provide clear evidence of a protective effect of folic acid supplementation they are consistent with those of the Medical Research Council (MRC) trial which demonstrated the efficacy of folic acid in preventing recurrence of NTDs and they raise the possibility that folic acid may be protective at a much lower dosage than that used in the MRC trial. PMID:1489222

  7. Maternal consumption of non-staple food in the first trimester and risk of neural tube defects in offspring.

    PubMed

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

    2015-05-01

    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 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. PMID:25919306

  8. Nausea and Vomiting in Early Pregnancy and the Risk of Neural Tube Defects: a Case-Control Study

    PubMed Central

    Lu, Qing-Bin; Wang, Zhi-Ping; Gao, Li-Jie; Gong, Rui; Sun, Xi-Hong; Wang, Meng; Zhao, Zhong-Tang

    2015-01-01

    There has been considerable professional debate on the association between nausea and vomiting in early pregnancy (NVP) and neural tube defects (NTDs) risk. This study explored the association between NVP and NTDs risk, and the effect of folic acid supplements on the association. A 1:1 matched case-control study was conducted and conditional logistic regression model was used to analyze the associations. The result showed the odds ratio (OR) of severe NVP for NTDs was 2.403 (95%CI 1.437,4.017; P<0.001) and that of moderate NVP was 1.469 (95%CI 1.063,2.031; P = 0.020) compared with light NVP when adjusted by the potential confounders. Stratified by intake of folic acid supplements, the ORs for severe and moderate NVP turned to 2.147 (95%CI 1.140, 4.043; P = 0.018) and 2.055 (95%CI 1.320, 3.199; P = 0.001) in the stratum of non-intake of folic acid supplements while ORs reduced to 1.851 (95%CI 0.729, 4.699; P = 0.195) and 1.003 (95%CI 0.594, 1.694; P = 0.992) in the stratum of intake of folic acid supplements, respectively. We conclude that severe/moderate NVP has an association with the risk of NTDs, which was not found in the group with intake of folic acid supplements. Folic acid supplements should be recommended to use for the prevention of NTDs. PMID:25567703

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

    PubMed

    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. PMID:25131448

  10. Neural Tube Defects

    MedlinePlus

    ... folate. Good sources of folate are: Beans Leafy green vegetables Orange juice You have to eat a ... folate. Good sources of folate are: Beans Leafy green vegetables Orange juice You have to eat a ...

  11. A consideration of the evidence that genetic defects in planar cell polarity contribute to the etiology of human neural tube defects.

    PubMed

    Juriloff, Diana M; Harris, Muriel J

    2012-10-01

    A variety of human birth defects originate in failure of closure of the embryonic neural tube. The genetic cause of the most common nonsyndromic defects, spina bifida (SB) or anencephaly, is considered to be combinations of variants at multiple genes. The genes contributing to the etiology of neural tube closure defects (NTDs) are unknown. Mutations in planar cell polarity (PCP) genes in mice cause a variety of defects including the NTD, craniorachischisis, and sometimes SB or exencephaly (EX); they also demonstrate the role of digenic combinations of PCP mutants in NTDs. Recent studies have sought rare predicted-to-be-deleterious alterations (putative mutations) in coding sequence of PCP genes in human cases with various anomalies of the neural tube. This review summarizes the cumulative results of these studies according to a framework based on the embryopathogenesis of NTDs, and considers some of the insights from the approaches used and the limitations. Rare putative mutations in the PCP genes VANGL2, SCRIB, DACT1, and CELSR1 cumulatively contributed to over 20% of cases with craniorachischisis, a rare defect; no contributing variants were found for PRICKLE1 or PTK7. PCP rare putative mutations had a weaker role in myelomeningocele (SB), being found in approximately 6% of cases and cumulated across CELSR1, FUZ, FZD6, PRICKLE1, VANGL1, and VANGL2. These results demonstrate that PCP gene alterations contribute to the etiology of human NTDs. We recommend that future research should explore other types of PCP gene variant such as regulatory mutations and low frequency (1 to 5%) deleterious polymorphisms. PMID:23024041

  12. Health needs assessment for congenital anomalies in middle-income countries: Examining the case for neural tube defects in Brazil.

    PubMed

    Schuler-Faccini, Lavinia; Sanseverino, Maria Teresa V; de Rocha Azevedo, Lígia Marques; Moorthie, Sowmiya; Alberg, Corinna; Chowdhury, Susmita; Sagoo, Gurdeep S; Burton, Hilary; Nacul, Luis C

    2014-04-01

    Recent economic improvement in Brazil has been reflected in better maternal-child health indicators, with decreases in infant and perinatal mortality. However, under-five mortality due to congenital disorders remained unchanged, and congenital disorders have become the second leading cause of infant mortality. In the present study, we used the PHG Foundation Health Needs Assessment (HNA) Toolkit with the objective of first assessing the burden of disease caused by neural tube defects (NTDs) in Brazil and the impact of interventions already put in place to address the burden, and second to evaluate and prioritize further interventions and policies required for its prevention and treatment. The results from these two components of the HNA process are described in this paper. The published literature was reviewed to identify studies of NTDs (prevalence; morbidity; prenatal, perinatal, and postnatal mortality; treatment or prevention). Data on indicators of maternal and child health were obtained directly from the Brazilian Ministry of Health, through the online Live Births Information System (SINASC) and from the Mortality Information System (SIM). Descriptive analyses included reports of the rates of NTD in liveborns, fetal, and infant deaths. Differences between folic acid flour pre-fortification (2001-2004) and post-fortification (2006-2010) periods were expressed as prevalence rate ratios. Around 20 % of fetal deaths were related to congenital disorders with approximately 5 % of those being NTDs. For infant mortality, congenital disorders were notified in approximately 15 % of cases, with NTDs present in 10 % of the malformed children. Although statistically significant, the prevalence rate ratio (PRR) for spina bifida in live births was only 0.937 (95 % confidence interval (CI) 0.884-0.994), a decrease of 6.3 % when comparing the pre and post-fortification periods. The impact of fortification seemed to be more visible in fetal deaths due to anencephaly (PRR = 0.727, 95 % CI 0.681-0.777) and for spina bifida (PRR = 0.700, 95 % CI 0.507-0.967) with associated decreases of 27.3 and 30 %. The lower impact of folic acid fortification in Brazil, compared to other Latin-American countries, can be due to differences in dietary habits, concentration of folic acid in flour, as well as characteristic population ethnic composition. The HNA led to the identification of the needs to be addressed in Brazil, including the improvement of reporting congenital disorders within the nationwide birth certification system, and revision of the policy of flour folic acid fortification. PMID:23990401

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

    PubMed Central

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

    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 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. PMID:25919306

  14. 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

    PubMed Central

    Ma, Fukai; Xiao, Zhifeng; Meng, Danqing; Hou, Xianglin; Zhu, Jianhong; Dai, Jianwu; Xu, Ruxiang

    2014-01-01

    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. PMID:25322152

  15. Polymorphisms in MTHFD1 Gene and Susceptibility to Neural Tube Defects: A Case-Control Study in a Chinese Han Population with Relatively Low Folate Levels

    PubMed Central

    Wu, Jian; Bao, Yihua; Lu, Xiaolin; Wu, Lihua; Zhang, Ting; Guo, Jin; Yang, Jian

    2015-01-01

    Background The polymorphism of methylenetetrahydrofolate dehydrogenase (MTHFD1) has been reported as a risk factor for neural tube defects (NTDs). In the present study, we aimed to investigate whether the single-nucleotide polymorphisms (SNPs) of MTHFD1 gene are associated with NTDs in a Chinese population and to determine their mechanism of action. Material/Methods MTHFD1 gene was scanned in a total of 270 NTDs cases and 192 healthy controls by using next-generation sequencing (NGS) method. After quality control procedures, 208 selected SNP sites in MTHFD1 gene were enrolled for follow-up statistical association analyses. Functional analyses were also performed for significant SNPs through bioinformatics analysis. Folic acid levels of brain tissue in available NTDs cases and healthy controls (113 and 123, respectively) were measured. Statistical and bioinformatics analyses were performed to investigate the relationship between SNPs in MTHFD1 and susceptibility to NTDs. Results Statistical analysis showed that 2 independent SNPs, rs1956545 and rs56811449, confer the risk of NTDs (P value=0.0195, OR (odds ratio)=1.41, 95% CI (confidence interval)=1.06–1.88; P value=0.0107, OR=0.56, 95% CI=0.36–0.87). The haplotype GGGG, which consists of 4 SNPs (rs2236225, rs2236224, rs1256146, and rs6573559), is also associated with risk of NTDs (P value=0.0438, OR=0.7180, 95% CI=0.5214–0.9888). The risk allele C of rs1956545 is also associated with decreased folic acid levels in the brain (P value=0.0222, standard beta=−0.2238, 95% CI=−0.4128 – −0.0349) according to analysis in the subset of NTDs cases and healthy controls. Bioinformatics analysis indicates that rs1956545 and rs56811449 are within ENCODE regulatory regions, the open chromatin regions of blastula Trophoblast cell line, and histone-marked region of brain astrocyte cell line. Conclusions The polymorphism of SNP loci rs1956545 and rs56811449 as well as a haplotype in MTHFD1 gene could serve as an indicator for the occurrence of NTDs in Chinese population and some specific genotypes of the loci may have lower risk of developing NTDs. PMID:26343515

  16. Female predisposition to cranial neural tube defects is not because of a difference between the sexes in the rate of embryonic growth or development during neurulation.

    PubMed Central

    Brook, F A; Estibeiro, J P; Copp, A J

    1994-01-01

    The susceptibility of females to anencephaly is well established and has been suggested to result from a slower rate of growth and development of female embryos during cranial neurulation. We have tested this hypothesis by measuring the rates of growth and development, both in utero and in vitro, of male and female embryos of the curly tail (ct) mutant mouse strain, in which cranial neural tube defects occur primarily in females. Embryonic growth was assessed by increase in protein content, while development progression was judged from increase in somite number and morphological score. Embryos were sexed by use of the polymerase chain reaction to amplify a DNA sequence specific to the Y chromosome, and by sex chromatin analysis. We find that, during neurulation (between 8.5 and 10.5 days of gestation), males are advanced in growth and development relative to their female litter mates, but that the rates of growth and development do not differ between the sexes during this period. We conclude that rate of embryonic growth and development is unlikely to determine susceptibility to cranial neural tube defects. It seems more likely that male and female embryos differ in some specific aspect(s) of the neurulation process that increases the susceptibility of females to development of anencephaly. Images PMID:8064816

  17. Single-tube multiplexed molecular detection of endemic porcine viruses in combination with background screening for transboundary diseases.

    PubMed

    Wernike, Kerstin; Hoffmann, Bernd; Beer, Martin

    2013-03-01

    Detection of several pathogens with multiplexed real-time quantitative PCR (qPCR) assays in a one-step setup allows the simultaneous detection of two endemic porcine and four different selected transboundary viruses. Reverse transcription (RT)-qPCR systems for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), two of the most economically important pathogens of swine worldwide, were combined with a screening system for diseases notifiable to the World Organization of Animal Health, namely, classical and African swine fever, foot-and-mouth disease, and Aujeszky's disease. Background screening was implemented using the identical fluorophore for all four different RT-qPCR assays. The novel multiplex RT-qPCR system was validated with a large panel of different body fluids and tissues from pigs and other animal species. Both reference samples and clinical specimens were used for a complete evaluation. It could be demonstrated that a highly sensitive and specific parallel detection of the different viruses was possible. The assays for the notifiable diseases were even not affected by the simultaneous amplification of very high loads of PRRSV- and PCV2-specific sequences. The novel broad-spectrum multiplex assay allows in a unique form the routine investigation for endemic porcine pathogens with exclusion diagnostics of the most important transboundary diseases in samples from pigs with unspecific clinical signs, such as fever or hemorrhages. The new system could significantly improve early detection of the most important notifiable diseases of swine and could lead to a new approach in syndromic surveillance. PMID:23303496

  18. Neural Segregation of Concurrent Speech: Effects of Background Noise and Reverberation on Auditory Scene Analysis in the Ventral Cochlear Nucleus.

    PubMed

    Sayles, Mark; Stasiak, Arkadiusz; Winter, Ian M

    2016-01-01

    Concurrent complex sounds (e.g., two voices speaking at once) are perceptually disentangled into separate "auditory objects". This neural processing often occurs in the presence of acoustic-signal distortions from noise and reverberation (e.g., in a busy restaurant). A difference in periodicity between sounds is a strong segregation cue under quiet, anechoic conditions. However, noise and reverberation exert differential effects on speech intelligibility under "cocktail-party" listening conditions. Previous neurophysiological studies have concentrated on understanding auditory scene analysis under ideal listening conditions. Here, we examine the effects of noise and reverberation on periodicity-based neural segregation of concurrent vowels /a/ and /i/, in the responses of single units in the guinea-pig ventral cochlear nucleus (VCN): the first processing station of the auditory brain stem. In line with human psychoacoustic data, we find reverberation significantly impairs segregation when vowels have an intonated pitch contour, but not when they are spoken on a monotone. In contrast, noise impairs segregation independent of intonation pattern. These results are informative for models of speech processing under ecologically valid listening conditions, where noise and reverberation abound. PMID:27080680

  19. Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

    SciTech Connect

    Haghighi Poodeh, Saeid; Alhonen, Leena; Salonurmi, Tuire; Savolainen, Markku J.

    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 stage is so vulnerable to the development of neural tube defect, and growth restriction, the findings previously observed in fetal alcohol syndrome.

  20. Generation and characterization of a novel neural crest marker allele, Inka1-LacZ, reveals a role for Inka1 in mouse neural tube closure

    PubMed Central

    Reid, Bethany S.; Sargent, Thomas D.; Williams, Trevor

    2010-01-01

    Previous studies identified Inka1 as a gene regulated by AP-2α in the neural crest required for craniofacial morphogenesis in fish and frog. Here, we extend the analysis of Inka1 function and regulation to the mouse by generating a LacZ knock-in allele. Inka1-LacZ allele expression occurs in the cephalic mesenchyme, heart, and paraxial mesoderm prior to E8.5. Subsequently, expression is observed in the migratory neural crest cells and their derivatives. Consistent with expression of Inka1 in tissues of the developing head during neurulation, a low percentage of Inka1−/− mice show exencephaly while the remainder are viable and fertile. Further studies indicate that AP-2α is not required for Inka1 expression in the mouse, and suggest that there is no significant genetic interaction between these two factors during embryogenesis. Together, these data demonstrate that while the expression domain of Inka1 is conserved among vertebrates, its function and regulation are not. PMID:20175189

  1. [Prevention of neural tube defects: prevalence of folic acid supplementation during pregnancy and associated factors in Pelotas, Rio Grande do Sul State, Brazil].

    PubMed

    Mezzomo, Cíntia Leal Sclowitz; Garcias, Gilberto de Lima; Sclowitz, Marcelo Leal; Sclowitz, Iandora Timm; Brum, Clarice Brinck; Fontana, Tiago; Unfried, Ricardo Issler

    2007-11-01

    To determine folic acid use and associated factors, a cross-sectional population-based study was conducted in all five maternity hospitals in Pelotas, Rio Grande do Sul State, Brazil. Data were collected from April 1 to August 15, 2006 (n = 1,450 women). A standard questionnaire was applied in the hospitals. Statistical analysis used Poisson regression. Prevalence of folic acid consumption during pregnancy was 31.8%, and periconceptional use was 4.3%. The following were associated with folic acid use: white skin color, schooling > 9 years, family income > R$600, age > 30 years, planned pregnancy, > or =7 prenatal visits, knowledge on folic acid, and prenatal care in the private health system. In order to prevent neural tube defects, it is important to promote folic acid use among childbearing-age women and to supply folic acid to poor women. PMID:17952264

  2. Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks

    PubMed Central

    Bártfai, Zoltán; Bánhidy, Ferenc

    2011-01-01

    The history of intervention trials of periconception folic acid with multivitamin and folic acid supplementation in women has shown a recent breakthrough in the primary prevention of structural birth defects, namely neural-tube defects and some other congenital abnormalities. Recently, some studies have demonstrated the efficacy of this new method in reducing congenital abnormalities with specific origin; for example, in the offspring of diabetic and epileptic mothers, and in pregnancy with high fever. The benefits and drawbacks of four possible uses of periconception folate/folic acid and multivitamin supplementation are discussed: we believe there has been a missed opportunity to implement this preventive approach in medical practice. The four methods are as follows: (i) dietary intake of folate and other vitamins, (ii) periconception folic acid/multivitamin supplementation, (iii) food fortification with folic acid, and (iv) the combination of oral contraceptives with 6S-5-methytetrahydrofolate (‘folate’). PMID:25083211

  3. Maternal PCMT1 gene polymorphisms and the risk of neural tube defects in a Chinese population of Lvliang high-risk area.

    PubMed

    Zhao, Huizhi; Wang, Fang; Wang, Jianhua; Xie, Hua; Guo, Jin; Liu, Chi; Wang, Li; Lu, Xiaolin; Bao, Yihua; Wang, Guoliang; Zhong, Rugang; Niu, Bo; Zhang, Ting

    2012-09-01

    Protein-L-isoaspartate (D-aspartate) O-methyltransferase 1 (PCMT1) gene encodes for the protein repair enzyme L-isoaspartate (D-aspartate) O-methyltransferase (PIMT), which is known to protect certain neural cells from Bax-induced apoptosis. Previous study has shown that PCMT1 polymorphisms rs4552 and rs4816 of infant are associated with spina bifida in the Californian population. The association between maternal polymorphism and neural tube defects is still uncovered. A case-control study was conducted to investigate a possible association between maternal PCMT1 and NTDs in Lvliang high-risk area of Shanxi Province in China, using a high-resolution DNA melting analysis genotyping method. We found that increased risk for anencephaly in isolated NTDs compared with the normal control group was observed for the G (vs. A) allele (p=0.034, OR=1.896, 95% CI, 1.04-3.45) and genotypes GG+GA (p=0.025, OR=2.237, 95% CI, 1.09-4.57). Although the significance was lost after multiple comparison correction, the results implied that maternal polymorphisms in PCMT1 might be a potential genetic risk factor for isolated anencephaly in this Chinese population. PMID:22647835

  4. The roof plate boundary is a bi-directional organiser of dorsal neural tube and choroid plexus development.

    PubMed

    Broom, Emma R; Gilthorpe, Jonathan D; Butts, Thomas; Campo-Paysaa, Florent; Wingate, Richard J T

    2012-11-01

    The roof plate is a signalling centre positioned at the dorsal midline of the central nervous system and generates dorsalising morphogenic signals along the length of the neuraxis. Within cranial ventricles, the roof plate gives rise to choroid plexus, which regulates the internal environment of the developing and adult brain and spinal cord via the secretion of cerebrospinal fluid. Using the fourth ventricle as our model, we show that the organiser properties of the roof plate are determined by its boundaries with the adjacent neuroepithelium. Through a combination of in ovo transplantation, co-culture and electroporation techniques in chick embryos between embryonic days 3 and 6, we demonstrate that organiser properties are maintained by interactions between the non-neural roof plate and the neural rhombic lip. At the molecular level, this interaction is mediated by Delta-Notch signalling and upregulation of the chick homologue of Hes1: chairy2. Gain- and loss-of-function approaches reveal that cdelta1 is both necessary and sufficient for organiser function. Our results also demonstrate that while chairy2 is specifically required for the maintenance of the organiser, its ectopic expression is not sufficient to recapitulate organiser properties. Expression of atonal1 in the rhombic lip adjacent at the roof plate boundary is acutely dependent on both boundary cell interactions and Delta-Notch signalling. Correspondingly, the roof plate boundary organiser also signals to the roof plate itself to specify the expression of early choroid plexus markers. Thus, the roof plate boundary organiser signals bi-directionally to acutely coordinate the development of adjacent neural and non-neural tissues. PMID:23052907

  5. Rare and private variations in neural crest, apoptosis and sarcomere genes define the polygenic background of isolated Tetralogy of Fallot.

    PubMed

    Grunert, Marcel; Dorn, Cornelia; Schueler, Markus; Dunkel, Ilona; Schlesinger, Jenny; Mebus, Siegrun; Alexi-Meskishvili, Vladimir; Perrot, Andreas; Wassilew, Katharina; Timmermann, Bernd; Hetzer, Roland; Berger, Felix; Sperling, Silke R

    2014-06-15

    Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Its genetic basis is demonstrated by an increased recurrence risk in siblings and familial cases. However, the majority of TOF are sporadic, isolated cases of undefined origin and it had been postulated that rare and private autosomal variations in concert define its genetic basis. To elucidate this hypothesis, we performed a multilevel study using targeted re-sequencing and whole-transcriptome profiling. We developed a novel concept based on a gene's mutation frequency to unravel the polygenic origin of TOF. We show that isolated TOF is caused by a combination of deleterious private and rare mutations in genes essential for apoptosis and cell growth, the assembly of the sarcomere as well as for the neural crest and secondary heart field, the cellular basis of the right ventricle and its outflow tract. Affected genes coincide in an interaction network with significant disturbances in expression shared by cases with a mutually affected TOF gene. The majority of genes show continuous expression during adulthood, which opens a new route to understand the diversity in the long-term clinical outcome of TOF cases. Our findings demonstrate that TOF has a polygenic origin and that understanding the genetic basis can lead to novel diagnostic and therapeutic routes. Moreover, the novel concept of the gene mutation frequency is a versatile measure and can be applied to other open genetic disorders. PMID:24459294

  6. IRDL Cloning: A One-Tube, Zero-Background, Easy-to-Use, Directional Cloning Method Improves Throughput in Recombinant DNA Preparation

    PubMed Central

    Wang, Jiancai; Xu, Ronghua; Liu, Aizhong

    2014-01-01

    Rapid and efficient construction of expression vectors and subsequent transformation are basic recombinant methods for the investigation of gene functionality. Although novel cloning methods have recently been developed, many laboratories worldwide continue to use traditional restriction digestion-ligation methods to construct expression vectors owing to financial constraints and the unavailability of appropriate vectors. We describe an improved restriction digestion-ligation (IRDL) cloning method that combines the advantage of directional cloning from double digestion-ligation with that of a low background observed by using a positive selection marker gene ccdB to facilitate digestion and ligation in a single tube. The IRDL cloning overcomes the time-consuming and laborious limits of traditional methods, thereby providing an easy-to-use, low-cost, and one-step strategy for directional cloning of target DNA fragments into an expression vector. As a proof-of-concept example, we developed two yeast vectors to demonstrate the feasibility and the flexibility of the IRDL cloning method. This method would provide an effective and easy-to-use system for gene cloning and functional genomics studies. PMID:25243603

  7. Human amniotic fluid-derived mesenchymal cells from fetuses with a neural tube defect do not deposit collagen type i protein after TGF-β1 stimulation in vitro.

    PubMed

    Hosper, Nynke A; Bank, Ruud A; van den Berg, Paul P

    2014-03-01

    In spina bifida, the neural tube fails to close during the embryonic period. Exposure of the neural tube to the amniotic fluid during pregnancy causes additional neural damage. Intrauterine tissue engineering using a biomaterial seeded with stem cells might prevent this additional damage. For this purpose, autologous cells from the amniotic fluid are an attractive source. To close the defect, it is important that these cells deposit an extracellular matrix. However, it is not known if amniotic fluid mesenchymal cells (AFMCs) from a fetus with a neural tube defect (NTD) share the same characteristics as AFMCs from a healthy fetus. We found that cells derived from fetuses with a NTD, in contrast to healthy human amniotic fluid cells, did not deposit collagen type I. Furthermore, the NTD cells showed, compared with both healthy amniotic fluid cells and fetal fibroblasts, much lower mRNA expression levels of genes that are involved in collagen biosynthesis [procollagen C-endopeptidase enhancer proteins (PCOLCE), PCOLCE2, ADAM metallopeptidase with thrombospondin type 1 motif, 2 (ADAMTS2), ADAMTS14]. This indicates that NTD-AFMCs have different characteristics compared with healthy AFMCs and might not be suitable for fetal therapy to close the defect in spina bifida patients. PMID:24171700

  8. Protein kinase A acts at the basal body of the primary cilium to prevent Gli2 activation and ventralization of the mouse neural tube.

    PubMed

    Tuson, Miquel; He, Mu; Anderson, Kathryn V

    2011-11-01

    Protein kinase A (PKA) is an evolutionarily conserved negative regulator of the hedgehog (Hh) signal transduction pathway. PKA is known to be required for the proteolytic processing event that generates the repressor forms of the Ci and Gli transcription factors that keep target genes off in the absence of Hh. Here, we show that complete loss of PKA activity in the mouse leads to midgestation lethality and a completely ventralized neural tube, demonstrating that PKA is as strong a negative regulator of the sonic hedgehog (Shh) pathway as patched 1 (Ptch1) or suppressor of fused (Sufu). Genetic analysis shows that although PKA is important for production of the repressor form of Gli3, the principal function of PKA in the Shh pathway in neural development is to restrain activation of Gli2. Activation of the Hh pathway in PKA mutants depends on cilia, and the catalytic and regulatory subunits of PKA are localized to a compartment at the base of the primary cilia, just proximal to the basal body. The data show that PKA does not affect cilia length or trafficking of smoothened (Smo) in the cilium. Instead, we find that there is a significant increase in the level of Gli2 at the tips of cilia of PKA-null cells. The data suggest a model in which PKA acts at the base of the cilium after Gli proteins have transited the primary cilium; in this model the sequential movement of Gli proteins between compartments in the cilium and at its base controls accessibility of Gli proteins to PKA, which determines the fates of Gli proteins and the activity of the Shh pathway. PMID:22007132

  9. Abnormal epigenetic regulation of the gene expression levels of Wnt2b and Wnt7b: Implications for neural tube defects

    PubMed Central

    BAI, BAOLING; CHEN, SHUYUAN; ZHANG, QIN; JIANG, QIAN; LI, HUILI

    2016-01-01

    The association between Wnt genes and neural tube defects (NTDs) is recognized, however, it remains to be fully elucidated. Our previous study demonstrated that epigenetic mechanisms are affected in human NTDs. Therefore, the present study aimed to evaluate whether Wnt2b and Wnt7b are susceptible to abnormal epigenetic modification in NTDs, using chromatin immunoprecipitation assays to evaluate histone enrichments and the MassARRAY platform to detect the methylation levels of target regions within Wnt genes. The results demonstrated that the transcriptional activities of Wnt2b and Wnt7b were abnormally upregulated in mouse fetuses with NTDs and, in the GC-rich promoters of these genes, histone 3 lysine 4 (H3K4) acetylation was enriched, whereas H3K27 trimethylation was reduced. Furthermore, several CpG sites in the altered histone modification of target regions were significantly hypomethylated. The present study also detected abnormal epigenetic modifications of these Wnt genes in human NTDs. In conclusion, the present study detected abnormal upregulation in the levels of Wnt2b and Wnt7b, and hypothesized that the alterations may be due to the ectopic opening of chromatin structure. These results improve understanding of the dysregulation of epigenetic modification of Wnt genes in NTDs. PMID:26548512

  10. Promotion of folate for the prevention of neural tube defects: knowledge and use of periconceptional folic acid supplements in Western Australia, 1992 to 1995.

    PubMed

    Bower, C; Blum, L; O'Daly, K; Higgins, C; Loutsky, F; Kosky, C

    1997-12-01

    To assess changes in knowledge and use of folic acid supplements in relation to a statewide health promotion project for the prevention of neural tube defects, we surveyed general practitioners, pharmacists, women of child-bearing age and pregnant women in Western Australia. We also collected data on wholesale sales of folic acid supplements. By the end of the project, 56.5 per cent of general practitioner respondents knew that the recommended dose of folic acid was 0.5 mg and 70 per cent offered folic acid supplements to women planning pregnancy, 82.5 per cent of responding pharmacists knew the recommended dose, and 87.5 per cent reported an increase in sales of 0.5 mg folic acid. Wholesale sales of 0.5 mg folic acid increased markedly in Western Australia compared with other states. From shopping centre surveys of women of child-bearing age we estimated that their knowledge of the association between folate and spina bifida increased from 8.2 per cent before the project to 67.5 per cent 2.5 years later, and doctors were a major source of information for women. In a 1995 survey of a sample of pregnant women, 43.1 per cent with planned pregnancies had taken folic acid supplements periconceptionally, compared with 19.1 per cent in a similar survey in 1993. PMID:9489188

  11. Identification of PCSK9 as a novel serum biomarker for the prenatal diagnosis of neural tube defects using iTRAQ quantitative proteomics

    PubMed Central

    An, Dong; Wei, Xiaowei; Li, Hui; Gu, Hui; Huang, Tianchu; Zhao, Guifeng; Liu, Bo; Wang, Weilin; Chen, Lizhu; Ma, Wei; Zhang, Henan; Cao, Songying; Yuan, Zhengwei

    2015-01-01

    To identify candidate serum molecule biomarkers for the non-invasive early prenatal diagnosis of neural tube defects (NTDs), we employed an iTRAQ-based quantitative proteomic approach to analyze the proteomic changes in serum samples from embryonic day (E) 11 and E13 pregnant rats with spina bifida aperta (SBA) induced by all-trans retinoic acid. Among the 390 proteins identified, 40 proteins at E11 and 26 proteins at E13 displayed significant differential expression in the SBA groups. We confirmed 5 candidate proteins by ELISA. We observed the space-time expression changes of proprotein convertase subtilisin/kexin type 9 (PCSK9) at different stages of fetal development, including a marked decrease in the sera of NTD pregnancies and gradual increase in the sera of normal pregnancies with embryonic development. PCSK9 demonstrated the diagnostic efficacy of potential NTD biomarkers [with an area under the receiver operating characteristic curve of 0.763, 95% CI: 065–0.88]. Additionally, PCSK9 expression in the spinal cords and placentas of SBA rat fetuses was markedly decreased. PCSK9 could serve as a novel molecular biomarker for the non-invasive prenatal screening of NTDs and may be involved in the pathogenesis of NTDs at critical periods of fetal development. PMID:26691006

  12. Genetic effects on variation in red-blood-cell folate in adults: Implications for the familial aggregation of neural tube defects

    SciTech Connect

    Mitchell, L.E.; Duffy, P.; Bellingham, G.

    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.

  13. Synergistic interactions between XPC and p53 mutations in double-mutant mice: neural tube abnormalities and accelerated UV radiation-induced skin cancer.

    PubMed

    Cheo, D L; Meira, L B; Hammer, R E; Burns, D K; Doughty, A T; Friedberg, E C

    1996-12-01

    The significance of DNA repair to human health has been well documented by studies on xeroderma pigmentosum (XP) patients, who suffer a dramatically increased risk of cancer in sun-exposed areas of their skin [1,2]. This autosomal recessive disorder has been directly associated with a defect in nucleotide excision-repair (NER) [1,2]. Like human XP individuals, mice carrying homozygous mutations in XP genes manifest a predisposition to skin carcinogenesis following exposure to ultraviolet (UV) radiation [3-5]. Recent studies have suggested that, in addition to roles in apoptosis [6] and cell-cycle checkpoint control [7] in response to DNA damage, p53 protein may modulate NER [8]. Mutations in the p53 gene have been observed in 50% of all human tumors [9] and have been implicated in both the early [10] and late [11] stages of skin cancer. To examine the consequences of a combined deficiency of the XPC and the p53 proteins in mice, we generated double-mutant animals. We document a spectrum of neural tube defects in XPC p53 mutant embryos. Additionally, we show that, following exposure to UV-B radiation, XPC p53 mutant mice have more severe solar keratosis and suffer accelerated skin cancer compared with XPC mutant mice that are wild-type with respect to p53. PMID:8994835

  14. Effects of Korean red ginseng extracts on neural tube defects and impairment of social interaction induced by prenatal exposure to valproic acid.

    PubMed

    Kim, Pitna; Park, Jin Hee; Kwon, Kyoung Ja; Kim, Ki Chan; Kim, Hee Jin; Lee, Jong Min; Kim, Hahn Young; Han, Seol-Heui; Shin, Chan Young

    2013-01-01

    Ginseng is one of the most widely used medicinal plants, which belongs to the genus Panax. Compared to uncured white ginseng, red ginseng has been generally regarded to produce superior pharmacological effects with lesser side/adverse effects, which made it popular in a variety of formulation from tea to oriental medicine. Using the prenatal valproic acid (VPA)-injection model of autism spectrum disorder (ASD) in rats, which produces social impairrment and altered seizure susceptibility as in human ASD patients as well as mild neural tube defects like crooked tail phenotype, we examined whether chronic administration of red ginseng extract may rescue the social impairment and crooked tail phenotype in prenatally VPA-exposed rat offspring. VPA-induced impairment in social interactions tested using sociability and social preference paradigms as well as crooked tail phenotypes were significantly improved by administration of Korean red ginseng (KRG) in a dose dependent manner. Rat offspring prenatally exposed to VPA showed higher sensitivity to electric shock seizure and increased locomotor activity in open-field test. KRG treatment reversed abnormal locomotor activity and sensitivity to electric shock to control level. These results suggest that KRG may modulate neurobehavioral and structural organization of nervous system adversely affected by prenatal exposure to VPA. PMID:23104247

  15. 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

    NASA Astrophysics Data System (ADS)

    Rahimi, Masoud; Beigzadeh, Reza; Parvizi, Mehdi; Eiamsa-ard, Smith

    2015-09-01

    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.

  16. Increased DNA methyltransferase 3b (Dnmt3b)-mediated CpG island methylation stimulated by oxidative stress inhibits expression of a gene required for neural tube and neural crest development in diabetic pregnancy.

    PubMed

    Wei, Dan; Loeken, Mary R

    2014-10-01

    Previous studies have shown that diabetic embryopathy results from impaired expression of genes that are required for formation of embryonic structures. We have focused on Pax3, a gene that is expressed in embryonic neuroepithelium and is required for neural tube closure. Pax3 expression is inhibited in embryos of diabetic mice due to hyperglycemia-induced oxidative stress. DNA methylation silences developmentally expressed genes before differentiation. We hypothesized that hypomethylation of Pax3 upon neuroepithelial differentiation may be inhibited by hyperglycemia-induced oxidative stress. We tested this using embryos of pregnant hyperglycemic mice and mouse embryonic stem cells (ESC). Methylation of a Pax3 CpG island decreased upon neurulation of embryos and formation of neuronal precursors from ESC. In ESC, this was inhibited by oxidative stress. Use of short hairpin RNA in ESC demonstrated that DNA methyltransferase 3b (Dnmt3b) was responsible for methylation and silencing of Pax3 before differentiation and by oxidative stress. Although expression of Dnmt3b was not affected by oxidative stress, DNA methyltransferase activity was increased. These results indicate that hyperglycemia-induced oxidative stress stimulates Dnmt3b activity, thereby inhibiting chromatin modifications necessary for induction of Pax3 expression during neurulation and thus providing a molecular mechanism for defects caused by Pax3 insufficiency in diabetic pregnancy. PMID:24834974

  17. Increased DNA Methyltransferase 3b (Dnmt3b)-Mediated CpG Island Methylation Stimulated by Oxidative Stress Inhibits Expression of a Gene Required for Neural Tube and Neural Crest Development in Diabetic Pregnancy

    PubMed Central

    Wei, Dan

    2014-01-01

    Previous studies have shown that diabetic embryopathy results from impaired expression of genes that are required for formation of embryonic structures. We have focused on Pax3, a gene that is expressed in embryonic neuroepithelium and is required for neural tube closure. Pax3 expression is inhibited in embryos of diabetic mice due to hyperglycemia-induced oxidative stress. DNA methylation silences developmentally expressed genes before differentiation. We hypothesized that hypomethylation of Pax3 upon neuroepithelial differentiation may be inhibited by hyperglycemia-induced oxidative stress. We tested this using embryos of pregnant hyperglycemic mice and mouse embryonic stem cells (ESC). Methylation of a Pax3 CpG island decreased upon neurulation of embryos and formation of neuronal precursors from ESC. In ESC, this was inhibited by oxidative stress. Use of short hairpin RNA in ESC demonstrated that DNA methyltransferase 3b (Dnmt3b) was responsible for methylation and silencing of Pax3 before differentiation and by oxidative stress. Although expression of Dnmt3b was not affected by oxidative stress, DNA methyltransferase activity was increased. These results indicate that hyperglycemia-induced oxidative stress stimulates Dnmt3b activity, thereby inhibiting chromatin modifications necessary for induction of Pax3 expression during neurulation and thus providing a molecular mechanism for defects caused by Pax3 insufficiency in diabetic pregnancy. PMID:24834974

  18. Regulation of Hoxb4 induction after neurulation by somite signal and neural competence

    PubMed Central

    Amirthalingam, Gayana S; Howard, Sara; Alvarez, Susana; de Lera, Angel R; Itasaki, Nobue

    2009-01-01

    Background While the body axis is largely patterned along the anterior-posterior (A-P) axis during gastrulation, the central nervous system (CNS) shows dynamic changes in the expression pattern of Hox genes during neurulation, suggesting that the CNS refines the A-P pattern continuously after neural tube formation. This study aims at clarifying the role of somites in up-regulating Hoxb4 expression to eventually establish its final pattern and how the neural tube develops a competence to respond to extrinsic signals. Results We show that somites are required for the up-regulation of Hoxb4 in the neural tube at the level of somites 1 to 5, the anterior-most domain of expression. However, each somite immediately adjacent to the neural tube is not sufficient at each level; planar signaling is additionally required particularly at the anterior-most segments of the expression domain. We also show that the dorsal side of the neural tube has a greater susceptibility to expressing Hoxb4 than the ventral region, a feature associated with dorsalization of the neural tube by BMP signals. BMP4 is additionally able to up-regulate Hoxb4 ventrally, but the effect is restricted to the axial levels at which Hoxb4 is normally expressed, and only in the presence of retinoic acid (RA) or somites, suggesting a role for BMP in rendering the neural tube competent to express Hoxb4 in response to RA or somite signals. Conclusion In identifying the collaboration between somites and neural tube competence in the induction of Hoxb4, this study demonstrates interplay between A-P and dorsal-ventral (D-V) patterning systems, whereby a specific feature of D-V polarity may be a prerequisite for proper A-P patterning by Hox genes. PMID:19243620

  19. The C677T polymorphism of the methylenetetrahydrofolate reductase gene in Mexican mestizo neural-tube defect parents, control mestizo and native populations.

    PubMed

    Dávalos, I P; Olivares, N; Castillo, M T; Cantú, J M; Ibarra, B; Sandoval, L; Morán, M C; Gallegos, M P; Chakraborty, R; Rivas, F

    2000-01-01

    The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene, associated with the thermolabile form of the enzyme, has reportedly been found to be increased in neural-tube defects (NTD), though this association is still unclear. A group of 107 mestizo parents of NTD children and five control populations: 101 mestizo (M), 50 Huichol (H), 38 Tarahumara (T), 21 Purepecha (P) and 20 Caucasian (C) individuals were typed for the MTHFR C677T variant by the PCR/RFLP (HinfI) method. Genotype frequencies were in agreement with the Hardy-Weinberg expectations in all six populations. Allele frequency (%) of the C677T variant was 45 in NTD, 44 in M, 56 in H, 36 in T, 57 in P, 35 in C. Pairwise inter-population comparisons of allele frequency disclosed a very similar distribution between NTD and M groups (exact test, P=0.92). Among controls, differences between M and individual native groups were NS (0.06

  20. Supplement use and other characteristics among pregnant women with a previous pregnancy affected by a neural tube defect - United States, 1997-2009.

    PubMed

    Arth, Annelise; Tinker, Sarah; Moore, Cynthia; Canfield, Mark; Agopian, Aj; Reefhuis, Jennita

    2015-01-16

    Neural tube defects (NTDs) include anomalies of the brain (anencephaly and encephalocele) and spine (spina bifida). Even with ongoing mandatory folic acid fortification of enriched cereal grain products, the U.S. Preventive Services Task Force recommends that women of childbearing potential consume a daily supplement containing 400 µg-800 µg of folic acid. Women with a prior NTD-affected pregnancy have an increased risk for having another NTD-affected pregnancy, and if they are planning another pregnancy, the recommendation is that they consume high-dosage folic acid supplements (4.0 mg/day) beginning ≥4 weeks before conception and continuing through the first 12 weeks of pregnancy. To learn whether folic acid supplementation (from multivitamins or single- ingredient supplements) was commonly used during pregnancy by women with a previous NTD-affected pregnancy, supplement use was assessed among a convenience sample of women with a previous NTD-affected pregnancy who participated in the National Birth Defects Prevention Study (NBDPS), a case-control study of major birth defects in the United States. Characteristics of women who previously had an NTD-affected pregnancy and whose index pregnancy (pregnancy included in NBDPS) was either affected by an NTD (N = 17) (i.e., recurrence-cases) or resulted in a live-born infant without a major birth defect (N = 10) (i.e., recurrence-controls) were assessed. Taking a supplement that included folic acid was more common among recurrence-control mothers (80%) than recurrence-case mothers (35%). The recommendation that women should take folic acid supplements just before and during early pregnancy is not being followed by many women and offers an opportunity for NTD prevention, especially among women who are at a higher risk because they have had a previous pregnancy affected by an NTD. PMID:25590679

  1. Elevated Nuclear and Cytoplasmic FTY720-Phosphate in Mouse Embryonic Fibroblasts Suggests the Potential for Multiple Mechanisms in FTY720-Induced Neural Tube Defects.

    PubMed

    Gardner, Nicole M; Riley, Ronald T; Showker, Jency L; Voss, Kenneth A; Sachs, Andrew J; Maddox, Joyce R; Gelineau-van Waes, Janee B

    2016-03-01

    FTY720 (fingolimod) is a U.S. Food and Drug Administration-approved drug to treat relapsing remitting multiple sclerosis. FTY720 treatment in pregnant inbred LM/Bc mice results in approximately 60% of embryos having a neural tube defect (NTD). Sphingosine kinases (Sphk1, Sphk2) phosphorylate FTY720 in vivo to form the bioactive metabolite FTY720-1-phosphate (FTY720-P). Cytoplasmic FTY720-P is an agonist for 4 of the 5 sphingosine-1-phosphate (S1P) receptors (S1P1, 3-5) and can also act as a functional antagonist of S1P1, whereas FTY720-P generated in the nucleus inhibits histone deacetylases (HDACs), leading to increased histone acetylation. This study demonstrates that treatment of LM/Bc mouse embryonic fibroblasts (MEFs) with FTY720 results in a significant accumulation of FTY720-P in both the cytoplasmic and nuclear compartments. Elevated nuclear FTY720-P is associated with decreased HDAC activity and increased histone acetylation at H3K18 and H3K23 in LM/Bc MEFs. Treatment of LM/Bc MEFs with FTY720 and a selective Sphk2 inhibitor, ABC294640, significantly reduces the amount of FTY720-P that accumulates in the nucleus. The data provide insight into the relative amounts of FTY720-P generated in the nuclear versus cytoplasmic subcellular compartments after FTY720 treatment and the specific Sphk isoforms involved. The results of this study suggest that FTY720-induced NTDs may involve multiple mechanisms, including: (1) sustained and/or altered S1P receptor activation and signaling by FTY720-P produced in the cytoplasm and (2) HDAC inhibition and histone hyperacetylation by FTY720-P generated in the nucleus that could lead to epigenetic changes in gene regulation. PMID:26719367

  2. Evaluation of proton-coupled folate transporter (SLC46A1) polymorphisms as risk factors for neural tube defects and oral clefts.

    PubMed

    VanderMeer, Julia E; Carter, Tonia C; Pangilinan, Faith; Mitchell, Adam; Kurnat-Thoma, Emma; Kirke, Peadar N; Troendle, James F; Molloy, Anne M; Munger, Ronald G; Feldkamp, Marcia L; Mansilla, Maria A; Mills, James L; Murray, Jeff C; Brody, Lawrence C

    2016-04-01

    Many folate-related genes have been investigated for possible causal roles in neural tube defects (NTDs) and oral clefts. However, no previous reports have examined the major gene responsible for folate uptake, the proton-coupled folate transporter (SLC46A1). We tested for association between these birth defects and single nucleotide polymorphisms in the SLC46A1 gene. The NTD study population included 549 complete and incomplete case-family triads, and 999 controls from Ireland. The oral clefts study population comprised a sample from Utah (495 complete and incomplete case-family triads and 551 controls) and 221 Filipino multiplex cleft families. There was suggestive evidence of increased NTD case risk with the rs17719944 minor allele (odds ratio (OR): 1.29; 95% confidence intervals (CI): [1.00-1.67]), and decreased maternal risk of an NTD pregnancy with the rs4795436 minor allele (OR: 0.62; [0.39-0.99]). In the Utah sample, the rs739439 minor allele was associated with decreased case risk for cleft lip with cleft palate (genotype relative risk (GRR): 0.56 [0.32-0.98]). Additionally, the rs2239907 minor allele was associated with decreased case risk for cleft lip with cleft palate in several models, and with cleft palate only in a recessive model (OR: 0.41; [0.20-0.85]). These associations did not remain statistically significant after correcting for multiple hypothesis testing. Nominal associations between SLC46A1 polymorphisms and both Irish NTDs and oral clefts in the Utah population suggest some role in the etiology of these birth defects, but further investigation in other populations is needed. © 2016 Wiley Periodicals, Inc. PMID:26789141

  3. What Are Neural Tube Defects?

    MedlinePlus

    ... An infant born with spina bifida usually has paralysis of the nerves below the affected area of ... no symptoms, but other people might experience partial paralysis or other symptoms. In some cases, the only ...

  4. Massive-training artificial neural network (MTANN) for reduction of false positives in computer-aided detection of polyps: Suppression of rectal tubes

    SciTech Connect

    Suzuki, Kenji; Yoshida, Hiroyuki; Naeppi, Janne; Dachman, Abraham H.

    2006-10-15

    One of the limitations of the current computer-aided detection (CAD) of polyps in CT colonography (CTC) is a relatively large number of false-positive (FP) detections. Rectal tubes (RTs) are one of the typical sources of FPs because a portion of a RT, especially a portion of a bulbous tip, often exhibits a cap-like shape that closely mimics the appearance of a small polyp. Radiologists can easily recognize and dismiss RT-induced FPs; thus, they may lose their confidence in CAD as an effective tool if the CAD scheme generates such ''obvious'' FPs due to RTs consistently. In addition, RT-induced FPs may distract radiologists from less common true positives in the rectum. Therefore, removal RT-induced FPs as well as other types of FPs is desirable while maintaining a high sensitivity in the detection of polyps. We developed a three-dimensional (3D) massive-training artificial neural network (MTANN) for distinction between polyps and RTs in 3D CTC volumetric data. The 3D MTANN is a supervised volume-processing technique which is trained with input CTC volumes and the corresponding ''teaching'' volumes. The teaching volume for a polyp contains a 3D Gaussian distribution, and that for a RT contains zeros for enhancement of polyps and suppression of RTs, respectively. For distinction between polyps and nonpolyps including RTs, a 3D scoring method based on a 3D Gaussian weighting function is applied to the output of the trained 3D MTANN. Our database consisted of CTC examinations of 73 patients, scanned in both supine and prone positions (146 CTC data sets in total), with optical colonoscopy as a reference standard for the presence of polyps. Fifteen patients had 28 polyps, 15 of which were 5-9 mm and 13 were 10-25 mm in size. These CTC cases were subjected to our previously reported CAD scheme that included centerline-based segmentation of the colon, shape-based detection of polyps, and reduction of FPs by use of a Bayesian neural network based on geometric and texture features. Application of this CAD scheme yielded 96.4% (27/28) by-polyp sensitivity with 3.1 (224/73) FPs per patient, among which 20 FPs were caused by RTs. To eliminate the FPs due to RTs and possibly other normal structures, we trained a 3D MTANN with ten representative polyps and ten RTs, and applied the trained 3D MTANN to the above CAD true- and false-positive detections. In the output volumes of the 3D MTANN, polyps were represented by distributions of bright voxels, whereas RTs and other normal structures partly similar to RTs appeared as darker voxels, indicating the ability of the 3D MTANN to suppress RTs as well as other normal structures effectively. Application of the 3D MTANN to the CAD detections showed that the 3D MTANN eliminated all RT-induced 20 FPs, as well as 53 FPs due to other causes, without removal of any true positives. Overall, the 3D MTANN was able to reduce the FP rate of the CAD scheme from 3.1 to 2.1 FPs per patient (33% reduction), while the original by-polyp sensitivity of 96.4% was maintained.

  5. Recommendations on the use of folic acid supplementation to prevent the recurrence of neural tube defects. Clinical Teratology Committee, Canadian College of Medical Geneticists.

    PubMed Central

    Van Allen, M I; Fraser, F C; Dallaire, L; Allanson, J; McLeod, D R; Andermann, E; Friedman, J M

    1993-01-01

    OBJECTIVE: To prevent the recurrence of neural tube defects (NTDs) in families at increased risk of having offspring with NTDs with the use of periconceptional folic acid supplementation. OPTIONS: Genetic counselling and prenatal diagnosis of NTDs. OUTCOMES: NTDs cause stillbirth, neonatal death and severe disabilities. The cost for medical care and rehabilitation in the first 10 years of life of a child with spina bifida cystica was estimated to be $42,507 in 1987. EVIDENCE: The authors reviewed the medical literature, communicated with investigators from key studies, reviewed policy recommendations from other organizations and drew on their own expertise. A recent multicentre randomized controlled trial showed that among women at high risk of having a child with an NTD those who received 4 mg/d of folic acid had 72% fewer cases of NTD-affected offspring than nonsupplemented women. Two previous intervention studies also demonstrated that folic acid supplementation was effective in reducing the rate of NTD recurrence. Several retrospective studies support this conclusion. VALUES: Recommendations are the consensus of the Clinical Teratology Committee of the Canadian College of Medical Geneticists (CCMG) and have been approved by the CCMG Board. The committee believes that primary prevention of NTDs is preferable to treatment or to prenatal detection and abortion. BENEFITS, HARMS AND COSTS: Folic acid supplementation should result in fewer NTDs among infants in Canada and ancillary savings in medical costs. The recommended dosage of folic acid is not known to be associated with adverse effects. Higher dosages of folic acid may make vitamin B12 deficiency difficult to diagnose and may alter seizure frequency in patients with epilepsy due to drug interactions with anticonvulsants. RECOMMENDATIONS: A minimum dosage of folic acid of 0.8 mg/d, not to exceed 5.0 mg/d, is recommended along with a well-balanced, nutritious diet for all women who are at increased risk of having offspring with NTDs and who are planning a pregnancy or may become pregnant. Supplementation should begin before conception and continue for at least 10 to 12 weeks of pregnancy. VALIDATION: These guidelines are similar to those of the Society of Obstetricians and Gynaecologists of Canada, the US Centers for Disease Control and Prevention and the Department of Health in Britain. SPONSORS: These guidelines were developed by the CCMG Clinical Teratology Committee and endorsed by the Board of the CCMG. No funding for the development of these guidelines was obtained from any other sources. PMID:8221478

  6. Feeding Tubes

    MedlinePlus

    ... administer the TPN. Tubes Used for Enteral Feeds NG (Nasogastric Tube) A flexible tube is placed via ... down through the esophagus into the stomach. The NG tube can be used to empty the stomach ...

  7. Zebrafish arl6ip1 Is Required for Neural Crest Development during Embryogenesis

    PubMed Central

    Tu, Chi-Tang; Yang, Tzu-Ching; Huang, Hsing-Yen; Tsai, Huai-Jen

    2012-01-01

    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. PMID:22427906

  8. Tracheostomy tubes.

    PubMed

    Hess, Dean R; Altobelli, Neila P

    2014-06-01

    Tracheostomy tubes are used to administer positive-pressure ventilation, to provide a patent airway, and to provide access to the lower respiratory tract for airway clearance. They are available in a variety of sizes and styles from several manufacturers. The dimensions of tracheostomy tubes are given by their inner diameter, outer diameter, length, and curvature. Differences in dimensions between tubes with the same inner diameter from different manufacturers are not commonly appreciated but may have important clinical implications. Tracheostomy tubes can be cuffed or uncuffed and may be fenestrated. Some tracheostomy tubes are designed with an inner cannula. It is important for clinicians caring for patients with a tracheostomy tube to appreciate the nuances of various tracheostomy tube designs and to select a tube that appropriately fits the patient. The optimal frequency of changing a chronic tracheostomy tube is controversial. Specialized teams may be useful in managing patients with a tracheostomy. Speech can be facilitated with a speaking valve in patients with a tracheostomy tube who are breathing spontaneously. In mechanically ventilated patients with a tracheostomy, a talking tracheostomy tube, a deflated cuff technique with a speaking valve, or a deflated cuff technique without a speaking valve can be used to facilitate speech. PMID:24891201

  9. Nasogastric feeding tube

    MedlinePlus

    Feeding - nasogastric tube; NG tube; Bolus feeding; Continuous pump feeding; Gavage tube ... A nasogastric tube (NG tube) is a special tube that carries food and medicine to the stomach through the nose. It can be ...

  10. Feeding tube insertion - gastrostomy

    MedlinePlus

    ... tube insertion; G-tube insertion; PEG tube insertion; Stomach tube insertion; Percutaneous endoscopic gastrostomy tube insertion ... and down the esophagus, which leads to the stomach. After the endoscopy tube is inserted, the skin ...

  11. Gastrostomy Tube (G-Tube)

    MedlinePlus

    ... warmth at the tube site; discharge that's yellow, green, or foul-smelling; fever) excessive bleeding or drainage from the tube site severe abdominal pain persistent vomiting or diarrhea trouble passing gas or having a bowel movement pink-red tissue (called granulation tissue) coming out ...

  12. Ear Tubes

    MedlinePlus

    ... of recurrent ear infections and the need for repeat surgery in children four years and older. What happens ... soon (which is unpredictable), fluid may return and repeat surgery may be needed. Ear tubes that remain too ...

  13. Protective tubes for sodium heated water tubes

    DOEpatents

    Essebaggers, Jan

    1979-01-01

    A heat exchanger in which water tubes are heated by liquid sodium which minimizes the results of accidental contact between the water and the sodium caused by failure of one or more of the water tubes. A cylindrical protective tube envelopes each water tube and the sodium flows axially in the annular spaces between the protective tubes and the water tubes.

  14. Folic acid and homocysteine affect neural crest and neuroepithelial cell outgrowth and differentiation in vitro.

    PubMed

    Boot, Marit J; Steegers-Theunissen, Régine P M; Poelmann, Robert E; Van Iperen, Liesbeth; Lindemans, Jan; Gittenberger-de Groot, Adriana C

    2003-06-01

    The beneficial effect of additional folic acid in the periconceptional period to prevent neural tube defects, orofacial clefts, and conotruncal heart defects in the offspring has been shown. Folate shortage results in homocysteine accumulation. Elevated levels of homocysteine have been related to neural tube defects. We studied the behavior of neuroepithelial cells and cranial and cardiac neural crest cells in vitro. Neural tube explants were cultured for 24 and 48 hr in medium after addition of folic acid and/or homocysteine. Folic acid addition increased neuroepithelial cell outgrowth and increased neural crest cell differentiation into nerve and smooth muscle cells. Addition of homocysteine increased neural crest cell outgrowth and migration from the neural tube and inhibited neural crest cell differentiation. Our findings suggest that neural tube defects caused by folate deficiency and hyperhomocysteinemia develop due to increased neuroepithelial to neural crest cell transformation. This increased transformation leads to a shortage of neuroepithelial cells in the neural tube. Defects in orofacial and conotruncal development are explained by abnormal differentiation of neural crest cells in the presence of high homocysteine concentrations. Our findings supports a critical role for folic acid and homocysteine in the development of neural tube defects and neural crest related heart malformations. PMID:12761857

  15. Multiple tube premixing device

    DOEpatents

    Uhm, Jong Ho; Naidu, Balachandar; Ziminksy, Willy Steve; Kraemer, Gilbert Otto; Yilmaz, Ertan; Lacy, Benjamin; Stevenson, Christian; Felling, David

    2013-08-13

    The present application provides a premixer for a combustor. The premixer may include a fuel plenum with a number of fuel tubes and a burner tube with a number of air tubes. The fuel tubes extend about the air tubes.

  16. Multiple tube premixing device

    SciTech Connect

    Uhm, Jong Ho; Varatharajan, Balachandar; Ziminsky, Willy Steve; Kraemer, Gilbert Otto; Yilmaz, Ertan; Lacy, Benjamin; Stevenson, Christian; Felling, David

    2012-12-11

    The present application provides a premixer for a combustor. The premixer may include a fuel plenum with a number of fuel tubes and a burner tube with a number of air tubes. The fuel tubes extend about the air tubes.

  17. Ear tube insertion

    MedlinePlus

    Myringotomy; Tympanostomy; Ear tube surgery; Pressure equalization tubes; Ventilating tubes; Ear infection - tubes; Otitis - tubes ... trapped fluid can flow out of the middle ear. This prevents hearing loss and reduces the risk ...

  18. Tubing guide

    SciTech Connect

    Laky, T.

    1992-05-26

    This patent describes a tubing guide. It comprises a pod adapted to be supported on a wellhead and to support means thereabove for injecting and retrieving tubing through the wellhead; the pod having upper and lower vertically spaced horizontal beams and at least three vertical support legs extending between the beams and providing a window for attaching equipment to a tubing; a support arm rotatably mounted on at least two support legs between the beams; arm connecting plate means supported by at least one of the arms and connectable with the other arm or arms; an annular pipe guard vertically split into sections and carried by the plate means; means for connecting the pipe guard sections together in an annular relationship and with the upper and lower beams.

  19. Folic Acid Helps Prevent Neural Tube Defects

    MedlinePlus

    ... Stages & Populations Travelers' Health Workplace Safety & Health Features Media Sign up for Features Get Email Updates To ... choose to search for a specific topic . Features Media Sign up for Features Get Email Updates To ...

  20. Estimating an individual's risk of having a fetus with open spina bifida and the value of repeat alpha-fetoprotein testing: FOURTH REPORT OF THE UK COLLABORATIVE STUDY ON ALPHA-FETOPROTEIN IN RELATION TO NEURAL TUBE DEFECTS*

    PubMed Central

    1982-01-01

    Data from the United Kingdom Collaborative Alpha-fetoprotein (AFP) Study were used to estimate an individual woman's risk of having a fetus with an open neural tube defect based on her particular maternal serum or amniotic fluid AFP concentration, and also to indicate the value of obtaining fresh specimens for repeat AFP testing. This was done by first showing that the AFP distribution adequately fitted a log Gaussian distribution and then estimating the mean and standard deviation of those distributions as well as the components of variance due to assay imprecision and within-person AFP fluctuations. In the United Kingdom as a whole the odds of having a fetus with open spina bifida among women with maternal serum AFP concentrations of 2·0, 3·0, and 4·0 multiples of the normal median (MoM) at 16-18 weeks' gestation are roughly 1:400, 1:59, and 1:13 respectively. Among women who have a single serum AFP concentration ≥2·5 MoM at 16-18 weeks' gestation which remained raised after the revision of gestational age by ultrasound and who proceed to amniocentesis, the odds are 1:84, 1:1, and 24:1 for women who have amniotic fluid AFP values of 2·0, 3·0, and 4·0 MoM respectively at 16-18 weeks' gestation. If the amniotic fluid sample is blood-stained these odds are lower, if it is not they are higher— for example, 1:4 and 5:1 respectively at 3·0 MoM. If an amniotic fluid AFP result is borderline there is practical value in obtaining a fresh amniotic fluid sample and performing a repeat AFP test, but if a maternal serum AFP result is borderline or high there is little value in testing a second maternal serum sample. Centres in which women with raised serum AFP concentrations routinely have a repeat test may therefore wish to reconsider this policy. PMID:6181181

  1. Tube Feedings.

    ERIC Educational Resources Information Center

    Plummer, Nancy

    This module on tube feedings is intended for use in inservice or continuing education programs for persons who work in long-term care. Instructor information, including teaching suggestions and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then provided. A brief discussion follows…

  2. Bone Morphogenetic Protein signaling is required in the dorsal neural folds before neurulation for the induction of spinal neural crest cells and dorsal neurons

    PubMed Central

    Stottmann, Rolf W.; Klingensmith, John

    2011-01-01

    Bone Morphogenetic Protein (BMP) activity has been implicated as a key regulator of multiple aspects of dorsal neural tube development. BMP signaling in the dorsalmost neuroepithelial cells presumably plays a critical role. We use tissue-specific gene ablation to probe the roles of BMPR1A, the type 1 BMP receptor that is seemingly the best candidate to mediate the activities of BMPs on early dorsal neural development. We use two different Cre lines expressed in the dorsal neural folds, one prior to spinal neurulation and one shortly afterward, together with a Bmpr1a conditional null mutation. Our findings indicate that BMPR1A signaling in the dorsal neural folds is important for hindbrain neural tube closure, but suggest it is dispensable for spinal neurulation. Our results also demonstrate a requirement for BMP signaling in patterning of dorsal neural tube cell fate and in neural crest cell formation, and imply a critical period shortly before neural tube closure. PMID:21394823

  3. QUANTIZING TUBE

    DOEpatents

    Jensen, A.S.; Gray, G.W.

    1958-07-01

    Beam deflection tubes are described for use in switching or pulse amplitude analysis. The salient features of the invention reside in the target arrangement whereby outputs are obtained from a plurality of collector electrodes each correspondlng with a non-overlapping range of amplitudes of the input sigmal. The tube is provded with mcans for deflecting the electron beam a1ong a line in accordance with the amplitude of an input signal. The target structure consists of a first dymode positioned in the path of the beam wlth slots spaced a1ong thc deflection line, and a second dymode posltioned behind the first dainode. When the beam strikes the solid portions along the length of the first dymode the excited electrons are multiplied and collected in separate collector electrodes spaced along the beam line. Similarly, the electrons excited when the beam strikes the second dynode are multiplied and collected in separate electrodes spaced along the length of the second dyode.

  4. Neutron tubes

    DOEpatents

    Leung, Ka-Ngo; Lou, Tak Pui; Reijonen, Jani

    2008-03-11

    A neutron tube or generator is based on a RF driven plasma ion source having a quartz or other chamber surrounded by an external RF antenna. A deuterium or mixed deuterium/tritium (or even just a tritium) plasma is generated in the chamber and D or D/T (or T) ions are extracted from the plasma. A neutron generating target is positioned so that the ion beam is incident thereon and loads the target. Incident ions cause D-D or D-T (or T-T) reactions which generate neutrons. Various embodiments differ primarily in size of the chamber and position and shape of the neutron generating target. Some neutron generators are small enough for implantation in the body. The target may be at the end of a catheter-like drift tube. The target may have a tapered or conical surface to increase target surface area.

  5. Electron tube

    DOEpatents

    Suyama, Motohiro; Fukasawa, Atsuhito; Arisaka, Katsushi; Wang, Hanguo

    2011-12-20

    An electron tube of the present invention includes: a vacuum vessel including a face plate portion made of synthetic silica and having a surface on which a photoelectric surface is provided, a stem portion arranged facing the photoelectric surface and made of synthetic silica, and a side tube portion having one end connected to the face plate portion and the other end connected to the stem portion and made of synthetic silica; a projection portion arranged in the vacuum vessel, extending from the stem portion toward the photoelectric surface, and made of synthetic silica; and an electron detector arranged on the projection portion, for detecting electrons from the photoelectric surface, and made of silicon.

  6. Tube Feeding Troubleshooting Guide

    MedlinePlus

    ... profile tube also has a stem length). Note: NG and NJ tubes (that go through a person’s ... Immediate Action: • Discontinue feeding. • If you have an NG or NJ tube, and the tube is curled ...

  7. Chest tube insertion

    MedlinePlus

    Chest drainage tube insertion; Insertion of tube into chest; Tube thoracostomy; Pericardial drain ... When your chest tube is inserted, you will lie on your side or sit partly upright, with one arm over your ...

  8. Neural crest migration methods in the chicken embryo.

    PubMed

    Elena de Bellard, Maria; Bronner-Fraser, Marianne

    2005-01-01

    Neural crest cells emerge from the neural tube early in development. They migrate extensively throughout the embryo and form most of the head and peripheral nervous system, giving rise to sensory and sympathetic ganglia, heart regions, adrenal cells, head bones, teeth, muscle cells, sensory organs, melanocytes, and other cell types. The neural crest is interesting because of its unique origin, development and differentiation. These cells are initially part of the dorsal neural tube, with a clear epithelial character; later, they transform into actively motile mesenchymal cells. Little is known about the underlying mechanism directing this process. It remains unknown why neural crest cells target particular derivatives (neurons, heart muscle and glia) and body regions (peripheral nerves, heart, skin, head and gut). Neural crest migration can be divided into three stages: 1) emigration from the neural tube; 2) migration along defined pathways; and 3) cessation of migration. At the onset of migration, neural crest cells lose their epithelial nature within the neural tube and transform into a migratory, mesenchymal cell type. Neural crest development has been best studied in avian embryos, which are amenable to surgical manipulation, cell marking techniques, cell culture and transgenesis by electroporation and retrovirally mediate gene transfer. The methods outlined below are those typically used to study and understand the different factors and signals necessary for the neural crest development before and during their migration. PMID:15576917

  9. Epigenetic regulation in neural crest development.

    PubMed

    Hu, Na; Strobl-Mazzulla, Pablo H; Bronner, Marianne E

    2014-12-15

    The neural crest is a migratory and multipotent cell population that plays a crucial role in many aspects of embryonic development. In all vertebrate embryos, these cells emerge from the dorsal neural tube then migrate long distances to different regions of the body, where they contribute to formation of many cell types and structures. These include much of the peripheral nervous system, craniofacial skeleton, smooth muscle, and pigmentation of the skin. The best-studied regulatory events guiding neural crest development are mediated by transcription factors and signaling molecules. In recent years, however, growing evidence supports an important role for epigenetic regulation as an additional mechanism for controlling the timing and level of gene expression at different stages of neural crest development. Here, we summarize the process of neural crest formation, with focus on the role of epigenetic regulation in neural crest specification, migration, and differentiation as well as in neural crest related birth defects and diseases. PMID:25446277

  10. Tube furnace

    SciTech Connect

    Foster, K.G.; Frohwein, E.J.; Taylor, R.W.; Bowen, D.W.

    1990-12-31

    A vermiculite insulated tube furnace is heated by a helically-wound resistance wire positioned within a helical groove on the surface of a ceramic cylinder, that in turn is surroundingly disposed about a doubly slotted stainless steel cylindrical liner. For uniform heating, the pitch of the helix is of shorter length over the two end portions of the ceramic cylinder. The furnace is of large volume, provides uniform temperature, offers an extremely precise programmed heating capability, features very rapid cool-down, and has a modest electrical power requirement.

  11. Tube furnace

    SciTech Connect

    Foster, K.G.; Frohwein, E.J.; Taylor, R.W.; Bowen, D.W.

    1990-01-01

    A vermiculite insulated tube furnace is heated by a helically-wound resistance wire positioned within a helical groove on the surface of a ceramic cylinder, that in turn is surroundingly disposed about a doubly slotted stainless steel cylindrical liner. For uniform heating, the pitch of the helix is of shorter length over the two end portions of the ceramic cylinder. The furnace is of large volume, provides uniform temperature, offers an extremely precise programmed heating capability, features very rapid cool-down, and has a modest electrical power requirement.

  12. Tube furnace

    SciTech Connect

    Foster, Kenneth G.; Frohwein, Eugene J.; Taylor, Robert W.; Bowen, David W.

    1991-01-01

    A vermiculite insulated tube furnace is heated by a helically-wound resistance wire positioned within a helical groove on the surface of a ceramic cylinder, that in turn is surroundingly disposed about a doubly slotted stainless steel cylindrical liner. For uniform heating, the pitch of the helix is of shorter length over the two end portions of the ceramic cylinder. The furnace is of large volume, provides uniform temperature, offers an extremely precise programmed heating capability, features very rapid cool-down, and has a modest electrical power requirement.

  13. Collapse Tubes

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Context image for PIA02154 Collapse Tubes

    The discontinuous channels in this image are collapsed lava tubes.

    Image information: VIS instrument. Latitude -19.7N, Longitude 317.5E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  14. Tapered pulse tube for pulse tube refrigerators

    DOEpatents

    Swift, Gregory W.; Olson, Jeffrey R.

    1999-01-01

    Thermal insulation of the pulse tube in a pulse-tube refrigerator is maintained by optimally varying the radius of the pulse tube to suppress convective heat loss from mass flux streaming in the pulse tube. A simple cone with an optimum taper angle will often provide sufficient improvement. Alternatively, the pulse tube radius r as a function of axial position x can be shaped with r(x) such that streaming is optimally suppressed at each x.

  15. The olfactory sensory system develops from coordinated movements within the neural plate

    PubMed Central

    Torres-Paz, Jorge

    2014-01-01

    Background The peripheral olfactory sensory system arises from morphologically identifiable structures called placodes. Placodes are relatively late developing structures, evident only well after the initiation of somitogenesis. Placodes are generally described as being induced from the ectoderm suggesting that their development is separate from the coordinated cell movements generating the central nervous system. Results With the advent of modern techniques it is possible to follow the development of the neurectoderm giving rise to the anterior neural tube, including the olfactory placodes. The cell movements giving rise to the optic cup are coordinated with those generating the olfactory placodes and adjacent telencephalon. The formation of the basal lamina separating the placode from the neural tube is coincident with the anterior migration of cranial neural crest. Conclusions Olfactory placodes are transient morphological structures arising from a continuous sheet of neurectoderm that gives rise to the peripheral and central nervous system. This field of cells is specified at the end of gastrulation and not secondarily induced from ectoderm. The separation of olfactory placodes and telencephalon occurs through complex cell movements within the developing neural plate similar to that observed for the developing optic cup. PMID:25255735

  16. Tube-in-tube thermophotovoltaic generator

    DOEpatents

    Ashcroft, J.; Campbell, B.; DePoy, D.

    1998-06-30

    A thermophotovoltaic device includes at least one thermal radiator tube, a cooling tube concentrically disposed within each thermal radiator tube and an array of thermophotovoltaic cells disposed on the exterior surface of the cooling tube. A shell having a first end and a second end surrounds the thermal radiator tube. Inner and outer tubesheets, each having an aperture corresponding to each cooling tube, are located at each end of the shell. The thermal radiator tube extends within the shell between the inner tubesheets. The cooling tube extends within the shell through the corresponding apertures of the two inner tubesheets to the corresponding apertures of the two outer tubesheets. A plurality of the thermal radiator tubes can be arranged in a staggered or an in-line configuration within the shell. 8 figs.

  17. Tube-in-tube thermophotovoltaic generator

    DOEpatents

    Ashcroft, John; Campbell, Brian; DePoy, David

    1998-01-01

    A thermophotovoltaic device includes at least one thermal radiator tube, a cooling tube concentrically disposed within each thermal radiator tube and an array of thermophotovoltaic cells disposed on the exterior surface of the cooling tube. A shell having a first end and a second end surrounds the thermal radiator tube. Inner and outer tubesheets, each having an aperture corresponding to each cooling tube, are located at each end of the shell. The thermal radiator tube extends within the shell between the inner tubesheets. The cooling tube extends within the shell through the corresponding apertures of the two inner tubesheets to the corresponding apertures of the two outer tubesheets. A plurality of the thermal radiator tubes can be arranged in a staggered or an in-line configuration within the shell.

  18. Thermal neutron background measurement in CJPL

    NASA Astrophysics Data System (ADS)

    Zeng, Z. M.; Gong, H.; Yue, Q.; Li, J. M.

    2015-12-01

    This paper describes the measurement of thermal neutron flux in the CJPL underground laboratory in the proximity of the CDEX experiment. A low background thermal neutron detection system is designed which applies a combination of a 3He proportional tube and a 4He proportional tube as the detector. Thermal neutrons can be captured by the 3He proportional tube while the 4He proportional tube is for the purpose of background measurement. The tube wall is made up of oxygen-free copper to reduce the background due to radioactivity of the wall material. The electronics readout system has been developed to store triggered events' waveforms so as to get the amplitude spectrum and monitor the data quality. We observed an average thermal neutron flux of Φ = 4.00 ± 0.08 ×10-6 /cm2 s in the CJPL experiment hall in the proximity of CDEX experiment and the neutron and background events both distribute uniformly along the tube.

  19. Neural crest contributions to the lamprey head

    NASA Technical Reports Server (NTRS)

    McCauley, David W.; Bronner-Fraser, Marianne

    2003-01-01

    The neural crest is a vertebrate-specific cell population that contributes to the facial skeleton and other derivatives. We have performed focal DiI injection into the cranial neural tube of the developing lamprey in order to follow the migratory pathways of discrete groups of cells from origin to destination and to compare neural crest migratory pathways in a basal vertebrate to those of gnathostomes. The results show that the general pathways of cranial neural crest migration are conserved throughout the vertebrates, with cells migrating in streams analogous to the mandibular and hyoid streams. Caudal branchial neural crest cells migrate ventrally as a sheet of cells from the hindbrain and super-pharyngeal region of the neural tube and form a cylinder surrounding a core of mesoderm in each pharyngeal arch, similar to that seen in zebrafish and axolotl. In addition to these similarities, we also uncovered important differences. Migration into the presumptive caudal branchial arches of the lamprey involves both rostral and caudal movements of neural crest cells that have not been described in gnathostomes, suggesting that barriers that constrain rostrocaudal movement of cranial neural crest cells may have arisen after the agnathan/gnathostome split. Accordingly, neural crest cells from a single axial level contributed to multiple arches and there was extensive mixing between populations. There was no apparent filling of neural crest derivatives in a ventral-to-dorsal order, as has been observed in higher vertebrates, nor did we find evidence of a neural crest contribution to cranial sensory ganglia. These results suggest that migratory constraints and additional neural crest derivatives arose later in gnathostome evolution.

  20. Transporting a tube in a tube.

    PubMed

    Li, Jieling; Jia, Yi; Dong, Weiguang; Feng, Xiyun; Fei, Jinbo; Li, Junbai

    2014-11-12

    LbL-assembled tubes were employed for micro/nanoscale cargo transportation through the kinesin-microtubule system. Selectively modified with kinesins onto the inner tube walls through Ni-NTA complexes, these tubes can work as channels for microtubules. A motility assay shows the smooth movement of microtubules along the tube inner wall powered by the inside immobilized kinesins. It could be envisioned that cargoes with different sizes can be transported through these tubular channels with little outside interruption. PMID:25303630

  1. Heat exchanger tube mounts

    DOEpatents

    Wolowodiuk, W.; Anelli, J.; Dawson, B.E.

    1974-01-01

    A heat exchanger in which tubes are secured to a tube sheet by internal bore welding is described. The tubes may be moved into place in preparation for welding with comparatively little trouble. A number of segmented tube support plates are provided which allow a considerable portion of each of the tubes to be moved laterally after the end thereof has been positioned in preparation for internal bore welding to the tube sheet. (auth)

  2. Stage-dependent plasticity of the anterior neural folds to form neural crest.

    PubMed

    Ezin, Maxellende; Barembaum, Meyer; Bronner, Marianne E

    2014-01-01

    The anterior neural fold (ANF) is the only region of the neural tube that does not produce neural crest cells. Instead, ANF cells contribute to the olfactory and lens placodes, as well as to the forebrain and epidermis. Here, we test the ability of the ANF to form neural crest by performing heterotopic transplantation experiments in the chick embryo. We find that, at the neurula stage (HH stage 7), the chick ANF retains the ability to form migrating neural crest cells when transplanted caudally to rostral hindbrain levels. This ability is gradually lost, such that by HH9, this tissue appears to no longer have the potential to form neural crest. In contrast to the ANF, hindbrain dorsal neural folds transplanted rostrally fail to contribute to the olfactory placode but instead continue to generate neural crest cells. The transcription factor GANF is expressed in the ANF and its morpholino-mediated knock-down expands the neural crest domain rostrally and results in the production of migratory cells emerging from the ANF; however, these cells fail to express the HNK1 neural crest marker, suggesting only partial conversion. Our results show that environmental factors can imbue the chick anterior neural folds to assume a neural crest cell fate via a mechanism that partially involves loss of GANF. PMID:25264214

  3. Data analysis for steam generator tubing samples

    SciTech Connect

    Dodd, C.V.

    1996-07-01

    The objective of the Improved Eddy-Current ISI for Steam Generators program is to upgrade and validate eddy-current inspections, including probes, instrumentation, and data processing techniques for inservice inspection of new, used, and repaired steam generator tubes; to improve defect detection, classification and characterization as affected by diameter and thickness variations, denting, probe wobble, tube sheet, tube supports, copper and sludge deposits, even when defect types and other variables occur in combination; to transfer this advanced technology to NRC`s mobile NDE laboratory and staff. This report provides a description of the application of advanced eddy-current neural network analysis methods for the detection and evaluation of common steam generator tubing flaws including axial and circumferential outer-diameter stress-corrosion cracking and intergranular attack. The report describes the training of the neural networks on tubing samples with known defects and the subsequent evaluation results for unknown samples. Evaluations were done in the presence of artifacts. Computer programs are given in the appendix.

  4. New laser tracheal tube

    NASA Astrophysics Data System (ADS)

    Ungemach, Josef; Foth, Hans-Jochen; Hoermann, Karl; Preponis, E.

    1996-09-01

    The complication of a laser induced tube fire during surgery was first published in 1979. The protection of tracheal tubes against ignition is necessary to enable a safe laser surgery of the upper airway. in an experimental study a new compound tube was tested: this tube had a higher laser resistance than a pure metal tube. The damage threshold of this tube was tested against the emission of various lasers as CO2. The metal tube was damaged within seconds at CO2 laser power densities of 103 W/cm2 whereas the damage threshold of the compound tube was 3.106 W/cm2. We compared the compound laser tube to the so far used metal tube in a prospective clinical trial in our department of ENT in patients undergoing CO2-laser surgery of the upper airway. 66 patients were included into the study: 33 received the compound tube, 33 the metal tube. During endotracheal intubation the handling of the compound tube was better. During laser surgery high airway pressures occured more often with the metal tube. Whereas kinking was the problem of the compound tubes. Destruction of cuffs occured in both groups but did not cause any complications. No tube or cuff fire was noticed.

  5. Neural networks for triggering

    SciTech Connect

    Denby, B. ); Campbell, M. ); Bedeschi, F. ); Chriss, N.; Bowers, C. ); Nesti, F. )

    1990-01-01

    Two types of neural network beauty trigger architectures, based on identification of electrons in jets and recognition of secondary vertices, have been simulated in the environment of the Fermilab CDF experiment. The efficiencies for B's and rejection of background obtained are encouraging. If hardware tests are successful, the electron identification architecture will be tested in the 1991 run of CDF. 10 refs., 5 figs., 1 tab.

  6. Evolvable synthetic neural system

    NASA Technical Reports Server (NTRS)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  7. Neural Networks

    SciTech Connect

    Smith, Patrick I.

    2003-09-23

    Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing information [2]. Each one of these cells acts as a simple processor. When individual cells interact with one another, the complex abilities of the brain are made possible. In neural networks, the input or data are processed by a propagation function that adds up the values of all the incoming data. The ending value is then compared with a threshold or specific value. The resulting value must exceed the activation function value in order to become output. The activation function is a mathematical function that a neuron uses to produce an output referring to its input value. [8] Figure 1 depicts this process. Neural networks usually have three components an input, a hidden, and an output. These layers create the end result of the neural network. A real world example is a child associating the word dog with a picture. The child says dog and simultaneously looks a picture of a dog. The input is the spoken word ''dog'', the hidden is the brain processing, and the output will be the category of the word dog based on the picture. This illustration describes how a neural network functions.

  8. Torsion Tests of Tubes

    NASA Technical Reports Server (NTRS)

    Stang, Ambrose H; Ramberg, Walter; Back, Goldie

    1937-01-01

    This report presents the results of tests of 63 chromium-molybdenum steel tubes and 102 17st aluminum-alloy tubes of various sizes and lengths made to study the dependence of the torsional strength on both the dimensions of the tube and the physical properties of the tube material. Three types of failure are found to be important for sizes of tubes frequently used in aircraft construction: (1) failure by plastic shear, in which the tube material reached its yield strength before the critical torque was reached; (2) failure by elastic two-lobe buckling, which depended only on the elastic properties of the tube material and the dimensions of the tube; and (3) failure by a combination of (1) and (2) that is, by buckling taking place after some yielding of the tube material.

  9. Glass tube splitting tool

    NASA Technical Reports Server (NTRS)

    Klein, J. A.; Murray, C. D.; Stein, J. A.

    1971-01-01

    Tool accurately splits glass tubing so cuts are aligned 180 deg apart and reassembled tube forms low pressure, gastight enclosure. Device should interest industries using cylindrical closed glass containers.

  10. Eustachian tube (image)

    MedlinePlus

    ... are more common in children because their eustachian tubes are shorter, narrower, and more horizontal than in ... become trapped when the tissue of the eustachian tube becomes swollen from colds or allergies. Bacteria trapped ...

  11. Hydraulic Tube Expander

    NASA Technical Reports Server (NTRS)

    Burley, R. K.

    1984-01-01

    Portable hydraulic tube expander expands small, thick-walled tubes in hard-to-reach locations. Tool particularly useful in situations where mechanical expander too fragile to produce desired expansion.

  12. Microhole Tubing Bending Report

    DOE Data Explorer

    Oglesby, Ken

    2012-01-01

    A downhole tubing bending study was made and is reported herein. IT contains a report and 2 excel spreadsheets to calculate tubing bending and to estimate contact points of the tubing to the drilled hole wall (creating a new support point).

  13. Eustachian Tube Dysfunction

    MedlinePlus

    ... diving may also make your symptoms worse. Causes & Risk Factors What causes eustachian tube dysfunction? The most common cause of eustachian tube dysfunction is excessive mucus and inflammation of the tube caused by a cold, the flu, a sinus infection or allergies. Who is at ...

  14. Gastrostomy feeding tube - bolus

    MedlinePlus

    ... a gastrostomy tube. Delmar’s Fundamental and Advanced Nursing Skills . 2nd Ed. Albany, NY: Delmar Thomson Learning; 2003: 742-749. Simmons, Remmington R.The percutaneous endoscopic gastrostomy tube: a nurse's guide to PEG tubes. Medsurg Nurs . 2013 Mar- ...

  15. EFFECTS OF TOXICANTS ON NEURAL DIFFERENTIATION

    EPA Science Inventory

    This manuscript describes in vitro measures of neural differentiation. This overview provides the background and literature review for measures that could be employed in both screening assays and mechanistic studies. this chapter also reviews data from key endpoints like neurite ...

  16. 21 CFR 868.5800 - Tracheostomy tube and tube cuff.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tracheostomy tube and tube cuff. 868.5800 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices 868.5800 Tracheostomy tube and tube cuff. (a) Identification. A tracheostomy tube and tube cuff is a device intended to be placed into...

  17. 21 CFR 868.5800 - Tracheostomy tube and tube cuff.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tracheostomy tube and tube cuff. 868.5800 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices 868.5800 Tracheostomy tube and tube cuff. (a) Identification. A tracheostomy tube and tube cuff is a device intended to be placed into...

  18. 21 CFR 868.5800 - Tracheostomy tube and tube cuff.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tracheostomy tube and tube cuff. 868.5800 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices 868.5800 Tracheostomy tube and tube cuff. (a) Identification. A tracheostomy tube and tube cuff is a device intended to be placed into...

  19. Telescoping tube assembly

    NASA Technical Reports Server (NTRS)

    Sturm, Albert J. (Inventor); Marrinan, Thomas E. (Inventor)

    1995-01-01

    An extensible and retractable telescoping tube positions test devices that inspect large stationary objects. The tube has three dimensional adjustment capabilities and is vertically suspended from a frame. The tube sections are independently supported with each section comprising U-shaped housing secured to a thicker support plate. Guide mechanisms preferably mounted only to the thicker plates guide each tube section parallel to a reference axis with improved accuracy so that the position of the remote end of the telescoping tube is precisely known.

  20. Neural Networks

    NASA Astrophysics Data System (ADS)

    Schwindling, Jerome

    2010-04-01

    This course presents an overview of the concepts of the neural networks and their aplication in the framework of High energy physics analyses. After a brief introduction on the concept of neural networks, the concept is explained in the frame of neuro-biology, introducing the concept of multi-layer perceptron, learning and their use as data classifer. The concept is then presented in a second part using in more details the mathematical approach focussing on typical use cases faced in particle physics. Finally, the last part presents the best way to use such statistical tools in view of event classifers, putting the emphasis on the setup of the multi-layer perceptron. The full article (15 p.) corresponding to this lecture is written in french and is provided in the proceedings of the book SOS 2008.

  1. Pulse Tube Refrigerator

    NASA Astrophysics Data System (ADS)

    Matsubara, Yoichi

    The pulse tube refrigerator is one of the regenerative cycle refrigerators such as Stirling cycle or Gifford-McMahon cycle which gives the cooling temperature below 150 K down to liquid helium temperature. In 1963, W. E. Gifford invented a simple refrigeration cycle which is composed of compressor, regenerator and simple tube named as pulse tube which gives a similar function of the expander in Stirling or Gifford-McMahon cycle. The thermodynamically performance of this pulse tube refrigerator is inferior to that of other regenerative cycles. In 1984, however, Mikulin and coworkers made a significant advance in pulse tube configuration called as orifice pulse tube. After this, several modifications of the pulse tube hot end configuration have been developed. With those modifications, the thermodynamic performance of the pulse tube refrigerator became the same order to that of Stirling and Gifford-McMahon refrigerator. This article reviews the brief history of the pulse tube refrigerator development in the view point of its thermodynamically efficiency. Simplified theories of the energy flow in the pulse tube have also been described.

  2. Lunar lava tube sensing

    NASA Astrophysics Data System (ADS)

    York, Cheryl Lynn; Walden, Bryce; Billings, Thomas L.; Reeder, P. Douglas

    1992-12-01

    Large (greater than 300 m diameter) lava tube caverns appear to exist on the Moon and could provide substantial safety and cost benefits for lunar bases. Over 40 m of basalt and regolith constitute the lava tube roof and would protect both construction and operations. Constant temperatures of -20 C reduce thermal stress on structures and machines. Base designs need not incorporate heavy shielding, so lightweight materials can be used and construction can be expedited. Identification and characterization of lava tube caverns can be incorporated into current precursor lunar mission plans. Some searches can even be done from Earth. Specific recommendations for lunar lava tube search and exploration are (1) an Earth-based radar interferometer, (2) an Earth-penetrating radar (EPR) orbiter, (3) kinetic penetrators for lunar lava tube confirmation, (4) a 'Moon Bat' hovering rocket vehicle, and (5) the use of other proposed landers and orbiters to help find lunar lava tubes.

  3. Lunar Lava Tube Sensing

    NASA Technical Reports Server (NTRS)

    York, Cheryl Lynn; Walden, Bryce; Billings, Thomas L.; Reeder, P. Douglas

    1992-01-01

    Large (greater than 300 m diameter) lava tube caverns appear to exist on the Moon and could provide substantial safety and cost benefits for lunar bases. Over 40 m of basalt and regolith constitute the lava tube roof and would protect both construction and operations. Constant temperatures of -20 C reduce thermal stress on structures and machines. Base designs need not incorporate heavy shielding, so lightweight materials can be used and construction can be expedited. Identification and characterization of lava tube caverns can be incorporated into current precursor lunar mission plans. Some searches can even be done from Earth. Specific recommendations for lunar lava tube search and exploration are (1) an Earth-based radar interferometer, (2) an Earth-penetrating radar (EPR) orbiter, (3) kinetic penetrators for lunar lava tube confirmation, (4) a 'Moon Bat' hovering rocket vehicle, and (5) the use of other proposed landers and orbiters to help find lunar lava tubes.

  4. Kaumana lava tube

    NASA Technical Reports Server (NTRS)

    Greeley, R.

    1974-01-01

    The entrance to Kaumana Lava Tube is in a picnic ground next to Highway 20 (Kaumana Drive) about 6.5 km southwest of Hilo. The area is passed on the way to the Kona Coast via the Saddle Road and is identified by a Hawaii Visitors Bureau sign. Although it is not the largest lava tube in the islands, Kaumana Lava Tube is an interesting geological formation, displaying many of the features typical of lava tube interiors. It is accessible, relatively easy to walk through, and is in an excellent state of preservation. The tube developed in a historic lava flow (1881, from Mauna Loa), and many aspects of lava tube activity are observed.

  5. Tube Thoracostomy: Complications and Its Management

    PubMed Central

    Kesieme, Emeka B.; Dongo, Andrew; Ezemba, Ndubueze; Irekpita, Eshiobo; Jebbin, Nze; Kesieme, Chinenye

    2012-01-01

    Background. Tube thoracostomy is widely used throughout the medical, surgical, and critical care specialities. It is generally used to drain pleural collections either as elective or emergency. Complications resulting from tube thoracostomy can occasionally be life threatening. Aim. To present an update on the complications and management of complications of tube thoracostomy. Methods. A review of the publications obtained from Medline search, medical libraries, and Google on tube thoracostomy and its complications was done. Results. Tube thoracostomy is a common surgical procedure which can be performed by either the blunt dissection technique or the trocar technique. Complication rates are increased by the trocar technique. These complications have been broadly classified as either technical or infective. Technical causes include tube malposition, blocked drain, chest drain dislodgement, reexpansion pulmonary edema, subcutaneous emphysema, nerve injuries, cardiac and vascular injuries, oesophageal injuries, residual/postextubation pneumothorax, fistulae, tumor recurrence at insertion site, herniation through the site of thoracostomy, chylothorax, and cardiac dysrhythmias. Infective complications include empyema and surgical site infection. Conclusion. Tube thoracostomy, though commonly performed is not without risk. Blunt dissection technique has lower risk of complications and is hence recommended. PMID:22028963

  6. Streak tube channel capacity

    SciTech Connect

    Whiteson, A.

    1991-01-01

    The channel capacity is the number of bits of information that can be encoded in a single sweep of a streak tube. Imitating the standard practice for digitizers, this channel capacity could serve as a figure of merit for comparing the relative values of streak tubes. An expression for tube channel capacity is developed in terms of its main performance characteristics. 2 refs., 1 fig.

  7. COAXIAL TUBE COUPLING

    DOEpatents

    Niemoth, H.R.

    1963-02-26

    BS>This patent shows a device for quickly coupling coaxial tubes in metal-to-metal fashion, so as to be suitable for use in a nuclear reactor. A threaded coliar urges a tapered metal extension on the outer coaxial tube into a tapered seat in the device and simultaneously exerts pressure through a coaxial helical spring so that a similar extension on the inner tube seats in a similar seat near the other end. (AEC)

  8. Conduction cooled tube supports

    DOEpatents

    Worley, Arthur C.; Becht, IV, Charles

    1984-01-01

    In boilers, process tubes are suspended by means of support studs that are in thermal contact with and attached to the metal roof casing of the boiler and the upper bend portions of the process tubes. The support studs are sufficiently short that when the boiler is in use, the support studs are cooled by conduction of heat to the process tubes and the roof casing thereby maintaining the temperature of the stud so that it does not exceed 1400.degree. F.

  9. TUBE SPLITTING APPARATUS

    DOEpatents

    Frantz, C.E.; Cawley, W.E.

    1961-05-01

    A tool is described for cutting a coolant tube adapted to contain fuel elements to enable the tube to be removed from a graphite moderator mass. The tool splits the tube longitudinally into halves and curls the longitudinal edges of the halves inwardly so that they occupy less space and can be moved radially inwardly away from the walls of the hole in the graphite for easy removal from the graphite.

  10. Wound tube heat exchanger

    DOEpatents

    Ecker, Amir L.

    1983-01-01

    What is disclosed is a wound tube heat exchanger in which a plurality of tubes having flattened areas are held contiguous adjacent flattened areas of tubes by a plurality of windings to give a double walled heat exchanger. The plurality of windings serve as a plurality of effective force vectors holding the conduits contiguous heat conducting walls of another conduit and result in highly efficient heat transfer. The resulting heat exchange bundle is economical and can be coiled into the desired shape. Also disclosed are specific embodiments such as the one in which the tubes are expanded against their windings after being coiled to insure highly efficient heat transfer.

  11. Streak tube characterization

    SciTech Connect

    Hinrichs, C.K.

    1985-04-01

    An explanation is given of some of the phenomena that occur in electrostatically focused streak tubes and how they can affect various measurements. These phenomena have to do with the overall tube voltage (cathode to anode/screen), cathode resistivity, space charge effects, chromatic effects (those caused by the spread in energy distribution of photoelectrons), off-axis focus, deflection defocusing, and the phosphor screen. Some important static and dynamic streak tube measurements are then described. The static measurements include those of photocathode spectral sensitivity and uniformity, phosphor screen measurements, tube radiant gain, extinction ratio, static resolution, magnification, and distortion. The dynamic measurements include spatial and time resolution. (LEW)

  12. Sapphire tube pressure vessel

    DOEpatents

    Outwater, John O.

    2000-01-01

    A pressure vessel is provided for observing corrosive fluids at high temperatures and pressures. A transparent Teflon bag contains the corrosive fluid and provides an inert barrier. The Teflon bag is placed within a sapphire tube, which forms a pressure boundary. The tube is received within a pipe including a viewing window. The combination of the Teflon bag, sapphire tube and pipe provides a strong and inert pressure vessel. In an alternative embodiment, tie rods connect together compression fittings at opposite ends of the sapphire tube.

  13. Composite Pulse Tube

    NASA Technical Reports Server (NTRS)

    Martin, Jerry L.; Cloyd, Jason H.

    2007-01-01

    A modification of the design of the pulse tube in a pulse-tube cryocooler reduces axial thermal conductance while preserving radial thermal conductance. It is desirable to minimize axial thermal conductance in the pulse-tube wall to minimize leakage of heat between the warm and cold ends of the pulse tube. At the same time, it is desirable to maximize radial thermal conductance at the cold end of the pulse tube to ensure adequate thermal contact between (1) a heat exchanger in the form of a stack of copper screens inside the pulse tube at the cold end and (2) the remainder of the cold tip, which is the object to which the heat load is applied and from which heat must be removed. The modified design yields a low-heat-leak pulse tube that can be easily integrated with a cold tip. A typical pulse tube of prior design is either a thin-walled metal tube or a metal tube with a nonmetallic lining. It is desirable that the outer surface of a pulse tube be cylindrical (in contradistinction to tapered) to simplify the design of a regenerator that is also part of the cryocooler. Under some conditions, it is desirable to taper the inner surface of the pulse tube to reduce acoustic streaming. The combination of a cylindrical outer surface and a tapered inner surface can lead to unacceptably large axial conduction if the pulse tube is made entirely of metal. Making the pulse-tube wall of a nonmetallic, lowthermal- conductivity material would not solve the problem because the wall would not afford the needed thermal contact for the stack of screens in the cold end. The modified design calls for fabricating the pulse tube in two parts: a longer, nonmetallic part that is tapered on the inside and cylindrical on the outside and a shorter, metallic part that is cylindrical on both the inside and the outside. The nonmetallic part can be made from G-10 fiberglass-reinforced epoxy or other low-thermal-conductivity, cryogenically compatible material. The metallic part must have high thermal conductivity in the cryogenic temperature range and would typically be made of pure copper to satisfy this requirement. The metallic part is bonded to the nonmetallic part with epoxy. Copper screens are inserted in the metallic part to form the cold-end heat exchanger, then the assembled pulse tube is inserted in the cold tip.

  14. Steam generator tube failures

    SciTech Connect

    MacDonald, P.E.; Shah, V.N.; Ward, L.W.; Ellison, P.G.

    1996-04-01

    A review and summary of the available information on steam generator tubing failures and the impact of these failures on plant safety is presented. The following topics are covered: pressurized water reactor (PWR), Canadian deuterium uranium (CANDU) reactor, and Russian water moderated, water cooled energy reactor (VVER) steam generator degradation, PWR steam generator tube ruptures, the thermal-hydraulic response of a PWR plant with a faulted steam generator, the risk significance of steam generator tube rupture accidents, tubing inspection requirements and fitness-for-service criteria in various countries, and defect detection reliability and sizing accuracy. A significant number of steam generator tubes are defective and are removed from service or repaired each year. This wide spread damage has been caused by many diverse degradation mechanisms, some of which are difficult to detect and predict. In addition, spontaneous tube ruptures have occurred at the rate of about one every 2 years over the last 20 years, and incipient tube ruptures (tube failures usually identified with leak detection monitors just before rupture) have been occurring at the rate of about one per year. These ruptures have caused complex plant transients which have not always been easy for the reactor operators to control. Our analysis shows that if more than 15 tubes rupture during a main steam line break, the system response could lead to core melting. Although spontaneous and induced steam generator tube ruptures are small contributors to the total core damage frequency calculated in probabilistic risk assessments, they are risk significant because the radionuclides are likely to bypass the reactor containment building. The frequency of steam generator tube ruptures can be significantly reduced through appropriate and timely inspections and repairs or removal from service.

  15. Looking Southeast Along Kilauea TEB Tube System

    View looking southeast along the fuming trace of the TEB tube system. The growing rootless shield field is in the background just above and to the left of center frame. The low, rounded shape of the shields--especially the shield in shadow to the left--are evident in this photo....

  16. Streak tube dynamic range

    SciTech Connect

    Whiteson, A.

    1991-01-01

    Experimental results indicate that, up to their saturation point, streak tubes are linear, shot noise devices with no clearly defined noise floor. Also, we have shown that the dynamic range of a tube depends on the operator's choice of acceptable risk and of pixel size. 2 refs., 3 figs., 1 tab.

  17. Hologram recording tubes

    NASA Technical Reports Server (NTRS)

    Rajchman, J. H.

    1973-01-01

    Optical memories allow extremely large numbers of bits to be stored and recalled in a matter of microseconds. Two recording tubes, similar to conventional image-converting tubes, but having a soft-glass surface on which hologram is recorded, do not degrade under repeated hologram read/write cycles.

  18. Welding Tubes In Place

    NASA Technical Reports Server (NTRS)

    Meredith, R.

    1984-01-01

    Special welding equipment joins metal tubes that carry pressurized cyrogenic fluids. Equipment small enough to be used in confined spaces in which such tubes often mounted. Welded joints lighter in weight and more leak-proof than joints made with mechanical fittings.

  19. Pyrotechnic Tubing Connector

    NASA Technical Reports Server (NTRS)

    Graves, Thomas J.; Yang, Robert A.

    1988-01-01

    Tool forms mechanical seal at joint without levers or hydraulic apparatus. Proposed tool intended for use in outer space used on Earth by heavily garbed workers to join tubing in difficult environments. Called Pyrotool, used with Lokring (or equivalent) fittings. Piston slides in cylinder when pushed by gas from detonating pyrotechnic charge. Impulse of piston compresses fittings, sealing around butting ends of tubes.

  20. Method for shaping polyethylene tubing

    NASA Technical Reports Server (NTRS)

    Kramer, R. C.

    1981-01-01

    Method forms polyethylene plastic tubing into configurations previously only possible with metal tubing. By using polyethylene in place of copper or stain less steel tubing inlow pressure systems, fabrication costs are significantly reduced. Polyethylene tubing can be used whenever low pressure tubing is needed in oil operations, aircraft and space applications, powerplants, and testing laboratories.

  1. 56. INTERIOR VIEW OF TUBES OF UNCERTAIN USE BELOW THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    56. INTERIOR VIEW OF TUBES OF UNCERTAIN USE BELOW THE LOWER WEST END OF THE AMALGAMATIONS PLATES. NOTE CUT STONE FOUNDATION WALLS ALONG THE BACKGROUND RIGHT. - Standard Gold Mill, East of Bodie Creek, Northeast of Bodie, Bodie, Mono County, CA

  2. Neural induction, neural fate stabilization, and neural stem cells.

    PubMed

    Moody, Sally A; Je, Hyun-Soo

    2002-04-28

    The promise of stem cell therapy is expected to greatly benefit the treatment of neurodegenerative diseases. An underlying biological reason for the progressive functional losses associated with these diseases is the extremely low natural rate of self-repair in the nervous system. Although the mature CNS harbors a limited number of self-renewing stem cells, these make a significant contribution to only a few areas of brain. Therefore, it is particularly important to understand how to manipulate embryonic stem cells and adult neural stem cells so their descendants can repopulate and functionally repair damaged brain regions. A large knowledge base has been gathered about the normal processes of neural development. The time has come for this information to be applied to the problems of obtaining sufficient, neurally committed stem cells for clinical use. In this article we review the process of neural induction, by which the embryonic ectodermal cells are directed to form the neural plate, and the process of neural-fate stabilization, by which neural plate cells expand in number and consolidate their neural fate. We will present the current knowledge of the transcription factors and signaling molecules that are known to be involved in these processes. We will discuss how these factors may be relevant to manipulating embryonic stem cells to express a neural fate and to produce large numbers of neurally committed, yet undifferentiated, stem cells for transplantation therapies. PMID:12805974

  3. Robotic Tube-Gap Inspector

    NASA Technical Reports Server (NTRS)

    Gilbert, Jeffrey L.; Gutow, David A.; Maslakowski, John E.

    1993-01-01

    Robotic vision system measures small gaps between nearly parallel tubes. Robot-held video camera examines closely spaced tubes while computer determines gaps between tubes. Video monitor simultaneously displays data on gaps.

  4. Building Background Knowledge

    ERIC Educational Resources Information Center

    Neuman, Susan B.; Kaefer, Tanya; Pinkham, Ashley

    2014-01-01

    This article make a case for the importance of background knowledge in children's comprehension. It suggests that differences in background knowledge may account for differences in understanding text for low- and middle-income children. It then describes strategies for building background knowledge in the age of common core standards.

  5. Differentiation state determines neural effects on microvascular endothelial cells

    SciTech Connect

    Muffley, Lara A.; Pan, Shin-Chen; Smith, Andria N.; Ga, Maricar; Hocking, Anne M.; Gibran, Nicole S.

    2012-10-01

    Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. Black-Right-Pointing-Pointer Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell production of nitric oxide. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons have different secretory profiles for angiogenic mediators.

  6. Preliminary research on eddy current bobbin quantitative test for heat exchange tube in nuclear power plant

    NASA Astrophysics Data System (ADS)

    Qi, Pan; Shao, Wenbin; Liao, Shusheng

    2016-02-01

    For quantitative defects detection research on heat transfer tube in nuclear power plants (NPP), two parts of work are carried out based on the crack as the main research objects. (1) Production optimization of calibration tube. Firstly, ASME, RSEM and homemade crack calibration tubes are applied to quantitatively analyze the defects depth on other designed crack test tubes, and then the judgment with quantitative results under crack calibration tube with more accuracy is given. Base on that, weight analysis of influence factors for crack depth quantitative test such as crack orientation, length, volume and so on can be undertaken, which will optimize manufacture technology of calibration tubes. (2) Quantitative optimization of crack depth. Neural network model with multi-calibration curve adopted to optimize natural crack test depth generated in in-service tubes shows preliminary ability to improve quantitative accuracy.

  7. Electronic Neural Networks

    NASA Technical Reports Server (NTRS)

    Thakoor, Anil

    1990-01-01

    Viewgraphs on electronic neural networks for space station are presented. Topics covered include: electronic neural networks; electronic implementations; VLSI/thin film hybrid hardware for neurocomputing; computations with analog parallel processing; features of neuroprocessors; applications of neuroprocessors; neural network hardware for terrain trafficability determination; a dedicated processor for path planning; neural network system interface; neural network for robotic control; error backpropagation algorithm for learning; resource allocation matrix; global optimization neuroprocessor; and electrically programmable read only thin-film synaptic array.

  8. Directed differentiation of pluripotent cells to neural lineages: homogeneous formation and differentiation of a neurectoderm population.

    PubMed

    Rathjen, Joy; Haines, Bryan P; Hudson, Kathryn M; Nesci, Antonietta; Dunn, Stephanie; Rathjen, Peter D

    2002-06-01

    During embryogenesis the central and peripheral nervous systems arise from a neural precursor population, neurectoderm, formed during gastrulation. We demonstrate the differentiation of mouse embryonic stem cells to neurectoderm in culture, in a manner which recapitulates embryogenesis, with the sequential and homogeneous formation of primitive ectoderm, neural plate and neural tube. Formation of neurectoderm occurs in the absence of extraembryonic endoderm or mesoderm and results in a stratified epithelium of cells with morphology, gene expression and differentiation potential consistent with positionally unspecified neural tube. Differentiation of this population to homogeneous populations of neural crest or glia was also achieved. Neurectoderm formation in culture allows elucidation of signals involved in neural specification and generation of implantable cell populations for therapeutic use. PMID:12015293

  9. Fallopian Tube Cancer

    MedlinePlus

    ... medical, surgical, radiation, gynecologic, and pediatric oncologists, oncology nurses, physician assistants, social workers, and patient advocates. Cancer.Net Guide Fallopian Tube ... with Side Effects After Treatment Questions to Ask ...

  10. Integrated structure vacuum tube

    NASA Technical Reports Server (NTRS)

    Dimeff, J.; Kerwin, W. J. (Inventor)

    1976-01-01

    High efficiency, multi-dimensional thin film vacuum tubes suitable for use in high temperature, high radiation environments are described. The tubes are fabricated by placing thin film electrode members in selected arrays on facing interior wall surfaces of an alumina substrate envelope. Cathode members are formed using thin films of triple carbonate. The photoresist used in photolithography aids in activation of the cathodes by carbonizing and reacting with the reduced carbonates when heated in vacuum during forming. The finely powdered triple carbonate is mixed with the photoresist used to delineate the cathode locations in the conventional solid state photolithographic manner. Anode and grid members are formed using thin films of refractory metal. Electron flow in the tubes is between grid elements from cathode to anode as in a conventional three-dimensional tube.

  11. Building with Tubes.

    ERIC Educational Resources Information Center

    D'Eugenio, Terrance, Ed.

    Text and illustrations show how to assemble furniture and toys out of cardboard tubes and sheets. Basic directions are provided, and the tools and materials necessary to the assembly of specific items are described. (MLF)

  12. Tube Alinement for Machining

    NASA Technical Reports Server (NTRS)

    Garcia, J.

    1984-01-01

    Tool with stepped shoulders alines tubes for machining in preparation for welding. Alinement with machine tool axis accurate to within 5 mils (0.13mm) and completed much faster than visual setup by machinist.

  13. Laparoscopic Cecostomy Tube Placement.

    PubMed

    Church, Joseph T; Teitelbaum, Daniel H; Jarboe, Marcus D

    2015-12-01

    Fecal incontinence is a debilitating problem for many children, especially those with anorectal malformations. Historically, surgical options have included the Malone antegrade continence enema, using an appendicostomy for antegrade colonic enemas. Since the development of this procedure, multiple alternatives have been developed, including the Chait cecostomy tube. Here, we present our technique for laparoscopic cecostomy tube placement. We find that this approach has several advantages, including mobilization of the cecum to allow the tube to be placed below the waistline for optimal cosmesis and comfort, increased safety provided by direct vision of needle access to the cecum, and increased security of the cecum to the abdominal wall allowing for safer tube replacement should it become dislodged in the early postoperative period. PMID:26551235

  14. Using a nasogastric tube.

    PubMed

    Candy, C

    1986-09-01

    This discussion of the use of a nasogastric tube covers the equipment needed, the method, rehydration and feeding, prolonged nasogastric feeding, and stopping nasogastric feeding. A nasogastric tube is useful when children are unable to drink safely and in sufficient amounts for any of the following reasons: severe dehydration; if intravenous (IV) therapy is unavailable; low birth weight infants; or the child is drowsy or vomiting. Severely malnourished children may be fed initially in this way if they are too weak or anorexic to eat or drink normally. The following equipment is needed: nasogastric tube; lubricating fluid; a syringe; blue litmus paper, if available; adhesive tape; stethoscope if available; and fluid to be given. Explain to the child's parents and the child, if old enough to understand, what will be done; lie infants flat; measure the approximate length from the child's nostril to the ear lobe and then to the top of the abdomen with the tube and mark the position; clean the nostrils to remove the mucus, and lubricate the tip of the tube and gently insert into the nostril; give the child a drink of water if he or she is conscious; continue to pass the tube down until the position marked reaches the nostril; use the syringe to suck up some fluid and test with blue litmus paper to check that the tube is in the stomach; and inject 5-10 ml of fluid (saline or oral rehydration solution, not milk formula) by syringe if satisfied the tube is in the correct position. Where possible, give a continuous drip of fluid. If this is not possible, give frequent small amounts using the syringe as a funnel. If feeding continues for more than 24 hours, clean the nostrils daily with warm water and change the tube to the other nostril every few days. Also keep the mouth very clean with a dilute solution of 8% sodium bicarbonate, if available, or citrus fruit juice. To remove the tube, remove the adhesive tape, take the tube out gently and smoothly, and offer the child a drink and gently cleanse the nostrils. After prolonged nasogastric feeding, a child may experience feeding problems or loss of appetite. Patient and encouragement are needed to establish feeding by mouth again. PMID:12315288

  15. Tubing crimping pliers

    DOEpatents

    Lindholm, G.T.

    1981-02-27

    The disclosure relates to pliers and more particularly to pliers for crimping two or more pieces of copper tubing together prior to their being permanently joined by brazing, soldering or the like. A die containing spring-loaded pins rotates within a cammed ring in the head of the pliers. As the die rotates, the pins force a crimp on tubing held within the pliers.

  16. Comparative analysis of neural crest cell death, migration, and function during vertebrate embryogenesis.

    PubMed

    Kulesa, Paul; Ellies, Debra L; Trainor, Paul A

    2004-01-01

    Cranial neural crest cells are a multipotent, migratory population that generates most of the cartilage, bone, connective tissue and peripheral nervous system in the vertebrate head. Proper neural crest cell patterning is essential for normal craniofacial morphogenesis and is highly conserved among vertebrates. Neural crest cell patterning is intimately connected to the early segmentation of the neural tube, such that neural crest cells migrate in discrete segregated streams. Recent advances in live embryo imaging have begun to reveal the complex behaviour of neural crest cells which involve intricate cell-cell and cell-environment interactions. Despite the overall similarity in neural crest cell migration between distinct vertebrates species there are important mechanistic differences. Apoptosis for example, is important for neural crest cell patterning in chick embryos but not in mouse, frog or fish embryos. In this paper we highlight the potential evolutionary significance of such interspecies differences in jaw development and evolution. Developmental Dynamics 229:14-29, 2004. PMID:14699574

  17. Dynamics of tubes in fluid with tube-baffle interaction

    SciTech Connect

    Chen, S.S.; Jendrzejczyk, J.A.; Wambsganss, M.W.

    1983-09-01

    Three series of tests are performed to evaluate the effects of tube to tube-support-plate (TSP) clearance on tube dynamic characteristics and instability phenomena for tube arrays in crossflow. Test results show that, for relatively large clearances, tubes may possess TSP-inactive modes in which the tubes rattle inside some of the tube-support-plate holes, and that the natural frequencies of TSP-inactive modes are lower than those of TSP-active modes, in which the support plates provide knife-edge type support. Tube response characteristics associated with TSP-inactive modes are sensitive to tube-to-TSP clearance, TSP thickness, excitation amplitude, tube alignment, and the fluid inside the clearance. In addition, tube response is intrinsically nonlinear, with the dominance of TSP-inactive or TSP-active modes depending on the magnitudes of different system parameters. In general, such a system is difficult to model; only a full-scale test can provide all the necessary characteristics. A tube array supported by TSPs with relatively large clearances may be subjected to dynamic instability in some of the TSP-inactive modes; tube response characteristics and impact forces on TSPs for a tube row are studied in detail in this report. Tube displacements associated with the instability of a TSP-inactive mode are small; however, impacts of the tube against TSPs may result in significant damage in a relatively short time. 52 figures.

  18. 21 CFR 868.5800 - Tracheostomy tube and tube cuff.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tracheostomy tube and tube cuff. 868.5800 Section 868.5800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5800 Tracheostomy tube and tube cuff. (a) Identification. A tracheostomy...

  19. Callose plug deposition patterns vary in pollen tubes of Arabidopsis thaliana ecotypes and in tomato species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background The pollen grain contains the male gametophyte that extends a pollen tube that grows through female tissues in order to deliver sperm to the embryo sac for double fertilization. Growing pollen tubes form periodic callose plugs that are thought to block off the older parts of the tube and ...

  20. PE on YouTube--Investigating Participation in Physical Education Practice

    ERIC Educational Resources Information Center

    Quennerstedt, Mikael

    2013-01-01

    Background: In this article, students' diverse ways of participating in physical education (PE) practice shown in clips on YouTube were investigated. YouTube is the largest user-generated video-sharing website on the Internet, where different video content is presented. The clips on YouTube, as used in this paper, can be seen as a user-generated…

  1. The Cosmic Background Explorer.

    ERIC Educational Resources Information Center

    Gulkis, Samuel; And Others

    1990-01-01

    Outlines the Cosmic Background Explorer (COBE) mission to measure celestial radiation. Describes the instruments used and experiments involving differential microwave radiometers, and a far infrared absolute spectrophotometer. (YP)

  2. FGF8 Signaling is Chemotactic for Cardiac Neural Crest Cells

    PubMed Central

    Sato, Asako; Scholl, Ann Marie; Kuhn, EB; Stadt, Harriett A.; Decker, Jennifer R.; Pegram, Kelly; Hutson, Mary R.; Kirby, Margaret L.

    2011-01-01

    SUMMARY Cardiac neural crest cells migrate into the pharyngeal arches where they support development of the pharyngeal arch arteries. The pharyngeal endoderm and ectoderm both express high levels of FGF8. We hypothesized that FGF8 is chemotactic for cardiac crest cells. To begin testing this hypothesis, cardiac crest was explanted for migration assays under various conditions. Cardiac neural crest cells migrated more in response to FGF8. Single cell tracing indicated that this was not due to proliferation and subsequent transwell assays showed that the cells migrate toward an FGF8 source. The migratory response was mediated by FGF receptors (FGFR) 1 and 3 and MAPK/ERK intracellular signaling. To test whether FGF8 is chemokinetic and/or chemotactic in vivo, dominant negative FGFR1 was electroporated into the premigratory cardiac neural crest. Cells expressing the dominant negative receptor migrated slower than normal cardiac neural crest cells and were prone to remain in the vicinity of the neural tube and die. Treating with the FGFR1 inhibitor, SU5402 or an FGFR3 function-blocking antibody also slowed neural crest migration. FGF8 over-signaling enhanced neural crest migration. Neural crest cells migrated to an FGF8-sosked bead placed dorsal to the pharynx. Finally, an FGF8 producing plasmid was electroporated into an ectopic site in the ventral pharyngeal endoderm. The FGF8 producing cells attracted a thick layer of mesenchymal cells. DiI labeling of the neural crest as well as quail-to-chick neural crest chimeras showed that neural crest cells migrated to and around the ectopic site of FGF8 expression. These results showing that FGF8 is chemotactic and chemokinetic for cardiac neural crest adds another dimension to understanding the relationship of FGF8 and cardiac neural crest in cardiovascular defects. PMID:21419761

  3. Ethical Problems of Screening for Neural Tube Defects.

    ERIC Educational Resources Information Center

    Habgood, J. S.

    1978-01-01

    Among the ethical problems in screening for severe spina bifida in a fetus are deciding who should be screened; whether the procedure, which has medical risks, is justified; and how to deal with the only known solution--abortion. Journal availability: see EC 114 865. (PHR)

  4. Neural tube defects in New South Wales, Australia

    PubMed Central

    Field, Barbara

    1978-01-01

    Cases of spina bifida cystica, encephalocele, and anencephaly occurring over a 9-year period, 1965 to 1973, in New South Wales, Australia, were identified. A low frequency of 1·1 for spina bifida and encephalocele (SB) and 0·9 for anencephaly (A) was found. Secular trends parallel to those observed in the northern hemisphere were noted. Detailed analysis of 1575 cases showed an excess of births in spring, corresponding with conception in the summer months, after correction for shorter gestation in anencephalus, which varies from the peak of spring conceptions observed in British studies. An excess of female cases for each abnormality and a social class effect with a deficit of cases in classes I and II and an excess in classes IV and V and ex-nuptial births were apparent. The first birth rank for younger mothers did not show a significantly increased risk; however, the effect of high birth rank and older maternal age was more significant. Migration studies showed that in migrating from areas of high incidence these parents maintain a higher risk than the Australian population. The highest risk group was that in which both parents were born in the UK, and the next highest that in which an English-born mother was married to an Australian father. Mothers from Malta, and either or both parents from Lebanon, Egypt, and Austria were also at high risk. Part-aboriginal children had a higher risk rate for ASB than white Australian children. The proportion of older sibs affected was 4·12% of sibs of both sexes of an index case of spina bifida, and 3·19% of an index case of anencephaly. The abnormalities alternate or recur in families. An increased perinatal mortality rate in sibs was shown. Twin studies showed a higher concordance rate for monochorionic pairs. A sequential interaction in an excess of opposite sex sib before an index case was apparent. The results of this study support a multifactorial aetiology for ASB resulting from genetic environmental interaction. New South Wales is the eastern coastal state of Australia, with an area of 309 433 square miles and a population of 4 640 800 at the 1971 Census. The continent is geographically isolated with a large migrant population, seasonal reversal, and a hot climate. PMID:739521

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

    MedlinePlus

    ... Health Education Campaigns & Programs Safe to Sleep, Media-Smart Youth, Maternal/Child Health Education Program NICHD Publications ... display nonverbal learning disabilities? An empirical approach to classification. Journal of the International Neuropsychological Society, 9, 653– ...

  6. What Are the Treatments for Neural Tube Defects?

    MedlinePlus

    ... or within the first few days after birth. Hydrocephalus. If an infant with spina bifida has hydrocephalus (water on the brain), a surgeon can implant ... fluid—to relieve pressure on the brain. Treating hydrocephalus can prevent problems such as blindness. Tethered spinal ...

  7. Correlators in nontrivial backgrounds

    SciTech Connect

    Mello Koch, Robert de; Ives, Norman; Stephanou, Michael

    2009-01-15

    Operators in N=4 super Yang-Mills theory with an R-charge of O(N{sup 2}) are dual to backgrounds which are asymtotically AdS{sub 5}xS{sup 5}. In this article we develop efficient techniques that allow the computation of correlation functions in these backgrounds. We find that (i) contractions between fields in the string words and fields in the operator creating the background are the field theory accounting of the new geometry, (ii) correlation functions of probes in these backgrounds are given by the free field theory contractions but with rescaled propagators and (iii) in these backgrounds there are no open string excitations with their special end point interactions; we have only closed string excitations.

  8. The Athena Background

    NASA Astrophysics Data System (ADS)

    Piro, Luigi; Lotti, Simone; Macculi, Claudio; Molendi, Silvano; Eraerds, Tanja; Laurent, Philippe

    2015-09-01

    Estimating, reducing and controlling the residual particle background is fundamental for achieving the objectives of several science topics of Athena, in particular those connected with background dominated observations of faint and/or diffuse sources. This requires assessing the particle environment in L2, propagating the various particle components throughout the mirror, spacecraft, and instruments via proper modelling and simulations of various physical processes, implementing design and h/w measures at instrument and mission level to reduce the un-rejected background and identifying proper calibration methods to control the background variations. Likewise, an adequate knowledge of the XRB, made of components that may vary spatially or temporally, is required as well. Here we will review the present status of the background knowledge, and summarize the activities on-going within Athena at various levels.

  9. Background-independence

    NASA Astrophysics Data System (ADS)

    Belot, Gordon

    2011-10-01

    Intuitively speaking, a classical field theory is background-independent if the structure required to make sense of its equations is itself subject to dynamical evolution, rather than being imposed ab initio. The aim of this paper is to provide an explication of this intuitive notion. Background-independence is not a not formal property of theories: the question whether a theory is background-independent depends upon how the theory is interpreted. Under the approach proposed here, a theory is fully background-independent relative to an interpretation if each physical possibility corresponds to a distinct spacetime geometry; and it falls short of full background-independence to the extent that this condition fails.

  10. Tube plug inspection system

    SciTech Connect

    Pirl, W.E.; Ray, E.A.; Costlow, A.M.; Roth, C.H. Jr.; Gradich, F.X.; Chizmar, D.A.

    1992-03-31

    This patent describes a system for inspecting a tube plug defining a chamber therein and having an open end in communication with the chamber, the chamber having disposed therein an expander element having a bore therethrough. It comprises: probe means having a sensor probe connected thereto for inspecting the tube plug, the probe means capable of being connected to the tube plug for extending the sensor probe a predetermined distance into the chamber through the open end of the tube plug; means connected to the probe means for rotating and translating the sensor probe within the chamber to provide an inspection scan interiorly of the tube plug, the rotating and translating means including: a flexible hose connected to the probe means for translating and rotating the probe means, the hose having adjacent segments so that the hose is flexible; and a connector interposed between adjacent segments of the hose for maintaining the hose in a tangle-free state; and drive means engaging the rotating and translating means for driving the rotating and translating means.

  11. A Comparison of the Haider Tube-Guard® Endotracheal Tube Holder Versus Adhesive Tape to Determine if This Novel Device Can Reduce Endotracheal Tube Movement and Prevent Unplanned Extubation

    PubMed Central

    Buckley, Jack C.; Brown, Adam P.; Shin, John S.; Rogers, Kirsten M.

    2016-01-01

    BACKGROUND: Endotracheal tube security is a critical safety issue. We compared the mobility of an in situ endotracheal tube secured with adhesive tape to the one secured with a new commercially available purpose-designed endotracheal tube-holder device (Haider Tube-Guard®). We also observed for the incidence of oropharyngeal or facial trauma associated with the 2 tube fixation methods. METHODS: Thirty adult patients undergoing general anesthesia with neuromuscular blockade were prospectively enrolled. Immediately after intubation, a single study author positioned the endotracheal tube tip in the distal trachea using a bronchoscope. Anesthesiologists caring for patients secured the tube in their normal fashion (always with adhesive tape). A force transducer was used to apply linear force, increasing to 15 N or until the principal investigator deemed that the force be aborted for safety reasons. The displacement of the endotracheal tube was measured with the bronchoscope. Any tape was then removed and the endotracheal tube secured with the Haider Tube-Guard device. The linear force was reapplied and the displacement of the endotracheal tube measured. The Haider Tube-Guard device was left in place for the duration of the case. The patient’s face and oropharynx were examined for any evidence of trauma during surgery and in the recovery room. On discharge from the postanesthesia care unit, the patient answered a brief survey assessing for any subjective evidence of minor facial or oropharyngeal trauma. RESULTS: Under standardized tension, the endotracheal tube withdrew a mean distance of 3.4 cm when secured with adhesive tape versus 0.3 cm when secured with the Haider Tube-Guard (P <0.001). Ninety-seven percent of patients (29/30) experienced clinically significant endotracheal tube movement (>1 cm) when adhesive tape was used to secure the tube versus 3% (1/30) when the Haider Tube-Guard was used (P <0.001). Thirty percent of patients (9/30) were potentially deemed a high extubation risk (endotracheal tube movement >4 cm) when the endotracheal tube was secured with tape versus 0% (0/30) when secured with the Haider Tube-Guard (P = 0.004). Six patients with taped endotracheal tubes required the traction to be aborted before 15 N of force was achieved to prevent potential extubation as the tape either separated from the face or stretched to allow excessive endotracheal tube movement. None of the patients appeared to sustain any injury from the Haider Tube-Guard device. CONCLUSIONS: The Haider Tube-Guard significantly reduced the mobility of the endotracheal tube when compared with adhesive tape and was well tolerated in our observations. PMID:26983051

  12. Adaptive background model

    NASA Astrophysics Data System (ADS)

    Lu, Xiaochun; Xiao, Yijun; Chai, Zhi; Wang, Bangping

    2007-11-01

    An adaptive background model aiming at outdoor vehicle detection is presented in this paper. This model is an improved model of PICA (pixel intensity classification algorithm), it classifies pixels into K-distributions by color similarity, and then a hypothesis that the background pixel color appears in image sequence with a high frequency is used to evaluate all the distributions to determine which presents the current background color. As experiments show, the model presented in this paper is a robust, adaptive and flexible model, which can deal with situations like camera motions, lighting changes and so on.

  13. The cosmic neutrino background

    NASA Technical Reports Server (NTRS)

    Dar, Arnon

    1991-01-01

    The cosmic neutrino background is expected to consist of relic neutrinos from the big bang, of neutrinos produced during nuclear burning in stars, of neutrinos released by gravitational stellar collapse, and of neutrinos produced by cosmic ray interactions with matter and radiation in the interstellar and intergalactic medium. Formation of baryonic dark matter in the early universe, matter-antimatter annihilation in a baryonic symmetric universe, and dark matter annihilation could have also contributed significantly to the cosmic neutrino background. The purpose of this paper is to review the properties of these cosmic neutrino backgrounds, the indirect evidence for their existence, and the prospects for their detection.

  14. Advanced evacuated tube collectors

    NASA Astrophysics Data System (ADS)

    Schertz, W. W.; Hull, J. R.; Winston, R.; Ogallagher, J.

    1985-04-01

    The essence of the design concept for these new collectors is the integration of moderate levels of nonimaging concentration inside the evacuated tube itself. This permanently protects the reflection surfaces and allows the use of highly reflecting front surface mirrors with reflectances greater than 95%. Previous fabrication and long term testing of a proof-of-concept prototype has established the technical success of the concept. Present work is directed toward the development of a manufacturable unit that will be suitable for the widest possible range of applications. Design alternatives include scaling up the original prototype's tube diameter from 5 cm to 10 cm, using an internal shaped metal concentrating reflector, using a variety of profile shapes to minimize so-called gap losses and accommodate both single ended and double-ended flow geometries, and allowing the use of heat pipes for the absorber tube.

  15. The GLAST Background Model

    SciTech Connect

    Ormes, J.F.; Atwood, W.; Burnett, T.; Grove, E.; Longo, F.; McEnery, J.; Mizuno, T.; Ritz, S.; /NASA, Goddard

    2007-10-17

    In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect.

  16. The GLAST Background Model

    SciTech Connect

    Ormes, J. F.; Atwood, W.; Burnett, T.; Grove, E.; Longo, F.; McEnery, J.; Ritz, S.; Mizuno, T.

    2007-07-12

    In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect.

  17. Bayesian background estimation

    NASA Astrophysics Data System (ADS)

    Fischer, R.; Dose, V.; Hanson, K. M.; von der Linden, W.

    2001-05-01

    The ubiquitous problem of estimating the background of a measured spectrum is solved with Bayesian probability theory. A mixture model is used to capture the defining characteristics of the problem, namely that the background is smoother than the signal. The smoothness property is quantified in terms of a cubic spline basis where a variable degree of smoothness is attained by allowing the number of knots and the knot positions to be adaptively chosen on the basis of the data. The fully Bayesian approach taken provides a natural way to handle knot adaptivity, allows uncertainties in the background to be estimated and data points to be classified in groups containing only background and groups with additional signal contribution. Our technique is demonstrated on a PIXE spectrum from a geological sample and an Auger spectrum from an 10 monolayer iron film on tungsten.

  18. a Non-Tube Inertance Device for Pulse Tube Cryocoolers

    NASA Astrophysics Data System (ADS)

    Yuan, S. W. K.; Curran, D. G. T.; Cha, J. S.

    2010-04-01

    Inertance Pulse Tube Cryocoolers make use of a long tube for phase shifting and optimization of performance. This long tube presents a challenge for packaging in most applications, and is also a concern for environments where vibration is present (e.g., launch). In the present invention, a gap configuration is used in place of the tube, resulting in a more compact inertance device. Using the SAGE software, the performance of this new device is found to be comparable to that of an inertance tube. Significantly, this new invention offers the flexibility to change the inertance value during testing and operation, which cannot be done with the tube configuration.

  19. Background Studies for EXIST

    NASA Technical Reports Server (NTRS)

    Wilson, Colleen A.; Pendleton, G. N.; Fishman, G. J.

    2004-01-01

    We present results from a study of the trapped proton and electron background for several orbital inclinations and altitudes. This study includes time dependent effects. In addition we describe a 3 component cosmic background model developed at the University of Southampton, UK. The three components are cosmic diffuse gamma rays, atmospheric albedo gamma rays, and cosmic ray protons. We present examples of how this model was applied to BATSE and discuss its application to EXIST.

  20. Neutron streak tube

    SciTech Connect

    Wang, C.L.; Lerche, R.A.; Medecki, H.; Phillips, G.E.; Singh, M.S.

    1986-08-01

    We present the design and construction of a simple neutron streak tube. The cathode is a 10-..mu..m-thick U/sup 238/ strip, 25 mm wide and 1.5 mm high, vacuum deposited on a stainless-steel substrate which replaces the cathode of a Lawrence Livermore National Laboratory (LLNL) model 3 x-ray streak camera. Accompanying a fission fragment, about 200 low-energy secondary electrons are emitted from the cathode. The streak tube was tested at a rotating target neutron source and at the Nova laser which produced 10/sup 13/ neutrons from the fusion target. Preliminary results are presented.

  1. Fill tube fitted spheres

    SciTech Connect

    Ives, B.H.

    1981-07-13

    The high temperature diffusion technique for fuel filling of some future direct drive cryogenic ICF targets may be unacceptable. The following describes a technique of fitting a 1 mm diameter x 6 ..mu..m thick glass microsphere with an approx. 50 ..mu..m O.D. glass fill tube. The process of laser drilling a 50 ..mu..m diameter hole in the microsphere wall, technique for making the epoxy joint between the sphere and fill tube, as well as the assembly procedure are also discussed.

  2. PRODUCTION OF URANIUM TUBING

    DOEpatents

    Creutz, E.C.

    1958-04-15

    The manufacture of thin-walled uranium tubing by the hot-piercing techique is described. Uranium billets are preheated to a temperature above 780 d C. The heated billet is fed to a station where it is engaged on its external surface by three convex-surfaced rotating rollers which are set at an angle to the axis of the billet to produce a surface friction force in one direction to force the billet over a piercing mandrel. While being formed around the mandrel and before losing the desired shape, the tube thus formed is cooled by a water spray.

  3. Sound Analysis in an In Vitro Endotracheal Tube Model

    PubMed Central

    Park, Young Sik; Kee, Young Wook; Park, Kwang Suk; Lee, Jinwoo; Lee, Sang-Min; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo

    2011-01-01

    Background/Aims Complete endotracheal tube obstruction is a medical emergency, and partial occlusion causes increased breathing rates and failure to wean off mechanical ventilation. Partial occlusion may be underestimated due to the lack of proper detection methods. We tested whether the sound of an endotracheal tube could be used to detect an endotracheal tube obstruction using an in vitro model. Methods An endotracheal tube was connected to a ventilator on one end and a test lung on the other. Sounds were recorded with a microphone located inside the endotracheal tube via a connector. During mechanical ventilation, we changed the endotracheal tube internal diameter from 5.0 to 8.0 mm and different grades of obstruction at different sites were used along the tube. Sound energy was compared among the different conditions. Results The energy of endotracheal tube sounds was positively correlated with the internal diameter and negatively correlated with the degree of obstruction. The rate of decline in energy differed with obstruction location. When the obstruction was more distal, the rate of decline in endotracheal sound energy was more rapid. Conclusions Changes in the sound of an endotracheal tube can be used to detect an obstruction. Further studies are needed for clinical application. PMID:22205842

  4. Optical Neural Interfaces

    PubMed Central

    Warden, Melissa R.; Cardin, Jessica A.; Deisseroth, Karl

    2014-01-01

    Genetically encoded optical actuators and indicators have changed the landscape of neuroscience, enabling targetable control and readout of specific components of intact neural circuits in behaving animals. Here, we review the development of optical neural interfaces, focusing on hardware designed for optical control of neural activity, integrated optical control and electrical readout, and optical readout of population and single-cell neural activity in freely moving mammals. PMID:25014785

  5. Nested Neural Networks

    NASA Technical Reports Server (NTRS)

    Baram, Yoram

    1992-01-01

    Report presents analysis of nested neural networks, consisting of interconnected subnetworks. Analysis based on simplified mathematical models more appropriate for artificial electronic neural networks, partly applicable to biological neural networks. Nested structure allows for retrieval of individual subpatterns. Requires fewer wires and connection devices than fully connected networks, and allows for local reconstruction of damaged subnetworks without rewiring entire network.

  6. Generalized classifier neural network.

    PubMed

    Ozyildirim, Buse Melis; Avci, Mutlu

    2013-03-01

    In this work a new radial basis function based classification neural network named as generalized classifier neural network, is proposed. The proposed generalized classifier neural network has five layers, unlike other radial basis function based neural networks such as generalized regression neural network and probabilistic neural network. They are input, pattern, summation, normalization and output layers. In addition to topological difference, the proposed neural network has gradient descent based optimization of smoothing parameter approach and diverge effect term added calculation improvements. Diverge effect term is an improvement on summation layer calculation to supply additional separation ability and flexibility. Performance of generalized classifier neural network is compared with that of the probabilistic neural network, multilayer perceptron algorithm and radial basis function neural network on 9 different data sets and with that of generalized regression neural network on 3 different data sets include only two classes in MATLAB environment. Better classification performance up to %89 is observed. Improved classification performances proved the effectivity of the proposed neural network. PMID:23298551

  7. Electronic neural networks

    SciTech Connect

    Howard, R.E.; Jackel, L.D.; Graf, H.P.

    1988-02-01

    The use of electronic neural networks to handle some complex computing problems is discussed. A simple neural model is shown and discussed in terms of its computational aspects. The use of electronic neural networks in machine pattern recognition and classification and in machine learning is examined. CMOS programmable networks are discussed. 15 references.

  8. Patterns in neural processing

    NASA Astrophysics Data System (ADS)

    Engineer, Sunu

    2012-03-01

    In this paper we propose a model for neural processing that addresses both the evolutionary and functional aspects of neural systems that are observed in nature, from the simplest neural collections to dense large scale associations such as human brains. We propose both an architecture and a process in which these components interact to create the emergent behavior that we define as the 'mind'.

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

    PubMed Central

    2011-01-01

    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. PMID:21864354

  10. Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns

    NASA Technical Reports Server (NTRS)

    Meulemans, Daniel; Bronner-Fraser, Marianne

    2002-01-01

    The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However, migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.

  11. Overview of artificial neural networks.

    PubMed

    Zou, Jinming; Han, Yi; So, Sung-Sau

    2008-01-01

    The artificial neural network (ANN), or simply neural network, is a machine learning method evolved from the idea of simulating the human brain. The data explosion in modem drug discovery research requires sophisticated analysis methods to uncover the hidden causal relationships between single or multiple responses and a large set of properties. The ANN is one of many versatile tools to meet the demand in drug discovery modeling. Compared to a traditional regression approach, the ANN is capable of modeling complex nonlinear relationships. The ANN also has excellent fault tolerance and is fast and highly scalable with parallel processing. This chapter introduces the background of ANN development and outlines the basic concepts crucially important for understanding more sophisticated ANN. Several commonly used learning methods and network setups are discussed briefly at the end of the chapter. PMID:19065803

  12. Intelligent Space Tube Optimization for speeding ground water remedial design.

    PubMed

    Kalwij, Ineke M; Peralta, Richard C

    2008-01-01

    An innovative Intelligent Space Tube Optimization (ISTO) two-stage approach facilitates solving complex nonlinear flow and contaminant transport management problems. It reduces computational effort of designing optimal ground water remediation systems and strategies for an assumed set of wells. ISTO's stage 1 defines an adaptive mobile space tube that lengthens toward the optimal solution. The space tube has overlapping multidimensional subspaces. Stage 1 generates several strategies within the space tube, trains neural surrogate simulators (NSS) using the limited space tube data, and optimizes using an advanced genetic algorithm (AGA) with NSS. Stage 1 speeds evaluating assumed well locations and combinations. For a large complex plume of solvents and explosives, ISTO stage 1 reaches within 10% of the optimal solution 25% faster than an efficient AGA coupled with comprehensive tabu search (AGCT) does by itself. ISTO input parameters include space tube radius and number of strategies used to train NSS per cycle. Larger radii can speed convergence to optimality for optimizations that achieve it but might increase the number of optimizations reaching it. ISTO stage 2 automatically refines the NSS-AGA stage 1 optimal strategy using heuristic optimization (we used AGCT), without using NSS surrogates. Stage 2 explores the entire solution space. ISTO is applicable for many heuristic optimization settings in which the numerical simulator is computationally intensive, and one would like to reduce that burden. PMID:18754799

  13. Resonance tube igniter

    NASA Technical Reports Server (NTRS)

    Conrad, E. W.; Pavli, A. J.; Phillips, B. R.

    1970-01-01

    Reasonance induced in stoichiometric mixtures of gaseous hydrogen-oxygen produces temperatures /over 1100 deg F/ high enough to cause ignition. Resonance tube phenomenon occurs when high pressure gas is forced through sonic or supersonic nozzle into short cavity. Various applications for the phenomenon are discussed.

  14. Tube welding and brazing

    NASA Technical Reports Server (NTRS)

    Poorman, R. M.

    1969-01-01

    Brochures outline the tools, equipment, materials, and techniques used for joining tubes by automatic and semiautomatic welding and brazing. A few of the metals being joined are stainless steels of various diameters and thickness. Techniques have been developed for on-site or work-bench repair.

  15. Investigation of Pitot tubes

    NASA Technical Reports Server (NTRS)

    Herschel, W H; Buckingham, E

    1917-01-01

    Report describes the principles of operation and characteristics of some of the instruments which have been devised or used to measure both low and high speeds of aeroplanes. Since the pitot tube is the instrument which has been most commonly used in the United States and Great Britain as a speedometer for aeroplanes, it is treated first and somewhat more fully than the others.

  16. Tube Feeding Transition Plateaus

    ERIC Educational Resources Information Center

    Klein, Marsha Dunn

    2007-01-01

    The journey children make from tube feeding to oral feeding is personal for each child and family. There is a sequence of predictable plateaus that children climb as they move toward orally eating. By better understanding this sequence, parents and children can maximize the development, learning, enjoyment and confidence at each plateau. The…

  17. Orbital tube flaring system produces tubing connectors with zero leakage

    NASA Technical Reports Server (NTRS)

    Williams, J. R.

    1967-01-01

    An orbital tube flaring system produces tubing connectors with a zero-leak potential needed in high pressure hydraulic and pneumatic systems. The flaring system incorporates a rolling cone and rolling die to closely control flare characteristics.

  18. Galactic Meteoroid Background

    NASA Astrophysics Data System (ADS)

    Chugai, N. N.

    2001-07-01

    The density of the Galactic meteoroid background formed by the loss of large dust grains escaped from circumstellar disks during the formation of a star is estimated. This density is shown to be substantially higher than the local density of meteoroids that escaped from dusty stellar disks as a result of two-star collisions. The flux of meteors of the Galactic background near the Earth is calculated for a given latitude of the observing site taking into account the velocity distribution of dust particles and the motion of particles in the solar gravity field. The expected rate of the Galactic background meteor events at the AMOR radar latitude is lower by at least a factor of 30 than the reported frequency of interstellar meteor events that are supposedly registered in the AMOR experiment.

  19. Optical flash background rates

    NASA Technical Reports Server (NTRS)

    Schaefer, B. E.; Pedersen, H.; Gouiffes, C.; Poulsen, J. M.; Pizzichini, G.

    1987-01-01

    Flash background rates are measured from August 18-September 5, 1985 using the Lowell 0.61-m telescope at CTIO and the 28-cm f/10 Schmidt-Cassegrain telescope at ESO. During 230.1 hours of observing 40 flash events were detected, and it was observed that the background events were dominated by meteors and satellites passing through the field-of-view. The measured flash rate is compared with that of Pedersen et al. (1984), and it is determined that the background flash rate that is applicable to the data of Pedersen et al. for February 8, 1984 is 0.023 events/hr. The morphology of that flash, which appears to be controlled by a gamma-ray burster, is examined.

  20. Cosmic Tachyon Background Radiation

    NASA Astrophysics Data System (ADS)

    Tomaschitz, Roman

    The equilibrium statistical mechanics of a background radiation of superluminal particles is investigated, based on a vectorial wave equation for tachyons of the Proca type. The partition function, the spectral energy density, and the various thermodynamic variables of an ideal Bose gas of tachyons in an open Robertson-Walker cosmology are derived. The negative mass square in the wave equation changes the frequency scaling in the Rayleigh-Jeans law, and there are also significant changes in the low temperature regime as compared to the microwave background, in particular in the caloric and thermal equations of state.

  1. The cosmic microwave background

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1991-01-01

    Recent limits on spectral distortions and angular anisotropies in the cosmic microwave background are reviewed. The various backgrounds are described, and the theoretical implications are assessed. Constraints on inflationary cosmology dominated by cold dark matter (CDM) and on open cosmological models dominated by baryonic dark matter (BDM), with, respectively, primordial random phase scale-invariant curvature fluctuations or non-gaussian isocurvature fluctuations are described. More exotic theories are addressed, and I conclude with the 'bottom line': what theorists expect experimentalists to be measuring within the next two to three years without having to abandon their most cherished theories.

  2. The Cosmic Background Explorer

    NASA Technical Reports Server (NTRS)

    Gulkis, Samuel; Lubin, Philip M.; Meyer, Stephan S.; Silverberg, Robert F.

    1990-01-01

    The Cosmic Background Explorer (CBE), NASA's cosmological satellite which will observe a radiative relic of the big bang, is discussed. The major questions connected to the big bang theory which may be clarified using the CBE are reviewed. The satellite instruments and experiments are described, including the Differential Microwave Radiometer, which measures the difference between microwave radiation emitted from two points on the sky, the Far-Infrared Absolute Spectrophotometer, which compares the spectrum of radiation from the sky at wavelengths from 100 microns to one cm with that from an internal blackbody, and the Diffuse Infrared Background Experiment, which searches for the radiation from the earliest generation of stars.

  3. Morphogenesis of the mouse neural plate depends on distinct roles of cofilin 1 in apical and basal epithelial domains.

    PubMed

    Grego-Bessa, Joaquim; Hildebrand, Jeffrey; Anderson, Kathryn V

    2015-04-01

    The genetic control of mammalian epithelial polarity and dynamics can be studied in vivo at cellular resolution during morphogenesis of the mouse neural tube. The mouse neural plate is a simple epithelium that is transformed into a columnar pseudostratified tube over the course of ∼ 24 h. Apical F-actin is known to be important for neural tube closure, but the precise roles of actin dynamics in the neural epithelium are not known. To determine how the organization of the neural epithelium and neural tube closure are affected when actin dynamics are blocked, we examined the cellular basis of the neural tube closure defect in mouse mutants that lack the actin-severing protein cofilin 1 (CFL1). Although apical localization of the adherens junctions, the Par complex, the Crumbs complex and SHROOM3 is normal in the mutants, CFL1 has at least two distinct functions in the apical and basal domains of the neural plate. Apically, in the absence of CFL1 myosin light chain does not become phosphorylated, indicating that CFL1 is required for the activation of apical actomyosin required for neural tube closure. On the basal side of the neural plate, loss of CFL1 has the opposite effect on myosin: excess F-actin and myosin accumulate and the ectopic myosin light chain is phosphorylated. The basal accumulation of F-actin is associated with the assembly of ectopic basal tight junctions and focal disruptions of the basement membrane, which eventually lead to a breakdown of epithelial organization. PMID:25742799

  4. Morphogenesis of the mouse neural plate depends on distinct roles of cofilin 1 in apical and basal epithelial domains

    PubMed Central

    Grego-Bessa, Joaquim; Hildebrand, Jeffrey; Anderson, Kathryn V.

    2015-01-01

    The genetic control of mammalian epithelial polarity and dynamics can be studied in vivo at cellular resolution during morphogenesis of the mouse neural tube. The mouse neural plate is a simple epithelium that is transformed into a columnar pseudostratified tube over the course of ∼24 h. Apical F-actin is known to be important for neural tube closure, but the precise roles of actin dynamics in the neural epithelium are not known. To determine how the organization of the neural epithelium and neural tube closure are affected when actin dynamics are blocked, we examined the cellular basis of the neural tube closure defect in mouse mutants that lack the actin-severing protein cofilin 1 (CFL1). Although apical localization of the adherens junctions, the Par complex, the Crumbs complex and SHROOM3 is normal in the mutants, CFL1 has at least two distinct functions in the apical and basal domains of the neural plate. Apically, in the absence of CFL1 myosin light chain does not become phosphorylated, indicating that CFL1 is required for the activation of apical actomyosin required for neural tube closure. On the basal side of the neural plate, loss of CFL1 has the opposite effect on myosin: excess F-actin and myosin accumulate and the ectopic myosin light chain is phosphorylated. The basal accumulation of F-actin is associated with the assembly of ectopic basal tight junctions and focal disruptions of the basement membrane, which eventually lead to a breakdown of epithelial organization. PMID:25742799

  5. Electromagnetic PIC modeling with a background gas

    NASA Astrophysics Data System (ADS)

    Verboncoeur, J. P.; Cooperberg, D.

    1997-02-01

    Modeling the interaction of relativistic electromagnetic plasmas with a background gas is described. The timescales range over many orders of magnitude, from the electromagnetic Courant condition (˜10-12 sec) to electron-neutral collision times (˜10-7 sec) to ion transit times (˜10-5 sec). For this work, the traditional Monte Carlo algorithm [1] is described for relativistic electrons. Subcycling is employed to improve efficiency, and smoothing is employed to reduce particle noise. Applications include plasma-focused electron guns, gas-filled microwave tubes, surface wave discharges driven at microwave frequencies, and electron-cyclotron resonance discharges. The method is implemented in the OOPIC code [2].

  6. Electromagnetic PIC modeling with a background gas

    SciTech Connect

    Verboncoeur, J. P.; Cooperberg, D.

    1997-02-01

    Modeling the interaction of relativistic electromagnetic plasmas with a background gas is described. The timescales range over many orders of magnitude, from the electromagnetic Courant condition ({approx}10{sup -12} sec) to electron-neutral collision times ({approx}10{sup -7} sec) to ion transit times ({approx}10{sup -5} sec). For this work, the traditional Monte Carlo algorithm [1] is described for relativistic electrons. Subcycling is employed to improve efficiency, and smoothing is employed to reduce particle noise. Applications include plasma-focused electron guns, gas-filled microwave tubes, surface wave discharges driven at microwave frequencies, and electron-cyclotron resonance discharges. The method is implemented in the OOPIC code [2].

  7. Rubens Flame-Tube Demonstration.

    ERIC Educational Resources Information Center

    Ficken, George W.; Stephenson, Francis C.

    1979-01-01

    Investigates and explains the phenomenon associated with Rubens flame-tube demonstration, specifically the persistance of flames at regular intervals along the tube for few minutes after the gas is turned off. (GA)

  8. Vanadium tube processing and analysis

    SciTech Connect

    Kautz, D.D.; Tanaka, G.J.

    1993-08-11

    Vanadium tubing obtained from Century Tubes, a custom tubing manufacturer, was studied to determine as-received quality and fabricability. Applications for this tubing involve crimping and sealing operations at Pantex Plant requiring very high levels of leak-tightness (leak rates less than 10{sup {minus}8} atm-cc He/sec). The as-received material had poor OD and ID surface finish and cleanliness that needed to be improved before use in component fabrication. Savannah River Technical Center (SRTC) personnel developed a cleaning procedure to make this tubing acceptable for crimping and sealing operations. After suitably cleaning the tubing, we tested several tube sealing techniques and all showed some degree of success. Pantex Plant personnel are now implementing a tube sealing process very similar to one of the techniques studied, a mechanical crimp followed by seal welding.

  9. Ear tube insertion - series (image)

    MedlinePlus

    Ear tube insertion is recommended for: fluid in the middle ear (present for more than 12 weeks) recurrent ear ... the accumulated fluid is suctioned out. A small tube is inserted through the incised eardrum in order ...

  10. Multiple test tubes stirred mechanically

    NASA Technical Reports Server (NTRS)

    Leon, H. J.; Strong, I. J.

    1965-01-01

    Mechanical device simultaneously stirs multiple test tubes under controlled laboratory conditions. The invention provides a variable stirring rate, minimal amount of contamination of tube contents, unattended and simple operation, and easy maintenance and cleaning.

  11. China: Background Notes Series.

    ERIC Educational Resources Information Center

    Reams, Joanne Reppert

    Concise background information on the People's Republic of China is provided. The publication begins with a profile of the country, outlining the people, geography, economy, and membership in international organizations. The bulk of the document then discusses in more detail China's people, geography, history, government, education, economy, and…

  12. Taiwan: Background Notes Series.

    ERIC Educational Resources Information Center

    Reams, Joanne Reppert

    Concise background information on Taiwan is provided. The publication begins with a profile of Taiwan, discussing the people, geography, political establishment, and economy. A map of the country is provided. The bulk of the publication then provides more detailed information on Taiwan's people, geography, history, administration, political…

  13. Building Background Knowledge

    ERIC Educational Resources Information Center

    Fisher, Douglas; Ross, Donna; Grant, Maria

    2010-01-01

    Too often, students enter our classrooms with insufficient knowledge of physical science. As a result, they have a difficult time understanding content in texts, lectures, and laboratory activities. This lack of background knowledge can have an impact on their ability to ask questions and wonder--both key components of inquiry. In this article,…

  14. Nonthermal cosmic neutrino background

    NASA Astrophysics Data System (ADS)

    Chen, Mu-Chun; Ratz, Michael; Trautner, Andreas

    2015-12-01

    We point out that, for Dirac neutrinos, in addition to the standard thermal cosmic neutrino background (C ν B ), there could also exist a nonthermal neutrino background with comparable number density. As the right-handed components are essentially decoupled from the thermal bath of standard model particles, relic neutrinos with a nonthermal distribution may exist until today. The relic density of the nonthermal (nt) background can be constrained by the usual observational bounds on the effective number of massless degrees of freedom Neff and can be as large as nν nt≲0.5 nγ. In particular, Neff can be larger than 3.046 in the absence of any exotic states. Nonthermal relic neutrinos constitute an irreducible contribution to the detection of the C ν B and, hence, may be discovered by future experiments such as PTOLEMY. We also present a scenario of chaotic inflation in which a nonthermal background can naturally be generated by inflationary preheating. The nonthermal relic neutrinos, thus, may constitute a novel window into the very early Universe.

  15. School Law: Background Checks.

    ERIC Educational Resources Information Center

    Splitt, David A.

    1988-01-01

    In an Oklahoma case, the district court ruled that the school district had failed to investigate the background of a teacher convicted of a second sexual abuse charge. School districts should examine personnel polices and practices, and the school lawyer should review state laws, regulations, and court cases. (MLF)

  16. Berkeley Low Background Facility

    NASA Astrophysics Data System (ADS)

    Thomas, K. J.; Smith, A. R.; Poon, A. W. P.; Chan, Y. D.; Norman, E. B.; Lesko, K. T.

    2015-08-01

    The Berkeley Low Background Facility (BLBF) at Lawrence Berkeley National Laboratory (LBNL) in Berkeley, California provides low background gamma spectroscopy services to a wide array of experiments and projects. The analysis of samples takes place within two unique facilities; locally within a carefully-constructed, low background laboratory on the surface at LBNL and at the Sanford Underground Research Facility (SURF) in Lead, SD. These facilities provide a variety of gamma spectroscopy services to low background experiments primarily in the form of passive material screening for primordial radioisotopes (U, Th, K) or common cosmogenic/anthropogenic products; active screening via neutron activation analysis for U,Th, and K as well as a variety of stable isotopes; and neutron flux/beam characterization measurements through the use of monitors. A general overview of the facilities, services, and sensitivities will be presented. Recent activities and upgrades will also be described including an overview of the recently installed counting system at SURF (recently relocated from Oroville, CA in 2014), the installation of a second underground counting station at SURF in 2015, and future plans. The BLBF is open to any users for counting services or collaboration on a wide variety of experiments and projects.

  17. Performance of photomultiplier tubes and sodium iodide scintillation detector systems

    NASA Technical Reports Server (NTRS)

    Meegan, C. A.

    1981-01-01

    The performance of photomultiplier tubes (PMT's) and scintillation detector systems incorporating 50.8 by 1.27 cm NaI (T l) crystals was investigated to determine the characteristics of the photomultiplier tubes and optimize the detector geometry for the Burst and Transient Source Experiment on the Gamma Ray Observatory. Background information on performance characteristics of PMT's and NaI (T l) detectors is provided, procedures for measurement of relevant parameters are specified, and results of these measurements are presented.

  18. Determination of tube-to-tube support interaction characteristics. [PWR

    SciTech Connect

    Haslinger, K.H.

    1983-11-01

    Tube-to-tube support interaction characteristics were determined on a multi-span tube geometry representative of the hot-leg side of the C-E, System 80 steam generator design. Results will become input for an autoclave type wear test program on steam generator tubes, performed by Kraftwerk Union (KWU). Correlation of test data reported here with similar data obtained from the wear tests will be performed in an attempt to make predictions about the long-term fretting behavior of steam generator tubes.

  19. Enteral Tube Feeding and Pneumonia

    ERIC Educational Resources Information Center

    Gray, David Sheridan; Kimmel, David

    2006-01-01

    To determine the effects of enteral tube feeding on the incidence of pneumonia, we performed a retrospective review of all clients at our institution who had gastrostomy or jejunostomy tubes placed over a 10-year period. Ninety-three subjects had a history of pneumonia before feeding tube insertion. Eighty had gastrostomy and 13, jejunostomy

  20. Enteral Tube Feeding and Pneumonia

    ERIC Educational Resources Information Center

    Gray, David Sheridan; Kimmel, David

    2006-01-01

    To determine the effects of enteral tube feeding on the incidence of pneumonia, we performed a retrospective review of all clients at our institution who had gastrostomy or jejunostomy tubes placed over a 10-year period. Ninety-three subjects had a history of pneumonia before feeding tube insertion. Eighty had gastrostomy and 13, jejunostomy…

  1. Calibration of image dissector tubes

    NASA Technical Reports Server (NTRS)

    Klingman, E. E., III

    1976-01-01

    Technique employs computer-controlled light-emitting diode (LED), precision machined mask, and analog-to-digital coverter (ADC). Computer turns on LED which floods masked face of tube. Intensity pattern, generated as tube is electromagnetically swept, is fed to ADC which controls tube calibration.

  2. Tubing rotator reduces tubing wear in rod pumped wells

    SciTech Connect

    Graham, M. ); Brown, C. )

    1994-04-04

    Tubing failures are both expensive and time-consuming. The most common failure results from rod cutting, or, erosion of the tubing ID because of continuous, reciprocating contact with the rod string. Installation of tubing rotators has decreased tubing failures in West Texas waterflood sucker-rod pumped wells. Pumping unit movement powers the rotator system, turning the tubing string at about 1 revolution/day. The rotator system has both surface and subsurface components. A reduction gear box attached to the walking beam converts the pumping unit's reciprocating strokes into rotary motion. A drive line transfers this rotary motion to a gear-driven suspension mandrel in the rotating tubing hanger. Near the bottom of the tubing string, a rotating tubing anchor/catcher allows the entire tubing string, including the tail pipe, seating nipple, and gas and mud anchor to rotate. The rotator hanger suspends the weight of the tubing string on a bearing system. One model of the hanger has a load capacity of 135,000 lb. A surface swivel allows rotation below the pumping tee so that the flow lines remain stationary. Also included in the string is a safety shear coupling to prevent over torquing the tubing.

  3. Statistical Study of Plasma-depleted Flux Tubes in Saturnian Magnetosphere

    NASA Astrophysics Data System (ADS)

    Lai, H. R.; Russell, C. T.; Wei, H. Y.; Dougherty, M. K.; Jia, Y. D.

    2015-10-01

    We have surveyed the occurrence of flux tubes with both enhanced and depressed field strength relative to their surroundings as observed in Cassini magnetometer data. Consistent with earlier studies, enhanced field flux tubes are concentrated near the equator while depressed field flux tubes are distributed in a larger latitudinal region. For both types of flux tubes, their occurrence rates vary with the local time in the same pattern and they contain the same magnetic flux. Therefore, we suggest that those two types of tubes are just different manifestations of the same phenomenon. Near the equator with high ambient plasma density, the flux tubes convecting in from the tail are compressed, resulting in increased field strength. Off the equator,these flux tubes expand slightly, resulting in decreased field strength. The enhanced flux tubes gradually break into smaller ones as they convect inward. Inside an L value of about 5, they become indistinguishable from the background.

  4. Environmental test report for the WX-32335 SEC camera tube. [for International Ultraviolet Explorer

    NASA Technical Reports Server (NTRS)

    Malanoski, R. J.

    1973-01-01

    The environmental testing activity on the WX-32335 was carried out to determine if this tube type could withstand the environmental requirements established for the International Ultraviolet Explorer (IUE) camera tube (WX-32224). The results of the tests led to the following conclusions: (1) The WX-32335 as processed with a CsTe photocathode surface can withstand the temperature extremes established for the IUE camera tube without damage to the photocathode surface or without introducing background signal in the tube after one hour of dark integration. (2) The WX-32335 built with a WX-32224 type target support structure can withstand the sinusoidal vibration requirements established for the IUE camera tube. (3) Although the vibration test of the WX-32335 type tubes built with the flat target ring structure could not be completed, there was no indication that these tubes could not withstand the sinusoidal vibration requirements established for the IUE camera tube.

  5. Tube coupling device

    NASA Technical Reports Server (NTRS)

    Myers, William N. (Inventor); Hein, Leopold A. (Inventor)

    1987-01-01

    A first annular ring of a tube coupling device has a keyed opening sized to fit around the nut region of a male coupling, and a second annular ring has a keyed opening sized to fit around the nut of a female coupling. Each ring has mating ratchet teeth and these rings are biased together, thereby engaging these teeth and preventing rotation of these rings. This in turn prevents the rotation of the male nut region with respect to the female nut. For tube-to-bulkhead locking, one facet of one ring is notched, and a pin is pressed into an opening in the bulkhead. This pin is sized to fit within one of the notches in the ring, thereby preventing rotation of this ring with respect to the bulkhead.

  6. Induction plasma tube

    DOEpatents

    Hull, Donald E.

    1984-01-01

    An induction plasma tube having a segmented, fluid-cooled internal radiation shield is disclosed. The individual segments are thick in cross-section such that the shield occupies a substantial fraction of the internal volume of the plasma enclosure, resulting in improved performance and higher sustainable plasma temperatures. The individual segments of the shield are preferably cooled by means of a counterflow fluid cooling system wherein each segment includes a central bore and a fluid supply tube extending into the bore. The counterflow cooling system results in improved cooling of the individual segments and also permits use of relatively larger shield segments which permit improved electromagnetic coupling between the induction coil and a plasma located inside the shield. Four embodiments of the invention, each having particular advantages, are disclosed.

  7. Induction plasma tube

    DOEpatents

    Hull, D.E.

    1982-07-02

    An induction plasma tube having a segmented, fluid-cooled internal radiation shield is disclosed. The individual segments are thick in cross-section such that the shield occupies a substantial fraction of the internal volume of the plasma enclosure, resulting in improved performance and higher sustainable plasma temperatures. The individual segments of the shield are preferably cooled by means of a counterflow fluid cooling system wherein each segment includes a central bore and a fluid supply tube extending into the bore. The counterflow cooling system results in improved cooling of the individual segments and also permits use of relatively larger shield segments which permit improved electromagnetic coupling between the induction coil and a plasma located inside the shield. Four embodiments of the invention, each having particular advantages, are disclosed.

  8. Photomultiplier tube characterization for MiniCLEAN

    NASA Astrophysics Data System (ADS)

    Jaditz, Stephen; Miniclean Collaboration

    2011-10-01

    MiniCLEAN is a single-phase dark matter experiment which uses liquid argon (87 K) or neon (27 K) as an active medium. Photomultiplier tubes (PMTs) submerged in the cryogen detect light emitted by tetraphenyl butadiene, which fluoresces at short optical wavelengths when excited by the primary ultraviolet scintillation of the argon or neon. The collaboration has chosen to use 8'' Hamamatsu R5912-02MOD PMTs, the low-temperature successor of the R1408-R5912 lineage. The bialkali photocathode of the R5912-02MOD has a platinum underlay which increases electron mobility, enabling operation at temperatures lower than 150 K where traditional bialkali cathodes fail. The number of dynodes in the tube has also been increased to 14, which lowers the bias required to attain reasonable gain and saves heat load in the voltage divider chain of the base. This talk describes characterization of the tube and base for use in MiniCLEAN. I present gain and dark rate measurements as a function of temperature, considerations that inform the base design, and implications of using this tube in a low-background experiment.

  9. [Patulous eustachian tube].

    PubMed

    Kovacević, D; Radosavljević, M; Jelesijević, J

    1995-01-01

    Patulous eustachian tube is a pathological condition which exists more often than we make a diagnosis, and a patient is not often aware of his disease. This disease can be manifested with various symptoms: respiratory synchrony noises in the ear, because of the penetration of the air current through the eustachian tube and with the movement of the eardrum outwards and inside, with autophony, reduction of the hearing, the buzzing, dizziness and disturbance of the balance. Two patients are presented. The first one was sick for many years from various chronics exhausted diseases: Jackson's epilepsy, temporary vascular brain disturbances, tuberculosis of lung, stomach ulcer, heart diseases, the patient is from low class, on one side, and also suffers from some local diseases: a paralysis of soft palate and palatal arcs, a chronic catarrhal rhinitis and sinusitis, a deviation of nasal dividing wall and hindered breathing through the nose, on the other side. Many years the patient didn't know for patological condition in the ears and in the eustachian tubes. After improving the hygienic conditions, the physical condition and local therapy, the patient felt much better. The second patient, with considerable shorter evolution of the disease and mild symptomatology, showed the amplified symptoms of the disease of the Eustachian tube in the course of the acute otitis. It is attained a satisfying calming of the manifestative symptoms by remedy therapie. Man must thing about possibility of the appearance of this pathology condition in various disease or conditions, which can take to the fast lost of the weight and physical and moral exhaustion of the patient, i.e. an adult, first as the protection of the appearance of the disease (condition) and afterwards, eventually early and regulary treatment in order to prevent various possible, above mentioned complications. PMID:16296237

  10. Joined concentric tubes

    DOEpatents

    DeJonghe, Lutgard; Jacobson, Craig; Tucker, Michael; Visco, Steven

    2013-01-01

    Tubular objects having two or more concentric layers that have different properties are joined to one another during their manufacture primarily by compressive and friction forces generated by shrinkage during sintering and possibly mechanical interlocking. It is not necessary for the concentric tubes to display adhesive-, chemical- or sinter-bonding to each other in order to achieve a strong bond. This facilitates joining of dissimilar materials, such as ceramics and metals.

  11. Reduction of Endotracheal Tube Biofilms Using Antimicrobial Photodynamic Therapy

    PubMed Central

    Biel, Merrill A.; Sievert, Chet; Usacheva, Marina; Teichert, Matthew; Wedell, Eric; Loebel, Nicolas; Rose, Andreas; Zimmermann, Ron

    2011-01-01

    Background Ventilator-associated pneumonia (VAP) is reported to occur in 12 to 25% of patients who require mechanical ventilation with a mortality rate of 24 to 71%. The endotracheal (ET) tube has long been recognized as a major factor in the development of VAP since biofilm harbored within the ET tube become dislodged during mechanical ventilation and have direct access to the lungs. The objective of this study was to demonstrate the safety and effectiveness of a non-invasive antimicrobial photodynamic therapy (aPDT) treatment method of eradicating antibiotic resistant biofilms from ET tubes in an in vitro model. Methods Antibiotic resistant polymicrobial biofilms of Pseudomonas aerugenosa and MRSA were grown in ET tubes and treated, under standard ventilator conditions, with a methylene blue (MB) photosensitizer and 664nm non-thermal activating light. Cultures of the lumen of the ET tube were obtained before and after light treatment to determine efficacy of biofilm reduction. Results The in vitro ET tube biofilm study demonstrated that aPDT reduced the ET tube polymicrobial biofilm by >99.9% (p<0.05%) after a single treatment. Conclusions MB aPDT can effectively treat polymicrobial antibiotic resistant biofilms in an ET tube. PMID:21987599

  12. Extragalactic UV background

    NASA Astrophysics Data System (ADS)

    Khaire, Vikram; Srianand, Raghunathan

    We have developed a numerical code to generate extragalactic UV background spectrum. For that we have solved the radiative transfer equation in expanding universe for given quasar and galaxy emissivity taking into account the effective optical depth encountered by radiation due to the presence of diffused inter-galactic clouds. We use the results of this code to probe the physics of He II re-ionization.

  13. The cosmic microwave background

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1989-01-01

    Recent observational and theoretical investigations of the cosmic microwave background radiation (CMBR) are reviewed. Particular attention is given to spectral distortions and CMBR temperature anisotropies at large, intermediate, and small angular scales. The implications of the observations for inflationary cosmological models with curvature fluctuation are explored, and it is shown that the limits determined for intermediate-scale CMBR anisotropy almost rule out a baryon-dominated cosmology.

  14. Executive Summary: Background

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Background information on, and the objectives of, the NASA Global Biology Research Program are given. The following issues were addressed: (1) geographic distribution of wetland parameters, (2) the processes of wetland material fluxes, and (3) the relation of local fluxes with global processes. Wetland inventorying and categorizing, gas-phase exchanges with the atmosphere, material exchange with the aquatic environment, and material storage in wetland sediments were identified as topics requiring further research.

  15. TUBE SHEARING VALVE

    DOEpatents

    Wilner, L.B.

    1960-05-24

    Explosive operated valves can be used to join two or more containers in fluid flow relationship, one such container being a sealed reservoir. The valve is most simply disposed by mounting it on the reservoir so thst a tube extends from the interior of the reservoir through the valve body, terminating at the bottom of the bore in a closed end; other containers may be similarly connected or may be open connected, as desired. The piston of the valve has a cutting edge at its lower end which shears off the closed tube ends and a recess above the cutting edge to provide a flow channel. Intermixing of the fluid being transferred with the explosion gases is prevented by a copper ring at the top of the piston which is force fitted into the bore at the beginning of the stroke. Although designed to avoid backing up of the piston at pressures up to 10,000 psi in the transferred fluid, proper operation is independent of piston position, once the tube ends were sheared.

  16. Traveling-Wave Tubes

    NASA Technical Reports Server (NTRS)

    Kory, Carol L.

    1998-01-01

    The traveling-wave tube (TWT) is a vacuum device invented in the early 1940's used for amplification at microwave frequencies. Amplification is attained by surrendering kinetic energy from an electron beam to a radio frequency (RF) electromagnetic wave. The demand for vacuum devices has been decreased largely by the advent of solid-state devices. However, although solid state devices have replaced vacuum devices in many areas, there are still many applications such as radar, electronic countermeasures and satellite communications, that require operating characteristics such as high power (Watts to Megawatts), high frequency (below 1 GHz to over 100 GHz) and large bandwidth that only vacuum devices can provide. Vacuum devices are also deemed irreplaceable in the music industry where musicians treasure their tube-based amplifiers claiming that the solid-state and digital counterparts could never provide the same "warmth" (3). The term traveling-wave tube includes both fast-wave and slow-wave devices. This article will concentrate on slow-wave devices as the vast majority of TWTs in operation fall into this category.

  17. Concentric tube support assembly

    SciTech Connect

    Rubio, Mark F.; Glessner, John C.

    2012-09-04

    An assembly (45) includes a plurality of separate pie-shaped segments (72) forming a disk (70) around a central region (48) for retaining a plurality of tubes (46) in a concentrically spaced apart configuration. Each segment includes a support member (94) radially extending along an upstream face (96) of the segment and a plurality of annularly curved support arms (98) transversely attached to the support member and radially spaced apart from one another away from the central region for receiving respective upstream end portions of the tubes in arc-shaped spaces (100) between the arms. Each segment also includes a radial passageway (102) formed in the support member for receiving a fluid segment portion (106) and a plurality of annular passageways (104) formed in the support arms for receiving respective arm portions (108) of the fluid segment portion from the radial passageway and for conducting the respective arm portions into corresponding annular spaces (47) formed between the tubes retained by the disk.

  18. Tube bundle system

    PubMed Central

    Marchewka, W.; Mohamed, K.; Addis, J.; Karnack, F.

    2015-01-01

    A tube bundle system (TBS) is a mechanical system for continuously drawing gas samples through tubes from multiple monitoring points located in an underground coal mine. The gas samples are drawn via vacuum pump to the surface and are typically analyzed for oxygen, methane, carbon dioxide and carbon monoxide. Results of the gas analyses are displayed and recorded for further analysis. Trends in the composition of the mine atmosphere, such as increasing methane or carbon monoxide concentration, can be detected early, permitting rapid intervention that prevents problems, such as a potentially explosive atmosphere behind seals, fire or spontaneous combustion. TBS is a well-developed technology and has been used in coal mines around the world for more than 50 years. Most longwall coal mines in Australia deploy a TBS, usually with 30 to 40 monitoring points as part of their atmospheric monitoring. The primary uses of a TBS are detecting spontaneous combustion and maintaining sealed areas inert. The TBS might also provide mine atmosphere gas composition data after a catastrophe occurs in an underground mine, if the sampling tubes are not damaged. TBSs are not an alternative to statutory gas and ventilation airflow monitoring by electronic sensors or people; rather, they are an option to consider in an overall mine atmosphere monitoring strategy. This paper describes the hardware, software and operation of a TBS and presents one example of typical data from a longwall coal mine PMID:26306052

  19. Evolvable Neural Software System

    NASA Technical Reports Server (NTRS)

    Curtis, Steven A.

    2009-01-01

    The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

  20. The LILARTI neural network system

    SciTech Connect

    Allen, J.D. Jr.; Schell, F.M.; Dodd, C.V.

    1992-10-01

    The material of this Technical Memorandum is intended to provide the reader with conceptual and technical background information on the LILARTI neural network system of detail sufficient to confer an understanding of the LILARTI method as it is presently allied and to facilitate application of the method to problems beyond the scope of this document. Of particular importance in this regard are the descriptive sections and the Appendices which include operating instructions, partial listings of program output and data files, and network construction information.

  1. Neural decoding based on probabilistic neural network.

    PubMed

    Yu, Yi; Zhang, Shao-min; Zhang, Huai-jian; Liu, Xiao-chun; Zhang, Qiao-sheng; Zheng, Xiao-xiang; Dai, Jian-hua

    2010-04-01

    Brain-machine interface (BMI) has been developed due to its possibility to cure severe body paralysis. This technology has been used to realize the direct control of prosthetic devices, such as robot arms, computer cursors, and paralyzed muscles. A variety of neural decoding algorithms have been designed to explore relationships between neural activities and movements of the limbs. In this paper, two novel neural decoding methods based on probabilistic neural network (PNN) in rats were introduced, the PNN decoder and the modified PNN (MPNN) decoder. In the experiment, rats were trained to obtain water by pressing a lever over a pressure threshold. Microelectrode array was implanted in the motor cortex to record neural activity, and pressure was recorded by a pressure sensor synchronously. After training, the pressure values were estimated from the neural signals by PNN and MPNN decoders. Their performances were evaluated by a correlation coefficient (CC) and a mean square error (MSE). The results show that the MPNN decoder, with a CC of 0.8657 and an MSE of 0.2563, outperformed the traditionally-used Wiener filter (WF) and Kalman filter (KF) decoders. It was also observed that the discretization level did not affect the MPNN performance, indicating that the MPNN decoder can handle different tasks in BMI system, including the detection of movement states and estimation of continuous kinematic parameters. PMID:20349527

  2. Evaluation of a large format image tube camera for the shuttle sortie mission

    NASA Technical Reports Server (NTRS)

    Tifft, W. C.

    1976-01-01

    A large format image tube camera of a type under consideration for use on the Space Shuttle Sortie Missions is evaluated. The evaluation covers the following subjects: (1) resolving power of the system (2) geometrical characteristics of the system (distortion etc.) (3) shear characteristics of the fiber optic coupling (4) background effects in the tube (5) uniformity of response of the tube (as a function of wavelength) (6) detective quantum efficiency of the system (7) astronomical applications of the system. It must be noted that many of these characteristics are quantitatively unique to the particular tube under discussion and serve primarily to suggest what is possible with this type of tube.

  3. Two developmentally distinct populations of neural crest cells contribute to the zebrafish heart.

    PubMed

    Cavanaugh, Ann M; Huang, Jie; Chen, Jau-Nian

    2015-08-15

    Cardiac neural crest cells are essential for outflow tract remodeling in animals with divided systemic and pulmonary circulatory systems, but their contributions to cardiac development in animals with a single-loop circulatory system are less clear. Here we genetically labeled neural crest cells and examined their contribution to the developing zebrafish heart. We identified two populations of neural crest cells that contribute to distinct compartments of zebrafish cardiovascular system at different developmental stages. A stream of neural crest cells migrating through pharyngeal arches 1 and 2 integrates into the myocardium of the primitive heart tube between 24 and 30 h post fertilization and gives rise to cardiomyocytes. A second wave of neural crest cells migrating along aortic arch 6 envelops the endothelium of the ventral aorta and invades the bulbus arteriosus after three days of development. Interestingly, while inhibition of FGF signaling has no effect on the integration of neural crest cells to the primitive heart tube, it prevents these cells from contributing to the outflow tract, demonstrating disparate responses of neural crest cells to FGF signaling. Furthermore, neural crest ablation in zebrafish leads to multiple cardiac defects, including reduced heart rate, defective myocardial maturation and a failure to recruit progenitor cells from the second heart field. These findings add to our understanding of the contribution of neural crest cells to the developing heart and provide insights into the requirement for these cells in cardiac maturation. PMID:26086691

  4. Sip1 mediates an E-cadherin-to-N-cadherin switch during cranial neural crest EMT

    PubMed Central

    Rogers, Crystal D.; Saxena, Ankur

    2013-01-01

    The neural crest, an embryonic stem cell population, initially resides within the dorsal neural tube but subsequently undergoes an epithelial-to-mesenchymal transition (EMT) to commence migration. Although neural crest and cancer EMTs are morphologically similar, little is known regarding conservation of their underlying molecular mechanisms. We report that Sip1, which is involved in cancer EMT, plays a critical role in promoting the neural crest cell transition to a mesenchymal state. Sip1 transcripts are expressed in premigratory/migrating crest cells. After Sip1 loss, the neural crest specifier gene FoxD3 was abnormally retained in the dorsal neuroepithelium, whereas Sox10, which is normally required for emigration, was diminished. Subsequently, clumps of adherent neural crest cells remained adjacent to the neural tube and aberrantly expressed E-cadherin while lacking N-cadherin. These findings demonstrate two distinct phases of neural crest EMT, detachment and mesenchymalization, with the latter involving a novel requirement for Sip1 in regulation of cadherin expression during completion of neural crest EMT. PMID:24297751

  5. Fuzzy and neural control

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.

    1992-01-01

    Fuzzy logic and neural networks provide new methods for designing control systems. Fuzzy logic controllers do not require a complete analytical model of a dynamic system and can provide knowledge-based heuristic controllers for ill-defined and complex systems. Neural networks can be used for learning control. In this chapter, we discuss hybrid methods using fuzzy logic and neural networks which can start with an approximate control knowledge base and refine it through reinforcement learning.

  6. Exploring neural network technology

    SciTech Connect

    Naser, J.; Maulbetsch, J.

    1992-12-01

    EPRI is funding several projects to explore neural network technology, a form of artificial intelligence that some believe may mimic the way the human brain processes information. This research seeks to provide a better understanding of fundamental neural network characteristics and to identify promising utility industry applications. Results to date indicate that the unique attributes of neural networks could lead to improved monitoring, diagnostic, and control capabilities for a variety of complex utility operations. 2 figs.

  7. Liquid-Nitrogen Test for Blocked Tubes

    NASA Technical Reports Server (NTRS)

    Wagner, W. R.

    1984-01-01

    Nondestructive test identifies obstructed tube in array of parallel tubes. Trickle of liquid nitrogen allowed to flow through tube array until array accumulates substantial formation of frost from moisture in air. Flow stopped and warm air introduced into inlet manifold to heat tubes in array. Tubes still frosted after others defrosted identified as obstructed tubes. Applications include inspection of flow systems having parallel legs.

  8. Effects of retinoic acid on the neural crest-controlled organs of fetal rats.

    PubMed

    Yu, Jiakang; Gonzalez, Salome; Martinez, Leopoldo; Diez-Pardo, Juan A; Tovar, Juan A

    2003-07-01

    Prenatal exposure of rat embryos to retinoic acid induces severe malformations involving various organs. The mechanisms of this embryopathy are known only in part. This study describes the malformations of the neural crest-derived organs in this model and shows that many of them fit into the pattern of disturbed neural crest organogenic control. Pregnant rats were exposed to either all-trans retinoic acid (125 mg/kg; n=17) or vehicle ( n=10) on E10. Fetuses were recovered on E21 and external and internal malformations were sought. The craniofacial area, the trachea, parathyroids, thymus, thyroid, heart, great vessels, and adrenals were examined. In contrast with normal controls, 100% of retinoic acid animals had craniofacial, 94% anorectal, 90% limb, and 55% neural tube defects. The thymus was absent or ectopic in 76%, the parathyroids were absent or single in 88%, and the thyroid was abnormal in 41%. There were neural crest-type (outflow tract and/or pharyngeal aortic arch defects) cardiovascular malformations in 90% and the adrenals were absent in 52%. Interestingly, 9 of 11 (88%) animals with neural tube defects had absent adrenal glands. This association was significant ( p<0.01) by Fisher exact test. Among the complex mechanisms of retinoic acid teratogenesis, severe disturbances of the neural crest pathway play a leading role. The simultaneous development of neural tube defects and adrenal agenesis suggests common pathogenic pathways. PMID:12898162

  9. Neural-Network Simulator

    NASA Technical Reports Server (NTRS)

    Mitchell, Paul H.

    1991-01-01

    F77NNS (FORTRAN 77 Neural Network Simulator) computer program simulates popular back-error-propagation neural network. Designed to take advantage of vectorization when used on computers having this capability, also used on any computer equipped with ANSI-77 FORTRAN Compiler. Problems involving matching of patterns or mathematical modeling of systems fit class of problems F77NNS designed to solve. Program has restart capability so neural network solved in stages suitable to user's resources and desires. Enables user to customize patterns of connections between layers of network. Size of neural network F77NNS applied to limited only by amount of random-access memory available to user.

  10. Neural assembly computing.

    PubMed

    Ranhel, João

    2012-06-01

    Spiking neurons can realize several computational operations when firing cooperatively. This is a prevalent notion, although the mechanisms are not yet understood. A way by which neural assemblies compute is proposed in this paper. It is shown how neural coalitions represent things (and world states), memorize them, and control their hierarchical relations in order to perform algorithms. It is described how neural groups perform statistic logic functions as they form assemblies. Neural coalitions can reverberate, becoming bistable loops. Such bistable neural assemblies become short- or long-term memories that represent the event that triggers them. In addition, assemblies can branch and dismantle other neural groups generating new events that trigger other coalitions. Hence, such capabilities and the interaction among assemblies allow neural networks to create and control hierarchical cascades of causal activities, giving rise to parallel algorithms. Computing and algorithms are used here as in a nonstandard computation approach. In this sense, neural assembly computing (NAC) can be seen as a new class of spiking neural network machines. NAC can explain the following points: 1) how neuron groups represent things and states; 2) how they retain binary states in memories that do not require any plasticity mechanism; and 3) how branching, disbanding, and interaction among assemblies may result in algorithms and behavioral responses. Simulations were carried out and the results are in agreement with the hypothesis presented. A MATLAB code is available as a supplementary material. PMID:24806763

  11. Syringosubarachnoid shunting using a myringotomy tube

    PubMed Central

    Leschke, Jack M.; Mumert, Michael L.; Kurpad, Shekar N.

    2016-01-01

    Background: Syringomyelia results from obstruction of cerebrospinal fluid (CSF) flow due to a multitude of causes. Often symptoms of pain, weakness, and sensory disturbance are progressive and require surgical treatment. We present here a rare technique for syringosubarachnoid shunting. Case Description: We present the case of a 38-year-old male who suffered a traumatic cervical spinal cord injury due to a motor vehicle accident. With progressive pain and motor decline, a magnetic resonance imaging was obtained and showed a new syrinx extending cervical multiple segments. A unique surgical procedure using a myringotomy tube to shunt CSF into the subarachnoid space was employed in this case. The patient's examination stabilized postoperatively, and at 2 months and 6 months follow-up visits, his strength and sensation continued to improve. Conclusion: We used a myringotomy tube for syringosubarachnoid shunting for the surgical management of a posttraumatic syrinx with good results. This technique minimizes suturing and may minimize shunt-related complications. PMID:26862456

  12. Signal dispersion within a hippocampal neural network

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.; Mates, J. W. B.

    1975-01-01

    A model network is described, representing two neural populations coupled so that one population is inhibited by activity it excites in the other. Parameters and operations within the model represent EPSPs, IPSPs, neural thresholds, conduction delays, background activity and spatial and temporal dispersion of signals passing from one population to the other. Simulations of single-shock and pulse-train driving of the network are presented for various parameter values. Neuronal events from 100 to 300 msec following stimulation are given special consideration in model calculations.

  13. The Backgrounds Data Center

    NASA Technical Reports Server (NTRS)

    Snyder, W. A.; Gursky, H.; Heckathorn, H. M.; Lucke, R. L.; Berg, S. L.; Dombrowski, E. G.; Kessel, R. A.

    1993-01-01

    The Strategic Defense Initiative Organization has created data centers for midcourse, plumes, and backgrounds phenomenologies. The Backgrounds Data Center (BDC) has been designated as the prime archive for data collected by SDIO programs. The BDC maintains a Summary Catalog that contains 'metadata,' that is, information about data, such as when the data were obtained, what the spectral range of the data is, and what region of the Earth or sky was observed. Queries to this catalog result in a listing of all data sets (from all experiments in the Summary Catalog) that satisfy the specified criteria. Thus, the user can identify different experiments that made similar observations and order them from the BDC for analysis. On-site users can use the Science Analysis Facility (SAFE for this purpose. For some programs, the BDC maintains a Program Catalog, which can classify data in as many ways as desired (rather than just by position, time, and spectral range as in the Summary Catalog). For example, data sets could be tagged with such diverse parameters as solar illumination angle, signal level, or the value of a particular spectral ratio, as long as these quantities can be read from the digital record or calculated from it by the ingest program. All unclassified catalogs and unclassified data will be remotely accessible.

  14. Neural-specific Sox2 input and differential Gli-binding affinity provide context and positional information in Shh-directed neural patterning

    PubMed Central

    Peterson, Kevin A.; Nishi, Yuichi; Ma, Wenxiu; Vedenko, Anastasia; Shokri, Leila; Zhang, Xiaoxiao; McFarlane, Matthew; Baizabal, José-Manuel; Junker, Jan Philipp; van Oudenaarden, Alexander; Mikkelsen, Tarjei; Bernstein, Bradley E.; Bailey, Timothy L.; Bulyk, Martha L.; Wong, Wing H.; McMahon, Andrew P.

    2012-01-01

    In the vertebrate neural tube, regional Sonic hedgehog (Shh) signaling invokes a time- and concentration-dependent induction of six different cell populations mediated through Gli transcriptional regulators. Elsewhere in the embryo, Shh/Gli responses invoke different tissue-appropriate regulatory programs. A genome-scale analysis of DNA binding by Gli1 and Sox2, a pan-neural determinant, identified a set of shared regulatory regions associated with key factors central to cell fate determination and neural tube patterning. Functional analysis in transgenic mice validates core enhancers for each of these factors and demonstrates the dual requirement for Gli1 and Sox2 inputs for neural enhancer activity. Furthermore, through an unbiased determination of Gli-binding site preferences and analysis of binding site variants in the developing mammalian CNS, we demonstrate that differential Gli-binding affinity underlies threshold-level activator responses to Shh input. In summary, our results highlight Sox2 input as a context-specific determinant of the neural-specific Shh response and differential Gli-binding site affinity as an important cis-regulatory property critical for interpreting Shh morphogen action in the mammalian neural tube. PMID:23249739

  15. Lava Tube Collapse Pits

    NASA Technical Reports Server (NTRS)

    2004-01-01

    [figure removed for brevity, see original site]

    We will be looking at collapse pits for the next two weeks. Collapse pits on Mars are formed in several ways. In volcanic areas, channelized lava flows can form roofs which insulate the flowing lava. These features are termed lava tubes on Earth and are common features in basaltic flows. After the lava has drained, parts of the roof of the tube will collapse under its own weight. These collapse pits will only be as deep as the bottom of the original lava tube. Another type of collapse feature associated with volcanic areas arises when very large eruptions completely evacuate the magma chamber beneath the volcano. The weight of the volcano will cause the entire edifice to subside into the void space below it. Structural features including fractures and graben will form during the subsidence. Many times collapse pits will form within the graben. In addition to volcanic collapse pits, Mars has many collapse pits formed when volatiles (such as subsurface ice) are released from the surface layers. As the volatiles leave, the weight of the surrounding rock causes collapse pits to form.

    These collapse pits are found in the southern hemisphere of Mars. They are likely lava tube collapse pits related to flows from Hadriaca Patera.

    Image information: VIS instrument. Latitude -36.8, Longitude 89.6 East (270.4 West). 19 meter/pixel resolution. Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  16. The Cosmic Microwave Background

    NASA Astrophysics Data System (ADS)

    Richards, Paul L.

    2007-03-01

    Measurements of the Cosmic Microwave Background (CMB) provide our earliest direct information about the evolving Universe. This talk will begin with a summary of how the CMB was produced and why it is important. The focus will than shift to the nature of the experimental challenge of extracting Cosmological information from the CMB. Examples will be given of technology development in small-scale experiments leading to major space missions which produce definitive data sets. The millimeter-wave spectral range of the signals corresponds to the crossover between coherent (radio) techniques and bolometric (optical) techniques. These challenges have stimulated enormous development of bolometric detectors, which are used to measure both the spectrum and the anisotropy of the CMB. The next generation of CMB experiments will require a new generation of bolometric detectors in large format arrays. This year, the Keithly Prize is given to Kent Irwin for ideas that have made this next step possible.

  17. Cosmic microwave background theory.

    PubMed

    Bond, J R

    1998-01-01

    A long-standing goal of theorists has been to constrain cosmological parameters that define the structure formation theory from cosmic microwave background (CMB) anisotropy experiments and large-scale structure (LSS) observations. The status and future promise of this enterprise is described. Current band-powers in -space are consistent with a DeltaT flat in frequency and broadly follow inflation-based expectations. That the levels are approximately (10(-5))2 provides strong support for the gravitational instability theory, while the Far Infrared Absolute Spectrophotometer (FIRAS) constraints on energy injection rule out cosmic explosions as a dominant source of LSS. Band-powers at 100 suggest that the universe could not have re-ionized too early. To get the LSS of Cosmic Background Explorer (COBE)-normalized fluctuations right provides encouraging support that the initial fluctuation spectrum was not far off the scale invariant form that inflation models prefer: e.g., for tilted Lambda cold dark matter sequences of fixed 13-Gyr age (with the Hubble constant H0 marginalized), ns = 1.17 +/- 0.3 for Differential Microwave Radiometer (DMR) only; 1.15 +/- 0.08 for DMR plus the SK95 experiment; 1.00 +/- 0.04 for DMR plus all smaller angle experiments; 1.00 +/- 0.05 when LSS constraints are included as well. The CMB alone currently gives weak constraints on Lambda and moderate constraints on Omegatot, but theoretical forecasts of future long duration balloon and satellite experiments are shown which predict percent-level accuracy among a large fraction of the 10+ parameters characterizing the cosmic structure formation theory, at least if it is an inflation variant. PMID:9419321

  18. Ultraviolet Background Radiation

    NASA Astrophysics Data System (ADS)

    Henry, R. C.; Murthy, J.

    1993-12-01

    The UVX experiment was carried on the Space Shuttle Columbia between 1986 January 12 and 19 (STS-61C). Several ultraviolet spectrometers were used to obtain measurements of the diffuse ultraviolet background at 8 locations in the sky. We have reanalysed the UVX measurements of the surface brightness of the diffuse ultraviolet background above b = 40 using the dust-scattering model of Onaka & Kodaira (1991), which explicitly takes into account the variation of the source function with galactic longitude. The range of allowed values of interstellar grain albedoJa, and scattering asymmetry parameter g, is considerably expanded over those of a previous analysis. The new chi square probability contours come close to, but do not include, the values of a and g found for the interstellar grains by Witt et al. (1992) using the Ultraviolet Imaging Telescope (UIT) on the Astro mission. If we hypothesize in additon to the dust-scattered light an extragalactic component, of 300 1 100 photons cm-2 s-1 sr-1 A-1, attenuated by a cosecant b law, the new reduction of the UVX data gives complete consistency with the Witt et al. determination of the optical parameters of the grains in the ultraviolet. This work was supported by United States Air Force Contract F19628-93-K-0004, and by National Aeronautics and Space Administration grant NASA NAG5-619. We are grateful for the encouragement of Dr. Stephan Price, and we thank Dr. L. Danly for information. Onaka, T., & Kodaira, K. 1991, ApJ, 379, 532 Witt, A. N., Petersohn, J. K., Bohlin, R. C., O'Connell, R. W., Roberts, M. S., Smith, A. M., & Stecher, T. P. 1992, ApJ, 395, L5

  19. Adaptive Temporal Encoding Leads to a Background Insensitive Cortical Representation of Speech

    PubMed Central

    Ding, Nai; Simon, Jonathan Z.

    2013-01-01

    Speech recognition is remarkably robust to the listening background, even when the energy of background sounds strongly overlaps with that of speech. How the brain transforms the corrupted acoustic signal into a reliable neural representation suitable for speech recognition, however, remains elusive. Here, we hypothesize that this transformation is performed at the level of auditory cortex through adaptive neural encoding, and we test the hypothesis by recording, using magnetoencephalography (MEG), the neural responses of human subjects listening to a narrated story. Spectrally matched stationary noise, which has maximal acoustic overlap with the speech, is mixed in at various intensity levels. Despite the severe acoustic interference caused by this noise, it is here demonstrated that low-frequency auditory cortical activity is reliably synchronized to the slow temporal modulations of speech, even when the noise is twice as strong as the speech. Such a reliable neural representation is maintained by intensity contrast gain control, and by adaptive processing of temporal modulations at different time scales, corresponding to the neural delta and theta bands. Critically, the precision of this neural synchronization predicts how well a listener can recognize speech in noise, indicating that the precision of the auditory cortical representation limits the performance of speech recognition in noise. Taken together, these results suggest that, in a complex listening environment, auditory cortex can selectively encode a speech stream in a background insensitive manner, and this stable neural representation of speech provides a plausible basis for background-invariant recognition of speech. PMID:23536086

  20. Migratory neuronal progenitors arise from the neural plate borders in tunicates.

    PubMed

    Stolfi, Alberto; Ryan, Kerrianne; Meinertzhagen, Ian A; Christiaen, Lionel

    2015-11-19

    The neural crest is an evolutionary novelty that fostered the emergence of vertebrate anatomical innovations such as the cranium and jaws. During embryonic development, multipotent neural crest cells are specified at the lateral borders of the neural plate before delaminating, migrating and differentiating into various cell types. In invertebrate chordates (cephalochordates and tunicates), neural plate border cells express conserved factors such as Msx, Snail and Pax3/7 and generate melanin-containing pigment cells, a derivative of the neural crest in vertebrates. However, invertebrate neural plate border cells have not been shown to generate homologues of other neural crest derivatives. Thus, proposed models of neural crest evolution postulate vertebrate-specific elaborations on an ancestral neural plate border program, through acquisition of migratory capabilities and the potential to generate several cell types. Here we show that a particular neuronal cell type in the tadpole larva of the tunicate Ciona intestinalis, the bipolar tail neuron, shares a set of features with neural-crest-derived spinal ganglia neurons in vertebrates. Bipolar tail neuron precursors derive from caudal neural plate border cells, delaminate and migrate along the paraxial mesoderm on either side of the neural tube, eventually differentiating into afferent neurons that form synaptic contacts with both epidermal sensory cells and motor neurons. We propose that the neural plate borders of the chordate ancestor already produced migratory peripheral neurons and pigment cells, and that the neural crest evolved through the acquisition of a multipotent progenitor regulatory state upstream of multiple, pre-existing neural plate border cell differentiation programs. PMID:26524532