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Sample records for zebrafish neural tube

  1. Small GTPase R-Ras participates in neural tube formation in zebrafish embryonic spinal cord.

    Science.gov (United States)

    Ohata, Shinya; Uga, Hideko; Okamoto, Hitoshi; Katada, Toshiaki

    2018-06-27

    Ras related (R-Ras), a small GTPase, is involved in the maintenance of apico-basal polarity in neuroepithelial cells of the zebrafish hindbrain, axonal collapse in cultured murine hippocampal neurons, and maturation of blood vessels in adult mice. However, the role of R-Ras in neural tube formation remains unknown. Using antisense morpholino oligonucleotides (AMOs), we found that in the spinal cord of zebrafish embryos, the lumen was formed bilaterally in rras morphants, whereas it was formed at the midline in control embryos. As AMO can cause off-target effects, we generated rras mutant zebrafish lines using CRISPR/Cas9 technology. Although these rras mutant embryos did not have a bilateral lumen in the spinal cord, the following findings suggest that the phenotype is unlikely due to an off-target effect of rras AMO: 1) The rras morphant phenotype was rescued by an injection of AMO-resistant rras mRNA, and 2) a bilaterally segregated spinal cord was not observed in rras mutant embryos injected with rras AMO. The results suggest that the function of other ras family genes may be redundant in rras mutants. Previous research reported a bilaterally formed lumen in the spinal cord of zebrafish embryos with a mutation in a planar cell polarity (PCP) gene, van gogh-like 2 (vangl2). In the present study, in cultured cells, R-Ras was co-immunoprecipitated with Vangl2 but not with another PCP regulator, Pricke1. Interestingly, the interaction between R-Ras and Vangl2 was stronger in guanine-nucleotide free point mutants of R-Ras than in wild-type or constitutively active (GTP-bound) forms of R-Ras. R-Ras may regulate neural tube formation in cooperation with Vangl2 in the developing zebrafish spinal cord. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Neural Tube Defects

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

  3. Neural Tube Defects and Pregnancy

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    Emine Çoşar

    2009-09-01

    Full Text Available OBJECTIVE: Neural tube defects are congenital malformations those mostly causing life-long morbidities. They are prevented by the periconseptional folic acid usage and prenatal diagnostic methods. MATERIALS-METHODS: Pregnants from Afyonkarahisar and neighbourhood cities applied to our hospital and determined NTD, were investigated. RESULTS: In our obstetrics clinic 1403 delivery were made and 43 of them had fetus with NTD. Among these fetuses 41.3% had meningomyelocel, 17.4% had meningocel, 21.7% had encephalocel, 8.7% had unencephali and 4.3% had iniencephali. CONCLUSION: Incidence of NTD is high in our region and geographic region, nutrition and other socioeconomic factors may be related to the high incidence. Education of the mother and periconceptional folic acid usage may reduce teh incidence of NTD.

  4. The neural basis of visual behaviors in the larval zebrafish.

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    Portugues, Ruben; Engert, Florian

    2009-12-01

    We review visually guided behaviors in larval zebrafish and summarise what is known about the neural processing that results in these behaviors, paying particular attention to the progress made in the last 2 years. Using the examples of the optokinetic reflex, the optomotor response, prey tracking and the visual startle response, we illustrate how the larval zebrafish presents us with a very promising model vertebrate system that allows neurocientists to integrate functional and behavioral studies and from which we can expect illuminating insights in the near future. Copyright 2009 Elsevier Ltd. All rights reserved.

  5. Time-lapse imaging of neural development: zebrafish lead the way into the fourth dimension.

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    Rieger, Sandra; Wang, Fang; Sagasti, Alvaro

    2011-07-01

    Time-lapse imaging is often the only way to appreciate fully the many dynamic cell movements critical to neural development. Zebrafish possess many advantages that make them the best vertebrate model organism for live imaging of dynamic development events. This review will discuss technical considerations of time-lapse imaging experiments in zebrafish, describe selected examples of imaging studies in zebrafish that revealed new features or principles of neural development, and consider the promise and challenges of future time-lapse studies of neural development in zebrafish embryos and adults. Copyright © 2011 Wiley-Liss, Inc.

  6. Radioactive fallout and neural tube defects

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    Nejat Akar

    2015-10-01

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

  7. Radioactive fallout and neural tube defects

    African Journals Online (AJOL)

    Nejat Akar

    2015-07-10

    Jul 10, 2015 ... It is a prenatal failure of the embryonic neural tube to close over the ... and the ability of radioisotopes to attach to cells, tissues, and ... The Egyptian Journal of Medical Human Genetics .... Stem Cells 1997;15(Suppl 2):255–60.

  8. Skeletogenic fate of zebrafish cranial and trunk neural crest.

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    Erika Kague

    Full Text Available The neural crest (NC is a major contributor to the vertebrate craniofacial skeleton, detailed in model organisms through embryological and genetic approaches, most notably in chick and mouse. Despite many similarities between these rather distant species, there are also distinct differences in the contribution of the NC, particularly to the calvariae of the skull. Lack of information about other vertebrate groups precludes an understanding of the evolutionary significance of these differences. Study of zebrafish craniofacial development has contributed substantially to understanding of cartilage and bone formation in teleosts, but there is currently little information on NC contribution to the zebrafish skeleton. Here, we employ a two-transgene system based on Cre recombinase to genetically label NC in the zebrafish. We demonstrate NC contribution to cells in the cranial ganglia and peripheral nervous system known to be NC-derived, as well as to a subset of myocardial cells. The indelible labeling also enables us to determine NC contribution to late-forming bones, including the calvariae. We confirm suspected NC origin of cartilage and bones of the viscerocranium, including cartilages such as the hyosymplectic and its replacement bones (hymandibula and symplectic and membranous bones such as the opercle. The cleithrum develops at the border of NC and mesoderm, and as an ancestral component of the pectoral girdle was predicted to be a hybrid bone composed of both NC and mesoderm tissues. However, we find no evidence of a NC contribution to the cleithrum. Similarly, in the vault of the skull, the parietal bones and the caudal portion of the frontal bones show no evidence of NC contribution. We also determine a NC origin for caudal fin lepidotrichia; the presumption is that these are derived from trunk NC, demonstrating that these cells have the ability to form bone during normal vertebrate development.

  9. The role of zebrafish (Danio rerio in dissecting the genetics and neural circuits of executive function

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    Matthew O Parker

    2013-04-01

    Full Text Available Zebrafish have great potential to contribute to our understanding of behavioural genetics and thus to contribute to our understanding of the aetiology of psychiatric disease. However, progress is dependent upon the rate at which behavioural assays addressing complex behavioural phenotypes are designed, reported and validated. Here we critically review existing behavioural assays with particular focus on the use of adult zebrafish to explore executive processes and phenotypes associated with human psychiatric disease. We outline the case for using zebrafish as models to study impulse control and attention, discussing the validity of applying extant rodent assays to zebrafish and evidence for the conservation of relevant neural circuits.

  10. Neural Tube Defects, Folic Acid and Methylation

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    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

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

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

    2017-04-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  13. NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects.

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    Sequerra, Eduardo B; Goyal, Raman; Castro, Patricio A; Levin, Jacqueline B; Borodinsky, Laura N

    2018-05-16

    Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that NMDA receptors are important for the formation of the neural tube and that the loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation. SIGNIFICANCE STATEMENT Neural tube defects are one of the most common birth defects. Clinical investigations have determined that the use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that they are side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy. Copyright © 2018 the authors 0270-6474/18/384762-12$15.00/0.

  14. Single-site neural tube closure in human embryos revisited.

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    de Bakker, Bernadette S; Driessen, Stan; Boukens, Bastiaan J D; van den Hoff, Maurice J B; Oostra, Roelof-Jan

    2017-10-01

    Since the multi-site closure theory was first proposed in 1991 as explanation for the preferential localizations of neural tube defects, the closure of the neural tube has been debated. Although the multi-site closure theory is much cited in clinical literature, single-site closure is most apparent in literature concerning embryology. Inspired by Victor Hamburgers (1900-2001) statement that "our real teacher has been and still is the embryo, who is, incidentally, the only teacher who is always right", we decided to critically review both theories of neural tube closure. To verify the theories of closure, we studied serial histological sections of 10 mouse embryos between 8.5 and 9.5 days of gestation and 18 human embryos of the Carnegie collection between Carnegie stage 9 (19-21 days) and 13 (28-32 days). Neural tube closure was histologically defined by the neuroepithelial remodeling of the two adjoining neural fold tips in the midline. We did not observe multiple fusion sites in neither mouse nor human embryos. A meta-analysis of case reports on neural tube defects showed that defects can occur at any level of the neural axis. Our data indicate that the human neural tube fuses at a single site and, therefore, we propose to reinstate the single-site closure theory for neural tube closure. We showed that neural tube defects are not restricted to a specific location, thereby refuting the reasoning underlying the multi-site closure theory. Clin. Anat. 30:988-999, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

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    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.

  16. Radioactive fallout and neural tube defects | Akar | Egyptian Journal ...

    African Journals Online (AJOL)

    Possible link between radioactivity and the occurrence of neural tube defects is a long lasting debate since the Chernobyl nuclear fallout in 1986. A recent report on the incidence of neural defects in the west coast of USA, following Fukushima disaster, brought another evidence for effect of radioactive fallout on the ...

  17. Prevalence of neural tube defect and hydrocephalus in Northern ...

    African Journals Online (AJOL)

    All the cases reported in this study were open neural tube defect (NTD). The most common defect was hydrocephalus occurring in 33 patients representing 57.9%, with spinal bifida occurring in 21 patients representing 38.6%. Encephalocele or cranium bifida occurred in only 5.3% (3 patients). Among the spinal bifida cases ...

  18. Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish.

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    Subhra Prakash Hui

    Full Text Available Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration.

  19. cables1 Is Required for Embryonic Neural Development: Molecular, Cellular, and Behavioral Evidence From the Zebrafish

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    GROENEWEG, JOLIJN W.; WHITE, YVONNE A.R.; KOKEL, DAVID; PETERSON, RANDALL T.; ZUKERBERG, LAWRENCE R.; BERIN, INNA; RUEDA, BO R.; WOOD, ANTONY W.

    2014-01-01

    SUMMARY In vitro studies have suggested that the Cables1 gene regulates epithelial cell proliferation, whereas other studies suggest a role in promoting neural differentiation. In efforts to clarify the functions of Cables1 in vivo, we conducted gain- and loss-of-function studies targeting its ortholog (cables1) in the zebrafish embryo. Similar to rodents, zebrafish cables1 mRNA expression is detected most robustly in embryonic neural tissues. Antisense knockdown of cables1 leads to increased numbers of apoptotic cells, particularly in brain tissue, in addition to a distinct behavioral phenotype, characterized by hyperactivity in response to stimulation. Apoptosis and the behavioral abnormality could be rescued by co-expression of a morpholino-resistant cables1 construct. Suppression of p53 expression in cables1 morphants partially rescued both apoptosis and the behavioral phenotype, suggesting that the phenotype of cables1 morphants is due in part to p53-dependent apoptosis. Alterations in the expression patterns of several neural transcription factors were observed in cables1 morphants during early neurulation, suggesting that cables1 is required for early neural differentiation. Ectopic overexpression of cables1 strongly disrupted embryonic morphogenesis, while overexpression of a cables1 mutant lacking the C-terminal cyclin box had little effect, suggesting functional importance of the cyclin box. Lastly, marked reductions in p35, but not Cdk5, were observed in cables1 morphants. Collectively, these data suggest that cables1 is important for neural differentiation during embryogenesis, in a mechanism that likely involves interactions with the Cdk5/p35 kinase pathway. PMID:21268180

  20. Neural tube defects – recent advances, unsolved questions and controversies

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

    2014-01-01

    Neural tube defects (NTDs) are severe congenital malformations affecting around 1 in every 1000 pregnancies. Here we review recent advances and currently unsolved issues in the NTD field. An innovation in clinical management has come from the demonstration that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention by folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in UK. Genetic predisposition comprises the majority of NTD risk, 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 study of mouse NTD models shows that anencephaly, open spina bifida and craniorachischisis result from failure of primary neurulation, while skin-covered spinal dysraphism results from defective secondary neurulation. Other ‘NTD’ malformations, such as encephalocele, are likely to be post-neurulation disorders. PMID:23790957

  1. Preventing neural tube defects in Europe: a missed opportunity.

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    Busby, Araceli; Abramsky, Lenore; Dolk, Helen; Armstrong, Ben; Addor, Marie-Claude; Anneren, Goran; Armstrong, Nicola; Baguette, Andre; Barisic, Ingeborg; Berghold, Andrea; Bianca, Sebastiano; Braz, Paula; Calzolari, Elisa; Christiansen, Marianne; Cocchi, Guido; Daltveit, Anne Kjersti; De Walle, Hermien; Edwards, Grace; Gatt, Miriam; Gener, Blanca; Gillerot, Yves; Gjergja, Romana; Goujard, Janine; Haeusler, Martin; Latos-Bielenska, Anna; McDonnell, Robert; Neville, Amanda; Olars, Birgitta; Portillo, Isabel; Ritvanen, Annukka; Robert-Gnansia, Elizabeth; Rösch, Christine; Scarano, Gioacchino; Steinbicker, Volker

    2005-01-01

    Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects (NTD). Unambiguous evidence of the effectiveness of periconceptional folic acid in preventing the majority of neural tube defects has been available since 1991. We report on trends in the total prevalence of neural tube defects up to 2002, in the context of a survey in 18 European countries of periconceptional folic acid supplementation (PFAS) policies and their implementation. EUROCAT is a network of population-based registries in Europe collaborating in the epidemiological surveillance of congenital anomalies. Representatives from 18 participating countries provided information about policy, health education campaigns and surveys of PFAS uptake. The yearly total prevalence of neural tube defects including livebirths, stillbirths and terminations of pregnancy was calculated from 1980 to 2002 for 34 registries, with UK and Ireland estimated separately from the rest of Europe. A meta-analysis of changes in NTD total prevalence between 1989-1991 and 2000-2002 according to PFAS policy was undertaken for 24 registries. By 2005, 13 countries had a government recommendation that women planning a pregnancy should take 0.4mg folic acid supplement daily, accompanied in 7 countries by government-led health education initiatives. In the UK and Ireland, countries with PFAS policy, there was a 30% decline in NTD total prevalence (95% CI 16-42%) but it was difficult to distinguish this from the pre-existing strong decline. In other European countries with PFAS policy, there was virtually no decline in NTD total prevalence whether a policy was in place by 1999 (2%, 95% CI 28% reduction to 32% increase) or not (8%, 95% CI 26% reduction to 16% increase). The potential for preventing NTDs by periconceptional folic acid supplementation is still far from being fulfilled in Europe. Only a public health policy including folic acid fortification of staple foods is likely to result in large

  2. Malformations du tube neural en chirurgie pediatrique du chu de ...

    African Journals Online (AJOL)

    encéphalocèle et 6 cas de sipina bifida. La cure chirurgicale a été le principal mode de prise en charge des patients. Seuls 91,38% des cas ont été opérés. Pour toutes les malformations du tube neural, nous avons enregistré 7 décès dont 2 décès ...

  3. Diagnosis of fetal neural tube defects by MRI

    International Nuclear Information System (INIS)

    Dong Suzhen; Zhu Ming; Zhong Yumin; Zhang Hong; Pan Huihong

    2010-01-01

    Objective: To explore the diagnostic value of MRI on fetal neural tube defects. Methods: Ten pregnant women, aged from 25 to 35 years (average 28 years) and with gestation from 20-39 weeks (average 33 weeks) were studied with a 1.5 T superconductive MR unit within 24 to 48 hours after ultrasound (US) studies. The imaging protocol included fast-imaging employing steady-state acquisition, single-shot FSE and T 1 -weighted fast inversion recovery motion insensitive sequences in the axial, fromtal, and sagittal planes relative to the fetal brain, thorax, abdomen, and spines. Prenatal US and MRI findings were compared with postnatal MRI diagnoses (3 fetuses) or autopsy (7 fetuses). Results: Ten pregnant women (9 with a single fetus and 1 with twin fetuses) were examined. For all cases, the diagnoses established by MRI were correct when compared with postnatal diagnosis or autopsy. In 7 cases, US and MRI findings were in complete agreement with postnatal diagnoses. US missed the diagnosis in 1 cases and misdiagnosed in 2 cases. Ten neural tube defects in this study included anencephaly (1 case), exencephaly (1 case), meningoencephalocele associated with amniotic band sequence (1 case), meningocele (1 case), thoracic myelomeningocele (1 case), lumbar spinal bifida (1 case), sacroiliac myelomeningocele (2 cases), sacroiliac large cystic spinal meningocele (1 case), sacroiliac spinal bifida (1 case). Conclusions: Prenatal MRI is effective in the assessment of fetal neural tube defects. It can exactly discriminate herniated contents and locate the spinal lesion level. (authors)

  4. Periconceptional Folate Deficiency and Implications in Neural Tube Defects

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    J. Safi

    2012-01-01

    Full Text Available 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.

  5. Sinup, a novel Siaz-interacting nuclear protein, modulates neural plate formation in the zebrafish embryos

    International Nuclear Information System (INIS)

    Ro, Hyunju; Won, Minho; Lee, Su-Ui; Kim, Kyoon E.; Huh, Tae-Lin; Kim, Cheol-Hee; Rhee, Myungchull

    2005-01-01

    Siah, the vertebrate homologue of the Drosophila seven in absentia (sina) gene, is well conserved from Drosophila to mammal and involved in ubiquitination and proteasome-dependent degradation of various target proteins. To identify cellular proteins interacting with Siah, we screened a zebrafish cDNA library with zebrafish Siah (Siaz) as bait in a yeast two-hybrid assay. We identified a cDNA encoding a novel protein composed of 145 amino acids and termed it as Sinup (Siaz-interacting-nuclear-protein). Sinup is a novel nuclear protein that binds to the highly conserved C-terminal protein-interacting domain of Siaz both in vivo and in vitro. During development, sinup transcripts are abundant from the one-cell stage to the early blastula and then markedly diminished, suggesting sinup largely exists as maternal transcripts. sinup overexpression induced lateral expansion of the neural plate and in consequence caused ectopic expression of otx-2 and hoxb1b during the late gastrula stage. In addition, the lateral/paraxial expression of wnt8 at the onset of gastrulation is suppressed by the forced expression of sinup while the expression levels of various dorso-ventral markers are unaffected. In contrast, interfering with sinup functions using sinup morpholino oligonucleotides gradually diminished the anterior neuroectoderm from the posterior region, and resulted in compete loss of hindbrain at the 3-somites stage. Our report suggests that sinup expression should be tightly regulated during early embryonic development for the proper neural plate formation

  6. Unjoined primary and secondary neural tubes: junctional neural tube defect, a new form of spinal dysraphism caused by disturbance of junctional neurulation.

    Science.gov (United States)

    Eibach, Sebastian; Moes, Greg; Hou, Yong Jin; Zovickian, John; Pang, Dachling

    2017-10-01

    Primary and secondary neurulation are the two known processes that form the central neuraxis of vertebrates. Human phenotypes of neural tube defects (NTDs) mostly fall into two corresponding categories consistent with the two types of developmental sequence: primary NTD features an open skin defect, an exposed, unclosed neural plate (hence an open neural tube defect, or ONTD), and an unformed or poorly formed secondary neural tube, and secondary NTD with no skin abnormality (hence a closed NTD) and a malformed conus caudal to a well-developed primary neural tube. We encountered three cases of a previously unrecorded form of spinal dysraphism in which the primary and secondary neural tubes are individually formed but are physically separated far apart and functionally disconnected from each other. One patient was operated on, in whom both the lumbosacral spinal cord from primary neurulation and the conus from secondary neurulation are each anatomically complete and endowed with functioning segmental motor roots tested by intraoperative triggered electromyography and direct spinal cord stimulation. The remarkable feature is that the two neural tubes are unjoined except by a functionally inert, probably non-neural band. The developmental error of this peculiar malformation probably occurs during the critical transition between the end of primary and the beginning of secondary neurulation, in a stage aptly called junctional neurulation. We describe the current knowledge concerning junctional neurulation and speculate on the embryogenesis of this new class of spinal dysraphism, which we call junctional neural tube defect.

  7. Novel Mutation of LRP6 Identified in Chinese Han Population Links Canonical WNT Signaling to Neural Tube Defects.

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    Shi, Zhiwen; Yang, Xueyan; Li, Bin-Bin; Chen, Shuxia; Yang, Luming; Cheng, Liangping; Zhang, Ting; Wang, Hongyan; Zheng, Yufang

    2018-01-15

    Neural tube defects (NTDs), the second most frequent cause of human congenital abnormalities, are debilitating birth defects due to failure of neural tube closure. It has been shown that noncanonical WNT/planar cell polarity (PCP) signaling is required for convergent extension (CE), the initiation step of neural tube closure (NTC). But the effect of canonical WNT//β-catenin signaling during NTC is still elusive. LRP6 (low density lipoprotein receptor related proteins 6) was identified as a co-receptor for WNT/β-catenin signaling, but recent studies showed that it also can mediate WNT/PCP signaling. In this study, we screened mutations in the LRP6 gene in 343 NTDs and 215 ethnically matched normal controls of Chinese Han population. Three rare missense mutations (c.1514A>G, p.Y505C); c.2984A>G, p.D995G; and c.4280C>A, p.P1427Q) of the LRP6 gene were identified in Chinese NTD patients. The Y505C mutation is a loss-of-function mutation on both WNT/β-catenin and PCP signaling. The D995G mutation only partially lost inhibition on PCP signaling without affecting WNT/β-catenin signaling. The P1427Q mutation dramatically increased WNT/β-catenin signaling but only mildly loss of inhibition on PCP signaling. All three mutations failed to rescue CE defects caused by lrp6 morpholino oligos knockdown in zebrafish. Of interest, when overexpressed, D995G did not induce any defects, but Y505C and P1427Q caused more severe CE defects in zebrafish. Our results suggested that over-active canonical WNT signaling induced by gain-of-function mutation in LRP6 could also contribute to human NTDs, and a balanced WNT/β-catenin and PCP signaling is probably required for proper neural tube development. Birth Defects Research 110:63-71, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Mehdi Kehila

    2015-01-01

    Full Text Available 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.

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

    OpenAIRE

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

    2005-01-01

    In order to unravel morphogenetic mechanisms involved in neural tube closure, critical cell movements that are fundamental to remodelling of the cranial neural tube in the chick embryo were studied in vitro by quantitative time-lapse video microscopy. Two main directions of movements were observed. The earliest was directed medially; these cells invaginated into a median groove and were the main contributors to the initial neural tube closure. Once the median groove was completed, cells chang...

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

    Science.gov (United States)

    Hoffbrand, A Victor

    2014-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Joseph E

    2014-11-01

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

  12. Epidemiology of neural tube defects in Saudi Arabia.

    Science.gov (United States)

    AlShail, Essam; De Vol, Edward; Yassen, Ahsan; Elgamal, Essam A

    2014-12-01

    To evaluate the distribution and pattern of neural tube defects in Saudi Arabia by creating a hospital based registry. All cases registered in the King Faisal Specialist Hospital and Research Center (KFSH&RC) neural tube defect (NTD) registry since it was established in October 2000 until December 2012 were studied through active surveillance comprising a registrar who collects NTD information by reviewing the patient's medical records, and interviewing patient's families. The total number of patients registered from October 2000 to December 2012 was 718 patients. There were more females (417, 58%) than males (301, 42%). Of 620 mothers who underwent antenatal ultrasonography; 392 (63%) were diagnosed at birth, and 204 (33%) were diagnosed with antenatal hydrocephalus. In our registry sample, most mothers (95%) did not take folic acid 3 months prior to pregnancy, and 76% did not take folic acid during the 3 months after conception with the affected child. Only 5% received folic acid prior to conception. The KFSH&RC-NTD registry has met its objectives as a source of data that may significantly contribute to the prevention of NTDs, and improving quality of care for NTD patients through active publication of registry findings and management approaches.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-05-01

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

  14. A panel of recombinant monoclonal antibodies against zebrafish neural receptors and secreted proteins suitable for wholemount immunostaining.

    Science.gov (United States)

    Staudt, Nicole; Müller-Sienerth, Nicole; Fane-Dremucheva, Alla; Yusaf, Shahnaz P; Millrine, David; Wright, Gavin J

    2015-01-02

    Cell surface receptors and secreted proteins play important roles in neural recognition processes, but because their site of action can be a long distance from neuron cell bodies, antibodies that label these proteins are valuable to understand their function. The zebrafish embryo is a popular vertebrate model for neurobiology, but suffers from a paucity of validated antibody reagents. Here, we use the entire ectodomain of neural zebrafish cell surface or secreted proteins expressed in mammalian cells to select monoclonal antibodies to ten different antigens. The antibodies were characterised by Western blotting and the sensitivity of their epitopes to formalin fixation was determined. The rearranged antigen binding regions of the antibodies were amplified and cloned which enabled expression in a recombinant form from a single plasmid. All ten antibodies gave specific staining patterns within formalin-treated embryonic zebrafish brains, demonstrating that this generalised approach is particularly efficient to elicit antibodies that stain native antigen in fixed wholemount tissue. Finally, we show that additional tags can be easily added to the recombinant antibodies for convenient multiplex staining. The antibodies and the approaches described here will help to address the lack of well-defined antibody reagents in zebrafish research. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. 21 CFR 101.79 - Health claims: Folate and neural tube defects.

    Science.gov (United States)

    2010-04-01

    ... pregnancy had a reduced risk of having a child with a neural tube defect. (Products containing this level of... neural tube defect, those with insulin-dependent diabetes mellitus, and women with seizure disorders who... mcg) when labeled for use by adults and children 4 or more years of age, or 800 mcg when labeled for...

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  18. Spinal neural tube defects on in utero MRI

    International Nuclear Information System (INIS)

    Williams, F.; Griffiths, P.D.

    2013-01-01

    Spinal neural tube defects are a heterogeneous group of disorders, which remain relatively common, with a prevalence of 1–2 per 1000 live births despite advances in maternal antenatal care. They range from mild disorders with limited neurodevelopmental sequelae to extensive abnormalities with significant morbidity and mortality. The advent of in utero magnetic resonance imaging has enabled accurate anatomical characterization of an increasing number of abnormalities with increasing confidence. Recognition of the salient radiological features of these disorders and their relationship to the embryogenesis of the spinal cord and its coverings is now possible. This review describes the radiological appearances of these disorders with examples from Fetal Imaging Unit, University of Sheffield to illustrate the key anatomical and radiological features to aid the radiologist in their recognition

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

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2007-12-01

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

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

    Science.gov (United States)

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

    2012-06-02

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

  1. Mechanisms underlying metabolic and neural defects in zebrafish and human multiple acyl-CoA dehydrogenase deficiency (MADD.

    Directory of Open Access Journals (Sweden)

    Yuanquan Song

    2009-12-01

    Full Text Available In humans, mutations in electron transfer flavoprotein (ETF or electron transfer flavoprotein dehydrogenase (ETFDH lead to MADD/glutaric aciduria type II, an autosomal recessively inherited disorder characterized by a broad spectrum of devastating neurological, systemic and metabolic symptoms. We show that a zebrafish mutant in ETFDH, xavier, and fibroblast cells from MADD patients demonstrate similar mitochondrial and metabolic abnormalities, including reduced oxidative phosphorylation, increased aerobic glycolysis, and upregulation of the PPARG-ERK pathway. This metabolic dysfunction is associated with aberrant neural proliferation in xav, in addition to other neural phenotypes and paralysis. Strikingly, a PPARG antagonist attenuates aberrant neural proliferation and alleviates paralysis in xav, while PPARG agonists increase neural proliferation in wild type embryos. These results show that mitochondrial dysfunction, leading to an increase in aerobic glycolysis, affects neurogenesis through the PPARG-ERK pathway, a potential target for therapeutic intervention.

  2. Epidemiology of neural tube defects in the world and Iran

    International Nuclear Information System (INIS)

    Farhud, D.; Hadavi, V.; Sadighi, H.

    2000-01-01

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

  3. Phenothiourea sensitizes zebrafish cranial neural crest and extraocular muscle development to changes in retinoic acid and IGF signaling.

    Directory of Open Access Journals (Sweden)

    Brenda L Bohnsack

    Full Text Available 1-Phenyl 2-thiourea (PTU is a tyrosinase inhibitor commonly used to block pigmentation and aid visualization of zebrafish development. At the standard concentration of 0.003% (200 µM, PTU inhibits melanogenesis and reportedly has minimal other effects on zebrafish embryogenesis. We found that 0.003% PTU altered retinoic acid and insulin-like growth factor (IGF regulation of neural crest and mesodermal components of craniofacial development. Reduction of retinoic acid synthesis by the pan-aldehyde dehydrogenase inhibitor diethylbenzaldehyde, only when combined with 0.003% PTU, resulted in extraocular muscle disorganization. PTU also decreased retinoic acid-induced teratogenic effects on pharyngeal arch and jaw cartilage despite morphologically normal appearing PTU-treated controls. Furthermore, 0.003% PTU in combination with inhibition of IGF signaling through either morpholino knockdown or pharmacologic inhibition of tyrosine kinase receptor phosphorylation, disrupted jaw development and extraocular muscle organization. PTU in and of itself inhibited neural crest development at higher concentrations (0.03% and had the greatest inhibitory effect when added prior to 22 hours post fertilization (hpf. Addition of 0.003% PTU between 4 and 20 hpf decreased thyroxine (T4 in thyroid follicles in the nasopharynx of 96 hpf embryos. Treatment with exogenous triiodothyronine (T3 and T4 improved, but did not completely rescue, PTU-induced neural crest defects. Thus, PTU should be used with caution when studying zebrafish embryogenesis as it alters the threshold of different signaling pathways important during craniofacial development. The effects of PTU on neural crest development are partially caused by thyroid hormone signaling.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-12-01

    To ascertain the incidence, and describe the various forms of neural tube defects (NTDs) due to genetic, chromosomal, and syndromic causes. 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. 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. 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.

  6. Morphogens, modeling and patterning the neural tube: an interview with James Briscoe.

    Science.gov (United States)

    Briscoe, James

    2015-01-20

    James Briscoe has a BSc in Microbiology and Virology (from the University of Warwick, UK) and a PhD in Molecular and Cellular Biology (from the Imperial Cancer Research Fund, London, now Cancer Research UK). He started working on the development of the neural tube in the lab of Tom Jessel as a postdoctoral fellow, establishing that there was graded sonic hedgehog signaling in the ventral neural tube. He is currently a group leader and Head of Division in Developmental Biology at the MRC National Institute for Medical Research (which will become part of the Francis Crick Institute in April 2015). He is working to understand the molecular and cellular mechanisms of graded signaling in the vertebrate neural tube.We interviewed him about the development of ideas on morphogenetic gradients and his own work on modeling the development of the neural tube for our series on modeling in biology.

  7. hmmr mediates anterior neural tube closure and morphogenesis in the frog Xenopus.

    Science.gov (United States)

    Prager, Angela; Hagenlocher, Cathrin; Ott, Tim; Schambony, Alexandra; Feistel, Kerstin

    2017-10-01

    Development of the central nervous system requires orchestration of morphogenetic processes which drive elevation and apposition of the neural folds and their fusion into a neural tube. The newly formed tube gives rise to the brain in anterior regions and continues to develop into the spinal cord posteriorly. Conspicuous differences between the anterior and posterior neural tube become visible already during neural tube closure (NTC). Planar cell polarity (PCP)-mediated convergent extension (CE) movements are restricted to the posterior neural plate, i.e. hindbrain and spinal cord, where they propagate neural fold apposition. The lack of CE in the anterior neural plate correlates with a much slower mode of neural fold apposition anteriorly. The morphogenetic processes driving anterior NTC have not been addressed in detail. Here, we report a novel role for the breast cancer susceptibility gene and microtubule (MT) binding protein Hmmr (Hyaluronan-mediated motility receptor, RHAMM) in anterior neurulation and forebrain development in Xenopus laevis. Loss of hmmr function resulted in a lack of telencephalic hemisphere separation, arising from defective roof plate formation, which in turn was caused by impaired neural tissue narrowing. hmmr regulated polarization of neural cells, a function which was dependent on the MT binding domains. hmmr cooperated with the core PCP component vangl2 in regulating cell polarity and neural morphogenesis. Disrupted cell polarization and elongation in hmmr and vangl2 morphants prevented radial intercalation (RI), a cell behavior essential for neural morphogenesis. Our results pinpoint a novel role of hmmr in anterior neural development and support the notion that RI is a major driving force for anterior neurulation and forebrain morphogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  9. Mediterranean diet, folic acid, and neural tube defects.

    Science.gov (United States)

    Fischer, Maximilian; Stronati, Mauro; Lanari, Marcello

    2017-08-17

    The Mediterranean diet has been for a very long time the basis of food habits all over the countries of the Mediterranean basin, originally founded on rural models and low consumption of meat products and high-fat/high-processed foods. However, in the modern era, the traditional Mediterranean diet pattern is now progressively eroding due to the widespread dissemination of the Western-type economy, life-style, technology-driven culture, as well as the globalisation of food production, availability and consumption, with consequent homogenisation of food culture and behaviours. This transition process may affect many situations, including pregnancy and offspring's health. The problem of the diet during pregnancy and the proper intake of nutrients are nowadays a very current topic, arousing much debate. The Mediterranean dietary pattern, in particular, has been associated with the highest risk reduction of major congenital anomalies, like the heterogeneous class of neural tube defects (NTDs). NTDs constitute a major health burden (0.5-2/1000 pregnancies worldwide) and still remain a preventable cause of still birth, neonatal and infant death, or significant lifelong disabilities. Many studies support the finding that appropriate folate levels during pregnancy may confer protection against these diseases. In 1991 one randomised controlled trial (RCT) demonstrated for the first time that periconceptional supplementation of folic acid is able to prevent the recurrence of NTDs, finding confirmed by many other subsequent studies. Anyway, the high rate of unplanned/unintended pregnancies and births and other issues hindering the achievement of adequate folate levels in women in childbearing age, induced the US government and many other countries to institute mandatory food fortification with folic acid. The actual strategy adopted by European Countries (including Italy) suggests that women take 0,4 mg folic acid/die before conception. The main question is which intervention

  10. Neural tube defects in Waardenburg syndrome: A case report and review of the literature.

    Science.gov (United States)

    Hart, Joseph; Miriyala, Kalpana

    2017-09-01

    Waardenburg syndrome type 1 (WS1) is an autosomal dominant genetic condition characterized by sensorineural deafness and pigment abnormalities, and is caused by variants in the PAX3 homeodomain. PAX3 variants have been associated with severe neural tube defects in mice and humans, but the frequency and clinical manifestations of this symptom remain largely unexplored in humans. Consequently, the role of PAX3 in human neural tube formation remains a study of interest, for clinical as well as research purposes. Though the association between spina bifida and WS1 is now well-documented, no study has attempted to characterize the range of spina bifida phenotypes seen in WS. Spina bifida encompasses several diagnoses with a wide scope of clinical severity, ranging from spina bifida occulta to myelomeningocele. We present a patient with Waardenburg syndrome type 1 caused by a novel missense variant in PAX3, presenting with myelomeningocele, Arnold-Chiari malformation, and hydrocephalus at birth. Additionally, we review 32 total cases of neural tube defects associated with WS. Including this report, there have been 15 published cases of myelomeningocele, 10 cases of unspecified spina bifida, 3 cases of sacral dimples, 0 cases of meningocele, and 4 cases of miscellaneous other neural tube defects. Though the true frequency of each phenotype cannot be determined from this collection of cases, these results demonstrate that Waardenburg syndrome type 1 carries a notable risk of severe neural tube defects, which has implications in prenatal and genetic counseling. © 2017 Wiley Periodicals, Inc.

  11. Cutaneous vascular anomalies associated with neural tube defects: nomenclature and pathology revisited.

    Science.gov (United States)

    Maugans, Todd; Sheridan, Rachel M; Adams, Denise; Gupta, Anita

    2011-07-01

    Lumbosacral cutaneous vascular anomalies associated with neural tube defects are frequently described in the literature as "hemangiomas." The classification system for pediatric vascular anomalies developed by the International Society for the Study of Vascular Anomalies provides a framework to accurately diagnose these lesions. To apply this classification to vascular cutaneous anomalies overlying myelodysplasias. A retrospective analysis of patients with neural tube defects and lumbosacral cutaneous vascular lesions was performed. All eligible patients had detailed histopathologic analysis of skin and spinal cord/placode lesions. Clinical and radiologic features were analyzed. Conventional histology and GLUT-1 immunostaining were performed to differentiate infantile capillary hemangiomas from capillary vascular malformations. Ten cases with cutaneous lesions associated with neural tube defects were reviewed. Five lesions were diagnosed as infantile capillary hemangiomas based upon histology and positive GLUT-1 endothelial reactivity. These lesions had a strong association with dermal sinus tracts. No reoperations were required for residual intraspinal vascular lesions, and overlying cutaneous vascular anomalies involuted with time. The remaining 5 lesions were diagnosed as capillary malformations. These occurred with both open and closed neural tube defects, did not involute, and demonstrated enlargement and darkening due to vascular congestion. The International Society for the Study of Vascular Anomalies scheme should be used to describe the cutaneous vascular lesions associated with neural tube defects: infantile capillary hemangiomas and capillary malformations. We advocate that these lesions be described as "vascular anomalies" or "stains" pending accurate diagnosis by clinical, histological, and immunohistochemical evaluations.

  12. Neural tube closure depends on expression of Grainyhead-like 3 in multiple tissues.

    Science.gov (United States)

    De Castro, Sandra C P; Hirst, Caroline S; Savery, Dawn; Rolo, Ana; Lickert, Heiko; Andersen, Bogi; Copp, Andrew J; Greene, Nicholas D E

    2018-03-15

    Failure of neural tube closure leads to neural tube defects (NTDs), common congenital abnormalities in humans. Among the genes whose loss of function causes NTDs in mice, Grainyhead-like3 (Grhl3) is essential for spinal neural tube closure, with null mutants exhibiting fully penetrant spina bifida. During spinal neurulation Grhl3 is initially expressed in the surface (non-neural) ectoderm, subsequently in the neuroepithelial component of the neural folds and at the node-streak border, and finally in the hindgut endoderm. Here, we show that endoderm-specific knockout of Grhl3 causes late-arising spinal NTDs, preceded by increased ventral curvature of the caudal region which was shown previously to suppress closure of the spinal neural folds. This finding supports the hypothesis that diminished Grhl3 expression in the hindgut is the cause of spinal NTDs in the curly tail, carrying a hypomorphic Grhl3 allele. Complete loss of Grhl3 function produces a more severe phenotype in which closure fails earlier in neurulation, before the stage of onset of expression in the hindgut of wild-type embryos. This implicates additional tissues and NTD mechanisms in Grhl3 null embryos. Conditional knockout of Grhl3 in the neural plate and node-streak border has minimal effect on closure, suggesting that abnormal function of surface ectoderm, where Grhl3 transcripts are first detected, is primarily responsible for early failure of spinal neurulation in Grhl3 null embryos. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Transcriptomic Analysis Of Purified Embryonic Neural Stem Cells From Zebrafish Embryos Reveals Signalling Pathways Involved In Glycine-dependent Neurogenesis

    Directory of Open Access Journals (Sweden)

    Eric eSAMARUT

    2016-03-01

    Full Text Available How is the initial set of neurons correctly established during the development of the vertebrate central nervous system? In the embryo, glycine and GABA are depolarizing due the immature chloride gradient, which is only reversed to become hyperpolarizing later in post-natal development. We previously showed that glycine regulates neurogenesis via paracrine signalling that promotes calcium transients in neural stem cells (NSCs and their differentiation into interneurons within the spinal cord of the zebrafish embryo. However, the subjacent molecular mechanisms are not yet understood. Our previous work suggests that early neuronal progenitors were not differentiating correctly in the developing spinal cord. As a result, we aimed at identifying the downstream molecular mechanisms involved specifically in NSCs during glycine-dependent embryonic neurogenesis. Using a gfap:GFP transgenic line, we successfully purified NSCs by fluorescence-activated cell sorting (FACS from whole zebrafish embryos and in embryos in which the glycine receptor was knocked down. The strength of this approach is that it focused on the NSC population while tackling the biological issue in an in vivo context in whole zebrafish embryos. After sequencing the transcriptome by RNA-sequencing, we analyzed the genes whose expression was changed upon disruption of glycine signalling and we confirmed the differential expression by independent RTqPCR assay. While over a thousand genes showed altered expression levels, through pathway analysis we identified 14 top candidate genes belonging to five different canonical signalling pathways (signalling by calcium, TGF-beta, sonic hedgehog, Wnt and p53-related apoptosis that are likely to mediate the promotion of neurogenesis by glycine.

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

    International Nuclear Information System (INIS)

    Huang Yanping; Chen Bingde; Lang Xuemei; Wang Xiaojun; Shan Jianqiang; Jia Dounan

    2004-01-01

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

  15. Correlating Whole Brain Neural Activity with Behavior in Head-Fixed Larval Zebrafish.

    Science.gov (United States)

    Orger, Michael B; Portugues, Ruben

    2016-01-01

    We present a protocol to combine behavioral recording and imaging using 2-photon laser-scanning microscopy in head-fixed larval zebrafish that express a genetically encoded calcium indicator. The steps involve restraining the larva in agarose, setting up optics that allow projection of a visual stimulus and infrared illumination to monitor behavior, and analysis of the neuronal and behavioral data.

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

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  18. Zebrafish msxB, msxC and msxE function together to refine the neural-nonneural border and regulate cranial placodes and neural crest development.

    Science.gov (United States)

    Phillips, Bryan T; Kwon, Hye-Joo; Melton, Colt; Houghtaling, Paul; Fritz, Andreas; Riley, Bruce B

    2006-06-15

    The zebrafish muscle segment homeobox genes msxB, msxC and msxE are expressed in partially overlapping domains in the neural crest and preplacodal ectoderm. We examined the roles of these msx genes in early development. Disrupting individual msx genes causes modest variable defects, whereas disrupting all three produces a reproducible severe phenotype, suggesting functional redundancy. Neural crest differentiation is blocked at an early stage. Preplacodal development begins normally, but placodes arising from the msx expression domain later show elevated apoptosis and are reduced in size. Cell proliferation is normal in these tissues. Unexpectedly, Msx-deficient embryos become ventralized by late gastrulation whereas misexpression of msxB dorsalizes the embryo. These effects appear to involve Distal-less (Dlx) protein activity, as loss of dlx3b and dlx4b suppresses ventralization in Msx-depleted embryos. At the same time, Msx-depletion restores normal preplacodal gene expression to dlx3b-dlx4b mutants. These data suggest that mutual antagonism between Msx and Dlx proteins achieves a balance of function required for normal preplacodal differentiation and placement of the neural-nonneural border.

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

    NARCIS (Netherlands)

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

    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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  1. Self-organising aggregates of zebrafish retinal cells for investigating mechanisms of neural lamination.

    Science.gov (United States)

    Eldred, Megan K; Charlton-Perkins, Mark; Muresan, Leila; Harris, William A

    2017-03-15

    To investigate the cell-cell interactions necessary for the formation of retinal layers, we cultured dissociated zebrafish retinal progenitors in agarose microwells. Within these wells, the cells re-aggregated within hours, forming tight retinal organoids. Using a Spectrum of Fates zebrafish line, in which all different types of retinal neurons show distinct fluorescent spectra, we found that by 48 h in culture, the retinal organoids acquire a distinct spatial organisation, i.e. they became coarsely but clearly laminated. Retinal pigment epithelium cells were in the centre, photoreceptors and bipolar cells were next most central and amacrine cells and retinal ganglion cells were on the outside. Image analysis allowed us to derive quantitative measures of lamination, which we then used to find that Müller glia, but not RPE cells, are essential for this process. © 2017. Published by The Company of Biologists Ltd.

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

    LENUS (Irish Health Repository)

    Molloy, Anne M

    2009-07-09

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  4. Regional neural tube closure defined by the Grainy head-like transcription factors.

    Science.gov (United States)

    Rifat, Yeliz; Parekh, Vishwas; Wilanowski, Tomasz; Hislop, Nikki R; Auden, Alana; Ting, Stephen B; Cunningham, John M; Jane, Stephen M

    2010-09-15

    Primary neurulation in mammals has been defined by distinct anatomical closure sites, at the hindbrain/cervical spine (closure 1), forebrain/midbrain boundary (closure 2), and rostral end of the forebrain (closure 3). Zones of neurulation have also been characterized by morphologic differences in neural fold elevation, with non-neural ectoderm-induced formation of paired dorso-lateral hinge points (DLHP) essential for neural tube closure in the cranial and lower spinal cord regions, and notochord-induced bending at the median hinge point (MHP) sufficient for closure in the upper spinal region. Here we identify a unifying molecular basis for these observations based on the function of the non-neural ectoderm-specific Grainy head-like genes in mice. Using a gene-targeting approach we show that deletion of Grhl2 results in failed closure 3, with mutants exhibiting a split-face malformation and exencephaly, associated with failure of neuro-epithelial folding at the DLHP. Loss of Grhl3 alone defines a distinct lower spinal closure defect, also with defective DLHP formation. The two genes contribute equally to closure 2, where only Grhl gene dosage is limiting. Combined deletion of Grhl2 and Grhl3 induces severe rostral and caudal neural tube defects, but DLHP-independent closure 1 proceeds normally in the upper spinal region. These findings provide a molecular basis for non-neural ectoderm mediated formation of the DLHP that is critical for complete neuraxis closure. (c) 2010 Elsevier Inc. All rights reserved.

  5. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

    Science.gov (United States)

    Ignatius, Myron S; Unal Eroglu, Arife; Malireddy, Smitha; Gallagher, Glen; Nambiar, Roopa M; Henion, Paul D

    2013-01-01

    The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382) mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382) mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382) mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382) defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

  6. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

    Directory of Open Access Journals (Sweden)

    Myron S Ignatius

    Full Text Available The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382 mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382 mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382 mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382 defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

  7. The Wnt Co-Receptor Lrp5 Is Required for Cranial Neural Crest Cell Migration in Zebrafish.

    Directory of Open Access Journals (Sweden)

    Bernd Willems

    Full Text Available During vertebrate neurulation, cranial neural crest cells (CNCCs undergo epithelial to mesenchymal transition (EMT, delaminate from the neural plate border, and migrate as separate streams into different cranial regions. There, they differentiate into distinct parts of the craniofacial skeleton. Canonical Wnt signaling has been shown to be essential for this process at different levels but the involved receptors remained unclear. Here we show that the frizzled co-receptor low-density-lipoprotein (LDL receptor-related protein 5 (Lrp5 plays a crucial role in CNCC migration and morphogenesis of the cranial skeleton. Early during induction and migration of CNCCs, lrp5 is expressed ubiquitously but later gets restricted to CNCC derivatives in the ventral head region besides different regions in the CNS. A knock-down of lrp5 does not interfere with induction of CNCCs but leads to reduced proliferation of premigratory CNCCs. In addition, cell migration is disrupted as CNCCs are found in clusters at ectopic positions in the dorsomedial neuroepithelium after lrp5 knock-down and transient CRISPR/Cas9 gene editing. These migratory defects consequently result in malformations of the craniofacial skeleton. To date, Lrp5 has mainly been associated with bone homeostasis in mammals. Here we show that in zebrafish, lrp5 also controls cell migration during early morphogenetic processes and contributes to shaping the craniofacial skeleton.

  8. The murine homeobox gene Msx-3 shows highly restricted expression in the developing neural tube.

    Science.gov (United States)

    Shimeld, S M; McKay, I J; Sharpe, P T

    1996-04-01

    The mouse homeobox-genes Msx-1 and Msx-2 are expressed in several areas of the developing embryo, including the neural tube, neural crest, facial processes and limb buds. Here we report the characterisation of a third mouse Msx gene, which we designate Msx-3. The embryonic expression of Msx-3 was found to differ from that of Msx-1 and -2 in that it was confined to the dorsal neural tube. In embryos with 5-8 somites a segmental pattern of expression was observed in the hindbrain, with rhombomeres 3 and 5 lacking Msx-3 while other rhombomeres expressed Msx-3. This pattern was transient, however, such that in embryos with 18 or more somites expression was continuous throughout the dorsal hindbrain and anterior dorsal spinal cord. Differentiation of dorsal cell types in the neural tube can be induced by addition of members of the Tgf-beta family. Additionally, Msx-1 and -2 have been shown to be activated by addition of the Tgf-beta family member Bmp-4. To determine if Bmp-4 could activate Msx-3, we incubated embryonic hindbrain explants with exogenous Bmp-4. The dorsal expression of Msx-3 was seen to expand into more ventral regions of the neurectoderm in Bmp-4-treated cultures, implying that Bmp-4 may be able to mimic an in vivo signal that induces Msx-3.

  9. SINs and SOMs: Neural microcircuits for size tuning in the zebrafish and mouse visual pathway.

    Directory of Open Access Journals (Sweden)

    Alison J. Barker

    2013-05-01

    Full Text Available In many animals, a fast and reliable circuit for discriminating between predator-sized objects and edible (prey-sized objects is necessary for survival. How are receptive fields in visual brain areas organized to extract information about size? Recent studies from the zebrafish optic tectum and the mouse visual cortex suggest de novo shaping of receptive fields by subtypes of inhibitory neurons. Del Bene et al. (2010 describe a population of GABAergic neurons in the zebrafish optic tectum (Superficial Interneurons, SINs that are necessary for size filtering during prey capture. Adesnik et al. (2012 describe a somatostatin-expressing interneuron population (SOMs that confers surround suppression on layer II/III pyramidal cells in mouse V1. Strikingly both the SINs and the SOMs, display size-dependent response properties. Increasing visual stimulus size increases excitatory input to these neurons. Dampening SIN or SOM activity alters tuning of neighboring circuits such that they lose preference for small objects. Both results provide exciting evidence for mechanisms of size filtering in visual circuits. Here we review the roles of the SINs and the SOMs and speculate on the similarity of such spatial filters across species.

  10. review of current evidence for folate in the prevention of neural tube ...

    African Journals Online (AJOL)

    The incidence of neural tube defects (NTD) among black South. Africans living in urban areas is low compared with reports of _". I\\TTD incidence in rural areasY A NTD incidence of 0.95 per -;:-. 1000 live births was reported in Cape Town,l while an incidence of 0.99 per 1 000 live births was reported in a study performed at ...

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

    OpenAIRE

    Chen, Chih-Ping

    2008-01-01

    Fetuses with neural tube defects (NTDs) may be associated with maternal and fetal risk factors. This article provides a comprehensive review of maternal and fetal risk factors associated with NTDs, such as infertility, periconceptional clomiphene use and assisted reproductive technology, periconceptional folic acid deficiency and effects offolic acid supplementation and fortification on NTD rates, periconceptional vitamin B1 2 deficiency, single nucleotide polymorphisms and polymorphisms in g...

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

    Directory of Open Access Journals (Sweden)

    F Haghollahi

    2008-06-01

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

  13. Air Pollution, Neighbourhood Socioeconomic Factors, and Neural Tube Defects in the San Joaquin Valley of California.

    Science.gov (United States)

    Padula, Amy M; Yang, Wei; Carmichael, Suzan L; Tager, Ira B; Lurmann, Frederick; Hammond, S Katharine; Shaw, Gary M

    2015-11-01

    Environmental pollutants and neighbourhood socioeconomic factors have been associated with neural tube defects, but the potential impact of interaction between ambient air pollution and neighbourhood socioeconomic factors on the risks of neural tube defects is not well understood. We used data from the California Center of the National Birth Defects Study and the Children's Health and Air Pollution Study to investigate whether associations between air pollutant exposure in early gestation and neural tube defects were modified by neighbourhood socioeconomic factors in the San Joaquin Valley of California, 1997-2006. There were 5 pollutant exposures, 3 outcomes, and 9 neighbourhood socioeconomic factors included for a total of 135 investigated associations. Estimates were adjusted for maternal race-ethnicity, education, and multivitamin use. We present below odds ratios (ORs) that exclude 1 and a chi-square test of homogeneity P-value of <0.05. We observed increased odds of spina bifida comparing the highest to lowest quartile of particulate matter <10 μm (PM10 ) among those living in a neighbourhood with: (i) median household income of less than $30 000 per year [OR 5.1, 95% confidence interval (CI) 1.7, 15.3]; (ii) more than 20% living below the federal poverty level (OR 2.6, 95% CI 1.1, 6.0); and (iii) more than 30% with less than or equal to a high school education (OR 3.2, 95% CI 1.4, 7.4). The ORs were not statistically significant among those higher socioeconomic status (SES) neighbourhoods. Our results demonstrate effect modification by neighbourhood socioeconomic factors in the association of particulate matter and neural tube defects in California. © 2015 John Wiley & Sons Ltd.

  14. A comparison of neural tube defects identified by two independent routine recording systems for congenital malformations in Northern Ireland.

    Science.gov (United States)

    Nevin, N C; McDonald, J R; Walby, A L

    1978-12-01

    The efficiency of two systems for recording congenital malformations has been compared; one system, the Registrar General's Congenital Malformation Notification, is based on registering all malformed infants, and the other, the Child Health System, records all births. In Northern Ireland for three years [1974--1976], using multiple sources of ascertainment, a total of 686 infants with neural tube defects was identified among 79 783 live and stillbirths. The incidence for all neural tube defects in 8 60 per 1 000 births. The Registrar General's Congenital Malformation Notification System identified 83.6% whereas the Child Health System identified only 63.3% of all neural tube defects. Both systems together identified 86.2% of all neural tube defects. The two systems are suitable for monitoring of malformations and the addition of information from the Genetic Counselling Clinics would enhance the data for epidemiological studies.

  15. Flexible deep brain neural probes based on a parylene tube structure

    Science.gov (United States)

    Zhao, Zhiguo; Kim, Eric; Luo, Hao; Zhang, Jinsheng; Xu, Yong

    2018-01-01

    Most microfabricated neural probes have limited shank length, which prevents them from reaching many deep brain structures. This paper reports deep brain neural probes with ultra-long penetrating shanks based on a simple but novel parylene tube structure. The mechanical strength of the parylene tube shank is temporarily enhanced during implantation by inserting a metal wire. The metal wire can be removed after implantation, making the implanted probe very flexible and thus minimizing the stress caused by micromotions of brain tissues. Optogenetic stimulation and chemical delivery capabilities can be potentially integrated by taking advantage of the tube structure. Single-shank prototypes with a shank length of 18.2 mm have been developed. The microfabrication process comprises of deep reactive ion etching (DRIE) of silicon, parylene conformal coating/refilling, and XeF2 isotropic silicon etching. In addition to bench-top insertion characterization, the functionality of developed probes has been preliminarily demonstrated by implanting into the amygdala of a rat and recording neural signals.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Title: Maternal bereavement after death of a close relative and neural tube defect in the offspring Background: Neural tube defects are the second most common and often lethal congenital anomaly in the world leaving surviving children with life-long severe disabilities. A low intake of folic acid...... was seen (OR 1.61, 95% CI: 1.07; 2.41). Discussion: We only studied live born children but about 2/3 of children with spina bifida survive the birth or longer with corrective surgery. We did not adjust for folic acid, but a sub-analysis of approximately 85,000 mothers showed no difference in intake during...... all children born in Denmark from 1978-2008 and their mothers (n=1,734,190). In the time window of one year before pregnancy or during the first trimester of pregnancy 34,407 mothers were exposed to bereavement. Results: A total of 5,031 cases of neural tube defects were identified: 889 with spina...

  17. An amphioxus Msx gene expressed predominantly in the dorsal neural tube.

    Science.gov (United States)

    Sharman, A C; Shimeld, S M; Holland, P W

    1999-04-01

    Genomic and cDNA clones of an Msx class homeobox gene were isolated from amphioxus (Branchiostoma floridae). The gene, AmphiMsx, is expressed in the neural plate from late gastrulation; in later embryos it is expressed in dorsal cells of the neural tube, excluding anterior and posterior regions, in an irregular reiterated pattern. There is transient expression in dorsal cells within somites, reminiscent of migrating neural crest cells of vertebrates. In larvae, mRNA is detected in two patches of anterior ectoderm proposed to be placodes. Evolutionary analyses show there is little phylogenetic information in Msx protein sequences; however, it is likely that duplication of Msx genes occurred in the vertebrate lineage.

  18. Partitioning of One-Carbon Units in Folate and Methionine Metabolism Is Essential for Neural Tube Closure

    Directory of Open Access Journals (Sweden)

    Kit-Yi Leung

    2017-11-01

    Full Text Available Summary: Abnormal folate one-carbon metabolism (FOCM is implicated in neural tube defects (NTDs, severe malformations of the nervous system. MTHFR mediates unidirectional transfer of methyl groups from the folate cycle to the methionine cycle and, therefore, represents a key nexus in partitioning one-carbon units between FOCM functional outputs. Methionine cycle inhibitors prevent neural tube closure in mouse embryos. Similarly, the inability to use glycine as a one-carbon donor to the folate cycle causes NTDs in glycine decarboxylase (Gldc-deficient embryos. However, analysis of Mthfr-null mouse embryos shows that neither S-adenosylmethionine abundance nor neural tube closure depend on one-carbon units derived from embryonic or maternal folate cycles. Mthfr deletion or methionine treatment prevents NTDs in Gldc-null embryos by retention of one-carbon units within the folate cycle. Overall, neural tube closure depends on the activity of both the methionine and folate cycles, but transfer of one-carbon units between the cycles is not necessary. : Leung at al. find that embryonic neural tube closure depends both on the supply of one-carbon units to the folate cycle from glycine cleavage and on the methionine cycle. In contrast, transfer of one-carbon units from the folate cycle to the methionine cycle by MTHFR is dispensable. Keywords: one-carbon metabolism, folic acid, neural tube defects, spina bifida, glycine cleavage system, non-ketotic hyperglycinemia, eye, Mthfr, Gldc

  19. Maternal Diabetes Alters Expression of MicroRNAs that Regulate Genes Critical for Neural Tube Development

    Directory of Open Access Journals (Sweden)

    Seshadri Ramya

    2017-07-01

    Full Text Available Maternal diabetes is known to cause neural tube defects (NTDs in embryos and neuropsychological deficits in infants. Several metabolic pathways and a plethora of genes have been identified to be deregulated in developing brain of embryos by maternal diabetes, although the exact mechanism remains unknown. Recently, miRNAs have been shown to regulate genes involved in brain development and maturation. Therefore, we hypothesized that maternal diabetes alters the expression of miRNAs that regulate genes involved in biological pathways critical for neural tube development and closure during embryogenesis. To address this, high throughput miRNA expression profiling in neural stem cells (NSCs isolated from the forebrain of embryos from normal or streptozotocin-induced diabetic pregnancy was carried out. It is known that maternal diabetes results in fetal hypoglycemia/hyperglycemia or hypoxia. Hence, NSCs from embryos of control pregnant mice were exposed to low or high glucose or hypoxia in vitro. miRNA pathway analysis revealed distinct deregulation of several biological pathways, including axon guidance pathway, which are critical for brain development in NSCs exposed to different treatments. Among the differentially expressed miRNAs, the miRNA-30 family members which are predicted to target genes involved in brain development was upregulated in NSCs from embryos of diabetic pregnancy when compared to control. miRNA-30b was found to be upregulated while its target gene Sirtuin 1 (Sirt1, as revealed by luciferase assay, was down regulated in NSCs from embryos of diabetic pregnancy. Further, overexpression of miRNA-30b in NSCs, resulted in decreased expression of Sirt1 protein, and altered the neuron/glia ratio. On the other hand, siRNA mediated knockdown of Sirt1 in NSCs promoted astrogenesis, indicating that miRNA-30b alters lineage specification via Sirt1. Overall, these results suggest that maternal diabetes alters the genes involved in neural tube

  20. Neural control and modulation of swimming speed in the larval zebrafish.

    Science.gov (United States)

    Severi, Kristen E; Portugues, Ruben; Marques, João C; O'Malley, Donald M; Orger, Michael B; Engert, Florian

    2014-08-06

    Vertebrate locomotion at different speeds is driven by descending excitatory connections to central pattern generators in the spinal cord. To investigate how these inputs determine locomotor kinematics, we used whole-field visual motion to drive zebrafish to swim at different speeds. Larvae match the stimulus speed by utilizing more locomotor events, or modifying kinematic parameters such as the duration and speed of swimming bouts, the tail-beat frequency, and the choice of gait. We used laser ablations, electrical stimulation, and activity recordings in descending neurons of the nucleus of the medial longitudinal fasciculus (nMLF) to dissect their contribution to controlling forward movement. We found that the activity of single identified neurons within the nMLF is correlated with locomotor kinematics, and modulates both the duration and oscillation frequency of tail movements. By identifying the contribution of individual supraspinal circuit elements to locomotion kinematics, we build a better understanding of how the brain controls movement. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-02-01

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

  2. Evaluation of the cranial base in amnion rupture sequence involving the anterior neural tube: implications regarding recurrence risk.

    Science.gov (United States)

    Jones, Kenneth Lyons; Robinson, Luther K; Benirschke, Kurt

    2006-09-01

    Amniotic bands can cause disruption of the cranial end of the developing fetus, leading in some cases to a neural tube closure defect. Although recurrence for unaffected parents of an affected child with a defect in which the neural tube closed normally but was subsequently disrupted by amniotic bands is negligible; for a primary defect in closure of the neural tube to which amnion has subsequently adhered, recurrence risk is 1.7%. In that primary defects of neural tube closure are characterized by typical abnormalities of the base of the skull, evaluation of the cranial base in such fetuses provides an approach for making a distinction between these 2 mechanisms. This distinction has implications regarding recurrence risk. The skull base of 2 fetuses with amnion rupture sequence involving the cranial end of the neural tube were compared to that of 1 fetus with anencephaly as well as that of a structurally normal fetus. The skulls were cleaned, fixed in 10% formalin, recleaned, and then exposed to 10% KOH solution. After washing and recleaning, the skulls were exposed to hydrogen peroxide for bleaching and photography. Despite involvement of the anterior neural tube in both fetuses with amnion rupture sequence, in Case 3 the cranial base was normal while in Case 4 the cranial base was similar to that seen in anencephaly. This technique provides a method for determining the developmental pathogenesis of anterior neural tube defects in cases of amnion rupture sequence. As such, it provides information that can be used to counsel parents of affected children with respect to recurrence risk.

  3. Access to health care for children with neural tube defects: Experiences of mothers in Zambia

    Directory of Open Access Journals (Sweden)

    Micah M. Simpamba

    2016-12-01

    Full Text Available Introduction: In Zambia, all children born with neural tube defects requiring surgery need to be referred to a tertiary level hospital in Lusaka, the capital city, where the specialists are based. The aim of this study was to explore the experiences of mothers accessing health care who had recently given birth to a child with a neural tube defect. Methods and analysis: In-depth interviews were conducted with a purposively selected sample of 20 mothers at the tertiary level hospital. The interviews were audiotaped, transcribed verbatim and translated. Content analysis was used to identify codes, which were later collapsed into categories and themes. Findings: Five themes emerged: access to health care, access to transport, access to information, concerns about family and support needs. Discussion: Barriers to access to health care included geographical barriers and barriers linked to availability. Geographical barriers were related to distance between home and the health centre, and referral between health facilities. Barriers to availability included the lack of specialist health workers at various levels, and insufficient hospital vehicles to transport mothers and children to the tertiary level hospital. The main barrier to affordability was the cost of transport, which was alleviated by either family or government support. Acceptability of the health services was affected by a lack of information, incorrect advice, the attitude of health workers and the beliefs of the family. Conclusion: Access to health care by mothers of children with neural tube defects in Zambia is affected by geographical accessibility, availability, affordability and acceptability. The supply-side barriers and demand-side barriers require different interventions to address them. This suggests that health policy is needed which ensures access to surgery and follow-up care.

  4. Systems biological approach to investigate the lack of familial link between Down's Syndrome & Neural Tube Disorders.

    Science.gov (United States)

    Ragunath, Pk; Abhinand, Pa

    2013-01-01

    Systems Biology involves the study of the interactions of biological systems and ultimately their functions. Down's syndrome (DS) is one of the most common genetic disorders which are caused by complete, or occasionally partial, triplication of chromosome 21, characterized by cognitive and language dysfunction coupled with sensory and neuromotor deficits. Neural Tube Disorders (NTDs) are a group of congenital malformations of the central nervous system and neighboring structures related to defective neural tube closure during the first trimester of pregnancy usually occurring between days 18-29 of gestation. Several studies in the past have provided considerable evidence that abnormal folate and methyl metabolism are associated with onset of DS & NTDs. There is a possible common etiological pathway for both NTDs and Down's syndrome. But, various research studies over the years have indicated very little evidence for familial link between the two disorders. Our research aimed at the gene expression profiling of microarray datasets pertaining to the two disorders to identify genes whose expression levels are significantly altered in these conditions. The genes which were 1.5 fold unregulated and having a p-value disorders were recognized and over representation analysis was carried out for each of the constituent genes. The comprehensive manual analysis of these genes yields a hypothetical understanding of the lack of familial link between DS and NTDs. There were no genes involved with folic acid present in the dense cliques. Only - CBL, EGFR genes were commonly present, which makes the allelic variants of these genes - good candidates for future studies regarding the familial link between DS and NTDs. NTD - Neural Tube Disorders, DS - Down's Syndrome, MTHFR - Methylenetetrahydrofolate reductase, MTRR- 5 - methyltetrahydrofolate-homocysteine methyltransferase reductase.

  5. Fgf8-related secondary organizers exert different polarizing planar instructions along the mouse anterior neural tube.

    Science.gov (United States)

    Crespo-Enriquez, Ivan; Partanen, Juha; Martinez, Salvador; Echevarria, Diego

    2012-01-01

    Early brain patterning depends on proper arrangement of positional information. This information is given by gradients of secreted signaling molecules (morphogens) detected by individual cells within the responding tissue, leading to specific fate decisions. Here we report that the morphogen FGF8 exerts initially a differential signal activity along the E9.5 mouse neural tube. We demonstrate that this polarizing activity codes by RAS-regulated ERK1/2 signaling and depends on the topographical location of the secondary organizers: the isthmic organizer (IsO) and the anterior neural ridge (anr) but not on zona limitans intrathalamica (zli). Our results suggest that Sprouty2, a negative modulator of RAS/ERK pathway, is important for regulating Fgf8 morphogenetic signal activity by controlling Fgf8-induced signaling pathways and positional information during early brain development.

  6. Study on tube critical heat flux data treatment with artificial neural networks

    International Nuclear Information System (INIS)

    Han Lang; Shan Jianqiang

    2005-01-01

    Prediction of the Critical Heat Flux (CHF) are analyzed by Artificial Neural Networks (ANN) to a CHF database for upward flow of water in uniformly heated vertical round tubes. The analysis is performed with three viewpoints hypothesis, i.e. for fixed inlet condition, fixed exit condition and local condition. Half of 6941 from CHF database data is trained through ANN, the trained ANN predicts the total CHF data better than any other conventional correlations, showing RMS error of 6.6%, 10.39% and 21.39%, respectively. (author)

  7. ETHANOL EXPOSURE DISRUPTS CRANIAL NEURAL CREST MIGRATION AND PRIMARY CILIA IN DEVELOPING ZEBRAFISH EMBRYOS

    OpenAIRE

    BORIC BRENET, KATICA ANDREA; BORIC BRENET, KATICA ANDREA

    2012-01-01

    Durante el desarrollo temprano la exposición a etanol (EtOH) puede causar el Síndrome de Alcohol Fetal (SAF), el cual afecta estructuras craneofaciales (CF) y partes del sistema nervioso (SN), ambos derivados de las células de la cresta neural craneal (CCNC). Por lo tanto, proponemos que la migración de las CCNC se ve afectada por la exposición a EtOH. Para determinar si la exposición a EtOH altera la migración celular, incubamos embriones de pez cebra durante 20 horas usando conc...

  8. Disruption of the folate pathway in zebrafish causes developmental defects

    Directory of Open Access Journals (Sweden)

    Lee Marina S

    2012-04-01

    Full Text Available Abstract Background Folic acid supplementation reduces the risk of neural tube defects and congenital heart defects. The biological mechanisms through which folate prevents birth defects are not well understood. We explore the use of zebrafish as a model system to investigate the role of folate metabolism during development. Results We first identified zebrafish orthologs of 12 human folate metabolic genes. RT-PCR and in situ analysis indicated maternal transcripts supply the embryo with mRNA so that the embryo has an intact folate pathway. To perturb folate metabolism we exposed zebrafish embryos to methotrexate (MTX, a potent inhibitor of dihydrofolate reductase (Dhfr an essential enzyme in the folate metabolic pathway. Embryos exposed to high doses of MTX exhibited developmental arrest prior to early segmentation. Lower doses of MTX resulted in embryos with a shortened anterior-posterior axis and cardiac defects: linear heart tubes or incomplete cardiac looping. Inhibition of dhfr mRNA with antisense morpholino oligonucleotides resulted in embryonic lethality. One function of the folate pathway is to provide essential one-carbon units for dTMP synthesis, a rate-limiting step of DNA synthesis. After 24 hours of exposure to high levels of MTX, mutant embryos continue to incorporate the thymidine analog BrdU. However, additional experiments indicate that these embryos have fewer mitotic cells, as assayed with phospho-histone H3 antibodies, and that treated embryos have perturbed cell cycles. Conclusions Our studies demonstrate that human and zebrafish utilize similar one-carbon pathways. Our data indicate that folate metabolism is essential for early zebrafish development. Zebrafish studies of the folate pathway and its deficiencies could provide insight into the underlying etiology of human birth defects and the natural role of folate in development.

  9. [Difficulties of the methods for studying environmental exposure and neural tube defects].

    Science.gov (United States)

    Borja-Aburto, V H; Bermúdez-Castro, O; Lacasaña-Navarro, M; Kuri, P; Bustamante-Montes, P; Torres-Meza, V

    1999-01-01

    To discuss the attitudes in the assessment of environmental exposures as risk factors associated with neural tube defects, and to present the main risk factors studied to date. Environmental exposures have been suggested to have a roll in the genesis of birth defects. However, studies conducted in human populations have found difficulties in the design and conduction to show such an association for neural tube defects (anencephaly, espina bifida and encephalocele) because of problems raised from: a) the frequency measures used to compare time trends and communities, b) the classification of heterogeneous malformations, c) the inclusion of maternal, paternal and fetal factors as an integrated process and, d) the assessment of environmental exposures. Hypothetically both maternal and paternal environmental exposures can produce damage before and after conception by direct action on the embryo and the fetus-placenta complex. Therefore, in the assessment of environmental exposures we need to take into account: a) both paternal and maternal exposures; b) the critical exposure period, three months before conception for paternal exposures and one month around the conceptional period for maternal exposures; c) quantitatively evaluate environmental exposures when possible, avoiding a dichotomous classification; d) the use of biological markers of exposure is highly recommended as well as markers of genetic susceptibility.

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

    Directory of Open Access Journals (Sweden)

    Komal Preet Allagh

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

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

    Science.gov (United States)

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

    2002-12-01

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

  12. Neural tube defects – disorders of neurulation and related embryonic processes

    Science.gov (United States)

    Copp, Andrew J.; Greene, Nicholas D. E.

    2014-01-01

    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 exteriorised 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 signalling 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 BMP 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, when taken as a peri-conceptional supplement, can prevent many cases. Not all NTDs respond to folic acid, however, and adjunct therapies are required for prevention of this folic acid-resistant category. PMID:24009034

  13. A case of junctional neural tube defect associated with a lipoma of the filum terminale: a new subtype of junctional neural tube defect?

    Science.gov (United States)

    Florea, Simona Mihaela; Faure, Alice; Brunel, Hervé; Girard, Nadine; Scavarda, Didier

    2018-06-01

    The embryological development of the central nervous system takes place during the neurulation process, which includes primary and secondary neurulation. A new form of dysraphism, named junctional neural tube defect (JNTD), was recently reported, with only 4 cases described in the literature. The authors report a fifth case of JNTD. This 5-year-old boy, who had been operated on during his 1st month of life for a uretero-rectal fistula, was referred for evaluation of possible spinal dysraphism. He had urinary incontinence, clubfeet, and a history of delayed walking ability. MRI showed a spinal cord divided in two, with an upper segment ending at the T-11 level and a lower segment at the L5-S1 level, with a thickened filum terminale. The JNTDs represent a recently classified dysraphism caused by an error during junctional neurulation. The authors suggest that their patient should be included in this category as the fifth case reported in the literature and note that this would be the first reported case of JNTD in association with a lipomatous filum terminale.

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

    Science.gov (United States)

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

    2015-11-01

    Melatonin, an endogenous neurohormone secreted by the pineal gland, has a variety of physiological functions and neuroprotective effects. However, its protective role on the neural tube defects (NTDs) was not very clear. The aim of this study was to investigate the effects of melatonin on the incidence of NTDs (including anencephaly, encephalocele, and spina bifida) of offspring from diabetic pregnant mice as well as its underlying mechanisms. Pregnant mice were given 10 mg/kg melatonin by daily i.p. injection from embryonic day (E) 0.5 until being killed on E11.5. Here, we showed that melatonin decreased the NTDs (especially exencephaly) rate of embryos exposed to maternal diabetes. Melatonin stimulated proliferation of neural stem cells (NSCs) under hyperglycemic condition through the extracellular regulated protein kinases (ERK) pathway. Furthermore, as a direct free radical scavenger, melatonin decreased apoptosis of NSCs exposed to hyperglycemia. In the light of these findings, it suggests that melatonin supplementation may play an important role in the prevention of neural malformations in diabetic pregnancy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Vijayraghavan, Deepthi S; Davidson, Lance A

    2017-01-30

    Neural tube defects arise from mechanical failures in the process of neurulation. At the most fundamental level, formation of the neural tube relies on coordinated, complex tissue movements that mechanically transform the flat neural epithelium into a lumenized epithelial tube (Davidson, 2012). The nature of this mechanical transformation has mystified embryologists, geneticists, and clinicians for more than 100 years. Early embryologists pondered the physical mechanisms that guide this transformation. Detailed observations of cell and tissue movements as well as experimental embryological manipulations allowed researchers to generate and test elementary hypotheses of the intrinsic and extrinsic forces acting on the neural tissue. Current research has turned toward understanding the molecular mechanisms underlying neurulation. Genetic and molecular perturbation have identified a multitude of subcellular components that correlate with cell behaviors and tissue movements during neural tube formation. In this review, we focus on methods and conceptual frameworks that have been applied to the study of amphibian neurulation that can be used to determine how molecular and physical mechanisms are integrated and responsible for neurulation. We will describe how qualitative descriptions and quantitative measurements of strain, force generation, and tissue material properties as well as simulations can be used to understand how embryos use morphogenetic programs to drive neurulation. Birth Defects Research 109:153-168, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis.

    Science.gov (United States)

    Carucci, Nicoletta; Cacci, Emanuele; Nisi, Paola S; Licursi, Valerio; Paul, Yu-Lee; Biagioni, Stefano; Negri, Rodolfo; Rugg-Gunn, Peter J; Lupo, Giuseppe

    2017-04-01

    During vertebrate neural development, positional information is largely specified by extracellular morphogens. Their distribution, however, is very dynamic due to the multiple roles played by the same signals in the developing and adult neural tissue. This suggests that neural progenitors are able to modify their competence to respond to morphogen signalling and autonomously maintain positional identities after their initial specification. In this work, we take advantage of in vitro culture systems of mouse neural stem/progenitor cells (NSPCs) to show that NSPCs isolated from rostral or caudal regions of the mouse neural tube are differentially responsive to retinoic acid (RA), a pivotal morphogen for the specification of posterior neural fates. Hoxb genes are among the best known RA direct targets in the neural tissue, yet we found that RA could promote their transcription only in caudal but not in rostral NSPCs. Correlating with these effects, key RA-responsive regulatory regions in the Hoxb cluster displayed opposite enrichment of activating or repressing histone marks in rostral and caudal NSPCs. Finally, RA was able to strengthen Hoxb chromatin activation in caudal NSPCs, but was ineffective on the repressed Hoxb chromatin of rostral NSPCs. These results suggest that the response of NSPCs to morphogen signalling across the rostrocaudal axis of the neural tube may be gated by the epigenetic configuration of target patterning genes, allowing long-term maintenance of intrinsic positional values in spite of continuously changing extrinsic signals.

  17. Management of Labor and Delivery After Fetoscopic Repair of an Open Neural Tube Defect.

    Science.gov (United States)

    Kohn, Jaden R; Rao, Vibha; Sellner, Allison A; Sharhan, Dina; Espinoza, Jimmy; Shamshirsaz, Alireza A; Whitehead, William E; Belfort, Michael A; Sanz Cortes, Magdalena

    2018-06-01

    To report labor, delivery, and neonatal outcomes in a cohort of women delivering neonates who had undergone fetoscopic neural tube defect repair. We conducted a retrospective cohort study from April 2014 to January 2018. All patients met Management of Myelomeningocele Study eligibility criteria. We included patients with completed second-trimester fetoscopic neural tube defect repair (laparotomy, uterine exteriorization, and minimally invasive access through two or three uterine ports) followed by standardized management of labor and delivery at our institution. Outcomes included rates of vaginal delivery, term delivery, and intrapartum cesarean delivery as well as obstetric and neonatal outcomes after oxytocin. Complications of interest included preterm prelabor rupture of membranes, chorioamnionitis, uterine dehiscence or rupture, 5-minute Apgar score less than 7, and neonatal acidosis (umbilical artery pH less than 7.15). Thirty-four patients had fetoscopic repair, followed by 17 vaginal deliveries (50%, 95% CI 32-68%). Median gestational age was 38 1/7 weeks at vaginal delivery (range 26 0/7-40 2/7 weeks of gestation) and 37 1/7 weeks of gestation at cesarean delivery (range 25 5/7-40 5/7 weeks of gestation); 62% of deliveries occurred at term. Eight patients had prelabor cesarean delivery: three nonurgent and five urgent (for nonreassuring fetal heart tracings). Twenty-six patients labored; six were induced and 20 labored spontaneously. Of the latter, five were augmented. Of 26 laboring patients, 17 delivered vaginally and nine underwent urgent cesarean delivery (35%, 95% CI 17-56%; seven nonreassuring fetal heart tracings and two breech). There were no cases of uterine rupture or dehiscence. Most (94%, 95% CI 80-99%) had normal 5-minute Apgar scores; one neonate (3%, 95% CI 0-15%) had acidosis but normal Apgar scores. Our data regarding trial of labor, use of low-dose oxytocin, and vaginal delivery after prenatal fetoscopic neural tube defect repair are

  18. Syndromes, disorders and maternal risk factors associated with neural tube defects (I).

    Science.gov (United States)

    Chen, Chih-Ping

    2008-03-01

    Fetuses with neural tube defects (NTDs) may be associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization ( Ds )-like human malformations, isolated hemihyperplasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

  19. Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (IV

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-06-01

    Full Text Available Fetuses with neural tube defects (NTDs may be associated with maternal and fetal risk factors. This article provides a comprehensive review of maternal and fetal risk factors associated with NTDs, such as infertility, periconceptional clomiphene use and assisted reproductive technology, periconceptional folic acid deficiency and effects offolic acid supplementation and fortification on NTD rates, periconceptional vitamin B1 2 deficiency, single nucleotide polymorphisms and polymorphisms in genes of folate metabolism, and maternal autoantibodies to folate receptors. NTDs associated with maternal and fetal risk factors are an important cause of NTDs. Perinatal identification of NTDs should alert the clinician to the maternal and fetal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling. [Taiwan J Obstet Cynecol 2008;47(2:141-1 50

  20. Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (II

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-03-01

    Full Text Available Fetuses with neural tube defects (NTDs maybe associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as Currarino syndrome, sacral defect with anterior meningocele, Jarcho-Levin syndrome (spondylo-costal dysostosis, lateral meningocele syndrome, neurofibromatosis type I, Marfan syndrome, and hyperthermia. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

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

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-09-01

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

  2. Long term trends in prevalence of neural tube defects in Europe

    DEFF Research Database (Denmark)

    Khoshnood, Babak; Loane, Maria; Walle, Hermien de

    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......-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...

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

    Directory of Open Access Journals (Sweden)

    Xiaoqing Zhu

    2016-02-01

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

  4. Are concentrations of alkaline earth elements in maternal hair associated with risk of neural tube defects?

    Science.gov (United States)

    Li, Zhenjiang; Wang, Bin; Huo, Wenhua; Liu, Yingying; Zhu, Yibing; Xie, Jing; Li, Zhiwen; Ren, Aiguo

    2017-12-31

    The relationship between maternal intake of alkaline earth elements (AEEs) during the period of neural tube closure and the risk of neural tube defects (NTDs) is still unclear. We propose that AEE deficiency during the early period of pregnancy is associated with an elevated risk of NTDs in the offspring. In this study, we recruited 191 women with NTD-affected pregnancies (cases) and 261 women who delivered healthy infants (controls). The concentrations of four AEEs (Ca, Mg, Sr, Ba) in maternal hair sections that grew during early pregnancy were analyzed. Information on the dietary habits of the mothers was also collected by questionnaire. Higher concentrations of the four AEEs in hair had protective effects against the risk of total NTDs, with odds ratios with 95% confidence interval (comparing groups separated by each median level) of 0.44 (0.28-0.68) for Mg, 0.56 (0.36-0.87) for Ca, 0.45 (0.28-0.70) for Sr, and 0.41 (0.26-0.65) for Ba. Significant negative dose-response trends were identified for the relationships between the four AEE concentrations in maternal hair and the risks of anencephaly and spina bifida, but not for encephalocele. The frequencies of maternal consumption of fresh green vegetables, fresh fruit, and meat or fish were positively correlated with the concentrations of AEEs in hair. We concluded that the maternal intake of AEEs may play an important role in preventing NTD formation in offspring, and that this intake is related to maternal dietary habits of consuming fresh green vegetables, fresh fruit, and fish or meat. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-03-28

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

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

    International Nuclear Information System (INIS)

    Wlodarczyk, Bogdan J.; Tang, Louisa S.; Triplett, Aleata; Aleman, Frank; Finnell, Richard H.

    2006-01-01

    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 α-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

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

    Directory of Open Access Journals (Sweden)

    Jennifer N. Murdoch

    2014-10-01

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

  8. Prenatal screening, diagnosis, and pregnancy management of fetal neural tube defects.

    Science.gov (United States)

    Wilson, R Douglas

    2014-10-01

    To provide obstetrical and genetic health care practitioners with guidelines and recommendations for prenatal screening, diagnosis, and obstetrical management of fetal open and closed neural tube defects (OCNTD). This review includes prenatal screening and diagnostic techniques currently being used for the detection of OCNTD including maternal serum alpha fetoprotein screening, ultrasound, fetal magnetic resonance imaging, and amniocentesis. To improve prenatal screening, diagnosis, and obstetrical management of OCNTD while taking into consideration patient care, efficacy, cost, and care procedures. Published literature was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in November, 2013, using appropriate controlled vocabulary and key words (e.g., prenatal screening, congenital anomalies, neural tube defects, alpha fetoprotein, ultrasound scan, magnetic resonance imaging). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from 1977 to 2012. Searches were updated on a regular basis and incorporated in the guideline to November 30, 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. An online survey of health care practitioners was also reviewed. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). This review will provide health care practitioners with a better understanding of the available prenatal screening methods for OCNTD and the benefits and risks associated with each technique to allow evidenced-based decisions on OCNTD screening, diagnosis, and obstetrical management.

  9. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?

    Science.gov (United States)

    Obeid, Rima; Holzgreve, Wolfgang; Pietrzik, Klaus

    2013-09-01

    Women have higher requirements for folate during pregnancy. An optimal folate status must be achieved before conception and in the first trimester when the neural tube closes. Low maternal folate status is causally related to neural tube defects (NTDs). Many NTDs can be prevented by increasing maternal folate intake in the preconceptional period. Dietary folate is protective, but recommending increasing folate intake is ineffective on a population level particularly during periods of high demands. This is because the recommendations are often not followed or because the bioavailability of food folate is variable. Supplemental folate [folic acid (FA) or 5-methyltetrahydrofolate (5-methylTHF)] can effectively increase folate concentrations to the level that is considered to be protective. FA is a synthetic compound that has no biological functions unless it is reduced to dihydrofolate and tetrahydrofolate. Unmetabolized FA appears in the circulation at doses of >200 μg. Individuals show wide variations in their ability to reduce FA. Carriers of certain polymorphisms in genes related to folate metabolism or absorption can better benefit from 5-methylTHF instead of FA. 5-MethylTHF [also known as (6S)-5-methylTHF] is the predominant natural form that is readily available for transport and metabolism. In contrast to FA, 5-methylTHF has no tolerable upper intake level and does not mask vitamin B12 deficiency. Supplementation of the natural form, 5-methylTHF, is a better alternative to supplementation of FA, especially in countries not applying a fortification program. Supplemental 5-methylTHF can effectively improve folate biomarkers in young women in early pregnancy in order to prevent NTDs.

  10. A regulating element essential for PDGFRA transcription is recognized by neural tube defect-associated PRX homeobox transcription factors

    NARCIS (Netherlands)

    Joosten, Paul H. L. J.; Toepoel, Mascha; van Oosterhout, Dirk; Afink, Gijs B.; van Zoelen, Everardus J. J.

    2002-01-01

    We have previously shown that deregulated expression of the platelet-derived growth factor alpha-receptor (PDGFRA) can be associated with neural tube defects (NTDs) in both men and mice. In the present study, we have investigated the transcription factors that control the up-regulation of PDGFRA

  11. Prevalentie, klinisch beeld en prognose van neuralebuisdefecten in Nederland [Prevalence, presentation and prognosis of neural tube defects in the Netherlands

    NARCIS (Netherlands)

    Ouden, A.L. den; Hirasing, R.A.; Buitendijk, S.E.; Jong-van de Berg, L.T.W. de; Walle, H.E.K. de; Cornel, M.C.

    1996-01-01

    Objective. To determine the live birth prevalence of neural tube defects (NTD) in the Netherlands and describe the clinical picture. Design. Descriptive. Setting. TNO Prevention and Health, Leiden, the Netherlands. Method. Data collected through active surveillance of NTD on a monthly basis by

  12. Epigenetic profiles in children with a neural tube defect; a case-control study in two populations

    NARCIS (Netherlands)

    L. Stolk (Lisette); M.I. Both (Marieke); N.H. van Mill (Nina); M.M.P.J. Verbiest (Michael); P.H.C. Eilers (Paul); H. Zhu (Huiping); L. Suarez (Lucina); A.G. Uitterlinden (André); R.P.M. Steegers-Theunissen (Régine)

    2013-01-01

    textabstractFolate 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

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

    NARCIS (Netherlands)

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

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

  14. Maternal Antenatal Bereavement and Neural Tube Defect in Live-Born Offspring: A Cohort Study.

    Directory of Open Access Journals (Sweden)

    Katja Glejsted Ingstrup

    Full Text Available Maternal emotional stress during pregnancy has previously been associated with congenital neural malformations, but most studies are based on data collected retrospectively. The objective of our study was to investigate associations between antenatal maternal bereavement due to death of a close relative and neural tube defects (NTDs in the offspring.We performed a register-based cohort study including all live-born children (N = 1,734,190 from 1978-2008. Exposure was bereavement due to loss of a close relative from one year before conception to the end of the first trimester of pregnancy. The outcome was NTDs in the offspring according to the International Classification of Disease. We used multivariate logistic regression to estimate prevalence odds ratios (ORs.A total of 2% children were born to mothers who lost a close relative prenatally. During 30 years of follow-up, 1,115 children were diagnosed with any NTDs: spina bifida (n = 889, anencephaly (n = 85 and encephalocele (n = 164. And 23 children were diagnosed with two types of NTDs. Overall, when comparing bereaved mothers to non-bereaved mothers, no significant increased prevalence of NTDs in the offspring was seen (OR = 0.84; 95% confidence interval: 0.52-1.33.Overall maternal bereavement in the antenatal period was not related to NTDs in liveborn offspring.

  15. Risk factors of neural tube defects: A reality of Batna region in Algeria

    Directory of Open Access Journals (Sweden)

    Romyla Bourouba

    2018-07-01

    Full Text Available Background: Neural tube defects (NTDs are severe birth defects, with genetic and/or environmental risk factors. Aim: The objective of this study was to analyze data on NTDs cases at the Batna Maternity Hospital and to investigate some environmental and two genetic risk factors suspected in the etiology of NTDs. Subjects and methods: This study was conducted on 82 healthy participants and 48 mothers with an NTD child. Peripheral blood samples were collected, in EDTA tubes and frozen at −20 °C until DNA extraction by conventional method. Genetic analysis of methylene tetrahydrofolate reductase C677T polymorphism was determined by real time PCR, while cystathionine-beta-synthase 844 insertion was investigated by traditional PCR. Chi-square analyses were used to evaluate differences in the distribution of data. The odds-ratio was also calculated. A P-value less than 0.05 were significant. Results: The incidence of NTD in Batna region was 1.58 per 1000 births. The rate of NTD was significantly higher in females than males, highest affected NTD newborn’s was observed in mothers aged between 25 and 29 years and the consanguinity among all NTD cases was 30%. Data showed no significant association of NTDs with personal education, obesity, diabetes, but regarding folic acid consumption, about 86% of NTD’s mothers in our region didn’t take pre-conceptional supplementation with this vitamin .Genetic factors results didn't show a significant association of NTDs with specific mutations of the variant C677T MTHFR, and no gene-gene interaction of CBS insertion and C677T polymorphism was found, despite a significant difference in heterozygote frequency of CBS 844ins68 genotype between NTD’s mothers and controls, OR: 2.85(1.18–6.88. Conclusion: NTD represents a real public health problem in Batna, Algeria. Various genetic and/or nutritional factors are implicated, although the mechanism is not clear. We suggest that further research should continue

  16. Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (I

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-03-01

    Full Text Available Fetuses with neural tube defects (NTDs maybe associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization (Ds-like human malformations, isolated hemihyper-plasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

  17. Predicting diametral creep of the pressure tubes in CANDU reactors using fuzzy neural networks

    International Nuclear Information System (INIS)

    Lee, Jae Yong; Na, Man Gyun; Park, Jong Ho

    2011-01-01

    Pressure tube (PT) creep is one of the principal aging mechanisms governing the heat transfer and hydraulic degradation of the heat transport system (HTS) in Canada deuterium uranium reactors. PT diametral creep affects the thermal hydraulic characteristics of coolant channels and the critical heat flux (CHF). CHF is a key parameter in determining the critical channel power, which is used in the trip setpoint calculations of regional overpower protection systems. This paper aims to predict PT diametral creep using the measured signals of the HTS by applying fuzzy neural networks (FNNs) according to operating conditions. The FNN model was optimized in terms of its fuzzy rules and parameters by a genetic algorithm combined with the least-squares method. Informative data that demonstrate the system's characteristic behavior were selected to train the FNN model using the subtractive clustering method. The proposed FNN model for predicting PT diametral creep was verified using the operating data of the Wolsong Unit 1 nuclear power plant in Korea. It was known that the FNN could predict the PT diametral creep accurately. Statistical and analytical uncertainty analysis methods were applied to the models and their uncertainties were evaluated using 60 sampled training and optimization data sets, as well as two fixed test data sets. (author)

  18. Folate status in women of reproductive age as basis of neural tube defect risk assessment.

    Science.gov (United States)

    Bailey, Lynn B; Hausman, Dorothy B

    2018-02-01

    Reliable folate status data for women of reproductive age (WRA) to assess global risk for neural tube defects (NTDs) are needed. We focus on a recent recommendation by the World Health Organization that a specific "optimal" red blood cell (RBC) folate concentration be used as the sole indicator of NTD risk within a population and discuss how to best apply this guidance to reach the goal of assessing NTD risk globally. We also emphasize the importance of using the microbiologic assay (MBA) as the most reliable assay for obtaining comparable results for RBC folate concentration across time and countries, the need for harmonization of the MBA through use of consistent key reagents and procedures within laboratories, and the requirement to apply assay-matched cutoffs for folate deficiency and insufficiency. To estimate NTD risk globally, the ideal scenario would be to have country-specific population-based surveys of RBC folate in WRA determined utilizing a harmonized MBA, as was done in recent studies in Guatemala and Belize. We conclude with guidance on next steps to best navigate the road map toward the goal of generating reliable folate status data on which to assess NTD risk in WRA in low- and middle-income countries. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

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

    LENUS (Irish Health Repository)

    Delany, C

    2011-01-01

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

  20. Drinking water treatment is not associated with an observed increase in neural tube defects in mice

    Science.gov (United States)

    Melin, Vanessa E.; Johnstone, David W.; Etzkorn, Felicia A.

    2018-01-01

    Disinfection by-products (DBPs) arise when natural organic matter in source water reacts with disinfectants used in the water treatment process. Studies have suggested an association between DBPs and birth defects. Neural tube defects (NTDs) in embryos of untreated control mice were first observed in-house in May 2006 and have continued to date. The source of the NTD-inducing agent was previously determined to be a component of drinking water. Tap water samples from a variety of sources were analyzed for trihalomethanes (THMs) to determine if they were causing the malformations. NTDs were observed in CD-1 mice provided with treated and untreated surface water. Occurrence of NTDs varied by water source and treatment regimens. THMs were detected in tap water derived from surface water but not detected in tap water derived from a groundwater source. THMs were absent in untreated river water and laboratory purified waters, yet the percentage of NTDs in untreated river water were similar to the treated water counterpart. These findings indicate that THMs were not the primary cause of NTDs in the mice since the occurrence of NTDs was unrelated to drinking water disinfection. PMID:24497082

  1. Risk factors for neural tube defects in Riyadh City, Saudi Arabia: Case-control study.

    Science.gov (United States)

    Salih, Mustafa A M; Murshid, Waleed R; Mohamed, Ashry Gad; Ignacio, Lena C; de Jesus, Julie E; Baabbad, Rubana; El Bushra, Hassan M

    2014-01-01

    Both genetic and non-genetic environmental factors are involved in the etiology of neural tube defects (NTD) which affect 0.5-2/1000 pregnancies worldwide. This study aimed to explore the risk factors for the development of NTD in Saudi population, and highlight identifiable and preventable causes. Similar studies are scarce in similar populations ofthe Arabian Peninsula and North Africa. This is an unmatched concurrent case-control study including NTD cases born at King Khalid University Hospital, Riyadh during a 4-year period (2002-2006). The case-control study included 25 cases and 125 controls (case: control ratio of 1:5). Years of formal education, employment, household environment (including availability of air conditioning) and rate of parental consanguinity did not differ between mothers of cases and controls. Significantly higher proportion of mothers of cases had history of stillbirth compared to control mothers (16% vs 4.1%, P=0.02). Also family history of hydrocephalus and congenital anomalies were more prevalent in cases than controls (P values=0.0000 and 0.003, respectively). There was significant protective effect of periconceptional folic acid consumption both prior to conception (OR 0.02, 95% CI 0.00-0.07) and during the first 6 weeks of conception (OR 0.13, 95% CI 0.04-0.39). Further research, including a larger cohort, is required to enable ascertainment of gene-nutrient and gene environment interactions associated with NTD in Saudi Arabia.

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

    LENUS (Irish Health Repository)

    McDonnell, R

    2014-03-18

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

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

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-09-01

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

  5. MTHFD1 polymorphism as maternal risk for neural tube defects: a meta-analysis.

    Science.gov (United States)

    Zheng, Jinyu; Lu, Xiaocheng; Liu, Hao; Zhao, Penglai; Li, Kai; Li, Lixin

    2015-04-01

    Recently, the association between methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G1958A polymorphism and neural tube defects (NTD) susceptibility has been widely investigated; however, the results remained inconclusive. Hence, we conducted a meta-analysis to evaluate the effect of MTHFD1 G1958A polymorphism on NTD. The relative literatures were identified by search of the electronic databases PubMed, MEDLINE, and EMBASE. The extracted data were statistically analyzed, and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the association strength using Stata version 11.0 software. Finally, ten studies met our inclusion criteria, including 2,132/4,082 in NTD infants and controls; 1,402/3,136 in mothers with NTD offspring and controls; and 993/2,879 in fathers with NTD offspring and controls. This meta-analysis showed that, compared with the mothers with GG genotype, the women with AA genotype had an increased risk of NTD in their offspring, with OR values and 95 % CI at 1.39 (1.16-1.68), p < 0.001. Interestingly, fathers with AG genotype had a significant decreased risk of NTD offspring (OR = 0.79, 95 % CI = 0.66-0.94, p = 0.009). However, there was no significant association between the MTHFD1 G1958A polymorphism in NTD patients and the risk of NTD. In conclusion, the present meta-analysis provided evidence of the association between maternal MTHFD1 G1958A polymorphism and NTD susceptibility.

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

    Science.gov (United States)

    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

  7. Management of abnormal serum markers in the absence of aneuploidy or neural tube defects

    Science.gov (United States)

    Schnettler, William T.; Hacker, Michele R.; Barber, Rachel E.; Rana, Sarosh

    2013-01-01

    Objective Few guidelines address the management of pregnancies complicated by abnormal maternal serum analytes (MSAs) in the absence of aneuploidy or neural tube defects (NTDs). Our objective was to gather preliminary data regarding current opinions and management strategies among perinatologists in the US. Methods This survey of Maternal Fetal Medicine (MFM) physicians and fellows used a secure electronic web-based data capture tool. Results A total of 545 potential participants were contacted, and 136 (25%) responded. The majority were experienced academic physicians with robust practices. Nearly all (97.7%) respondents reported a belief in an association between abnormal MSAs and adverse pregnancy outcomes other than aneuploidy or NTDs. Plasma protein A (PAPP-A) and α-fetoprotein (AFP) were most often chosen as markers demonstrating a strong association with adverse outcomes. Most (86.9%) respondents acknowledged that abnormal MSAs influenced their counseling approach, and the majority (80.1%) offered additional ultrasound examinations. Nearly half started at 28 weeks and almost one-third at 32 weeks. Respondents acknowledging a relevant protocol in their hospital or practice were more likely to offer additional antenatal testing (p = 0.01). Conclusions Although most perinatologists were in agreement regarding the association of MSAs with adverse pregnancy outcomes, a lack of consensus exists regarding management strategies. PMID:22372385

  8. U-tube steam generator empirical model development and validation using neural networks

    International Nuclear Information System (INIS)

    Parlos, A.G.; Chong, K.T.; Atiya, A.

    1992-01-01

    Empirical modeling techniques that use model structures motivated from neural networks research have proven effective in identifying complex process dynamics. A recurrent multilayer perception (RMLP) network was developed as a nonlinear state-space model structure along with a static learning algorithm for estimating the parameter associated with it. The methods developed were demonstrated by identifying two submodels of a U-tube steam generator (UTSG), each valid around an operating power level. A significant drawback of this approach is the long off-line training times required for the development of even a simplified model of a UTSG. Subsequently, a dynamic gradient descent-based learning algorithm was developed as an accelerated alternative to train an RMLP network for use in empirical modeling of power plants. The two main advantages of this learning algorithm are its ability to consider past error gradient information for future use and the two forward passes associated with its implementation. The enhanced learning capabilities provided by the dynamic gradient descent-based learning algorithm were demonstrated via the case study of a simple steam boiler power plant. In this paper, the dynamic gradient descent-based learning algorithm is used for the development and validation of a complete UTSG empirical model

  9. Incidence of neural tube defects in the natural radiation coastal areas of Kerala

    International Nuclear Information System (INIS)

    Jaikrishan, G.; Sudheer, K.R.; Andrews, V.J.; Koya, P.K.M.; Cheriyan, V.D.; Seshadri, M.

    2010-01-01

    All consecutive births in selected government hospitals in and around the high level natural background radiation areas (HLNRA) of Kerala were monitored for congenital malformations observable at birth since 1995. The HLNR area, a coastal strip of land about 55 km in length and 0.5 km in breadth from Purakkad in the north in Alleppey district to Sakthikulangara in the south of Quilon district, stands out among the most prominent background radiation areas of the world. Natural deposit of monazite sand, containing Thorium (8-10%), Uranium (0.3%) and corresponding decay products, is the source of elevated background radiation, ranging from < 1 to 45 mGy/year. Wide variation in dose, due to the patchy and non-uniform distribution of Monazite sand, enables in built controls. High population density, limited migration, ethnic diversity, good literacy, health awareness, institutionalized births and acceptance of small family norm are some of the key features of the population. Areas with a mean radiation dose of more than 1.5 mGy/year were treated as HLNR areas and areas with a dose level of 1.5 mGy/year or less were treated as normal level radiation (NLNR) areas. The study carried out since 1995 does not seem to implicate HLNR in the incidence of neural tube defects among newborns

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

    Directory of Open Access Journals (Sweden)

    Kelei Li

    2016-11-01

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

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

    Science.gov (United States)

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

    2013-10-01

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

  12. Mature teratoma in association with neural tube defect (occipital encephalocele): series of four cases and review of the literature.

    Science.gov (United States)

    Goyal, Nishant; Singh, Pankaj Kumar; Kakkar, Aanchal; Sharma, Meher Chand; Mahapatra, Ashok Kumar

    2012-01-01

    Both occipital encephalocele and teratomas are midline congenital malformations. Encephalocele is a form of neural tube defect in which there is a congenital defect of the cranium through which occurs a protrusion of brain matter or meninges, while teratoma is a tumor derived from all three germ layers. The association between occipital encephalocele and teratoma has not been reported to date. In the present study, the authors present a series of four such cases. Copyright © 2012 S. Karger AG, Basel.

  13. Influence of the neural tube/notochord complex on MyoD expression and cellular proliferation in chicken embryos

    Directory of Open Access Journals (Sweden)

    H.J. Alves

    2003-02-01

    Full Text Available Important advances have been made in understanding the genetic processes that control skeletal muscle formation. Studies conducted on quails detected a delay in the myogenic program of animals selected for high growth rates. These studies have led to the hypothesis that a delay in myogenesis would allow somitic cells to proliferate longer and consequently increase the number of embryonic myoblasts. To test this hypothesis, recently segmented somites and part of the unsegmented paraxial mesoderm were separated from the neural tube/notochord complex in HH12 chicken embryos. In situ hybridization and competitive RT-PCR revealed that MyoD transcripts, which are responsible for myoblast determination, were absent in somites separated from neural tube/notochord (1.06 and 0.06 10-3 attomol MyoD/1 attomol ß-actin for control and separated somites, respectively; P<0.01. However, reapproximation of these structures allowed MyoD to be expressed in somites. Cellular proliferation was analyzed by immunohistochemical detection of incorporated BrdU, a thymidine analogue. A smaller but not significant (P = 0.27 number of proliferating cells was observed in somites that had been separated from neural tube/notochord (27 and 18 for control and separated somites, respectively. These results confirm the influence of the axial structures on MyoD activation but do not support the hypothesis that in the absence of MyoD transcripts the cellular proliferation would be maintained for a longer period of time.

  14. A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization.

    Science.gov (United States)

    Jao, Li-En; Appel, Bruce; Wente, Susan R

    2012-04-01

    In humans, GLE1 is mutated in lethal congenital contracture syndrome 1 (LCCS1) leading to prenatal death of all affected fetuses. Although the molecular roles of Gle1 in nuclear mRNA export and translation have been documented, no animal models for this disease have been reported. To elucidate the function of Gle1 in vertebrate development, we used the zebrafish (Danio rerio) model system. gle1 mRNA is maternally deposited and widely expressed. Altering Gle1 using an insertional mutant or antisense morpholinos results in multiple defects, including immobility, small eyes, diminished pharyngeal arches, curved body axis, edema, underdeveloped intestine and cell death in the central nervous system. These phenotypes parallel those observed in LCCS1 human fetuses. Gle1 depletion also results in reduction of motoneurons and aberrant arborization of motor axons. Unexpectedly, the motoneuron deficiency results from apoptosis of neural precursors, not of differentiated motoneurons. Mosaic analyses further indicate that Gle1 activity is required extrinsically in the environment for normal motor axon arborization. Importantly, the zebrafish phenotypes caused by Gle1 deficiency are only rescued by expressing wild-type human GLE1 and not by the disease-linked Fin(Major) mutant form of GLE1. Together, our studies provide the first functional characterization of Gle1 in vertebrate development and reveal its essential role in actively dividing cells. We propose that defective GLE1 function in human LCCS1 results in both neurogenic and non-neurogenic defects linked to the apoptosis of proliferative organ precursors.

  15. Deep Convolutional Neural Networks for Endotracheal Tube Position and X-ray Image Classification: Challenges and Opportunities.

    Science.gov (United States)

    Lakhani, Paras

    2017-08-01

    The goal of this study is to evaluate the efficacy of deep convolutional neural networks (DCNNs) in differentiating subtle, intermediate, and more obvious image differences in radiography. Three different datasets were created, which included presence/absence of the endotracheal (ET) tube (n = 300), low/normal position of the ET tube (n = 300), and chest/abdominal radiographs (n = 120). The datasets were split into training, validation, and test. Both untrained and pre-trained deep neural networks were employed, including AlexNet and GoogLeNet classifiers, using the Caffe framework. Data augmentation was performed for the presence/absence and low/normal ET tube datasets. Receiver operating characteristic (ROC), area under the curves (AUC), and 95% confidence intervals were calculated. Statistical differences of the AUCs were determined using a non-parametric approach. The pre-trained AlexNet and GoogLeNet classifiers had perfect accuracy (AUC 1.00) in differentiating chest vs. abdominal radiographs, using only 45 training cases. For more difficult datasets, including the presence/absence and low/normal position endotracheal tubes, more training cases, pre-trained networks, and data-augmentation approaches were helpful to increase accuracy. The best-performing network for classifying presence vs. absence of an ET tube was still very accurate with an AUC of 0.99. However, for the most difficult dataset, such as low vs. normal position of the endotracheal tube, DCNNs did not perform as well, but achieved a reasonable AUC of 0.81.

  16. Feature Binding in Zebrafish

    Directory of Open Access Journals (Sweden)

    P Neri

    2012-07-01

    Full Text Available Binding operations are primarily ascribed to cortex or similarly complex avian structures. My experiments show that the zebrafish, a lower vertebrate lacking cortex, supports visual feature binding of form and motion for the purpose of social behavior. These results challenge the notion that feature binding may require highly evolved neural structures and demonstrate that the nervous system of lower vertebrates can afford unexpectedly complex computations.

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

    International Nuclear Information System (INIS)

    Garcia, Gabe V.

    2005-01-01

    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

  18. Do neural tube defects lead to structural alterations in the human bladder?

    Science.gov (United States)

    Pazos, Helena M F; Lobo, Márcio Luiz de P; Costa, Waldemar S; Sampaio, Francisco J B; Cardoso, Luis Eduardo M; Favorito, Luciano Alves

    2011-05-01

    Anencephaly is the most severe neural tube defect in human fetuses. The objective of this paper is to analyze the structure of the bladder in anencephalic human fetuses. We studied 40 bladders of normal human fetuses (20 male and 20 female, aged 14 to 23 WPC) and 12 bladders of anencephalic fetuses (5 male and 7 female, aged 18 to 22 WPC). The bladders were removed and processed by routine histological techniques. Stereological analysis of collagen, elastic system fibers and smooth muscle was performed in sections. Data were expressed as volumetric density (Vv-%). The images were captured with Olympus BX51 microscopy and Olympus DP70 camera. The stereological analysis was done using the software Image Pro and Image J. For biochemical analysis, samples were fixed in acetone, and collagen concentrations were expressed as micrograms of hydroxyproline per mg of dry tissue. Means were statistically compared using the unpaired t-test (p<0.05). We observed a significant increase (p<0.0001) in the Vv of collagen in the bladders of anencephalic fetuses (69.71%) when compared to normal fetuses (52.74%), and a significant decrease (p<0.0001) in the Vv of smooth muscle cells in the bladders of anencephalic fetuses (23.96%) when compared to normal fetuses (38.35%). The biochemical analyses showed a higher concentration of total collagen in the bladders of anencephalic fetuses (37354 µg/mg) when compared to normal fetuses (48117 µg/mg, p<0.02). The structural alterations of the bladder found in this study may suggest the existence of functional alterations in the bladder of anencephalic human fetuses.

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

    LENUS (Irish Health Repository)

    Ward, M

    2004-10-01

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

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

    International Nuclear Information System (INIS)

    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 (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-α-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.

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

    International Nuclear Information System (INIS)

    Brender, Jean D.; Suarez, Lucina; Felkner, Marilyn; Gilani, Zunera; Stinchcomb, David; Moody, Karen; Henry, Judy; Hendricks, Katherine

    2006-01-01

    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 >=5.62μg/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

  2. Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

    Science.gov (United States)

    Trovato, Maria; D'Armiento, Maria; Lavra, Luca; Ulivieri, Alessandra; Dominici, Roberto; Vitarelli, Enrica; Grosso, Maddalena; Vecchione, Raffaella; Barresi, Gaetano; Sciacchitano, Salvatore

    2007-02-01

    Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

  3. Differences in neural crest sensitivity to ethanol account for the infrequency of anterior segment defects in the eye compared with craniofacial anomalies in a zebrafish model of fetal alcohol syndrome.

    Science.gov (United States)

    Eason, Jessica; Williams, Antionette L; Chawla, Bahaar; Apsey, Christian; Bohnsack, Brenda L

    2017-09-01

    Ethanol (ETOH) exposure during pregnancy is associated with craniofacial and neurologic abnormalities, but infrequently disrupts the anterior segment of the eye. In these studies, we used zebrafish to investigate differences in the teratogenic effect of ETOH on craniofacial, periocular, and ocular neural crest. Zebrafish eye and neural crest development was analyzed by means of live imaging, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, immunostaining, detection of reactive oxygen species, and in situ hybridization. Our studies demonstrated that foxd3-positive neural crest cells in the periocular mesenchyme and developing eye were less sensitive to ETOH than sox10-positive craniofacial neural crest cells that form the pharyngeal arches and jaw. ETOH increased apoptosis in the retina, but did not affect survival of periocular and ocular neural crest cells. ETOH also did not increase reactive oxygen species within the eye. In contrast, ETOH increased ventral neural crest apoptosis and reactive oxygen species production in the facial mesenchyme. In the eye and craniofacial region, sod2 showed high levels of expression in the anterior segment and in the setting of Sod2 knockdown, low levels of ETOH decreased migration of foxd3-positive neural crest cells into the developing eye. However, ETOH had minimal effect on the periocular and ocular expression of transcription factors (pitx2 and foxc1) that regulate anterior segment development. Neural crest cells contributing to the anterior segment of the eye exhibit increased ability to withstand ETOH-induced oxidative stress and apoptosis. These studies explain the rarity of anterior segment dysgenesis despite the frequent craniofacial abnormalities in fetal alcohol syndrome. Birth Defects Research 109:1212-1227, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

    LENUS (Irish Health Repository)

    Pangilinan, Faith

    2012-08-02

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

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

    Directory of Open Access Journals (Sweden)

    Xiaoli Chen

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

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

    Directory of Open Access Journals (Sweden)

    Pangilinan Faith

    2012-08-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ibrahim Zaganjor

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

  9. Reduced folate carrier polymorphism (80A-->G) and neural tube defects.

    Science.gov (United States)

    De Marco, Patrizia; Calevo, Maria Grazia; Moroni, Anna; Merello, Elisa; Raso, Alessandro; Finnell, Richard H; Zhu, Huiping; Andreussi, Luciano; Cama, Armando; Capra, Valeria

    2003-03-01

    Transport of folates in mammalian cells occurs by a carrier-mediated mechanism. The human folate carrier (RFC-1) gene has been isolated and characterized. Within this gene, a common polymorphism, 80A-->G, changing a histidine to an arginine in exon 2 (H27R), was recently identified. Defects in folate metabolism, such as defective carrier molecules, could be implicated in the etiology of neural tube defects (NTDs). In the present case-control study, we recruited 174 Italian probands with nonsyndromic NTD, 43 mothers, 53 fathers and 156 control individuals and evaluated the impact of RFC-1 variant on NTD risk. A statistically significant risk was calculated for the 80GG genotype of the NTD cases (OR=2.35; 95% CI 1.21-4.58) and mothers (OR=2.74; 95% CI 0.92-8.38). On the contrary, the heterozygous genotype of the mothers and both heterozygous and homozygous genotypes of the fathers did not seem to be significant NTD risk factors. Furthemore, according to the multifactorial inheritance of NTDs, we demonstrated that the combined genotypes for MTHFR 1298A-->C and RFC-1 80A-->G polymorphisms of cases resulted in greater NTD risk than heterozygosity or homozygosity for RFC-1 80A-->G variant alone. Conversely, our data provide no evidence for an association between NTD phenotype and combined MTHFR C677T/RFC-1 A80G genotypes. Moreover, here we describe the combinations of the two MTHFR polymorphic sites (677CT and 1298AC) with RFC-1 genotypes. We found that both patients and controls could have at most quadruple-mutation combinations. Interestingly, 27% (7/26) of the mothers and 18.75% (30/160) of the cases genotyped presented four mutant alleles in comparison with 8.5% (11/129) of the controls. Finally, the frequency of NTD cases and mothers carrying combined heterozygosity for the two MTHFR polymorphisms and RFC-1 80GG homozygosity (677CT/1298AC/80GG) (cases=11.3%; mothers 11.5%) was increased compared with controls (1.6%). Altogether, our findings support the hypothesis

  10. Radioimmunoassay of alpha-foetoprotein in the eluate of dried blood. A method for antenatal screening of neural tube defects

    International Nuclear Information System (INIS)

    Travert, G.; Herlicoviez, M.; Laroche, D.

    1979-01-01

    A radioimmunoassay for alpha-foetoprotein (AFP) in dried blood spots is reported. The main technical characteristics (reproducibility, sensitivity, recovery of exogenous AFP added and AFP stability in dried blood) are evaluated. They indicate that this method is feasible and well adapted to AFP measurement during pregnancy. AFP determination in maternal serum allows early detection of at least 80% of neural tube defects. The use of dried blood spots as samples for AFP assay makes our method a possible mass screening test for these malformations, which occur with an incidence of 12 for 10,000 [fr

  11. Epigenetic profiles in children with a neural tube defect; a case-control study in two populations.

    Directory of Open Access Journals (Sweden)

    Lisette Stolk

    Full Text Available 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

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

    Directory of Open Access Journals (Sweden)

    Gizele Thame

    1998-09-01

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

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

    Science.gov (United States)

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

    2015-01-01

    Measurements of heat collection rate and heat loss coefficient are crucial for the evaluation of in service water-in-glass evacuated tube solar water heaters. However, conventional measurement requires expensive detection devices and undergoes a series of complicated procedures. To simplify the measurement and reduce the cost, software based on artificial neural networks for measuring heat collection rate and heat loss coefficient of water-in-glass evacuated tube solar water heaters was developed. Using multilayer feed-forward neural networks with back-propagation algorithm, we developed and tested our program on the basis of 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

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Non-SMC condensin I complex proteins control chromosome segregation and survival of proliferating cells in the zebrafish neural retina

    Directory of Open Access Journals (Sweden)

    Harris William A

    2009-07-01

    Full Text Available Abstract Background The condensation of chromosomes and correct sister chromatid segregation during cell division is an essential feature of all proliferative cells. Structural maintenance of chromosomes (SMC and non-SMC proteins form the condensin I complex and regulate chromosome condensation and segregation during mitosis. However, due to the lack of appropriate mutants, the function of the condensin I complex during vertebrate development has not been described. Results Here, we report the positional cloning and detailed characterization of retinal phenotypes of a zebrafish mutation at the cap-g locus. High resolution live imaging reveals that the progression of mitosis between prometa- to telophase is delayed and that sister chromatid segregation is impaired upon loss of CAP-G. CAP-G associates with chromosomes between prometa- and telophase of the cell cycle. Loss of the interaction partners CAP-H and CAP-D2 causes cytoplasmic mislocalization of CAP-G throughout mitosis. DNA content analysis reveals increased genomic imbalances upon loss of non-SMC condensin I subunits. Within the retina, loss of condensin I function causes increased rates of apoptosis among cells within the proliferative ciliary marginal zone (CMZ whereas postmitotic retinal cells are viable. Inhibition of p53-mediated apoptosis partially rescues cell numbers in cap-g mutant retinae and allows normal layering of retinal cell types without alleviating their aberrant nuclear sizes. Conclusion Our findings indicate that the condensin I complex is particularly important within rapidly amplifying progenitor cell populations to ensure faithful chromosome segregation. In contrast, differentiation of postmitotic retinal cells is not impaired upon polyploidization.

  16. Syndromes and Disorders Associated with Omphalocele (III: Single Gene Disorders, Neural Tube Defects, Diaphragmatic Defects and Others

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2007-06-01

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

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

    Science.gov (United States)

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

    2014-08-01

    Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects. © 2014 Wiley Periodicals, Inc.

  18. Brain tissue aspiration neural tube defect Aspiração de tecido cerebral em casos de defeitos de fechamento do tubo neural

    Directory of Open Access Journals (Sweden)

    Luiz Cesar Peres

    2005-09-01

    Full Text Available The study aimed to find out how frequent is brain tissue aspiration and if brain tissue heterotopia could be found in the lung of human neural tube defect cases. Histological sections of each lobe of both lungs of 22 fetuses and newborn with neural tube defect were immunostained for glial fibrillary acidic protein (GFAP. There were 15 (68.2% females and 7 (31.8% males. Age ranged from 18 to 40 weeks of gestation (mean= 31.8. Ten (45.5% were stillborn, the same newborn, and 2 (9.1% were abortuses. Diagnosis were: craniorrhachischisis (9 cases, 40.9%, anencephaly (8 cases, 36,4%, ruptured occipital encephalocele and rachischisis (2 cases, 9.1% each, and early amniotic band disruption sequence (1 case, 4.5%. Only one case (4.5% exhibited GFAP positive cells inside bronchioles and alveoli admixed to epithelial amniotic squames. No heterotopic tissue was observed in the lung interstitium. We concluded that aspiration of brain tissue from the amniotic fluid in neural tube defect cases may happen but it is infrequent and heterotopia was not observed.O objetivo do estudo foi identificar qual a freqüência de aspiração de tecido cerebral e a existência de heterotopia nos pulmões de casos humanos de defeito de fechamento do tubo neural através da reação imuno-histoquímica para proteína fibrilar glial ácida (GFAP em cortes histológicos de todos os lobos de ambos os pulmões de 22 casos de fetos e neonatos com defeito de fechamento do tubo neural. Havia 15 casos femininos (68,2% e 7 masculinos (31,8%, com idade gestacional variando de 18 a 40 semanas (média= 31,8, sendo natimortos e neomortos 10 (45,5% cada e 2 (9,1% abortos. Os diagnósticos foram: Craniorraquisquise (9 casos, 40,9%, anencefalia (8 casos, 36,4%, encefalocele occipital rota e raquisquise (2 casos, 9,1% e 1 (4,5%caso de seqüência de disruptura amniótica precoce. Somente 1 caso (4,5% apresentou células positivas dentro de bronquíolos e alvéolos em meio a células epiteliais

  19. Maternal Antenatal Bereavement and Neural Tube Defect in Live-Born Offspring

    DEFF Research Database (Denmark)

    Ingstrup, Katja Glejsted; Wu, Chun Sen; Olsen, Jørn

    2016-01-01

    BACKGROUND: Maternal emotional stress during pregnancy has previously been associated with congenital neural malformations, but most studies are based on data collected retrospectively. The objective of our study was to investigate associations between antenatal maternal bereavement due to death...

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

    Directory of Open Access Journals (Sweden)

    Keith S. K. Fong

    2016-05-01

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

  1. Learning and memory in zebrafish larvae

    Science.gov (United States)

    Roberts, Adam C.; Bill, Brent R.; Glanzman, David L.

    2013-01-01

    Larval zebrafish possess several experimental advantages for investigating the molecular and neural bases of learning and memory. Despite this, neuroscientists have only recently begun to use these animals to study memory. However, in a relatively short period of time a number of forms of learning have been described in zebrafish larvae, and significant progress has been made toward their understanding. Here we provide a comprehensive review of this progress; we also describe several promising new experimental technologies currently being used in larval zebrafish that are likely to contribute major insights into the processes that underlie learning and memory. PMID:23935566

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

    Science.gov (United States)

    Yu, Jingwen; Wu, Yanqing; Yang, Peixin

    2016-05-01

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

  3. From disability to ability: comprehensive rehabilitation providing a holistic functional improvement in a child with neglected neural tube defect.

    Science.gov (United States)

    Mishra, Kriti; Siddharth, V

    2017-09-25

    Neural Tube defects are one of the most common congenital disorders, presenting in a paediatric rehabilitation set-up. With its wide spectrum of clinical presentation and possible complications, the condition can significantly impact an individual's functional capacity and quality of life. The condition also affects the family of the child leaving them with a lifelong impairment to cope up with. Through this 16-year-old child, we shed light on the effects of providing rehabilitation, even at a later stage and its benefits. We also get a glimpse of difficulties in availing rehabilitation services in developing countries and the need to reach out many more neglected children like him with good functional abilities. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

    Directory of Open Access Journals (Sweden)

    Asaranti Kar

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, Jennifer E [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Raymond, Angela M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Winn, Louise M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada)

    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.

  6. INCREASED MATERNAL SERUM ALPHA-FETOPROTEIN AND HUMAN CHORIONIC-GONADOTROPIN IN COMPROMISED PREGNANCIES OTHER THAN FOR NEURAL-TUBE DEFECTS OR DOWN-SYNDROME

    NARCIS (Netherlands)

    BEEKHUIS, [No Value; VANLITH, JMM; DEWOLF, BTHM; MANTINGH, A

    Intrauterine fetal death occurred in four women who were 'screen-positive' in a screening programme for neural tube defects (NTDs) and Down syndrome (DS). These women had very high levels of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG). Therefore,

  7. HETEROGENEITY OF NEURAL-TUBE DEFECTS IN EUROPE - THE SIGNIFICANCE OF SITE OF DEFECT AND PRESENCE OF OTHER MAJOR ANOMALIES IN RELATION TO GEOGRAPHIC DIFFERENCES IN PREVALENCE

    NARCIS (Netherlands)

    DOLK, H; DEWALS, P; GILLEROT, Y; LECHAT, MF; AYME, S; CORNEL, M; CUSCHIERI, A; GARNE, E; GOUJARD, J; LAURENCE, KM; LILLIS, D; LYS, F; NEVIN, N; OWENS, J; RADIC, A; STOLL, C; STONE, D; TENKATE, L

    1991-01-01

    In the period 1980-1987, neural tube defects were two to three times more prevalent in populations covered by EUROCAT registries in the United Kingdom and Ireland (UKI) than in Continental Europe and Malta (CEM). 1864 NTD cases in a total population of 580,000 births in UKI and 455 cases in a

  8. Neural crest contributions to the lamprey head

    Science.gov (United States)

    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.

  9. Mortalidad por defectos del tubo neural en México, 1980-1997 Mortality due to neural tube defects in Mexico, 1980-1997

    Directory of Open Access Journals (Sweden)

    José A Ramírez-Espitia

    2003-10-01

    Full Text Available OBJETIVO: Describir la mortalidad en México por defectos del tubo neural, durante el periodo 1980-1997. MATERIAL Y MÉTODOS: Las tasas anuales de mortalidad estatales y nacionales, por defectos del tubo neural, se calcularon por 10 000 nacidos vivos. La tendencia temporal fue evaluada por el porcentaje de cambio anual obtenido mediante un modelo de regresión de Poisson. Se calculó la razón de mortalidad, tomando la media nacional como referencia. Las tasas y las razones se representaron gráficamente en mapas. RESULTADOS: Durante el periodo la tasa bruta de mortalidad por defectos del tubo neural fue de 5.8 por 10 000 nacidos vivos. La anencefalia fue el tipo de defecto más frecuente (37.7%, seguida de la espina bífida sin hidrocefalia (31.6%. La tendencia nacional de la mortalidad por defectos del tubo neural fue ascendente entre 1980 y 1990 (porcentaje de cambio anual 7.5 IC 95% 6.5, 8.6 y descendente entre 1990-1997 (porcentaje de cambio anual -2.3 IC 95% -3.6, -0.9. CONCLUSIONES: Las altas tasas de mortalidad por defectos del tubo neural fueron debidas principalmente a la elevada frecuencia de las anencefalias. El incremento observado parece no ser sólo atribuible a cuestiones puramente diagnósticas o de mejora en los registros. La influencia de factores asociados a estos defectos, como determinados polimorfismos genéticos, la deficiencia de ácido fólico, la obesidad materna, la exposición laboral a plaguicidas y la pobreza deberán evaluarse mediante estudios específicos.OBJECTIVE: To describe the mortality due to neural tube defects (NTD in Mexico for the 1980-1997 period. MATERIAL AND METHODS: The annual NTD mortality rates per 10000 liveborn infants were calculated by state and for the country. The time trend was evaluated with the annual percent change (APC obtained using a Poisson regression model. The NTD mortality ratio was calculated using the average national rate as reference. NTD mortality rates and ratios were

  10. Dificultades en los métodos de estudio de exposiciones ambientales y defectos del tubo neural Methodological challenges to assess environmental exposures related to neural tube defects

    Directory of Open Access Journals (Sweden)

    Víctor Hugo Borja-Aburto

    1999-11-01

    susceptibilidad genética.Objective. To discuss the attitudes in the assessment of environmental exposures as risk factors associated with neural tube defects, and to present the main risk factors studied to date. Results. Environmental exposures have been suggested to have a roll in the genesis of birth defects. However, studies conducted in human populations have found difficulties in the design and conduction to show such an association for neural tube defects (anencephaly, espina bifida and encefalocele because of problems raised from: a the frequency measures used to compare time trends and communities, b the classification of heterogeneous malformations, c the inclusion of maternal, paternal and fetal factors as an integrated process and, d the assessment of environmental exposures. Conclusions. Hypothetically both maternal and paternal environmental exposures can produce damage before and after conception by direct action on the embryo and the fetus-placenta complex. Therefore, in the assessment of environmental exposures we need to take into account: a both paternal and maternal exposures; b the critical exposure period, three months before conception for paternal exposures and one month around the conceptional period for maternal exposures; c quantitatively evaluate environmental exposures when possible, avoiding a dichotomous classification; d the use of biological markers of exposure is highly recommended as well as markers of genetic susceptibility.

  11. Disostose espôndilo-costal associada a defeitos de fechamento do tubo neural Spondylocostal dysostosis associated with neural tube defects

    Directory of Open Access Journals (Sweden)

    Rafael Fabiano M. Rosa

    2009-09-01

    Full Text Available OBJETIVO: Salientar a relação dos defeitos de fechamento do tubo neural com a disostose espôndilo-costal (DEC por meio da descrição de três pacientes. DESCRIÇÃO DOS CASOS: Paciente 1: menina branca, 22 meses, nascida com mielomeningocele lombar. Na avaliação, apresentava hipotonia, baixa estatura, dolicocefalia, fendas palpebrais oblíquas para cima, pregas epicânticas e tronco curto com tórax assimétrico. A avaliação radiográfica revelou hemivértebras múltiplas, vértebras em borboleta e fusão e ausência de algumas costelas. Paciente 2: menina branca, 22 meses, com moderado atraso do desenvolvimento neuropsicomotor, baixa estatura, olhos profundos, pregas epicânticas, pescoço e tronco curtos com assimetria do tórax, abdome protruso, hemangioma plano na altura da transição lombossacra e fosseta sacral profunda no dorso. A avaliação radiográfica identificou hemivértebras, fusão incompleta de vértebras e vértebras em borboleta, malformações de costelas e espinha bífida oculta em L5/S1. Paciente 3: menina branca, 9 dias de vida, com fendas palpebrais oblíquas para cima, ponte nasal alargada, orelhas baixo implantadas e rotadas posteriormente, tronco curto, tórax assimétrico e meningocele tóraco-lombar. A avaliação radiográfica evidenciou hemivértebras, malformação e ausência de algumas costelas e agenesia diafragmática à esquerda. A tomografia computadorizada de encéfalo mostrou estenose de aqueduto. COMENTÁRIOS: Vários defeitos de fechamento do tubo neural, de espinha bífida oculta a grandes mielomeningoceles, são observados em pacientes com DEC, indicando que tais pacientes devem ser cuidadosamente avaliados quanto à possível presença desses defeitos.OBJECTIVE: To highlight the relationship between neural tube defects and spondylocostal dysostosis (SCD through the description of three patients. CASES DESCRIPTION: Patient 1: white girl, 22 months old, born with a lumbar meningomyelocele. At

  12. Mortality due to neural tube defects and risk factors in Hidalgo, Mexico

    OpenAIRE

    Muñoz-Juárez, Sergio; Vargas-Flores, Humberto; Hernández-Prado, Bernardo; López-Ríos, Olga; Ortiz-Espinosa, Rosa María

    2002-01-01

    Objetivo. Calcular el riesgo de muerte fetal secundaria a defectos del cierre del tubo neural y estimar factores asociados con este tipo de muertes en el estado de Hidalgo. Material y métodos. La información analizada en el año 2000 fue obtenida de los certificados de muerte fetal del periodo 1990-1995 en el estado de Hidalgo. Se utilizó un diseño de mortalidad proporcional, considerado como una variante del diseño de casos y controles. Los casos fueron aquellas muertes fetales secundarias a ...

  13. Zebrafish Adar2 Edits the Q/R site of AMPA receptor Subunit gria2α transcript to ensure normal development of nervous system and cranial neural crest cells.

    Directory of Open Access Journals (Sweden)

    I-Chen Li

    Full Text Available BACKGROUND: Adar2 deaminates selective adenosines to inosines (A-to-I RNA editing in the double-stranded region of nuclear transcripts. Although the functions of mouse Adar2 and its biologically most important substrate gria2, encoding the GluA2 subunit of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, have been extensively studied, the substrates and functions of zebrafish Adar2 remain elusive. METHODS/PRINCIPAL FINDINGS: Expression of Adar2 was perturbed in the adar2 morphant (adar2MO, generated by antisense morpholio oligonucleotides. The Q/R editing of gria2α was reduced in the adar2MO and was enhanced by overexpression of Adar2, demonstrating an evolutionarily conserved activity between zebrafish and mammalian Adar2 in editing the Q/R site of gria2. To delineate the role of Q/R editing of gria2α in the developmental defects observed in the adar2MO, the Q/R editing of gria2α was specifically perturbed in the gria2αQRMO, generated by a morpholio oligonucleotide complementary to the exon complementary sequence (ECS required for the Q/R editing. Analogous to the adar2-deficient and Q/R-editing deficient mice displaying identical neurological defects, the gria2αQRMO and adar2MO displayed identical developmental defects in the nervous system and cranial cartilages. Knockdown p53 abolished apoptosis and partially suppressed the loss of spinal cord motor neurons in these morphants. However, reducing p53 activity neither replenished the brain neuronal populations nor rescued the developmental defects. The expressions of crestin and sox9b in the neural crest cells were reduced in the adar2MO and gria2αQRMO. Overexpressing the edited GluA2αR in the adar2MO restored normal expressions of cresting and sox9b. Moreover, overexpressing the unedited GluA2αQ in the wild type embryos resulted in reduction of crestin and sox9b expressions. These results argue that an elevated GluA2αQ level is sufficient for generating the

  14. A spontaneous and novel Pax3 mutant mouse that models Waardenburg syndrome and neural tube defects.

    Science.gov (United States)

    Ohnishi, Tetsuo; Miura, Ikuo; Ohba, Hisako; Shimamoto, Chie; Iwayama, Yoshimi; Wakana, Shigeharu; Yoshikawa, Takeo

    2017-04-05

    Genes responsible for reduced pigmentation phenotypes in rodents are associated with human developmental defects, such as Waardenburg syndrome, where patients display congenital deafness along with various abnormalities mostly related to neural crest development deficiency. In this study, we identified a spontaneous mutant mouse line Rwa, which displays variable white spots on mouse bellies and white digits and tail, on a C57BL/6N genetic background. Curly tail and spina bifida were also observed, although at a lower penetrance. These phenotypes were dominantly inherited by offspring. We searched for the genetic mechanism of the observed phenotypes. We harnessed a rapid mouse gene mapping system newly developed in our laboratories to identify a responsible gene. We detected a region within chromosome 1 as a probable locus for the causal mutation. Dense mapping using interval markers narrowed the locus down to a 670-kbp region, containing four genes including Pax3, a gene known to be implicated in the types I and III Waardenburg syndrome. Extensive mutation screening of Pax3 detected an 841-bp deletion, spanning the promoter region and intron 1 of the gene. The defective allele of Pax3, named Pax3 Rwa , lacked the first coding exon and co-segregated perfectly with the phenotypes, confirming its causal nature. The genetic background of Rwa mice is almost identical to that of inbred C57BL/6N. These results highlight Pax3 Rwa mice as a beneficial tool for analyzing biological processes involving Pax3, in particular the development and migration of neural crest cells and melanocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Cordero, Amy M; Crider, Krista S; Rogers, Lisa M; Cannon, Michael J; Berry, R J

    2015-04-24

    Neural tube defects (NTDs) such as spina bifida, anencephaly, and encephalocele are serious birth defects of the brain and spine that occur during the first month of pregnancy when the neural tube fails to close completely. Randomized controlled trials and observational studies have shown that adequate daily consumption of folic acid before and during early pregnancy considerably reduces the risk for NTDs. The U.S. Public Health Service recommends that women capable of becoming pregnant consume 400 µg of folic acid daily for NTD prevention. Furthermore, fortification of staple foods (e.g., wheat flour) with folic acid has decreased folate-sensitive NTD prevalence in multiple settings and is a highly cost-effective intervention.

  16. Epidemiologic study of neural tube defects in Los Angeles County. I. Prevalence at birth based on multiple sources of case ascertainment

    Energy Technology Data Exchange (ETDEWEB)

    Sever, L.E. (Pacific Northwest Lab., Richland, WA); Sanders, M.; Monsen, R.

    1982-01-01

    Epidemiologic studies of the neural tube defects (NTDs), anencephalus and spina bifida, have for the most part been based on single sources of case ascertainment in past studies. The present investigation attempts total ascertainment of NTD cases in the newborn population of Los Angeles County residents for the period 1966 to 1972. Design of the study, sources of data, and estimates of prevalence rates based on single and multiple sources of case ascertainment are here discussed. Anencephalus cases totaled 448, spina bifida 442, and encephalocele 72, giving prevalence rates of 0.52, 0.51, and 0.08 per 1000 total births, respectively, for these neural tube defects - rates considered to be low. The Los Angeles County prevalence rates are compared with those of other recent North American studies and support is provided for earlier suggestions of low rates on the West Coast.

  17. Neuronal patterning of the tubular collar cord is highly conserved among enteropneusts but dissimilar to the chordate neural tube.

    Science.gov (United States)

    Kaul-Strehlow, Sabrina; Urata, Makoto; Praher, Daniela; Wanninger, Andreas

    2017-08-01

    A tubular nervous system is present in the deuterostome groups Chordata (cephalochordates, tunicates, vertebrates) and in the non-chordate Enteropneusta. However, the worm-shaped enteropneusts possess a less complex nervous system featuring only a short hollow neural tube, whereby homology to its chordate counterpart remains elusive. Since the majority of data on enteropneusts stem from the harrimaniid Saccoglossus kowalevskii, putative interspecific variations remain undetected resulting in an unreliable ground pattern that impedes homology assessments. In order to complement the missing data from another enteropneust family, we investigated expression of key neuronal patterning genes in the ptychoderid Balanoglossus misakiensis. The collar cord of B. misakiensis shows anterior Six3/6 and posterior Otx + Engrailed expression, in a region corresponding to the chordate brain. Neuronal Nk2.1/Nk2.2 expression is absent. Interestingly, we found median Dlx and lateral Pax6 expression domains, i.e., a condition that is reversed compared to chordates. Comparative analyses reveal that adult nervous system patterning is highly conserved among the enteropneust families Harrimaniidae, Spengelidae and Ptychoderidae. BmiDlx and BmiPax6 have no corresponding expression domains in the chordate brain, which may be indicative of independent acquisition of a tubular nervous system in Enteropneusta and Chordata.

  18. Evolution of posterior fossa and brain morphology after in utero repair of open neural tube defects assessed by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Rethmann, Christin; Scheer, Ianina; Kellenberger, Christian Johannes [University Children' s Hospital Zurich, Department of Diagnostic Imaging, Zurich (Switzerland); University of Zurich, The Zurich Center for Fetal Diagnosis and Therapy, Zurich (Switzerland); Children' s Research Center (CRC), Zurich (Switzerland); Meuli, Martin; Mazzone, Luca; Moehrlen, Ueli [University of Zurich, The Zurich Center for Fetal Diagnosis and Therapy, Zurich (Switzerland); Children' s Research Center (CRC), Zurich (Switzerland); University Children' s Hospital Zurich, Department of Pediatric Surgery, Zurich (Switzerland)

    2017-11-15

    To describe characteristics of foetuses undergoing in utero repair of open neural tube defects (ONTD) and assess postoperative evolution of posterior fossa and brain morphology. Analysis of pre- and postoperative foetal as well as neonatal MRI of 27 foetuses who underwent in utero repair of ONTD. Type and level of ONTD, hindbrain configuration, posterior fossa and liquor space dimensions, and detection of associated findings were compared between MRI studies and to age-matched controls. Level of bony spinal defect was defined with exactness of ± one vertebral body. Of surgically confirmed 18 myelomeningoceles (MMC) and 9 myeloschisis (MS), 3 MMC were misdiagnosed as MS due to non-visualisation of a flat membrane on MRI. Hindbrain herniation was more severe in MS than MMC (p < 0.001). After repair, hindbrain herniation resolved in 25/27 cases at 4 weeks and liquor spaces increased. While posterior fossa remained small (p < 0.001), its configuration normalised. Lateral ventricle diameter indexed to cerebral width decreased in 48% and increased in 12% of cases, implying a low rate of progressive obstructive hydrocephalus. Neonatally evident subependymal heterotopias were detected in 33% at preoperative and 50% at postoperative foetal MRI. MRI demonstrates change of Chiari malformation type II (CM-II) features. (orig.)

  19. A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly.

    Science.gov (United States)

    Ishida, M; Cullup, T; Boustred, C; James, C; Docker, J; English, C; Lench, N; Copp, A J; Moore, G E; Greene, N D E; Stanier, P

    2018-04-01

    Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to lifelong neurological handicap. Collectively, NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n = 85 anencephaly and n = 5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N = 509), we identified 397 rare variants (minor allele frequency, MAF < 1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly. © 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Evolution of posterior fossa and brain morphology after in utero repair of open neural tube defects assessed by MRI

    International Nuclear Information System (INIS)

    Rethmann, Christin; Scheer, Ianina; Kellenberger, Christian Johannes; Meuli, Martin; Mazzone, Luca; Moehrlen, Ueli

    2017-01-01

    To describe characteristics of foetuses undergoing in utero repair of open neural tube defects (ONTD) and assess postoperative evolution of posterior fossa and brain morphology. Analysis of pre- and postoperative foetal as well as neonatal MRI of 27 foetuses who underwent in utero repair of ONTD. Type and level of ONTD, hindbrain configuration, posterior fossa and liquor space dimensions, and detection of associated findings were compared between MRI studies and to age-matched controls. Level of bony spinal defect was defined with exactness of ± one vertebral body. Of surgically confirmed 18 myelomeningoceles (MMC) and 9 myeloschisis (MS), 3 MMC were misdiagnosed as MS due to non-visualisation of a flat membrane on MRI. Hindbrain herniation was more severe in MS than MMC (p < 0.001). After repair, hindbrain herniation resolved in 25/27 cases at 4 weeks and liquor spaces increased. While posterior fossa remained small (p < 0.001), its configuration normalised. Lateral ventricle diameter indexed to cerebral width decreased in 48% and increased in 12% of cases, implying a low rate of progressive obstructive hydrocephalus. Neonatally evident subependymal heterotopias were detected in 33% at preoperative and 50% at postoperative foetal MRI. MRI demonstrates change of Chiari malformation type II (CM-II) features. (orig.)

  1. Inositol- and folate-resistant neural tube defects in mice lacking the epithelial-specific factor Grhl-3.

    Science.gov (United States)

    Ting, Stephen B; Wilanowski, Tomasz; Auden, Alana; Hall, Mark; Voss, Anne K; Thomas, Tim; Parekh, Vishwas; Cunningham, John M; Jane, Stephen M

    2003-12-01

    The neural tube defects (NTDs) spina bifida and anencephaly are widely prevalent severe birth defects. The mouse mutant curly tail (ct/ct) has served as a model of NTDs for 50 years, even though the responsible genetic defect remained unrecognized. Here we show by gene targeting, mapping and genetic complementation studies that a mouse homolog of the Drosophila grainyhead (grh) gene, grainyhead-like-3 (Grhl3), is a compelling candidate for the gene underlying the curly tail phenotype. The NTDs in Grhl3-null mice are more severe than those in the curly tail strain, as the Grhl3 alleles in ct/ct mice are hypomorphic. Spina bifida in ct/ct mice is folate resistant, but its incidence can be markedly reduced by maternal inositol supplementation periconceptually. The NTDs in Grhl3-/- embryos are also folate resistant, but unlike those in ct/ct mice, they are resistant to inositol. These findings suggest that residual Grhl3 expression in ct/ct mice may be required for inositol rescue of folate-resistant NTDs.

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

    Science.gov (United States)

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

    2009-03-01

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

  3. Myo-inositol soft gel capsules may prevent the risk of coffee-induced neural tube defects.

    Science.gov (United States)

    De Grazia, Sara; Carlomagno, Gianfranco; Unfer, Vittorio; Cavalli, Pietro

    2012-09-01

    Neural tube defects (NTDs) are classified as folate sensitive (about 70%) and folate resistant (about 30%); although folic acid is able to prevent the former, several data have shown that inositol may prevent the latter. It has recently been proposed that coffee intake might represent a risk factor for NTD, likely by interfering with the inositol signaling. In the present study, we tested the hypothesis that, beside affecting the inositol signaling pathway, coffee also interferes with inositol absorption. In order to evaluate coffee possible negative effects on inositol gastrointestinal absorption, a single-dose bioavailability trial was conducted. Pharmacokinetics (PK) parameters of myo-inositol (MI) powder and MI soft gelatin capsules swallowed with water and with a single 'espresso' were compared. PK profiles were obtained by analysis of MI plasma concentration, and the respective MI bioavailability was compared. Myo-inositol powder administration was negatively affected by coffee intake, thus suggesting an additional explanation to the interference between inositol deficiency and coffee consumption. On the contrary, the concomitant single 'espresso' consumption did not affect MI absorption following MI soft gelatin capsules administration. Furthermore, it was observed that MI soft gelatin capsule administration resulted in improved bioavailability compared to the MI powder form. Myo-inositol soft gelatin capsules should be considered for the preventive treatment of NTDs in folate-resistant subjects due to their higher bioavailability and to the capability to reduce espresso interference.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2013-01-01

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

  6. Assessing the prevalence of spina bifida and encephalocele in a Kenyan hospital from 2005–2010: implications for a neural tube defects surveillance system

    Science.gov (United States)

    Githuku, Jane N; Azofeifa, Alejandro; Valencia, Diana; Ao, Trong; Hamner, Heather; Amwayi, Samuel; Gura, Zeinab; Omolo, Jared; Albright, Leland; Guo, Jing; Arvelo, Wences

    2014-01-01

    Introduction Neural tube defects such as anencephaly, spina bifida, and encephalocele are congenital anomalies of the central nervous system. Data on the prevalence of neural tube defects in Kenya are limited. This study characterizes and estimates the prevalence of spina bifida and encephalocele reported in a referral hospital in Kenya from 2005-2010. Methods Cases were defined as a diagnosis of spina bifida or encephalocele. Prevalence was calculated as the number of cases by year and province of residence divided by the total number of live-births per province. Results From a total of 6,041 surgical records; 1,184 (93%) had reported diagnosis of spina bifida and 88 (7%) of encephalocele. Estimated prevalence of spina bifida and encephalocele from 2005-2010 was 3.3 [95% Confidence Interval (CI): 3.1-3.5] cases per 10,000 live-births. The highest prevalence of cases were reported in 2007 with 4.4 (95% CI: 3.9-5.0) cases per 10,000 live-births. Rift Valley province had the highest prevalence of spina bifida and encephalocele at 6.9 (95% CI: 6.3-7.5) cases per 10,000 live-births from 2005-2010. Conclusion Prevalence of spina bifida and encephalocele is likely underestimated, as only patients seeking care at the hospital were included. Variations in regional prevalence could be due to referral patterns and healthcare access. Implementation of a neural tube defects surveillance system would provide a more thorough assessment of the burden of neural tube defects in Kenya. PMID:26113894

  7. Assessing the prevalence of spina bifida and encephalocele in a Kenyan hospital from 2005-2010: implications for a neural tube defects surveillance system.

    Science.gov (United States)

    Githuku, Jane N; Azofeifa, Alejandro; Valencia, Diana; Ao, Trong; Hamner, Heather; Amwayi, Samuel; Gura, Zeinab; Omolo, Jared; Albright, Leland; Guo, Jing; Arvelo, Wences

    2014-01-01

    Neural tube defects such as anencephaly, spina bifida, and encephalocele are congenital anomalies of the central nervous system. Data on the prevalence of neural tube defects in Kenya are limited. This study characterizes and estimates the prevalence of spina bifida and encephalocele reported in a referral hospital in Kenya from 2005-2010. Cases were defined as a diagnosis of spina bifida or encephalocele. Prevalence was calculated as the number of cases by year and province of residence divided by the total number of live-births per province. From a total of 6,041 surgical records; 1,184 (93%) had reported diagnosis of spina bifida and 88 (7%) of encephalocele. Estimated prevalence of spina bifida and encephalocele from 2005-2010 was 3.3 [95% Confidence Interval (CI): 3.1-3.5] cases per 10,000 live-births. The highest prevalence of cases were reported in 2007 with 4.4 (95% CI: 3.9-5.0) cases per 10,000 live-births. Rift Valley province had the highest prevalence of spina bifida and encephalocele at 6.9 (95% CI: 6.3-7.5) cases per 10,000 live-births from 2005-2010. Prevalence of spina bifida and encephalocele is likely underestimated, as only patients seeking care at the hospital were included. Variations in regional prevalence could be due to referral patterns and healthcare access. Implementation of a neural tube defects surveillance system would provide a more thorough assessment of the burden of neural tube defects in Kenya.

  8. Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport

    International Nuclear Information System (INIS)

    Zhang, Gui-Bin; Wang, Hua; Hu, Jun; Guo, Min-Yin; Wang, Ying; Zhou, Yan; Yu, Zhen; Fu, Lin; Chen, Yuan-Hua; Xu, De-Xiang

    2016-01-01

    Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl 2 (2.5 or 5.0 mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl 2 on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl 2 . Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl 2 on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl 2 on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters. - Highlights: • Maternal Cd exposure during organogenesis causes NTDs and FGR. • Maternal Cd exposure during organogenesis impairs placental development. • Cd disturbs transport of folate by down-regulating placental folate transporters.

  9. Association of main folate metabolic pathway gene polymorphisms with neural tube defects in Han population of Northern China.

    Science.gov (United States)

    Fang, Yulian; Zhang, Ruiping; Zhi, Xiufang; Zhao, Linsheng; Cao, Lirong; Wang, Yizheng; Cai, Chunquan

    2018-04-01

    Neural tube defects (NTDs) are one of the most prevalent and the most severe congenital malformations worldwide. Studies have confirmed that folic acid supplementation could effectively reduce NTDs risk, but the genetic mechanism remains unclear. In this study, we explored association of single nucleotide polymorphisms (SNP) within folate metabolic pathway genes with NTDs in Han population of Northern China. We performed a case-control study to compare genotype and allele distributions of SNPs in 152 patients with NTDs and 169 controls. A total of 16 SNPs within five genes were genotyped by the Sequenom MassARRAY assay. Our results indicated that three SNPs associated significantly with NTDs (P<0.05). For rs2236225 within MTHFD1, children with allele A or genotype AA had a high NTDs risk (OR=1.500, 95%CI=1.061~2.120; OR=2.862, 95%CI=1.022~8.015, respectively). For rs1801133 within MTHFR, NTDs risk markedly increased in patients with allele T or genotype TT (OR=1.552, 95%CI=1.130~2.131; OR=2.344, 95%CI=1.233~4.457, respectively). For rs1801394 within MTRR, children carrying allele G and genotype GG had a higher NTDs risk (OR=1.533, 95%CI=1.102~2.188; OR=2.355, 95%CI=1.044~5.312, respectively). Our results suggest that rs2236225 of MTHFD1 gene, rs1801133 of MTHFR gene and rs1801394 of MTRR gene were associated with NTDs in Han population of Northern China.

  10. [C677T polymorphism of the methylentetrahydrofolate reductase gene in mothers of children affected with neural tube defects].

    Science.gov (United States)

    Morales de Machín, Alisandra; Méndez, Karile; Solís, Ernesto; Borjas de Borjas, Lisbeth; Bracho, Ana; Hernández, María Luisa; Negrón, Aimara; Delgado, Wilmer; Sánchez, Yanira

    2015-09-01

    Neural tube defects (NTD) are the most common congenital anomalies of the central nervous system, with a multifactorial pattern of inheritance, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene 677C>T polymorphism has been implicated as a risk factor for NTD. The main objective of this research was to investigate the association of the 677C>T polymorphism of the MTHFR gene as a genetic risk factor for NTD. Molecular analysis was performed in DNA samples from 52 mothers with antecedent of NTD offspring and from 119 healthy control mothers. Using the Polymerase Chain Reaction, a 198 bases pairs fragment was digested with the restriction enzyme Hinfi. 677T MTHFR allele frequencies for the problem and the control groups were 51.92% and 34.45%, respectively, and 677C MTHFR allele frequencies were 48.08% and 65.55%, respectively. There were significant differences in allele (p: 0.002) and genotype (p: 0.007) frequencies between these two groups. The odds ratio (OR) to the TT genotype vs. the CC genotype was estimated as OR: 4.9 [95% CI: 1,347-6.416] p: 0.002; CT+TT vs. CC: OR: 2.9 [95% CI: 1.347-6.416] p: 0.005; TT vs. CT+CC: OR: 2.675 [95% CI: 1,111-6.441] p: 0.024. The data presented in this study support the relationship between MTHFR 677C>T polymorphism and risk in mothers with antecedent of NTD offspring.

  11. Maternal Use of Weight Loss Products and the Risk of Neural Tube Defects in Offspring: A Systematic Literature Review.

    Science.gov (United States)

    Hoang, Thanh T; Agopian, A J; Mitchell, Laura E

    2018-01-15

    Several studies have assessed potential associations between use of weight loss products in the periconceptional period and neural tube defects (NTDs). However, the individual studies are inconclusive and there has not been a systematic review of this literature. We conducted a systematic search, using Ovid MEDLINE and PubMed, to identify studies that evaluated the association between products used for weight loss and the risk of NTDs. Because many studies of birth defects only evaluate a composite birth defect outcome, we evaluated studies that defined the outcome as "any major birth defect" or as NTDs. We abstracted data on study design, exposure definition, outcome definition, covariates and effect size estimates from each article that met our inclusion criteria. For studies that evaluated a composite birth defect outcome, we also abstracted the number of NTD cases included in the composite outcome. We used a modified version of the Newcastle-Ottawa Scale to assess the quality of each article. We screened 865 citations and identified nine articles that met our inclusion criteria. The majority of studies reported positive associations between maternal use of weight loss products and birth defects (overall and NTDs). However, there were few significant associations and there was considerable heterogeneity in the specific exposures assessed across the nine studies. Our systematic review of weight loss products and NTDs indicates that the literature on this topic is sparse. Because several studies reported modest, positive associations between risk and use of weight loss products, additional studies are warranted. Birth Defects Research 110:48-55, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Fetoscopic Open Neural Tube Defect Repair: Development and Refinement of a Two-Port, Carbon Dioxide Insufflation Technique.

    Science.gov (United States)

    Belfort, Michael A; Whitehead, William E; Shamshirsaz, Alireza A; Bateni, Zhoobin H; Olutoye, Oluyinka O; Olutoye, Olutoyin A; Mann, David G; Espinoza, Jimmy; Williams, Erin; Lee, Timothy C; Keswani, Sundeep G; Ayres, Nancy; Cassady, Christopher I; Mehollin-Ray, Amy R; Sanz Cortes, Magdalena; Carreras, Elena; Peiro, Jose L; Ruano, Rodrigo; Cass, Darrell L

    2017-04-01

    To describe development of a two-port fetoscopic technique for spina bifida repair in the exteriorized, carbon dioxide-filled uterus and report early results of two cohorts of patients: the first 15 treated with an iterative technique and the latter 13 with a standardized technique. This was a retrospective cohort study (2014-2016). All patients met Management of Myelomeningocele Study selection criteria. The intraoperative approach was iterative in the first 15 patients and was then standardized. Obstetric, maternal, fetal, and early neonatal outcomes were compared. Standard parametric and nonparametric tests were used as appropriate. Data for 28 patients (22 endoscopic only, four hybrid, two abandoned) are reported, but only those with a complete fetoscopic repair were analyzed (iterative technique [n=10] compared with standardized technique [n=12]). Maternal demographics and gestational age (median [range]) at fetal surgery (25.4 [22.9-25.9] compared with 24.8 [24-25.6] weeks) were similar, but delivery occurred at 35.9 (26-39) weeks of gestation with the iterative technique compared with 39 (35.9-40) weeks of gestation with the standardized technique (Pmet in 9 of 12 (75%) and 3 of 10 (30%), respectively, and 7 of 12 (58%) compared with 2 of 10 (20%) have been treated for hydrocephalus to date. These latter differences were not statistically significant. Fetoscopic open neural tube defect repair does not appear to increase maternal-fetal complications as compared with repair by hysterotomy, allows for vaginal delivery, and may reduce long-term maternal risks. ClinicalTrials.gov, https://clinicaltrials.gov, NCT02230072.

  13. Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Gui-Bin; Wang, Hua, E-mail: wanghuadev@126.com; Hu, Jun; Guo, Min-Yin; Wang, Ying; Zhou, Yan; Yu, Zhen; Fu, Lin; Chen, Yuan-Hua; Xu, De-Xiang, E-mail: xudex@126.com

    2016-09-01

    Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl{sub 2} (2.5 or 5.0 mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl{sub 2} on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl{sub 2}. Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl{sub 2} on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl{sub 2} on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters. - Highlights: • Maternal Cd exposure during organogenesis causes NTDs and FGR. • Maternal Cd exposure during organogenesis impairs placental development. • Cd disturbs transport of folate by down-regulating placental folate transporters.

  14. Interaction between the SLC19A1 gene and maternal first trimester fever on offspring neural tube defects.

    Science.gov (United States)

    Pei, Lijun; Zhu, Huiping; Ye, Rongwei; Wu, Jilei; Liu, Jianmeng; Ren, Aiguo; Li, Zhiwen; Zheng, Xiaoying

    2015-01-01

    Many studies have indicated that the reduced folate carrier gene (SLC19A1) is associated with an increased risk of neural tube defects (NTDs). However, the interaction between the SLC19A1 gene variant and maternal fever exposure and NTD risk remains unknown. The aim of this study was to investigate whether the risk for NTDs was influenced by the interactions between the SLC19A1 (rs1051266) variant and maternal first trimester fever. We investigated the potential interaction between maternal first trimester fever and maternal or offspring SLC19A1 polymorphism through a population-based case-control study. One hundred and four nuclear families with NTDs and 100 control families with nonmal newborns were included in the study. SLC19A1 polymorphism was determined using polymerase chain reaction-restricted fragment length polymorphism. Mothers who had the GG/GA genotype and first trimester fever had an elevated risk of NTDs (adjusted odds ratio, 11.73; 95% confidence interval, 3.02-45.58) as compared to absence of maternal first trimester fever and AA genotype after adjusting for maternal education, paternal education, and age, and had a significant interactive coefficient (γ = 3.17) between maternal GG/GA genotype and first trimester fever. However, there was no interaction between offspring's GG/GA genotype and maternal first trimester fever (the interactive coefficient γ = 0.97) after adjusting for confounding factors. Our findings suggested that the risk of NTDs was potentially influenced by a gene-environment interaction between maternal SLC19A1 rs1051266 GG/GA genotype and first trimester fever. Maternal GG/GA genotype may strengthen the effect of maternal fever exposure on NTD risk in this Chinese population. © 2014 Wiley Periodicals, Inc.

  15. Frecuencia de los defectos del tubo neural en Asturias: impacto del diagnóstico prenatal Prevalence of neural tube defects in Asturias (Spain: impact of prenatal diagnosis

    Directory of Open Access Journals (Sweden)

    Enrique García López

    2009-12-01

    Full Text Available Objetivo Describir la frecuencia de defectos del tubo neural (DTN -anencefalia, espina bífida y encefalocele-en Asturias, su evolución temporal y el impacto del diagnóstico prenatal. Métodos: Se estudiaron los casos de DTN en nacidos y abortos inducidos durante el período 1990-2004, utilizando la base de datos del Registro de Defectos Congénitos de Asturias, de base poblacional. Se calcularon las tasas de prevalencia total y al nacimiento. Resultados: La prevalencia total de DTN fue de 12,2 casos por 10.000 nacidos (5,9 anencefalias, 5,0 espinas bífidas y 1,3 encefaloceles y mostró una tendencia ligeramente descendente, con un descenso significativo de la espina bífida, mientras que las cifras de anencefalia y encefalocele se mantuvieron estables. Finalizaron en aborto inducido tras el diagnóstico prenatal el 88% de los casos (anencefalia 96,7%; espina bífida 80%; encefalocele 84,6%, lo que determinó una prevalencia al nacimiento muy baja (1,4 DTN por 10.000 nacidos. Conclusiones: En Asturias, en los últimos 15 años se ha producido un descenso selectivo en la prevalencia total de espina bífida de causa no aclarada. La prevención secundaria, mediante los programas de diagnóstico prenatal y la consiguiente interrupción del embarazo, fue el motivo del marcado descenso de la frecuencia en los nacidos; la simple recomendación de suplementación periconcepcional con ácido fólico no parece haber logrado el efecto buscado.Objective: To describe the frequency and prevalence trend for neural tube defects (NTD (anencephaly, spina bifida and encephalocele in Asturias (Spain, as well as the impact of prenatal diagnosis programs. Methods: All cases of NTD in births and induced abortions were studied, using data from the Registry of Congenital Defects of Asturias for 1990-2004. Total and birth prevalence rates were calculated. Results: The prevalence of NTD for 1990-2004 was 12.2 per 10,000 births (5.9 anencephaly, 5.0 spina bifida and 1

  16. Examination of a Palatogenic Gene Program in Zebrafish

    Science.gov (United States)

    Swartz, Mary E.; Sheehan-Rooney, Kelly; Dixon, Michael J.; Eberhart, Johann K.

    2011-01-01

    Human palatal clefting is debilitating and difficult to rectify surgically. Animal models enhance our understanding of palatogenesis and are essential in strategies designed to ameliorate palatal malformations in humans. Recent studies have shown that the zebrafish palate, or anterior neurocranium, is under similar genetic control to the amniote palatal skeleton. We extensively analyzed palatogenesis in zebrafish to determine the similarity of gene expression and function across vertebrates. By 36 hpf palatogenic cranial neural crest cells reside in homologous regions of the developing face compared to amniote species. Transcription factors and signaling molecules regulating mouse palatogenesis are expressed in similar domains during palatogenesis in zebrafish. Functional investigation of a subset of these genes, fgf10a, tgfb2, pax9 and smad5 revealed their necessity in zebrafish palatogenesis. Collectively, these results suggest that the gene regulatory networks regulating palatogenesis may be conserved across vertebrate species, demonstrating the utility of zebrafish as a model for palatogenesis. PMID:22016187

  17. Frecuencia y algunos factores de riesgo de mortalidad en el estado de Hidalgo, México, por defectos de cierre del tubo neural Mortality due to neural tube defects and risk factors in Hidalgo, Mexico

    Directory of Open Access Journals (Sweden)

    Sergio Muñoz-Juárez

    2002-09-01

    Full Text Available Objetivo. Calcular el riesgo de muerte fetal secundaria a defectos del cierre del tubo neural y estimar factores asociados con este tipo de muertes en el estado de Hidalgo. Material y métodos. La información analizada en el año 2000 fue obtenida de los certificados de muerte fetal del periodo 1990-1995 en el estado de Hidalgo. Se utilizó un diseño de mortalidad proporcional, considerado como una variante del diseño de casos y controles. Los casos fueron aquellas muertes fetales secundarias a defectos del tubo neural y los controles las muertes fetales por otros motivos. Se utilizó ji cuadrada de Pearson para estimar las diferencias entre los casos y controles. Para el riesgo crudo de morir por defectos de cierre del tubo neural se empleó la razón de momios, y para el riesgo ajustado se usó la regresión logística no condicional. Resultados. Se analizaron 3 673 certificados de muerte fetal, identificándose 8.06% de muertes por defectos del tubo neural; el resto lo constituyeron muertes por otras causas. Se encontró como variables asociadas con la muerte fetal por defectos del tubo neural a los fetos que pesaron menos de 2 500 gramos (RM 5.0, IC 95% 3.6, 6.7, a los productos del sexo femenino (RM 1.7, IC 95% 1.3, 2.3 y a las muertes ocurridas en el periodo fetal tardío (RM 5.5 IC 95% 3.8, 8.1. Conclusiones. Los resultados indican que el riesgo de muerte fetal debida a defectos del tubo neural es mayor en productos de bajo peso, en los del sexo femenino y los que ocurren en el periodo fetal tardío.Objective. To calculate the risk of fetal death due to neural tube defects and estimate associated factors in the state of Hidalgo, Mexico. Material and Methods. Data were abstracted from death certificates registered during 1990-1995 in the state of Hidalgo, Mexico. The design was a proportional mortality study, which is considered as a variant of the case control design. Cases were deaths with any type of neural tube defect, and controls

  18. Defeitos de fechamento do tubo neural e fatores associados em recém-nascidos vivos e natimortos Neural tube defects and associated factors among liveborn and stillborn infants

    Directory of Open Access Journals (Sweden)

    Marcos J.B. Aguiar

    2003-04-01

    evaluate the prevalence and factors associated to neural tube defects in liveborn and stillborn infants delivered at the Hospital das Clínicas, UFMG, from January 8, 1999 to July 31, 2000. METHODS: this is a descriptive study, based on a database, according to the Latin-American Collaborative Study of Congenital Malformation (ECLAMC rules. Reports on liveborn and stillborn infants with congenital anomalies were prepared including information about morphological description, necropsy results, complementary exams, family, social and pregnancy histories and other clinical data. Each malformed liveborn infant originated a control of the same sex, without malformations. The liveborn and stillborn infants with neural tube defects delivered during that period were classified according to their defect and the presence or absence of associated defects. The liveborn and stillborn infants with neural tube defects were compared to newborns without neural tube defects according to their weight and sex and their mother's age and parity. Epi-Info 6.0 Program was used for the statistical analysis of the results. RESULTS: the prevalence of neural tube defects was 4.73 to 1,000 deliveries (89:18,807; it was significantly higher among stillborn infants (23.7:1,000 than among liveborn infants (4.16:1,000, p < 0.001. Neural tube defects were more often found among low weight liveborn infants (< 2,500 g, p < 0.001 and less frequently among women who had had more than three gestations, p = 0.007. No association was found regarding newborn's sex or maternal age. There was no association with newborn's sex and weight, maternal parity or age among stillborn infants. The most common neural tube defects were myelomeningocele (47.2%, anencephaly (26.9% and encephalocele (16.9%. The defects were found as isolated anomalies in 71.1% of the liveborn and 38.5% of the stillborn infants; they were part of a syndrome in 9.2% (liveborn and 7.7% (stillborn. CONCLUSIONS: the neural tube defect prevalence found

  19. Mis-expression of grainyhead-like transcription factors in zebrafish leads to defects in enveloping layer (EVL) integrity, cellular morphogenesis and axial extension.

    Science.gov (United States)

    Miles, Lee B; Darido, Charbel; Kaslin, Jan; Heath, Joan K; Jane, Stephen M; Dworkin, Sebastian

    2017-12-14

    The grainyhead-like (grhl) transcription factors play crucial roles in craniofacial development, epithelial morphogenesis, neural tube closure, and dorso-ventral patterning. By utilising the zebrafish to differentially regulate expression of family members grhl2b and grhl3, we show that both genes regulate epithelial migration, particularly convergence-extension (CE) type movements, during embryogenesis. Genetic deletion of grhl3 via CRISPR/Cas9 results in failure to complete epiboly and pre-gastrulation embryonic rupture, whereas morpholino (MO)-mediated knockdown of grhl3 signalling leads to aberrant neural tube morphogenesis at the midbrain-hindbrain boundary (MHB), a phenotype likely due to a compromised overlying enveloping layer (EVL). Further disruptions of grhl3-dependent pathways (through co-knockdown of grhl3 with target genes spec1 and arhgef19) confirm significant MHB morphogenesis and neural tube closure defects. Concomitant MO-mediated disruption of both grhl2b and grhl3 results in further extensive CE-like defects in body patterning, notochord and somite morphogenesis. Interestingly, over-expression of either grhl2b or grhl3 also leads to numerous phenotypes consistent with disrupted cellular migration during gastrulation, including embryo dorsalisation, axial duplication and impaired neural tube migration leading to cyclopia. Taken together, our study ascribes novel roles to the Grhl family in the context of embryonic development and morphogenesis.

  20. Neural Tube Defects

    Science.gov (United States)

    ... March of Dimes Premature Birth Report Card Grades Cities, Counties; Focuses on Racial and Ethnic Disparities March ... folate. Good sources of folate are: Beans Leafy green vegetables Orange juice You have to eat a ...

  1. 2017 Midwest Zebrafish Meeting Report.

    Science.gov (United States)

    Sandquist, Elizabeth; Petersen, Sarah C; Smith, Cody J

    2017-12-01

    The 2017 Midwest Zebrafish meeting was held from June 16 to 18 at the University of Cincinnati, sponsored by the Cincinnati Children's Hospital Divisions of Developmental Biology, Molecular Cardiovascular Biology, and Gastroenterology, Hepatology, and Nutrition. The meeting, organized by Saulius Sumanas, Joshua Waxman, and Chunyue Yin, hosted >130 attendees from 16 different states. Scientific sessions were focused on morphogenesis, neural development, novel technologies, and disease models, with Steve Ekker, Stephen Potter, and Lila Solnica-Krezel presenting keynote talks. In this article, we highlight the results and emerging themes from the meeting.

  2. Magnitude of Neural Tube Defects and Associated Risk Factors at Three Teaching Hospitals in Addis Ababa, Ethiopia

    Directory of Open Access Journals (Sweden)

    Abel Gedefaw

    2018-01-01

    Full Text Available There is scarcity of data on prevalence of neural tube defects (NTDs in lower-income countries. Local data are important to understand the real burden of the problem and explore risk factors to design and implement preventive approaches. This study aimed to determine prevalence and risk factors of NTDs. A hospital-based cross-sectional and unmatched case-control study was conducted at three teaching hospitals of Addis Ababa University. NTDs were defined as cases of anencephaly, spina bifida, and encephalocele based on ICD-10 criteria. The prevalence of NTDs was calculated per 10,000 births for both birth and total prevalence. During seven months, we observed 55 cases of NTDs out of 8677 births after 28 weeks of gestation—birth prevalence of 63.4 per 10,000 births (95% confidence interval (CI, 51–77. A total of 115 cases were medically terminated after 12 weeks of gestation. Fifty-six of these terminations (48.7% were due to NTDs. Thus, total prevalence of NTDs after 12 weeks’ gestation is 126 per 10,000 births (95% CI, 100–150. Planned pregnancy (adjusted odds ratio (aOR, 0.47; 95% CI, 0.24–0.92, male sex (aOR, 0.56; 95% CI, 0.33–0.94, normal or underweight body mass index (aOR, 0.49; 95%, 0.29–0.95, and taking folic acid or multivitamins during first trimester (aOR, 0.47; 95%, 0.23–0.95 were protective of NTDs. However, annual cash family income less than $1,300 USD (aOR, 2.5; 95%, 1.2–5.5, $1,300–1,800 USD (aOR, 2.8; 95%, 1.3–5.8, and $1,801–2,700 USD (aOR, 2.6; 95%, 1.2–5.8 was found to be risk factors compared to income greater than $2,700 USD. The prevalence of NTDs was found to be high in this setting. Comprehensive preventive strategies focused on identified risk factors should be urgently established. More studies on prevention strategies, including folic acid supplementations, should be conducted in the setting.

  3. Magnitude of Neural Tube Defects and Associated Risk Factors at Three Teaching Hospitals in Addis Ababa, Ethiopia.

    Science.gov (United States)

    Gedefaw, Abel; Teklu, Sisay; Tadesse, Birkneh Tilahun

    2018-01-01

    There is scarcity of data on prevalence of neural tube defects (NTDs) in lower-income countries. Local data are important to understand the real burden of the problem and explore risk factors to design and implement preventive approaches. This study aimed to determine prevalence and risk factors of NTDs. A hospital-based cross-sectional and unmatched case-control study was conducted at three teaching hospitals of Addis Ababa University. NTDs were defined as cases of anencephaly, spina bifida, and encephalocele based on ICD-10 criteria. The prevalence of NTDs was calculated per 10,000 births for both birth and total prevalence. During seven months, we observed 55 cases of NTDs out of 8677 births after 28 weeks of gestation-birth prevalence of 63.4 per 10,000 births (95% confidence interval (CI), 51-77). A total of 115 cases were medically terminated after 12 weeks of gestation. Fifty-six of these terminations (48.7%) were due to NTDs. Thus, total prevalence of NTDs after 12 weeks' gestation is 126 per 10,000 births (95% CI, 100-150). Planned pregnancy (adjusted odds ratio (aOR), 0.47; 95% CI, 0.24-0.92), male sex (aOR, 0.56; 95% CI, 0.33-0.94), normal or underweight body mass index (aOR, 0.49; 95%, 0.29-0.95), and taking folic acid or multivitamins during first trimester (aOR, 0.47; 95%, 0.23-0.95) were protective of NTDs. However, annual cash family income less than $1,300 USD (aOR, 2.5; 95%, 1.2-5.5), $1,300-1,800 USD (aOR, 2.8; 95%, 1.3-5.8), and $1,801-2,700 USD (aOR, 2.6; 95%, 1.2-5.8) was found to be risk factors compared to income greater than $2,700 USD. The prevalence of NTDs was found to be high in this setting. Comprehensive preventive strategies focused on identified risk factors should be urgently established. More studies on prevention strategies, including folic acid supplementations, should be conducted in the setting.

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

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    Meng Wang

    2015-04-01

    Full Text Available To study the associations between maternal consumption of non-staple food in the first trimester and risk of neural tube defects (NTDs in offspring. Data collected from a hospital-based case-control study conducted between 2006 and 2008 in Shandong/Shanxi provinces including 459 mothers with NTDs-affected births and 459 mothers without NTDs-affected births. Logistic regression models were used to examine the associations between maternal consumption of non-staple food in the first trimester and risk of NTDs in offspring. The effects were evaluated by odds ratio (OR and 95% confidence intervals (95% CIs with SAS9.1.3.software. Maternal consumption of milk, fresh fruits and nuts in the first trimester were protective factors for total NTDs. Compared with consumption frequency of ˂1 meal/week, the ORs for milk consumption frequency of 1–2, 3–6, ≥7 meals/week were 0.50 (95% CI: 0.28–0.88, 0.56 (0.32–0.99, and 0.59 (0.38–0.90, respectively; the ORs for fresh fruits consumption frequency of 1–2, 3–6, ≥7 meals/week were 0.29 (95% CI: 0.12–0.72, 0.22 (0.09–0.53, and 0.32 (0.14–0.71, respectively; the ORs for nuts consumption frequency of 1–2, 3–6, ≥7 meals/week were 0.60 (95% CI: 0.38–0.94, 0.49 (0.31–0.79, and 0.63 (0.36–1.08, respectively. Different effects of above factors on NTDs were found for subtypes of anencephaly and spina bifida. Maternal non-staple food consumption of milk, fresh fruits and nuts in the first trimester was associated with reducing NTDs risk in offspring.

  5. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects

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    Lam Angeline

    2004-09-01

    Full Text Available Abstract Background Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD. In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. Methods This study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I Determination of rates of NTDs; II Dietary assessment; III Blood analysis; IV Assessment of knowledge and use of folic acid supplements. Results The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991–93 and 1994–97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76–1.34. The rates of NTDs fell by 78% (95% CI 65%–86% after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35. The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B12 deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B12 deficiency. The proportion of women aged 19–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. Conclusions Based on these findings, mandatory food fortification in Canada should continue at the

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

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    Noa Safra

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

  7. Depicting mass flow rate of R134a /LPG refrigerant through straight and helical coiled adiabatic capillary tubes of vapor compression refrigeration system using artificial neural network approach

    Science.gov (United States)

    Gill, Jatinder; Singh, Jagdev

    2018-07-01

    In this work, an experimental investigation is carried out with R134a and LPG refrigerant mixture for depicting mass flow rate through straight and helical coil adiabatic capillary tubes in a vapor compression refrigeration system. Various experiments were conducted under steady-state conditions, by changing capillary tube length, inner diameter, coil diameter and degree of subcooling. The results showed that mass flow rate through helical coil capillary tube was found lower than straight capillary tube by about 5-16%. Dimensionless correlation and Artificial Neural Network (ANN) models were developed to predict mass flow rate. It was found that dimensionless correlation and ANN model predictions agreed well with experimental results and brought out an absolute fraction of variance of 0.961 and 0.988, root mean square error of 0.489 and 0.275 and mean absolute percentage error of 4.75% and 2.31% respectively. The results suggested that ANN model shows better statistical prediction than dimensionless correlation model.

  8. Cadmium inhibits neurogenesis in zebrafish embryonic brain development

    Energy Technology Data Exchange (ETDEWEB)

    Chow, Elly Suk Hen [Division of Biology, California Institute of Technology, 1200 California Boulevard, Pasadena, CA 91125 (United States); Hui, Michelle Nga Yu; Lin Chunchi [Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong (China); Cheng Shukhan [Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong (China)], E-mail: bhcheng@cityu.edu.hk

    2008-05-01

    Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected by cadmium. We observe prominent reductions in the expression of several proneuronal genes including ngn1 in cell clusters, zash1a in the developing optic tectum, and zash1b in the telencephalon and tectum. Cadmium-treated embryos also have fewer differentiated neurons and glia in the facial sensory ganglia as indicated by decreased zn-12 expression. Also, a lower transcription level of neurogenic genes, ngn1 and neuroD, is observed in neurons. Our data suggest that cadmium-induced neurotoxicity can be caused by impaired neurogenesis, resulting in markedly reduced neuronal differentiation and axonogenesis.

  9. Cadmium inhibits neurogenesis in zebrafish embryonic brain development

    International Nuclear Information System (INIS)

    Chow, Elly Suk Hen; Hui, Michelle Nga Yu; Lin Chunchi; Cheng Shukhan

    2008-01-01

    Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected by cadmium. We observe prominent reductions in the expression of several proneuronal genes including ngn1 in cell clusters, zash1a in the developing optic tectum, and zash1b in the telencephalon and tectum. Cadmium-treated embryos also have fewer differentiated neurons and glia in the facial sensory ganglia as indicated by decreased zn-12 expression. Also, a lower transcription level of neurogenic genes, ngn1 and neuroD, is observed in neurons. Our data suggest that cadmium-induced neurotoxicity can be caused by impaired neurogenesis, resulting in markedly reduced neuronal differentiation and axonogenesis

  10. Variations in dysfunction of sister chromatid cohesion in esco2 mutant zebrafish reflect the phenotypic diversity of Roberts syndrome

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    Stefanie M. Percival

    2015-08-01

    Full Text Available Mutations in ESCO2, one of two establishment of cohesion factors necessary for proper sister chromatid cohesion (SCC, cause a spectrum of developmental defects in the autosomal-recessive disorder Roberts syndrome (RBS, warranting in vivo analysis of the consequence of cohesion dysfunction. Through a genetic screen in zebrafish targeting embryonic-lethal mutants that have increased genomic instability, we have identified an esco2 mutant zebrafish. Utilizing the natural transparency of zebrafish embryos, we have developed a novel technique to observe chromosome dynamics within a single cell during mitosis in a live vertebrate embryo. Within esco2 mutant embryos, we observed premature chromatid separation, a unique chromosome scattering, prolonged mitotic delay, and genomic instability in the form of anaphase bridges and micronuclei formation. Cytogenetic studies indicated complete chromatid separation and high levels of aneuploidy within mutant embryos. Amongst aneuploid spreads, we predominantly observed decreases in chromosome number, suggesting that either cells with micronuclei or micronuclei themselves are eliminated. We also demonstrated that the genomic instability leads to p53-dependent neural tube apoptosis. Surprisingly, although many cells required Esco2 to establish cohesion, 10-20% of cells had only weakened cohesion in the absence of Esco2, suggesting that compensatory cohesion mechanisms exist in these cells that undergo a normal mitotic division. These studies provide a unique in vivo vertebrate view of the mitotic defects and consequences of cohesion establishment loss, and they provide a compensation-based model to explain the RBS phenotypes.

  11. ESTIMATION OF THE DEVELOPMENT STANDARD OF NEURAL TUBE IN EMBRYOS FROM TRANSYLVANIAN NAKED NECK AND PLYMOUTH ROCK HEN BREEDS, DURING EARLY EMBRYOGENESIS

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    D. DRONCA

    2007-05-01

    Full Text Available In Romania, the Transylvanian Naked Neck hen breed is considered to be an“endangered” population, reason for which we consider that a special attentionshould have been given until now. Plymouth Rock breed was imported for the firsttime to Romania from the Studler Company, France in 1969. This paper is aimingto perform a profound analysis of the development patterns of the neural tube inthe two breeds, by measurements carried out at 30, 40, 50, and 60 hours ofincubation. Observations show that the closure of the neural canal and itstransformation into a tube follows an undulatory pattern, of which positive andnegative curls are diametrically opposed in the two breeds, while the developmentspeed during the whole studied period have a relative similar value between thetwo breeds. We estimate that the two breeds have a good combinative capacity,which recommend the utilization of these genetic materials to obtain hybrids forproducing “peasant-type” chicken meat, very well-appreciated by the Europeansbetween the two World Wars.

  12. Modulation of nuclear factor-κB signaling and reduction of neural tube defects by quercetin-3-glucoside in embryos of diabetic mice.

    Science.gov (United States)

    Tan, Chengyu; Meng, Fantong; Reece, E Albert; Zhao, Zhiyong

    2018-05-04

    Diabetes mellitus in early pregnancy increases the risk of birth defects in infants. Maternal hyperglycemia stimulates the expression of nitric oxide (NO) synthase 2 (NOS2), which can be regulated by transcription factors of the nuclear factor-κB (NF-κB) family. Increases in reactive nitrogen species (RNS) generate intracellular stress conditions, including nitrosative, oxidative, and endoplasmic reticulum (ER) stresses, and trigger programmed cell death (or apoptosis) in the neural folds, resulting in neural tube defects (NTDs) in the embryo. Inhibiting NOS2 can reduce NTDs; however, the underlying mechanisms require further delineation. Targeting NOS2 and associated nitrosative stress using naturally occurring phytochemicals is a potential approach to preventing birth defects in diabetic pregnancies. This study aims to investigate the effect of quercetin-3-glucoside (Q3G), a polyphenol flavonoid found in fruit, in reducing maternal diabetes-induced NTDs in an animal model, and to delineate the molecular mechanisms underlying Q3G action in regulating NOS2 expression. Female mice (C57BL/6) were induced to develop diabetes using streptozotocin before pregnancy. Diabetic pregnant mice were administered Q3G (100 mg/kg) daily via gavage feeding, introduction of drug to the stomach directly via a feeding needle, during neurulation from embryonic (E) day 6.5 to E9.5. After treatment, E10.5 embryos were collected and examined for the presence of NTDs and apoptosis in the neural tube. Expression of Nos2 and superoxide dismutase 1 (Sod1; an antioxidative enzyme) was quantified using Western blot assay. Nitrosative, oxidative, and endoplasmic reticulum (ER) stress conditions were assessed using specific biomarkers. Expression and posttranslational modification of factors in the NF-κB system were investigated. Treatment with Q3G (suspended in water) significantly decreased NTD rate (24.7%) and apoptosis in the embryos of diabetic mice, compared with those in the water

  13. Prevalência de defeitos de fechamento de tubo neural no Vale do Paraíba, São Paulo Prevalence of neural tube defects in Vale do Paraíba, São Paulo, Brazil

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    Luiz Fernando C. Nascimento

    2008-12-01

    Full Text Available OBJETIVO: Estimar a prevalência de defeitos de fechamento do tubo neural no Vale do Paraíba paulista e identificar possíveis fatores maternos e neonatais associados a tais defeitos. MÉTODOS: Realizou-se um estudo transversal com dados secundários obtidos na Secretaria Estadual da Saúde referentes aos nascimentos ocorridos em 2004 no Vale do Paraíba paulista, que compreende 35 municípios e conta com população de 2 milhões de habitantes. Anencefalia, encefalocele e espina bífida (mielocele e mielomeningocele foram considerados defeitos de fechamento do tubo neural. As variáveis maternas foram: idade, escolaridade, cor da pele, número de consultas no pré-natal, número de filhos vivos e relato de óbito fetal prévio. As variáveis relativas ao recém-nascido foram: peso, idade gestacional e escore de Apgar. Realizou-se comparação das médias por meio do teste t de Student e obtiveram-se os valores das razões de chance com intervalos de confiança de 95%. RESULTADOS: Foram analisados 33.653 nascidos vivos. Trinta e oito recém-nascidos com o defeito foram encontrados (1,13/1.000 nascidos vivos, sendo 23 casos de espina bífida. Houve associação com baixo peso ao nascimento, prematuridade e menores escores de Apgar de cinco minutos. CONCLUSÕES: A prevalência desta anomalia foi inferior à de outros estudos nacionais e sua presença esteve associada ao baixo peso, à prematuridade e à baixa vitalidade ao nascer.OBJECTIVE: To estimate the prevalence of neural tube defects in Vale do Paraíba, São Paulo, Brazil, and to identify possible maternal and neonatal variables associated with these defects. METHODS: This cross-sectional study used secondary records of the Health Department of São Paulo State related live births during 2004 in Vale do Paraíba, São Paulo, Brazil. This region has 35 cities and 2 million inhabitants. Anencephaly, encephalocele and spina bifida (myelocele and myelomeningocele were considered as neural tube

  14. Novel Method for Measuring the Heat Collection Rate and Heat Loss Coefficient of Water-in-Glass Evacuated Tube Solar Water Heaters Based on Artificial Neural Networks and Support Vector Machine

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    Zhijian Liu

    2015-08-01

    Full Text Available The determinations 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, the direct determination requires complex detection devices and a series of standard experiments, which also wastes too much time and manpower. To address this problem, we propose machine learning models including artificial neural networks (ANNs and support vector machines (SVM to predict the heat collection rate and heat loss coefficient without a direct determination. Parameters that can be easily obtained by “portable test instruments” were set as independent variables, including tube length, number of tubes, tube center distance, heat water mass in tank, collector area, final temperature and angle between tubes and ground, while the heat collection rate and heat loss coefficient determined by the detection device were set as dependent variables respectively. Nine hundred fifteen samples from in-service water-in-glass evacuated tube solar water heaters were used for training and testing the models. Results show that the multilayer feed-forward neural network (MLFN with 3 nodes is the best model for the prediction of heat collection rate and the general regression neural network (GRNN is the best model for the prediction of heat loss coefficient due to their low root mean square (RMS errors, short training times, and high prediction accuracies (under the tolerances of 30%, 20%, and 10%, respectively.

  15. Social learning of an associative foraging task in zebrafish

    Science.gov (United States)

    Zala, Sarah M.; Määttänen, Ilmari

    2013-05-01

    The zebrafish ( Danio rerio) is increasingly becoming an important model species for studies on the genetic and neural mechanisms controlling behaviour and cognition. Here, we utilized a conditioned place preference (CPP) paradigm to study social learning in zebrafish. We tested whether social interactions with conditioned demonstrators enhance the ability of focal naïve individuals to learn an associative foraging task. We found that the presence of conditioned demonstrators improved focal fish foraging behaviour through the process of social transmission, whereas the presence of inexperienced demonstrators interfered with the learning of the control focal fish. Our results indicate that zebrafish use social learning for finding food and that this CPP paradigm is an efficient assay to study social learning and memory in zebrafish.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi [Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland); Alhonen, Leena [Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Kuopio (Finland); School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio (Finland); Salonurmi, Tuire; Savolainen, Markku J. [Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland)

    2014-03-28

    Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this

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

    Science.gov (United States)

    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

  19. Towards a comprehensive catalog of zebrafish behavior 1.0 and beyond.

    Science.gov (United States)

    Kalueff, Allan V; Gebhardt, Michael; Stewart, Adam Michael; Cachat, Jonathan M; Brimmer, Mallorie; Chawla, Jonathan S; Craddock, Cassandra; Kyzar, Evan J; Roth, Andrew; Landsman, Samuel; Gaikwad, Siddharth; Robinson, Kyle; Baatrup, Erik; Tierney, Keith; Shamchuk, Angela; Norton, William; Miller, Noam; Nicolson, Teresa; Braubach, Oliver; Gilman, Charles P; Pittman, Julian; Rosemberg, Denis B; Gerlai, Robert; Echevarria, David; Lamb, Elisabeth; Neuhauss, Stephan C F; Weng, Wei; Bally-Cuif, Laure; Schneider, Henning

    2013-03-01

    Zebrafish (Danio rerio) are rapidly gaining popularity in translational neuroscience and behavioral research. Physiological similarity to mammals, ease of genetic manipulations, sensitivity to pharmacological and genetic factors, robust behavior, low cost, and potential for high-throughput screening contribute to the growing utility of zebrafish models in this field. Understanding zebrafish behavioral phenotypes provides important insights into neural pathways, physiological biomarkers, and genetic underpinnings of normal and pathological brain function. Novel zebrafish paradigms continue to appear with an encouraging pace, thus necessitating a consistent terminology and improved understanding of the behavioral repertoire. What can zebrafish 'do', and how does their altered brain function translate into behavioral actions? To help address these questions, we have developed a detailed catalog of zebrafish behaviors (Zebrafish Behavior Catalog, ZBC) that covers both larval and adult models. Representing a beginning of creating a more comprehensive ethogram of zebrafish behavior, this effort will improve interpretation of published findings, foster cross-species behavioral modeling, and encourage new groups to apply zebrafish neurobehavioral paradigms in their research. In addition, this glossary creates a framework for developing a zebrafish neurobehavioral ontology, ultimately to become part of a unified animal neurobehavioral ontology, which collectively will contribute to better integration of biological data within and across species.

  20. Zebrafish models for the functional genomics of neurogenetic disorders.

    Science.gov (United States)

    Kabashi, Edor; Brustein, Edna; Champagne, Nathalie; Drapeau, Pierre

    2011-03-01

    In this review, we consider recent work using zebrafish to validate and study the functional consequences of mutations of human genes implicated in a broad range of degenerative and developmental disorders of the brain and spinal cord. Also we present technical considerations for those wishing to study their own genes of interest by taking advantage of this easily manipulated and clinically relevant model organism. Zebrafish permit mutational analyses of genetic function (gain or loss of function) and the rapid validation of human variants as pathological mutations. In particular, neural degeneration can be characterized at genetic, cellular, functional, and behavioral levels. Zebrafish have been used to knock down or express mutations in zebrafish homologs of human genes and to directly express human genes bearing mutations related to neurodegenerative disorders such as spinal muscular atrophy, ataxia, hereditary spastic paraplegia, amyotrophic lateral sclerosis (ALS), epilepsy, Huntington's disease, Parkinson's disease, fronto-temporal dementia, and Alzheimer's disease. More recently, we have been using zebrafish to validate mutations of synaptic genes discovered by large-scale genomic approaches in developmental disorders such as autism, schizophrenia, and non-syndromic mental retardation. Advances in zebrafish genetics such as multigenic analyses and chemical genetics now offer a unique potential for disease research. Thus, zebrafish hold much promise for advancing the functional genomics of human diseases, the understanding of the genetics and cell biology of degenerative and developmental disorders, and the discovery of therapeutics. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Swimming Effects on Developing Zebrafish

    NARCIS (Netherlands)

    Kranenbarg, S.; Pelster, B.

    2013-01-01

    Zebrafish represent an important vertebrate model species in developmental biology. This chapter reviews the effects of exercise on the development of the musculoskeletal system, the cardiovascular system, metabolic capacities of developing zebrafish, and regulation of these processes on the gene

  2. Graph theoretical model of a sensorimotor connectome in zebrafish.

    Science.gov (United States)

    Stobb, Michael; Peterson, Joshua M; Mazzag, Borbala; Gahtan, Ethan

    2012-01-01

    Mapping the detailed connectivity patterns (connectomes) of neural circuits is a central goal of neuroscience. The best quantitative approach to analyzing connectome data is still unclear but graph theory has been used with success. We present a graph theoretical model of the posterior lateral line sensorimotor pathway in zebrafish. The model includes 2,616 neurons and 167,114 synaptic connections. Model neurons represent known cell types in zebrafish larvae, and connections were set stochastically following rules based on biological literature. Thus, our model is a uniquely detailed computational representation of a vertebrate connectome. The connectome has low overall connection density, with 2.45% of all possible connections, a value within the physiological range. We used graph theoretical tools to compare the zebrafish connectome graph to small-world, random and structured random graphs of the same size. For each type of graph, 100 randomly generated instantiations were considered. Degree distribution (the number of connections per neuron) varied more in the zebrafish graph than in same size graphs with less biological detail. There was high local clustering and a short average path length between nodes, implying a small-world structure similar to other neural connectomes and complex networks. The graph was found not to be scale-free, in agreement with some other neural connectomes. An experimental lesion was performed that targeted three model brain neurons, including the Mauthner neuron, known to control fast escape turns. The lesion decreased the number of short paths between sensory and motor neurons analogous to the behavioral effects of the same lesion in zebrafish. This model is expandable and can be used to organize and interpret a growing database of information on the zebrafish connectome.

  3. Graph theoretical model of a sensorimotor connectome in zebrafish.

    Directory of Open Access Journals (Sweden)

    Michael Stobb

    Full Text Available Mapping the detailed connectivity patterns (connectomes of neural circuits is a central goal of neuroscience. The best quantitative approach to analyzing connectome data is still unclear but graph theory has been used with success. We present a graph theoretical model of the posterior lateral line sensorimotor pathway in zebrafish. The model includes 2,616 neurons and 167,114 synaptic connections. Model neurons represent known cell types in zebrafish larvae, and connections were set stochastically following rules based on biological literature. Thus, our model is a uniquely detailed computational representation of a vertebrate connectome. The connectome has low overall connection density, with 2.45% of all possible connections, a value within the physiological range. We used graph theoretical tools to compare the zebrafish connectome graph to small-world, random and structured random graphs of the same size. For each type of graph, 100 randomly generated instantiations were considered. Degree distribution (the number of connections per neuron varied more in the zebrafish graph than in same size graphs with less biological detail. There was high local clustering and a short average path length between nodes, implying a small-world structure similar to other neural connectomes and complex networks. The graph was found not to be scale-free, in agreement with some other neural connectomes. An experimental lesion was performed that targeted three model brain neurons, including the Mauthner neuron, known to control fast escape turns. The lesion decreased the number of short paths between sensory and motor neurons analogous to the behavioral effects of the same lesion in zebrafish. This model is expandable and can be used to organize and interpret a growing database of information on the zebrafish connectome.

  4. Zebrafish Health Conditions in the China Zebrafish Resource Center and 20 Major Chinese Zebrafish Laboratories.

    Science.gov (United States)

    Liu, Liyue; Pan, Luyuan; Li, Kuoyu; Zhang, Yun; Zhu, Zuoyan; Sun, Yonghua

    2016-07-01

    In China, the use of zebrafish as an experimental animal in the past 15 years has widely expanded. The China Zebrafish Resource Center (CZRC), which was established in 2012, is becoming one of the major resource centers in the global zebrafish community. Large-scale use and regular exchange of zebrafish resources have put forward higher requirements on zebrafish health issues in China. This article reports the current aquatic infrastructure design, animal husbandry, and health-monitoring programs in the CZRC. Meanwhile, through a survey of 20 Chinese zebrafish laboratories, we also describe the current health status of major zebrafish facilities in China. We conclude that it is of great importance to establish a widely accepted health standard and health-monitoring strategy in the Chinese zebrafish research community.

  5. Efeito da fortificação alimentar com ácido fólico na prevalência de defeitos do tubo neural Efecto de la fortificación alimentaria con ácido fólico en la prevalencia de defectos del tubo neural Effects of folic acid fortification on the prevalence of neural tube defects

    Directory of Open Access Journals (Sweden)

    Sâmya Silva Pacheco

    2009-08-01

    defectos del cierre del tubo neural fueron definidos de acuerdo con el Códigos Internacional de Enfermedades- 10ª Revisión: anencefalia, encefalocele y espina bífida. Se compararon las prevalencias en los períodos anterior (2000 - 2004 y posterior (2005-2006 al período obligatorio de fortificación. Se analizó la tendencia temporal de las prevalencias trimestrales de defectos del cierre del tubo neural por las pruebas de Mann-Kendall y Sen's Slope. RESULTADOS: No se identificó tendencia de reducción en la ocurrencia del hecho (Teste de Mann-Kendall; p= 0,270; Sen's Slope = - 0,008 en el período estudiado. No hubo diferencia estadísticamente significativa entre las prevalencias de defectos de cierre del tubo neural en los períodos anterior y posterior a la fortificación de los alimentos con ácido fólico de acuerdo con las características maternas. CONCLUSIONES: A pesar de que no haya sido observada reducción de los defectos de cierre del tubo neural posterior al período obligatorio de fortificación de alimentos con ácido fólico, los resultados encontrados no permiten descartar el beneficio del mismo en la prevención de esta malformación. Son necesarios estudios evaluando mayor período y considerando el nivel de consumo de los productos fortificados por las mujeres en edad fértil.OBJECTIVE:To analyze the effect of folic acid-fortified foods on the prevalence of neural tube defects in live newborns. METHODS: Longitudinal study with newborns from the city of Recife, Northeastern Brazil, between 2000 and 2006. Data analyzed were obtained from the Sistema Nacional de Informações de Nascidos Vivos (National Information System on Live Births. Neural tube defects were defined in accordance with the International Classification of Diseases, 10th revision (ICD-10: anencephaly, encephalocele, and spina bifida. Prevalences from the periods before (2000-2004 and after (2005-2006 the mandatory fortification period were compared. Time trend of three

  6. Tissue-Specific Methylation of Long Interspersed Nucleotide Element-1 of Homo Sapiens (L1Hs) During Human Embryogenesis and Roles in Neural Tube Defects.

    Science.gov (United States)

    Wang, L; Chang, S; Guan, J; Shangguan, S; Lu, X; Wang, Z; Wu, L; Zou, J; Zhao, H; Bao, Y; Qiu, Z; Niu, B; Zhang, T

    2015-01-01

    Epigenetic regulation of long interspersed nucleotide element-1 (LINE-1) retrotransposition events plays crucial roles during early development. Previously we showed that LINE-1 hypomethylation in neuronal tissues is associated with pathogenesis of neural tube defect (NTD). Herein, we further evaluated LINE-1 Homo sapiens (L1Hs) methylation in tissues derived from three germ layers of stillborn NTD fetuses, to define patterns of tissue specific methylation and site-specific hypomethylation at CpG sites within an L1Hs promoter region. Stable, tissue-specific L1Hs methylation patterns throughout three germ layer lineages of the fetus, placenta, and maternal peripheral blood were observed. Samples from maternal peripheral blood exhibited the highest level of L1Hs methylation (64.95%) and that from placenta showed the lowest (26.82%). Between samples from NTDs and controls, decrease in L1Hs methylation was only significant in NTD-affected brain tissue at 7.35%, especially in females (8.98%). L1Hs hypomethylation in NTDs was also associated with a significant increase in expression level of an L1Hs-encoded transcript in females (r = -0.846, p = 0.004). This could be due to genomic DNA instability and alternation in chromatins accessibility resulted from abnormal L1Hs hypomethylation, as showed in this study with HCT-15 cells treated with methylation inhibitor 5-Aza.

  7. Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study.

    Science.gov (United States)

    Cadenas-Benitez, N M; Yanes-Sosa, F; Gonzalez-Meneses, A; Cerrillos, L; Acosta, D; Praena-Fernandez, J M; Neth, O; Gomez de Terreros, I; Ybot-González, P

    2014-03-26

    Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

  8. CERKL knockdown causes retinal degeneration in zebrafish.

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    Marina Riera

    Full Text Available The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration.

  9. The neurogenetic frontier—lessons from misbehaving zebrafish

    Science.gov (United States)

    Granato, Michael

    2008-01-01

    One of the central questions in neuroscience is how refined patterns of connectivity in the brain generate and monitor behavior. Genetic mutations can influence neural circuits by disrupting differentiation or maintenance of component neuronal cells or by altering functional patterns of nervous system connectivity. Mutagenesis screens therefore have the potential to reveal not only the molecular underpinnings of brain development and function, but to illuminate the cellular basis of behavior. Practical considerations make the zebrafish an organism of choice for undertaking forward genetic analysis of behavior. The powerful array of experimental tools at the disposal of the zebrafish researcher makes it possible to link molecular function to neuronal properties that underlie behavior. This review focuses on specific challenges to isolating and analyzing behavioral mutants in zebrafish. PMID:18836206

  10. The neurogenetic frontier--lessons from misbehaving zebrafish.

    Science.gov (United States)

    Burgess, Harold A; Granato, Michael

    2008-11-01

    One of the central questions in neuroscience is how refined patterns of connectivity in the brain generate and monitor behavior. Genetic mutations can influence neural circuits by disrupting differentiation or maintenance of component neuronal cells or by altering functional patterns of nervous system connectivity. Mutagenesis screens therefore have the potential to reveal not only the molecular underpinnings of brain development and function, but to illuminate the cellular basis of behavior. Practical considerations make the zebrafish an organism of choice for undertaking forward genetic analysis of behavior. The powerful array of experimental tools at the disposal of the zebrafish researcher makes it possible to link molecular function to neuronal properties that underlie behavior. This review focuses on specific challenges to isolating and analyzing behavioral mutants in zebrafish.

  11. Imaging a seizure model in zebrafish with structured illumination light sheet microscopy

    Science.gov (United States)

    Liu, Yang; Dale, Savannah; Ball, Rebecca; VanLeuven, Ariel J.; Baraban, Scott; Sornborger, Andrew; Lauderdale, James D.; Kner, Peter

    2018-02-01

    Zebrafish are a promising vertebrate model for elucidating how neural circuits generate behavior under normal and pathological conditions. The Baraban group first demonstrated that zebrafish larvae are valuable for investigating seizure events and can be used as a model for epilepsy in humans. Because of their small size and transparency, zebrafish embryos are ideal for imaging seizure activity using calcium indicators. Light-sheet microscopy is well suited to capturing neural activity in zebrafish because it is capable of optical sectioning, high frame rates, and low excitation intensities. We describe work in our lab to use light-sheet microscopy for high-speed long-time imaging of neural activity in wildtype and mutant zebrafish to better understand the connectivity and activity of inhibitory neural networks when GABAergic signaling is altered in vivo. We show that, with light-sheet microscopy, neural activity can be recorded at 23 frames per second in twocolors for over 10 minutes allowing us to capture rare seizure events in mutants. We have further implemented structured illumination to increase resolution and contrast in the vertical and axial directions during high-speed imaging at an effective frame rate of over 7 frames per second.

  12. Plasma folate levels and associated factors in women planning to become pregnant in a population with high prevalence of neural tube defects.

    Science.gov (United States)

    Ma, Rui; Wang, Linlin; Jin, Lei; Li, Zhiwen; Ren, Aiguo

    2017-07-17

    Optimal blood folate levels of women before pregnancy are critical to the prevention of neural tube defects (NTDs). However, few studies have focused on blood folate levels of women planning to become pregnant. The aims of this study were to assess plasma folate levels in women who planned to become pregnant in a population with high prevalence of NTDs, to identify factors associated with plasma folate levels, and to evaluate the risk of NTDs at the population level. A total of 2065 women were enrolled at the time of premarital health check-up in two rural counties in northern China from November 2009 to December 2012. Fasting venous blood samples were collected and plasma folate concentrations were measured by microbiological method. The overall median of plasma folate was 10.5 nmol/L. 50% of the women had a plasma folate level below 10.5 nmol/L, a cutoff for megaloblastic anemia, and 88% below 18 nmol/L, a proposed optimal plasma folate level for the prevention of NTDs. Folic acid supplementation was the only factor to be associated with plasma folate concentrations, but only 1.9% of the women reported having taken folic acid supplements. A population risk of 29.3 NTD cases per 10,000 births was predicted. Women who planned to become pregnant had very low plasma folate in the population. Folic acid supplementation was the only factor to be associated with a high plasma folate concentration. High NTD risk would remain if women would get pregnant without having taken folic acid supplements. Birth Defects Research 109:1039-1047, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2008-11-01

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

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

    Directory of Open Access Journals (Sweden)

    S Leah Etheridge

    2008-11-01

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

  15. Epidemiologic study of neural tube defects in Los Angeles County. II. Etiologic factors in an area with low prevalence at birth

    Energy Technology Data Exchange (ETDEWEB)

    Sever, L.E.

    1982-01-01

    Epidemiologic characteristics of neural tube defect (NTD) births occurring in Los Angeles County, California, residents during the period 1966-1972 are presented. The prevalence at birth was 0.52/1000 births for anencephalus, 0.51/1000 for spina bifida, and 0.08/1000 for encephalocele, rates considered to be low for a predominantly white population. We hypothesized that environmental (nongenetic) factors are of less etiologic importance in a low-prevalence population than in areas or time periods with high prevalence. We tested that hypothesis by examining epidemiologic characteristics of NTDs in Los Angeles County and comparing them with high-prevalence populations. The data did not support a major etiologic role for environmental factors: (1) no significant differences between rates by month of birth or conception; (2) no significant association with maternal age or parity for anencephalus; for spina bifida a significant maternal age effect (P < 0.01) and for encephalocele a parity effect (P < 0.02); and (3) no significant relationship with father's occupational class for either anencephalus or encephalocele but a marginally significant (P < 0.05) inverse association for spina bifida when a statistic based on ordinal relationships was used. Findings supporting the importance of genetic factors in etiology included: (1) a high percentage of males; (2) a higher twin concordance rate than in high-prevalence populations; and (3) an anencephalus rate among blacks comparable with rates for blacks in other United States populations. Our findings in conjunction with those from other areas and times of low prevalence suggest environmental factors play a relatively insignificant role in the etiology of NTDs in such populations.

  16. Knowledge and periconceptional use of folic acid for the prevention of neural tube defects in ethnic communities in the United Kingdom: systematic review and meta-analysis.

    Science.gov (United States)

    Peake, Jordana N; Copp, Andrew J; Shawe, Jill

    2013-07-01

    It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.). A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced sources published after 1991, the year of the landmark Medical Research Council's Vitamin Study, were included. A meta-analysis was performed of studies that assessed preconceptional folic acid use in Caucasians and non-Caucasians. Five studies met the inclusion criteria for assessment of knowledge and/or use of folic acid supplements in U.K. women including non-Caucasians. The available evidence indicates that South Asians specifically have less knowledge and lower periconceptional use of folic acid than Caucasians; one study found that West Indian and African women also had lower folic acid uptake. A synthesis of results from three of the studies, in a meta-analysis, shows that Caucasians are almost three times more likely to take folic acid before conception than non-Caucasians. From the limited evidence available, U.K. women of non-Caucasian ethnicity appear to have less knowledge and a lower uptake of folic acid supplementation than Caucasians during the periconceptional period. Implementing targeted, innovative education campaigns together with a mandatory fortification policy, including the fortification of ethnic minority foods, will be required for maximum prevention of folic acid-preventable NTDs across different ethnic groups. Copyright © 2013 Wiley Periodicals, Inc.

  17. Formate supplementation enhances folate-dependent nucleotide biosynthesis and prevents spina bifida in a mouse model of folic acid-resistant neural tube defects.

    Science.gov (United States)

    Sudiwala, Sonia; De Castro, Sandra C P; Leung, Kit-Yi; Brosnan, John T; Brosnan, Margaret E; Mills, Kevin; Copp, Andrew J; Greene, Nicholas D E

    2016-07-01

    The curly tail mouse provides a model for neural tube defects (spina bifida and exencephaly) that are resistant to prevention by folic acid. The major ct gene, responsible for spina bifida, corresponds to a hypomorphic allele of grainyhead-like 3 (Grhl3) but the frequency of NTDs is strongly influenced by modifiers in the genetic background. Moreover, exencephaly in the curly tail strain is not prevented by reinstatement of Grhl3 expression. In the current study we found that expression of Mthfd1L, encoding a key component of mitochondrial folate one-carbon metabolism (FOCM), is significantly reduced in ct/ct embryos compared to a partially congenic wild-type strain. This expression change is not attributable to regulation by Grhl3 or the genetic background at the Mthfd1L locus. Mitochondrial FOCM provides one-carbon units as formate for FOCM reactions in the cytosol. We found that maternal supplementation with formate prevented NTDs in curly tail embryos and also resulted in increased litter size. Analysis of the folate profile of neurulation-stage embryos showed that formate supplementation resulted in an increased proportion of formyl-THF and THF but a reduction in proportion of 5-methyl THF. In contrast, THF decreased and 5-methyl THF was relatively more abundant in the liver of supplemented dams than in controls. In embryos cultured through the period of spinal neurulation, incorporation of labelled thymidine and adenine into genomic DNA was suppressed by supplemental formate, suggesting that de novo folate-dependent biosynthesis of nucleotides (thymidylate and purines) was enhanced. We hypothesise that reduced Mthfd1L expression may contribute to susceptibility to NTDs in the curly tail strain and that formate acts as a one-carbon donor to prevent NTDs. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Redundant roles of PRDM family members in zebrafish craniofacial development.

    Science.gov (United States)

    Ding, Hai-Lei; Clouthier, David E; Artinger, Kristin B

    2013-01-01

    PRDM proteins are evolutionary conserved Zn-Finger transcription factors that share a characteristic protein domain organization. Previous studies have shown that prdm1a is required for the specification and differentiation of neural crest cells in the zebrafish. Here we examine other members of this family, specifically prdm3, 5, and 16, in the differentiation of the zebrafish craniofacial skeleton. prdm3 and prdm16 are strongly expressed in the pharyngeal arches, while prdm5 is expressed specifically in the area of the forming neurocranium. Knockdown of prdm3 and prdm16 results in a reduction in the neural crest markers dlx2a and barx1 and defects in both the viscerocranium and the neurocranium. The knockdown of prdm3 and prdm16 in combination is additive in the neurocranium, but not in the viscerocranium. Injection of sub-optimal doses of prdm1a with prdm3 or prdm16 Morpholinos together leads to more severe phenotypes in the viscerocranium and neurocranium. prdm5 mutants have defects in the neurocranium and prdm1a and prdm5 double mutants also show more severe phenotypes. Overall, our data reveal that prdm3, 5, and 16 are involved in the zebrafish craniofacial development and that prdm1a may interact with prdm3, 5, and 16 in the formation of the craniofacial skeleton in zebrafish. Copyright © 2012 Wiley Periodicals, Inc.

  19. Neural Development in tsc2-Deficient Zebrafish

    Science.gov (United States)

    2011-10-01

    the cells in this region normally give rise to forebrain and retina (Woo and Fraser, 1995). Analyses of chimeric embryos at 7.5 dpf revealed that...white matter. Green color is tissue autofluorescence ; blue is DAPI staining. P, pallium; Po, preoptic region; Sd, dorsal division of subpallium; Tve

  20. Bioluminescence Monitoring of Neuronal Activity in Freely Moving Zebrafish Larvae

    Science.gov (United States)

    Knafo, Steven; Prendergast, Andrew; Thouvenin, Olivier; Figueiredo, Sophie Nunes; Wyart, Claire

    2017-01-01

    The proof of concept for bioluminescence monitoring of neural activity in zebrafish with the genetically encoded calcium indicator GFP-aequorin has been previously described (Naumann et al., 2010) but challenges remain. First, bioluminescence signals originating from a single muscle fiber can constitute a major pitfall. Second, bioluminescence signals emanating from neurons only are very small. To improve signals while verifying specificity, we provide an optimized 4 steps protocol achieving: 1) selective expression of a zebrafish codon-optimized GFP-aequorin, 2) efficient soaking of larvae in GFP-aequorin substrate coelenterazine, 3) bioluminescence monitoring of neural activity from motor neurons in free-tailed moving animals performing acoustic escapes and 4) verification of the absence of muscle expression using immunohistochemistry. PMID:29130058

  1. What Are Neural Tube Defects?

    Science.gov (United States)

    ... are born with spina bifida will have normal intelligence, but some will have learning or intellectual disabilities . 1 There are several common types of spina bifida: Spina bifida occulta (pronounced o- ...

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

    International Nuclear Information System (INIS)

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

    2006-01-01

    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

  3. Levels of PAH-DNA adducts in cord blood and cord tissue and the risk of fetal neural tube defects in a Chinese population.

    Science.gov (United States)

    Yi, Deqing; Yuan, Yue; Jin, Lei; Zhou, Guodong; Zhu, Huiping; Finnell, Richard H; Ren, Aiguo

    2015-01-01

    Maternal exposure to polycyclic aromatic hydrocarbons (PAHs) has been shown to be associated with an elevated risk for neural tube defects (NTDs). In the human body, PAHs are bioactivated and the resultant reactive epoxides can covalently bind to DNA to form PAH-DNA adducts, which may, in turn, cause transcription errors, changes in gene expression or altered patterns of apoptosis. During critical developmental phases, these changes can result in abnormal morphogenesis. We aimed to examine the relationship between the levels of PAH-DNA adducts in cord blood and cord tissue and the risk of NTDs. From 2010 to 2012, 60 NTD cases and 60 healthy controls were recruited from a population-based birth defects surveillance system in five counties of Shanxi Province in Northern China, where the emission of PAHs remains one of the highest in the country and PAHs exposure is highly prevalent. PAH-DNA adducts in cord blood of 15 NTD cases and 15 control infants, and in cord tissue of 60 NTD cases and 60 control infants were measured using the (32)P-postlabeling method. PAH-DNA adduct levels in cord blood tend to be higher in the NTD group (28.5 per 10(8) nucleotides) compared with controls (19.7 per 10(8) nucleotides), although the difference was not statistically significant (P=0.377). PAH-DNA adducts in cord tissue were significantly higher in the NTD group (24.6 per 10(6) nucleotides) than in the control group (15.3 per 10(6) nucleotides), P=0.010. A positive dose-response relationship was found between levels of PAH-DNA adducts in cord tissue and the risk of NTDs (P=0.009). When the lowest tertile was used as the referent and potential confounding factors were adjusted for, a 1.03-fold (95% CI, 0.37-2.89) and 2.96-fold (95% CI, 1.16-7.58) increase in the risk of NTDs was observed for fetuses whose cord tissue PAH-DNA adduct levels were in the second and highest tertile, respectively. High levels of PAH-DNA adducts in fetal tissues were associated with increased risks of

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

    Directory of Open Access Journals (Sweden)

    Paudyal Anju

    2010-08-01

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

  5. Skin too thin? The developing utility of zebrafish skin (neuro)pharmacology for CNS drug discovery research.

    Science.gov (United States)

    Nguyen, Michael; Poudel, Manoj K; Stewart, Adam Michael; Kalueff, Allan V

    2013-09-01

    Skin coloration can be affected by many genetic, environmental and pharmacological factors. Zebrafish (Danio rerio) are a useful and versatile model organism in biomedical research due to their genetic tractability, physiological homology to mammals, low cost, reproducibility and high throughput. Zebrafish coloration is mediated by chromatophores - the skin color pigment cells largely controlled by endocrine and neural mechanisms. The characteristic darkening of zebrafish skin is caused by the dispersion (and paling - by aggregation) of melanosomes (pigment-containing organelles), which show high homology to mammalian structures. Various pharmacological agents potently affect zebrafish coloration - the phenotype that often accompanies behavioral effects of the drugs, and may be used for drug discovery. Although zebrafish behavior and skin responses are usually not directly related, they share common regulatory (neural, endocrine) mechanisms, and therefore may be assessed in parallel during psychotropic drug screening. For example, some psychoactive drugs can potently affect zebrafish skin coloration. Can we use this knowledge to refine phenotype-driven psychotropic drug discovery? Here, we present current models using zebrafish skin coloration assays, and discuss how these models may be applied to enhance in vivo CNS drug discovery. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Egfl6 is involved in zebrafish notochord development.

    Science.gov (United States)

    Wang, Xueqian; Wang, Xin; Yuan, Wei; Chai, Renjie; Liu, Dong

    2015-08-01

    The epidermal growth factor (EGF) repeat motif defines a superfamily of diverse protein involved in regulating a variety of cellular and physiological processes, such as cell cycle, cell adhesion, proliferation, migration, and neural development. Egfl6, an EGF protein, also named MAGE was first cloned in human tissue. Up to date, the study of zebrafish Egfl6 expression pattern and functional analysis of Egfl6 involved in embryonic development of vertebrate in vivo is thus far lacking. Here we reported that Egfl6 was involved in zebrafish notochord development. It was shown that Egfl6 mRNA was expressed in zebrafish, developing somites, fin epidermis, pharyngeal arches, and hindbrain region. Particularly the secreted Egfl6 protein was significantly accumulated in notochord. Loss of Egfl6 function in zebrafish embryos resulted in curved body with distorted notochord in the posterior trunk. It was observed that expression of all Notch ligand and receptors in notochord of 28 hpf Egfl6 morphants was not affected, except notch2, which was up-regulated. We found that inhibition of Notch signaling by DAPT efficiently rescued notochord developmental defect of Egfl6 deficiency embryos.

  7. Knockdown of Laminin gamma-3 (Lamc3 impairs motoneuron guidance in the zebrafish embryo [version 1; referees: 2 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Alexander M. J. Eve

    2017-11-01

    Full Text Available Background: Previous work in the zebrafish embryo has shown that laminin γ-3 (lamc3 is enriched in endothelial cells marked by expression of fli1a, but the role of Lamc3 has been unknown. Methods: We use antisense morpholino oligonucleotides, and CRISPR/Cas9 mutagenesis of F0 embryos, to create zebrafish embryos in which lamc3 expression is compromised. Transgenic imaging, immunofluorescence, and in situ hybridisation reveal that Lamc3 loss-of-function affects the development of muscle pioneers, endothelial cells, and motoneurons. Results: Lamc3 is enriched in endothelial cells during zebrafish development, but it is also expressed by other tissues. Depletion of Lamc3 by use of antisense morpholino oligonucleotides perturbs formation of the parachordal chain and subsequently the thoracic duct, but Lamc3 is not required for sprouting of the cardinal vein. F0 embryos in which lamc3 expression is perturbed by a CRISPR/Cas9 approach also fail to form a parachordal chain, but we were unable to establish a stable lamc3 null line. Lamc3 is dispensable for muscle pioneer specification and for the expression of netrin-1a in these cells. Lamc3 knockdown causes netrin-1a up-regulation in the neural tube and there is increased Netrin-1 protein throughout the trunk of the embryo. Axonal guidance of rostral primary motoneurons is defective in Lamc3 knockdown embryos. Conclusions: We suggest that knockdown of Lamc3 perturbs migration of rostral primary motoneurons at the level of the horizontal myoseptum, indicating that laminin γ3 plays a role in motoneuron guidance.

  8. Ethanol exposure affects cell movement during gastrulation and induces split axes in zebrafish embryos.

    Science.gov (United States)

    Zhang, Ying; Shao, Ming; Wang, Lifeng; Liu, Zhongzhen; Gao, Ming; Liu, Chao; Zhang, Hongwei

    2010-06-01

    To explore the toxic effects of ethanol on axis formation during embryogenesis, zebrafish embryos at different developmental stages were treated with 3% ethanol for 3h. The effects of ethanol exposure appeared to be stage-dependent. The dome stage embryo was most sensible to form posterior split axes upon ethanol exposure. Morphological and histological observations and whole-mount in situ hybridization results showed that ethanol exposure at this stage caused a general gastrulation delay, and induced double notochords, double neural tubes and two sets of somites in the posterior trunk. Mechanistically, no ectopic organizer was found by examining the expression patterns of dorsoventral markers including goosecoid, chordin and eve1 at the onset of gastrulation. However, radial intercalation, epiboly and convergence extension were inhibited by ethanol exposure as revealed by cell labeling, phenotypic observation and the expression patterns of axial or paraxial markers. Further investigation showed that the cell aggregation might be affected by ethanol exposure, as indicated by the much more scattered expression pattern of chordin, eve1 and wnt11 at the early gastrula stage, and the discontinuous gsc positive cells during migration. These results imply that ethanol might affect cell movement before and during gastrulation and as a consequence, induces a split axes phenotype. Copyright 2010 ISDN. Published by Elsevier Ltd. All rights reserved.

  9. Tube plug

    International Nuclear Information System (INIS)

    Zafred, P. R.

    1985-01-01

    The tube plug comprises a one piece mechanical plug having one open end and one closed end which is capable of being inserted in a heat exchange tube and internally expanded into contact with the inside surface of the heat exchange tube for preventing flow of a coolant through the heat exchange tube. The tube plug also comprises a groove extending around the outside circumference thereof which has an elastomeric material disposed in the groove for enhancing the seal between the tube plug and the tube

  10. Apical Polarity Protein PrkCi Is Necessary for Maintenance of Spinal Cord Precursors in Zebrafish

    OpenAIRE

    Roberts, Randolph K.; Appel, Bruce

    2009-01-01

    During development, neural precursors divide to produce new precursors and cells that differentiate as neurons and glia. In Drosophila, apicobasal polarity and orientation of the mitotic spindle play important roles in specifying the progeny of neural precursors for different fates. We examined orientation of zebrafish spinal cord precursors using time-lapse imaging and tested the function of protein kinase C, iota (PrkCi), a member of the Par complex of proteins necessary for apicobasal pola...

  11. Developmental nephrotoxicity of aristolochic acid in a zebrafish model

    International Nuclear Information System (INIS)

    Ding, Yu-Ju; Chen, Yau-Hung

    2012-01-01

    Aristolochic acid (AA) is a component of Aristolochia plant extracts which is used as a treatment for different pathologies and their toxicological effects have not been sufficiently studied. The aim of this study was to evaluate AA-induced nephrotoxicity in zebrafish embryos. After soaking zebrafish embryos in AA, the embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tubes, pronephric ducts, and cases of atrophic glomeruli. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. Furthermore, AA-treated embryos exhibited significantly reduced glomerular filtration rates (GFRs) in comparison with mock-control littermates (mock-control: 100 ± 2.24% vs. 10 ppm AA treatment for 3–5 h: 71.48 ± 18.84% ∼ 39.41 ± 15.88%), indicating that AA treatment not only caused morphological kidney changes but also induced renal failure. In addition to kidney malformations, AA-treated zebrafish embryos also exhibited deformed hearts, swollen pericardiums, impaired blood circulation and the accumulation(s) of red blood cells. Whole-mount in situ hybridization studies using cmlc2 and wt1b as riboprobes indicated that the kidney is more sensitive than the heart to AA damage. Real-time PCR showed that AA can up-regulate the expression of proinflammatory genes like TNFα, cox2 and mpo. These results support the following conclusions: (1) AA-induced renal failure is mediated by inflammation, which causes circulation dysfunction followed by serious heart malformation; and (2) the kidney is more sensitive than the heart to AA injury. -- Highlights: ► Zebrafish were used to evaluate aristolochic acid (AA)-induced nephrotoxicity. ► AA-treated zebrafish embryos exhibited deformed heart as well as malformed kidney. ► Kidney is more sensitive to AA injury than the heart.

  12. Developmental nephrotoxicity of aristolochic acid in a zebrafish model

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yu-Ju; Chen, Yau-Hung, E-mail: yauhung@mail.tku.edu.tw

    2012-05-15

    Aristolochic acid (AA) is a component of Aristolochia plant extracts which is used as a treatment for different pathologies and their toxicological effects have not been sufficiently studied. The aim of this study was to evaluate AA-induced nephrotoxicity in zebrafish embryos. After soaking zebrafish embryos in AA, the embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tubes, pronephric ducts, and cases of atrophic glomeruli. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. Furthermore, AA-treated embryos exhibited significantly reduced glomerular filtration rates (GFRs) in comparison with mock-control littermates (mock-control: 100 ± 2.24% vs. 10 ppm AA treatment for 3–5 h: 71.48 ± 18.84% ∼ 39.41 ± 15.88%), indicating that AA treatment not only caused morphological kidney changes but also induced renal failure. In addition to kidney malformations, AA-treated zebrafish embryos also exhibited deformed hearts, swollen pericardiums, impaired blood circulation and the accumulation(s) of red blood cells. Whole-mount in situ hybridization studies using cmlc2 and wt1b as riboprobes indicated that the kidney is more sensitive than the heart to AA damage. Real-time PCR showed that AA can up-regulate the expression of proinflammatory genes like TNFα, cox2 and mpo. These results support the following conclusions: (1) AA-induced renal failure is mediated by inflammation, which causes circulation dysfunction followed by serious heart malformation; and (2) the kidney is more sensitive than the heart to AA injury. -- Highlights: ► Zebrafish were used to evaluate aristolochic acid (AA)-induced nephrotoxicity. ► AA-treated zebrafish embryos exhibited deformed heart as well as malformed kidney. ► Kidney is more sensitive to AA injury than the heart.

  13. Gastrostomy Tube (G-Tube)

    Science.gov (United States)

    ... any of these problems: a dislodged tube a blocked or clogged tube any signs of infection (including redness, swelling, or 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 lasting ...

  14. Reprimo tissue-specific expression pattern is conserved between zebrafish and human.

    Directory of Open Access Journals (Sweden)

    Ricardo J Figueroa

    Full Text Available Reprimo (RPRM, a member of the RPRM gene family, is a tumor-suppressor gene involved in the regulation of the p53-mediated cell cycle arrest at G2/M. RPRM has been associated with malignant tumor progression and proposed as a potential biomarker for early cancer detection. However, the expression and role of RPRM, as well as its family, are poorly understood and their physiology is as yet unstudied. In this scenario, a model system like the zebrafish could serve to dissect the role of the RPRM family members in vivo. Phylogenetic analysis reveals that RPRM and RPRML have been differentially retained by most species throughout vertebrate evolution, yet RPRM3 has been retained only in a small group of distantly related species, including zebrafish. Herein, we characterized the spatiotemporal expression of RPRM (present in zebrafish as an infraclass duplication rprma/rprmb, RPRML and RPRM3 in the zebrafish. By whole-mount in situ hybridization (WISH and fluorescent in situ hybridization (FISH, we demonstrate that rprm (rprma/rprmb and rprml show a similar spatiotemporal expression profile during zebrafish development. At early developmental stages rprmb is expressed in somites. After one day post-fertilization, rprm (rprma/rprmb and rprml are expressed in the notochord, brain, blood vessels and digestive tube. On the other hand, rprm3 shows the most unique expression profile, being expressed only in the central nervous system (CNS. We assessed the expression patterns of RPRM gene transcripts in adult zebrafish and human RPRM protein product in tissue samples by RT-qPCR and immunohistochemistry (IHC staining, respectively. Strikingly, tissue-specific expression patterns of the RPRM transcripts and protein are conserved between zebrafish and humans. We propose the zebrafish as a powerful tool to elucidate the both physiological and pathological roles of the RPRM gene family.

  15. The Zebrafish Model Organism Database (ZFIN)

    Data.gov (United States)

    U.S. Department of Health & Human Services — ZFIN serves as the zebrafish model organism database. It aims to: a) be the community database resource for the laboratory use of zebrafish, b) develop and support...

  16. Expression of neuronal antigens and related ventral and dorsal proteins in the normal spinal cord and a surgically induced open neural tube defect of the spine in chick embryos: an immunohistochemical study.

    Science.gov (United States)

    Lee, Do-Hun; Phi, Ji Hoon; Chung, You-Nam; Lee, Yun-Jin; Kim, Seung-Ki; Cho, Byung-Kyu; Kim, Dong Won; Park, Moon-Sik; Wang, Kyu-Chang

    2010-05-01

    The aims of this study were to elucidate the processes of neuronal differentiation and ventrodorsal patterning in the spinal cord of the chick embryo from embryonic day (E) 3 to E17 and to study the effect of a prenatal spinal open neural tube defect (ONTD) on these processes. Expression patterns of neuronal antigens (neuronal nuclear antigen, neurofilament-associated protein (NAP), and synaptophysin) and related ventral markers [sonic hedgehog, paired box gene (PAX)6, and islet-1], and dorsal markers (bone morphogenetic protein, Notch homolog 1, and PAX7) were investigated in the normal spinal cord and in a surgically induced spinal ONTD in chick embryos. Four normal and ONTD chick embryos were used for each antigen group. There were no differences in the expression of neuronal and ventrodorsal markers between the control and ONTD groups. NAP and synaptophysin were useful for identifying dorsal structures in the distorted anatomy of the ONTD chicks.

  17. Interaction between Maternal and Paternal SHMT1 C1420T Predisposes to Neural Tube Defects in the Fetus: Evidence from Case-Control and Family-Based Triad Approaches.

    Science.gov (United States)

    K Rebekah, Prasoona; Tella, Sunitha; Buragadda, Srinadh; Tiruvatturu, Muni Kumari; Akka, Jyothy

    2017-07-17

    Neural tube defects (NTDs) are caused by the failure of neural tube formation which occurs during early embryonic development. NTDs are the most severe and leading cause of fetal mortality. Serine hydroxymethyl transferase (SHMT1) provides one-carbon units necessary for embryogenesis and defects in one-carbon production result in specific pathological conditions during pregnancy. The present study is aimed to evaluate the association of SHMT1 C1420T with NTD risk in the fetus using fetal, maternal and paternal groups by applying both case-control and family-based triad approaches. A total of 924 subjects including 124 NTD case-parent trios (n = 124 × 3 = 372) and 184 healthy control-parent trios (n = 184 × 3 = 552) from Telangana State, South India were analyzed. DNA from umbilical cord tissues and parental blood samples were extracted, and genotyped by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis used were SPSS, parent-of-origin effect (POE) analysis. Case-control study design demonstrated fetuses with homozygous variant genotype (TT) to be at risk toward spina bifida subtype (p = 0.022). Among parents, fathers with TT genotype were associated with anencephaly (p = 0.018) and spina bifida subtypes (p = 0.027) in the offspring. Of interest, maternal-paternal-offspring genotype incompatibility revealed maternal CT genotype in combination with paternal TT genotype increased risk for NTDs in the fetus (CTxTT = TT; p = 0.021). Family-based parent-of-origin effect linkage analysis revealed significant maternal over-transmission of variant allele to NTD fetuses (p < 0.01). The present study, using both case-control and family-based triad approach is the first report to demonstrate parental association of SHMT1 C1420T variant in conferring NTD risk in the fetus. Birth Defects Research 109:1020-1029, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Survey of prenatal screening policies in Europe for structural malformations and chromosome anomalies, and their impact on detection and termination rates for neural tube defects and Down's syndrome

    DEFF Research Database (Denmark)

    Boyd, P A; Devigan, C; Khoshnood, B

    2008-01-01

    tube defects (NTDs) using the EUROCAT database. MAIN OUTCOME MEASURES: Existence of national prenatal screening policies, legal gestation limit for TOPFA, prenatal detection and termination rates for Down's syndrome and NTD. RESULTS: Ten of the 18 countries had a national country-wide policy for Down...... cases. Six of the 18 countries had a legal gestational age limit for TOPFA, and in two countries, termination of pregnancy was illegal at any gestation. CONCLUSIONS: There are large differences in screening policies between countries in Europe. These, as well as organisational and cultural factors...

  19. Object recognition memory in zebrafish.

    Science.gov (United States)

    May, Zacnicte; Morrill, Adam; Holcombe, Adam; Johnston, Travis; Gallup, Joshua; Fouad, Karim; Schalomon, Melike; Hamilton, Trevor James

    2016-01-01

    The novel object recognition, or novel-object preference (NOP) test is employed to assess recognition memory in a variety of organisms. The subject is exposed to two identical objects, then after a delay, it is placed back in the original environment containing one of the original objects and a novel object. If the subject spends more time exploring one object, this can be interpreted as memory retention. To date, this test has not been fully explored in zebrafish (Danio rerio). Zebrafish possess recognition memory for simple 2- and 3-dimensional geometrical shapes, yet it is unknown if this translates to complex 3-dimensional objects. In this study we evaluated recognition memory in zebrafish using complex objects of different sizes. Contrary to rodents, zebrafish preferentially explored familiar over novel objects. Familiarity preference disappeared after delays of 5 mins. Leopard danios, another strain of D. rerio, also preferred the familiar object after a 1 min delay. Object preference could be re-established in zebra danios by administration of nicotine tartrate salt (50mg/L) prior to stimuli presentation, suggesting a memory-enhancing effect of nicotine. Additionally, exploration biases were present only when the objects were of intermediate size (2 × 5 cm). Our results demonstrate zebra and leopard danios have recognition memory, and that low nicotine doses can improve this memory type in zebra danios. However, exploration biases, from which memory is inferred, depend on object size. These findings suggest zebrafish ecology might influence object preference, as zebrafish neophobia could reflect natural anti-predatory behaviour. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Morphological and molecular evidence for functional organization along the rostrocaudal axis of the adult zebrafish intestine

    Directory of Open Access Journals (Sweden)

    Lam Siew

    2010-06-01

    Full Text Available Abstract Background The zebrafish intestine is a simple tapered tube that is folded into three sections. However, whether the intestine is functionally similar along its length remains unknown. Thus, a systematic structural and functional characterization of the zebrafish intestine is desirable for future studies of the digestive tract and the intestinal biology and development. Results To characterize the structure and function of the adult zebrafish intestine, we divided the intestine into seven roughly equal-length segments, S1-S7, and systematically examined the morphology of the mucosal lining, histology of the epithelium, and molecular signatures from transcriptome analysis. Prominent morphological features are circumferentially-oriented villar ridges in segments S1-S6 and the absence of crypts. Molecular characterization of the transcriptome from each segment shows that segments S1-S5 are very similar while S6 and S7 unique. Gene ontology analyses reveal that S1-S5 express genes whose functions involve metabolism of carbohydrates, transport of lipids and energy generation, while the last two segments display relatively limited function. Based on comparative Gene Set Enrichment Analysis, the first five segments share strong similarity with human and mouse small intestine while S6 shows similarity with human cecum and rectum, and S7 with human rectum. The intestinal tract does not display the anatomical, morphological, and molecular signatures of a stomach and thus we conclude that this organ is absent from the zebrafish digestive system. Conclusions Our genome-wide gene expression data indicate that, despite the lack of crypts, the rostral, mid, and caudal portions of the zebrafish intestine have distinct functions analogous to the mammalian small and large intestine, respectively. Organization of ridge structures represents a unique feature of zebrafish intestine, though they produce similar cross sections to mammalian intestines

  1. Dosagem de folatos maternos e fetais, séricos e eritrocitários em malformações por defeito de fechamento do tubo neural no feto Maternal and fetal serum and red blood cell folate levels in pregnancies complicated by neural tube defects

    Directory of Open Access Journals (Sweden)

    Victor Bunduki

    1998-07-01

    Full Text Available Objetivos: avaliar os níveis de folatos maternos e fetais gestações com malformações por defeitos de fechamento do tubo neural (DFTN. Métodos: o estudo foi do tipo caso-controle, no qual 14 casos de fetos com DFTN (grupo estudo e 14 casos de fetos com outras malformações (grupo controle foram estudados em gestantes de baixo risco para DFTN. Propusemo-nos a dosar o ácido fólico, na sua forma total e metilada, nos compartimentos fetal e materno, utilizando dosagens séricas e tissulares (eritrocitárias, assim como o volume corpuscular médio, o hematócrito e a hemoglobina. As coletas foram realizadas imediatamente antes da interrupção da gestação. Os resultados nos dois grupos foram comparados pelo teste t de Student, método de amostras pareados pela idade gestacional. Resultados: não se encontrou diferença nas taxas de folatos fetais e nos parâmetros hematológicos dos fetos, entre os dois grupos. Por outro lado, taxas anormalmente baixas de folatos foram encontradas nos eritrócitos das mães portadoras de fetos com DFTN, tanto para as formas totais(293,9 ng/mL contra 399,1 ng/mL no grupo controle, p=0,01 quanto para as formas metiladas (201,9 ng/mL contra 314,0 ng/mL para o grupo controle, p=0,02. Os folatos séricos maternos não se mostraram diferentes nos grupos estudo e controle. Conclusão: este estudo demonstrou que há uma menor taxa de folatos intratissulares, nas mães de fetos acometidos por DFTN, porém com taxas de folatos séricos semelhantes em relação ao grupo controle.Objective: to analyze maternal and fetal folate status in cases of neural tube defects (NTD. Methods: a case-control study was designed with 14 cases of fetuses with neural tube defects (study group and 14 cases of fetuses with other unrelated malformations (control group gestational age matched, in low-risk pregnant women. Both total and methylated folic acid levels in fetal and maternal compartments using serum and tissular (red blood cells

  2. Arsenic transport by zebrafish aquaglyceroporins

    Directory of Open Access Journals (Sweden)

    Landfear Scott M

    2009-11-01

    Full Text Available Abstract Background Arsenic is one of the most ubiquitous toxins and endangers the health of tens of millions of humans worldwide. It is a mainly a water-borne contaminant. Inorganic trivalent arsenic (AsIII is one of the major species that exists environmentally. The transport of AsIII has been studied in microbes, plants and mammals. Members of the aquaglyceroporin family have been shown to actively conduct AsIII and its organic metabolite, monomethylarsenite (MAsIII. However, the transport of AsIII and MAsIII in in any fish species has not been characterized. Results In this study, five members of the aquaglyceroporin family from zebrafish (Danio rerio were cloned, and their ability to transport water, glycerol, and trivalent arsenicals (AsIII and MAsIII and antimonite (SbIII was investigated. Genes for at least seven aquaglyceroporins have been annotated in the zebrafish genome project. Here, five genes which are close homologues to human AQP3, AQP9 and AQP10 were cloned from a zebrafish cDNA preparation. These genes were named aqp3, aqp3l, aqp9a, aqp9b and aqp10 according to their similarities to the corresponding human AQPs. Expression of aqp9a, aqp9b, aqp3, aqp3l and aqp10 in multiple zebrafish organs were examined by RT-PCR. Our results demonstrated that these aquaglyceroporins exhibited different tissue expression. They are all detected in more than one tissue. The ability of these five aquaglyceroporins to transport water, glycerol and the metalloids arsenic and antimony was examined following expression in oocytes from Xenopus leavis. Each of these channels showed substantial glycerol transport at equivalent rates. These aquaglyceroporins also facilitate uptake of inorganic AsIII, MAsIII and SbIII. Arsenic accumulation in fish larvae and in different tissues from adult zebrafish was studied following short-term arsenic exposure. The results showed that liver is the major organ of arsenic accumulation; other tissues such as gill, eye

  3. Properties of the Visible Light Phototaxis and UV Avoidance Behaviors in the Larval Zebrafish.

    Science.gov (United States)

    Guggiana-Nilo, Drago A; Engert, Florian

    2016-01-01

    For many organisms, color is an essential source of information from visual scenes. The larval zebrafish has the potential to be a model for the study of this topic, given its tetrachromatic retina and high dependence on vision. In this study we took a step toward understanding how the larval zebrafish might use color sensing. To this end, we used a projector-based paradigm to force a choice of a color stimulus at every turn of the larva. The stimuli used spanned most of the larval spectral range, including activation of its Ultraviolet (UV) cone, which has not been described behaviorally before. We found that zebrafish larvae swim toward visible wavelengths (>400 nm) when choosing between them and darkness, as has been reported with white light. However, when presented with UV light and darkness zebrafish show an intensity dependent avoidance behavior. This UV avoidance does not interact cooperatively with phototaxis toward longer wavelengths, but can compete against it in an intensity dependent manner. Finally, we show that the avoidance behavior depends on the presence of eyes with functional UV cones. These findings open future avenues for studying the neural circuits that underlie color sensing in the larval zebrafish.

  4. Effect of social isolation on anxiety-related behaviors, cortisol, and monoamines in adult zebrafish.

    Science.gov (United States)

    Shams, Soaleha; Seguin, Diane; Facciol, Amanda; Chatterjee, Diptendu; Gerlai, Robert

    2017-12-01

    Social isolation can be used to study behavioral, neural, and hormonal mechanisms that regulate interactions in social animals. Although isolation effects have been reported in social mammals and various fish species, systematic studies with isolated zebrafish are rare. Here, the authors examined behavior (social and nonsocial), physiological stress (whole-body cortisol levels), and neurochemicals (serotonin, dopamine, and their metabolites), following acute and chronic social isolation in adult zebrafish. To observe how isolated fish respond behaviorally to social stimuli, they exposed zebrafish to live conspecifics or animated images after acute (24 hr) or chronic (6 months) social isolation. The authors observed that isolation did not affect locomotor activity, but acute isolation had weak nonsignificant anxiogenic effects in adult zebrafish. They also found that all isolated fish responded to both live and animated social stimuli, and the stress hormone, cortisol was lower in chronically isolated fish. Finally, neurochemical analyses showed that serotonin levels increased when fish were exposed to social stimulus after acute isolation, but its metabolite 5HIAA decreased in response to social stimulus following both acute and chronic isolation. Levels of both dopamine and its metabolite DOPAC were also reduced in fish exposed to social stimulus after acute and chronic isolation. Overall, these results show that isolation in zebrafish is an effective tool to study fundamental mechanisms controlling social interaction at behavioral and physiological levels. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Seeing the whole picture: A comprehensive imaging approach to functional mapping of circuits in behaving zebrafish.

    Science.gov (United States)

    Feierstein, C E; Portugues, R; Orger, M B

    2015-06-18

    In recent years, the zebrafish has emerged as an appealing model system to tackle questions relating to the neural circuit basis of behavior. This can be attributed not just to the growing use of genetically tractable model organisms, but also in large part to the rapid advances in optical techniques for neuroscience, which are ideally suited for application to the small, transparent brain of the larval fish. Many characteristic features of vertebrate brains, from gross anatomy down to particular circuit motifs and cell-types, as well as conserved behaviors, can be found in zebrafish even just a few days post fertilization, and, at this early stage, the physical size of the brain makes it possible to analyze neural activity in a comprehensive fashion. In a recent study, we used a systematic and unbiased imaging method to record the pattern of activity dynamics throughout the whole brain of larval zebrafish during a simple visual behavior, the optokinetic response (OKR). This approach revealed the broadly distributed network of neurons that were active during the behavior and provided insights into the fine-scale functional architecture in the brain, inter-individual variability, and the spatial distribution of behaviorally relevant signals. Combined with mapping anatomical and functional connectivity, targeted electrophysiological recordings, and genetic labeling of specific populations, this comprehensive approach in zebrafish provides an unparalleled opportunity to study complete circuits in a behaving vertebrate animal. Copyright © 2014. Published by Elsevier Ltd.

  6. A homeostatic, chip-based platform for zebrafish larvae immobilization and long-term imaging

    Science.gov (United States)

    Friedrich, Timo; Zhu, Feng; Wlodkowic, Donald; Kaslin, Jan

    2015-12-01

    Zebrafish larvae are ideal for toxicology and drug screens due to their transparency, small size and similarity to humans on the genetic level. Using modern imaging techniques, cells and tissues can be dynamically visualised and followed over days in multiple zebrafish. Yet continued imaging experiments require specialized conditions such as: moisture and heat control to maintain specimen homeostasis. Chambers that control the environment are generally very expensive and are not always available for all imaging platforms. A highly customizable mounting configuration with built-in means of controlling temperature and media flow would therefore be a valuable tool for long term imaging experiments. Rapid prototyping using 3D printing is particularly suitable as a production method as it offers high flexibility in design, is widely available and allows a high degree of customizing. We study neural regeneration in zebrafish. Regeneration is limited in humans, but zebrafish recover from neural damage within days. Yet, the underlying regenerative mechanisms remain unclear. We developed an agarose based mounting system that holds the embryos in defined positions along removable strips. Homeostasis and temperature control is ensured by channels circulating buffer and heated water. This allows to image up to 120 larvae simultaneously for more than two days. Its flexibility and the low-volume, high larvae ratio will allow screening of small compound libraries. Taken together, we offer a low cost, highly adaptable solution for long term in-vivo imaging.

  7. Towards Developmental Models of Psychiatric Disorders in Zebrafish

    Directory of Open Access Journals (Sweden)

    William Howard James Norton

    2013-04-01

    Full Text Available Psychiatric disorders are a diverse set of diseases that affect all aspects of mental function including social interaction, thinking, feeling and mood. Although psychiatric disorders place a large economic burden on society, the drugs available to treat them are often palliative with variable efficacy and intolerable side-effects. The development of novel drugs has been hindered by a lack of knowledge about the etiology of these diseases. It is thus necessary to further investigate psychiatric disorders using a combination of human molecular genetics, gene-by-environment studies, in vitro pharmacological and biochemistry experiments, animal models and investigation of the non-biological basis of these diseases, such as environmental effects.Many psychiatric disorders, including autism spectrum disorder, attention-deficit/hyperactivity disorder, mental retardation and schizophrenia can be triggered by alterations to neural development. The zebrafish is a popular model for developmental biology that is increasingly used to study human disease. Recent work has extended this approach to examine psychiatric disorders as well. However, since psychiatric disorders affect complex mental functions that might be human specific, it is not possible to fully model them in fish. In this review, I will propose that the suitability of zebrafish for developmental studies, and the genetic tools available to manipulate them, provide a powerful model to study the roles of genes that are linked to psychiatric disorders during neural development. The relative speed and ease of conducting experiments in zebrafish can be used to address two areas of future research: the contribution of environmental factors to disease onset, and screening for novel therapeutic compounds.

  8. Generation and characterization of Kctd15 mutations in zebrafish.

    Directory of Open Access Journals (Sweden)

    Alison Heffer

    Full Text Available Potassium channel tetramerization domain containing 15 (Kctd15 was previously found to have a role in early neural crest (NC patterning, specifically delimiting the region where NC markers are expressed via repression of transcription factor AP-2a and inhibition of Wnt signaling. We used transcription activator-like effector nucleases (TALENs to generate null mutations in zebrafish kctd15a and kctd15b paralogs to study the in vivo role of Kctd15. We found that while deletions producing frame-shift mutations in each paralog showed no apparent phenotype, kctd15a/b double mutant zebrafish are smaller in size and show several phenotypes including some affecting the NC, such as expansion of the early NC domain, increased pigmentation, and craniofacial defects. Both melanophore and xanthophore pigment cell numbers and early markers are up-regulated in the double mutants. While we find no embryonic craniofacial defects, adult mutants have a deformed maxillary segment and missing barbels. By confocal imaging of mutant larval brains we found that the torus lateralis (TLa, a region implicated in gustatory networks in other fish, is absent. Ablation of this brain tissue in wild type larvae mimics some aspects of the mutant growth phenotype. Thus kctd15 mutants show deficits in the development of both neural crest derivatives, and specific regions within the central nervous system, leading to a strong reduction in normal growth rates.

  9. Low maternal folate concentrations and maternal MTHFR C677T polymorphism are associated with an increased risk for neural tube defects in offspring: a case-control study among Pakistani case and control mothers.

    Science.gov (United States)

    Nauman, Nuzhat; Jalali, Samina; Shami, Sajjad; Rafiq, Shireen; Große, Greta; Hilger, Alina C; Zhang, Rhong; Mansoor, Saira; Ludwig, Michael; Reutter, Heiko

    2018-01-01

    There is considerable evidence that periconceptional maternal folate deficiency and coding variants in maternal genes coding for critical enzymes in the folate pathway are associated with neural tube defects (NTDs) in offspring. In a case-control study we investigated C677T polymorphism in the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene in case and control mothers of Pakistani origin, and compared these with the respective maternal folate concentrations measured at the time of delivery. A case-control study was conducted among 109 case and 100 control mothers identified through the Holy Family Hospital Rawalpindi, Quaid-i-Azam University, Islamabad, Pakistan. Red blood cell (RBC) and serum folate concentrations and MTHFRC677T polymorphism were compared between case and control mothers. Mean RBC folate and serum folate concentrations were significantly lower in cases compared with control mothers (pcases compared with control mothers (CC vs TT pcases compared with control mothers (C vs T pCase mothers with 677CT or 677TT genotypes had significantly lower serum (pstudy provides further evidence that maternal folate deficiency and MTHFRC677T polymorphism might be associated with an increased risk for NTDs in offspring. Our results are limited by the fact that maternal folate concentrations were not obtained during the periconceptional period, but at delivery. Further analyses, including maternal folate levels during the periconceptional period, are warranted.

  10. Is MSAFP still a useful test for detecting open neural tube defects and ventral wall defects in the era of first-trimester and early second-trimester fetal anatomical ultrasounds?

    Science.gov (United States)

    Roman, Ashley S; Gupta, Simi; Fox, Nathan S; Saltzman, Daniel; Klauser, Chad K; Rebarber, Andrei

    2015-01-01

    To evaluate whether maternal serum α-fetoprotein (MSAFP) improves the detection rate for open neural tube defects (ONTDs) and ventral wall defects (VWD) in patients undergoing first-trimester and early second-trimester fetal anatomical survey. A cohort of women undergoing screening between 2005 and 2012 was identified. All patients were offered an ultrasound at between 11 weeks and 13 weeks and 6 days of gestational age for nuchal translucency/fetal anatomy followed by an early second-trimester ultrasound at between 15 weeks and 17 weeks and 6 days of gestational age for fetal anatomy and MSAFP screening. All cases of ONTD and VWD were identified via query of billing and reporting software. Sensitivity and specificity for detection of ONTD/VWD were calculated, and groups were compared using the Fisher exact test, with p met the criteria for inclusion. Overall, 15 cases of ONTD and 17 cases of VWD were identified; 100% of cases were diagnosed by ultrasound prior to 18 weeks' gestation; none were diagnosed via MSAFP screening (p < 0.001). First-trimester and early second-trimester ultrasound had 100% sensitivity and 100% specificity for diagnosing ONTD/VWD. Ultrasound for fetal anatomy during the first and early second trimester detected 100% of ONTD/VWD in our population. MSAFP is not useful as a screening tool for ONTD and VWD in the setting of this ultrasound screening protocol. © 2014 S. Karger AG, Basel.

  11. Feeding Tubes

    Science.gov (United States)

    ... feeding therapies have been exhausted. Please review product brand and method of placement carefully with your physician ... Total Parenteral Nutrition. Resources: Oley Foundation Feeding Tube Awareness Foundation Children’s Medical Nutrition Alliance APFED’s Educational Webinar ...

  12. Mind the fish: zebrafish as a model in cognitive social neuroscience

    Directory of Open Access Journals (Sweden)

    Rui F Oliveira

    2013-08-01

    Full Text Available Understanding how the brain implements social behavior on one hand, and how social processes feedback on the brain to promote fine-tuning of behavioural output according to changes in the social environment is a major challenge in contemporary neuroscience. A critical step to take this challenge successfully is finding the appropriate level of analysis when relating social to biological phenomena. Given the enormous complexity of both the neural networks of the brain and social systems, the use of a cognitive level of analysis (in an information processing perspective is proposed here as an explanatory interface between brain and behavior. A conceptual framework for a cognitive approach to comparative social neuroscience is proposed, consisting of the following steps to be taken across different species with varying social systems: (1 identification of the functional building blocks of social skills; (2 identification of the cognitive mechanisms underlying the previously identified social skills; and (3 mapping these information processing mechanisms onto the brain. Teleost fish are presented here as a group of choice to develop this approach, given the diversity of social systems present in closely related species that allows for planned phylogenetic comparisons, and the availability of neurogenetic tools that allows the visualization and manipulation of selected neural circuits in model species such as the zebrafish. Finally, the state-of-the art of zebrafish social cognition and of the tools available to map social cognitive abilities to neural circuits in zebrafish are reviewed.

  13. Modeling Myeloid Malignancies Using Zebrafish

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    Kathryn S. Potts

    2017-12-01

    Full Text Available Human myeloid malignancies represent a substantial disease burden to individuals, with significant morbidity and death. The genetic underpinnings of disease formation and progression remain incompletely understood. Large-scale human population studies have identified a high frequency of potential driver mutations in spliceosomal and epigenetic regulators that contribute to malignancies, such as myelodysplastic syndromes (MDS and leukemias. The high conservation of cell types and genes between humans and model organisms permits the investigation of the underlying mechanisms of leukemic development and potential therapeutic testing in genetically pliable pre-clinical systems. Due to the many technical advantages, such as large-scale screening, lineage-tracing studies, tumor transplantation, and high-throughput drug screening approaches, zebrafish is emerging as a model system for myeloid malignancies. In this review, we discuss recent advances in MDS and leukemia using the zebrafish model.

  14. Mechanisms of cadmium-caused eye hypoplasia and hypopigmentation in zebrafish embryos

    International Nuclear Information System (INIS)

    Zhang, Ting; Zhou, Xin-Ying; Ma, Xu-Fa; Liu, Jing-Xia

    2015-01-01

    Highlights: Using high-throughput in situ hybridization screening, we found that genes labeling the neural crest and its derivative pigment cells were sensitive to cadmium toxicity during zebrafish organogenesis, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in cadmium-exposed embryos. Based on neural crest markers, we identified the doses and times of cadmium exposure that cause damage to the zebrafish organogenesis, and we also found that compounds BIO or RA could neutralize the toxic effects of cadmium. - Abstract: Cadmium-caused head and eye hypoplasia and hypopigmentation has been recognized for a long time, but knowledge of the underlying mechanisms is limited. In this study, we found that high mortality occurred in exposed embryos after 24 hpf, when cadmium (Cd) dosage was above 17.8 μM. Using high-throughput in situ hybridization screening, we found that genes labelling the neural crest and its derivative pigment cells exhibited obviously reduced expression in Cd-exposed embryos from 24 hpf, 2 days earlier than head and eye hypoplasia and hypopigmentation occurred. Moreover, based on expression of crestin, a neural crest marker, we found that embryos before the gastrula stage were more sensitive to cadmium toxicity and that damage caused by Cd on embryogenesis was dosage dependent. In addition, by phenotype observation and detection of neural crest and pigment cell markers, we found that BIO and retinoic acid (RA) could neutralize the toxic effects of Cd on zebrafish embryogenesis. In this study, we first determined that Cd blocked the formation of the neural crest and inhibited specification of pigment cells, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in Cd-exposed embryos. Moreover, we found that compounds BIO or RA could neutralize the toxic effects of Cd.

  15. Mechanisms of cadmium-caused eye hypoplasia and hypopigmentation in zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ting, E-mail: zting@webmail.hzau.edu.cn; Zhou, Xin-Ying, E-mail: 290356082@qq.com; Ma, Xu-Fa, E-mail: xufama@mail.hzau.edu.cn; Liu, Jing-Xia, E-mail: ichliu@mail.hzau.edu.cn

    2015-10-15

    Highlights: Using high-throughput in situ hybridization screening, we found that genes labeling the neural crest and its derivative pigment cells were sensitive to cadmium toxicity during zebrafish organogenesis, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in cadmium-exposed embryos. Based on neural crest markers, we identified the doses and times of cadmium exposure that cause damage to the zebrafish organogenesis, and we also found that compounds BIO or RA could neutralize the toxic effects of cadmium. - Abstract: Cadmium-caused head and eye hypoplasia and hypopigmentation has been recognized for a long time, but knowledge of the underlying mechanisms is limited. In this study, we found that high mortality occurred in exposed embryos after 24 hpf, when cadmium (Cd) dosage was above 17.8 μM. Using high-throughput in situ hybridization screening, we found that genes labelling the neural crest and its derivative pigment cells exhibited obviously reduced expression in Cd-exposed embryos from 24 hpf, 2 days earlier than head and eye hypoplasia and hypopigmentation occurred. Moreover, based on expression of crestin, a neural crest marker, we found that embryos before the gastrula stage were more sensitive to cadmium toxicity and that damage caused by Cd on embryogenesis was dosage dependent. In addition, by phenotype observation and detection of neural crest and pigment cell markers, we found that BIO and retinoic acid (RA) could neutralize the toxic effects of Cd on zebrafish embryogenesis. In this study, we first determined that Cd blocked the formation of the neural crest and inhibited specification of pigment cells, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in Cd-exposed embryos. Moreover, we found that compounds BIO or RA could neutralize the toxic effects of Cd.

  16. A novel transgenic zebrafish model for blood-brain and blood-retinal barrier development

    Directory of Open Access Journals (Sweden)

    Sugimoto Masahiko

    2010-07-01

    Full Text Available Abstract Background Development and maintenance of the blood-brain and blood-retinal barrier is critical for the homeostasis of brain and retinal tissue. Despite decades of research our knowledge of the formation and maintenance of the blood-brain (BBB and blood-retinal (BRB barrier is very limited. We have established an in vivo model to study the development and maintenance of these barriers by generating a transgenic zebrafish line that expresses a vitamin D-binding protein fused with enhanced green fluorescent protein (DBP-EGFP in blood plasma, as an endogenous tracer. Results The temporal establishment of the BBB and BRB was examined using this transgenic line and the results were compared with that obtained by injection of fluorescent dyes into the sinus venosus of embryos at various stages of development. We also examined the expression of claudin-5, a component of tight junctions during the first 4 days of development. We observed that the BBB of zebrafish starts to develop by 3 dpf, with expression of claudin-5 in the central arteries preceding it at 2 dpf. The hyaloid vasculature in the zebrafish retina develops a barrier function at 3 dpf, which endows the zebrafish with unique advantages for studying the BRB. Conclusion Zebrafish embryos develop BBB and BRB function simultaneously by 3 dpf, which is regulated by tight junction proteins. The Tg(l-fabp:DBP-EGFP zebrafish will have great advantages in studying development and maintenance of the blood-neural barrier, which is a new application for the widely used vertebrate model.

  17. Steam generator tube extraction

    International Nuclear Information System (INIS)

    Delorme, H.

    1985-05-01

    To enable tube examination on steam generators in service, Framatome has now developed a process for removing sections of steam generator tubes. Tube sections can be removed without being damaged for treating the tube section expanded in the tube sheet

  18. Predição do comportamento térmico de tubos compósitos através de redes neurais Prediction of thermal behavior of composite tubes using neural networks

    Directory of Open Access Journals (Sweden)

    Sheila Contant

    2004-12-01

    Full Text Available Compósitos poliméricos (plásticos reforçados são materiais formados a partir de um reforço (fase descontínua, normalmente uma fibra e uma matriz polimérica. Esse tipo de material apresenta várias vantagens em relação aos materiais convencionais de engenharia. Entre os métodos de fabricação de compósitos poliméricos está o filament winding (filamento contínuo ou enrolamento filamentar, um processo empregado na fabricação de sólidos de revolução, como tubos e tanques. Neste trabalho, redes neurais artificiais, uma ferramenta computacional inspirada no funcionamento do cérebro humano, foram aplicadas ao processo de filament winding para predição do comportamento térmico de tubos compósitos durante a etapa de cura. Informações sobre o comportamento térmico das peças compósitas podem auxiliar na seleção do ciclo de cura, que é um dos desafios na obtenção de peças de qualidade e a um baixo custo. As redes neurais foram treinadas com dados obtidos através do modelo Lee-Springer. A metodologia foi validada com resultados experimentais da literatura.Polymeric composites or reinforced plastics are materials made with a polymer matrix and a reinforcement. These materials have many advantages when compared to conventional engineering materials. Among the manufacturing methods for composite parts from continuous fiber reinforcement is the filament winding, often used to fabricate closed-surface structures such as tubes and tanks. In this work artificial neural networks, a computational tool inspired in the human brain, were applied in the filament winding process to predict the thermal behavior of composite tubes during the curing step. Information about the thermal behavior of composite parts may help in the selection of the appropriate cure cycle, which is one of the challenges in obtaining quality parts at low cost. Networks were trained with data obtained with the Lee-Springer model. The methodology was validated

  19. Impacto de la fortificación de alimentos con ácido fólico en los defectos del tubo neural en Costa Rica Impact of the fortification of food with folic acid on neural tube defects in Costa Rica

    Directory of Open Access Journals (Sweden)

    María de la Paz Barboza Argüello

    2011-07-01

    Full Text Available OBJETIVO: Evaluar el impacto de la fortificación de alimentos con ácido fólico en las tendencias de las prevalencias de los defectos del tubo neural (DTN y la tasa de mortalidad infantil (TMI por este trastorno en Costa Rica. MÉTODOS: Se analizaron los datos de vigilancia del Centro de Registro de Enfermedades Congénitas y el Centro Centroamericano de Población. Se consideraron defectos del tubo neural la anencefalia, la espina bífida y el encefalocele. Se examinaron las tendencias durante 1987-2009, así como las diferencias de tasas (intervalo de confianza [IC] 95% de prevalencia y mortalidad antes de la fortificación de alimentos con ácido fólico y hasta 12 años después de su implementación. Se determinó el aporte de la fortificación al descenso en la TMI general. RESULTADOS: En 1987-1997, previo al período de fortificación de alimentos con ácido fólico, la prevalencia de DTN fue de 12/10 000 nacidos (IC95%: 11,1-12,8, mientras que en 2009 fue de 5,1/10 000 nacidos (3,3-6,5. La TMI por DTN en 1997 fue de 0,64/1 000 nacimientos (46-0,82 y en 2009 de 0,19/1 000 (0,09-0,3. La TMI por DTN y su prevalencia disminuyeron en forma significativa, 71% y 58% respectivamente (P OBJECTIVE: Evaluate the impact of the fortification of food with folic acid on prevalence trends for neural tube defects (NTD and the infant mortality rate (IMR associated with this disorder in Costa Rica. METHODS: The surveillance data from the Congenital Disease Registry Center and the Central American Population Center were analyzed. The neural tube defects considered were anencephaly, spina bifida, and encephalocele. The trends from 1987-2009, as well as the differences in prevalence and mortality rates prior to and up to 12 years after food fortification with folic acid, were examined (95% confidence interval [CI]. The contribution of fortification to the decrease in the overall IMR was determined. RESULTS: During 1987-1997, prior to the period of food

  20. A simple automated system for appetitive conditioning of zebrafish in their home tanks.

    Science.gov (United States)

    Doyle, Jillian M; Merovitch, Neil; Wyeth, Russell C; Stoyek, Matthew R; Schmidt, Michael; Wilfart, Florentin; Fine, Alan; Croll, Roger P

    2017-01-15

    We describe here an automated apparatus that permits rapid conditioning paradigms for zebrafish. Arduino microprocessors were used to control the delivery of auditory or visual stimuli to groups of adult or juvenile zebrafish in their home tanks in a conventional zebrafish facility. An automatic feeder dispensed precise amounts of food immediately after the conditioned stimuli, or at variable delays for controls. Responses were recorded using inexpensive cameras, with the video sequences analysed with ImageJ or Matlab. Fish showed significant conditioned responses in as few as 5 trials, learning that the conditioned stimulus was a predictor of food presentation at the water surface and at the end of the tank where the food was dispensed. Memories of these conditioned associations persisted for at least 2days after training when fish were tested either as groups or as individuals. Control fish, for which the auditory or visual stimuli were specifically unpaired with food, showed no comparable responses. This simple, low-cost, automated system permits scalable conditioning of zebrafish with minimal human intervention, greatly reducing both variability and labour-intensiveness. It will be useful for studies of the neural basis of learning and memory, and for high-throughput screening of compounds modifying those processes. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Ear Tubes

    Science.gov (United States)

    ... of the ear drum or eustachian tube, Down Syndrome, cleft palate, and barotrauma (injury to the middle ear caused by a reduction of air pressure, ... specialist) may be warranted if you or your child has experienced repeated ... fluid in the middle ear, barotrauma, or have an anatomic abnormality that ...

  2. Distribution and chronotropic effects of serotonin in the zebrafish heart.

    Science.gov (United States)

    Stoyek, Matthew R; Jonz, Michael G; Smith, Frank M; Croll, Roger P

    2017-09-01

    Several lines of evidence suggest that serotonin (5-HT) has a regulatory role in cardiovascular function from embryogenesis through adulthood. However, the reported actions of 5-HT are often contradictory and include bradycardia or tachycardia, hypotension or hypertension, and vasodilation or vasoconstriction. Clarifying such cardiac effects requires further research and may benefit from utilizing a model simpler than the mammalian hearts traditionally used in these studies. In the present study, we describe the cardiac distribution and chronotropic responses of 5-HT in the zebrafish heart. A combined anatomical, electrophysiological, and pharmacological approach was used to investigate the involvement of 5-HT pathways, and to compare neural and direct myocardial pathways of biological action. Immunohistochemical methods revealed 5-HT in endocardial cells, glial-like cells, and intracardiac neurons in the atrium. Electrocardiogram (ECG) recordings combined with the administration of pharmacological agents demonstrated that 5-HT acted predominantly through direct myocardial pathways resulting in a reduction of heart rate. Overall, the results of this study contribute significant advances in the establishment of the zebrafish as a new model for studies of the role of 5-HT in autonomic cardiac control. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Mechanisms of social buffering of fear in zebrafish.

    Science.gov (United States)

    Faustino, Ana I; Tacão-Monteiro, André; Oliveira, Rui F

    2017-03-31

    Some humans thrive whereas others resign when exposed to threatening situations throughout life. Social support has been identified as an important modulator of these discrepancies in human behaviour, and other social animals also exhibit phenomena in which individuals recover better from aversive events when conspecifics are present - aka social buffering. Here we studied social buffering in zebrafish, by exposing focal fish to an aversive stimulus (alarm substance - AS) either in the absence or presence of conspecific cues. When exposed to AS in the presence of both olfactory (shoal water) and visual (sight of shoal) conspecific cues, focal fish exhibited a lower fear response than when tested alone, demonstrating social buffering in zebrafish. When separately testing each cue's effectiveness, we verified that the visual cue was more effective than the olfactory in reducing freezing in a persistent threat scenario. Finally, we verified that social buffering was independent of shoal size and coincided with a distinct pattern of co-activation of brain regions known to be involved in mammalian social buffering. Thus, this study suggests a shared evolutionary origin for social buffering in vertebrates, bringing new evidence on the behavioural, sensory and neural mechanisms underlying this phenomenon.

  4. The importance of Zebrafish in biomedical research.

    Science.gov (United States)

    Tavares, Bárbara; Santos Lopes, Susana

    2013-01-01

    Zebrafish (Danio rerio) is an ideal model organism for the study of vertebrate development. This is due to the large clutches that each couple produces, with up to 200 embryos every 7 days, and to the fact that the embryos and larvae are small, transparent and undergo rapid external development. Using scientific literature research tools available online and the keywords Zebrafish, biomedical research, human disease, and drug screening, we reviewed original studies and reviews indexed in PubMed. In this review we summarized work conducted with this model for the advancement of our knowledge related to several human diseases. We also focused on the biomedical research being performed in Portugal with the zebrafish model. Powerful live imaging and genetic tools are currently available for zebrafish making it a valuable model in biomedical research. The combination of these properties with the optimization of automated systems for drug screening has transformed the zebrafish into "a top model" in biomedical research, drug discovery and toxicity testing. Furthermore, with the optimization of xenografts technology it will be possible to use zebrafish to aide in the choice of the best therapy for each patient. Zebrafish is an excellent model organism in biomedical research, drug development and in clinical therapy.

  5. Sprouting Buds of Zebrafish Research in Malaysia: First Malaysia Zebrafish Disease Model Workshop.

    Science.gov (United States)

    Okuda, Kazuhide Shaun; Tan, Pei Jean; Patel, Vyomesh

    2016-04-01

    Zebrafish is gaining prominence as an important vertebrate model for investigating various human diseases. Zebrafish provides unique advantages such as optical clarity of embryos, high fecundity rate, and low cost of maintenance, making it a perfect complement to the murine model equivalent in biomedical research. Due to these advantages, researchers in Malaysia are starting to take notice and incorporate the zebrafish model into their research activities. However, zebrafish research in Malaysia is still in its infancy stage and many researchers still remain unaware of the full potential of the zebrafish model or have limited access to related tools and techniques that are widely utilized in many zebrafish laboratories worldwide. To overcome this, we organized the First Malaysia Zebrafish Disease Model Workshop in Malaysia that took place on 11th and 12th of November 2015. In this workshop, we showcased how the zebrafish model is being utilized in the biomedical field in international settings as well as in Malaysia. For this, notable international speakers and those from local universities known to be carrying out impactful research using zebrafish were invited to share some of the cutting edge techniques that are used in their laboratories that may one day be incorporated in the Malaysian scientific community.

  6. Brain-wide neuronal dynamics during motor adaptation in zebrafish.

    Science.gov (United States)

    Ahrens, Misha B; Li, Jennifer M; Orger, Michael B; Robson, Drew N; Schier, Alexander F; Engert, Florian; Portugues, Ruben

    2012-05-09

    A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioural adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behaviour.

  7. Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH neurons

    Directory of Open Access Journals (Sweden)

    Christian Cortés-Campos

    2015-09-01

    Full Text Available Gonadotropin-releasing hormone (GnRH is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons.

  8. A review of monoaminergic neuropsychopharmacology in zebrafish.

    Science.gov (United States)

    Maximino, Caio; Herculano, Anderson Manoel

    2010-12-01

    Monoamine neurotransmitters are the major regulatory mechanisms in the vertebrate brain, involved in the adjustment of motivation, emotion, and cognition. The chemical anatomy of these systems is thought to be highly conserved in the brain of all vertebrates, including zebrafish. Recently, the development of behavioral assays in zebrafish allowed the neuropsychopharmacological investigation of these circuits and its functions. Here we review neuroanatomical, genetic, neurochemical, and psychopharmacological evidence regarding the roles of histaminergic, dopaminergic, noradrenergic, serotonergic, and melatonergic systems in this species. We conclude that, in spite of species differences, zebrafish are suitable for the investigation of neuropsychopharmacology of drugs that affect theses systems; nonetheless, more thorough validation of behavioral methods is still needed.

  9. Electron tube

    Science.gov (United States)

    Suyama, Motohiro [Hamamatsu, JP; Fukasawa, Atsuhito [Hamamatsu, JP; Arisaka, Katsushi [Los Angeles, CA; Wang, Hanguo [North Hills, CA

    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.

  10. Whole-brain activity mapping onto a zebrafish brain atlas

    Science.gov (United States)

    Randlett, Owen; Wee, Caroline L.; Naumann, Eva A.; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E.; Portugues, Ruben; Lacoste, Alix M.B.; Riegler, Clemens; Engert, Florian; Schier, Alexander F.

    2015-01-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open source atlas containing molecular labels and anatomical region definitions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated-Extracellular signal-regulated kinase (ERK/MAPK) as a readout of neural activity, we have developed a system to create and contextualize whole brain maps of stimulus- and behavior-dependent neural activity. This MAP-Mapping (Mitogen Activated Protein kinase – Mapping) assay is technically simple, fast, inexpensive, and data analysis is completely automated. Since MAP-Mapping is performed on fish that are freely swimming, it is applicable to nearly any stimulus or behavior. We demonstrate the utility of our high-throughput approach using hunting/feeding, pharmacological, visual and noxious stimuli. The resultant maps outline hundreds of areas associated with behaviors. PMID:26778924

  11. Whole-brain activity mapping onto a zebrafish brain atlas.

    Science.gov (United States)

    Randlett, Owen; Wee, Caroline L; Naumann, Eva A; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E; Portugues, Ruben; Lacoste, Alix M B; Riegler, Clemens; Engert, Florian; Schier, Alexander F

    2015-11-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open-source atlas containing molecular labels and definitions of anatomical regions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated extracellular signal–regulated kinase (ERK) as a readout of neural activity, we have developed a system to create and contextualize whole-brain maps of stimulus- and behavior-dependent neural activity. This mitogen-activated protein kinase (MAP)-mapping assay is technically simple, and data analysis is completely automated. Because MAP-mapping is performed on freely swimming fish, it is applicable to studies of nearly any stimulus or behavior. Here we demonstrate our high-throughput approach using pharmacological, visual and noxious stimuli, as well as hunting and feeding. The resultant maps outline hundreds of areas associated with behaviors.

  12. Chest tube insertion

    Science.gov (United States)

    Chest drainage tube insertion; Insertion of tube into chest; Tube thoracostomy; Pericardial drain ... Be careful there are no kinks in your tube. The drainage system should always sit upright and be placed ...

  13. Neural Tube Defects: Epidemiologic Factors, Clinical Presentation ...

    African Journals Online (AJOL)

    Of the 103 babies, 87 (84.5%) had spina bifida cystica, 15 (14.6%) had occipital encephalocele, while 1 (0.9%) had anencephaly and died within 8 hours of delivery. All the 87 patients with spina bifida cystica were ruptured and infected at presentation, with seven of them dying from overwhelming sepsis. Most of the babies ...

  14. Opioid Use and Neural Tube Defects

    Science.gov (United States)

    ... of the Aorta D-Transposition of the Great Arteries Hypoplastic Left Heart Syndrome Pulmonary Atresia Tetralogy of ... Privacy FOIA No Fear Act OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO ( ...

  15. Peru's national folic acid fortification program and its effect on neural tube defects in Lima Programa nacional del Perú de fortificación con ácido fólico y su efecto sobre los defectos del tubo neural en Lima

    Directory of Open Access Journals (Sweden)

    Daniel J. Ricks

    2012-12-01

    Full Text Available OBJECTIVE: To evaluate the impact of Peru's national folic acid fortification program on folic acid content in wheat flour, and the effect on birth prevalence of neural tube defects (NTDs in Lima, and to compare the program's legislative requirements with international standards. METHODS: Bread was sampled from six sites across Peru and tested for folic acid. Data were obtained from the largest obstetric hospital in Lima on the prevalence of births (live and still with NTDs during both the pre-fortification period (2004-2005 and post-fortification years (2007-2008. RESULTS: Folic acid content in the sampled bread met national legislative requirements but was less than one-half of the level recommended for Peru by the World Health Organization (WHO (2.6 mg/kg wheat flour. Birth prevalence of NTDs was 18.4/10 000 in the pre-fortification period and 20.0/10 000 during post-fortification years. Relative risk for NTDs after fortification was 1.02 (95% confidence interval 0.77-1.35, P = 0.90. CONCLUSIONS: Peruvian legislative requirements for folic acid fortification are below international (WHO recommendations; birth prevalence of NTDs in Lima is higher than international benchmarks; and no decrease in NTDs following fortification of flour with folic acid (according to Peruvian national standards was observed. As increasing the level of folic acid in flour remains the most sustainable way of preventing NTDs, it is recommended that Peru increase its folic acid fortification requirements to meet those recommended by WHO (2.6 mg/kg.OBJETIVO: Evaluar la repercusión que el programa nacional del Perú de fortificación con ácido fólico tiene en el contenido de ácido fólico de la harina de trigo y en la prevalencia de nacimientos de niños con defectos del tubo neural en Lima, así como comparar los requisitos legislativos del programa con las normas internacionales. MÉTODOS: Se hizo un muestreo del pan en seis zonas de Perú y se analizó su

  16. Episodic-like memory in zebrafish.

    Science.gov (United States)

    Hamilton, Trevor J; Myggland, Allison; Duperreault, Erika; May, Zacnicte; Gallup, Joshua; Powell, Russell A; Schalomon, Melike; Digweed, Shannon M

    2016-11-01

    Episodic-like memory tests often aid in determining an animal's ability to recall the what, where, and which (context) of an event. To date, this type of memory has been demonstrated in humans, wild chacma baboons, corvids (Scrub jays), humming birds, mice, rats, Yucatan minipigs, and cuttlefish. The potential for this type of memory in zebrafish remains unexplored even though they are quickly becoming an essential model organism for the study of a variety of human cognitive and mental disorders. Here we explore the episodic-like capabilities of zebrafish (Danio rerio) in a previously established mammalian memory paradigm. We demonstrate that when zebrafish were presented with a familiar object in a familiar context but a novel location within that context, they spend more time in the novel quadrant. Thus, zebrafish display episodic-like memory as they remember what object they saw, where they saw it (quadrant location), and on which occasion (yellow or blue walls) it was presented.

  17. photomultiplier tubes

    CERN Multimedia

    photomultiplier tubes. A device to convert light into an electric signal (the name is often abbreviated to PM). Photomultipliers are used in all detectors based on scintillating material (i.e. based on large numbers of fibres which produce scintillation light at the passage of a charged particle). A photomultiplier consists of 3 main parts: firstly, a photocathode where photons are converted into electrons by the photoelectric effect; secondly, a multiplier chain consisting of a serie of dynodes which multiply the number of electron; finally, an anode, which collects the resulting current.

  18. photomultiplier tube

    CERN Multimedia

    photomultiplier tubes. A device to convert light into an electric signal (the name is often abbreviated to PM). Photomultipliers are used in all detectors based on scintillating material (i.e. based on large numbers of fibres which produce scintillation light at the passage of a charged particle). A photomultiplier consists of 3 main parts: firstly, a photocathode where photons are converted into electrons by the photoelectric effect; secondly, a multiplier chain consisting of a serie of dynodes which multiply the number of electron; finally, an anode, which collects the resulting current.

  19. Identification and characterization of zebrafish thrombocytes.

    Science.gov (United States)

    Jagadeeswaran, P; Sheehan, J P; Craig, F E; Troyer, D

    1999-12-01

    To analyse primary haemostasis in the zebrafish we have identified and characterized the zebrafish thrombocyte by morphologic, immunologic and functional approaches. Novel methods were developed for harvesting zebrafish blood with preservation of thrombocytes, and assaying whole blood adhesion/aggregation responses in microtitre plates. Light and electron microscopy of the thrombocyte illustrated morphological characteristics including the formation of aggregates, pseudopodia, and surface-connected vesicles analagous to the platelet canalicular system. Immunostaining with polyclonal antisera versus human platelet glycoproteins demonstrated the presence of glycoprotein Ib and IIb/IIIa-like complexes on the thrombocyte surface. Whole blood assays for adhesion/aggregation and ATP release showed ristocetin-induced adhesion without ATP release, and platelet agonist (collagen, arachidonic acid) induced aggregation with ATP release. Blood harvested from zebrafish treated with aspirin demonstrated inhibition of arachidonic acid induced aggregation and agonist induced ATP release, consistent with at least partial dependence on an intact cyclo oxygenase pathway. The combined morphologic immunologic and functional evidence suggest that the zebrafish thrombocyte is the haemostatic homologue of the mammalian platelet. Conservation of major haemostatic pathways involved in platelet function and coagulation suggests that the zebrafish is a relevant model for mammalian haemostasis and thrombosis.

  20. Genomic Organization of Zebrafish microRNAs

    Directory of Open Access Journals (Sweden)

    Paydar Ima

    2008-05-01

    Full Text Available Abstract Background microRNAs (miRNAs are small (~22 nt non-coding RNAs that regulate cell movement, specification, and development. Expression of miRNAs is highly regulated, both spatially and temporally. Based on direct cloning, sequence conservation, and predicted secondary structures, a large number of miRNAs have been identified in higher eukaryotic genomes but whether these RNAs are simply a subset of a much larger number of noncoding RNA families is unknown. This is especially true in zebrafish where genome sequencing and annotation is not yet complete. Results We analyzed the zebrafish genome to identify the number and location of proven and predicted miRNAs resulting in the identification of 35 new miRNAs. We then grouped all 415 zebrafish miRNAs into families based on seed sequence identity as a means to identify possible functional redundancy. Based on genomic location and expression analysis, we also identified those miRNAs that are likely to be encoded as part of polycistronic transcripts. Lastly, as a resource, we compiled existing zebrafish miRNA expression data and, where possible, listed all experimentally proven mRNA targets. Conclusion Current analysis indicates the zebrafish genome encodes 415 miRNAs which can be grouped into 44 families. The largest of these families (the miR-430 family contains 72 members largely clustered in two main locations along chromosome 4. Thus far, most zebrafish miRNAs exhibit tissue specific patterns of expression.

  1. An Assay for Permeability of the Zebrafish Embryonic Neuroepithelium

    OpenAIRE

    Chang, Jessica T.; Sive, Hazel

    2012-01-01

    The brain ventricular system is conserved among vertebrates and is composed of a series of interconnected cavities called brain ventricles, which form during the earliest stages of brain development and are maintained throughout the animal's life. The brain ventricular system is found in vertebrates, and the ventricles develop after neural tube formation, when the central lumen fills with cerebrospinal fluid (CSF) 1,2. CSF is a protein rich fluid that is essential for normal brain development...

  2. Zebrafish neurobehavioral phenomics for aquatic neuropharmacology and toxicology research.

    Science.gov (United States)

    Kalueff, Allan V; Echevarria, David J; Homechaudhuri, Sumit; Stewart, Adam Michael; Collier, Adam D; Kaluyeva, Aleksandra A; Li, Shaomin; Liu, Yingcong; Chen, Peirong; Wang, JiaJia; Yang, Lei; Mitra, Anisa; Pal, Subharthi; Chaudhuri, Adwitiya; Roy, Anwesha; Biswas, Missidona; Roy, Dola; Podder, Anupam; Poudel, Manoj K; Katare, Deepshikha P; Mani, Ruchi J; Kyzar, Evan J; Gaikwad, Siddharth; Nguyen, Michael; Song, Cai

    2016-01-01

    Zebrafish (Danio rerio) are rapidly emerging as an important model organism for aquatic neuropharmacology and toxicology research. The behavioral/phenotypic complexity of zebrafish allows for thorough dissection of complex human brain disorders and drug-evoked pathological states. As numerous zebrafish models become available with a wide spectrum of behavioral, genetic, and environmental methods to test novel drugs, here we discuss recent zebrafish phenomics methods to facilitate drug discovery, particularly in the field of biological psychiatry. Additionally, behavioral, neurological, and endocrine endpoints are becoming increasingly well-characterized in zebrafish, making them an inexpensive, robust and effective model for toxicology research and pharmacological screening. We also discuss zebrafish behavioral phenotypes, experimental considerations, pharmacological candidates and relevance of zebrafish neurophenomics to other 'omics' (e.g., genomic, proteomic) approaches. Finally, we critically evaluate the limitations of utilizing this model organism, and outline future strategies of research in the field of zebrafish phenomics. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Evaluating human cancer cell metastasis in zebrafish

    International Nuclear Information System (INIS)

    Teng, Yong; Xie, Xiayang; Walker, Steven; White, David T; Mumm, Jeff S; Cowell, John K

    2013-01-01

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

  4. Biosecurity and Health Monitoring at the Zebrafish International Resource Center

    OpenAIRE

    Murray, Katrina N.; Varga, Zolt?n M.; Kent, Michael L.

    2016-01-01

    The Zebrafish International Resource Center (ZIRC) is a repository and distribution center for mutant, transgenic, and wild-type zebrafish. In recent years annual imports of new zebrafish lines to ZIRC have increased tremendously. In addition, after 15 years of research, we have identified some of the most virulent pathogens affecting zebrafish that should be avoided in large production facilities, such as ZIRC. Therefore, while importing a high volume of new lines we prioritize safeguarding ...

  5. 8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Lifeng [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China); Zhou, Yong [Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Yu, Shanhe [Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025 (China); Ji, Guixiang [Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042 (China); Wang, Lei [Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Liu, Wei [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China); Gu, Aihua, E-mail: aihuagu@njmu.edu.cn [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China)

    2013-11-15

    Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes and nkx2.5{sup +} cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits. - Highlights: • A key DNA repair enzyme ogg1 is expressed in the embryonic heart in zebrafish. • We found that ogg1 is essential for normal cardiac morphogenesis in zebrafish. • The production of embryonic cardiomyocytes requires appropriate ogg1 expression. • Ogg1 critically regulated proliferation of cardiac progenitor cells in zebrafish. • foxh1 is a partner of ogg1 in the cardiac development in response to DNA damage.

  6. Multilayer mounting for long-term light sheet microscopy of zebrafish.

    Science.gov (United States)

    Weber, Michael; Mickoleit, Michaela; Huisken, Jan

    2014-02-27

    Light sheet microscopy is the ideal imaging technique to study zebrafish embryonic development. Due to minimal photo-toxicity and bleaching, it is particularly suited for long-term time-lapse imaging over many hours up to several days. However, an appropriate sample mounting strategy is needed that offers both confinement and normal development of the sample. Multilayer mounting, a new embedding technique using low-concentration agarose in optically clear tubes, now overcomes this limitation and unleashes the full potential of light sheet microscopy for real-time developmental biology.

  7. Cornelia de Lange Syndrome: NIPBL haploinsufficiency downregulates canonical Wnt pathway in zebrafish embryos and patients fibroblasts.

    Science.gov (United States)

    Pistocchi, A; Fazio, G; Cereda, A; Ferrari, L; Bettini, L R; Messina, G; Cotelli, F; Biondi, A; Selicorni, A; Massa, V

    2013-10-17

    Cornelia de Lange Syndrome is a severe genetic disorder characterized by malformations affecting multiple systems, with a common feature of severe mental retardation. Genetic variants within four genes (NIPBL (Nipped-B-like), SMC1A, SMC3, and HDAC8) are believed to be responsible for the majority of cases; all these genes encode proteins that are part of the 'cohesin complex'. Cohesins exhibit two temporally separated major roles in cells: one controlling the cell cycle and the other involved in regulating the gene expression. The present study focuses on the role of the zebrafish nipblb paralog during neural development, examining its expression in the central nervous system, and analyzing the consequences of nipblb loss of function. Neural development was impaired by the knockdown of nipblb in zebrafish. nipblb-loss-of-function embryos presented with increased apoptosis in the developing neural tissues, downregulation of canonical Wnt pathway genes, and subsequent decreased Cyclin D1 (Ccnd1) levels. Importantly, the same pattern of canonical WNT pathway and CCND1 downregulation was observed in NIPBL-mutated patient-specific fibroblasts. Finally, chemical activation of the pathway in nipblb-loss-of-function embryos rescued the adverse phenotype and restored the physiological levels of cell death.

  8. Transcriptome analysis of zebrafish embryogenesis using microarrays.

    Directory of Open Access Journals (Sweden)

    Sinnakaruppan Mathavan

    2005-08-01

    Full Text Available Zebrafish (Danio rerio is a well-recognized model for the study of vertebrate developmental genetics, yet at the same time little is known about the transcriptional events that underlie zebrafish embryogenesis. Here we have employed microarray analysis to study the temporal activity of developmentally regulated genes during zebrafish embryogenesis. Transcriptome analysis at 12 different embryonic time points covering five different developmental stages (maternal, blastula, gastrula, segmentation, and pharyngula revealed a highly dynamic transcriptional profile. Hierarchical clustering, stage-specific clustering, and algorithms to detect onset and peak of gene expression revealed clearly demarcated transcript clusters with maximum gene activity at distinct developmental stages as well as co-regulated expression of gene groups involved in dedicated functions such as organogenesis. Our study also revealed a previously unidentified cohort of genes that are transcribed prior to the mid-blastula transition, a time point earlier than when the zygotic genome was traditionally thought to become active. Here we provide, for the first time to our knowledge, a comprehensive list of developmentally regulated zebrafish genes and their expression profiles during embryogenesis, including novel information on the temporal expression of several thousand previously uncharacterized genes. The expression data generated from this study are accessible to all interested scientists from our institute resource database (http://giscompute.gis.a-star.edu.sg/~govind/zebrafish/data_download.html.

  9. Prevalência e distribuição espacial de defeitos do tubo neural no Estado de São Paulo, Brasil, antes e após a fortificação de farinhas com ácido fólico Prevalencia y distribución espacial de defectos del tubo neural en el Estado de São Paulo, Brasil, antes y después del enriquecimiento de harinas con ácido fólico Prevalence and spatial distribution of neural tube defects in São Paulo State, Brazil, before and after folic acid flour fortification

    Directory of Open Access Journals (Sweden)

    Elizabeth Fujimori

    2013-01-01

    Full Text Available Estudo transversal que analisou prevalência e distribuição espacial de defeitos do tubo neural, antes e após a fortificação das farinhas de trigo e milho com ácido fólico no Estado de São Paulo, Brasil, com uso do Sistema de Informações sobre Nascidos Vivos (SINASC. São apresentadas prevalências segundo características maternas por meio de odds ratio (OR e intervalos de 95% de confiança (IC95%. Para análise temporal e espacial, foram utilizados, respectivamente, regressão polinomial e mapas com suavização bayesiana empírica. A prevalência diminuiu 35%, de 0,57 para 0,37 por mil nascidos vivos após a fortificação (OR = 0,65; IC95%: 0,59-0,72. Verificou-se redução para mulheres de todas as idades (exceto Estudio transversal que analizó la prevalencia y distribución espacial de defectos del tubo neural, antes y después del enriquecimiento de las harinas de trigo y maíz con ácido fólico en el Estado de Sao Paulo, Brasil, con el uso del Sistema de Información sobre Nacidos Vivos (SINASC. Se presentaron prevalencias, según características maternas, mediante odds ratio (OR e intervalos de un 95% de confianza (IC95%. Para un análisis temporal y espacial, fueron utilizados, respectivamente, regresión polinomial y mapas con suavizamiento bayesiano empírico. La prevalencia disminuyó un 35%, de 0,57 a 0,37 por mil nacidos vivos tras el enriquecimiento (OR = 0,65; IC95%: 0,59-0,72. Se verificó la reducción en mujeres de todas las edades (excepto This cross-sectional study analyzed the prevalence and spatial distribution of neural tube defects before and after folic acid flour fortification. The study used the Information System on Live Births (SINASC and presented prevalence rates according to maternal characteristics with odds ratios (OR and 95% confidence intervals (95%CI. Polynomial regression was used in time trend analysis and empirical Bayesian smoothed maps for spatial analysis. Total prevalence of neural tube

  10. The zebrafish genome: a review and msx gene case study.

    Science.gov (United States)

    Postlethwait, J H

    2006-01-01

    Zebrafish is one of several important teleost models for understanding principles of vertebrate developmental, molecular, organismal, genetic, evolutionary, and genomic biology. Efficient investigation of the molecular genetic basis of induced mutations depends on knowledge of the zebrafish genome. Principles of zebrafish genomic analysis, including gene mapping, ortholog identification, conservation of syntenies, genome duplication, and evolution of duplicate gene function are discussed here using as a case study the zebrafish msxa, msxb, msxc, msxd, and msxe genes, which together constitute zebrafish orthologs of tetrapod Msx1, Msx2, and Msx3. Genomic analysis suggests orthologs for this difficult to understand group of paralogs.

  11. Whole-Volume Clustering of Time Series Data from Zebrafish Brain Calcium Images via Mixture Modeling.

    Science.gov (United States)

    Nguyen, Hien D; Ullmann, Jeremy F P; McLachlan, Geoffrey J; Voleti, Venkatakaushik; Li, Wenze; Hillman, Elizabeth M C; Reutens, David C; Janke, Andrew L

    2018-02-01

    Calcium is a ubiquitous messenger in neural signaling events. An increasing number of techniques are enabling visualization of neurological activity in animal models via luminescent proteins that bind to calcium ions. These techniques generate large volumes of spatially correlated time series. A model-based functional data analysis methodology via Gaussian mixtures is suggested for the clustering of data from such visualizations is proposed. The methodology is theoretically justified and a computationally efficient approach to estimation is suggested. An example analysis of a zebrafish imaging experiment is presented.

  12. Eustachian tube patency

    Science.gov (United States)

    Eustachian tube patency refers to how much the eustachian tube is open. The eustachian tube runs between the middle ear and the throat. It controls the pressure behind the eardrum and middle ear space. This helps keep ...

  13. Feeding tube - infants

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007235.htm Feeding tube - infants To use the sharing features on this page, please enable JavaScript. A feeding tube is a small, soft, plastic tube placed ...

  14. Developmental mechanisms of arsenite toxicity in zebrafish (Danio rerio) embryos

    International Nuclear Information System (INIS)

    Li Dan; Lu Cailing; Wang Ju; Hu Wei; Cao Zongfu; Sun Daguang; Xia Hongfei; Ma Xu

    2009-01-01

    Arsenic usually accumulates in soil, water and airborne particles, from which it is taken up by various organisms. Exposure to arsenic through food and drinking water is a major public health problem affecting some countries. At present there are limited laboratory data on the effects of arsenic exposure on early embryonic development and the mechanisms behind its toxicity. In this study, we used zebrafish as a model system to investigate the effects of arsenite on early development. Zebrafish embryos were exposed to a range of sodium arsenite concentrations (0-10.0 mM) between 4 and 120 h post-fertilization (hpf). Survival and early development of the embryos were not obviously influenced by arsenite concentrations below 0.5 mM. However, embryos exposed to higher concentrations (0.5-10.0 mM) displayed reduced survival and abnormal development including delayed hatching, retarded growth and changed morphology. Alterations in neural development included weak tactile responses to light (2.0-5.0 mM, 30 hpf), malformation of the spinal cord and disordered motor axon projections (2.0 mM, 48 hpf). Abnormal cardiac function was observed as bradycardia (0.5-2.0 mM, 60 hpf) and altered ventricular shape (2.0 mM, 48 hpf). Furthermore, altered cell proliferation (2.0 mM, 24 hpf) and apoptosis status (2.0 mM, 24 and 48 hpf), as well as abnormal genomic DNA methylation patterning (2.0 mM, 24 and 48 hpf) were detected in the arsenite-treated embryos. All of these indicate a possible relationship between arsenic exposure and developmental failure in early embryogenesis. Our studies suggest that the negative effects of arsenic on vertebrate embryogenesis are substantial

  15. Regulation of zebrafish sleep and arousal states: current and prospective approaches

    Directory of Open Access Journals (Sweden)

    Cindy N Chiu

    2013-04-01

    Full Text Available Every day, we shift among various states of sleep and arousal to meet the many demands of our bodies and environment. A central puzzle in neurobiology is how the brain controls these behavioral states, which are essential to an animal’s well-being and survival. Mammalian models have predominated sleep and arousal research, although in the past decade, invertebrate models have made significant contributions to our understanding of the genetic underpinnings of behavioral states. More recently, the zebrafish has emerged as a promising model system for sleep and arousal research. Here we review experimental evidence that the zebrafish, a diurnal vertebrate, exhibits fundamental behavioral and neurochemical characteristics of mammalian sleep and arousal. We also propose how specific advantages of the zebrafish can be harnessed to advance the field. These include tractable genetics to identify and manipulate molecular and cellular regulators of behavioral states, optical transparency to facilitate in vivo observation of neural structure and function, and amenability to high-throughput drug screens to discover novel therapies for neurological disorders.

  16. Tube holding system

    International Nuclear Information System (INIS)

    Cunningham, R.C.

    1978-01-01

    A tube holding rig is described for the lateral support of tubes arranged in tight parcels in a heat exchanger. This tube holding rig includes not less than two tube supporting assemblies, with a space between them, located crosswise with respect to the tubes, each supporting assembly comprising a first set of parallel components in contact with the tubes, whilst a second set of components is also in contact with the tubes. These two sets of parts together define apertures through which the tubes pass [fr

  17. New tides: using zebrafish to study renal regeneration.

    Science.gov (United States)

    McCampbell, Kristen K; Wingert, Rebecca A

    2014-02-01

    Over the past several decades, the zebrafish has become one of the major vertebrate model organisms used in biomedical research. In this arena, the zebrafish has emerged as an applicable system for the study of kidney diseases and renal regeneration. The relevance of the zebrafish model for nephrology research has been increasingly appreciated as the understanding of zebrafish kidney structure, ontogeny, and the response to damage has steadily expanded. Recent studies have documented the amazing regenerative characteristics of the zebrafish kidney, which include the ability to replace epithelial populations after acute injury and to grow new renal functional units, termed nephrons. Here we discuss how nephron composition is conserved between zebrafish and mammals, and highlight how recent findings from zebrafish studies utilizing transgenic technologies and chemical genetics can complement traditional murine approaches in the effort to dissect how the kidney responds to acute damage and identify therapeutics that enhance human renal regeneration. Copyright © 2014 Mosby, Inc. All rights reserved.

  18. Chitosan derived co-spheroids of neural stem cells and mesenchymal stem cells for neural regeneration.

    Science.gov (United States)

    Han, Hao-Wei; Hsu, Shan-Hui

    2017-10-01

    Chitosan has been considered as candidate biomaterials for neural applications. The effective treatment of neurodegeneration or injury to the central nervous system (CNS) is still in lack nowadays. Adult neural stem cells (NSCs) represents a promising cell source to treat the CNS diseases but they are limited in number. Here, we developed the core-shell spheroids of NSCs (shell) and mesenchymal stem cells (MSCs, core) by co-culturing cells on the chitosan surface. The NSCs in chitosan derived co-spheroids displayed a higher survival rate than those in NSC homo-spheroids. The direct interaction of NSCs with MSCs in the co-spheroids increased the Notch activity and differentiation tendency of NSCs. Meanwhile, the differentiation potential of MSCs in chitosan derived co-spheroids was significantly enhanced toward neural lineages. Furthermore, NSC homo-spheroids and NSC/MSC co-spheroids derived on chitosan were evaluated for their in vivo efficacy by the embryonic and adult zebrafish brain injury models. The locomotion activity of zebrafish receiving chitosan derived NSC homo-spheroids or NSC/MSC co-spheroids was partially rescued in both models. Meanwhile, the higher survival rate was observed in the group of adult zebrafish implanted with chitosan derived NSC/MSC co-spheroids as compared to NSC homo-spheroids. These evidences indicate that chitosan may provide an extracellular matrix-like environment to drive the interaction and the morphological assembly between NSCs and MSCs and promote their neural differentiation capacities, which can be used for neural regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Neutrophil Reverse Migration Becomes Transparent with Zebrafish

    Directory of Open Access Journals (Sweden)

    Taylor W. Starnes

    2012-01-01

    Full Text Available The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.

  20. Tributyltin and Zebrafish: Swimming in Dangerous Water

    Directory of Open Access Journals (Sweden)

    Clemilson Berto-Júnior

    2018-04-01

    Full Text Available Zebrafish has been established as a reliable biological model with important insertion in academy (morphologic, biochemical, and pathophysiological studies and pharmaceutical industry (toxicology and drug development due to its molecular complexity and similar systems biology that recapitulate those from other organisms. Considering the toxicological aspects, many efforts using zebrafish models are being done in order to elucidate the effects of endocrine disruptors, and some of them are focused on tributyltin (TBT and its mechanism of action. TBT is an antifouling agent applied in ship’s hull that is constantly released into the water and absorbed by marine organisms, leading to bioaccumulation and biomagnification effects. Thus, several findings of malformations and changes in the normal biochemical and physiologic aspects of these marine animals have been related to TBT contamination. In the present review, we have compiled the most significant studies related to TBT effects in zebrafish, also taking into consideration the effects found in other study models.

  1. Tributyltin and Zebrafish: Swimming in Dangerous Water

    Science.gov (United States)

    Berto-Júnior, Clemilson; de Carvalho, Denise Pires; Soares, Paula; Miranda-Alves, Leandro

    2018-01-01

    Zebrafish has been established as a reliable biological model with important insertion in academy (morphologic, biochemical, and pathophysiological studies) and pharmaceutical industry (toxicology and drug development) due to its molecular complexity and similar systems biology that recapitulate those from other organisms. Considering the toxicological aspects, many efforts using zebrafish models are being done in order to elucidate the effects of endocrine disruptors, and some of them are focused on tributyltin (TBT) and its mechanism of action. TBT is an antifouling agent applied in ship’s hull that is constantly released into the water and absorbed by marine organisms, leading to bioaccumulation and biomagnification effects. Thus, several findings of malformations and changes in the normal biochemical and physiologic aspects of these marine animals have been related to TBT contamination. In the present review, we have compiled the most significant studies related to TBT effects in zebrafish, also taking into consideration the effects found in other study models. PMID:29692757

  2. Culturable gut microbiota diversity in zebrafish.

    Science.gov (United States)

    Cantas, Leon; Sørby, Jan Roger Torp; Aleström, Peter; Sørum, Henning

    2012-03-01

    The zebrafish (Danio rerio) is an increasingly used laboratory animal model in basic biology and biomedicine, novel drug development, and toxicology. The wide use has increased the demand for optimized husbandry protocols to ensure animal health care and welfare. The knowledge about the correlation between culturable zebrafish intestinal microbiota and health in relation to environmental factors and management procedures is very limited. A semi-quantitative level of growth of individual types of bacteria was determined and associated with sampling points. A total of 72 TAB line zebrafish from four laboratories (Labs A-D) in the Zebrafish Network Norway were used. Diagnostic was based on traditional bacterial culture methods and biochemical characterization using commercial kits, followed by 16S rDNA gene sequencing from pure subcultures. Also selected Gram-negative isolates were analyzed for antibiotic susceptibility to 8 different antibiotics. A total of 13 morphologically different bacterial species were the most prevalent: Aeromonas hydrophila, Aeromonas sobria, Vibrio parahaemolyticus, Photobacterium damselae, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas luteola, Comamonas testosteroni, Ochrobactrum anthropi, Staphylococcus cohnii, Staphylococcus epidermidis, Staphylococcus capitis, and Staphylococcus warneri. Only Lab B had significantly higher levels of total bacterial growth (OR=2.03), whereas numbers from Lab C (OR=1.01) and Lab D (OR=1.12) were found to be similar to the baseline Lab A. Sexually immature individuals had a significantly higher level of harvested total bacterial growth than mature fish (OR=0.82), no statistically significant differences were found between male and female fish (OR=1.01), and the posterior intestinal segment demonstrated a higher degree of culturable bacteria than the anterior segment (OR=4.1). Multiple antibiotic (>3) resistance was observed in 17% of the strains. We propose that a rapid conventional

  3. Endogenous retinal neural stem cell reprogramming for neuronal regeneration

    Directory of Open Access Journals (Sweden)

    Romain Madelaine

    2017-01-01

    Full Text Available In humans, optic nerve injuries and associated neurodegenerative diseases are often followed by permanent vision loss. Consequently, an important challenge is to develop safe and effective methods to replace retinal neurons and thereby restore neuronal functions and vision. Identifying cellular and molecular mechanisms allowing to replace damaged neurons is a major goal for basic and translational research in regenerative medicine. Contrary to mammals, the zebrafish has the capacity to fully regenerate entire parts of the nervous system, including retina. This regenerative process depends on endogenous retinal neural stem cells, the Müller glial cells. Following injury, zebrafish Müller cells go back into cell cycle to proliferate and generate new neurons, while mammalian Müller cells undergo reactive gliosis. Recently, transcription factors and microRNAs have been identified to control the formation of new neurons derived from zebrafish and mammalian Müller cells, indicating that cellular reprogramming can be an efficient strategy to regenerate human retinal neurons. Here we discuss recent insights into the use of endogenous neural stem cell reprogramming for neuronal regeneration, differences between zebrafish and mammalian Müller cells, and the need to pursue the identification and characterization of new molecular factors with an instructive and potent function in order to develop theurapeutic strategies for eye diseases.

  4. Standardized orthotopic xenografts in zebrafish reveal glioma cell-line-specific characteristics and tumor cell heterogeneity

    Directory of Open Access Journals (Sweden)

    Alessandra M. Welker

    2016-02-01

    Full Text Available Glioblastoma (GBM is a deadly brain cancer, for which few effective drug treatments are available. Several studies have used zebrafish models to study GBM, but a standardized approach to modeling GBM in zebrafish was lacking to date, preventing comparison of data across studies. Here, we describe a new, standardized orthotopic xenotransplant model of GBM in zebrafish. Dose-response survival assays were used to define the optimal number of cells for tumor formation. Techniques to measure tumor burden and cell spread within the brain over real time were optimized using mouse neural stem cells as control transplants. Applying this standardized approach, we transplanted two patient-derived GBM cell lines, serum-grown adherent cells and neurospheres, into the midbrain region of embryonic zebrafish and analyzed transplanted larvae over time. Progressive brain tumor growth and premature larval death were observed using both cell lines; however, fewer transplanted neurosphere cells were needed for tumor growth and lethality. Tumors were heterogeneous, containing both cells expressing stem cell markers and cells expressing markers of differentiation. A small proportion of transplanted neurosphere cells expressed glial fibrillary acidic protein (GFAP or vimentin, markers of more differentiated cells, but this number increased significantly during tumor growth, indicating that these cells undergo differentiation in vivo. By contrast, most serum-grown adherent cells expressed GFAP and vimentin at the earliest times examined post-transplant. Both cell types produced brain tumors that contained Sox2+ cells, indicative of tumor stem cells. Transplanted larvae were treated with currently used GBM therapeutics, temozolomide or bortezomib, and this resulted in a reduction in tumor volume in vivo and an increase in survival. The standardized model reported here facilitates robust and reproducible analysis of glioblastoma tumor cells in real time and provides a

  5. Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulate Myelination in Zebrafish

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    Yuhei Nishimura

    2016-07-01

    Full Text Available Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS, and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs. Of the genes differentially expressed in both miconazole- and clobetasol-treated mouse OPCs compared with untreated cells, we identified differentially expressed genes (DEGs common to both drug treatments. Gene ontology analysis revealed that these DEGs are significantly associated with the sterol biosynthetic pathway, and further bioinformatics analysis suggested that sterol regulatory element binding factors (SREBFs might be key upstream regulators of the DEGs. In silico screening of a public database for chemicals associated with SREBF activation identified fenofibrate, a peroxisome proliferator-activated receptor α (PPARα agonist, as a drug that increases the expression of known SREBF targets, raising the possibility that fenofibrate may also stimulate myelination. To test this, we performed in vivo imaging of zebrafish expressing a fluorescent reporter protein under the control of the myelin basic protein (mbp promoter. Treatment of zebrafish with fenofibrate significantly increased expression of the fluorescent reporter compared with untreated zebrafish. This increase was attenuated by co-treatment with fatostatin, a specific inhibitor of SREBFs, confirming that the fenofibrate effect was mediated via SREBFs. Furthermore, incubation

  6. DNA methylation regulates gabrb2 mRNA expression: developmental variations and disruptions in l-methionine-induced zebrafish with schizophrenia-like symptoms.

    Science.gov (United States)

    Wang, L; Jiang, W; Lin, Q; Zhang, Y; Zhao, C

    2016-11-01

    Single nucleotide polymorphisms (SNPs) in the human type A gamma-aminobutyric acid (GABA) receptor β 2 subunit gene (GABRB2) have been associated with schizophrenia and quantitatively correlated with mRNA expression in the postmortem brain tissue of patients with schizophrenia. l-Methionine (MET) administration has been reported to cause a recrudescence of psychotic symptoms in patients with schizophrenia, and similar symptoms have been generated in MET-induced mice. In this study, a zebrafish animal model was used to evaluate the relationship between the gabrb2 mRNA expression and its promoter DNA methylation in developmental and MET-induced schizophrenia-like zebrafish. The results indicated developmental increases in global DNA methylation and decreases in gabrb2 promoter methylation in zebrafish. A significant increase in gabrb2 mRNA levels was observed after GABA was synthesized. Additionally, the MET-triggered schizophrenia-like symptoms in adult zebrafish, involving social withdrawal and cognitive dysfunction analyzed with social interaction and T-maze behavioral tests, were accompanied by significantly increased DNA methylation levels in the global genome and the gabrb2 promoter. Furthermore, the significant correlation between gabrb2 mRNA expression and gabrb2 promoter methylation observed in the developmental stages became non-significant in MET-triggered adult zebrafish. These findings demonstrate that gabrb2 mRNA expression is associated with DNA methylation varies by developmental stage and show that these epigenetic association mechanisms are disrupted in MET-triggered adult zebrafish with schizophrenia-like symptoms. In conclusion, these results provide plausible epigenetic evidence of the GABA A receptor β 2 subunit involvement in the schizophrenia-like behaviors and demonstrate the potential use of zebrafish models in neuropsychiatric research. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  7. Targeted knock-in of CreER T2 in zebrafish using CRISPR/Cas9.

    Science.gov (United States)

    Kesavan, Gokul; Hammer, Juliane; Hans, Stefan; Brand, Michael

    2018-04-01

    New genome-editing approaches, such as the CRISPR/Cas system, have opened up great opportunities to insert or delete genes at targeted loci and have revolutionized genetics in model organisms like the zebrafish. The Cre-loxp recombination system is widely used to activate or inactivate genes with high spatial and temporal specificity. Using a CRISPR/Cas9-mediated knock-in strategy, we inserted a zebrafish codon-optimized CreER T2 transgene at the otx2 gene locus to generate a conditional Cre-driver line. We chose otx2 as it is a patterning gene of the anterior neural plate that is expressed during early development. By knocking in CreER T2 upstream of the endogenous ATG of otx2, we utilized this gene's native promoter and enhancer elements to perfectly match CreER T2 and endogenous otx2 expression patterns. Next, by combining this novel driver line with a Cre-dependent reporter line, we show that only in the presence of tamoxifen can efficient Cre-loxp-mediated recombination be achieved in the anterior neural plate-derived tissues like the telencephalon, the eye and the optic tectum. Our results imply that the otx2:CreER T2 transgenic fish will be a valuable tool for lineage tracing and conditional mutant studies in larval and adult zebrafish.

  8. Zebrafish swimming in the flow: a particle image velocimetry study

    Directory of Open Access Journals (Sweden)

    Violet Mwaffo

    2017-11-01

    Full Text Available Zebrafish is emerging as a species of choice for the study of a number of biomechanics problems, including balance development, schooling, and neuromuscular transmission. The precise quantification of the flow physics around swimming zebrafish is critical toward a mechanistic understanding of the complex swimming style of this fresh-water species. Although previous studies have elucidated the vortical structures in the wake of zebrafish swimming in placid water, the flow physics of zebrafish swimming against a water current remains unexplored. In an effort to illuminate zebrafish swimming in a dynamic environment reminiscent of its natural habitat, we experimentally investigated the locomotion and hydrodynamics of a single zebrafish swimming in a miniature water tunnel using particle image velocimetry. Our results on zebrafish locomotion detail the role of flow speed on tail beat undulations, heading direction, and swimming speed. Our findings on zebrafish hydrodynamics offer a precise quantification of vortex shedding during zebrafish swimming and demonstrate that locomotory patterns play a central role on the flow physics. This knowledge may help clarify the evolutionary advantage of burst and cruise swimming movements in zebrafish.

  9. Bender/Coiler for Tubing

    Science.gov (United States)

    Stoltzfus, J. M.

    1983-01-01

    Easy-to-use tool makes coils of tubing. Tubing to be bend clamped with stop post. Die positioned snugly against tubing. Operator turns handle to slide die along tubing, pushing tubing into spiral groove on mandrel.

  10. Data analysis for steam generator tubing samples

    International Nuclear Information System (INIS)

    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

  11. Zebrafish in Toxicology and Environmental Health.

    Science.gov (United States)

    Bambino, Kathryn; Chu, Jaime

    2017-01-01

    As manufacturing processes and development of new synthetic compounds increase to keep pace with the expanding global demand, environmental health, and the effects of toxicant exposure are emerging as critical public health concerns. Additionally, chemicals that naturally occur in the environment, such as metals, have profound effects on human and animal health. Many of these compounds are in the news: lead, arsenic, and endocrine disruptors such as bisphenol A have all been widely publicized as causing disease or damage to humans and wildlife in recent years. Despite the widespread appreciation that environmental toxins can be harmful, there is limited understanding of how many toxins cause disease. Zebrafish are at the forefront of toxicology research; this system has been widely used as a tool to detect toxins in water samples and to investigate the mechanisms of action of environmental toxins and their related diseases. The benefits of zebrafish for studying vertebrate development are equally useful for studying teratogens. Here, we review how zebrafish are being used both to detect the presence of some toxins as well as to identify how environmental exposures affect human health and disease. We focus on areas where zebrafish have been most effectively used in ecotoxicology and in environmental health, including investigation of exposures to endocrine disruptors, industrial waste byproducts, and arsenic. © 2017 Elsevier Inc. All rights reserved.

  12. Visualizing infections and immune mechanisms in zebrafish

    DEFF Research Database (Denmark)

    Jørgensen, Louise von Gersdorff; Korbut, Rozalia; Mehrdana, Foojan

    , immunological reactions during e.g. transplant rejections or the spread and pathogenicity of pathogens. We have, in our laboratory, used the zebrafish as a model for aquacultured fish species and their pathogens. We have 1) visualized antigen uptake in vivo following a bath in a soup containing fluorescent...

  13. Highly Efficient ENU Mutagenesis in Zebrafish.

    NARCIS (Netherlands)

    de Bruijn, E.; Cuppen, E.; Feitsma, H.

    2009-01-01

    ENU (N-ethyl-N-nitrosourea) mutagenesis is a widely accepted and proven method to introduce random point mutations in the genome. Because there are no targeted knockout strategies available for zebrafish so far, random mutagenesis is currently the preferred method in both forward and reverse genetic

  14. Molecular genetics of pituitary development in zebrafish.

    Science.gov (United States)

    Pogoda, Hans-Martin; Hammerschmidt, Matthias

    2007-08-01

    The pituitary gland of vertebrates consists of two major parts, the neurohypophysis (NH) and the adenohypophysis (AH). As a central part of the hypothalamo-hypophyseal system (HHS), it constitutes a functional link between the nervous and the endocrine system to regulate basic body functions, such as growth, metabolism and reproduction. The development of the AH has been intensively studied in mouse, serving as a model for organogenesis and differential cell specification. However, given that the AH is a relatively recent evolutionary advance of the chordate phylum, it is also interesting to understand its development in lower chordate systems. In recent years, the zebrafish has emerged as a powerful lower vertebrate system for developmental studies, being amenable for large-scale genetic approaches, embryological manipulations, and in vivo imaging. Here, we present an overview of current knowledge of the mechanisms and genetic control of pituitary formation during zebrafish development. First, we describe the components of the zebrafish HHS, and the different pituitary cell types and hormones, followed by a description of the different steps of normal pituitary development. The central part of the review deals with the genes found to be essential for zebrafish AH development, accompanied by a description of the corresponding mutant phenotypes. Finally, we discuss future directions, with particular focus on evolutionary aspects, and some novel functional aspects with growing medical and social relevance.

  15. A zebrafish model of inflammatory lymphangiogenesis

    Directory of Open Access Journals (Sweden)

    Kazuhide S. Okuda

    2015-10-01

    Full Text Available Inflammatory bowel disease (IBD is a disabling chronic inflammatory disease of the gastrointestinal tract. IBD patients have increased intestinal lymphatic vessel density and recent studies have shown that this may contribute to the resolution of IBD. However, the molecular mechanisms involved in IBD-associated lymphangiogenesis are still unclear. In this study, we established a novel inflammatory lymphangiogenesis model in zebrafish larvae involving colitogenic challenge stimulated by exposure to 2,4,6-trinitrobenzenesulfonic acid (TNBS or dextran sodium sulphate (DSS. Treatment with either TNBS or DSS resulted in vascular endothelial growth factor receptor (Vegfr-dependent lymphangiogenesis in the zebrafish intestine. Reduction of intestinal inflammation by the administration of the IBD therapeutic, 5-aminosalicylic acid, reduced intestinal lymphatic expansion. Zebrafish macrophages express vascular growth factors vegfaa, vegfc and vegfd and chemical ablation of these cells inhibits intestinal lymphatic expansion, suggesting that the recruitment of macrophages to the intestine upon colitogenic challenge is required for intestinal inflammatory lymphangiogenesis. Importantly, this study highlights the potential of zebrafish as an inflammatory lymphangiogenesis model that can be used to investigate the role and mechanism of lymphangiogenesis in inflammatory diseases such as IBD.

  16. Axonal regeneration in zebrafish spinal cord

    Science.gov (United States)

    Hui, Subhra Prakash

    2018-01-01

    Abstract In the present review we discuss two interrelated events—axonal damage and repair—known to occur after spinal cord injury (SCI) in the zebrafish. Adult zebrafish are capable of regenerating axonal tracts and can restore full functionality after SCI. Unlike fish, axon regeneration in the adult mammalian central nervous system is extremely limited. As a consequence of an injury there is very little repair of disengaged axons and therefore functional deficit persists after SCI in adult mammals. In contrast, peripheral nervous system axons readily regenerate following injury and hence allow functional recovery both in mammals and fish. A better mechanistic understanding of these three scenarios could provide a more comprehensive insight into the success or failure of axonal regeneration after SCI. This review summarizes the present understanding of the cellular and molecular basis of axonal regeneration, in both the peripheral nervous system and the central nervous system, and large scale gene expression analysis is used to focus on different events during regeneration. The discovery and identification of genes involved in zebrafish spinal cord regeneration and subsequent functional experimentation will provide more insight into the endogenous mechanism of myelination and remyelination. Furthermore, precise knowledge of the mechanism underlying the extraordinary axonal regeneration process in zebrafish will also allow us to unravel the potential therapeutic strategies to be implemented for enhancing regrowth and remyelination of axons in mammals. PMID:29721326

  17. Patterns of free calcium in zebrafish embryos

    NARCIS (Netherlands)

    Creton, R; Speksnijder, JE; Jaffe, LF

    Direct knowledge of Ca2+ patterns in vertebrate development is largely restricted to early stages, in which they control fertilization, ooplasmic segregation and cleavage. To explore new roles of Ca2+ in vertebrate development, we injected the Ca2+ indicator aequorin into zebrafish eggs and imaged

  18. Effects of alpha particles on zebrafish embryos

    International Nuclear Information System (INIS)

    Yum, E.H.W.; Choi, V.W.Y.; Yu, K.N.; Li, V.W.T.; Cheng, S.H.

    2008-01-01

    Full text: Ionizing radiation such as X-ray and alpha particles can damage cellular macromolecules, which can lead to DNA single- and double-strand breaks. In the present work, we studied the effects of alpha particles on dechorionated zebrafish embryos. Thin polyallyldiglycol carbonate (PADC) films with a thickness of 16 μm were prepared from commercially available PADC films (with thickness of 100 μm) by chemical etching and used as support substrates for holding zebrafish embryos for alpha-particle irradiation. These films recorded alpha-particle hit positions, quantified the number and energy of alpha particles actually incident on the embryo cells, and thus enabled the calculation of the dose absorbed by the embryo cells. Irradiation was made at 1.25 hours post fertilization (hpf) with various absorbed dose. TdT-mediated dUTP Nick-End Labeling (TUNEL) assay was performed on the embryos at different time stages after irradiation. Marked apoptosis was detected only in embryos at earlier time stages. The results showed that DNA double-strand break during zebrafish embryogenesis can be induced by alpha-particle irradiation, which suggests that zebrafish is a potential model for assessing the effects of alpha-particle radiation

  19. Time course Analysis of Gene expression patterns in ZebrafIsh Eye during Optic Nerve Regeneration

    Directory of Open Access Journals (Sweden)

    Amy T. Mccurley

    2010-01-01

    Full Text Available It is well-established that neurons in the adult mammalian central nervous system (CNS are terminally differentiated and, if injured, will be unable to regenerate their connections. In contrast to mammals, zebrafish and other teleosts display a robust neuroregenerative response. Following optic nerve crush (ONX, retinal ganglion cells (RGC regrow their axons to synapse with topographically correct targets in the optic tectum, such that vision is restored in ~21 days. What accounts for these differences between teleostean and mammalian responses to neural injury is not fully understood. A time course analysis of global gene expression patterns in the zebrafish eye after ONX can help to elucidate cellular and molecular mechanisms that contribute to a successful neuroregeneration. To define different phases of regeneration after ONX, alpha tubulin 1 ( tuba1 and growth-associated protein 43 ( gap43 , markers previously shown to correspond to morphophological events, were measured by real time quantitative PCR (qPCR. Microarray analysis was then performed at defined intervals (6 hours, 1, 4, 12, and 21 days post-ONX and compared to SHAM. Results show that optic nerve damage induces multiple, phase-related transcriptional programs, with the maximum number of genes changed and highest fold-change occurring at 4 days. Several functional groups affected by optic nerve regeneration, including cell adhesion, apoptosis, cell cycle, energy metabolism, ion channel activity, and calcium signaling, were identified. Utilizing the whole eye allowed us to identify signaling contributions from the vitreous, immune and glial cells as well as the neural cells of the retina. Comparisons between our dataset and transcriptional profiles from other models of regeneration in zebrafish retina, heart and fin revealed a subset of commonly regulated transcripts, indicating shared mechanisms in different regenerating tissues. Knowledge of gene expression patterns in all

  20. The Neural Border: Induction, Specification and Maturation of the territory that generates Neural Crest cells.

    Science.gov (United States)

    Pla, Patrick; Monsoro-Burq, Anne H

    2018-05-28

    The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions. Copyright © 2018. Published by Elsevier Inc.

  1. Social conflict resolution regulated by two dorsal habenular subregions in zebrafish.

    Science.gov (United States)

    Chou, Ming-Yi; Amo, Ryunosuke; Kinoshita, Masae; Cherng, Bor-Wei; Shimazaki, Hideaki; Agetsuma, Masakazu; Shiraki, Toshiyuki; Aoki, Tazu; Takahoko, Mikako; Yamazaki, Masako; Higashijima, Shin-ichi; Okamoto, Hitoshi

    2016-04-01

    When animals encounter conflict they initiate and escalate aggression to establish and maintain a social hierarchy. The neural mechanisms by which animals resolve fighting behaviors to determine such social hierarchies remain unknown. We identified two subregions of the dorsal habenula (dHb) in zebrafish that antagonistically regulate the outcome of conflict. The losing experience reduced neural transmission in the lateral subregion of dHb (dHbL)-dorsal/intermediate interpeduncular nucleus (d/iIPN) circuit. Silencing of the dHbL or medial subregion of dHb (dHbM) caused a stronger predisposition to lose or win a fight, respectively. These results demonstrate that the dHbL and dHbM comprise a dual control system for conflict resolution of social aggression. Copyright © 2016, American Association for the Advancement of Science.

  2. Defects of the Glycinergic Synapse in Zebrafish

    Science.gov (United States)

    Ogino, Kazutoyo; Hirata, Hiromi

    2016-01-01

    Glycine mediates fast inhibitory synaptic transmission. Physiological importance of the glycinergic synapse is well established in the brainstem and the spinal cord. In humans, the loss of glycinergic function in the spinal cord and brainstem leads to hyperekplexia, which is characterized by an excess startle reflex to sudden acoustic or tactile stimulation. In addition, glycinergic synapses in this region are also involved in the regulation of respiration and locomotion, and in the nociceptive processing. The importance of the glycinergic synapse is conserved across vertebrate species. A teleost fish, the zebrafish, offers several advantages as a vertebrate model for research of glycinergic synapse. Mutagenesis screens in zebrafish have isolated two motor defective mutants that have pathogenic mutations in glycinergic synaptic transmission: bandoneon (beo) and shocked (sho). Beo mutants have a loss-of-function mutation of glycine receptor (GlyR) β-subunit b, alternatively, sho mutant is a glycinergic transporter 1 (GlyT1) defective mutant. These mutants are useful animal models for understanding of glycinergic synaptic transmission and for identification of novel therapeutic agents for human diseases arising from defect in glycinergic transmission, such as hyperekplexia or glycine encephalopathy. Recent advances in techniques for genome editing and for imaging and manipulating of a molecule or a physiological process make zebrafish more attractive model. In this review, we describe the glycinergic defective zebrafish mutants and the technical advances in both forward and reverse genetic approaches as well as in vivo visualization and manipulation approaches for the study of the glycinergic synapse in zebrafish. PMID:27445686

  3. Detection of vitellogenin incorporation into zebrafish oocytes by FITC fluorescence

    Directory of Open Access Journals (Sweden)

    Yokoi Hayato

    2011-04-01

    Full Text Available Abstract Background Large volumes of lymph can be collected from the eye-sacs of bubble-eye goldfish. We attempted to induce vitellogenin (Vtg in the eye-sac lymph of bubble-eye goldfish and develop a method for visualizing Vtg incorporation by zebrafish oocytes using FITC-labeling. Methods Estrogen efficiently induced Vtg in the eye-sac lymph of goldfish. After FITC-labeled Vtg was prepared, it was injected into mature female zebrafish. Results Incorporation of FITC-labeled Vtg by zebrafish oocytes was detected in in vivo and in vitro experiments. The embryos obtained from zebrafish females injected with FITC-labeled Vtg emitted FITC fluorescence from the yolk sac and developed normally. Conclusion This method for achieving Vtg incorporation by zebrafish oocytes could be useful in experiments related to the development and endocrinology of zebrafish oocytes.

  4. Analysis of Lethality and Malformations During Zebrafish (Danio rerio) Development.

    Science.gov (United States)

    Raghunath, Azhwar; Perumal, Ekambaram

    2018-01-01

    The versatility offered by zebrafish (Danio rerio) makes it a powerful and an attractive vertebrate model in developmental toxicity and teratogenicity assays. Apart from the newly introduced chemicals as drugs, xenobiotics also induce abnormal developmental abnormalities and congenital malformations in living organisms. Over the recent decades, zebrafish embryo/larva has emerged as a potential tool to test teratogenicity potential of these chemicals. Zebrafish responds to compounds as mammals do as they share similarities in their development, metabolism, physiology, and signaling pathways with that of mammals. The methodology used by the different scientists varies enormously in the zebrafish embryotoxicity test. In this chapter, we present methods to assess lethality and malformations during zebrafish development. We propose two major malformations scoring systems: binomial and relative morphological scoring systems to assess the malformations in zebrafish embryos/larvae. Based on the scoring of the malformations, the test compound can be classified as a teratogen or a nonteratogen and its teratogenic potential is evaluated.

  5. Biosecurity and Health Monitoring at the Zebrafish International Resource Center.

    Science.gov (United States)

    Murray, Katrina N; Varga, Zoltán M; Kent, Michael L

    2016-07-01

    The Zebrafish International Resource Center (ZIRC) is a repository and distribution center for mutant, transgenic, and wild-type zebrafish. In recent years annual imports of new zebrafish lines to ZIRC have increased tremendously. In addition, after 15 years of research, we have identified some of the most virulent pathogens affecting zebrafish that should be avoided in large production facilities, such as ZIRC. Therefore, while importing a high volume of new lines we prioritize safeguarding the health of our in-house fish colony. Here, we describe the biosecurity and health-monitoring program implemented at ZIRC. This strategy was designed to prevent introduction of new zebrafish pathogens, minimize pathogens already present in the facility, and ensure a healthy zebrafish colony for in-house uses and shipment to customers.

  6. Laser capture microdissection of gonads from juvenile zebrafish

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Nielsen, John; Morthorst, Jane Ebsen

    2009-01-01

    was adjusted and optimised to isolate juvenile zebrafish gonads. Results: The juvenile zebrafish gonad is not morphologically distinguishable when using dehydrated cryosections on membrane slides and a specific staining method is necessary to identify the gonads. The protocol setup in this study allows......Background: Investigating gonadal gene expression is important in attempting to elucidate the molecular mechanism of sex determination and differentiation in the model species zebrafish. However, the small size of juvenile zebrafish and correspondingly their gonads complicates this type...... of investigation. Furthermore, the lack of a genetic sex marker in juvenile zebrafish prevents pooling gonads from several individuals. The aim of this study was to establish a method to isolate the gonads from individual juvenile zebrafish allowing future investigations of gonadal gene expression during sex...

  7. Investigating the Flow and Biomechanics of the Embryonic Zebrafish Heart

    Science.gov (United States)

    Johnson, Brennan; Garrity, Deborah; Dasi, Lakshmi

    2010-11-01

    Understanding flow and kinematic characteristics of the embryonic heart is a prerequisite to devise early intervention or detection methods in the context of congenital heart defects. In this study, the kinematics and fluid dynamics of the embryonic zebrafish heart were analyzed through the early stages of cardiac development (24-48 hours post-fertilization) in vivo using optical microscopy and high-speed video. Endocardial walls and individual blood cells were segmented from raw images and were tracked through the cardiac cycle. Particle tracking velocimetry analysis yielded quantitative blood cell velocity field, chamber volume, and flow rate information. It was seen that the pumping mechanism starts as a combined peristaltic and suction pump while the heart is in the tube configuration and transforms into a positive displacement pump after cardiac looping. Strong two-phase nature of the fluid is evident. This work provides us new understanding of the spatio-temporal characteristics of kinematics and blood cell velocity field inside the developing heart.

  8. Development and regeneration of the zebrafish maxillary barbel: a novel study system for vertebrate tissue growth and repair.

    Science.gov (United States)

    LeClair, Elizabeth E; Topczewski, Jacek

    2010-01-15

    Barbels are integumentary sense organs found in fishes, reptiles and amphibians. The zebrafish, Danio rerio, develops paired nasal and maxillary barbels approximately one month post fertilization. Small in diameter and optically clear, these adult appendages offer a window on the development, maintenance and function of multiple cell types including skin cells, neural-crest derived pigment cells, circulatory vessels, taste buds and sensory nerves. Importantly, barbels in other otophysan fishes (e.g., catfish) are known to regenerate; however, this capacity has not been tested in zebrafish. We describe the development of the maxillary barbel in a staged series of wild type and transgenic zebrafish using light microscopy, histology and immunohistochemistry. By imaging transgenic zebrafish containing fluorescently labeled endothelial cells (Tg(fli1a:EGFP)), we demonstrate that the barbel contains a long ( approximately 2-3 mm) closed-end vessel that we interpret as a large lymphatic. The identity of this vessel was further supported by live imaging of the barbel circulation, extending recent descriptions of the lymphatic system in zebrafish. The maxillary barbel can be induced to regenerate by proximal amputation. After more than 750 experimental surgeries in which approximately 85% of the barbel's length was removed, we find that wound healing is complete within hours, followed by blastema formation ( approximately 3 days), epithelial redifferentiation (3-5 days) and appendage elongation. Maximum regrowth occurs within 2 weeks of injury. Although superficially normal, the regenerates are shorter and thicker than the contralateral controls, have abnormally organized mesenchymal cells and extracellular matrix, and contain prominent connective tissue "stumps" at the plane of section--a mode of regeneration more typical of mammalian scarring than other zebrafish appendages. Finally, we show that the maxillary barbel can regenerate after repeated injury and also in

  9. Development and regeneration of the zebrafish maxillary barbel: a novel study system for vertebrate tissue growth and repair.

    Directory of Open Access Journals (Sweden)

    Elizabeth E LeClair

    2010-01-01

    Full Text Available Barbels are integumentary sense organs found in fishes, reptiles and amphibians. The zebrafish, Danio rerio, develops paired nasal and maxillary barbels approximately one month post fertilization. Small in diameter and optically clear, these adult appendages offer a window on the development, maintenance and function of multiple cell types including skin cells, neural-crest derived pigment cells, circulatory vessels, taste buds and sensory nerves. Importantly, barbels in other otophysan fishes (e.g., catfish are known to regenerate; however, this capacity has not been tested in zebrafish.We describe the development of the maxillary barbel in a staged series of wild type and transgenic zebrafish using light microscopy, histology and immunohistochemistry. By imaging transgenic zebrafish containing fluorescently labeled endothelial cells (Tg(fli1a:EGFP, we demonstrate that the barbel contains a long ( approximately 2-3 mm closed-end vessel that we interpret as a large lymphatic. The identity of this vessel was further supported by live imaging of the barbel circulation, extending recent descriptions of the lymphatic system in zebrafish. The maxillary barbel can be induced to regenerate by proximal amputation. After more than 750 experimental surgeries in which approximately 85% of the barbel's length was removed, we find that wound healing is complete within hours, followed by blastema formation ( approximately 3 days, epithelial redifferentiation (3-5 days and appendage elongation. Maximum regrowth occurs within 2 weeks of injury. Although superficially normal, the regenerates are shorter and thicker than the contralateral controls, have abnormally organized mesenchymal cells and extracellular matrix, and contain prominent connective tissue "stumps" at the plane of section--a mode of regeneration more typical of mammalian scarring than other zebrafish appendages. Finally, we show that the maxillary barbel can regenerate after repeated injury and

  10. Antiangiogenic effects of AA-PMe on HUVECs in vitro and zebrafish in vivo

    Directory of Open Access Journals (Sweden)

    Jing Y

    2018-04-01

    Full Text Available Yue Jing,1,2,* Gang Wang,1,* Qi Xiao,1 Yachun Zhou,1 Yingjie Wei,3 Zhunan Gong1 1Center for New Drug Research and Development, College of Life Science, Nanjing Normal University, Nanjing, China; 2Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China; 3Key Laboratory of Oral Drug Delivery System of Chinese Materia Medica of State Administration of Traditional Chinese Medicine, Jiangsu Branch of China Academy of Chinese Medical Science, Nanjing, China *These authors contributed equally to this work Abstract: Angiogenesis plays a vital role in many physiological and pathological processes and several diseases are connected with its dysregulation. Asiatic acid (AA has demonstrated anticancer properties and we suspect this might be attributable to an effect on angiogenesis. A modified derivative of AA, N-(2α,3β,23-acetoxyurs-12-en-28-oyl-L-proline methyl ester (AA-PMe, has improved efficacy over its parent compound, but its effect on blood vessel development remains unclear. Methods: In this study, we investigated the antiangiogenic activity of AA and AA-PMe in zebrafish embryos and human umbilical vein endothelial cells (HUVECs. First of all, we treated HUVECs with increasing concentrations of AA-PMe or AA, with or without vascular endothelial growth factor (VEGF present, and assessed cell viability, tube formation, and cell migration and invasion. Quantitative real-time polymerase chain reaction and Western blot analysis were later used to determine the role of vascular endothelial growth factor receptor 2 (VEGFR2-mediated signaling in AA-PMe inhibition of angiogenesis. We extended these studies to follow angiogenesis using Tg(fli:EGFP transgenic zebrafish embryos. For these experiments, embryos were treated with varying concentrations of AA-PMe or AA from 24 to 72 hours postfertilization prior to morphological observation, angiogenesis assessment, and endogenous alkaline

  11. X-ray tubes

    International Nuclear Information System (INIS)

    Young, R.W.

    1979-01-01

    A form of x-ray tube is described which provides satisfactory focussing of the electron beam when the beam extends for several feet from gun to target. Such a tube can be used for computerised tomographic scanning. (UK)

  12. Pressure tube type reactors

    International Nuclear Information System (INIS)

    Komada, Masaoki.

    1981-01-01

    Purpose: To increase the safety of pressure tube type reactors by providing an additional ECCS system to an ordinary ECCS system and injecting heavy water in the reactor core tank into pressure tubes upon fractures of the tubes. Constitution: Upon fractures of pressure tubes, reduction of the pressure in the fractured tubes to the atmospheric pressure in confirmed and the electromagnetic valve is operated to completely isolate the pressure tubes from the fractured portion. Then, the heavy water in the reactor core tank flows into and spontaneously recycles through the pressure tubes to cool the fuels in the tube to prevent their meltdown. By additionally providing the separate ECCS system to the ordinary ECCS system, fuels can be cooled upon loss of coolant accidents to improve the safety of the reactors. (Moriyama, K.)

  13. Gastrostomy feeding tube - bolus

    Science.gov (United States)

    Feeding - gastrostomy tube - bolus; G-tube - bolus; Gastrostomy button - bolus; Bard Button - bolus; MIC-KEY - bolus ... KEY, 3 to 8 weeks after surgery. These feedings will help your child grow strong and healthy. ...

  14. Feeding tube insertion - gastrostomy

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002937.htm Feeding tube insertion - gastrostomy To use the sharing features on this page, please enable JavaScript. A gastrostomy feeding tube insertion is the placement of a feeding ...

  15. Evaluation of visible implant elastomer tags in zebrafish (Danio rerio

    Directory of Open Access Journals (Sweden)

    Claudia Hohn

    2013-11-01

    The use of the visible implant elastomer (VIE tagging system in zebrafish (Danio rerio was examined. Two tag orientations (horizontal and vertical at the dorsal fin base were tested for tag retention, tag fragmentation and whether VIE tags affected growth and survival of juvenile zebrafish (1–4 month post hatch. Six tag locations (abdomen, anal fin base, caudal peduncle, dorsal fin base, pectoral fin base, isthmus and 5 tag colors (yellow, red, pink, orange, blue were evaluated for ease of VIE tag application and tag visibility in adult zebrafish. Long-term retention (1 year and multiple tagging sites (right and left of dorsal fin and pectoral fin base were examined in adult zebrafish. Lastly, survival of recombination activation gene 1−/− (rag1−/− zebrafish was evaluated after VIE tagging. The best tag location was the dorsal fin base, and the most visible tag color was pink. Growth rate of juvenile zebrafish was not affected by VIE tagging. Horizontal tagging is recommended in early stages of fish growth (1–2 months post hatch. VIE tags were retained for 1 year and tagging did not interfere with long-term growth and survival. There was no mortality associated with VIE tagging in rag1−/− zebrafish. The VIE tagging system is highly suitable for small-sized zebrafish. When familiar with the procedure, 120 adult zebrafish can be tagged in one hour. It does not increase mortality in adult zebrafish or interfere with growth in juvenile or adult zebrafish.

  16. Neural networks

    International Nuclear Information System (INIS)

    Denby, Bruce; Lindsey, Clark; Lyons, Louis

    1992-01-01

    The 1980s saw a tremendous renewal of interest in 'neural' information processing systems, or 'artificial neural networks', among computer scientists and computational biologists studying cognition. Since then, the growth of interest in neural networks in high energy physics, fueled by the need for new information processing technologies for the next generation of high energy proton colliders, can only be described as explosive

  17. Monitoring of single-cell responses in the optic tectum of adult zebrafish with dextran-coupled calcium dyes delivered via local electroporation.

    Directory of Open Access Journals (Sweden)

    Vanessa Kassing

    Full Text Available The zebrafish (Danio rerio has become one of the major animal models for in vivo examination of sensory and neuronal computation. Similar to Xenopus tadpoles neural activity in the optic tectum, the major region controlling visually guided behavior, can be examined in zebrafish larvae by optical imaging. Prerequisites of these approaches are usually the transparency of larvae up to a certain age and the use of two-photon microscopy. This principle of fluorescence excitation was necessary to suppress crosstalk between signals from individual neurons, which is a critical issue when using membrane-permeant dyes. This makes the equipment to study neuronal processing costly and limits the approach to the study of larvae. Thus there is lack of knowledge about the properties of neurons in the optic tectum of adult animals. We established a procedure to circumvent these problems, enabling in vivo calcium imaging in the optic tectum of adult zebrafish. Following local application of dextran-coupled dyes single-neuron activity of adult zebrafish can be monitored with conventional widefield microscopy, because dye labeling remains restricted to tens of neurons or less. Among the neurons characterized with our technique we found neurons that were selective for a certain pattern orientation as well as neurons that responded in a direction-selective way to visual motion. These findings are consistent with previous studies and indicate that the functional integrity of neuronal circuits in the optic tectum of adult zebrafish is preserved with our staining technique. Overall, our protocol for in vivo calcium imaging provides a useful approach to monitor visual responses of individual neurons in the optic tectum of adult zebrafish even when only widefield microscopy is available. This approach will help to obtain valuable insight into the principles of visual computation in adult vertebrates and thus complement previous work on developing visual circuits.

  18. Dissection of vertebrate hematopoiesis using zebrafish thrombopoietin

    Czech Academy of Sciences Publication Activity Database

    Svoboda, Ondřej; Stachura, D.L.; Machoňová, Olga; Pajer, Petr; Brynda, Jiří; Zon, L.I.; Traver, D.; Bartůněk, Petr

    2014-01-01

    Roč. 124, č. 2 (2014), s. 220-228 ISSN 0006-4971 R&D Projects: GA ČR GAP305/10/0953 Grant - others:NIH(US) K01-DK087814-01A1; NIH(US) R01-DK074482 Keywords : Zebrafish * hematopoiesis * progenitors * thrombopoietin * erythropoietin Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.452, year: 2014

  19. Ethanol Exposure Causes Muscle Degeneration in Zebrafish

    Directory of Open Access Journals (Sweden)

    Elizabeth C. Coffey

    2018-03-01

    Full Text Available Alcoholic myopathies are characterized by neuromusculoskeletal symptoms such as compromised movement and weakness. Although these symptoms have been attributed to neurological damage, EtOH may also target skeletal muscle. EtOH exposure during zebrafish primary muscle development or adulthood results in smaller muscle fibers. However, the effects of EtOH exposure on skeletal muscle during the growth period that follows primary muscle development are not well understood. We determined the effects of EtOH exposure on muscle during this phase of development. Strikingly, muscle fibers at this stage are acutely sensitive to EtOH treatment: EtOH induces muscle degeneration. The severity of EtOH-induced muscle damage varies but muscle becomes more refractory to EtOH as muscle develops. NF-kB induction in muscle indicates that EtOH triggers a pro-inflammatory response. EtOH-induced muscle damage is p53-independent. Uptake of Evans blue dye shows that EtOH treatment causes sarcolemmal instability before muscle fiber detachment. Dystrophin-null sapje mutant zebrafish also exhibit sarcolemmal instability. We tested whether Trichostatin A (TSA, which reduces muscle degeneration in sapje mutants, would affect EtOH-treated zebrafish. We found that TSA and EtOH are a lethal combination. EtOH does, however, exacerbate muscle degeneration in sapje mutants. EtOH also disrupts adhesion of muscle fibers to their extracellular matrix at the myotendinous junction: some detached muscle fibers retain beta-Dystroglycan indicating failure of muscle end attachments. Overexpression of Paxillin, which reduces muscle degeneration in zebrafish deficient for beta-Dystroglycan, is not sufficient to rescue degeneration. Taken together, our results suggest that EtOH exposure has pleiotropic deleterious effects on skeletal muscle.

  20. Disease modeling in genetic kidney diseases: zebrafish.

    Science.gov (United States)

    Schenk, Heiko; Müller-Deile, Janina; Kinast, Mark; Schiffer, Mario

    2017-07-01

    Growing numbers of translational genomics studies are based on the highly efficient and versatile zebrafish (Danio rerio) vertebrate model. The increasing types of zebrafish models have improved our understanding of inherited kidney diseases, since they not only display pathophysiological changes but also give us the opportunity to develop and test novel treatment options in a high-throughput manner. New paradigms in inherited kidney diseases have been developed on the basis of the distinct genome conservation of approximately 70 % between zebrafish and humans in terms of existing gene orthologs. Several options are available to determine the functional role of a specific gene or gene sets. Permanent genome editing can be induced via complete gene knockout by using the CRISPR/Cas-system, among others, or via transient modification by using various morpholino techniques. Cross-species rescues succeeding knockdown techniques are employed to determine the functional significance of a target gene or a specific mutation. This article summarizes the current techniques and discusses their perspectives.

  1. Social dominance modulates eavesdropping in zebrafish

    Science.gov (United States)

    Abril-de-Abreu, Rodrigo; Cruz, Ana S.; Oliveira, Rui F.

    2015-01-01

    Group living animals may eavesdrop on signalling interactions between conspecifics and integrate it with their own past social experience in order to optimize the use of relevant information from others. However, little is known about this interplay between public (eavesdropped) and private social information. To investigate it, we first manipulated the dominance status of bystander zebrafish. Next, we either allowed or prevented bystanders from observing a fight. Finally, we assessed their behaviour towards the winners and losers of the interaction, using a custom-made video-tracking system and directional analysis. We found that only dominant bystanders who had seen the fight revealed a significant increase in directional focus (a measure of attention) towards the losers of the fights. Furthermore, our results indicate that information about the fighters' acquired status was collected from the signalling interaction itself and not from post-interaction status cues, which implies the existence of individual recognition in zebrafish. Thus, we show for the first time that zebrafish, a highly social model organism, eavesdrop on conspecific agonistic interactions and that this process is modulated by the eavesdroppers' dominance status. We suggest that this type of integration of public and private information may be ubiquitous in social learning processes. PMID:26361550

  2. Afferent connectivity of the zebrafish habenulae

    Directory of Open Access Journals (Sweden)

    Katherine Jane Turner

    2016-04-01

    Full Text Available The habenulae are bilateral nuclei located in the dorsal diencephalon that are conserved across vertebrates.Here we describe the main afferents to the habenulae in larval and adult zebrafish.We observe afferents from the subpallium, nucleus rostrolateralis,posterior tuberculum, posterior hypothalamic lobe, median raphe, olfactory bulb to the right habenula and from the parapineal to the lefthabenula.In addition,we find afferents from a ventrolateral telencephalic nucleus that neurochemical and hodological data identify as the ventral entopeduncular nucleus(vENT,confirming and extending observations of Amo et al.(2014.Fate map and marker studies suggest that vENT originates from the diencephalic prethalamic eminence and extends into the lateral telencephalon from 48 to 120 hpf.No afferents to the habenula were observed from the dorsal entopeduncular nucleus(dENT.Consequently,we confirm that the vENT(and not the dENT should be considered as the entopeduncular nucleus proper in zebrafish.Furthermore,comparison with data in other vertebrates suggests that the vENT is a conserved basal ganglia nucleus,being homologous to the entopeduncular nucleus of mammals(internal segment of the globus pallidus of primates by both embryonic origin and projections,as previously suggested by Amo et al.(2014.Key words: habenula,connections,afferents,entopeduncular nucleus,posterior tuberculum,basal ganglia,zebrafish

  3. Use of zebrafish to study Shigella infection

    Science.gov (United States)

    Duggan, Gina M.

    2018-01-01

    ABSTRACT Shigella is a leading cause of dysentery worldwide, responsible for up to 165 million cases of shigellosis each year. Shigella is also recognised as an exceptional model pathogen to study key issues in cell biology and innate immunity. Several infection models have been useful to explore Shigella biology; however, we still lack information regarding the events taking place during the Shigella infection process in vivo. Here, we discuss a selection of mechanistic insights recently gained from studying Shigella infection of zebrafish (Danio rerio), with a focus on cytoskeleton rearrangements and cellular immunity. We also discuss how infection of zebrafish can be used to investigate new concepts underlying infection control, including emergency granulopoiesis and the use of predatory bacteria to combat antimicrobial resistance. Collectively, these insights illustrate how Shigella infection of zebrafish can provide fundamental advances in our understanding of bacterial pathogenesis and vertebrate host defence. This information should also provide vital clues for the discovery of new therapeutic strategies against infectious disease in humans. PMID:29590642

  4. Use of zebrafish to study Shigella infection

    Directory of Open Access Journals (Sweden)

    Gina M. Duggan

    2018-02-01

    Full Text Available Shigella is a leading cause of dysentery worldwide, responsible for up to 165 million cases of shigellosis each year. Shigella is also recognised as an exceptional model pathogen to study key issues in cell biology and innate immunity. Several infection models have been useful to explore Shigella biology; however, we still lack information regarding the events taking place during the Shigella infection process in vivo. Here, we discuss a selection of mechanistic insights recently gained from studying Shigella infection of zebrafish (Danio rerio, with a focus on cytoskeleton rearrangements and cellular immunity. We also discuss how infection of zebrafish can be used to investigate new concepts underlying infection control, including emergency granulopoiesis and the use of predatory bacteria to combat antimicrobial resistance. Collectively, these insights illustrate how Shigella infection of zebrafish can provide fundamental advances in our understanding of bacterial pathogenesis and vertebrate host defence. This information should also provide vital clues for the discovery of new therapeutic strategies against infectious disease in humans.

  5. Cell migration during heart regeneration in zebrafish.

    Science.gov (United States)

    Tahara, Naoyuki; Brush, Michael; Kawakami, Yasuhiko

    2016-07-01

    Zebrafish possess the remarkable ability to regenerate injured hearts as adults, which contrasts the very limited ability in mammals. Although very limited, mammalian hearts do in fact have measurable levels of cardiomyocyte regeneration. Therefore, elucidating mechanisms of zebrafish heart regeneration would provide information of naturally occurring regeneration to potentially apply to mammalian studies, in addition to addressing this biologically interesting phenomenon in itself. Studies over the past 13 years have identified processes and mechanisms of heart regeneration in zebrafish. After heart injury, pre-existing cardiomyocytes dedifferentiate, enter the cell cycle, and repair the injured myocardium. This process requires interaction with epicardial cells, endocardial cells, and vascular endothelial cells. Epicardial cells envelope the heart, while endocardial cells make up the inner lining of the heart. They provide paracrine signals to cardiomyocytes to regenerate the injured myocardium, which is vascularized during heart regeneration. In addition, accumulating results suggest that local migration of these major cardiac cell types have roles in heart regeneration. In this review, we summarize the characteristics of various heart injury methods used in the research community and regeneration of the major cardiac cell types. Then, we discuss local migration of these cardiac cell types and immune cells during heart regeneration. Developmental Dynamics 245:774-787, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. 21 CFR 868.5800 - Tracheostomy tube and tube cuff.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 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 a...

  7. Mechanisms of cadmium-caused eye hypoplasia and hypopigmentation in zebrafish embryos.

    Science.gov (United States)

    Zhang, Ting; Zhou, Xin-Ying; Ma, Xu-Fa; Liu, Jing-Xia

    2015-10-01

    Cadmium-caused head and eye hypoplasia and hypopigmentation has been recognized for a long time, but knowledge of the underlying mechanisms is limited. In this study, we found that high mortality occurred in exposed embryos after 24 hpf, when cadmium (Cd) dosage was above 17.8 μM. Using high-throughput in situ hybridization screening, we found that genes labelling the neural crest and its derivative pigment cells exhibited obviously reduced expression in Cd-exposed embryos from 24 hpf, 2 days earlier than head and eye hypoplasia and hypopigmentation occurred. Moreover, based on expression of crestin, a neural crest marker, we found that embryos before the gastrula stage were more sensitive to cadmium toxicity and that damage caused by Cd on embryogenesis was dosage dependent. In addition, by phenotype observation and detection of neural crest and pigment cell markers, we found that BIO and retinoic acid (RA) could neutralize the toxic effects of Cd on zebrafish embryogenesis. In this study, we first determined that Cd blocked the formation of the neural crest and inhibited specification of pigment cells, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in Cd-exposed embryos. Moreover, we found that compounds BIO or RA could neutralize the toxic effects of Cd. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Lack of beta1 integrins in enteric neural crest cells leads to a Hirschsprung-like phenotype

    DEFF Research Database (Denmark)

    Breau, Marie A; Pietri, Thomas; Eder, Olivier

    2006-01-01

    The enteric nervous system arises mainly from vagal and sacral neural crest cells that colonise the gut between 9.5 and 14 days of development in mice. Using the Cre-LoxP system, we removed beta1 integrins in the neural crest cells when they emerge from the neural tube. beta1-null enteric neural...

  9. A zebrafish model for Waardenburg syndrome type IV reveals diverse roles for Sox10 in the otic vesicle.

    Science.gov (United States)

    Dutton, Kirsten; Abbas, Leila; Spencer, Joanne; Brannon, Claire; Mowbray, Catriona; Nikaido, Masataka; Kelsh, Robert N; Whitfield, Tanya T

    2009-01-01

    In humans, mutations in the SOX10 gene are a cause of the auditory-pigmentary disorder Waardenburg syndrome type IV (WS4) and related variants. SOX10 encodes an Sry-related HMG box protein essential for the development of the neural crest; deafness in WS4 and other Waardenburg syndromes is usually attributed to loss of neural-crest-derived melanocytes in the stria vascularis of the cochlea. However, SOX10 is strongly expressed in the developing otic vesicle and so direct roles for SOX10 in the otic epithelium might also be important. Here, we examine the otic phenotype of zebrafish sox10 mutants, a model for WS4. As a cochlea is not present in the fish ear, the severe otic phenotype in these mutants cannot be attributed to effects on this tissue. In zebrafish sox10 mutants, we see abnormalities in all otic placodal derivatives. Gene expression studies indicate deregulated expression of several otic genes, including fgf8, in sox10 mutants. Using a combination of mutant and morphant data, we show that the three sox genes belonging to group E (sox9a, sox9b and sox10) provide a link between otic induction pathways and subsequent otic patterning: they act redundantly to maintain sox10 expression throughout otic tissue and to restrict fgf8 expression to anterior macula regions. Single-cell labelling experiments indicate a small and transient neural crest contribution to the zebrafish ear during normal development, but this is unlikely to account for the strong defects seen in the sox10 mutant. We discuss the implication that the deafness in WS4 patients with SOX10 mutations might reflect a haploinsufficiency for SOX10 in the otic epithelium, resulting in patterning and functional abnormalities in the inner ear.

  10. Heat exchanger tube tool

    International Nuclear Information System (INIS)

    Gugel, G.

    1976-01-01

    Certain types of heat-exchangers have tubes opening through a tube sheet to a manifold having an access opening offset from alignment with the tube ends. A tool for inserting a device, such as for inspection or repair, is provided for use in such instances. The tool is formed by a flexible guide tube insertable through the access opening and having an inner end provided with a connector for connection with the opening of the tube in which the device is to be inserted, and an outer end which remains outside of the chamber, the guide tube having adequate length for this arrangement. A flexible transport hose for internally transporting the device slides inside of the guide tube. This hose is long enough to slide through the guide tube, into the heat-exchanger tube, and through the latter to the extent required for the use of the device. The guide tube must be bent to reach the end of the heat-exchanger tube and the latter may be constructed with a bend, the hose carrying anit-friction elements at interspaced locations along its length to make it possible for the hose to negotiate such bends while sliding to the location where the use of the device is required

  11. Characterization of behavioral and endocrine effects of LSD on zebrafish.

    Science.gov (United States)

    Grossman, Leah; Utterback, Eli; Stewart, Adam; Gaikwad, Siddharth; Chung, Kyung Min; Suciu, Christopher; Wong, Keith; Elegante, Marco; Elkhayat, Salem; Tan, Julia; Gilder, Thomas; Wu, Nadine; Dileo, John; Cachat, Jonathan; Kalueff, Allan V

    2010-12-25

    Lysergic acid diethylamide (LSD) is a potent hallucinogenic drug that strongly affects animal and human behavior. Although adult zebrafish (Danio rerio) are emerging as a promising neurobehavioral model, the effects of LSD on zebrafish have not been investigated previously. Several behavioral paradigms (the novel tank, observation cylinder, light-dark box, open field, T-maze, social preference and shoaling tests), as well as modern video-tracking tools and whole-body cortisol assay were used to characterize the effects of acute LSD in zebrafish. While lower doses (5-100 microg/L) did not affect zebrafish behavior, 250 microg/L LSD increased top dwelling and reduced freezing in the novel tank and observation cylinder tests, also affecting spatiotemporal patterns of activity (as assessed by 3D reconstruction of zebrafish traces and ethograms). LSD evoked mild thigmotaxis in the open field test, increased light behavior in the light-dark test, reduced the number of arm entries and freezing in the T-maze and social preference test, without affecting social preference. In contrast, LSD affected zebrafish shoaling (increasing the inter-fish distance in a group), and elevated whole-body cortisol levels. Overall, our findings show sensitivity of zebrafish to LSD action, and support the use of zebrafish models to study hallucinogenic drugs of abuse. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  12. FishNet: an online database of zebrafish anatomy

    Directory of Open Access Journals (Sweden)

    Gibson Abigail J

    2007-08-01

    Full Text Available Abstract Background Over the last two decades, zebrafish have been established as a genetically versatile model system for investigating many different aspects of vertebrate developmental biology. With the credentials of zebrafish as a developmental model now well recognized, the emerging new opportunity is the wider application of zebrafish biology to aspects of human disease modelling. This rapidly increasing use of zebrafish as a model for human disease has necessarily generated interest in the anatomy of later developmental phases such as the larval, juvenile, and adult stages, during which many of the key aspects of organ morphogenesis and maturation take place. Anatomical resources and references that encompass these stages are non-existent in zebrafish and there is therefore an urgent need to understand how different organ systems and anatomical structures develop throughout the life of the fish. Results To overcome this deficit we have utilized the technique of optical projection tomography to produce three-dimensional (3D models of larval fish. In order to view and display these models we have created FishNet http://www.fishnet.org.au, an interactive reference of zebrafish anatomy spanning the range of zebrafish development from 24 h until adulthood. Conclusion FishNet contains more than 36 000 images of larval zebrafish, with more than 1 500 of these being annotated. The 3D models can be manipulated on screen or virtually sectioned. This resource represents the first complete embryo to adult atlas for any species in 3D.

  13. A bioenergetic model for zebrafish Danio rerio (Hamilton)

    Science.gov (United States)

    Chizinski, C.J.; Sharma, Bibek; Pope, K.L.; Patino, R.

    2008-01-01

    A bioenergetics model was developed from observed consumption, respiration and growth rates for zebrafish Danio rerio across a range (18-32?? C) of water temperatures, and evaluated with a 50 day laboratory trial at 28?? C. No significant bias in variable estimates was found during the validation trial; namely, predicted zebrafish mass generally agreed with observed mass. ?? 2008 The Authors.

  14. Tcf7l1 protects the anterior neural fold from adopting the neural crest fate

    Czech Academy of Sciences Publication Activity Database

    Mašek, Jan; Machoň, Ondřej; Kořínek, Vladimír; Taketo, M.M.; Kozmik, Zbyněk

    2016-01-01

    Roč. 143, č. 12 (2016), s. 2206-2216 ISSN 0950-1991 R&D Projects: GA ČR GAP305/12/2042; GA ČR(CZ) GA14-33952S; GA MŠk(CZ) LK11214; GA MŠk LO1419; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : Tcf/Lef * Wnt dignaling * neural crest * forebrain * mouse * zebrafish Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.843, year: 2016

  15. Intercostal drainage tube or intracardiac drainage tube?

    Directory of Open Access Journals (Sweden)

    N Anitha

    2016-01-01

    Full Text Available Although insertion of chest drain tubes is a common medical practice, there are risks associated with this procedure, especially when inexperienced physicians perform it. Wrong insertion of the tube has been known to cause morbidity and occasional mortality. We report a case where the left ventricle was accidentally punctured leading to near-exsanguination. This report is to highlight the need for experienced physicians to supervise the procedure and train the younger physician in the safe performance of the procedure.

  16. Intercostal drainage tube or intracardiac drainage tube?

    Science.gov (United States)

    Anitha, N; Kamath, S Ganesh; Khymdeit, Edison; Prabhu, Manjunath

    2016-01-01

    Although insertion of chest drain tubes is a common medical practice, there are risks associated with this procedure, especially when inexperienced physicians perform it. Wrong insertion of the tube has been known to cause morbidity and occasional mortality. We report a case where the left ventricle was accidentally punctured leading to near-exsanguination. This report is to highlight the need for experienced physicians to supervise the procedure and train the younger physician in the safe performance of the procedure.

  17. Toxicity and cardiac effects of carbaryl in early developing zebrafish (Danio rerio) embryos

    International Nuclear Information System (INIS)

    Lin, C.C.; Hui, Michelle N.Y.; Cheng, S.H.

    2007-01-01

    Carbaryl, an acetylcholinesterase inhibitor, is known to be moderately toxic to adult zebrafish and has been reported to cause heart malformations and irregular heartbeat in medaka. We performed experiments to study the toxicity of carbaryl, specifically its effects on the heart, in early developing zebrafish embryos. LC50 and EC50 values for carbaryl at 28 h post-fertilization were 44.66 μg/ml and 7.52 μg/ml, respectively, and 10 μg/ml carbaryl was used in subsequent experiments. After confirming acetylcholinesterase inhibition by carbaryl using an enzymatic method, we observed red blood cell accumulation, delayed hatching and pericardial edema, but not heart malformation as described in some previous reports. Our chronic exposure data also demonstrated carbaryl-induced bradycardia, which is a common effect of acetylcholinesterase inhibitors due to the accumulation of acetylcholine, in embryos from 1 day post-fertilization (dpf) to 5 dpf. The distance between the sinus venosus, the point where blood enters the atrium, and the bulbus arteriosus, the point where blood leaves the ventricle, indicated normal looping of the heart tube. Immunostaining of myosin heavy chains with the ventricle-specific antibody MF20 and the atrium-specific antibody S46 showed normal development of heart chambers. At the same time, acute exposure resulted in carbaryl-induced bradycardia. Heart rate dropped significantly after a 10-min exposure to 100 μg/ml carbaryl but recovered when carbaryl was removed. The novel observation of carbaryl-induced bradycardia in 1- and 2-dpf embryos suggested that carbaryl affected cardiac function possibly through an alternative mechanism other than acetylcholinesterase inhibition such as inhibition of calcium ion channels, since acetylcholine receptors in zebrafish are not functional until 3 dpf. However, the exact nature of this mechanism is currently unknown, and thus further studies are required

  18. The heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome.

    Science.gov (United States)

    Garrity, Deborah M; Childs, Sarah; Fishman, Mark C

    2002-10-01

    Holt-Oram syndrome is one of the autosomal dominant human "heart-hand" disorders, with a combination of upper limb malformations and cardiac defects. Holt-Oram syndrome is caused by mutations in the TBX5 gene, a member of a large family of T-box transcription factors that play important roles in cell-type specification and morphogenesis. In a screen for mutations affecting zebrafish cardiac function, we isolated the recessive lethal mutant heartstrings, which lacks pectoral fins and exhibits severe cardiac dysfunction, beginning with a slow heart rate and progressing to a stretched, non-functional heart. We mapped and cloned the heartstrings mutation and find it to encode the zebrafish ortholog of the TBX5 gene. The heartstrings mutation causes premature termination at amino acid 316. Homozygous mutant embryos never develop pectoral fin buds and do not express several markers of early fin differentiation. The total absence of any fin bud differentiation distinguishes heartstrings from most other mutations that affect zebrafish fin development, suggesting that Tbx5 functions very early in the pectoral fin induction pathway. Moderate reduction of Tbx5 by morpholino causes fin malformations, revealing an additional early requirement for Tbx5 in coordinating the axes of fin outgrowth. The heart of heartstrings mutant embryos appears to form and function normally through the early heart tube stage, manifesting only a slight bradycardia compared with wild-type siblings. However, the heart fails to loop and then progressively deteriorates, a process affecting the ventricle as well as the atrium. Relative to mammals, fish require lower levels of Tbx5 to produce malformed appendages and display whole-heart rather than atrial-predominant cardiac defects. However, the syndromic deficiencies of tbx5 mutation are remarkably well retained between fish and mammals.

  19. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... YouTube Videos » NEI YouTube Videos: Amblyopia Listen NEI YouTube Videos YouTube Videos Home Age-Related Macular Degeneration ... Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Amblyopia Embedded video for NEI YouTube Videos: ...

  20. 3D Visualization of Developmental Toxicity of 2,4,6-Trinitrotoluene in Zebrafish Embryogenesis Using Light-Sheet Microscopy

    Directory of Open Access Journals (Sweden)

    Juneyong Eum

    2016-11-01

    Full Text Available Environmental contamination by trinitrotoluene is of global concern due to its widespread use in military ordnance and commercial explosives. Despite known long-term persistence in groundwater and soil, the toxicological profile of trinitrotoluene and other explosive wastes have not been systematically measured using in vivo biological assays. Zebrafish embryos are ideal model vertebrates for high-throughput toxicity screening and live in vivo imaging due to their small size and transparency during embryogenesis. Here, we used Single Plane Illumination Microscopy (SPIM/light sheet microscopy to assess the developmental toxicity of explosive-contaminated water in zebrafish embryos and report 2,4,6-trinitrotoluene-associated developmental abnormalities, including defects in heart formation and circulation, in 3D. Levels of apoptotic cell death were higher in the actively developing tissues of trinitrotoluene-treated embryos than controls. Live 3D imaging of heart tube development at cellular resolution by light-sheet microscopy revealed trinitrotoluene-associated cardiac toxicity, including hypoplastic heart chamber formation and cardiac looping defects, while the real time PCR (polymerase chain reaction quantitatively measured the molecular changes in the heart and blood development supporting the developmental defects at the molecular level. Identification of cellular toxicity in zebrafish using the state-of-the-art 3D imaging system could form the basis of a sensitive biosensor for environmental contaminants and be further valued by combining it with molecular analysis.

  1. Macrophage–Microbe Interactions: Lessons from the Zebrafish Model

    Directory of Open Access Journals (Sweden)

    Nagisa Yoshida

    2017-12-01

    Full Text Available Macrophages provide front line defense against infections. The study of macrophage–microbe interplay is thus crucial for understanding pathogenesis and infection control. Zebrafish (Danio rerio larvae provide a unique platform to study macrophage–microbe interactions in vivo, from the level of the single cell to the whole organism. Studies using zebrafish allow non-invasive, real-time visualization of macrophage recruitment and phagocytosis. Furthermore, the chemical and genetic tractability of zebrafish has been central to decipher the complex role of macrophages during infection. Here, we discuss the latest developments using zebrafish models of bacterial and fungal infection. We also review novel aspects of macrophage biology revealed by zebrafish, which can potentiate development of new therapeutic strategies for humans.

  2. Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

    Science.gov (United States)

    Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

    2013-01-01

    Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

  3. Habituation of the C-start response in larval zebrafish exhibits several distinct phases and sensitivity to NMDA receptor blockade.

    Directory of Open Access Journals (Sweden)

    Adam C Roberts

    Full Text Available The zebrafish larva has been a valuable model system for genetic and molecular studies of development. More recently, biologists have begun to exploit the surprisingly rich behavioral repertoire of zebrafish larvae to investigate behavior. One prominent behavior exhibited by zebrafish early in development is a rapid escape reflex (the C-start. This reflex is mediated by a relatively simple neural circuit, and is therefore an attractive model behavior for neurobiological investigations of simple forms of learning and memory. Here, we describe two forms of short-lived habituation of the C-start in response to brief pulses of auditory stimuli. A rapid form, persisting for ≥1 min but <15 min, was induced by 120 pulses delivered at 0.5-2.0 Hz. A more extended form (termed "short-term habituation" here, which persisted for ≥25 min but <1 h, was induced by spaced training. The spaced training consisted of 10 blocks of auditory pulses delivered at 1 Hz (5 min interblock interval, 900 pulses per block. We found that these two temporally distinguishable forms of habituation are mediated by different cellular mechanisms. The short-term form depends on activation of N-methyl-d-aspartate receptors (NMDARs, whereas the rapid form does not.

  4. Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

    Directory of Open Access Journals (Sweden)

    Schwend Tyler

    2009-11-01

    Full Text Available Abstract Background The vertebrate head skeleton is derived largely from cranial neural crest cells (CNCC. Genetic studies in zebrafish and mice have established that the Hedgehog (Hh-signaling pathway plays a critical role in craniofacial development, partly due to the pathway's role in CNCC development. Disruption of the Hh-signaling pathway in humans can lead to the spectral disorder of Holoprosencephaly (HPE, which is often characterized by a variety of craniofacial defects including midline facial clefting and cyclopia 12. Previous work has uncovered a role for Hh-signaling in zebrafish dorsal neurocranium patterning and chondrogenesis, however Hh-signaling mutants have not been described with respect to the ventral pharyngeal arch (PA skeleton. Lipid-modified Hh-ligands require the transmembrane-spanning receptor Dispatched 1 (Disp1 for proper secretion from Hh-synthesizing cells to the extracellular field where they act on target cells. Here we study chameleon mutants, lacking a functional disp1(con/disp1. Results con/disp1 mutants display reduced and dysmorphic mandibular and hyoid arch cartilages and lack all ceratobranchial cartilage elements. CNCC specification and migration into the PA primorida occurs normally in con/disp1 mutants, however disp1 is necessary for post-migratory CNCC patterning and differentiation. We show that disp1 is required for post-migratory CNCC to become properly patterned within the first arch, while the gene is dispensable for CNCC condensation and patterning in more posterior arches. Upon residing in well-formed pharyngeal epithelium, neural crest condensations in the posterior PA fail to maintain expression of two transcription factors essential for chondrogenesis, sox9a and dlx2a, yet continue to robustly express other neural crest markers. Histology reveals that posterior arch residing-CNCC differentiate into fibrous-connective tissue, rather than becoming chondrocytes. Treatments with Cyclopamine, to

  5. Pediatric cuffed endotracheal tubes

    Directory of Open Access Journals (Sweden)

    Neerja Bhardwaj

    2013-01-01

    Full Text Available Endotracheal intubation in children is usually performed utilizing uncuffed endotracheal tubes for conduct of anesthesia as well as for prolonged ventilation in critical care units. However, uncuffed tubes may require multiple changes to avoid excessive air leak, with subsequent environmental pollution making the technique uneconomical. In addition, monitoring of ventilatory parameters, exhaled volumes, and end-expiratory gases may be unreliable. All these problems can be avoided by use of cuffed endotracheal tubes. Besides, cuffed endotracheal tubes may be of advantage in special situations like laparoscopic surgery and in surgical conditions at risk of aspiration. Magnetic resonance imaging (MRI scans in children have found the narrowest portion of larynx at rima glottides. Cuffed endotracheal tubes, therefore, will form a complete seal with low cuff pressure of <15 cm H 2 O without any increase in airway complications. Till recently, the use of cuffed endotracheal tubes was limited by variations in the tube design marketed by different manufacturers. The introduction of a new cuffed endotracheal tube in the market with improved tracheal sealing characteristics may encourage increased safe use of these tubes in clinical practice. A literature search using search words "cuffed endotracheal tube" and "children" from 1980 to January 2012 in PUBMED was conducted. Based on the search, the advantages and potential benefits of cuffed ETT are reviewed in this article.

  6. Triclosan Lacks (Anti-Estrogenic Effects in Zebrafish Cells but Modulates Estrogen Response in Zebrafish Embryos

    Directory of Open Access Journals (Sweden)

    Hélène Serra

    2018-04-01

    Full Text Available Triclosan (TCS, an antimicrobial agent widely found in the aquatic environment, is suspected to act as an endocrine disrupting compound, however mechanistic information is lacking in regards to aquatic species. This study assessed the ability of TCS to interfere with estrogen receptor (ER transcriptional activity, in zebrafish-specific in vitro and in vivo reporter gene assays. We report that TCS exhibits a lack of either agonistic or antagonistic effects on a panel of ER-expressing zebrafish (ZELH-zfERα and -zfERβ and human (MELN cell lines. At the organism level, TCS at concentrations of up to 0.3 µM had no effect on ER-regulated brain aromatase gene expression in transgenic cyp19a1b-GFP zebrafish embryos. At a concentration of 1 µM, TCS interfered with the E2 response in an ambivalent manner by potentializing a low E2 response (0.625 nM, but decreasing a high E2 response (10 nM. Altogether, our study suggests that while modulation of ER-regulated genes by TCS may occur in zebrafish, it does so irrespective of a direct binding and activation of zfERs.

  7. A dominant negative zebrafish Ahr2 partially protects developing zebrafish from dioxin toxicity.

    Directory of Open Access Journals (Sweden)

    Kevin A Lanham

    Full Text Available The toxicity by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD is thought to be caused by activation of the aryl hydrocarbon receptor (AHR. However, our understanding of how AHR activation by TCDD leads to toxic effects is poor. Ideally we would like to manipulate AHR activity in specific tissues and at specific times. One route to this is expressing dominant negative AHRs (dnAHRs. This work describes the construction and characterization of dominant negative forms of the zebrafish Ahr2 in which the C-terminal transactivation domain was either removed, or replaced with the inhibitory domain from the Drosophila engrailed repressor protein. One of these dnAhr2s was selected for expression from the ubiquitously active e2fα promoter in transgenic zebrafish. We found that these transgenic zebrafish expressing dnAhr2 had reduced TCDD induction of the Ahr2 target gene cyp1a, as measured by 7-ethoxyresorufin-O-deethylase activity. Furthermore, the cardiotoxicity produced by TCDD, pericardial edema, heart malformation, and reduced blood flow, were all mitigated in the zebrafish expressing the dnAhr2. These results provide in vivo proof-of-principle results demonstrating the effectiveness of dnAHRs in manipulating AHR activity in vivo, and demonstrating that this approach can be a means for blocking TCDD toxicity.

  8. Animal models for studying neural crest development: is the mouse different?

    Science.gov (United States)

    Barriga, Elias H; Trainor, Paul A; Bronner, Marianne; Mayor, Roberto

    2015-05-01

    The neural crest is a uniquely vertebrate cell type and has been well studied in a number of model systems. Zebrafish, Xenopus and chick embryos largely show consistent requirements for specific genes in early steps of neural crest development. By contrast, knockouts of homologous genes in the mouse often do not exhibit comparable early neural crest phenotypes. In this Spotlight article, we discuss these species-specific differences, suggest possible explanations for the divergent phenotypes in mouse and urge the community to consider these issues and the need for further research in complementary systems. © 2015. Published by The Company of Biologists Ltd.

  9. Anti-angiogenic activity of a new andrographolide derivative in zebrafish and HUVECs.

    Science.gov (United States)

    Li, Jingjing; Peng, Yuran; Li, Shang; Sun, Yicheng; Chan, Judy Yuet-Wa; Cui, Guozhen; Wang, Decai; Zhou, Guo-Chun; Lee, Simon Ming-Yuen

    2016-10-15

    Andrographolide is among the most promising anti-tumor and anti-angiogenic components in Andrographis paniculata but its poor bioavailability and limited efficacy pose difficulties for its therapeutic development. Therefore, improving its pharmaceutical features and potency, by modifying its chemical structure, is desirable. In the present study, a new andrographolide derivative (AGP-40) was synthesized and characterized for its anti-angiogenic properties. Human umbilical vein endothelial cells (HUVECs) and zebrafish models were used to identify the anti-angiogenic activity of AGP-40. AGP-40 significantly suppressed the formation of blood vessels in zebrafish and inhibited proliferation, migration and tube formation in vitro. The anti-angiogenic effects of AGP-40 are at least partially mediated via the PI3K/Akt and MEK/Erk(1/2) signaling pathways. Furthermore, AGP-40 exhibited stronger anti-proliferative effects than andrographolide against A549, HepG2, Hela cancer cell lines. This study is the first to demonstrate the promising anti-angiogenic activity of the new andrographolide derivative AGP-40. Our results indicate that AGP-40 could serve as a potential therapeutic agent for the treatment and prevention of diseases associated with excessive angiogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Multi-organ abnormalities and mTORC1 activation in zebrafish model of multiple acyl-CoA dehydrogenase deficiency.

    Directory of Open Access Journals (Sweden)

    Seok-Hyung Kim

    2013-06-01

    Full Text Available Multiple Acyl-CoA Dehydrogenase Deficiency (MADD is a severe mitochondrial disorder featuring multi-organ dysfunction. Mutations in either the ETFA, ETFB, and ETFDH genes can cause MADD but very little is known about disease specific mechanisms due to a paucity of animal models. We report a novel zebrafish mutant dark xavier (dxa(vu463 that has an inactivating mutation in the etfa gene. dxa(vu463 recapitulates numerous pathological and biochemical features seen in patients with MADD including brain, liver, and kidney disease. Similar to children with MADD, homozygote mutant dxa(vu463 zebrafish have a spectrum of phenotypes ranging from moderate to severe. Interestingly, excessive maternal feeding significantly exacerbated the phenotype. Homozygous mutant dxa(vu463 zebrafish have swollen and hyperplastic neural progenitor cells, hepatocytes and kidney tubule cells as well as elevations in triacylglycerol, cerebroside sulfate and cholesterol levels. Their mitochondria were also greatly enlarged, lacked normal cristae, and were dysfunctional. We also found increased signaling of the mechanistic target of rapamycin complex 1 (mTORC1 with enlarged cell size and proliferation. Treatment with rapamycin partially reversed these abnormalities. Our results indicate that etfa gene function is remarkably conserved in zebrafish as compared to humans with highly similar pathological, biochemical abnormalities to those reported in children with MADD. Altered mTORC1 signaling and maternal nutritional status may play critical roles in MADD disease progression and suggest novel treatment approaches that may ameliorate disease severity.

  11. Zebrafish: an animal model for research in veterinary medicine.

    Science.gov (United States)

    Nowik, N; Podlasz, P; Jakimiuk, A; Kasica, N; Sienkiewicz, W; Kaleczyc, J

    2015-01-01

    The zebrafish (Danio rerio) has become known as an excellent model organism for studies of vertebrate biology, vertebrate genetics, embryonal development, diseases and drug screening. Nevertheless, there is still lack of detailed reports about usage of the zebrafish as a model in veterinary medicine. Comparing to other vertebrates, they can lay hundreds of eggs at weekly intervals, externally fertilized zebrafish embryos are accessible to observation and manipulation at all stages of their development, which makes possible to simplify the research techniques such as fate mapping, fluorescent tracer time-lapse lineage analysis and single cell transplantation. Although zebrafish are only 2.5 cm long, they are easy to maintain. Intraperitoneal and intracerebroventricular injections, blood sampling and measurement of food intake are possible to be carry out in adult zebrafish. Danio rerio is a useful animal model for neurobiology, developmental biology, drug research, virology, microbiology and genetics. A lot of diseases, for which the zebrafish is a perfect model organism, affect aquatic animals. For a part of them, like those caused by Mycobacterium marinum or Pseudoloma neutrophila, Danio rerio is a natural host, but the zebrafish is also susceptible to the most of fish diseases including Itch, Spring viraemia of carp and Infectious spleen and kidney necrosis. The zebrafish is commonly used in research of bacterial virulence. The zebrafish embryo allows for rapid, non-invasive and real time analysis of bacterial infections in a vertebrate host. Plenty of common pathogens can be examined using zebrafish model: Streptococcus iniae, Vibrio anguillarum or Listeria monocytogenes. The steps are taken to use the zebrafish also in fungal research, especially that dealing with Candida albicans and Cryptococcus neoformans. Although, the zebrafish is used commonly as an animal model to study diseases caused by external agents, it is also useful in studies of metabolic

  12. Lunar Lava Tube Sensing

    Science.gov (United States)

    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.

  13. Categorising YouTube

    DEFF Research Database (Denmark)

    Simonsen, Thomas Mosebo

    2011-01-01

    This article provides a genre analytical approach to creating a typology of the User Generated Content (UGC) of YouTube. The article investigates the construction of navigation processes on the YouTube website. It suggests a pragmatic genre approach that is expanded through a focus on YouTube......’s technological affordances. Through an analysis of the different pragmatic contexts of YouTube, it is argued that a taxonomic understanding of YouTube must be analysed in regards to the vacillation of a user-driven bottom-up folksonomy and a hierarchical browsing system that emphasises a culture of competition...... and which favours the already popular content of YouTube. With this taxonomic approach, the UGC videos are registered and analysed in terms of empirically based observations. The article identifies various UGC categories and their principal characteristics. Furthermore, general tendencies of the UGC within...

  14. Steam generator tube performance

    International Nuclear Information System (INIS)

    Tatone, O.S.; Pathania, R.S.

    1983-08-01

    A review of the performance of steam generator tubes in 110 water-cooled nuclear power reactors showed that tubes were plugged at 46 (42 percent) of the reactors. The number of tubes removed from service increased from 1900 (0.14 percent) in 1980 to 4692 (0.30 percent) in 1981. The leading causes of tube failures were stress corrosion cracking from the primary side, stress corrosion cracking (or intergranular attack) from the secondary side and pitting corrosion. The lowest incidence of corrosion-induced defects from the secondary side occurred in reactors that used all-volatile treatment since start-up. At one reactor a large number of degraded tubes were repaired by sleeving which is expected to become an important method of tube repair in the future

  15. Zebrafish heart as a model to study the integrative autonomic control of pacemaker function

    Science.gov (United States)

    Stoyek, Matthew R.; Quinn, T. Alexander; Croll, Roger P.

    2016-01-01

    The cardiac pacemaker sets the heart's primary rate, with pacemaker discharge controlled by the autonomic nervous system through intracardiac ganglia. A fundamental issue in understanding the relationship between neural activity and cardiac chronotropy is the identification of neuronal populations that control pacemaker cells. To date, most studies of neurocardiac control have been done in mammalian species, where neurons are embedded in and distributed throughout the heart, so they are largely inaccessible for whole-organ, integrative studies. Here, we establish the isolated, innervated zebrafish heart as a novel alternative model for studies of autonomic control of heart rate. Stimulation of individual cardiac vagosympathetic nerve trunks evoked bradycardia (parasympathetic activation) and tachycardia (sympathetic activation). Simultaneous stimulation of both vagosympathetic nerve trunks evoked a summative effect. Effects of nerve stimulation were mimicked by direct application of cholinergic and adrenergic agents. Optical mapping of electrical activity confirmed the sinoatrial region as the site of origin of normal pacemaker activity and identified a secondary pacemaker in the atrioventricular region. Strong vagosympathetic nerve stimulation resulted in a shift in the origin of initial excitation from the sinoatrial pacemaker to the atrioventricular pacemaker. Putative pacemaker cells in the sinoatrial and atrioventricular regions expressed adrenergic β2 and cholinergic muscarinic type 2 receptors. Collectively, we have demonstrated that the zebrafish heart contains the accepted hallmarks of vertebrate cardiac control, establishing this preparation as a viable model for studies of integrative physiological control of cardiac function by intracardiac neurons. PMID:27342878

  16. GLUT2-mediated glucose uptake and availability are required for embryonic brain development in zebrafish.

    Science.gov (United States)

    Marín-Juez, Rubén; Rovira, Mireia; Crespo, Diego; van der Vaart, Michiel; Spaink, Herman P; Planas, Josep V

    2015-01-01

    Glucose transporter 2 (GLUT2; gene name SLC2A2) has a key role in the regulation of glucose dynamics in organs central to metabolism. Although GLUT2 has been studied in the context of its participation in peripheral and central glucose sensing, its role in the brain is not well understood. To decipher the role of GLUT2 in brain development, we knocked down slc2a2 (glut2), the functional ortholog of human GLUT2, in zebrafish. Abrogation of glut2 led to defective brain organogenesis, reduced glucose uptake and increased programmed cell death in the brain. Coinciding with the observed localization of glut2 expression in the zebrafish hindbrain, glut2 deficiency affected the development of neural progenitor cells expressing the proneural genes atoh1b and ptf1a but not those expressing neurod. Specificity of the morphant phenotype was demonstrated by the restoration of brain organogenesis, whole-embryo glucose uptake, brain apoptosis, and expression of proneural markers in rescue experiments. These results indicate that glut2 has an essential role during brain development by facilitating the uptake and availability of glucose and support the involvement of glut2 in brain glucose sensing.

  17. Molecular cloning and developmental expression of Tlx (Hox11) genes in zebrafish (Danio rerio).

    Science.gov (United States)

    Langenau, D M; Palomero, T; Kanki, J P; Ferrando, A A; Zhou, Y; Zon, L I; Look, A T

    2002-09-01

    Tlx (Hox11) genes are orphan homeobox genes that play critical roles in the regulation of early developmental processes in vertebrates. Here, we report the identification and expression patterns of three members of the zebrafish Tlx family. These genes share similar, but not identical, expression patterns with other vertebrate Tlx-1 and Tlx-3 genes. Tlx-1 is expressed early in the developing hindbrain and pharyngeal arches, and later in the putative splenic primordium. However, unlike its orthologues, zebrafish Tlx-1 is not expressed in the cranial sensory ganglia or spinal cord. Two homologues of Tlx-3 were identified: Tlx-3a and Tlx-3b, which are both expressed in discrete regions of the developing nervous system, including the cranial sensory ganglia and Rohon-Beard neurons. However, only Tlx-3a is expressed in the statoacoustic cranial ganglia, enteric neurons and non-neural tissues such as the fin bud and pharyngeal arches and Tlx-3b is only expressed in the dorsal root ganglia. Copyright 2002 Elsevier Science Ireland Ltd.

  18. Prey capture in zebrafish larvae serves as a model to study cognitive functions

    Directory of Open Access Journals (Sweden)

    Akira eMuto

    2013-06-01

    Full Text Available Prey capture in zebrafish larvae is an innate behavior which can be observed as early as 4 days post fertilization, the day when they start to swim. This simple behavior apparently involves several neural processes including visual perception, recognition, decision-making, and motor control, and, therefore, serves as a good model system to study cognitive functions underlying natural behaviors in vertebrates. Recent progresses in imaging techniques provided us with a unique opportunity to image neuronal activity in the brain of an intact fish in real-time while the fish perceives a natural prey, paramecium. By expanding this approach, it would be possible to image entire brain areas at a single cell resolution in real-time during prey capture, and identify neuronal circuits important for cognitive functions. Further, activation or inhibition of those neuronal circuits with recently developed optogenetic tools or neurotoxins should shed light on their roles. Thus, we will be able to explore the prey capture in zebrafish larvae more thoroughly at cellular levels, which should establish a basis of understanding of the cognitive function in vertebrates.

  19. Rectangular drift tube characteristics

    International Nuclear Information System (INIS)

    Denisov, D.S.; Musienko, Yu.V.

    1985-01-01

    Results on the study of the characteristics of a 50 x 100 mm aluminium drift tube are presented. The tube was filled with argon-methane and argon-isobutane mixtures. With 16 per cent methane concentration the largest deviation from a linear relation between the drift time and the drift path over 50 mm is less than 2 mm. The tube filled with argon-isobutane mixture is capable of operating in a limited streamer mode

  20. Increased radial glia quiescence, decreased reactivation upon injury and unaltered neuroblast behavior underlie decreased neurogenesis in the aging zebrafish telencephalon.

    Science.gov (United States)

    Edelmann, Kathrin; Glashauser, Lena; Sprungala, Susanne; Hesl, Birgit; Fritschle, Maike; Ninkovic, Jovica; Godinho, Leanne; Chapouton, Prisca

    2013-09-01

    The zebrafish has recently become a source of new data on the mechanisms of neural stem cell (NSC) maintenance and ongoing neurogenesis in adult brains. In this vertebrate, neurogenesis occurs at high levels in all ventricular regions of the brain, and brain injuries recover successfully, owing to the recruitment of radial glia, which function as NSCs. This new vertebrate model of adult neurogenesis is thus advancing our knowledge of the molecular cues in use for the activation of NSCs and fate of their progeny. Because the regenerative potential of somatic stem cells generally weakens with increasing age, it is important to assess the extent to which zebrafish NSC potential decreases or remains unaltered with age. We found that neurogenesis in the ventricular zone, in the olfactory bulb, and in a newly identified parenchymal zone of the telencephalon indeed declines as the fish ages and that oligodendrogenesis also declines. In the ventricular zone, the radial glial cell population remains largely unaltered morphologically but enters less frequently into the cell cycle and hence produces fewer neuroblasts. The neuroblasts themselves do not change their behavior with age and produce the same number of postmitotic neurons. Thus, decreased neurogenesis in the physiologically aging zebrafish brain is correlated with an increasing quiescence of radial glia. After injuries, radial glia in aged brains are reactivated, and the percentage of cell cycle entry is increased in the radial glia population. However, this reaction is far less pronounced than in younger animals, pointing to irreversible changes in aging zebrafish radial glia. Copyright © 2013 Wiley Periodicals, Inc.

  1. Acute Exposure to Fluoxetine Alters Aggressive Behavior of Zebrafish and Expression of Genes Involved in Serotonergic System Regulation

    Directory of Open Access Journals (Sweden)

    Michail Pavlidis

    2017-04-01

    Full Text Available Zebrafish, Danio rerio, is an emerging model organism in stress and neurobehavioral studies. In nature, the species forms shoals, yet when kept in pairs it exhibits an agonistic and anxiety-like behavior that leads to the establishment of dominant-subordinate relationships. Fluoxetine, a selective serotonin reuptake inhibitor, is used as an anxiolytic tool to alter aggressive behavior in several vertebrates and as an antidepressant drug in humans. Pairs of male zebrafish were held overnight to develop dominant—subordinate behavior, either treated or non-treated for 2 h with fluoxetine (5 mg L−1, and allowed to interact once more for 1 h. Behavior was recorded both prior and after fluoxetine administration. At the end of the experiment, trunk and brain samples were also taken for cortisol determination and mRNA expression studies, respectively. Fluoxetine treatment significantly affected zebrafish behavior and the expression levels of several genes, by decreasing offensive aggression in dominants and by eliminating freezing in the subordinates. There was no statistically significant difference in whole-trunk cortisol concentrations between dominant and subordinate fish, while fluoxetine treatment resulted in higher (P = 0.004 cortisol concentrations in both groups. There were statistically significant differences between dominant and subordinate fish in brain mRNA expression levels of genes involved in stress axis (gr, mr, neural activity (bdnf, c-fos, and the serotonergic system (htr2b, slc6a4b. The significant decrease in the offensive and defensive aggression following fluoxetine treatment was concomitant with a reversed pattern in c-fos expression levels. Overall, an acute administration of a selective serotonin reuptake inhibitor alters aggressive behavior in male zebrafish in association with changes in the neuroendocrine mediators of coping styles.

  2. Categorising YouTube

    OpenAIRE

    Simonsen, Thomas Mosebo

    2011-01-01

    This article provides a genre analytical approach to creating a typology of the User Generated Content (UGC) of YouTube. The article investigates the construction of navigation processes on the YouTube website. It suggests a pragmatic genre approach that is expanded through a focus on YouTube’s technological affordances. Through an analysis of the different pragmatic contexts of YouTube, it is argued that a taxonomic understanding of YouTube must be analysed in regards to the vacillation of a...

  3. Pressure tube reactor

    International Nuclear Information System (INIS)

    Susuki, Akira; Murata, Shigeto; Minato, Akihiko.

    1993-01-01

    In a pressure tube reactor, a reactor core is constituted by arranging more than two units of a minimum unit combination of a moderator sealing pipe containing a calandria tube having moderators there between and a calandria tube and moderators. The upper header and a lower header of the calandria tank containing moderators are communicated by way of the moderator sealing tube. Further, a gravitationally dropping mechanism is disposed for injecting neutron absorbing liquid to a calandria gas injection portion. A ratio between a moderator volume and a fuel volume is defined as a function of the inner diameter of the moderator sealing tube, the outer diameter of the calandria tube and the diameter of fuel pellets, and has no influence to intervals of a pressure tube lattice. The interval of the pressure tube lattice is enlarged without increasing the size of the pressure tube, to improve production efficiency of the reactor and set a coolant void coefficient more negative, thereby enabling to improve self controllability and safety. Further, the reactor scram can be conducted by injecting neutron absorbing liquid. (N.H.)

  4. Heated Tube Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Heated Tube Facility at NASA GRC investigates cooling issues by simulating conditions characteristic of rocket engine thrust chambers and high speed airbreathing...

  5. Steam generator tube performance

    International Nuclear Information System (INIS)

    Tatone, O.S.; Pathania, R.S.

    1984-10-01

    A review of the performance of steam generator tubes in 116 water-cooled nuclear power reactors showed that tubes were plugged at 54 (46 percent) of the reactors. The number of tubes removed from service decreased from 4 692 (0.30 percent) in 1981 to 3 222 (0.20 percent) in 1982. The leading causes of tube failures were stress corrosion cracking from the primary side, stress corrosion cracking (or intergranular attack) from the secondary side and pitting corrosion. The lowest incidence of corrosion-induced defects from the secondary side occurred in reactors that have used only volatile treatment, with or without condensate demineralization

  6. Steam generator tube performance

    International Nuclear Information System (INIS)

    Tatone, O.S.; Tapping, R.L.; Stipan, L.

    1992-03-01

    A survey of steam generator operating experience for 1986 has been carried out for 184 pressurized water and pressurized heavy-water reactors, and 1 water-cooled, graphite-moderated reactor. Tubes were plugged at 75 of the reactors (40.5%). In 1986, 3737 tubes were plugged (0.14% of those in service) and 3148 tubes were repaired by sleeving. A small number of reactors accounted for the bulk of the plugged tubes, a phenomenon consistent with previous years. For 1986, the available tubesheet sludge data for 38 reactors has been compiled into tabular form, and sludge/deposit data will be incorporated into all future surveys

  7. Immunostaining of dissected zebrafish embryonic heart.

    Science.gov (United States)

    Yang, Jingchun; Xu, Xiaolei

    2012-01-10

    Zebrafish embryo becomes a popular in vivo vertebrate model for studying cardiac development and human heart diseases due to its advantageous embryology and genetics. About 100-200 embryos are readily available every week from a single pair of adult fish. The transparent embryos that develop ex utero make them ideal for assessing cardiac defects. The expression of any gene can be manipulated via morpholino technology or RNA injection. Moreover, forward genetic screens have already generated a list of mutants that affect different perspectives of cardiogenesis. Whole mount immunostaining is an important technique in this animal model to reveal the expression pattern of the targeted protein to a particular tissue. However, high resolution images that can reveal cellular or subcellular structures have been difficult, mainly due to the physical location of the heart and the poor penetration of the antibodies. Here, we present a method to address these bottlenecks by dissecting heart first and then conducting the staining process on the surface of a microscope slide. To prevent the loss of small heart samples and to facilitate solution handling, we restricted the heart samples within a circle on the surface of the microscope slides drawn by an immEdge pen. After the staining, the fluorescence signals can be directly observed by a compound microscope. Our new method significantly improves the penetration for antibodies, since a heart from an embryonic fish only consists of few cell layers. High quality images from intact hearts can be obtained within a much reduced procession time for zebrafish embryos aged from day 2 to day 6. Our method can be potentially extended to stain other organs dissected from either zebrafish or other small animals. Copyright © 2012 Journal of Visualized Experiments

  8. Adaptive locomotor behavior in larval zebrafish.

    Science.gov (United States)

    Portugues, Ruben; Engert, Florian

    2011-01-01

    In this study we report that larval zebrafish display adaptive locomotor output that can be driven by unexpected visual feedback. We develop a new assay that addresses visuomotor integration in restrained larval zebrafish. The assay involves a closed-loop environment in which the visual feedback a larva receives depends on its own motor output in a way that resembles freely swimming conditions. The experimenter can control the gain of this closed feedback loop, so that following a given motor output the larva experiences more or less visual feedback depending on whether the gain is high or low. We show that increases and decreases in this gain setting result in adaptive changes in behavior that lead to a generalized decrease or increase of motor output, respectively. Our behavioral analysis shows that both the duration and tail beat frequency of individual swim bouts can be modified, as well as the frequency with which bouts are elicited. These changes can be implemented rapidly, following an exposure to a new gain of just 175 ms. In addition, modifications in some behavioral parameters accumulate over tens of seconds and effects last for at least 30 s from trial to trial. These results suggest that larvae establish an internal representation of the visual feedback expected from a given motor output and that the behavioral modifications are driven by an error signal that arises from the discrepancy between this expectation and the actual visual feedback. The assay we develop presents a unique possibility for studying visuomotor integration using imaging techniques available in the larval zebrafish.

  9. GROWTH AND BEHAVIOR OF LARVAL ZEBRAFISH Danio ...

    Science.gov (United States)

    Because Zebrafish (Danio rerio) have become a popular and important model for scientific research, the capability to rear larval zebrafish to adulthood is of great importance. Recently research examining the effects of diet (live versus processed) have been published. In the current study we examined whether the larvae can be reared on a processed diet alone, live food alone, or the combination while maintaining normal locomotor behavior, and acceptable survival, length and weight at 14 dpf in a static system. A 14 day feeding trial was conducted in glass crystallizing dishes containing 500 ml of 4 ppt Instant Ocean. On day 0 pdf 450 embryos were selected as potential study subjects and placed in a 26○C incubator on a 14:10 (light:dark) light cycle. At 4 dpf 120 normally developing embryos were selected per treatment and divided into 3 bowls of 40 embryos (for an n=3 per treatment; 9 bowls total). Treatment groups were: G (Gemma Micro 75 only), R (L-type marine rotifers (Brachionus plicatilis) only) or B (Gemma and rotifers). Growth (length), survival, water quality and rotifer density were monitored on days 5-14. On day 14, weight of larva in each bowl was measured and 8 larva per bowl were selected for use in locomotor testing. This behavior paradigm tests individual larval zebrafish under both light and dark conditions in a 24-well plate.After 14 dpf, survival among the groups was not different (92-98%). By days 7 -14 R and B larvae were ~2X longer

  10. Premature aging in telomerase-deficient zebrafish

    Directory of Open Access Journals (Sweden)

    Monique Anchelin

    2013-09-01

    The study of telomere biology is crucial to the understanding of aging and cancer. In the pursuit of greater knowledge in the field of human telomere biology, the mouse has been used extensively as a model. However, there are fundamental differences between mouse and human cells. Therefore, additional models are required. In light of this, we have characterized telomerase-deficient zebrafish (Danio rerio as the second vertebrate model for human telomerase-driven diseases. We found that telomerase-deficient zebrafish show p53-dependent premature aging and reduced lifespan in the first generation, as occurs in humans but not in mice, probably reflecting the similar telomere length in fish and humans. Among these aging symptoms, spinal curvature, liver and retina degeneration, and infertility were the most remarkable. Although the second-generation embryos died in early developmental stages, restoration of telomerase activity rescued telomere length and survival, indicating that telomerase dosage is crucial. Importantly, this model also reproduces the disease anticipation observed in humans with dyskeratosis congenita (DC. Thus, telomerase haploinsufficiency leads to anticipation phenomenon in longevity, which is related to telomere shortening and, specifically, with the proportion of short telomeres. Furthermore, p53 was induced by telomere attrition, leading to growth arrest and apoptosis. Importantly, genetic inhibition of p53 rescued the adverse effects of telomere loss, indicating that the molecular mechanisms induced by telomere shortening are conserved from fish to mammals. The partial rescue of telomere length and longevity by restoration of telomerase activity, together with the feasibility of the zebrafish for high-throughput chemical screening, both point to the usefulness of this model for the discovery of new drugs able to reactivate telomerase in individuals with DC.

  11. Novel biomarkers of perchlorate exposure in zebrafish

    Science.gov (United States)

    Mukhi, S.; Carr, J.A.; Anderson, T.A.; Patino, R.

    2005-01-01

    Perchlorate inhibits iodide uptake by thyroid follicles and lowers thyroid hormone production. Although several effects of perchlorate on the thyroid system have been reported, the utility of these pathologies as markers of environmental perchlorate exposures has not been adequately assessed. The present study examined time-course and concentration-dependent effects of perchlorate on thyroid follicle hypertrophy, colloid depletion, and angiogenesis; alterations in whole-body thyroxine (T4) levels; and somatic growth and condition factor of subadult and adult zebrafish. Changes in the intensity of the colloidal T4 ring previously observed in zebrafish also were examined immunohistochemically. Three-month-old zebrafish were exposed to ammonium perchlorate at measured perchlorate concentrations of 0, 11, 90, 1,131, and 11,480 ppb for 12 weeks and allowed to recover in clean water for 12 weeks. At two weeks of exposure, the lowest-observed-effective concentrations (LOECs) of perchlorate that induced angiogenesis and depressed the intensity of colloidal T4 ring were 90 and 1,131 ppb, respectively; other parameters were not affected (whole-body T4 was not determined at this time). At 12 weeks of exposure, LOECs for colloid depletion, hypertrophy, angiogenesis, and colloidal T4 ring were 11,480, 1,131, 90, and 11 ppb, respectively. All changes were reversible, but residual effects on angiogenesis and colloidal T4 ring intensity were still present after 12 weeks of recovery (LOEC, 11,480 ppb). Whole-body T 4 concentration, body growth (length and weight), and condition factor were not affected by perchlorate. The sensitivity and longevity of changes in colloidal T4 ring intensity and angiogenesis suggest their usefulness as novel markers of perchlorate exposure. The 12-week LOEC for colloidal T4 ring is the lowest reported for any perchlorate biomarker in aquatic vertebrates. ?? 2005 SETAC.

  12. Cholinergic innervation of the zebrafish olfactory bulb.

    Science.gov (United States)

    Edwards, Jeffrey G; Greig, Ann; Sakata, Yoko; Elkin, Dimitry; Michel, William C

    2007-10-20

    A number of fish species receive forebrain cholinergic input but two recent reports failed to find evidence of cholinergic cell bodies or fibers in the olfactory bulbs (OBs) of zebrafish. In the current study we sought to confirm these findings by examining the OBs of adult zebrafish for choline acetyltransferase (ChAT) immunoreactivity. We observed a diffuse network of varicose ChAT-positive fibers associated with the nervus terminalis ganglion innervating the mitral cell/glomerular layer (MC/GL). The highest density of these fibers occurred in the anterior region of the bulb. The cellular targets of this cholinergic input were identified by exposing isolated OBs to acetylcholine receptor (AChR) agonists in the presence of agmatine (AGB), a cationic probe that permeates some active ion channels. Nicotine (50 microM) significantly increased the activity-dependent labeling of mitral cells and juxtaglomerular cells but not of tyrosine hydroxlase-positive dopaminergic neurons (TH(+) cells) compared to control preparations. The nAChR antagonist mecamylamine, an alpha7-nAChR subunit-specific antagonist, calcium-free artificial cerebrospinal fluid, or a cocktail of ionotropic glutamate receptor (iGluR) antagonists each blocked nicotine-stimulated labeling, suggesting that AGB does not enter the labeled neurons through activated nAChRs but rather through activated iGluRs following ACh-stimulated glutamate release. Deafferentation of OBs did not eliminate nicotine-stimulated labeling, suggesting that cholinergic input is primarily acting on bulbar neurons. These findings confirm the presence of a functioning cholinergic system in the zebrafish OB.

  13. Learning and memory in zebrafish (Danio rerio).

    Science.gov (United States)

    Gerlai, R

    2016-01-01

    Learning and memory are defining features of our own species inherently important to our daily lives and to who we are. Without our memories we cease to exist as a person. Without our ability to learn individuals and collectively our society would cease to function. Diseases of the mind still remain incurable. The interest in understanding of the mechanisms of learning and memory is thus well founded. Given the complexity of such mechanisms, concerted efforts have been made to study them under controlled laboratory conditions, ie, with laboratory model organisms. The zebrafish, although new in this field, is one such model organism. The rapidly developing forward- and reverse genetic methods designed for the zebrafish and the increasing use of pharmacological tools along with numerous neurobiology techniques make this species perhaps the best model for the analysis of the mechanisms of complex central nervous system characteristics. The fact that it is an evolutionarily ancient and simpler vertebrate, but at the same time it possesses numerous conserved features across multiple levels of biological organization makes this species an excellent tool for the analysis of the mechanisms of learning and memory. The bottleneck lies in our understanding of its cognitive and mnemonic features, the topic of this chapter. The current paper builds on a chapter published in the previous edition and continues to focus on associative learning, but now it extends the discussion to other forms of learning and to recent discoveries on memory-related features and findings obtained both in adults and larval zebrafish. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Characterization of the Zebrafish Homolog of Zipper Interacting Protein Kinase

    Directory of Open Access Journals (Sweden)

    Brandon W. Carr

    2014-06-01

    Full Text Available Zipper-interacting protein kinase (ZIPK is a conserved vertebrate-specific regulator of actomyosin contractility in smooth muscle and non-muscle cells. Murine ZIPK has undergone an unusual divergence in sequence and regulation compared to other ZIPK orthologs. In humans, subcellular localization is controlled by phosphorylation of threonines 299 and 300. In contrast, ZIPK subcellular localization in mouse and rat is controlled by interaction with PAR-4. We carried out a comparative biochemical characterization of the regulation of the zebrafish ortholog of ZIPK. Like the human orthologs zebrafish ZIPK undergoes nucleocytoplasmic-shuttling and is abundant in the cytoplasm, unlike the primarily nuclear rat ZIPK. Rat ZIPK, but not human or zebrafish ZIPK, interacts with zebrafish PAR-4. Mutation of the conserved residues required for activation of the mammalian orthologs abrogated activity of the zebrafish ZIPK. In contrast to the human ortholog, mutation of threonine 299 and 300 in the zebrafish ZIPK has no effect on the activity or subcellular localization. Thus, we found that zebrafish ZIPK functions in a manner most similar to the human ZIPK and quite distinct from murine orthologs, yet the regulation of subcellular localization is not conserved.

  15. A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.

    Science.gov (United States)

    Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi

    2018-03-20

    Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

  16. Zebrafish: A Versatile Animal Model for Fertility Research

    Directory of Open Access Journals (Sweden)

    Jing Ying Hoo

    2016-01-01

    Full Text Available The utilization of zebrafish in biomedical research is very common in the research world nowadays. Today, it has emerged as a favored vertebrate organism for the research in science of reproduction. There is a significant growth in amount numbers of scientific literature pertaining to research discoveries in reproductive sciences in zebrafish. It has implied the importance of zebrafish in this particular field of research. In essence, the current available literature has covered from the very specific brain region or neurons of zebrafish, which are responsible for reproductive regulation, until the gonadal level of the animal. The discoveries and findings have proven that this small animal is sharing a very close/similar reproductive system with mammals. More interestingly, the behavioral characteristics and along with the establishment of animal courtship behavior categorization in zebrafish have laid an even stronger foundation and firmer reason on the suitability of zebrafish utilization in research of reproductive sciences. In view of the immense importance of this small animal for the development of reproductive sciences, this review aimed at compiling and describing the proximate close similarity of reproductive regulation on zebrafish and human along with factors contributing to the infertility, showing its versatility and its potential usage for fertility research.

  17. Genetic determinants of hyaloid and retinal vasculature in zebrafish

    Directory of Open Access Journals (Sweden)

    Hyde David R

    2007-10-01

    Full Text Available Abstract Background The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals. Developmental abnormalities or microvascular complications in the retinal vasculature result in severe human eye diseases that lead to blindness. To exploit the advantages of zebrafish for genetic, developmental and pharmacological studies of retinal vasculature, we characterised the intraocular vasculature in zebrafish. Results We show a detailed morphological and developmental analysis of the retinal blood supply in zebrafish. Similar to the transient hyaloid vasculature in mammalian embryos, vessels are first found attached to the zebrafish lens at 2.5 days post fertilisation. These vessels progressively lose contact with the lens and by 30 days post fertilisation adhere to the inner limiting membrane of the juvenile retina. Ultrastructure analysis shows these vessels to exhibit distinctive hallmarks of mammalian retinal vasculature. For example, smooth muscle actin-expressing pericytes are ensheathed by the basal lamina of the blood vessel, and vesicle vacuolar organelles (VVO, subcellular mediators of vessel-retinal nourishment, are present. Finally, we identify 9 genes with cell membrane, extracellular matrix and unknown identity that are necessary for zebrafish hyaloid and retinal vasculature development. Conclusion Zebrafish have a retinal blood supply with a characteristic developmental and adult morphology. Abnormalities of these intraocular vessels are easily observed, enabling application of genetic and chemical approaches in zebrafish to identify molecular regulators of hyaloid and retinal vasculature in development and disease.

  18. The zebrafish world of colors and shapes: preference and discrimination.

    Science.gov (United States)

    Oliveira, Jessica; Silveira, Mayara; Chacon, Diana; Luchiari, Ana

    2015-04-01

    Natural environment imposes many challenges to animals, which have to use cognitive abilities to cope with and exploit it to enhance their fitness. Since zebrafish is a well-established model for cognitive studies and high-throughput screening for drugs and diseases that affect cognition, we tested their ability for ambient color preference and 3D objects discrimination to establish a protocol for memory evaluation. For the color preference test, zebrafish were observed in a multiple-chamber tank with different environmental color options. Zebrafish showed preference for blue and green, and avoided yellow and red. For the 3D objects discrimination, zebrafish were allowed to explore two equal objects and then observed in a one-trial test in which a new color, size, or shape of the object was presented. Zebrafish showed discrimination for color, shape, and color+shape combined, but not size. These results imply that zebrafish seem to use some categorical system to discriminate items, and distracters affect their ability for discrimination. The type of variables available (color and shape) may favor zebrafish objects perception and facilitate discrimination processing. We suggest that this easy and simple memory test could serve as a useful screening tool for cognitive dysfunction and neurotoxicological studies.

  19. Steam generator tube failures

    International Nuclear Information System (INIS)

    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

  20. Feeding State Modulates Behavioral Choice and Processing of Prey Stimuli in the Zebrafish Tectum.

    Science.gov (United States)

    Filosa, Alessandro; Barker, Alison J; Dal Maschio, Marco; Baier, Herwig

    2016-05-04

    Animals use the sense of vision to scan their environment, respond to threats, and locate food sources. The neural computations underlying the selection of a particular behavior, such as escape or approach, require flexibility to balance potential costs and benefits for survival. For example, avoiding novel visual objects reduces predation risk but negatively affects foraging success. Zebrafish larvae approach small, moving objects ("prey") and avoid large, looming objects ("predators"). We found that this binary classification of objects by size is strongly influenced by feeding state. Hunger shifts behavioral decisions from avoidance to approach and recruits additional prey-responsive neurons in the tectum, the main visual processing center. Both behavior and tectal function are modulated by signals from the hypothalamic-pituitary-interrenal axis and the serotonergic system. Our study has revealed a neuroendocrine mechanism that modulates the perception of food and the willingness to take risks in foraging decisions. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Knockdown of Pnpla6 protein results in motor neuron defects in zebrafish

    Directory of Open Access Journals (Sweden)

    Yang Song

    2013-03-01

    Mutations in patatin-like phospholipase domain containing 6 (PNPLA6, also known as neuropathy target esterase (NTE or SPG39, cause hereditary spastic paraplegia (HSP. Although studies on animal models, including mice and Drosophila, have extended our understanding of PNPLA6, its roles in neural development and in HSP are not clearly understood. Here, we describe the generation of a vertebrate model of PNPLA6 insufficiency using morpholino oligonucleotide knockdown in zebrafish (Danio rerio. Pnpla6 knockdown resulted in developmental abnormalities and motor neuron defects, including axon truncation and branching. The phenotypes in pnpla6 knockdown morphants were rescued by the introduction of wild-type, but not mutant, human PNPLA6 mRNA. Our results also revealed the involvement of BMP signaling in pnpla6 knockdown phenotypes. Taken together, these results demonstrate an important role of PNPLA6 in motor neuron development and implicate overexpression of BMP signaling as a possible mechanism underlying the developmental defects in pnpla6 morphants.

  2. Navigation by environmental geometry: the use of zebrafish as a model.

    Science.gov (United States)

    Lee, Sang Ah; Vallortigara, Giorgio; Flore, Michele; Spelke, Elizabeth S; Sovrano, Valeria A

    2013-10-01

    Sensitivity to environmental shape in spatial navigation has been found, at both behavioural and neural levels, in virtually every species tested, starting early in development. Moreover, evidence that genetic deletions can cause selective deficits in such navigation behaviours suggests a genetic basis to navigation by environmental geometry. Nevertheless, the geometric computations underlying navigation have not been specified in any species. The present study teases apart the geometric components within the traditionally used rectangular enclosure and finds that zebrafish selectively represent distance and directional relationships between extended boundary surfaces. Similar behavioural results in geometric navigation tasks with human children provide prima facie evidence for similar underlying cognitive computations and open new doors for probing the genetic foundations that give rise to these computations.

  3. A microfluidic device to study neuronal and motor responses to acute chemical stimuli in zebrafish.

    Science.gov (United States)

    Candelier, Raphaël; Murmu, Meena Sriti; Romano, Sebastián Alejo; Jouary, Adrien; Debrégeas, Georges; Sumbre, Germán

    2015-07-21

    Zebrafish larva is a unique model for whole-brain functional imaging and to study sensory-motor integration in the vertebrate brain. To take full advantage of this system, one needs to design sensory environments that can mimic the complex spatiotemporal stimulus patterns experienced by the animal in natural conditions. We report on a novel open-ended microfluidic device that delivers pulses of chemical stimuli to agarose-restrained larvae with near-millisecond switching rate and unprecedented spatial and concentration accuracy and reproducibility. In combination with two-photon calcium imaging and recordings of tail movements, we found that stimuli of opposite hedonic values induced different circuit activity patterns. Moreover, by precisely controlling the duration of the stimulus (50-500 ms), we found that the probability of generating a gustatory-induced behavior is encoded by the number of neurons activated. This device may open new ways to dissect the neural-circuit principles underlying chemosensory perception.

  4. Method for somatic cell nuclear transfer in zebrafish.

    Science.gov (United States)

    Siripattarapravat, Kannika; Cibelli, Jose B

    2011-01-01

    Somatic cell nuclear transfer (SCNT) has been a well-known technique for decades and widely applied to generate identical animals, including ones with genetic alterations. The system has been demonstrated successfully in zebrafish. The elaborated requirements of SCNT, however, limit reproducibility of the established model to a few groups in zebrafish research community. In this chapter, we meticulously outline each step of the published protocol as well as preparations of equipments and reagents used in zebrafish SCNT. All describable detailed-tips are elaborated in texts and figures. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Neural Networks

    International Nuclear Information System (INIS)

    Smith, Patrick I.

    2003-01-01

    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

  6. Evolvable synthetic neural system

    Science.gov (United States)

    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. Method for shaping polyethylene tubing

    Science.gov (United States)

    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.

  8. Pyrotechnic Tubing Connector

    Science.gov (United States)

    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.

  9. Characterization of genetically targeted neuron types in the zebrafish optic tectum

    Directory of Open Access Journals (Sweden)

    Estuardo eRobles

    2011-02-01

    Full Text Available The optically transparent larval zebrafish is ideally suited for in vivo analyses of neural circuitry controlling visually guided behaviors. However, there is a lack of information regarding specific cell types in the major retinorecipient brain region of the fish, the optic tectum. Here we report the characterization of three previously unidentified tectal cell types that are specifically labeled by dlx5/6 enhancer elements. In vivo laser scanning microscopy in conjunction with ex vivo array tomography revealed that these neurons differ in their morphologies, synaptic connectivity, and neurotransmitter phenotypes. The first type is an excitatory bistratified periventricular interneuron (bsPVIN that forms a dendritic arbor in the retinorecipient stratum fibrosum griseum et superficiale (SFGS and an axonal arbor in the stratum griseum centrale (SGC. The second type, a GABAergic nonstratified periventricular interneuron (nsPVIN, extends a bushy arbor containing both dendrites and axons into the SGC and the deepest sublayers of the SFGS. The third type is a GABAergic periventricular projection neuron (PVPN that extends a dendritic arbor into the SGC and a long axon to the torus semicircularis, medulla oblongata, and anterior hindbrain. Interestingly, the same axons form en passant synapses within the deepest neuropil layer of the tectum, the stratum album centrale. This approach revealed several novel aspects of tectal circuitry, including: (1 a glutamatergic mode of transmission from the superficial, retinorecipient neuropil layers to the deeper, output layers, (2 the presence of interneurons with mixed dendrite/axon arbors likely involved in local processing, and (3 a heretofore unknown GABAergic tectofugal projection to midbrain and hindbrain. These observations establish a framework for studying the morphological and functional differentiation of neural circuits in the zebrafish visual system.

  10. Molybdenum Tube Characterization report

    Energy Technology Data Exchange (ETDEWEB)

    Beaux II, Miles Frank [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Usov, Igor Olegovich [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-02-07

    Chemical vapor deposition (CVD) techniques have been utilized to produce free-standing molybdenum tubes with the end goal of nuclear fuel clad applications. In order to produce tubes with properties desirable for this application, deposition rates were lowered requiring long deposition durations on the order of 50 hours. Standard CVD methods as well as fluidized-bed CVD (FBCVD) methods were applied towards these objectives. Characterization of the tubes produced in this manner revealed material suitable for fuel clad applications, but lacking necessary uniformity across the length of the tubes. The production of freestanding Mo tubes that possess the desired properties across their entire length represents an engineering challenge that can be overcome in a next iteration of the deposition system.

  11. Antiangiogenic effects of AA-PMe on HUVECs in vitro and zebrafish in vivo.

    Science.gov (United States)

    Jing, Yue; Wang, Gang; Xiao, Qi; Zhou, Yachun; Wei, Yingjie; Gong, Zhunan

    2018-01-01

    Angiogenesis plays a vital role in many physiological and pathological processes and several diseases are connected with its dysregulation. Asiatic acid (AA) has demonstrated anticancer properties and we suspect this might be attributable to an effect on angio-genesis. A modified derivative of AA, N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-L-proline methyl ester (AA-PMe), has improved efficacy over its parent compound, but its effect on blood vessel development remains unclear. In this study, we investigated the antiangiogenic activity of AA and AA-PMe in zebrafish embryos and human umbilical vein endothelial cells (HUVECs). First of all, we treated HUVECs with increasing concentrations of AA-PMe or AA, with or without vascular endothelial growth factor (VEGF) present, and assessed cell viability, tube formation, and cell migration and invasion. Quantitative real-time polymerase chain reaction and Western blot analysis were later used to determine the role of vascular endothelial growth factor receptor 2 (VEGFR2)-mediated signaling in AA-PMe inhibition of angiogenesis. We extended these studies to follow angiogenesis using Tg(fli:EGFP) transgenic zebrafish embryos. For these experiments, embryos were treated with varying concentrations of AA-PMe or AA from 24 to 72 hours postfertilization prior to morphological observation, angiogenesis assessment, and endogenous alkaline phosphatase assay. VEGFR2 expression in whole embryos following AA-PMe treatment was also determined. We found AA-PMe decreased cell viability and inhibited migration and tube formation in a dose-dependent manner in HUVECs. Similarly, AA-PMe disrupted the formation of intersegmental vessels, the dorsal aorta, and the posterior cardinal vein in zebrafish embryos. Both in vitro and in vivo AA-PMe surpassed AA in its ability to block angiogenesis by suppressing VEGF-induced phosphorylation of VEGFR2 and disrupting downstream extracellular regulated protein kinase and AKT signaling. For the first time

  12. Afferent Connectivity of the Zebrafish Habenulae

    Science.gov (United States)

    Turner, Katherine J.; Hawkins, Thomas A.; Yáñez, Julián; Anadón, Ramón; Wilson, Stephen W.; Folgueira, Mónica

    2016-01-01

    The habenulae are bilateral nuclei located in the dorsal diencephalon that are conserved across vertebrates. Here we describe the main afferents to the habenulae in larval and adult zebrafish. We observe afferents from the subpallium, nucleus rostrolateralis, posterior tuberculum, posterior hypothalamic lobe, median raphe; we also see asymmetric afferents from olfactory bulb to the right habenula, and from the parapineal to the left habenula. In addition, we find afferents from a ventrolateral telencephalic nucleus that neurochemical and hodological data identify as the ventral entopeduncular nucleus (vENT), confirming and extending observations of Amo et al. (2014). Fate map and marker studies suggest that vENT originates from the diencephalic prethalamic eminence and extends into the lateral telencephalon from 48 to 120 hour post-fertilization (hpf). No afferents to the habenula were observed from the dorsal entopeduncular nucleus (dENT). Consequently, we confirm that the vENT (and not the dENT) should be considered as the entopeduncular nucleus “proper” in zebrafish. Furthermore, comparison with data in other vertebrates suggests that the vENT is a conserved basal ganglia nucleus, being homologous to the entopeduncular nucleus of mammals (internal segment of the globus pallidus of primates) by both embryonic origin and projections, as previously suggested by Amo et al. (2014). PMID:27199671

  13. Eddy Current Flaw Characterization Using Neural Networks

    International Nuclear Information System (INIS)

    Song, S. J.; Park, H. J.; Shin, Y. K.

    1998-01-01

    Determination of location, shape and size of a flaw from its eddy current testing signal is one of the fundamental issues in eddy current nondestructive evaluation of steam generator tubes. Here, we propose an approach to this problem; an inversion of eddy current flaw signal using neural networks trained by finite element model-based synthetic signatures. Total 216 eddy current signals from four different types of axisymmetric flaws in tubes are generated by finite element models of which the accuracy is experimentally validated. From each simulated signature, total 24 eddy current features are extracted and among them 13 features are finally selected for flaw characterization. Based on these features, probabilistic neural networks discriminate flaws into four different types according to the location and the shape, and successively back propagation neural networks determine the size parameters of the discriminated flaw

  14. Phenotype classification of zebrafish embryos by supervised learning.

    Directory of Open Access Journals (Sweden)

    Nathalie Jeanray

    Full Text Available Zebrafish is increasingly used to assess biological properties of chemical substances and thus is becoming a specific tool for toxicological and pharmacological studies. The effects of chemical substances on embryo survival and development are generally evaluated manually through microscopic observation by an expert and documented by several typical photographs. Here, we present a methodology to automatically classify brightfield images of wildtype zebrafish embryos according to their defects by using an image analysis approach based on supervised machine learning. We show that, compared to manual classification, automatic classification results in 90 to 100% agreement with consensus voting of biological experts in nine out of eleven considered defects in 3 days old zebrafish larvae. Automation of the analysis and classification of zebrafish embryo pictures reduces the workload and time required for the biological expert and increases the reproducibility and objectivity of this classification.

  15. Directed Differentiation of Zebrafish Pluripotent Embryonic Cells to Functional Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Yao Xiao

    2016-09-01

    Full Text Available A cardiomyocyte differentiation in vitro system from zebrafish embryos remains to be established. Here, we have determined pluripotency window of zebrafish embryos by analyzing their gene-expression patterns of pluripotency factors together with markers of three germ layers, and have found that zebrafish undergoes a very narrow period of pluripotency maintenance from zygotic genome activation to a brief moment after oblong stage. Based on the pluripotency and a combination of appropriate conditions, we established a rapid and efficient method for cardiomyocyte generation in vitro from primary embryonic cells. The induced cardiomyocytes differentiated into functional and specific cardiomyocyte subtypes. Notably, these in vitro generated cardiomyocytes exhibited typical contractile kinetics and electrophysiological features. The system provides a new paradigm of cardiomyocyte differentiation from primary embryonic cells in zebrafish. The technology provides a new platform for the study of heart development and regeneration, in addition to drug discovery, disease modeling, and assessment of cardiotoxic agents.

  16. Functional inhibition of UQCRB suppresses angiogenesis in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Yoon Sun; Jung, Hye Jin [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Seok, Seung Hyeok [Department of Microbiology and Immunology, Institute for Experimental Animals, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Payumo, Alexander Y.; Chen, James K. [Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305 (United States); Kwon, Ho Jeong, E-mail: kwonhj@yonsei.ac.kr [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2013-04-19

    Highlights: ► This is the first functional characterization of UQCRB in vivo model. ► Angiogenesis is inhibited with UQCRB loss of function in zebrafish. ► UQCRB is introduced as a prognostic marker for mitochondria- and angiogenesis-related diseases. -- Abstract: As a subunit of mitochondrial complex III, UQCRB plays an important role in complex III stability, electron transport, and cellular oxygen sensing. Herein, we report UQCRB function regarding angiogenesis in vivo with the zebrafish (Danio rerio). UQCRB knockdown inhibited angiogenesis in zebrafish leading to the suppression of VEGF expression. Moreover, the UQCRB-targeting small molecule terpestacin also inhibited angiogenesis and VEGF levels in zebrafish, supporting the role of UQCRB in angiogenesis. Collectively, UQCRB loss of function by either genetic and pharmacological means inhibited angiogenesis, indicating that UQCRB plays a key role in this process and can be a prognostic marker of angiogenesis- and mitochondria-related diseases.

  17. Zebrafish models in neuropsychopharmacology and CNS drug discovery.

    Science.gov (United States)

    Khan, Kanza M; Collier, Adam D; Meshalkina, Darya A; Kysil, Elana V; Khatsko, Sergey L; Kolesnikova, Tatyana; Morzherin, Yury Yu; Warnick, Jason E; Kalueff, Allan V; Echevarria, David J

    2017-07-01

    Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets. © 2017 The British Pharmacological Society.

  18. Functional inhibition of UQCRB suppresses angiogenesis in zebrafish

    International Nuclear Information System (INIS)

    Cho, Yoon Sun; Jung, Hye Jin; Seok, Seung Hyeok; Payumo, Alexander Y.; Chen, James K.; Kwon, Ho Jeong

    2013-01-01

    Highlights: ► This is the first functional characterization of UQCRB in vivo model. ► Angiogenesis is inhibited with UQCRB loss of function in zebrafish. ► UQCRB is introduced as a prognostic marker for mitochondria- and angiogenesis-related diseases. -- Abstract: As a subunit of mitochondrial complex III, UQCRB plays an important role in complex III stability, electron transport, and cellular oxygen sensing. Herein, we report UQCRB function regarding angiogenesis in vivo with the zebrafish (Danio rerio). UQCRB knockdown inhibited angiogenesis in zebrafish leading to the suppression of VEGF expression. Moreover, the UQCRB-targeting small molecule terpestacin also inhibited angiogenesis and VEGF levels in zebrafish, supporting the role of UQCRB in angiogenesis. Collectively, UQCRB loss of function by either genetic and pharmacological means inhibited angiogenesis, indicating that UQCRB plays a key role in this process and can be a prognostic marker of angiogenesis- and mitochondria-related diseases

  19. Multiple zebrafish atoh1 genes specify a diversity of neuronal types in the zebrafish cerebellum.

    Science.gov (United States)

    Kidwell, Chelsea U; Su, Chen-Ying; Hibi, Masahiko; Moens, Cecilia B

    2018-06-01

    A single Atoh1 basic-helix-loop-helix transcription factor specifies multiple neuron types in the mammalian cerebellum and anterior hindbrain. The zebrafish genome encodes three paralagous atoh1 genes whose functions in cerebellum and anterior hindbrain development we explore here. With use of a transgenic reporter, we report that zebrafish atoh1c-expressing cells are organized in two distinct domains that are separated both by space and developmental time. An early isthmic expression domain gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cell progenitors that migrate to populate all four granule cell territories of the fish cerebellum. Using genetic mutants we find that of the three zebrafish atoh1 paralogs, atoh1c and atoh1a are required for the full complement of granule neurons. Surprisingly, the two genes are expressed in non-overlapping granule cell progenitor populations, indicating that fish use duplicate atoh1 genes to generate granule cell diversity that is not detected in mammals. Finally, live imaging of granule cell migration in wildtype and atoh1c mutant embryos reveals that while atoh1c is not required for granule cell specification per se, it is required for granule cells to delaminate and migrate away from the rhombic lip. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Two-Photon-Based Photoactivation in Live Zebrafish Embryos

    OpenAIRE

    Russek-Blum, Niva; Nabel-Rosen, Helit; Levkowitz, Gil

    2010-01-01

    Photoactivation of target compounds in a living organism has proven a valuable approach to investigate various biological processes such as embryonic development, cellular signaling and adult physiology. In this respect, the use of multi-photon microscopy enables quantitative photoactivation of a given light responsive agent in deep tissues at a single cell resolution. As zebrafish embryos are optically transparent, their development can be monitored in vivo. These traits make the zebrafish a...

  1. Study on radiation modifiers with zebrafish as a vertebrate model

    International Nuclear Information System (INIS)

    Lei Jixiao; Ni Jin; Cai Jianming; Shen Jianliang

    2010-01-01

    Zebrafish (Danio rerio) as a vertebrate model system has been used in a series of biomedical experiments by scientists. It offers distinctive benefits as a laboratory model system, especially for embryonic development, gene expression, drug screening and human disease model. In this paper, the typical radiation modifiers, such as Amifostine, DF-1, AG1478, Flavopiridol and DNA repair proteins involved in biomedical process by use of zebrafish have been reviewed. (authors)

  2. Microcystin-LR exposure induces developmental neurotoxicity in zebrafish embryo

    International Nuclear Information System (INIS)

    Wu, Qin; Yan, Wei; Liu, Chunsheng; Li, Li; Yu, Liqin; Zhao, Sujuan; Li, Guangyu

    2016-01-01

    Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing developmental neurotoxicity, but the exact mechanism is little known. In this study, zebrafish embryos were exposed to 0, 0.8, 1.6 or 3.2 mg/L MCLR for 120 h. MCLR exposure through submersion caused serious hatching delay and body length decrease. The content of MCLR in zebrafish larvae was analyzed and the results demonstrated that MCLR can accumulate in zebrafish larvae. The locomotor speed of zebrafish larvae was decreased. Furthermore, the dopamine and acetylcholine (ACh) content were detected to be significantly decreased in MCLR exposure groups. And the acetylcholinesterase (AChE) activity was significantly increased after exposure to 1.6 and 3.2 mg/L MCLR. The transcription pattern of manf, chrnα7 and ache gene was consistent with the change of the dopamine content, ACh content and AChE activity. Gene expression involved in the development of neurons was also measured. α1-tubulin and shha gene expression were down-regulated, whereas mbp and gap43 gene expression were observed to be significantly up-regulated upon exposure to MCLR. The above results indicated that MCLR-induced developmental toxicity might attribute to the disorder of cholinergic system, dopaminergic signaling, and the development of neurons. - Highlights: • MCLR accumulation induces developmental neurotoxicity in zebrafish embryo. • The decrease of dopamine levels might be associated with the MCLR-induced developmental neurotoxicity in zebrafish larvae. • The alternation of cholinergic system might contribute to the change of neurobehavior in zebrafish larvae exposure with MCLR. - MCLR accumulation induces developmental neurotoxicity by affecting cholinergic system, dopaminergic signaling, and the development of neurons in zebrafish embryo.

  3. Defective Glycinergic Synaptic Transmission in Zebrafish Motility Mutants

    OpenAIRE

    Hirata, Hiromi; Carta, Eloisa; Yamanaka, Iori; Harvey, Robert J.; Kuwada, John Y.

    2010-01-01

    Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo) mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR) β subunit genes. These mutants exhibit a loss of glycinergic synaptic ...

  4. Ionic channels underlying the ventricular action potential in zebrafish embryo.

    Science.gov (United States)

    Alday, Aintzane; Alonso, Hiart; Gallego, Monica; Urrutia, Janire; Letamendia, Ainhoa; Callol, Carles; Casis, Oscar

    2014-06-01

    Over the last years zebrafish has become a popular model in the study of cardiac physiology, pathology and pharmacology. Recently, the application of the 3Rs regulation and the characteristics of the embryo have reduced the use of adult zebrafish use in many studies. However, the zebrafish embryo cardiac physiology is poorly characterized since most works have used indirect techniques and direct recordings of cardiac action potential and ionic currents are scarce. In order to optimize the zebrafish embryo model, we used electrophysiological, pharmacological and immunofluorescence tools to identify the characteristics and the ionic channels involved in the ventricular action potentials of zebrafish embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated the cardiac electrical activity, indicating that the action potential upstroke depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type Ca(+2) channels since it is abolished by specific blockade. The direct channel blockade indicates that the action potential repolarization and diastolic potential depends on ERG K(+) channels. The presence in the embryonic heart of the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by immunofluorescence, while the absence of effect of specific blockers and immunostaining indicate that two K(+) repolarizing currents present in human heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results describe the ionic channels present and its role in the zebrafish embryo heart and support the use of zebrafish embryos to study human diseases and their use for drug testing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Automation in tube finishing bay

    International Nuclear Information System (INIS)

    Bhatnagar, Prateek; Satyadev, B.; Raghuraman, S.; Syama Sundara Rao, B.

    1997-01-01

    Automation concept in tube finishing bay, introduced after the final pass annealing of PHWR tubes resulted in integration of number of sub-systems in synchronisation with each other to produce final cut fuel tubes of specified length, tube finish etc. The tube finishing bay which was physically segregated into four distinct areas: 1. tube spreader and stacking area, 2. I.D. sand blasting area, 3. end conditioning, wad blowing, end capping and O.D. wet grinding area, 4. tube inspection, tube cutting and stacking area has been studied

  6. Whole-body and multispectral photoacoustic imaging of adult zebrafish

    Science.gov (United States)

    Huang, Na; Xi, Lei

    2016-10-01

    Zebrafish is a top vertebrate model to study developmental biology and genetics, and it is becoming increasingly popular for studying human diseases due to its high genome similarity to that of humans and the optical transparency in embryonic stages. However, it becomes difficult for pure optical imaging techniques to volumetric visualize the internal organs and structures of wild-type zebrafish in juvenile and adult stages with excellent resolution and penetration depth. Even with the establishment of mutant lines which remain transparent over the life cycle, it is still a challenge for pure optical imaging modalities to image the whole body of adult zebrafish with micro-scale resolution. However, the method called photoacoustic imaging that combines all the advantages of the optical imaging and ultrasonic imaging provides a new way to image the whole body of the zebrafish. In this work, we developed a non-invasive photoacoustic imaging system with optimized near-infrared illumination and cylindrical scanning to image the zebrafish. The lateral and axial resolution yield to 80 μm and 600 μm, respectively. Multispectral strategy with wavelengths from 690 nm to 930 nm was employed to image various organs inside the zebrafish. From the reconstructed images, most major organs and structures inside the body can be precisely imaged. Quantitative and statistical analysis of absorption for organs under illumination with different wavelengths were carried out.

  7. Zebrafish Lacking Circadian Gene per2 Exhibit Visual Function Deficiency

    Directory of Open Access Journals (Sweden)

    Deng-feng Huang

    2018-03-01

    Full Text Available The retina has an intrinsic circadian clock, but the importance of this clock for vision is unknown. Zebrafish offer many advantages for studying vertebrate vision and circadian rhythm. Here, we explored the role of zebrafish per2, a light-regulated gene, in visual behavior and the underlying mechanisms. We observed that per2 mutant zebrafish larvae showed decreased contrast sensitivity and visual acuity using optokinetic response (OKR assays. Using a visual motor response (VMR assay, we observed normal OFF responses but abnormal ON responses in mutant zebrafish larvae. Immunofluorescence showed that mutants had a normal morphology of cone photoreceptor cells and retinal organization. However, electron microscopy showed that per2 mutants displayed abnormal and decreased photoreceptor ribbon synapses with arciform density, which resulted in retinal ON pathway defect. We also examined the expression of three cone opsins by quantitative real-time PCR (qRT-PCR, and the expression of long-wave-sensitive opsin (opn1lw and short-wave-sensitive opsin (opn1sw was reduced in mutant zebrafish larvae. qRT-PCR analyses also showed a down-regulation of the clock genes cry1ba and bmal1b in the adult eye of per2 mutant zebrafish. This study identified a mechanism by which a clock gene affects visual function and defined important roles of per2 in retinal information processing.

  8. High magnetic field induced otolith fusion in the zebrafish larvae.

    Science.gov (United States)

    Pais-Roldán, Patricia; Singh, Ajeet Pratap; Schulz, Hildegard; Yu, Xin

    2016-04-11

    Magnetoreception in animals illustrates the interaction of biological systems with the geomagnetic field (geoMF). However, there are few studies that identified the impact of high magnetic field (MF) exposure from Magnetic Resonance Imaging (MRI) scanners (>100,000 times of geoMF) on specific biological targets. Here, we investigated the effects of a 14 Tesla MRI scanner on zebrafish larvae. All zebrafish larvae aligned parallel to the B0 field, i.e. the static MF, in the MRI scanner. The two otoliths (ear stones) in the otic vesicles of zebrafish larvae older than 24 hours post fertilization (hpf) fused together after the high MF exposure as short as 2 hours, yielding a single-otolith phenotype with aberrant swimming behavior. The otolith fusion was blocked in zebrafish larvae under anesthesia or embedded in agarose. Hair cells may play an important role on the MF-induced otolith fusion. This work provided direct evidence to show that high MF interacts with the otic vesicle of zebrafish larvae and causes otolith fusion in an "all-or-none" manner. The MF-induced otolith fusion may facilitate the searching for MF sensors using genetically amenable vertebrate animal models, such as zebrafish.

  9. ESX-5-deficient Mycobacterium marinum is hypervirulent in adult zebrafish

    KAUST Repository

    Weerdenburg, Eveline M.

    2012-02-15

    ESX-5 is a mycobacterial type VII protein secretion system responsible for transport of numerous PE and PPE proteins. It is involved in the induction of host cell death and modulation of the cytokine response in vitro. In this work, we studied the effects of ESX-5 in embryonic and adult zebrafish using Mycobacterium marinum. We found that ESX-5-deficient M.marinum was slightly attenuated in zebrafish embryos. Surprisingly, the same mutant showed highly increased virulence in adult zebrafish, characterized by increased bacterial loads and early onset of granuloma formation with rapid development of necrotic centres. This early onset of granuloma formation was accompanied by an increased expression of pro-inflammatory cytokines and tissue remodelling genes in zebrafish infected with the ESX-5 mutant. Experiments using RAG-1-deficient zebrafish showed that the increased virulence of the ESX-5 mutant was not dependent on the adaptive immune system. Mixed infection experiments with wild-type and ESX-5 mutant bacteria showed that the latter had a specific advantage in adult zebrafish and outcompeted wild-type bacteria. Together our experiments indicate that ESX-5-mediated protein secretion is used by M.marinum to establish a moderate and persistent infection. © 2012 Blackwell Publishing Ltd.

  10. Heart-specific expression of laminopathic mutations in transgenic zebrafish.

    Science.gov (United States)

    Verma, Ajay D; Parnaik, Veena K

    2017-07-01

    Lamins are key determinants of nuclear organization and function in the metazoan nucleus. Mutations in human lamin A cause a spectrum of genetic diseases that affect cardiac muscle and skeletal muscle as well as other tissues. A few laminopathies have been modeled using the mouse. As zebrafish is a well established model for the study of cardiac development and disease, we have investigated the effects of heart-specific lamin A mutations in transgenic zebrafish. We have developed transgenic lines of zebrafish expressing conserved lamin A mutations that cause cardiac dysfunction in humans. Expression of zlamin A mutations Q291P and M368K in the heart was driven by the zebrafish cardiac troponin T2 promoter. Homozygous mutant embryos displayed nuclear abnormalities in cardiomyocyte nuclei. Expression analysis showed the upregulation of genes involved in heart regeneration in transgenic mutant embryos and a cell proliferation marker was increased in adult heart tissue. At the physiological level, there was deviation of up to 20% from normal heart rate in transgenic embryos expressing mutant lamins. Adult homozygous zebrafish were fertile and did not show signs of early mortality. Our results suggest that transgenic zebrafish models of heart-specific laminopathies show cardiac regeneration and moderate deviations in heart rate during embryonic development. © 2017 International Federation for Cell Biology.

  11. Zebrafish Models of Human Leukemia: Technological Advances and Mechanistic Insights.

    Science.gov (United States)

    Harrison, Nicholas R; Laroche, Fabrice J F; Gutierrez, Alejandro; Feng, Hui

    2016-01-01

    Insights concerning leukemic pathophysiology have been acquired in various animal models and further efforts to understand the mechanisms underlying leukemic treatment resistance and disease relapse promise to improve therapeutic strategies. The zebrafish (Danio rerio) is a vertebrate organism with a conserved hematopoietic program and unique experimental strengths suiting it for the investigation of human leukemia. Recent technological advances in zebrafish research including efficient transgenesis, precise genome editing, and straightforward transplantation techniques have led to the generation of a number of leukemia models. The transparency of the zebrafish when coupled with improved lineage-tracing and imaging techniques has revealed exquisite details of leukemic initiation, progression, and regression. With these advantages, the zebrafish represents a unique experimental system for leukemic research and additionally, advances in zebrafish-based high-throughput drug screening promise to hasten the discovery of novel leukemia therapeutics. To date, investigators have accumulated knowledge of the genetic underpinnings critical to leukemic transformation and treatment resistance and without doubt, zebrafish are rapidly expanding our understanding of disease mechanisms and helping to shape therapeutic strategies for improved outcomes in leukemic patients.

  12. Normal anatomy and histology of the adult zebrafish.

    Science.gov (United States)

    Menke, Aswin L; Spitsbergen, Jan M; Wolterbeek, Andre P M; Woutersen, Ruud A

    2011-08-01

    The zebrafish has been shown to be an excellent vertebrate model for studying the roles of specific genes and signaling pathways. The sequencing of its genome and the relative ease with which gene modifications can be performed have led to the creation of numerous human disease models that can be used for testing the potential and the toxicity of new pharmaceutical compounds. Many pharmaceutical companies already use the zebrafish for prescreening purposes. So far, the focus has been on ecotoxicity and the effects on embryonic development, but there is a trend to expand the use of the zebrafish with acute, subchronic, and chronic toxicity studies that are currently still carried out with the more conventional test animals such as rodents. However, before we can fully realize the potential of the zebrafish as an animal model for understanding human development, disease, and toxicology, we must first greatly advance our knowledge of normal zebrafish physiology, anatomy, and histology. To further this knowledge, we describe, in the present article, location and histology of the major zebrafish organ systems with a brief description of their function.

  13. Development of teeth in chick embryos after mouse neural crest transplantations

    OpenAIRE

    Mitsiadis, Thimios A.; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

    2003-01-01

    Teeth were lost in birds 70–80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick ...

  14. Zebrafish: a model animal for analyzing the impact of environmental pollutants on muscle and brain mitochondrial bioenergetics.

    Science.gov (United States)

    Bourdineaud, Jean-Paul; Rossignol, R; Brèthes, D

    2013-01-01

    Mercury, anthropogenic release of uranium (U), and nanoparticles constitute hazardous environmental pollutants able to accumulate along the aquatic food chain with severe risk for animal and human health. The impact of such pollutants on living organisms has been up to now approached by classical toxicology in which huge doses of toxic compounds, environmentally irrelevant, are displayed through routes that never occur in the lifespan of organisms (for instance injecting a bolus of mercury to an animal although the main route is through prey and fish eating). We wanted to address the effect of such pollutants on the muscle and brain mitochondrial bioenergetics under realistic conditions, at unprecedented low doses, using an aquatic model animal, the zebrafish Danio rerio. We developed an original method to measure brain mitochondrial respiration: a single brain was put in 1.5 mL conical tube containing a respiratory buffer. Brains were gently homogenized by 13 strokes with a conical plastic pestle, and the homogenates were immediately used for respiration measurements. Skinned muscle fibers were prepared by saponin permeabilization. Zebrafish were contaminated with food containing 13 μg of methylmercury (MeHg)/g, an environmentally relevant dose. In permeabilized muscle fibers, we observed a strong inhibition of both state 3 mitochondrial respiration and cytochrome c oxidase activity after 49 days of MeHg exposure. We measured a dramatic decrease in the rate of ATP release by skinned muscle fibers. Contrarily to muscles, brain mitochondrial respiration was not modified by MeHg exposure although brain accumulated twice as much MeHg than muscles. When zebrafish were exposed to 30 μg/L of waterborne U, the basal mitochondrial respiratory control ratio was decreased in muscles after 28 days of exposure. This was due to an increase of the inner mitochondrial membrane permeability. The impact of a daily ration of food containing gold nanoparticles of two sizes (12 and

  15. Helically coiled tube heat exchanger

    International Nuclear Information System (INIS)

    Harris, A.M.

    1981-01-01

    In a heat exchanger such as a steam generator for a nuclear reactor, two or more bundles of helically coiled tubes are arranged in series with the tubes in each bundle integrally continuing through the tube bundles arranged in series therewith. Pitch values for the tubing in any pair of tube bundles, taken transverse to the path of the reactor coolant flow about the tubes, are selected as a ratio of two unequal integers to permit efficient operation of each tube bundle while maintaining the various tube bundles of the heat exchanger within a compact envelope. Preferably, the helix angle and tube pitch parallel to the path of coolant flow are constant for all tubes in a single bundle so that the tubes are of approximately the same length within each bundle

  16. Steam generator tube performance

    International Nuclear Information System (INIS)

    Tatone, O.S.; Pathania, R.S.

    1982-04-01

    The performance of steam generator tubes in water-cooled nuclear power reactors has been reviewed for 1980. Tube defects occurred at 38% of the 97 reactors surveyed. This is a marginal improvement over 1979 when defects occurred at 41% of the reactors. The number of failed tubes was also lower, 0.14% of the tubes in service in 1980 compared with 0.20% of those in service in 1979. Analysis of the causes of these failures indicates that stress corrosion cracking was the leading failure mechanism. Reactors that used all-volatile treatment of secondary water, with or without full-flow condensate demineralization since start-up showed the lowest incidence of corrosion-related defects

  17. X-ray tube

    International Nuclear Information System (INIS)

    Webley, R.S.

    1975-01-01

    The object of the invention described is to provide an X-ray tube providing a scanned X-ray output which does not require a scanned electron beam. This is obtained by an X-ray tube including an anode which is rotatable about an axis, and a source of a beam of energy, for example an electron beam, arranged to impinge on a surface of the anode to generate X-radiation substantially at the region of incidence on the anode surface. The anode is rotatable about the axis to move the region of incidence over the surface. The anode is so shaped that the rotation causes the region of incidence to move in a predetermined manner relative to fixed parts of the tube so that the generated X-radiation is scanned in a predetermined manner relative to the tube. (UK)

  18. Fuel assembly guide tube

    International Nuclear Information System (INIS)

    Jabsen, F.S.

    1979-01-01

    This invention is directed toward a nuclear fuel assembly guide tube arrangement which restrains spacer grid movement due to coolant flow and which offers secondary means for supporting a fuel assembly during handling and transfer operations

  19. Bull Moose Tube Company

    Science.gov (United States)

    The EPA is providing notice of a proposed Administrative Penalty Assessment against the Bull Moose Tube Company, a business located at 1819 Clarkson Road, Chesterfield, MO, 63017, for alleged violations at the facility located at 406 East Industrial Drive,

  20. Tracheostomy tube - eating

    Science.gov (United States)

    Trach - eating ... take your first bites. Certain factors may make eating or swallowing harder, such as: Changes in the ... easier to swallow. Suction the tracheostomy tube before eating. This will keep you from coughing while eating, ...

  1. Abnormal Nuclear Pore Formation Triggers Apoptosis in the Intestinal Epithelium of elys-Deficient Zebrafish

    NARCIS (Netherlands)

    de Jong-Curtain, Tanya A.; Parslow, Adam C.; Trotter, Andrew J.; Hall, Nathan E.; Verkade, Heather; Tabone, Tania; Christie, Elizabeth L.; Crowhurst, Meredith O.; Layton, Judith E.; Shepherd, Iain T.; Nixon, Susan J.; Parton, Robert G.; Zon, Leonard I.; Stainier, Didier Y. R.; Lieschke, Graham J.; Heath, Joan K.

    Background & Aims: Zebrafish mutants generated by ethylnitrosourea-mutagenesis provide a powerful toot for dissecting the genetic regulation of developmental processes, including organogenesis. One zebrafish mutant, "flotte lotte" (flo), displays striking defects in intestinal, liver, pancreas, and

  2. Quo natas, Danio?—Recent Progress in Modeling Cancer in Zebrafish

    Directory of Open Access Journals (Sweden)

    Stefanie Kirchberger

    2017-08-01

    Full Text Available Over the last decade, zebrafish has proven to be a powerful model in cancer research. Zebrafish form tumors that histologically and genetically resemble human cancers. The live imaging and cost-effective compound screening possible with zebrafish especially complement classic mouse cancer models. Here, we report recent progress in the field, including genetically engineered zebrafish cancer models, xenotransplantation of human cancer cells into zebrafish, promising approaches toward live investigation of the tumor microenvironment, and identification of therapeutic strategies by performing compound screens on zebrafish cancer models. Given the recent advances in genome editing, personalized zebrafish cancer models are now a realistic possibility. In addition, ongoing automation will soon allow high-throughput compound screening using zebrafish cancer models to be part of preclinical precision medicine approaches.

  3. Streak tube development

    International Nuclear Information System (INIS)

    Hinrichs, C.K.; Estrella, R.M.

    1979-01-01

    A research program for the development of a high-speed, high-resolution streak image tube is described. This is one task in the development of a streak camera system with digital electronic readout, whose primary application is for diagnostics in underground nuclear testing. This program is concerned with the development of a high-resolution streak image tube compatible with x-ray input and electronic digital output. The tube must be capable of time resolution down to 100 psec and spatial resolution to provide greater than 1000 resolution elements across the cathode (much greater than presently available). Another objective is to develop the capability to make design changes in tube configurations to meet different experimental requirements. A demountable prototype streak tube was constructed, mounted on an optical bench, and placed in a vacuum system. Initial measurements of the tube resolution with an undeflected image show a resolution of 32 line pairs per millimeter over a cathode diameter of one inch, which is consistent with the predictions of the computer simulations. With the initial set of unoptmized deflection plates, the resolution pattern appeared to remain unchanged for static deflections of +- 1/2-inch, a total streak length of one inch, also consistent with the computer simulations. A passively mode-locked frequency-doubled dye laser is being developed as an ultraviolet pulsed light source to measure dynamic tube resolution during streaking. A sweep circuit to provide the deflection voltage in the prototype tube has been designed and constructed and provides a relatively linear ramp voltage with ramp durations adjustable between 10 and 1000 nsec

  4. Researching YouTube

    OpenAIRE

    Arthurs, Jane; Drakopoulou, Sophia; Gandini, Alessandro

    2018-01-01

    ‘Researching YouTube’ introduces the special issue of Convergence which arose out of an international academic conference on YouTube that was held in London at Middlesex University in September 2016. The conference aimed to generate a robust overview of YouTube’s changing character and significance after its first ten years of development by creating a productive dialogue between speakers from different disciplines and cultures, and between YouTube-specific research and wider debates in media...

  5. Tubing crimping pliers

    Science.gov (United States)

    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.

  6. Pressure tube reactor

    International Nuclear Information System (INIS)

    Seki, Osamu; Kumasaka, Katsuyuki.

    1988-01-01

    Purpose: To remove the heat of reactor core using a great amount of moderators at the periphery of the reactor core as coolants. Constitution: Heat of a reactor core is removed by disposing a spontaneous recycling cooling device for cooling moderators in a moderator tank, without using additional power driven equipments. That is, a spontaneous recycling cooling device for cooling the moderators in the moderator tank is disposed. Further, the gap between the inner wall of a pressure tube guide pipe disposed through the vertical direction of a moderator tank and the outer wall of a pressure tube inserted through the guide pipe is made smaller than the rupture distortion caused by the thermal expansion upon overheating of the pressure tube and greater than the minimum gap required for heat shiels between the pressure tube and the pressure tube guide pipe during usual operation. In this way, even if such an accident as can not using a coolant cooling device comprising power driven equipment should occur in the pressure tube type reactor, the rise in the temperature of the reactor core can be retarded to obtain a margin with time. (Kamimura, M.)

  7. Preliminary research on eddy current bobbin quantitative test for heat exchange tube in nuclear power plant

    Science.gov (United States)

    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.

  8. Tube spacer grid for a heat-exchanger tube bundle

    International Nuclear Information System (INIS)

    Scheidl, H.

    1976-01-01

    A tube spacer grid for a heat-exchanger tube bundle is formed by an annular grid frame having a groove formed in its inner surface in which the interspaced grid bars have their ends positioned and held in interspaced relationship by short sections of tubes passed through holes axially formed in the grid frame so that the tubes are positioned between the ends of the grid bars in the grooves. The tube sections may be cut from the same tubes used to form the tube bundle. 5 claims, 3 drawing figures

  9. Developmental toxicity of cartap on zebrafish embryos.

    Science.gov (United States)

    Zhou, Shengli; Dong, Qiaoxiang; Li, Shaonan; Guo, Jiangfeng; Wang, Xingxing; Zhu, Guonian

    2009-12-13

    Cartap is a widely used insecticide which belongs to a member of nereistoxin derivatives and acts on nicotinic acetylcholine receptor site. Its effects on aquatic species are of grave concern. To explore the potential developmental toxicity of cartap, zebrafish embryos were continually exposed, from 0.5 to 144h post-fertilization, to a range of concentrations of 25-1000microg/l. Results of the experiment indicated that cartap concentrations of 100microg/l and above negatively affected embryo survival and hatching success. Morphological analysis uncovered a large suite of abnormalities such as less melanin pigmentation, wavy notochord, crooked trunk, fuzzy somites, neurogenesis defects and vasculature defects. The most sensitive organ was proved to be the notochord which displayed defects at concentrations as low as 25microg/l. Both sensitivity towards exposure and localization of the defect were stage specific. To elucidate mechanisms concerning notochord, pigmentation, and hatching defects, enzyme assay, RT Q-PCR, and different exposure strategies were performed. For embryos with hatching failure, chorion was verified not to be digested, while removing cartap from exposure at early pre-hatching stage could significantly increase the hatching success. However, cartap was proved, via vitro assay, to have no effect on proteolytic activity of hatching enzyme. These findings implied that the secretion of hatching enzyme might be blocked. We also revealed that cartap inhibited the activity of melanogenic enzyme tyrosinase and matrix enzyme lysyl oxidase and induced expression of their genes. These suggested that cartap could impaired melanin pigmentation of zebrafish embryos through inhibiting tyrosinase activity, while inhibition of lysyl oxidase activity was responsible for notochord undulation, which subsequently caused somite defect, and at least partially responsible for defects in vasculature and neurogenesis.

  10. An algorithm to track laboratory zebrafish shoals.

    Science.gov (United States)

    Feijó, Gregory de Oliveira; Sangalli, Vicenzo Abichequer; da Silva, Isaac Newton Lima; Pinho, Márcio Sarroglia

    2018-05-01

    In this paper, a semi-automatic multi-object tracking method to track a group of unmarked zebrafish is proposed. This method can handle partial occlusion cases, maintaining the correct identity of each individual. For every object, we extracted a set of geometric features to be used in the two main stages of the algorithm. The first stage selected the best candidate, based both on the blobs identified in the image and the estimate generated by a Kalman Filter instance. In the second stage, if the same candidate-blob is selected by two or more instances, a blob-partitioning algorithm takes place in order to split this blob and reestablish the instances' identities. If the algorithm cannot determine the identity of a blob, a manual intervention is required. This procedure was compared against a manual labeled ground truth on four video sequences with different numbers of fish and spatial resolution. The performance of the proposed method is then compared against two well-known zebrafish tracking methods found in the literature: one that treats occlusion scenarios and one that only track fish that are not in occlusion. Based on the data set used, the proposed method outperforms the first method in correctly separating fish in occlusion, increasing its efficiency by at least 8.15% of the cases. As for the second, the proposed method's overall performance outperformed the second in some of the tested videos, especially those with lower image quality, because the second method requires high-spatial resolution images, which is not a requirement for the proposed method. Yet, the proposed method was able to separate fish involved in occlusion and correctly assign its identity in up to 87.85% of the cases, without accounting for user intervention. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... search for current job openings visit HHS USAJobs Home >> NEI YouTube Videos >> NEI YouTube Videos: Amblyopia Listen NEI YouTube Videos YouTube Videos Home Age-Related Macular Degeneration Amblyopia Animations Blindness Cataract ...

  12. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... search for current job openings visit HHS USAJobs Home » NEI YouTube Videos » NEI YouTube Videos: Amblyopia Listen NEI YouTube Videos YouTube Videos Home Age-Related Macular Degeneration Amblyopia Animations Blindness Cataract ...

  13. Cyp1a reporter zebrafish reveals target tissues for dioxin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kun-Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Park, Hye-Jeong [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Jin Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Suhyun [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Williams, Darren R. [New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju (Korea, Republic of); Kim, Myeong-Kyu [Department of Neurology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Jung, Young Do [Department of Biochemistry, Chonnam National University Medical School, Gwangju (Korea, Republic of); Teraoka, Hiroki [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Park, Hae-Chul [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Choy, Hyon E., E-mail: hyonchoy@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Shin, Boo Ahn, E-mail: bashin@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Choi, Seok-Yong, E-mail: zebrafish@chonnam.ac.kr [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); School of Biological Sciences and Technology, Chonnam National University, Gwangju (Korea, Republic of)

    2013-06-15

    Highlights: •2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic anthropogenic substance ever identified. •Transgenic cyp1a reporter zebrafish reveals target tissues for TCDD. •The retinal bipolar cells, otic vesicle, lateral line, pancreas, cloaca and pectoral fin bud are novel targets in zebrafish for TCDD. •Our findings will further understanding of human health risks by TCDD. -- Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the unintentional byproduct of various industrial processes, is classified as human carcinogen and could disrupt reproductive, developmental and endocrine systems. Induction of cyp1a1 is used as an indicator of TCDD exposure. We sought to determine tissues that are vulnerable to TCDD toxicity using a transgenic zebrafish (Danio rerio) model. We inserted a nuclear enhanced green fluorescent protein gene (EGFP) into the start codon of a zebrafish cyp1a gene in a fosmid clone using DNA recombineering. The resulting recombineered fosmid was then used to generate cyp1a reporter zebrafish, embryos of which were exposed to TCDD. Expression pattern of EGFP in the reporter zebrafish mirrored that of endogenous cyp1a mRNA. In addition, exposure of the embryos to TCDD at as low as 10 pM for 72 h, which does not elicit morphological abnormalities of embryos, markedly increased GFP expression. Furthermore, the reporter embryos responded to other AhR ligands as well. Exposure of the embryos to TCDD revealed previously reported (the cardiovascular system, liver, pancreas, kidney, swim bladder and skin) and unreported target tissues (retinal bipolar cells, otic vesicle, lateral line, cloaca and pectoral fin bud) for TCDD. Transgenic cyp1a reporter zebrafish we have developed can further understanding of ecotoxicological relevance and human health risks by TCDD. In addition, they could be used to identify agonists of AhR and antidotes to TCDD toxicity.

  14. Evaluation of color preference in zebrafish for learning and memory.

    Science.gov (United States)

    Avdesh, Avdesh; Martin-Iverson, Mathew T; Mondal, Alinda; Chen, Mengqi; Askraba, Sreten; Morgan, Newman; Lardelli, Michael; Groth, David M; Verdile, Giuseppe; Martins, Ralph N

    2012-01-01

    There is growing interest in using zebrafish (Danio rerio) as a model of neurodegenerative disorders such as Alzheimer's disease. A zebrafish model of tauopathies has recently been developed and characterized in terms of presence of the pathological hallmarks (i.e., neurofibrillary tangles and cell death). However, it is also necessary to validate these models for function by assessing learning and memory. The majority of tools to assess memory and learning in animal models involve visual stimuli, including color preference. The color preference of zebrafish has received little attention. To validate zebrafish as a model for color-associated-learning and memory, it is necessary to evaluate its natural preferences or any pre-existing biases towards specific colors. In the present study, we have used four different colors (red, yellow, green, and blue) to test natural color preferences of the zebrafish using two procedures: Place preference and T-maze. Results from both experiments indicate a strong aversion toward blue color relative to all other colors (red, yellow, and green) when tested in combinations. No preferences or biases were found among reds, yellows, and greens in the place preference procedure. However, red and green were equally preferred and both were preferred over yellow by zebrafish in the T-maze procedure. The results from the present study show a strong aversion towards blue color compared to red, green, and yellow, with yellow being less preferred relative to red and green. The findings from this study may underpin any further designing of color-based learning and memory paradigms or experiments involving aversion, anxiety, or fear in the zebrafish.

  15. Pharmacological Modulation of Hemodynamics in Adult Zebrafish In Vivo.

    Directory of Open Access Journals (Sweden)

    Daniel Brönnimann

    Full Text Available Hemodynamic parameters in zebrafish receive increasing attention because of their important role in cardiovascular processes such as atherosclerosis, hematopoiesis, sprouting and intussusceptive angiogenesis. To study underlying mechanisms, the precise modulation of parameters like blood flow velocity or shear stress is centrally important. Questions related to blood flow have been addressed in the past in either embryonic or ex vivo-zebrafish models but little information is available for adult animals. Here we describe a pharmacological approach to modulate cardiac and hemodynamic parameters in adult zebrafish in vivo.Adult zebrafish were paralyzed and orally perfused with salt water. The drugs isoprenaline and sodium nitroprusside were directly applied with the perfusate, thus closely resembling the preferred method for drug delivery in zebrafish, namely within the water. Drug effects on the heart and on blood flow in the submental vein were studied using electrocardiograms, in vivo-microscopy and mathematical flow simulations.Under control conditions, heart rate, blood flow velocity and shear stress varied less than ± 5%. Maximal chronotropic effects of isoprenaline were achieved at a concentration of 50 μmol/L, where it increased the heart rate by 22.6 ± 1.3% (n = 4; p < 0.0001. Blood flow velocity and shear stress in the submental vein were not significantly increased. Sodium nitroprusside at 1 mmol/L did not alter the heart rate but increased blood flow velocity by 110.46 ± 19.64% (p = 0.01 and shear stress by 117.96 ± 23.65% (n = 9; p = 0.03.In this study, we demonstrate that cardiac and hemodynamic parameters in adult zebrafish can be efficiently modulated by isoprenaline and sodium nitroprusside. Together with the suitability of the zebrafish for in vivo-microscopy and genetic modifications, the methodology described permits studying biological processes that are dependent on hemodynamic alterations.

  16. Tube plug removal machine

    International Nuclear Information System (INIS)

    Hawkins, P.J.

    1987-01-01

    In a nuclear steam generator wherein some faulty tubes have been isolated by mechanical plugging, to remove a selected plug without damaging the associated tube, a plug removal machine is used. The machine drills into a plug portion with a tap drill bit having a drill portion a tap portion and a threaded portion, engaging that plug portion with the threaded portion after the drilled hole has been threaded by the tap portion thereof, and removing a portion of the plug in the tube with a counterbore drill bit mounted concentrically about the tap drill bit. A trip pin and trip spline disengage the tap drill bit from the motor. The counterbore drill bit is thereafter self-centered with respect to the tube and plug about the now stationary tap drill bit. After a portion of the plug has been removed by the counterbore drill bit, pulling on the top drill bit by grippers on slots will remove the remaining plug portion from the tube. (author)

  17. Categorising YouTube

    Directory of Open Access Journals (Sweden)

    Thomas Mosebo Simonsen

    2011-09-01

    Full Text Available This article provides a genre analytical approach to creating a typology of the User Generated Content (UGC of YouTube. The article investigates the construction of navigationprocesses on the YouTube website. It suggests a pragmatic genre approach that is expanded through a focus on YouTube’s technological affordances. Through an analysis of the different pragmatic contexts of YouTube, it is argued that a taxonomic understanding of YouTube must be analysed in regards to the vacillation of a user-driven bottom-up folksonomy and a hierarchical browsing system that emphasises a culture of competition and which favours the already popular content of YouTube. With this taxonomic approach, the UGC videos are registered and analysed in terms of empirically based observations. The article identifies various UGC categories and their principal characteristics. Furthermore, general tendencies of the UGC within the interacting relationship of new and old genres are discussed. It is argued that the utility of a conventional categorical system is primarily of analytical and theoretical interest rather than as a practical instrument.

  18. Measuring of tube expansion

    International Nuclear Information System (INIS)

    Vogeleer, J. P.

    1985-01-01

    The expansion of the primary tubes or sleeves of the steam generator of a nuclear reactor plant are measured while the tubes or sleeves are being expanded. A primary tube or sleeve is expanded by high pressure of water which flows through a channel in an expander body. The water is supplied through an elongated conductor and is introduced through a connector on the shank connected to the conductor at its outer end. A wire extends through the mandrel and through the conductor to the end of the connector. At its inner end the wire is connected to a tapered pin which is subject to counteracting forces produced by the pressure of the water. The force on the side where the wire is connected to the conductor is smaller than on the opposite side. The tapered pin is moved in the direction of the higher force and extrudes the wire outwardly of the conductor. The tapered surface of the tapered pin engages transverse captive plungers which are maintained in engagement with the expanding tube or sleeve as they are moved outwardly by the tapered pin. The wire and the connector extend out of the generator and, at its outer end, the wire is connected to an indicator which measures the extent to which the wire is moved by the tapered pin, thus measuring the expansion of the tube or sleeve as it progresses

  19. Neural Networks

    Directory of Open Access Journals (Sweden)

    Schwindling Jerome

    2010-04-01

    Full Text Available 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.

  20. Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Christen, Verena [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Capelle, Martinus [Crucell, P.O. Box 2048, NL-2301 Leiden (Netherlands); Fent, Karl, E-mail: karl.fent@fhnw.ch [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology Zürich, Department of Environmental Systems Science, CH-8092 Zürich (Switzerland)

    2013-10-15

    Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120 nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplasmatic reticulum (ER) stress response, and TNF-α. Transcriptional alterations also occur in pro-apoptotic genes p53 and Bax. The transcriptional profile differed in ZFL and Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6 h and 24 h exposure to 0.5 g/L and 0.05 g/L AgNPs, respectively. This indicates the induction of different pathways of the ER stress response. Moreover, AgNPs induce TNF-α. In zebrafish embryos exposed to 0.01, 0.1, 1 and 5 mg/L AgNPs hatching was affected and morphological defects occurred at high concentrations. ER stress related gene transcripts BiP and Synv are significantly up-regulated after 24 h at 0.1 and 5 mg/L AgNPs. Furthermore, transcriptional alterations occurred in the pro-apoptotic genes Noxa and p21. The ER stress response was strong in ZFL cells and occurred in zebrafish embryos as well. Our data demonstrate for the first time that AgNPs lead to induction of ER stress in zebrafish. The induction of ER stress can have several consequences including the activation of apoptotic and inflammatory pathways. - Highlights: • Effects of silver nanoparticles (120 nm AgNPs) are investigated in zebrafish. • AgNPs induce all ER stress reponses in vitro in zebrafish liver cells. • AgNPs induce weak ER stress in zebrafish embryos. • AgNPs induce oxidative stress and transcripts of pro-apoptosis genes.

  1. Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

    International Nuclear Information System (INIS)

    Christen, Verena; Capelle, Martinus; Fent, Karl

    2013-01-01

    Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120 nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplas