Note: This page contains sample records for the topic background neural tube from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: November 12, 2013.
1

Abnormal skull findings in neural tube defects  

PubMed Central

The human neural tube develops and closes during the third and fourth week after conception and is normally completed by 28 days post-conception. Malformations, knows as neural tube defects, occure, when the normal closure process fails. Several clinical types of neural tube defects are recognized, anencefaly and spina bifida being the most common. Such malformations are generally associated with cranial abnormlities

Imbruglia, Laura; Cacciatore, Alessandra; Carrara, Sabina; Recupero, Stefania; La Galia, Tindara; Pappalardo, Elisa Maria; Chiara Accardi, Manuela; Pedata, Rosa; Rapisarda, Giusi; Mammaro, Alessia

2009-01-01

2

Preconceptional Vitamin Use and Neural Tube Defects.  

National Technical Information Service (NTIS)

This study sought to establish the potential benefit of preconceptional vitamin supplementation in reducing the incidence of neural tube defects (NTDs), and examine some of the potential hazards of excessive preconceptional vitamin supplementation. The pr...

A. A. Mitchell

1992-01-01

3

Spina bifida and other neural tube defects  

Microsoft Academic Search

~ eural tube defects (NTDs) are the most common severely disabling birth defects in the United States, with a frequency of approximately 1 of every 2000 births. NTDs include all congenital anom- alies that involve failure of the neural tube to close during the fourth week of embryogenesis. NTDs can occur anywhere along the formation of the spinal cord, from

Kelly A. Volcik

2000-01-01

4

Epithelial fusion during neural tube morphogenesis  

PubMed Central

Adhesion and fusion of epithelial sheets marks the completion of many morphogenetic events during embryogenesis. Neural tube closure involves an epithelial fusion sequence in which the apposing neural folds adhere initially via cellular protrusions, proceed to a more stable union, and subsequently undergo remodelling of the epithelial structures to yield a separate neural tube roof plate and overlying non-neural ectoderm. Cellular protrusions comprise lamellipodia and filopodia, and studies in several different systems emphasise the critical role of RhoGTPases in their regulation. How epithelia establish initial adhesion is poorly understood but, in neurulation, may involve interactions between EphA receptors and their ephrinA ligands. Epithelial remodelling is spatially and temporally correlated with apoptosis in the dorsal neural tube midline, but experimental inhibition of this cell death does not prevent fusion and remodelling. A variety of molecular signalling systems have been implicated in the late events of morphogenesis, but genetic redundancy, for example among the integrins and laminins, makes identification of the critical players challenging. An improved understanding of epithelial fusion can provide insights into normal developmental processes, and may also indicate the mode of origin of clinically important birth defects.

Pai, Yun-Jin; Abdullah, N.L.; Mohd.-Zin, S.W.; Mohammed, R. S.; Rolo, Ana; Greene, Nicholas D.E.; Abdul-Aziz, Noraishah M.; Copp, Andrew J.

2013-01-01

5

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

Microsoft Academic Search

BACKGROUND: Nodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish. RESULTS: We find that the neural tube in the presumptive forebrain fails to close in zebrafish Nodal signaling mutants. For instance, the cells that will give rise to the

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

2007-01-01

6

Recurrent neural tube defects, risk factors and vitamins.  

PubMed Central

Data from our trial of periconceptional vitamin supplementation for the prevention of neural tube defects have been analysed to assess the influence of various factors on recurrence rates of neural tube defect. Our data suggest that the risk of recurrence of neural tube defect is influenced by the number of previous neural tube defects, area of residence, immediately prior miscarriage, and interpregnancy interval. None of these factors, however, contributed any significant differential risk between supplemented and unsupplemented mothers. Hence we conclude that the highly significant difference in recurrence rates of neural tube defect between supplemented and unsupplemented mothers was due to vitamin supplementation.

Wild, J; Read, A P; Sheppard, S; Seller, M J; Smithells, R W; Nevin, N C; Schorah, C J; Fielding, D W; Walker, S; Harris, R

1986-01-01

7

Metabolic Syndrome features and risk of neural tube defects  

Microsoft Academic Search

BACKGROUND: Maternal obesity and pre-pregnancy diabetes mellitus, features of the metabolic syndrome (MetSyn), are individual risk factors for neural tube defects (NTD). Whether they, in combination with additional features of MetSyn, alter this risk is not known. We evaluated the risk of NTD in association with maternal features of the MetSyn. METHODS: We used a population-based case-control study design in

Joel G Ray; Miles D Thompson; Marian J Vermeulen; Chris Meier; Philip R Wyatt; Pui-Yuen Wong; Anne M Summers; Sandra A Farrell; David EC Cole

2007-01-01

8

Neural Tube Defects, Folic Acid and Methylation  

PubMed Central

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.

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

2013-01-01

9

A low-background organic-type GM tube  

Microsoft Academic Search

A low-background, organic-type small GM tube with a short tungsten wire anode of 1 cm length and a cylindrical steel cathode was constructed. Reduction on the background caused by cosmic rays and contamination is achieved by using a short, small GM tube. At the same time, the problem of low counting efficiency caused by the short tube length is overcome.

Laila Fikri Fouad

1991-01-01

10

How Do Health Care Providers Diagnose Neural Tube Defects?  

MedlinePLUS

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

11

What Are the Treatments for Neural Tube Defects?  

MedlinePLUS

... and Publications What are the treatments for neural tube defects? Page Content Encephaloceles are sometimes treated with ... surgeon can implant a shunt—a small hollow tube to drain fluid—to relieve pressure on the ...

12

Multiple neural tube defects in a child: A rare developmental anomaly  

PubMed Central

Background: The presence of multiple neural tube defects (NTDs) is a rare entity. Published literature shows not more than 10 case reports. Such cases contradict the well-established “zipper model” of neural tube closure and support “multi-site closure model.” Case Description: We are reporting a unique case of multiple NTDs in a 5-month-o ld female child. Occipital encephalocele, dorsal meningomyelocele, Split cord malformation (SCM), and tethered cord were present in this case. Conclusion: This case report further substantiate the “multisite closure model,” however, more research work on human neuro-embryology is needed to overcome the controversies of neural tube closure.

Singh, Neha; Singh, Deepak Kumar; Aga, Pallavi; Singh, Ragini

2012-01-01

13

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

PubMed

Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention with folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in the UK. Genetic predisposition accounts for most of the risk of neural tube defects, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but studies of mouse models of neural tube defects show that anencephaly, open spina bifida, and craniorachischisis result from failure of primary neurulation, whereas skin-covered spinal dysraphism results from defective secondary neurulation. Other malformations, such as encephalocele, are likely to be postneurulation disorders. PMID:23790957

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

2013-06-19

14

[Morphometric analysis of neural tube cells in neurulating chick embryos].  

PubMed

Preliminary report on a morphometric study of the neuroepithelium of 1 S and 7 S -- stage chick embryos. We show first that the nucleo-cytoplasmic ratio and then, that the volume fraction of intercellular spaces, nuclei and cytoplasm as they relate to the neural tube, differ significatively from cephalic to caudal portion of the neural tube. At stage 7 S only the volume fraction of intercellular spaces, nuclei and cytoplasm in the neural tube change along the cephalo-caudal axis of the embryos. Finally, between the two stages, at the back of the head, 1) volume fraction of intercellular spaces in the neural tube remains unchanged 2) nucleo-cytoplasmic ratio increase 3) volumetric density and size of mitochondria do not change, while surface density of endoplasmic reticulum in cytoplasm increases. PMID:1178939

Mathieu, O; Messier, P E

15

Diplomyelia: caudal duplication of the neural tube in mice.  

PubMed

Diplomyelia (duplication of the neural tube or spinal cord) was studied histologically in nine cases of T/+ mouse embryos at 10-15 days of gestation. Grüneberg investigated T/+ fetuses and interpreted the extra neural tube to be notochord, but a reexamination of this material demonstrated that the interpretation is incorrect. Diplomyelia is produced in the mutations Fused, Kinky, vestigial tail, homozygous Brachyury, and t-haplotype t9 and in the new mutation, NM 529, described here. PMID:3798370

Cogliatti, S B

1986-12-01

16

Fate Map and Morphogenesis of Presumptive Neural Crest and Dorsal Neural Tube  

PubMed Central

In contrast to the classical assumption that neural crest cells are induced in chick as the neural folds elevate, recent data suggest that they are already specified during gastrulation. This prompted us to map the origin of the neural crest and dorsal neural tube in the early avian embryo. Using a combination of focal dye injections and time-lapse imaging, we find that neural crest and dorsal neural tube precursors are present in a broad, crescent-shaped region of the gastrula. Surprisingly, static fate maps together with dynamic confocal imaging reveal that the neural plate border is considerably broader and extends more caudally than expected. Interestingly, we find that the position of the presumptive neural crest broadly correlates with the BMP4 expression domain from gastrula to neurula stages. Some degree of rostrocaudal patterning, albeit incomplete, is already evident in the gastrula. Time-lapse imaging studies show that the neural crest and dorsal neural tube precursors undergo choreographed movements that follow a spatiotemporal progression and include convergence and extension, reorientation, cell intermixing, and motility deep within the embryo. Through these rearrangement and reorganization movements, the neural crest and dorsal neural tube precursors become regionally segregated, coming to occupy predictable rostrocaudal positions along the embryonic axis. This regionalization occurs progressively and appears to be complete in the neurula by stage 7 at levels rostral to Hensen's node.

Ezin, Akouavi M.; Fraser, Scott E.; Bronner-Fraser, Marianne

2009-01-01

17

Neural tube closure: the curious case of shrinking junctions.  

PubMed

Your brain and spinal cord began as a flat sheet, which narrowed, elongated, and rolled up to form a tube. A new study identifies a key molecular link underlying vertebrate neural tube formation, connecting planar cell polarity patterning to contraction of specific cell-cell junctions. PMID:22835793

Sullivan-Brown, Jessica; Goldstein, Bob

2012-07-24

18

Hemichordate neurulation and the origin of the neural tube.  

PubMed

The origin of the body plan of our own phylum, Chordata, is one of the most fascinating questions in evolutionary biology. Yet, after more than a century of debate, the evolutionary origins of the neural tube and notochord remain unclear. Here we examine the development of the collar nerve cord in the hemichordate Balanoglossus simodensis and find shared gene expression patterns between hemichordate and chordate neurulation. Moreover, we show that the dorsal endoderm of the buccal tube and the stomochord expresses Hedgehog RNA, and it seems likely that collar cord cells can receive the signal. Our data suggest that the endoderm functions as an organizer to pattern the overlying collar cord, similar to the relationship between the notochord and neural tube in chordates. We propose that the origin of the core genetic mechanisms for the development of the notochord and the neural tube date back to the last common deuterostome ancestor. PMID:24177053

Miyamoto, Norio; Wada, Hiroshi

2013-11-01

19

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

Microsoft Academic Search

Background: With the goal of preventing open neural tube defects (NTDs), recom- mendations for folic acid supplementation before conception were introduced in Canada in 1994, and by November 1998 Canadian grain products were being fortified with folic acid. We wished to determine whether the annual incidence of open NTDs in Nova Scotia, including those in stillbirths and terminated preg- nancies,

Vidia L. Persad; Michiel C. Van den Hof; Johanne M. Dubé; Pamela Zimmer

2002-01-01

20

Inhibition of methylation and changes in gene expression in relation to neural tube defects  

Microsoft Academic Search

BACKGROUND: An impaired DNA methylation has been suggested to underlie the complex etiology of neural tube defects (NTDs). Previously, we have demonstrated that inhibition of methylation by periodate oxidized adenosine (Adox) results in a widening of the anterior neuropore (ANP) in our in vitro chick embryo model. Since DNA methylation is the chief regulator of gene expression, we hypothesize that

Ivon J. M. van der Linden; Sandra G. Heil; Egmont-Petersen van M; Henny W. van Straaten; Martin den Heijer; Henk J. Blom

2008-01-01

21

Cellular mechanisms of posterior neural tube morphogenesis in the zebrafish.  

PubMed

The zebrafish is a well established model system for studying neural development, yet neurulation remains poorly understood in this organism. In particular, the morphogenetic movements that shape the posterior neural tube (PNT) have not been described. Using tools for imaging neural tissue and tracking the behavior of cells in real time, we provide the first comprehensive analysis of the cellular events shaping the PNT. We observe that this tissue is formed in a stepwise manner, beginning with merging of presumptive neural domains in the tailbud (Stage 1); followed by neural convergence and infolding to shape the neural rod (Stage 2); and continued elongation of the PNT, in absence of further convergence (Stage 3). We further demonstrate that cell proliferation plays only a minimal role in PNT elongation. Overall, these mechanisms resemble those previously described in anterior regions, suggesting that, in contrast to amniotes, neurulation is a fairly uniform process in zebrafish. PMID:20077475

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

2010-03-01

22

Periconceptional Folate Deficiency and Implications in Neural Tube Defects  

PubMed Central

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.

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

2012-01-01

23

Screening for fetal aneuploidy and neural tube defects  

PubMed Central

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

Driscoll, Deborah A.; Gross, Susan J.

2009-01-01

24

What are those cilia doing in the neural tube?  

PubMed Central

Primary cilia are present on almost all vertebrate cells, and they have diverse functions in distinct tissues. Cilia are important for sensation in multiple capacities in contexts as different as the retina, kidney, and inner ear. In addition to these roles, cilia play a critical part in various developmental processes. Of particular importance is the development of the neural tube, where cilia are essential for the transduction of the Sonic Hedgehog (Shh) signaling pathway that specifies neuronal cell fates. This relationship is well established and is the most recognizable function for cilia in the neural tube, but it may be part of a larger picture. Here, we discuss the links between cilia and Shh signaling, as well as suggesting additional roles for cilia, and mechanisms for their placement, in the neural tube.

2012-01-01

25

Neural Network Approach to Background Modeling for Video Object Segmentation  

Microsoft Academic Search

This paper presents a novel background modeling and subtraction approach for video object segmentation. A neural network (NN) architecture is proposed to form an unsupervised Bayesian classifier for this application domain. The constructed classifier efficiently handles the segmentation in natural-scene sequences with complex background motion and changes in illumination. The weights of the proposed NN serve as a model of

Dubravko Culibrk; Oge Marques; Daniel Socek; Hari Kalva; Borko Furht

2007-01-01

26

Management of neural tube defects in a Sub-Saharan African country: The situation in Yaounde, Cameroon  

Microsoft Academic Search

BackgroundNeural tube defect is a serious disabling but preventable congenital malformation with an incidence of 1.99 per 1000 births in Yaounde [A.K. Njamnshi, V. d e P. Djientcheu, A. Lekoubou, M. Guemse, M.T. Obama, R. Mbu, S. Takongmo, I. Kago. Neural tube defects are rare among black Americans but not in Sub-Saharan black Africans: The case of Yaounde – Cameroon.

Vincent de Paul Djientcheu; Alfred Kongnyu Njamnshi; Ambroise Wonkam; Julie Njiki; Mohamadou Guemse; Robinson Mbu; Marie Thérèse Obama; Samuel Takongmo; Innocent Kago; Ekoe Tetanye; Felix Tietche

2008-01-01

27

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

Code of Federal Regulations, 2013 CFR

...with a neural tube defect, those with insulin-dependent diabetes mellitus, and women with seizure disorders who are being...with a neural tube defect; those with insulin-dependent diabetes mellitus; those with seizure disorders who are being...

2013-04-01

28

The range of neural tube defects in southern India  

Microsoft Academic Search

During a prospective study of 3500 consecutive births from November 1985 to January 1987 at three hospitals, 40 babies were found to have neural tube defects, an extremely high incidence (11.4\\/1000 births). The defects comprised anencephaly (n = 18), meningomyelocele (n = 11), Arnold-Chiari deformity (n = 3), encephalocele (n = 3), iniencephaly (n = 2), and one each of

M L Kulkarni; M A Mathew; V Reddy

1989-01-01

29

Social networks and risk of neural tube defects  

Microsoft Academic Search

The contribution of social support and social networks to risk of neural tube defects (NTDs) has not been explored, despite evidence that various aspects of the social environment contribute to their etiology. Using data from a population-based case–control study of deliveries occurring in California from 1989 to 1991, this study investigates whether social networks, as measured by the presence and

Suzan L. Carmichael; Gary M. Shaw; Eric Neri; Donna M. Schaffer; Steve Selvin

2003-01-01

30

Transcription Factor TEAD2 Is Involved in Neural Tube Closure  

PubMed Central

Summary TEAD2, one of the first transcription factors expressed at the beginning of mammalian development, appears to be required during neural development. For example, Tead2 expression is greatest in the dorsal neural crest where it appears to regulate expression of Pax3, a gene essential for brain development. Consistent with this hypothesis, we found that inactivation of the Tead2 gene in mice significantly increased the risk of exencephaly (a defect in neural tube closure). However, none of the embryos exhibited spina bifida, the major phenotype of Pax3 nullizygous embryos, and expression of Pax3 in E11.5 Tead2 nullizygous embryos was normal. Thus, Tead2 plays a role in neural tube closure that is independent of its putative role in Pax3 regulation. In addition, the risk of exencephaly was greatest with Tead2 nullizygous females, and could be suppressed either by folic acid or pifithrin-?. These results reveal a maternal genetic contribution to neural tube closure, and suggest that Tead2-deficient mice provide a model for anencephaly, a common human birth defect that can be prevented by folic acid. genesis 45:577–587, 2007.

Kaneko, Kotaro J.; Kohn, Matthew J.; Liu, Chengyu; DePamphilis, Melvin L.

2009-01-01

31

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

Microsoft Academic Search

Although Rho-GTPases are well-known regulators of cytoskeletal reorganization, their in vivo distribution and physio- logical functions have remained elusive. In this study, we found marked apical accumulation of Rho in developing chick embryos undergoing folding of the neural plate during neural tube formation, with similar accumulation of activated myosin II. The timing of accumulation and biochemical activation of both Rho

Nagatoki Kinoshita; Noriaki Sasai; Kazuyo Misaki; Shigenobu Yonemura

2008-01-01

32

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

ERIC Educational Resources Information Center

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

Arc, Arlington, TX.

33

Neural tube defects are rare among black Americans but not in sub-Saharan black Africans: The case of Yaounde — Cameroon  

Microsoft Academic Search

BackgroundNeural tube defects (NTD) are complex malformations rare in black Americans and Japanese. The incidence related to births or community based studies have not been published in Cameroon or in black sub-Saharan countries, except one study in the Nigerian middle belt [A. Courtney, Adolfo Correa Rowland, Janet D. Cragan and Alverson J. Clinton, Are encephalocede neural tube defects? Official journal

A. K. Njamnshi; V. de P. Djientcheu; A. Lekoubou; M. Guemse; M. T. Obama; R. Mbu; S. Takongmo; I. Kago

2008-01-01

34

Neural development: Patterning cascades in the neural tube  

Microsoft Academic Search

The vertebrate central nervous system comprises an intricate array of neurons generated in a highly organized way. Examination of the genes expressed and required at early stages of neural differentiation reveals that a coordinated signalling cascade transforms progenitor cells into discrete neuronal subsets.

Marysia Placzek; Andrew Furley

1996-01-01

35

Meckel syndrome and the prenatal diagnosis of neural tube defects.  

PubMed Central

Two fetuses, terminated after prenatal diagnosis of aneural tube defect, had Meckel syndrome. There have now been three fetuses with this syndrome in a series of 35 terminated because of open lesions of the neural tube. It is suggested that such therapeutically aborted fetuses represent a highly selected group, among which a rare condition like Meckel syndrome will be concentrated. The need for a detailed examination of all terminated fetuses is emphasised, for the identification of such an autosomal recessive condition alters the genetic counselling for a future pregnancy. Images

Seller, M J

1978-01-01

36

Novel Mutations in VANGL1 in Neural Tube Defects  

PubMed Central

Neural tube defects (NTDs) are severe congenital malformations caused by failure of the neural tube to close during neurulation. Their etiology is complex involving both environmental and genetic factors. We have recently reported three mutations in the planar cell polarity gene VANGL1 associated with NTDs. The aim of the present study was to define the role of VANGL1 genetic variants in the development of NTDs in a large cohort of various ethnic origins. We identified five novel missense variants in VANGL1, p.Ser83Leu, p.Phe153Ser, p.Arg181Gln, p.Leu202Phe and p.Ala404Ser, occurring in sporadic and familial cases of spinal dysraphisms. All five variants affect evolutionary conserved residues and are absent from all controls analyzed. This study provides further evidence supporting the role of VANGL1 as a risk factor in the development of spinal NTDs.

Kibar, Zoha; Bosoi, Ciprian M.; Kooistra, Megan; Salem, Sandra; Finnell, Richard H.; Marco, Patrizia De; Merello, Elisa; Bassuk, Alexander G.; Capra, Valeria; Gros, Philippe

2010-01-01

37

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

PubMed

Disturbed neurulation fascinated scientists of all times. In Egypt, anencephalic infants were venerated as animal-headed gods. Roman law required them to be killed. The medieval world held the mother responsible, either because of assumed imagination or "miswatching," or because of suspected intercourse with animals or devils. Modern embryology and teratology began with the use of the microscope by Malpighi in 1672. Details of neural tube closure were described by Koelliker in 1861 and by His in 1874. From 1822, genetic disease and familial recurrence due to insufficient nutrition were discerned and lower social class identified as a risk factor. It took a century to define the malnutrition as insufficient folate intake. The mandatory supplementation of folate in staple foods successfully reduced the incidence of neural tube defects in the United States, Australia, Canada, and Chile, but it was not adopted by most European countries. PMID:21730342

Obladen, Michael

2011-07-05

38

Maternal serum alpha-fetoprotein screening for neural tube defects  

Microsoft Academic Search

The basis of maternal serum alpha-fetoprotein (AFP)-screening for neural tube defects is discussed. A report is given of a large scale screening study in the Federal Republic of Germany combining the experiences in Giessen and Hannover on over 50,000 pregnant women, about evently distributed among both centers. Published and known forthcoming data from other low incidence populations, particularly of European

Walter Fuhrmann; Hans K. Weitzel

1985-01-01

39

Socioeconomic status, neighborhood social conditions, and neural tube defects.  

PubMed Central

OBJECTIVES: This study evaluated the contributions of lower socioeconomic status (SES) and neighborhood socioeconomic characteristics to neural tube defect etiology. The influence of additional factors, including periconceptional multivitamin use and race/ethnicity, was also explored. METHODS: Data derived from a case-control study of California pregnancies from 1989 to 1991. Mothers of 538 (87.8% of eligible) case infants/fetuses with neural tube defects and mothers of 539 (88.2%) nonmalformed infants were interviewed about their SES. Reported addresses were linked to 1990 US census information to characterize neighborhoods. RESULTS: Twofold elevated risks were observed for several SES indicators. Risks were somewhat confounded by vitamin use, race/ethnicity, age, body mass index, and fever but remained elevated after adjustment. A risk gradient was seen with increasing number of lower SES indicators. Women with 1 to 3 and 4 to 6 lower SES indicators had adjusted odds ratios of 1.6 (1.1-2.2) and 3.2 (1.9-5.4), respectively, compared with women with no lower SES indicators. CONCLUSIONS: Both lower SES and residence in a SES-lower neighborhood increased the risk of an neural tube defect-affected pregnancy, with risks increasing across a gradient of SES indicators.

Wasserman, C R; Shaw, G M; Selvin, S; Gould, J B; Syme, S L

1998-01-01

40

Morphogen interpretation: the transcriptional logic of neural tube patterning.  

PubMed

The spatial organization of cell fates in developing tissues often involves the control of transcriptional networks by morphogen gradients. A well-studied example of this is the Sonic-hedgehog (Shh) controlled pattern of neuronal subtype differentiation in the vertebrate neural tube. Here we discuss recent studies involving genome wide analyses, functional experiments and theoretical models that have begun to characterise the molecular logic by which neural cells interpret Shh signalling. The view that emerges from this work is that cell identity results from the combined input of Shh signalling, uniformly expressed neural factors and the cross-regulatory network of downstream Shh target genes. A similar logic is also likely to underpin the patterning of many developing tissues. PMID:23725799

Cohen, Michael; Briscoe, James; Blassberg, Robert

2013-05-29

41

Neural network approach to background modeling for video object segmentation.  

PubMed

This paper presents a novel background modeling and subtraction approach for video object segmentation. A neural network (NN) architecture is proposed to form an unsupervised Bayesian classifier for this application domain. The constructed classifier efficiently handles the segmentation in natural-scene sequences with complex background motion and changes in illumination. The weights of the proposed NN serve as a model of the background and are temporally updated to reflect the observed statistics of background. The segmentation performance of the proposed NN is qualitatively and quantitatively examined and compared to two extant probabilistic object segmentation algorithms, based on a previously published test pool containing diverse surveillance-related sequences. The proposed algorithm is parallelized on a subpixel level and designed to enable efficient hardware implementation. PMID:18051181

Culibrk, Dubravko; Marques, Oge; Socek, Daniel; Kalva, Hari; Furht, Borko

2007-11-01

42

Folic acid to reduce neonatal mortality from neural tube disorders  

PubMed Central

Background Neural tube defects (NTDs) remain an important, preventable cause of mortality and morbidity. High-income countries have reported large reductions in NTDs associated with folic acid supplementation or fortification. The burden of NTDs in low-income countries and the effectiveness of folic acid fortification/supplementation are unclear. Objective To review the evidence for, and estimate the effect of, folic acid fortification/supplementation on neonatal mortality due to NTDs, especially in low-income countries. Methods We conducted systematic reviews, abstracted data meeting inclusion criteria and evaluated evidence quality using adapted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Where appropriate, meta-analyses were performed. Results Meta-analysis of three randomized controlled trials (RCTs) of folic acid supplementation for women with a previous pregnancy with NTD indicates a 70% [95% confidence interval (CI): 35–86] reduction in recurrence (secondary prevention). For NTD primary prevention through folic acid supplementation, combining one RCT with three cohort studies which adjusted for confounding, suggested a reduction of 62% (95% CI: 49–71). A meta-analysis of eight population-based observational studies examining folic acid food fortification gave an estimated reduction in NTD incidence of 46% (95% CI: 37–54). In low-income countries an estimated 29% of neonatal deaths related to visible congenital abnormalities are attributed to NTD. Assuming that fortification reduces the incidence of NTDs, but does not alter severity or case-fatality rates, we estimate that folic acid fortification could prevent 13% of neonatal deaths currently attributed to congenital abnormalities in low-income countries. Discussion Scale-up of periconceptional supplementation programmes is challenging. Our final effect estimate was therefore based on folic acid fortification data. If folic acid food fortification achieved 100% population coverage the number of NTDs in low-income countries could be approximately halved. Conclusion The evidence supports both folic acid supplementation and fortification as effective in reducing neonatal mortality from NTDs.

Blencowe, Hannah; Cousens, Simon; Modell, Bernadette; Lawn, Joy

2010-01-01

43

Contribution of VANGL2 mutations to isolated neural tube defects  

PubMed Central

Vangl2 was identified as the gene defective in the Looptail mouse model for neural tube defects (NTDs). This gene forms part of the planar cell polarity pathway, also called the non-canonical Frizzled/Dishevelled pathway, which mediates the morphogenetic process of convergent extension essential for proper gastrulation and neural tube formation in vertebrates. Genetic defects in PCP signaling have strongly been associated with NTDs in mouse models. To assess the role of VANGL2 in the complex etiology of NTDs in humans, we resequenced this gene in a large multi-ethnic cohort of 673 familial and sporadic NTD patients, including 453 open spina bifida and 202 closed spinal NTD cases. Six novel rare missense mutations were identified in 7 patients, five of which were affected with closed spinal NTDs. This suggests that VANGL2 mutations may predispose to NTDs in approximately 2.5% of closed spinal NTDs (5 in 202), at a frequency that is significantly different from that of 0.4% (2 in 453) detected in open spina bifida patients (P=0.027). Our findings strongly implicate VANGL2 in the genetic causation of spinal NTDs in a subset of patients and provide additional evidence for a pathogenic role of PCP signaling in these malformations.

Kibar, Zoha; Salem, Sandra; Bosoi, Ciprian M.; Pauwels, Elodie; De Marco, Patrizia; Merello, Elisa; Bassuk, Alexander G; Capra, Valeria; Gros, Philippe

2010-01-01

44

Bone morphogenetic proteins regulate hinge point formation during neural tube closure by dynamic modulation of apicobasal polarity  

PubMed Central

Background A critical event in neural tube closure is the formation of median (MHP) and dorsolateral hinge points (DLHP). Together, they buckle the ventral midline, elevate and juxtapose the neural folds for proper neural tube closure. Dynamic cell behaviors occur at hinge points (HPs), but their molecular regulation is largely unexplored. Bone Morphogenetic Proteins (BMPs) have been implicated in a variety of neural tube closure defects, although the underlying mechanisms are poorly understood. Methods In this study we used in vivo electroporations, high-resolution microscopy and biochemical analyses to explore the role of BMP signaling in chick midbrain neural tube closure. Results We identified a cell-cycle dependent BMP gradient in the midbrain neural plate, which results in low-level BMP activity at the MHP. We show that while BMP signaling does not play a role in midbrain cell-fate specification, its attenuation is necessary and sufficient for MHP formation and midbrain closure. BMP blockade induces MHP formation by regulating apical constriction and basal nuclear migration. Furthermore, BMP signaling is critically important for maintaining epithelial organization by biochemically interacting with apicobasal polarity proteins (e.g., PAR3). Thus prolonged BMP blockade disrupts apical junctions, desegregating the apical (PAR3+, ZO1+) and basolateral (LGL+) compartments. Direct apical LGL-GFP misexpression in turn is sufficient to induce ectopic HPs. Conclusions BMPs play a critical role in maintaining epithelial organization, a role that is conserved across species and tissue-types. Its’ cell-cycle dependent modulation in the neural plate dynamically regulates apicobasal polarity and helps bend, shape and close the neural tube.

Eom, Dae Seok; Amarnath, Smita; Fogel, Jennifer L.; Agarwala, Seema

2012-01-01

45

Embryonic hydromyelia: cystic dilatation of the lumbosacral neural tube in human embryos  

Microsoft Academic Search

In a large collection of human embryos (the Kyoto Collection of Human Embryos, Kyoto University), we encountered five cases with abnormal dilatation of the neural tube at the lumbosacral level. In these examples, the central canal was enlarged, and the roof plate of the neural tube was extremely thin and expanded. The mesenchymal tissue was scarce or lacking between the

Junichi Ikenouchi; Chigako Uwabe; Tomoko Nakatsu; Mizuki Hirose; Kohei Shiota

2002-01-01

46

Promoter haplotype combinations for the human PDGFRA gene are associated with risk of neural tube defects  

Microsoft Academic Search

Recent animal studies suggested that deregulated expression of the platelet-derived growth factor receptor alpha (PDGFR?) may contribute to the failure of normal neural tube closure (NTC). There is also suggestive evidence that the promoter haplotype of the PDGFRA is associated with genetic susceptibility in human neural tube defects (NTDs). The purpose of our study was to investigate the association between

Huiping Zhu; Ned J Wicker; Kelly Volcik; Jing Zhang; Gary M Shaw; Edward J Lammer; Lucina Suarez; Mark Canfield; Richard H Finnell

2004-01-01

47

Cell polarity pathways converge and extend to regulate neural tube closure.  

PubMed

Neural tube defects, such as spinabifida, craniorachischisis and anencephaly, are some of the most common birth defects in humans. Recent studies in mouse model systems suggest that craniorachischisis is associated with mutations in genes that regulate cell polarity. Using Xenopus as a model system, Wallingford and Harland have now shed light on the mechanism by which these pathways affect neural tube closure. PMID:12946622

Zohn, Irene E; Chesnutt, Catherine R; Niswander, Lee

2003-09-01

48

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

PubMed Central

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

Ramirez-Altamirano, Maria de Jesus; Fenton-Navarro, Patricia; Sivet-Chinas, Elvira; Harp-Iturribarria, Flor de Maria; Martinez-Cruz, Ruth; Cruz, Pedro Hernandez; Cruz, Margarito Martinez; Perez-Campos, Eduardo

2012-01-01

49

A Homeodomain Protein Code Specifies Progenitor Cell Identity and Neuronal Fate in the Ventral Neural Tube  

Microsoft Academic Search

Distinct classes of neurons are generated at defined positions in the ventral neural tube in response to a gradient of Sonic Hedgehog (Shh) activity. A set of homeodomain transcription factors expressed by neural progenitors act as intermediaries in Shh-dependent neural patterning. These homeodomain factors fall into two classes: class I proteins are repressed by Shh and class II proteins require

James Briscoe; Alessandra Pierani; Thomas M. Jessell; Johan Ericson

2000-01-01

50

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

PubMed

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 protocols optimized for the culture of rat NC. The advantages of this protocol compared to previous methods are that 1) the cells are not grown on a feeder layer, 2) FACS is not required to obtain a relatively pure NC population, 3) premigratory NC cells are isolated and 4) results are easily quantified. Furthermore, this protocol can be used for isolation of NC from any mutant mouse model, facilitating the study of NC characteristics with different genetic manipulations. The limitation of this approach is that the NC is removed from the context of the embryo, which is known to influence the survival, migration and differentiation of the NC. PMID:22688801

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

2012-06-02

51

The relationship between Sonic hedgehog signalling, cilia and neural tube defects  

PubMed Central

The Hedgehog signalling pathway is essential for many aspects of normal embryonic development, including formation and patterning of the neural tube. Absence of Shh ligand is associated with the midline defect holoprosencephaly, while increased Shh signalling is associated with exencephaly and spina bifida. To complicate this apparently simple relationship, mutation of proteins required for function of cilia often leads to impaired Shh signalling and to disruption of neural tube closure. In this manuscript, we review the literature on Shh pathway mutants and discuss the relationship between Shh signalling, cilia and neural tube defects.

Murdoch, Jennifer N.; Copp, Andrew J.

2013-01-01

52

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

PubMed Central

Pregnancies complicated by maternal diabetes have long been known to carry a higher risk for congenital malformations, such as neural tube defects. Using the FVB inbred mouse strain and the Streptozotocin-induced diabetes model, we tested whether the incidence of neural tube defects in diabetic pregnancies can be modulated by maternal diet. In a comparison of two commercial mouse diets, which are considered nutritionally replete, we found that maternal consumption of the unfavorable diet was associated with a more than three-fold higher rate of neural tube defects. Our results demonstrate that maternal diet can act as a modifier of the risk for abnormal development in high-risk pregnancies, and provide support for the possibility that neural tube defects in human diabetic pregnancies might be preventable by optimized maternal nutrition.

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

2010-01-01

53

Neural Tube Defects In Mice Exposed To Tap Water  

PubMed Central

In May of 2006 we suddenly began to observe neural tube defects (NTDs) in embryos of untreated control mice. We hypothesized the mice were being exposed unknowingly to a teratogenic agent and investigated the cause. Our results suggested that NTDs were not resulting from bedding material, feed, strain or source of the mice. Additionally, mice were negative for routine and comprehensive screens of pathogens. To further test whether the NTDs resulted from infectious or genetic cause localized to our facility, we obtained three strains of timed pregnant mice from commercial suppliers located in 4 different states. All strains and sources of mice arrived in our laboratory with NTDs, implying that commercially available mice were possibly exposed to a teratogen prior to purchase. Our investigation eventually concluded that exposure to tap water was causing the NTDs. The incidence of NTDs was greatest in purchased mice provided tap water and lowest in purchased mice provided distilled deionized water (DDI). Providing mice DDI water for two generations (F2-DDI) eliminated the NTDs. When F2-DDI mice were provided tap water from three different urban areas prior to breeding, their offspring again developed NTDs. Increased length of exposure to tap water significantly increased the incidence of NTDs. These results indicate that a contaminant in municipal tap water is likely causing NTDs in mice. The unknown teratogen appears to have a wide geographic distribution but has not yet been identified. Water analysis is currently underway to identify candidate contaminants that might be responsible for the malformations.

Mallela, Murali K; Werre, Stephen R; Hrubec, Terry C

2010-01-01

54

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

PubMed

Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes to block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1(+) migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug(+) pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1(+) migrating NCCs but reduced Pax7 expression and fewer Slug(+) pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube development by tightly coordinating cell proliferation and differentiation during neurulation. PMID:23438940

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

2013-02-21

55

Oxidant regulation of gene expression and neural tube development: Insights gained from diabetic pregnancy on molecular causes of neural tube defects  

Microsoft Academic Search

  \\u000a \\u000a Aims\\/hypothesis. Maternal diabetes increases oxidative stress in embryos. Maternal diabetes also inhibits expression of embryonic genes, most\\u000a notably, Pax-3, which is required for neural tube closure. Here we tested the hypothesis that oxidative stress inhibits expression of Pax-3, thereby providing a molecular basis for neural tube defects induced by diabetic pregnancy.\\u000a \\u000a \\u000a \\u000a \\u000a Methods. Maternal diabetes-induced oxidative stress was blocked with

T. I. Chang; M. Horal; S. K. Jain; F. Wang; R. Patel; M. R. Loeken

2003-01-01

56

Preventing neural tube defects: The importance of periconceptional folic acid supplements  

Microsoft Academic Search

Objective: To inform the obstetrician-gynecologist of recent scientific evidence regarding the use of supplemental folic acid for prevention of neural tube defects (NTDs).Data Sources: We selected English language articles via MEDLINE published from January 1990 through February 1997, using the search terms “folic acid” and “neural tube defect.” Additional sources were identified through cross-referencing and through searching selected journals published

GregoryJ Locksmith; Patrick Duff

1998-01-01

57

The etiology of neural tube defects: the role of folic acid  

Microsoft Academic Search

DiscussionWhile the cause of neural tube defects in humans is considered to be multifactorial, it is apparent that folic acid can prevent 70% of open neural tube defects. Even in laboratory animals with known genetic defects, folic acid can prevent the genetic expression.ConclusionWhile some of the metabolic pathways for folic acid are known, the true effects of folic acid on

David G. McLone

2003-01-01

58

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

PubMed

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

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

2012-08-15

59

Cell polarity pathways converge and extend to regulate neural tube closure  

Microsoft Academic Search

Neural tube defects, such as spinabifida, craniorachischisis and anencephaly, are some of the most common birth defects in humans. Recent studies in mouse model systems suggest that craniorachischisis is associated with mutations in genes that regulate cell polarity. Using Xenopus as a model system, Wallingford and Harland have now shed light on the mechanism by which these pathways affect neural

Irene E. Zohn; Catherine R. Chesnutt; Lee Niswander

2003-01-01

60

Bone morphogenetic proteins regulate neural tube closure by interacting with the apicobasal polarity pathway  

PubMed Central

During neural tube closure, specialized regions called hinge points (HPs) display dynamic and polarized cell behaviors necessary for converting the neural plate into a neural tube. The molecular bases of such cell behaviors (e.g. apical constriction, basal nuclear migration) are poorly understood. We have identified a two-dimensional canonical BMP activity gradient in the chick neural plate that results in low and temporally pulsed BMP activity at the ventral midline/median hinge point (MHP). Using in vivo manipulations, high-resolution imaging and biochemical analyses, we show that BMP attenuation is necessary and sufficient for MHP formation. Conversely, BMP overexpression abolishes MHP formation and prevents neural tube closure. We provide evidence that BMP modulation directs neural tube closure via the regulation of apicobasal polarity. First, BMP blockade produces partially polarized neural cells, which retain contact with the apical and basal surfaces but where basolateral proteins (LGL) become apically localized and apical junctional proteins (PAR3, ZO1) become targeted to endosomes. Second, direct LGL misexpression induces ectopic HPs identical to those produced by noggin or dominant-negative BMPR1A. Third, BMP-dependent biochemical interactions occur between the PAR3-PAR6-aPKC polarity complex and phosphorylated SMAD5 at apical junctions. Finally, partially polarized cells normally occur at the MHP, their frequencies inversely correlated with the BMP activity gradient in the neural plate. We propose that spatiotemporal modulation of the two-dimensional BMP gradient transiently alters cell polarity in targeted neuronal cells. This ensures that the neural plate is flexible enough to be focally bent and shaped into a neural tube, while retaining overall epithelial integrity.

Eom, Dae Seok; Amarnath, Smita; Fogel, Jennifer L.; Agarwala, Seema

2011-01-01

61

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

PubMed

Head morphogenesis is a complex process that is controlled by multiple signaling centers. The most common defects of cranial development are craniofacial defects, such as cleft lip and cleft palate, and neural tube defects, such as anencephaly and encephalocoele in humans. More than 400 genes that contribute to proper neural tube closure have been identified in experimental animals, but only very few causative gene mutations have been identified in humans, supporting the notion that environmental influences are critical. The intrauterine environment is influenced by maternal nutrition, and hence, maternal diet can modulate the risk for cranial and neural tube defects. This article reviews recent progress toward a better understanding of nutrients during pregnancy, with particular focus on mouse models for defective neural tube closure. At least four major patterns of nutrient responses are apparent, suggesting that multiple pathways are involved in the response, and likely in the underlying pathogenesis of the defects. Folic acid has been the most widely studied nutrient, and the diverse responses of the mouse models to folic acid supplementation indicate that folic acid is not universally beneficial, but that the effect is dependent on genetic configuration. If this is the case for other nutrients as well, efforts to prevent neural tube defects with nutritional supplementation may need to become more specifically targeted than previously appreciated. Mouse models are indispensable for a better understanding of nutrient-gene interactions in normal pregnancies, as well as in those affected by metabolic diseases, such as diabetes and obesity. © 2013 Wiley Periodicals, Inc. PMID:24124024

Kappen, Claudia

2013-10-04

62

Birth prevalence and recurrence rates of neural tube defects in southern Alberta in 1970-81.  

PubMed Central

Given the observed variation in birth prevalence and recurrence rates of neural tube defects, it is important to obtain such data specific to a given locality for research and genetic counseling purposes. A review of hospital medical charts, the patient lists of the Medical Genetics and Myelomeningocele clinics at Alberta Children's Hospital and data from the Canadian Congenital Anomalies Surveillance System revealed the annual birth prevalence rate of neural tube defects in southern Alberta in 1970-81 to be 1.62/1000 total births. This figure suggests southern Alberta to be a low-frequency area. There was no significant variation in the annual rates of spina bifida, encephalocele or all neural tube defects combined over the study period. A significant linear decline in the frequency of births of anencephalic infants, however, was noted (p = 0.025). Information on the total reproductive history of the mothers revealed that the empiric risk of recurrence of a neural tube defect was 2.2%, and the risk to all siblings was estimated to be 2.3%. In future prevalence studies multiple sources of case ascertainment should be used, including data on pregnancies terminated because of a fetal neural tube defect.

Thunem, N Y; Lowry, R B; Tucker, B J; Medd, B W

1988-01-01

63

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

PubMed Central

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

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

2013-01-01

64

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

PubMed

Syndecan 4 (Sdc4) is a cell-surface heparan sulfate proteoglycan (HSPG) that regulates gastrulation, neural tube closure and directed neural crest migration in Xenopus development. To determine whether Sdc4 participates in Wnt/PCP signaling during mouse development, we evaluated a possible interaction between a null mutation of Sdc4 and the loop-tail allele of Vangl2. Sdc4 is expressed in multiple tissues, but particularly in the non-neural ectoderm, hindgut and otic vesicles. Sdc4;Vangl2(Lp) compound mutant mice have defective spinal neural tube closure, disrupted orientation of the stereocilia bundles in the cochlea and delayed wound healing, demonstrating a strong genetic interaction. In Xenopus, co-injection of suboptimal amounts of Sdc4 and Vangl2 morpholinos resulted in a significantly greater proportion of embryos with defective neural tube closure than each individual morpholino alone. To probe the mechanism of this interaction, we overexpressed or knocked down Vangl2 function in HEK293 cells. The Sdc4 and Vangl2 proteins colocalize, and Vangl2, particularly the Vangl2(Lp) mutant form, diminishes Sdc4 protein levels. Conversely, Vangl2 knockdown enhances Sdc4 protein levels. Overall HSPG steady-state levels were regulated by Vangl2, suggesting a molecular mechanism for the genetic interaction in which Vangl2(Lp/+) enhances the Sdc4-null phenotype. This could be mediated via heparan sulfate residues, as Vangl2(Lp/+) embryos fail to initiate neural tube closure and develop craniorachischisis (usually seen only in Vangl2(Lp/Lp)) when cultured in the presence of chlorate, a sulfation inhibitor. These results demonstrate that Sdc4 can participate in the Wnt/PCP pathway, unveiling its importance during neural tube closure in mammalian embryos. PMID:23760952

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

2013-06-12

65

Disruption of palladin results in neural tube closure defects in mice  

Microsoft Academic Search

Palladin is a newly identified actin-associated protein which was proposed to be involved in actin cytoskeleton organization and nervous system development. Here, we show that inactivation of palladin leads to embryonic lethality due to severe defects of cranial neural tube closure and herniation of liver and intestine. It was found that palladin?\\/? embryos died around E15.5 and developed cranial neural

Huijun Luo; Xuesong Liu; Fang Wang; Qiuhua Huang; Shuhong Shen; Long Wang; Guojiang Xu; Xia Sun; Hui Kong; Mingmin Gu; Saijuan Chen; Zhu Chen; Zhugang Wang

2005-01-01

66

Morphogenetic movements driving neural tube closure in Xenopus require myosin IIB  

PubMed Central

Vertebrate neural tube formation involves two distinct morphogenetic events -convergent extension (CE) driven by medio-lateral cell intercalation, and bending of the neural plate driven largely by cellular apical constriction. However, the cellular and molecular biomechanics of these processes are not understood. Here, using tissue-targeting techniques, we show that the myosin IIB motor protein complex is essential for both these processes, as well as for conferring resistance to deformation to the neural plate tissue. We show that myosin IIB is required for actin-cytoskeletal organization in both superficial and deep layers of the Xenopus neural plate. In the superficial layer, myosin IIB is needed for apical actin accumulation, which underlies constriction of the neurepithelial cells, and that ultimately drive neural plate bending, whereas in the deep neural cells myosin IIB organizes a cortical actin cytoskeleton, which we describe for the first time, and that is necessary for both normal neural cell cortical tension and shape and for autonomous CE of the neural tissue. We also show that myosin IIB is required for resistance to deformation (‘stiffness’) in the neural plate, indicating that the cytoskeleton-organizing roles of this protein translate in regulation of the biomechanical properties of the neural plate at the tissue-level.

Rolo, Ana; Skoglund, Paul; Keller, Ray

2010-01-01

67

Coordinate regulation of neural tube patterning and proliferation by TGFbeta and WNT activity.  

PubMed

Pattern formation and growth must be tightly coupled during embryonic development. In vertebrates, however, little is known of the molecules that serve to link these two processes. Here we show that bone morphogenetic proteins (BMP) coordinate the acquisition of pattern information and the stimulation of proliferation in the embryonic spinal neural tube. We have blocked BMP and transforming growth factor-beta superfamily (TGFbeta) function in the chick embryo using Noggin, a BMP antagonist, and siRNA against Smad4. We show that BMPs/TGFbetas are necessary to regulate pattern formation and the specification of neural progenitor populations in the dorsal neural tube. BMPs also serve to establish discrete expression domains of Wnt ligands, receptors, and antagonists along the dorsal-ventral axis of the neural tube. Using the extracellular domain of Frizzled 8 to block Wnt signaling and Wnt3a ligand misexpression to activate WNT signaling, we demonstrate that the Wnt pathway acts mitogenically to expand the populations of neuronal progenitor cells specified by BMP. Thus, BMPs, acting through WNTs, couple patterning and growth to generate dorsal neuronal fates in the appropriate proportions within the neural tube. PMID:15385163

Chesnutt, Catherine; Burrus, Laura W; Brown, Anthony M C; Niswander, Lee

2004-10-15

68

Helium Background in the D0 Detector Related to the Photomultiplier Tubes  

SciTech Connect

Helium is present in the earth's atmosphere at about 5 parts per million. (ref. Technology of liquid helium, NBS monograph 111). The D-Zero detector uses helium for the cryogenic cooling of its superconducting magnet and visible light photon counter (VLPC) electronics chips. In addition, the tevatron accelerator has superconducting magnets that use helium Due to the possibility of leaks or releases of helium from these helium lines and components, the background helium level in the collision hall may exceed the natural level of 5 ppm. This engineering note will quantify the probability and level of helium background in the D-Zero detector. The photomultiplier tubes used in the D-Zero detector are sensitive to an elevated helium atmosphere. This is due to the permeation rate of helium gas through the glass tube, into the vacuum space inside. It is very important for the helium atmosphere surrounding the photomultiplier tubes is known and controlled. If the level of helium in the vacuum tube reaches a level above 5 ppm, then the photomuliplier tube may no longer work as designed. The process is an irreversible one.

Rucinski, R.; /Fermilab

1998-04-09

69

Generalized correlation of refrigerant mass flow rate through adiabatic capillary tubes using artificial neural network  

Microsoft Academic Search

A capillary tube is a common expansion device widely used in small-scale refrigeration and air-conditioning systems. Generalized correlation method for refrigerant flow rate through adiabatic capillary tubes is developed by combining dimensional analysis and artificial neural network (ANN). Dimensional analysis is utilized to provide the generalized dimensionless parameters and reduce the number of input parameters, while a three-layer feedforward ANN

Chun-Lu Zhang

2005-01-01

70

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

PubMed

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

Massarwa, R'ada; Niswander, Lee

2012-11-22

71

Coordinate regulation of neural tube patterning and proliferation by TGF? and WNT activity  

Microsoft Academic Search

Pattern formation and growth must be tightly coupled during embryonic development. In vertebrates, however, little is known of the molecules that serve to link these two processes. Here we show that bone morphogenetic proteins (BMP) coordinate the acquisition of pattern information and the stimulation of proliferation in the embryonic spinal neural tube. We have blocked BMP and transforming growth factor-?

Catherine Chesnutt; Laura W. Burrus; Anthony M. C. Brown; Lee Niswander

2004-01-01

72

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

ERIC Educational Resources Information Center

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

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

2010-01-01

73

Costs and Effects of Prenatal Screening Methods for Down Syndrome and Neural Tube Defects  

Microsoft Academic Search

Objectives: To evaluate prenatal screening methods for Down syndrome and neural tube defects (NTD) with regard to costs per detected case and the number of screening-related miscarriages. Methods: The screening methods compared were risk assessment tests, i.e. serum tests and nuchal translucency measurement (NT), and invasive testing through chorionic villus sampling (CVS) or amniocentesis. Costs, the number of cases detected

Mirjam Hoogendoorn; Silvia M. A. A. Evers; Peter C. J. I. Schielen; Marianne L. L. van Genugten; G. Ardine de Wit; André J. H. A. Ament

2008-01-01

74

Mice defective in Trpm6 show embryonic mortality and neural tube defects  

PubMed Central

The syndrome of hypomagnesemia with secondary hypocalcemia is caused by defective TRPM6. This protein is an ion channel that also contains a kinase in its C-terminus. It is usually diagnosed in childhood and, without treatment with supplemental Mg, affected children suffer from mental retardation, seizures and retarded development. We developed a mouse lacking Trpm6 in order to understand in greater detail the function of this protein. In contrast to our expectations, Trpm6?/? mice almost never survived to weaning. Many mice died by embryonic day 12.5. Most that survived to term had neural tube defects consisting of both exencephaly and spina bifida occulta, an unusual combination. Feeding dams a high Mg diet marginally improved offspring survival to weaning. The few Trpm6?/? mice that survived were fertile but matings between Trpm6?/? mice produced no viable pregnancies. Trpm6+/? mice had normal electrolytes except for modestly low plasma [Mg]. In addition, some Trpm6+/? mice died prematurely. Absence of Trpm6 produces an apparently different phenotype in mice than in humans. The presence of neural tube defects identifies a previously unsuspected role of Trpm6 in effecting neural tube closure. This genetic defect produces one of very few mouse models of spina bifida occulta. These results point to a critical role of Trpm6 in development and suggest an important role in neural tube closure.

Walder, Roxanne Y.; Yang, Baoli; Stokes, John B.; Kirby, Patricia A.; Cao, Xiao; Shi, Peijun; Searby, Charles C.; Husted, Russell F.; Sheffield, Val C.

2009-01-01

75

The Role of Folic Acid Fortification in Neural Tube Defects: A Review  

Microsoft Academic Search

The worldwide prevalence of neural tube defects (NTDs) has fallen noticeably during the past thirty years but the specific etiology and causative mechanism of NTDs remain unknown. Since introduction of mandatory fortification of grains with folic acid, a further decrease in NTD prevalence has been reported in North America and other countries with large variations among ethnic subgroups. However, a

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

2012-01-01

76

Improving the health and well-being of women at risk for neural tube defect recurrence  

Microsoft Academic Search

There is growing interest in providing women with internatal care, a package of healthcare and ancillary services that can improve their health during the period after the termination of one pregnancy but before the conception of the next pregnancy. Women who have had a pregnancy affected by a neural tube defect can especially benefit from internatal care because they are

Tasneem Husain

2009-01-01

77

Genetic interaction between members of the Vangl family causes neural tube defects in mice  

PubMed Central

Neural tube defects (NTDs) are very frequent congenital abnormalities in humans. Recently, we have documented independent association of Vangl1 and Vangl2 gene mutations with NTDs. In the Looptail mouse, homozygosity (but not heterozygosity) for loss-of-function alleles at Vangl2 causes the severe NTD craniorachischisis, whereas heterozygosity for mutant variants of VANGL1 is associated with NTDs in a human cohort of sporadic and familial cases. To understand the role of Vangl1 in normal development, we created a mouse mutant with an inactivating mutation at Vangl1 (Vangl1gt). Vangl1 shows a dynamic pattern of expression in the developing neural tube and notochord at the time of neural tube closure. Vangl1gt/+ heterozygotes and Vangl1gt/gt homozygotes are viable and fertile, although Vangl1gt/gt display subtle alterations in polarity of inner hair cells of the cochlea. Remarkably, and as opposed to healthy Vangl1gt/+ and Vangl2lp/+ heterozygotes, Vangl1gt/+;Vangl2lp/+ double heterozygotes show profound developmental defects that include severe craniorachischisis, inner ear defects (disorganization of the stereociliary bundles of hair cells of the organ of Corti), and cardiac abnormality (aberrant right subclavian artery). These results show that genetic interaction between Vangl1 and Vangl2 genes causes neural tube defects and raise the possibility that interaction between individual Vangl genes and other genetic loci and/or environmental factors may additionally contribute to the etiology of NTDs.

Torban, Elena; Patenaude, Anne-Marie; Leclerc, Severine; Rakowiecki, Staci; Gauthier, Susan; Andelfinger, Gregor; Epstein, Douglas J.; Gros, Philippe

2008-01-01

78

Effects of maternal oral morphine consumption on neural tube development in Wistar rats  

Microsoft Academic Search

Opiate abuse during pregnancy may result in abnormal nervous system function. In order to evaluate the effects of morphine on the development of the nervous system, the present study focused on the effects of maternal morphine consumption on neural tube development in Wistar rats.Female Wistar rats (250–300 g) were crossed with male rats and coupling time was recorded (embryonic day

Shiva Nasiraei-Moghadam; Hedayat Sahraei; Hossein Bahadoran; Mehrangiz Sadooghi; Seyed Hossein Salimi; Gholam Reza Kaka; Hossein Imani; Hossein Mahdavi-Nasab; Hossein Dashtnavard

2005-01-01

79

Morphogenetic movements during axolotl neural tube formation tracked by digital imaging  

Microsoft Academic Search

During neurulation in vertebrate embryos, epithelial cells of the neural plate undergo complex morphogenetic movements that culminate in rolling of the plate into a tube. Resolution of the determinants of this process requires an understanding of the precise movements of cells within the epithelial sheet. A computer algorithm that allows automated tracking of epithelial cells visible in digitized video images

G. Wayne Brodland; Michael J. Scott; Andrew F. MacLean; M. Globus; S. Vethamany-Globus; R. Gordon; Jim H. Veldhuis; R. Maestro

1996-01-01

80

Analysis of the human folate receptor ? gene for an association with neural tube defects  

Microsoft Academic Search

The folate receptor ? (FR?) gene encodes a receptor that binds and transports 5-methyltetrahydrofolate. FR? polymorphisms may potentially alter folate delivery and are likely candidates for an association with neural tube defect (NTD) risk. To look for association between FR? polymorphisms we studied NTD-affected children and their parents (254 triads) recruited throughout Ireland and a control population of 296 pregnant

Valerie B O’Leary; James L Mills; Peadar N Kirke; Anne Parle-McDermott; Deborah A Swanson; Andrea Weiler; Faith Pangilinan; Mary Conley; Anne M Molloy; Miriam Lynch; Christopher Cox; John M Scott; Lawrence C Brody

2003-01-01

81

Should women at high risk of neural tube defect have an amniocentesis?  

Microsoft Academic Search

As part of an investigation into the practical problems of a maternal serum alphafetoprotein (AFP) neural tube defect (NTD) screening programme carried out in Mid Glamorgan, South Wales, between 1977 and 1979, obstetricians were recommended to refer women with high risk pregnancies directly for counselling, high resolution ultrasonography, and amniocentesis without first carrying out serum screening. Out of 15 687

K M Laurence; G Elder; K T Evans; B M Hibbard; M Hoole; C J Roberts

1985-01-01

82

Time trends in neural tube defects prevalence in relation to preventive strategies: an international study  

Microsoft Academic Search

OBJECTIVE: To examine time trends in neural tube defects (NTD) prevalence from 1987 to 1996 in relation to the primary prevention policies for folic acid supplementation strategies in different countries. DESIGN: Retrospective time trends analysis of NTD prevalence. SETTING: 11 birth defect registries of congenital malformations participating in the International Clearinghouse for Birth Defects Monitoring System, in the period from

A. Rosano; D. Smithells; L. Cacciani; B. Botting; E. Castilla; M. Cornel; D. Erickson; J. Goujard; L. Irgens; P. Merlob; E. Robert; C. Siffel; C. Stoll; Y. Sumiyoshi

1999-01-01

83

Neural Tube Defects and Maternal Residential Proximity to Agricultural Pesticide Applications  

Microsoft Academic Search

Residential proximity to applications of agricultural pesticides may be an important source of exposure to agents that have been classified as developmental toxins. Data on two case-control study populations of infants with neural tube defects (NTDs) and nonmalformed controls delivered in California between 1987 and 1991 were pooled to investigate whether maternal residential proximity to applications of specific pesticides or

Rudolph P. Rull; Beate Ritz; Gary M. Shaw

2006-01-01

84

derived growth factor ? -receptor gene predispose to human neural tube defects  

Microsoft Academic Search

Neural tube defects (NTDs), including anencephaly and spina bifida, are multifactorial diseases that occur with an incidence of 1 in 300 births in the United Kingdom 1 . Mouse models have indicated that deregulated expression of the gene encoding the platelet-derived growth factor ? -receptor (Pdgfra) causes congenital NTDs (refs. 2-4), whereas mutant forms of Pax-1 that have been associated

Paul H. L. J. Joosten; Mascha Toepoel; Edwin C. M. Mariman; J. J. Van Zoelen

85

Methanol-induced neural tube defects in mice: Characterization of lesions, target and teratogen  

Microsoft Academic Search

The present studies investigated the hypothesis that methanol induces neural tube defects (e.g., exenephaly) through the cytotoxic action of its metabolite, formate, upon embryonic neuroepithelium during neurulation. Methanol was tested because of concerns raised by the proposed heavier use of this alcohol in automobile fuels, which could result in increased exposure of the general public. Neurulation (gestational days [GD] 7-9

Bolon

1993-01-01

86

Vitamin supplements and the risk for congenital anomalies other than neural tube defects  

Microsoft Academic Search

Randomized trials, supported by many observational studies, have shown that periconceptional use of folic acid, alone or in multivitamin supplements, is effective for the primary prevention of neural tube defects (NTDs). Whether this is true also for other congenital anomalies is a complex issue and the focus of this review. It is useful to consider the evidence not only for

Lorenzo D. Botto; Richard S. Olney; J. David Erickson

2004-01-01

87

Heat Transfer Coefficient and Friction Factor Prediction of Corrugated Tubes Combined With Twisted Tape Inserts Using Artificial Neural Network  

Microsoft Academic Search

In the research described here, artificial neural network (ANN) approach has been utilized to characterize the thermohydraulic behavior of corrugated tubes combined with twisted tape inserts in a turbulent flow regime. The experimental data sets were extracted from 57 tubes, 9 and 3 spirally corrugated tubes with varying geometries combined with 5 and 4 twisted tapes with different pitches. The

Mohammad Reza Jafari Nasr; Ali Habibi Khalaj

2010-01-01

88

Deletion of Mthfd1l causes embryonic lethality and neural tube and craniofacial defects in mice.  

PubMed

Maternal supplementation with folic acid is known to reduce the incidence of neural tube defects (NTDs) by as much as 70%. Despite the strong clinical link between folate and NTDs, the biochemical mechanisms through which folic acid acts during neural tube development remain undefined. The Mthfd1l gene encodes a mitochondrial monofunctional 10-formyl-tetrahydrofolate synthetase, termed MTHFD1L. This gene is expressed in adults and at all stages of mammalian embryogenesis with localized regions of higher expression along the neural tube, developing brain, craniofacial structures, limb buds, and tail bud. In both embryos and adults, MTHFD1L catalyzes the last step in the flow of one-carbon units from mitochondria to cytoplasm, producing formate from 10-formyl-THF. To investigate the role of mitochondrial formate production during embryonic development, we have analyzed Mthfd1l knockout mice. All embryos lacking Mthfd1l exhibit aberrant neural tube closure including craniorachischisis and exencephaly and/or a wavy neural tube. This fully penetrant folate-pathway mouse model does not require feeding a folate-deficient diet to cause this phenotype. Maternal supplementation with sodium formate decreases the incidence of NTDs and partially rescues the growth defect in embryos lacking Mthfd1l. These results reveal the critical role of mitochondrially derived formate in mammalian development, providing a mechanistic link between folic acid and NTDs. In light of previous studies linking a common splice variant in the human MTHFD1L gene with increased risk for NTDs, this mouse model provides a powerful system to help elucidate the specific metabolic mechanisms that underlie folate-associated birth defects, including NTDs. PMID:23267094

Momb, Jessica; Lewandowski, Jordan P; Bryant, Joshua D; Fitch, Rebecca; Surman, Deborah R; Vokes, Steven A; Appling, Dean R

2012-12-24

89

DiI labeling and homeobox gene Islet1 expression reveal the contribution of ventral neural tube cells to the formation of the avian trigeminal ganglion  

Microsoft Academic Search

Cells of the neural tube are thought to be committed to form only the central nervous system, whereas the peripheral nervous system is believed to be derived from neural crest cells and from placodes, which are specialized regions of the surface ectoderm. Neural crest cells arise early from the dorsal part of the neural tube. The possibility that after emigration

G. S. Sohal; D. E. Bockman; M. M. Ali; N. T. Tsai

1996-01-01

90

Control of cell pattern in the neural tube: motor neuron induction by diffusible factors from notochord and floor plate.  

PubMed

The identity of cell types generated along the dorsoventral axis of the neural tube depends on inductive signals that derive from both mesodermal and neural cells. To define the nature of these signals, we have analyzed the differentiation of cells in neural plate explants. Motor neurons and neural crest cells differentiate in vitro from appropriate regions of the neural plate, indicating that the specification of cell fate along the dorsoventral axis of the neural tube begins at the neural plate stage. Motor neuron differentiation can be induced by a diffusible factor that derives initially from the notochord and later from floor plate cells. By contrast, floor plate induction requires contact with the notochord. Thus, the identity and patterning of neural cell types appear to involve distinct contact-mediated and diffusible signals from the notochord and floor plate. PMID:8500163

Yamada, T; Pfaff, S L; Edlund, T; Jessell, T M

1993-05-21

91

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

PubMed Central

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

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

2013-01-01

92

Distinct regulatory mechanisms act to establish and maintain pax3 expression in the developing neural tube.  

PubMed

Pattern formation in developing tissues is driven by the interaction of extrinsic signals with intrinsic transcriptional networks that together establish spatially and temporally restricted profiles of gene expression. How this process is orchestrated at the molecular level by genomic cis-regulatory modules is one of the central questions in developmental biology. Here we have addressed this by analysing the regulation of Pax3 expression in the context of the developing spinal cord. Pax3 is induced early during neural development in progenitors of the dorsal spinal cord and is maintained as pattern is subsequently elaborated, resulting in the segregation of the tissue into dorsal and ventral subdivisions. We used a combination of comparative genomics and transgenic assays to define and dissect several functional cis-regulatory modules associated with the Pax3 locus. We provide evidence that the coordinated activity of two modules establishes and refines Pax3 expression during neural tube development. Mutational analyses of the initiating element revealed that in addition to Wnt signaling, Nkx family homeodomain repressors restrict Pax3 transcription to the presumptive dorsal neural tube. Subsequently, a second module mediates direct positive autoregulation and feedback to maintain Pax3 expression. Together, these data indicate a mechanism by which transient external signals are converted into a sustained expression domain by the activities of distinct regulatory elements. This transcriptional logic differs from the cross-repression that is responsible for the spatiotemporal patterns of gene expression in the ventral neural tube, suggesting that a variety of circuits are deployed within the neural tube regulatory network to establish and elaborate pattern formation. PMID:24098141

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

2013-10-03

93

Predicting the Crushing Behavior of Axially Loaded Elliptical Composite Tubes Using Artificial Neural Networks  

NASA Astrophysics Data System (ADS)

In this research work, the artificial neural networks (ANN) technique is used in predicting the crushing behavior and energy absorption characteristics of axially-loaded glass fiber/epoxy composite elliptical tubes. Predictions are compared to actual experimental results obtained from the literature and are shown to be in good agreement. Effects of parameters such as network architecture, number of hidden layers and number of neurons per hidden layer are also considered. The study shows that ANN techniques can effectively be used to predict the crushing response and the energy absorption characteristics of elliptical composite tubes with various ellipticity ratios subjected to axial loading.

El Kadi, Hany

2008-11-01

94

Folic acid for prevention of neural tube defects: pediatric anticipatory guidance.  

PubMed

The incidence of neural tube defects including myelomeningocele, which is one of the most common causes of infant and childhood disability, can be substantially reduced by folic acid supplementation to the diet of women before and during the early stages of pregnancy. All females of childbearing age should be taking folic acid supplements of 0.4 mg/day (400 micrograms/day) and consuming a diet rich in folate. Because many pregnancies are unplanned, supplementation should not await plans for pregnancy. Because pediatric nurse practitioners are in frequent contact with both adolescent patients and patients whose mothers are of childbearing age, and because pediatric nurse practitioners have an interest in preventing neural tube defects in future pediatric patients, they are in a good position to provide the necessary anticipatory guidance regarding the critical need for adequate folic acid intake by females of childbearing age. This article discusses and includes guidelines for providing this anticipatory guidance. PMID:9592437

Morrow, J D; Kelsey, K

95

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

PubMed

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

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

2012-04-03

96

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

PubMed

The objective of the present study was to determine the presence of risk factors for the occurrence of neural tube defects. Data for 33,535 births which occurred at Hospital do Servidor Público Estadual de São Paulo from July 1973 to December 1986 were collected in a prospective manner as recommended by "Estudo Colaborativo Latino-Americano de Malformações Congênitas" (ECLAMC, Collaborative Latin American Study on Congenital Malformations). Twenty-six cases of neural tube defects were detected (0.77/1000 births). Of these, 11 were cases of spina bifida (0.39/1000 births), 9 of anencephaly (0.27/1000 births) and 6 of encephalocele (0.18/1000 births). We observed a higher frequency of polyhydramnios, premature labor, Apgar scores of less than 7 at the first and fifth minutes, low birth weight and intrauterine growth retardation. PMID:1341003

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

97

Metabolic effects of C677T and A1298C mutations at the MTHFR gene in Brazilian children with neural tube defects  

Microsoft Academic Search

Background: Methylenetetrahydrofolate reductase (MTHFR) deficiency leads to impairment in folate metabolism and is implicated as a risk factor for neural tube defects (NTDs). Both C677T and A1298C MTHFR mutations are associated with NTDs, in some populations. Methods: The frequencies of the C677T and A1298C MTHFR mutations were determined in 25 children with NTDs, case mothers and 75 healthy individuals from

Andrea L. A Cunha; Mario H Hirata; Chong A Kim; Elvira M Guerra-Shinohara; Kymio Nonoyama; Rosario D. C Hirata

2002-01-01

98

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

PubMed Central

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

Chalasani, Kavita; Brewster, Rachel M.

2011-01-01

99

A comparison of methods for spatial relative risk mapping of human neural tube defects  

Microsoft Academic Search

Birth defects are a major cause of infant mortality and disability in many parts of the world. Yet the etiology of neural\\u000a tube defects (NTDs), the most common types of birth defects, is still unknown. The construction and analysis of maps of disease\\u000a incidence data can help explain the geographical distribution of NTDs and can point to possible environmental causes

Yi-Lan Liao; Jin-Feng Wang; Ji-Lei Wu; Jiao-Jiao Wang; Xiao-Ying Zheng

2011-01-01

100

Maternal Supplemental and Dietary Zinc Intake and the Occurrence of Neural Tube Defects in California  

Microsoft Academic Search

The authors investigated the association between maternal preconceptional supplemental and dietary zinc intake and risk of neural tube defects (NTDs) in a population-based case-control study conducted between 1989 and 1991 in California. Cases were 430 NTD-affected fetuses\\/infants, and controls were 429 randomly selected non-malformed infants. Mothers reported their preconceptional use of vitamin, mineral, and food supplements, and completed a 98-item

Ellen M. Velie; Gladys Block; Gary M. Shaw; Steven J. Samuels; Donna M Schaffer; Martin Kulldorff

101

Risk assessment of human neural tube defects using a Bayesian belief network  

Microsoft Academic Search

Neural tube defects (NTDs) constitute the most common type of birth defects. How much risk of NTDs could an area take? The\\u000a answer to this question will help people understand the geographical distribution of NTDs and explore its environmental causes.\\u000a Most existing methods usually take the spatial correlation of cases into account and rarely consider the effect of environmental\\u000a factors.

Yilan Liao; Jinfeng Wang; Yaoqin Guo; Xiaoying Zheng

2010-01-01

102

Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure.  

PubMed

Craniorachischisis is a rare but severe birth defect that results in a completely open neural tube. Mouse mutants in planar cell polarity (PCP) signalling components have deficits in the morphological movements of convergent extension that result in craniorachischisis. Using a forward genetic screen in mice, we identified Sec24b, a cargo-sorting member of the core complex of the endoplasmic reticulum (ER)-to-Golgi transport vesicle COPII, as critical for neural tube closure. Sec24bY613 mutant mice exhibit craniorachischisis, deficiencies in convergent extension and other PCP-related phenotypes. Vangl2, a key component of the PCP-signalling pathway critical for convergent extension, is selectively sorted into COPII vesicles by Sec24b. Moreover, Sec24bY613 genetically interacts with a loss-of-function Vangl2 allele (Vangl2LP), causing a marked increase in the prevalence of spina bifida. Interestingly, the Vangl2 looptail point mutants Vangl2D255E and Vangl2S464N, known to cause defects in convergent extension, fail to sort into COPII vesicles and are trapped in the ER. Thus, during COPII vesicle formation, Sec24b shows cargo specificity for a core PCP component, Vangl2, of which proper ER-to-Golgi transport is essential for the establishment of PCP, convergent extension and closure of the neural tube. PMID:19966784

Merte, Janna; Jensen, Devon; Wright, Kevin; Sarsfield, Sarah; Wang, Yanshu; Schekman, Randy; Ginty, David D

2009-12-06

103

Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure  

PubMed Central

Craniorachischisis is a rare but severe birth defect that results in a completely open neural tube. Mouse mutants in planar cell polarity (PCP) signaling components have deficits in the morphological movements of convergent extension (CE) that result in craniorachischisis. Using a forward-genetic screen in mice, we have identified Sec24b, a cargo-sorting member of the core complex of the COPII endoplasmic reticulum (ER)-Golgi transport vesicle, as critical for neural tube closure. Sec24bY613 mutants exhibit craniorachischisis, deficiencies in CE, and other PCP-related phenotypes. Vangl2, a key component of the PCP-signaling pathway critical for CE, is selectively sorted into COPII vesicles by Sec24b. Moreover, Sec24bY613 genetically interacts with a loss-of-function Vangl2 allele (Vangl2LP) causing a marked increase in the prevalence of spina bifida. Interestingly, the Vangl2 looptail point mutants D255E and S464N, known to cause defects in CE, fail to sort into COPII vesicles and are trapped in the ER. Thus, during COPII vesicle formation, Sec24b exhibits cargo specificity for a core PCP component, Vangl2, the proper ER to Golgi transport of which is essential for the establishment of PCP, convergent extension, and closure of the neural tube.

Merte, Janna; Jensen, Devon; Wright, Kevin; Sarsfield, Sarah; Wang, Yanshu; Schekman, Randy; Ginty, David D.

2010-01-01

104

C5a Receptor Signaling Prevents Folate Deficiency-Induced Neural Tube Defects in Mice  

PubMed Central

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

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

2013-01-01

105

The continuing challenge of understanding, preventing, and treating neural tube defects.  

PubMed

Human birth defects are a major public health burden: The Center for Disease Control estimates that 1 of every 33 United States newborns presents with a birth defect, and worldwide the estimate approaches 6% of all births. Among the most common and debilitating of human birth defects are those affecting the formation of the neural tube, the precursor to the central nervous system. Neural tube defects (NTDs) arise from a complex combination of genetic and environmental interactions. Although substantial advances have been made in the prevention and treatment of these malformations, NTDs remain a substantial public health problem, and we are only now beginning to understand their etiology. Here, we review the process of neural tube development and how defects in this process lead to NTDs, both in humans and in the animal models that serve to inform our understanding of these processes. The insights we are gaining will help generate new intervention strategies to tackle the clinical challenges and to alleviate the personal and societal burdens that accompany these defects. PMID:23449594

Wallingford, John B; Niswander, Lee A; Shaw, Gary M; Finnell, Richard H

2013-03-01

106

The Chromatin Targeting Protein Brd2 is Required for Neural Tube Closure and Embryogenesis  

PubMed Central

Chromatin modifications are essential for directing transcription during embryonic development. Bromodomain-containing protein 2 (Brd2; also called RING3 and Fsrg1) is one of four BET (bromodomain and extra terminal domain) family members known to selectively bind acetylated histones H3 and H4. Brd2 associates with multiple subunits of the transcriptional apparatus including the mediator, TFIID and Swi/Snf multi-protein complexes. While molecular interactions of Brd2 are known, the functions of Brd2 in mammalian embryogenesis remain unknown. In developing a mouse model deficient in Brd2, we find that Brd2 is required for the completion of embryogenesis and proper neural tube closure during development. Embryos lacking Brd2 expression survive up to embryonic day 13.5, soon after mid-gestation, and display fully penetrant neurulation defects that largely result in exencephaly of the developing hindbrain. In this study, we find that highest expression of Brd2 is detected in the developing neural tube, correlating with the neural tube defects found in Brd2-null embryos. Additionally, embryos lacking Brd2 expression display altered gene expression programs, including the mis-expression of multiple genes known to guide neuronal development. Together these results implicate essential roles for Brd2 as a critical integrator of chromatin structure and transcription during mammalian embryogenesis and neurogenesis.

Gyuris, Aron; Donovan, Diana J.; Seymour, Kimberly A.; Lovasco, Lindsay A.; Smilowitz, Nathaniel R.; Halperin, Anthony L. P.; Klysik, Jan E.; Freiman, Richard N.

2009-01-01

107

Expression of p53\\/hgf\\/c-met\\/STAT3 signal in fetuses with neural tube defects  

Microsoft Academic Search

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor\\u000a (HGF)\\/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF\\/c-met morphogenetic effects are\\u000a mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53.\\u000a The aim of our study was

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

2007-01-01

108

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

NASA Astrophysics Data System (ADS)

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

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

2010-03-01

109

Trehalose prevents neural tube defects by correcting maternal diabetes-suppressed autophagy and neurogenesis.  

PubMed

Preexisting maternal diabetes increases the risk of neural tube defects (NTDs). The mechanism underlying maternal diabetes-induced NTDs is not totally defined, and its prevention remains a challenge. Autophagy, an intracellular process to degrade dysfunction protein and damaged cellular organelles, regulates cell proliferation, differentiation, and apoptosis. Because autophagy impairment causes NTDs reminiscent of those observed in diabetic pregnancies, we hypothesize that maternal diabetes-induced autophagy impairment causes NTD formation by disrupting cellular homeostasis, leading to endoplasmic reticulum (ER) stress and apoptosis, and that restoration of autophagy by trehalose, a natural disaccharide, prevents diabetes-induced NTDs. Embryos from nondiabetic and type 1 diabetic mice fed with or without 2 or 5% trehalose water were used to assess markers of autophagy, ER stress, and neurogenesis, numbers of autophagosomes, gene expression that regulates autophagy, NTD rates, indices of mitochondrial dysfunction, and neuroepithelial cell apoptosis. Maternal diabetes suppressed autophagy by significantly reducing LC3-II expression, autophagosome numbers, and GFP-LC3 punctate foci in neuroepithelial cells and by altering autophagy-related gene expression. Maternal diabetes delayed neurogenesis by blocking Sox1 neural progenitor differentiation. Trehalose treatment reversed autophagy impairment and prevented NTDs in diabetic pregnancies. Trehalose resolved homeostatic imbalance by correcting mitochondrial defects, dysfunctional proteins, ER stress, apoptosis, and delayed neurogenesis in the neural tubes exposed to hyperglycemia. Our study demonstrates for the first time that maternal diabetes suppresses autophagy in neuroepithelial cells of the developing neural tube, leading to NTD formation, and provides evidence for the potential efficacy of trehalose as an intervention against hyperglycemia-induced NTDs. PMID:23880312

Xu, Cheng; Li, Xuezheng; Wang, Fang; Weng, Hongbo; Yang, Peixin

2013-07-23

110

Assessing local determinants of neural tube defects in the Heshun Region, Shanxi Province, China  

PubMed Central

Background Neural tube defect (NTD) prevalence in northern China is among the highest worldwide. Dealing with the NTD situation is ranked as the number one task in China's scientific development plan in population and health field for the next decade. Physical and social environments account for much of the disease's occurrence. The environmental determinants and their effects on NTD vary across geographical regions, whereas factors that play a significant role in NTD occurrence may be buried by global statistics analysis to a pooled dataset over the entire study area. This study aims at identification of the local determinants of NTD across the study area and exploration of the epidemiological implications of the findings. Methods NTD prevalence rate is represented in terms of the random field theory, and Rushton's circle method is used to stabilize NTD rate estimation across the geographical area of interest; NTD determinants are represented by their measurable proxy variables and the geographical weighted regression (GWR) technique is used to represent the spatial heterogeneity of the NTD determinants. Results Informative maps of the NTD rates and the statistically significant proxy variables are generated and rigorously assessed in quantitative terms. Conclusions The NTD determinants in the study area are investigated and interpreted on the basis of the maps of the proxy variables and the relationships between the proxy variables and the NTD determinants. No single determinant was found to dominate the NTD occurrence in the study area. Villages where NTD rates are significantly linked to environmental determinants are identified (some places are more closely linked to certain environmental factors than others). The results improve current understanding of NTD spread in China and provide valuable information for adequate disease intervention planning.

2010-01-01

111

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

PubMed Central

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

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

2012-01-01

112

A spatial model to predict the incidence of neural tube defects  

PubMed Central

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

2012-01-01

113

Natural history of hydrocephalus in children with spinal open neural tube defect  

PubMed Central

Background: The long-term prognosis of patients with Spinal Open Neural Tube Defect (SONTD)-associated hydrocephalus is not well known. This study was conducted to ascertain the incidence and natural history of hydrocephalus in patients with SONTD. Methods: All 82 patients with SONTD referred to Neurosurgery/Spina Bifida Clinics at King Khalid University Hospital, Riyadh, Saudi Arabia (January 1995 - July 2010) were studied and followed for a period of 1-16 years. Patients were divided into three groups: Group “A” with active hydrocephalus treated with ventriculoperitoneal shunt (VPS), or endoscopic third ventriculostomy (ETV); Group “B” with compensated hydrocephalus; and Group “C” with no hydrocephalus. Timing of shunt insertion, complications of treatment and status of hydrocephalus were analyzed. Results: The mean age of the 82 patients was 7.4 years (range 1-16 years). Group “A” included 59 (72%) patients, Group “B” 7 (8.5%) patients, and Group “C” 16 (19.5%) patients. Chiari malformation type II was found in 71 (86.6%) patients, 57 of whom (80%) were in Group “A” with active hydrocephalus. They were treated by VPS (51 patients) and ETV (8 patients). The shunts were revised or replaced in 10 (19.6%) patients due to obstruction or infection. Primary ETV failed in 3/8 patients, and treated by VPS. None of those in Groups “B” or “C” required treatment for hydrocephalus during the follow up. Conclusion: Hydrocephalus affects the majority of patients with SONTD who have Myelomeningocele (MMC) and CM II and requires close surveillance and prompt management. Children with SONTD should routinely undergo MRI examination of brain and craniocervical junction to clarify ventricular size, and the presence of CM II.

Elgamal, Essam A.

2012-01-01

114

Is PATCHED an important candidate gene for neural tube defects? Cranial and thoracic neural tube defects in a family with Gorlin syndrome: a case report.  

PubMed

. The relationship of mutations in the patched gene PTCH and nevoid basal cell carcinoma (NBCC) or Gorlin syndrome is well established. Animal studies have implicated the hedgehog-patched signalling pathway in neurulation and neural tube defects (NTDs). Spina bifida occulta and bifid vertebrae are well recognized in NBCCS, but there appears to be only one report of open spina bifida. We report a father and two sons with a truncating PTCH mutation and the major features of NBCCS. One son had open thoracic spina bifida and the other had an occipital meningocoele. We believe this to be the first report of cranial NTD in NBCCS and suggest that consideration be given to including PTCH analysis in genetic association studies in NTDs as the hedgehog pathway is integral to normal human neurulation. PMID:21651513

Roudgari, H; Farndon, P A; Murray, A D; Hardy, C; Miedzybrodzka, Z

2011-06-30

115

The amniotic fluid as a source of neural stem cells in the setting of experimental neural tube defects.  

PubMed

We sought to determine whether neural stem cells (NSCs) can be isolated from the amniotic fluid in the setting of neural tube defects (NTDs), as a prerequisite for eventual autologous perinatal therapies. Pregnant Sprague-Dawley dams (n=62) were divided into experimental (n=42) and control (n=20) groups, depending on prenatal exposure to retinoic acid for the induction of fetal NTDs. Animals were killed before term for analysis (n=685 fetuses). Amniotic fluid samples from both groups underwent epigenetic selection for NSCs, followed by exposure to neural differentiation media. Representative cell samples underwent multiple morphological and phenotypical analyses at different time points. No control fetus (n=267) had any structural abnormality, whereas at least one type of NTD developed in 52% (217/418) of the experimental fetuses (namely, isolated spina bifida, n=144; isolated exencephaly, n=24; or a combination of the two, n=49). Only amniotic samples from fetuses with a NTD yielded cells with typical neural progenitor morphology and robust expression of both Nestin and Sox-2, primary markers of NSCs. These cells responded to differentiation media by displaying typical morphological changes, along with expression of beta-tubulin III, glial fibrillary acidic protein, and/or O4, markers for immature neurons, astrocytes, and oligodendrocytes, respectively. This was concurrent with downregulation of Nestin and Sox-2. We conclude that the amniotic fluid can harbor disease-specific stem cells, for example, NSCs in the setting of experimental NTDs. The amniotic fluid may be a practical source of autologous NSCs applicable to novel forms of therapies for spina bifida. PMID:22957979

Turner, Christopher G; Klein, Justin D; Wang, Junmei; Thakor, Devang; Benedict, Darcy; Ahmed, Azra; Teng, Yang D; Fauza, Dario O

2012-11-02

116

Regulation of Patched by Sonic Hedgehog in the Developing Neural Tube  

NASA Astrophysics Data System (ADS)

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

Marigo, Valeria; Tabin, Clifford J.

1996-09-01

117

Neural network inversion of synthetic eddy current testing signals from flaws in steam generator tubes  

NASA Astrophysics Data System (ADS)

This paper reports our recent endeavor to develop automated, systematic inversion tools by the novel combination of neural networks and finite element modeling for eddy current flaw characterization in steam generator tubes. Specifically, this paper describes 1) development of the finite element models that can simulate synthetic ECT signals from axisymmetric flaws with arbitrary cross-sections, 2) construction of databases with abundant flaw signals, 3) implementation of effective feature extraction software and proposition of feature selection criteria, and finally 4) development of inversion tools by use of two neural networks for flaw classification and sizing. In addition, this paper also presents the performance of the proposed inversion tools for solving two sample problems: classification of flaws with non-symmetric cross-sections, and classification and sizing of flaws with tip variation. .

Song, S. J.; Kim, C. H.; Shin, Y. K.; Lee, H. B.; Park, Y. W.; Yim, C. J.

2001-04-01

118

Temporal control of BMP signalling determines neuronal subtype identity in the dorsal neural tube  

PubMed Central

The conventional explanation for how a morphogen patterns a tissue holds that cells interpret different concentrations of an extrinsic ligand by producing corresponding levels of intracellular signalling activity, which in turn regulate differential gene expression. However, this view has been challenged, raising the possibility that distinct mechanisms are used to interpret different morphogens. Here, we investigate graded BMP signalling in the vertebrate neural tube. We show that defined exposure times to Bmp4 generate distinct levels of signalling and induce specific dorsal identities. Moreover, we provide evidence that a dynamic gradient of BMP activity confers progressively more dorsal neural identities in vivo. These results highlight a strategy for morphogen interpretation in which the tight temporal control of signalling is important for the spatial pattern of cellular differentiation.

Tozer, Samuel; Le Dreau, Gwenvael; Marti, Elisa; Briscoe, James

2013-01-01

119

Mitotic spindle orientation can direct cell fate and bias Notch activity in chick neural tube.  

PubMed

Inheritance of apical membrane is proposed to maintain vertebrate neural stem cell proliferation. However, evidence for this is contradictory. Using direct clonal analysis and live imaging in chick neural tube, we show that divisions that separate apical and basal components generate an apical daughter, which becomes a neuron, and a basal daughter, which rapidly re-establishes apico-basal polarity and divides again. Using a recently described real-time reporter of Notch activity, we confirm progenitor status and demonstrate that division orientation can influence Notch signalling. In addition, we reveal loss of apical complex proteins on neuronal differentiation onset, suggesting that removal of this inherited complex is part of the neuronal differentiation mechanism. These findings reconcile contradictory data, link asymmetric division to Notch signalling dynamics and identify apical complex loss as a new step towards neuronal differentiation. PMID:22491029

Das, Raman M; Storey, Kate G

2012-05-01

120

Fgf8-Related Secondary Organizers Exert Different Polarizing Planar Instructions along the Mouse Anterior Neural Tube  

PubMed Central

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.

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

2012-01-01

121

Loss of membrane targeting of Vangl proteins causes neural tube defects.  

PubMed

In the mouse, the loop-tail mutation (Lp) causes a very severe neural tube defect, which is caused by mutations in the Vangl2 gene. In mammals, Vangl1 and Vangl2 code for integral membrane proteins that assemble into asymmetrically distributed membrane complexes that establish planar cell polarity in epithelial cells and that regulate convergent extension movements during embryogenesis. To date, VANGL are the only genes in which mutations cause neural tube defects in humans. Three independently arising Lp alleles have been described for Vangl2: D255E, S464N, and R259L. Here we report a common mechanism for both the naturally occurring Lp (S464N) and a novel ENU-induced mutation Lp(m2Jus)(R259L). We show that the S464N and R259L variants stably expressed in polarized MDCK kidney cells fail to reach the plasma membrane, their site for biological function. The mutant variants are retained intracellularly in the endoplasmic reticulum, colocalizing with ER chaperone calreticulin. Furthermore, the mutants also show a dramatically reduced half-life of ?3 h, compared to ?22 h for the wild-type protein, and are rapidly degraded in a proteasome-dependent and MG132-sensitive fashion. Coexpressing individually the three known allelic Lp variants with the wild-type protein does not influence the localization of the WT at the plasma membrane, suggesting that the codominant nature of the Lp trait in vivo is due to haploid insufficiency caused by a partial loss of function in a gene dosage-dependent pathway, as opposed to a dominant negative phenotype. Our study provides a biochemical framework for the study of recently identified mutations in hVANGL1 and hVANGL2 in sporadic or familial cases of neural tube defects. PMID:21142127

Iliescu, Alexandra; Gravel, Michel; Horth, Cynthia; Kibar, Zoha; Gros, Philippe

2011-01-13

122

Prevalence of neural tube defects in economically and socially deprived area of China  

Microsoft Academic Search

Objective  This paper aims to understand the situation and epidemiology trend of neural tube defects in Guizhou province, China from\\u000a 1996 to 2004.\\u000a \\u000a \\u000a \\u000a Study design  Pregnant women from 17 hospitals in Guizhou province were chosen for investigation of perinatal infants from January 1996\\u000a to December 2004.\\u000a \\u000a \\u000a \\u000a Results  Of 1,208 birth defect cases studied in this 9-year period, a total of 122 cases were

Jie Liu; Guo Z. Yang; Jin L. Zhou; Shi P. Cao; David H. W. Chau; Hsiang-fu Kung; Marie C. Lin

2007-01-01

123

Iron Status Indicators in Women with Prior Neural Tube Defect-Affected Pregnancies  

Microsoft Academic Search

\\u000a Objectives: Iron deficiency is the most common nutrient deficiency in pregnant women and has been linked to negative impacts on the\\u000a fetus. We describe the association of various iron-deficiency indices with risk of neural tube defect (NTD) among a high-risk\\u000a Mexican-American population. Methods: The study included 158 case-women (NTD-affected pregnancies) and 189 control-women (normal births) who were residents of\\u000a the

Marilyn M. Felkner; Lucina Suarez; Jean Brender; Barbara Scaife; Kate Hendricks

2005-01-01

124

The activin signaling pathway promotes differentiation of dI3 interneurons in the spinal neural tube.  

PubMed

The generation of the appropriate types and numbers of mature neurons during the development of the spinal cord requires the careful coordination of patterning, proliferation, and differentiation. In the dorsal neural tube, this coordination is achieved by the combined action of multiple ligands of both the Wnt and TGF-beta families, and their effectors, such as the bHLH proteins. TGF-beta signaling acting through the BMP receptors is necessary for the generation of several dorsal interneuron types. Other TGF-beta ligands expressed in the dorsal neural tube interact with the Activin receptors, which signal via a different set of SMAD proteins than BMPs. The effects of Activin signaling on the developing neural tube have not been described. Here we have activated the Activin signal transduction pathway in a cell-autonomous manner in the developing chick neural tube. We find that a constitutively active Activin receptor promotes differentiation throughout the neural tube. Although most differentiated cell populations are unaffected by Activin signaling, the number of dorsal interneuron 3 (dI3) cells is specifically increased. Our data suggest that Activin signaling may promote the formation of the dI3 precursor cells within a region circumscribed by BMP signaling and that this function is not dependent upon BMP signaling. PMID:16039645

Timmer, John; Chesnutt, Catherine; Niswander, Lee

2005-09-01

125

Maternal Mthfd1 disruption impairs fetal growth but does not cause neural tube defects in mice123  

PubMed Central

Background: MTHFD1 encodes C1-tetrahydrofolate synthase, which is a folate-dependent enzyme that catalyzes the formation and interconversion of folate-activated one-carbon groups for nucleotide biosynthesis and cellular methylation. A polymorphism in MTHFD1 (1958G?A) impairs enzymatic activity and is associated with increased risk of adverse pregnancy outcomes, but the mechanisms are unknown. Objective: The objective of this study was to determine whether disruption of the embryonic or maternal Mthfd1 gene or both interacts with impaired folate and choline status to affect neural tube closure, fetal growth, and fertility in mice and to investigate the underlying metabolic disruptions. Design: Dams with a gene-trapped (gt) allele in Mthfd1 and wild-type dams were fed a control or folate- and choline-deficient AIN93G diet (Dyets Inc). Litters were examined for gross morphologic defects, crown-rump length, and resorptions. Folate status and amounts of folate-related metabolites were determined in pregnant dams. Results: Reduced folate and choline status resulted in severe fetal growth restriction (FGR) and impaired fertility in litters harvested from Mthfd1gt/+ dams, but embryonic Mthfd1gt/+ genotype did not affect fetal growth. Gestational supplementation of Mthfd1gt/+ dams with hypoxanthine increased FGR frequency and caused occasional neural tube defects (NTDs) in Mthfd1gt/+ embryos. Mthfd1gt/+ dams exhibited lower red blood cell folate and plasma methionine concentrations than did wild-type dams. Conclusions: Maternal Mthfd1gt/+ genotype impairs fetal growth but does not cause NTDs when dams are maintained on a folate- and choline-deficient diet. Mthfd1gt/+ mice exhibit a spectrum of adverse reproductive outcomes previously attributed to the human MTHFD1 1958G?A polymorphism. Mthfd1 heterozygosity impairs folate status in pregnant mice but does not significantly affect homocysteine metabolism.

Beaudin, Anna E; Perry, Cheryll A; Stabler, Sally P; Allen, Robert H; Stover, Patrick J

2012-01-01

126

Novel association of VACTERL, neural tube defect and crossed renal ectopia: sonic hedgehog signaling: a point of coherence?  

PubMed

The present case report describes two patients with a novel combination of VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb), neural tube defect and crossed renal ectopia. Though cases of VACTERL associated with crossed renal ectopia have been described, the present case report is the first to describe its combination with neural tube defect. The cases reported here are significant because central nervous system manifestations are scarce in VACTERL syndrome. The role of sonic hedgehog pathway has been proposed in VACTERL association and neural tube defects. Axial Sonic hedgehog signaling has also been implicated in the mediolateral positioning of the renal parenchyma. With this knowledge, the etiopathogenesis of this novel combination is discussed to highlight the role of sonic hedgehog signaling as a point of coherence. PMID:23181497

Vaze, Dhananjay; Mahalik, Santosh; Rao, Katragadda L N

2012-12-01

127

The influence of laminin on the initial differentiation of cultured neural tube neurons.  

PubMed

Portions of the metencephalic neural tube containing the trigeminal (V) motor nucleus from 40-hr chick embryos were excised and held freely floating in culture medium for 36-40 hr, so that neuronal generation within motor V could be completed, but precluding neuronal differentiation. The explants were then dissociated and plated either on 1) glass coverslips that had been coated with the extracellular matrix (ECM) glycoprotein, laminin, and subsequently irradiated to produce a grid pattern; or 2) coverslips, one-half of which had been coated with laminin, and the other one-half with collagen, another component of the ECM. The purpose of these studies was to assess possible laminin influences on neuronal adhesion and nerve fiber expression and extension during these periods of initial neuronal differentiation. The early neural tube neurons selectively adhered to the established laminin grid pattern; neuronal survival, elaboration of neurites, and extent of neurites were significantly enhanced on the laminin side of the laminin/collagen preparations. These latter effects were specifically blocked by the application of anti-laminin. In demonstrating these influences during stages of initial neuronal differentiation, the results support the hypothesis that laminin may play a role in normal neurogenesis, presumably by providing an adhesive surface for outgrowing growth cones. PMID:3367395

Heaton, M B; Swanson, D J

1988-02-01

128

Folic acid supplementation can adversely affect murine neural tube closure and embryonic survival  

PubMed Central

Neural tube defects (NTDs), a common birth defect in humans, result from the failure of the embryonic neural tube (NT) to close properly. NT closure is a complex, poorly understood morphogenetic process influenced by genes and environment. The most effective environmental influence in decreasing the risk for NTDs is folic acid (FA) fortification and supplementation, and these findings led to the recommendation of periconceptual FA intake and mandatory fortification of the US grain supply in 1998. To explore the relationship between genetics and responsiveness to FA supplementation, we used five mouse NTDs models—Zic2, Shroom3, Frem2, Grhl2 (Grainyhead-like 2) and L3P (Line3P)—and a long-term generational FA supplementation scheme. Contrary to expectations, we find that three genetic mutants respond adversely to FA supplementation with increased incidence of NTDs in homozygous mutants, occurrence of NTDs in heterozygous embryos and embryonic lethality prior to NT closure. Because of these unexpected responses, we examined NTD risk after short-term FA supplementation. Our results indicate that, for the same genetic allele, NTD risk can depend on the length of FA exposure. Our data indicate that, depending on the gene mutation, FA supplementation may adversely influence embryonic development and NT closure.

Marean, Amber; Graf, Amanda; Zhang, Ying; Niswander, Lee

2011-01-01

129

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

PubMed

Differences between the left and right sides of the brain are present in many animal species. For instance, in humans the left cerebral hemisphere is largely responsible for language and tool use and the right for processing spatial information. Zebrafish have prominent left-right asymmetries in their epithalamus that have been associated with differential left and right eye use and navigational behavior. In wild-type (WT) zebrafish embryos, Nodal pathway genes are expressed in the left side of the pineal anlage. Shortly thereafter, a parapineal organ forms to the left of the pineal. The parapineal organ causes differences in gene expression, neuropil density, and connectivity of the left and right habenula nuclei. In embryos that have an open neural tube, such as embryos that are deficient in Nodal signaling or the cell adhesion protein N-cadherin, the left and right sides of the developing epithalamus remain separated from one another. We find that the brains of these embryos often become left isomerized: both sides of the brain develop morphology and gene expression patterns that are characteristic of the left side. However, other aspects of epithalamic development, such as differentiation of specific neuronal cell types, are intact. We propose that there is a mechanism in embryos with closed neural tubes that prevents both sides from developing like the left side. This mechanism fails when the two sides of the epithalamus are widely separated from one another, suggesting that it is dependent upon a signaling protein with limited range. PMID:23201575

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

2012-11-29

130

Folic acid supplementation can adversely affect murine neural tube closure and embryonic survival.  

PubMed

Neural tube defects (NTDs), a common birth defect in humans, result from the failure of the embryonic neural tube (NT) to close properly. NT closure is a complex, poorly understood morphogenetic process influenced by genes and environment. The most effective environmental influence in decreasing the risk for NTDs is folic acid (FA) fortification and supplementation, and these findings led to the recommendation of periconceptual FA intake and mandatory fortification of the US grain supply in 1998. To explore the relationship between genetics and responsiveness to FA supplementation, we used five mouse NTDs models-Zic2, Shroom3, Frem2, Grhl2 (Grainyhead-like 2) and L3P (Line3P)-and a long-term generational FA supplementation scheme. Contrary to expectations, we find that three genetic mutants respond adversely to FA supplementation with increased incidence of NTDs in homozygous mutants, occurrence of NTDs in heterozygous embryos and embryonic lethality prior to NT closure. Because of these unexpected responses, we examined NTD risk after short-term FA supplementation. Our results indicate that, for the same genetic allele, NTD risk can depend on the length of FA exposure. Our data indicate that, depending on the gene mutation, FA supplementation may adversely influence embryonic development and NT closure. PMID:21693562

Marean, Amber; Graf, Amanda; Zhang, Ying; Niswander, Lee

2011-06-21

131

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

PubMed

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

Copp, Andrew J; Greene, Nicholas D E

2012-05-29

132

Twist Function Is Required for the Morphogenesis of the Cephalic Neural Tube and the Differentiation of the Cranial Neural Crest Cells in the Mouse Embryo  

Microsoft Academic Search

Loss of Twist function in the cranial mesenchyme of the mouse embryo causes failure of closure of the cephalic neural tube and malformation of the branchial arches. In the Twist?\\/? embryo, the expression of molecular markers that signify dorsal forebrain tissues is either absent or reduced, but those associated with ventral tissues display expanded domains of expression. Dorsoventral organization of

Kenneth Soo; Meredith P. O'Rourke; Poh-Lynn Khoo; Kirsten A. Steiner; Nicole Wong; Richard R. Behringer; Patrick P. L. Tam

2002-01-01

133

Molecular Genetics and Pathogenic Mechanisms for the Severe Ciliopathies: Insights into Neurodevelopment and Pathogenesis of Neural Tube Defects  

Microsoft Academic Search

Meckel–Gruber syndrome (MKS) is a severe autosomal recessively inherited disorder characterized by developmental defects of\\u000a the central nervous system that comprise neural tube defects that most commonly present as occipital encephalocele. MKS is\\u000a considered to be the most common syndromic form of neural tube defect. MKS is genetically heterogeneous with six known disease\\u000a genes: MKS1, MKS2\\/TMEM216, MKS3\\/TMEM67, RPGRIP1L, CEP290, and

Clare V. Logan; Zakia Abdel-Hamed; Colin A. Johnson

2011-01-01

134

Modified neural network correlation of refrigerant mass flow rates through adiabatic capillary and short tubes: Extension to CO 2 transcritical flow  

Microsoft Academic Search

This paper presents a modified dimensionless neural network correlation of refrigerant mass flow rates through adiabatic capillary tubes and short tube orifices. In particular, CO2 transcritical flow is taken into account. The definition of neural network input and output dimensionless parameters is grounded on the homogeneous equilibrium model and extended to supercritical inlet conditions. 2000 sets of experimental mass flow-rate

Liang Yang; Chun-Lu Zhang

2009-01-01

135

STUDIES ON THE INDUCTION OF NEURAL TUBE DEFECTS IN THE LM/BC AND CD1 MOUSE STRAINS FOLLOWING ORAL OR INTRAPERITONEAL FUMONISIN EXPOSURE  

Technology Transfer Automated Retrieval System (TEKTRAN)

The human health effects of Fusarium verticillioides and fumonisins are uncertain. There is evidence however suggesting that fumonisins disrupt folate utilization and increase the risk of neural tube defects (NTDs = birth defects cause by failure of the neural tube to close properly) in populati...

136

Combination of a Gated Phtotomultiplier Tube and a Phase Sensitive Detector for Use in an Intensive Pulsed Background Light Situation  

Microsoft Academic Search

In order to detect a weak signal light that appears after an intensive pulsed background light, we constructed a light detection module that consisted of an internally-gated photomultiplier tube (PMT) and a phase sensitive detector (PSD). Plural even-numbered dynodes of a miniature PMT were controlled for the internal gate operation and the output signal from the PMT was fed into

Tetsuo Iwata; Tsuyoshi Takasu; Tsuyoshi Miyata; Tsutomu Araki

2002-01-01

137

Occurrence of Neural Tube Defects in Pregnancy: An Excess of Cases in a 2773-km2 Area in Central Italy  

Microsoft Academic Search

Neural tube defects (NTDs) have a complex and imperfectly understood etiology, in which both genetic and environmental factors might be involved. The aim of the study was to describe an excess of cases of NTDs in a small area in central Italy. Over a 2-wk period in autumn 2002, three diagnoses of anencephaly were made in a 2773-km area. As

Emilia Prospero; Pamela Barbadoro; Fabio Filippetti; Remo Appignanesi; Andrea Ciavattini; Flavia Carle

2008-01-01

138

The Activin signaling pathway promotes differentiation of dI3 interneurons in the spinal neural tube  

Microsoft Academic Search

The generation of the appropriate types and numbers of mature neurons during the development of the spinal cord requires the careful coordination of patterning, proliferation, and differentiation. In the dorsal neural tube, this coordination is achieved by the combined action of multiple ligands of both the Wnt and TGF-? families, and their effectors, such as the bHLH proteins. TGF-? signaling

John Timmer; Catherine Chesnutt; Lee Niswander

2005-01-01

139

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

140

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

141

Long term effects of periconceptional multivitamin supplements for prevention of neural tube defects: a seven to 10 year follow up  

Microsoft Academic Search

Periconceptional supplementation with Pregnavite Forte F was offered to women who presented consecutively to the Oxford genetic counselling service in the early 1980s who had previously had one or more pregnancies complicated by a neural tube defect. The first 100 children born alive to these women are the subject of this study. Birth weight, gestation, and congenital abnormalities were recorded.

M Holmes-Siedle; J Dennis; R H Lindenbaum; A Galliard

1992-01-01

142

Investigation of Folate Pathway Gene Polymorphisms and the Incidence of Neural Tube Defects in a Texas Hispanic Population  

Microsoft Academic Search

Neural tube defects (NTDs) are multifactorial in their etiology, having both genetic and environmental factors contributing to their development. Recent evidence demonstrates that periconceptional supplementation of the maternal diet with a multivitamin containing folic acid significantly reduces the occurrence and recurrence risk for having a pregnancy complicated by NTDs. Unfortunately, the mechanism underlying the beneficial effects of folic acid remains

Robert Barber; Stuart Shalat; Kate Hendricks; Brigitte Joggerst; Russell Larsen; Lucina Suarez; Richard Finnell

2000-01-01

143

Jarcho-Levin Syndrome Presenting as Neural Tube Defect: Report of Four Cases and Pitfalls of Diagnosis  

Microsoft Academic Search

Jarcho-Levin syndrome (JLS) causes severe vertebral and thoracic deformity and has an autosomal-recessive mode of inheritance. Prenatal diagnosis may be difficult in some cases without the history of an affected baby. We present 4 cases of JLS with neural tube defects as the prominent finding. In 2 of them the deformity of the thorax was minimal and was not detected

Banu Dane; Cem Dane; Figen Aksoy; Ahmet Cetin; Murat Yayla

2007-01-01

144

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

145

Neural tube defects: contemporary outcome data in a setting in which pregnancy termination is not locally available  

Microsoft Academic Search

Ireland continues to experience a high incidence of neural tube defects (NTD). Knowledge about the natural history of this condition is limited as pregnancy termination is practiced in most countries.We aimed to describe perinatal outcomes of pregnancies complicated by fetal NTDs in a setting in which pregnancy termination is not locally available. We conducted a retrospective cohort study over a

J Unterscheider; E Kent; N Burke; U Wiig; F Breathnach; F Malone

2011-01-01

146

Developing Effective Campaign Messages to Prevent Neural Tube Defects: A Qualitative Assessment of Women's Reactions to Advertising Concepts  

Microsoft Academic Search

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

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

2009-01-01

147

Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects  

PubMed Central

This overview addresses homocysteine and folate metabolism. Its functions and complexity are described, leading to explanations why disturbed homocysteine and folate metabolism is implicated in many different diseases, including congenital birth defects like congenital heart disease, cleft lip and palate, late pregnancy complications, different kinds of neurodegenerative and psychiatric diseases, osteoporosis and cancer. In addition, the inborn errors leading to hyperhomocysteinemia and homocystinuria are described. These extreme human hyperhomocysteinemia models provide knowledge about which part of the homocysteine and folate pathways are linked to which disease. For example, the very high risk for arterial and venous occlusive disease in patients with severe hyperhomocysteinemia irrespective of the location of the defect in remethylation or transsulphuration indicates that homocysteine itself or one of its “direct” derivatives is considered toxic for the cardiovascular system. Finally, common diseases associated with elevated homocysteine are discussed with the focus on cardiovascular disease and neural tube defects.

Smulders, Yvo

2010-01-01

148

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

PubMed Central

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

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

2012-01-01

149

Paracrine Pax6 activity regulates oligodendrocyte precursor cell migration in the chick embryonic neural tube.  

PubMed

Homeoprotein transcription factors play fundamental roles in development, ranging from embryonic polarity to cell differentiation and migration. Research in recent years has underscored the physiological importance of homeoprotein intercellular transfer in eye field development, axon guidance and retino-tectal patterning, and visual cortex plasticity. Here, we have used the embryonic chick neural tube to investigate a possible role for homeoprotein Pax6 transfer in oligodendrocyte precursor cell (OPC) migration. We report the extracellular expression of Pax6 and the effects of gain and loss of extracellular Pax6 activity on OPCs. Open book cultures with recombinant Pax6 protein or Pax6 blocking antibodies, as well as in ovo gene transfer experiments involving expression of secreted Pax6 protein or secreted Pax6 antibodies, provide converging evidences that OPC migration is promoted by extracellular Pax6. The paracrine effect of Pax6 on OPC migration is thus a new example of direct non-cell autonomous homeoprotein activity. PMID:22028031

Di Lullo, Elizabeth; Haton, Celine; Le Poupon, Chantal; Volovitch, Michel; Joliot, Alain; Thomas, Jean-Leon; Prochiantz, Alain

2011-11-01

150

Multiple neural tube defects in the same patient with no neurological deficit  

PubMed Central

Congenital deformities involving the coverings of the nervous system are called neural tube defects (NTDs). NTD can be classified as neurulation defects, which occur by stage 12, and postneurulation defects. Cervical meningocele and myelomeningocele are rare spinal dysraphic lesions. Unlike lumbosacral dysraphic lesions, there is often no neurologic deficits and thus the subtle features of cervical cord tethering may be overlooked on imaging. The presence of meningomyelocele and/or encephaloceles at multiple (two or more) sites along the vertebral axis is a very rare event occurring in <1% of cases. Less than 10 cases have been described in the published literature. We are reporting a case of multiple NTD in same patient with no neurological deficit.

Tungaria, Arun; Srivastav, Arun Kumar; Mahapatra, Ashok K.; Kumar, Raj

2010-01-01

151

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

PubMed

Methylenetetrahydrofolate reductase (MTHFR) gene mutations have been implicated as risk factors for neural tube defects (NTDs). The best-characterized MTHFR genetic mutation 677C?T is associated with a 2-4 fold increased risk of NTD if patient is homozygous for this mutation. This risk factor is modulated by folate levels in the body. A second mutation in the MTHFR gene is an A?C transition at position 1298. The 1298A?C mutation is also a risk factor for NTD, but with a smaller relative risk than 677C?T mutation. Under conditions of low folate intake or high folate requirements, such as pregnancy, this mutation could become of clinical importance. We present a case report with MTHFR genetic mutation, who presented with recurrent familial pregnancy losses due to anencephaly/NTDs. PMID:22754237

Yaliwal, Laxmi V; Desai, Rathnamala M

2012-01-01

152

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

PubMed

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 multifactorial 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. PMID:18603496

Chen, Chih-Ping

2008-06-01

153

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

PubMed Central

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

Yaliwal, Laxmi V.; Desai, Rathnamala M.

2012-01-01

154

DNA methyltransferase3A as a molecular switch mediating the neural tube-to-neural crest fate transition  

PubMed Central

Here, we explore whether silencing via promoter DNA methylation plays a role in neural versus neural crest cell lineage decisions. We show that DNA methyltransferase3A (DNMT3A) promotes neural crest specification by directly mediating repression of neural genes like Sox2 and Sox3. DNMT3A is expressed in the neural plate border, and its knockdown causes ectopic Sox2 and Sox3 expression at the expense of neural crest markers. In vivo chromatin immunoprecipitation of neural folds demonstrates that DNMT3A specifically associates with CpG islands in the Sox2 and Sox3 promoter regions, resulting in their repression by methylation. Thus, DNMT3A functions as a molecular switch, repressing neural to favor neural crest cell fate.

Hu, Na; Strobl-Mazzulla, Pablo; Sauka-Spengler, Tatjana; Bronner, Marianne E.

2012-01-01

155

DNA methyltransferase3A as a molecular switch mediating the neural tube-to-neural crest fate transition.  

PubMed

Here, we explore whether silencing via promoter DNA methylation plays a role in neural versus neural crest cell lineage decisions. We show that DNA methyltransferase3A (DNMT3A) promotes neural crest specification by directly mediating repression of neural genes like Sox2 and Sox3. DNMT3A is expressed in the neural plate border, and its knockdown causes ectopic Sox2 and Sox3 expression at the expense of neural crest markers. In vivo chromatin immunoprecipitation of neural folds demonstrates that DNMT3A specifically associates with CpG islands in the Sox2 and Sox3 promoter regions, resulting in their repression by methylation. Thus, DNMT3A functions as a molecular switch, repressing neural to favor neural crest cell fate. PMID:23124063

Hu, Na; Strobl-Mazzulla, Pablo; Sauka-Spengler, Tatjana; Bronner, Marianne E

2012-11-01

156

Dehydroepiandrosterone biosynthesis, role, and mechanism of action in the developing neural tube.  

PubMed

Dehydroepiandrosterone (DHEA) is synthesized from cholesterol by activity of P450scc and P450c17, enzymes that we previously characterized in the developing nervous system. We describe the localization of P450c17 in the differentiated field of the ventral spinal cord in different motor neuron subtypes. We show that, during organogenesis, P450c17 activity is regulated along the antero/posterior axis of the spinal cord concomitantly with the gradient of neurogenesis. To examine whether DHEA may modulate this process, we measured proliferation and differentiation of ventral neural precursors in primary and explant cultures. Our results showed that DHEA-induced the expression of class II protein Nkx6.1, motor neuron precursor Olig-2, and definitive motor neuron marker Isl-1/2. DHEA also promoted proliferation of ventrally committed precursors in isolated spinal cord precursor cultures and in whole spinal cord explants. Both the proliferative and inductive effects of DHEA were dependent on sonic hedgehog signaling. The possibilities that the effects observed with DHEA were due to its metabolism into androgens or to activation of NMDA receptors were excluded. These results support the hypothesis that the tight regulation of DHEA biosynthesis may be a biologic clock restricting the period of ventral neuronal-precursor proliferation, thus controlling the number of pre-committed neurons in the developing neural tube. PMID:22649409

Galdo, Mark; Gregonis, Jennifer; Fiore, Christelle S; Compagnone, Nathalie A

2012-02-07

157

Field emission characteristics of carbon nano tubes under varying background pressure conditions  

Microsoft Academic Search

In general, for plasma switches, the initiation of the plasma is critical and this is usually achieved by a ¿trigger¿ scheme. The seed electrons needed to initiate a breakdown can be generated by several means such as thermionic, field or optical emission. While the thermionic emission has been used mainly in vacuum tubes and is a mature technology, field emission

Shaomao Li; Hulya Kirkici

2009-01-01

158

Development of precision drift tube detectors for very high background rates at the super-LHC  

Microsoft Academic Search

The muon spectrometer of the ATLAS experiment at the large hadron collider (LHC) is instrumented with three layers of precision tracking detectors each consisting of 6 or 8 layers of pressurized aluminum drift tubes of 30 mm diameter. The magnetic field of the spectrometer is generated by superconducting air-core toroid magnets. Already at the LHC design luminosity of 1034 cm2s-1,

J. Dubbert; S. Horvat; H. Kroha; F. Legger; O. Kortner; R. Richter; F. Rauscher

2007-01-01

159

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

PubMed

The vacuolated lens (vl) mouse mutant arose spontaneously on the C3H/HeSn background and exhibits neural tube defects (NTDs), congenital cataract, and occasionally a white belly spot. We previously reported that 1) the vl phenotypes are due to a mutation in an orphan G protein-coupled receptor (GPCR), Gpr161; 2) the penetrance of the vl NTD and cataract phenotypes are affected by genetic background, allowing three unlinked quantitative trait loci (QTL) to be mapped (modifiers of vacuolated lens, Modvl1-3); and 3) phenotype-based bioinformatics followed by genetic and molecular analysis identified a lens-specific transcription factor that contributes to the cataract-modifying effect of Modvl3. We now extend this analysis in three ways. First, using the Gpr161 mutation to unequivocally identify mutant adults and embryos, we determined that approximately 50% of vl/vl NTD-affected embryos die during development. Second, the MOLF/Ei genetic background suppresses this embryonic lethality but increases the incidence of the adult belly spot phenotype. Additional QTL analysis was performed, and two novel modifiers were mapped [Modvl4, logarithm of odds ratio (LOD) 4.4; Modvl5, LOD 5.0]. Third, phenotype-based bioinformatics identified candidate genes for these modifiers including two GPCRs that cause NTD or skin/pigmentation defects (Modvl4: Frizzled homolog 6; Modvl5: Melanocortin 5 receptor). Because GPCRs form oligomeric complexes, these genes were resequenced and nonsynonymous coding variants were identified. Bioinformatics and protein modeling suggest that these variants may be functional. Our studies further establish vl as a multigenic mouse model for NTDs and identify additional QTL that interact with Gpr161 to regulate neurulation. PMID:18796533

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

2008-09-16

160

Temporal deletion of Arl13b reveals that a mispatterned neural tube corrects cell fate over time.  

PubMed

Cilia are necessary for sonic hedgehog (Shh) signaling, which is required to pattern the neural tube. We know that ventral neural cell fates are defined by a specific cohort of transcription factors that are induced by distinct thresholds of Shh activity mediated by opposing gradients of Gli activator (GliA) and Gli repressor (GliR). Despite this understanding, the role of Shh as an instructive morphogen is viewed as increasingly complex, with current models integrating positive inputs in terms of ligand concentration and time, along with negative feedback via the downstream gene regulatory network. To investigate the relative contributions of the positive and negative inputs from Shh signaling in neural patterning, we took advantage of a protein that uncouples the regulation of GliA and GliR: the cilia protein ADP-ribosylation factor-like 13b (Arl13b). By deleting Arl13b in mouse, we induced low-level constitutive GliA function at specific developmental stages and defined a crucial period prior to E10.5 when shifts in the level of GliA cause cells to change their fate. Strikingly, we found that improperly patterned cells in these mice converted to the wild-type pattern by E12.5. We further showed that the recovery of patterning did not occur when we also deleted Gli3, the primary GliR in the neural tube, revealing a crucial role of Gli3 in the maintenance of neural patterning. PMID:23014696

Su, Chen-Ying; Bay, Sarah N; Mariani, Laura E; Hillman, Michael J; Caspary, Tamara

2012-09-26

161

Transcriptome Profiling of Genes Involved in Neural Tube Closure During Human Embryonic Development Using Long Serial Analysis of Gene Expression (Long-SAGE)  

PubMed Central

Background Neural tube defects (NTDs) are common human birth defects with a complex etiology. To develop a comprehensive knowledge of the genes expressed during normal neurulation, we established transcriptomes from human neural tube fragments during and after neurulation using long Serial Analysis of Gene Expression (long-SAGE). Methods Rostral and caudal neural tubes were dissected from normal human embryos aged between 26 and 32 days of gestation. Tissues from the same region and Carnegie stage were pooled (n>=4) and total RNA extracted to construct four long-SAGE libraries. Tags were mapped using the UniGene Homo sapiens 17 bp tag-to-gene best mapping set. Differentially expressed genes were identified by chi-square or Fisher’s exact test and validation was performed for a subset of those transcripts using in situ hybridization. In silico analyses were performed with BinGO and EXPANDER. Results We observed most genes to be similarly regulated in rostral and caudal regions, but expression profiles differed during and after closure. In silico analysis found similar enrichments in both regions for biological process terms, transcription factor binding and miRNA target motifs. Twelve genes potentially expressing alternate isoforms by region or developmental stage, and the miRNAs miR-339-5p, miR-141/200a, miR-23ab, and miR-129/129-5p, are among several potential candidates identified here for future research. Conclusions Time appears to influence gene expression in the developing central nervous system more than location. These data provide a novel complement to traditional strategies of identifying genes associated with human NTDs, and offer unique insight into the genes associated with normal human neurulation.

Krupp, D. R.; Xu, P-T.; Thomas, S.; Dellinger, A.; Etchevers, H. C.; Vekemans, M.; Gilbert, J. R.; Speer, M.C.; Ashley-Koch, A. E.; Gregory, S. G.

2012-01-01

162

The neural background of hyper-emotional aggression induced by post-weaning social isolation.  

PubMed

Post-weaning social isolation in rats is believed to model symptoms of early social neglect-induced externalizing problems including aggression-related problems. We showed earlier that rats reared in social isolation were hyper-aroused during aggressive contacts, delivered substantially more attacks that were poorly signaled and were preferentially aimed at vulnerable body parts of opponents (head, throat and belly). Here we studied the neural background of this type of aggression by assessing the expression of the activation marker c-Fos in 22 brain areas of male Wistar rats submitted to resident-intruder conflicts. Post-weaning social isolation readily produced the behavioral alterations noticed earlier. Social isolation significantly increased the activation of brain areas that are known to directly or indirectly control inter-male aggression. Particularly, the medial and lateral orbitofrontal cortices, anterior cingulate cortex, bed nucleus of the stria terminalis, medial and basolateral amygdala, hypothalamic attack area, hypothalamic paraventricular nucleus and locus coeruleus showed increased activations. This contrasts our earlier findings obtained in rats with experimentally induced hypoarousal, where abnormal attack patterns were associated with over-activated central amygdala, lateral hypothalamus, and ventrolateral periaqueductal gray that are believed to control predatory attacks. We have observed no similar activation patterns in rats socially isolated from weaning. In summary, these findings suggest that despite some phenotypic similarities, the neuronal background of hypo and hyperarousal-associated abnormal forms of aggression are markedly different. While the neuronal activation patterns induced by normal rivalry and hypoarousal-driven aggression are qualitative different, hyperarousal-associated aggression appears to be an exaggerated form of rivalry aggression. PMID:22548916

Toth, Mate; Tulogdi, Aron; Biro, Laszlo; Soros, Petra; Mikics, Eva; Haller, Jozsef

2012-04-23

163

LRP6 exerts non-canonical effects on Wnt signaling during neural tube closure.  

PubMed

Low-density lipoprotein receptor related protein 6 (Lrp6) mutational effects on neurulation were examined using gain (Crooked tail, Lrp6(Cd)) and loss (Lrp6(-)) of function mouse lines. Two features often associated with canonical Wnt signaling, dorsal-ventral patterning and proliferation, were no different from wild-type (WT) in the Lrp6(Cd/Cd) neural tube. Lrp6(-/-) embryos showed reduced proliferation and subtle patterning changes in the neural folds. Cell polarity defects in both Lrp6(Cd/Cd) and Lrp6(-/-) cranial folds were indicated by cell shape, centrosome displacement and failure of F-actin and GTP-RhoA accumulation at the apical surface. Mouse embryonic fibroblasts (MEFs) derived from Lrp6(Cd/Cd) or Lrp6(-/-) embryos exhibited elevated and decreased RhoA basal activity levels, respectively. While ligand-independent activation of canonical Wnt signaling, bypassing Lrp-Frizzled receptors, did not activate RhoA, non-canonical Wnt5a stimulation of RhoA activity was impaired in Lrp6(-/-) MEFs. RhoA inhibition exacerbated NTDs in cultured Lrp6 knockout embryos compared with WT littermates. In contrast, a ROCK inhibitor rescued Lrp6(Cd/Cd) embryos from NTDs. Lrp6 co-immunoprecipitated with Disheveled-associated activator of morphogenesis 1 (DAAM1), a formin promoting GEF activity in Wnt signaling. Biochemical and cell biological data revealed intracellular accumulation of Lrp6(Cd) protein where interaction with DAAM1 could account for observed elevated RhoA activity. Conversely, null mutation that eliminates Lrp6 interaction with DAAM1 led to lower basal RhoA activity in Lrp6(-/-) embryos. These results indicate that Lrp6 mediates not only canonical Wnt signaling, but can also modulate non-canonical pathways involving RhoA-dependent mechanisms to impact neurulation, possibly through intracellular complexes with DAAM1. PMID:23773994

Gray, Jason D; Kholmanskikh, Stanislav; Castaldo, Bozena S; Hansler, Alex; Chung, Heekyung; Klotz, Brian; Singh, Shawn; Brown, Anthony M C; Ross, M Elizabeth

2013-06-16

164

Effects of methionine on the cytoplasmic distribution of actin and tubulin during neural tube closure in rat embryos  

PubMed Central

Research has previously shown that, without methionine supplements, neural tube proteins of rat embryos cultured on bovine sera were hypomethylated and neural tubes failed to close. In the present study, to identify the proteins that became methylated during neurulation, rat embryos were first cultured on methionine-deficient bovine serum for 40 hr, then incubated with puromycin for 1 hr, and, finally, incubated with [methyl-14C]methionine and puromycin for 5 hr. On the basis of molecular weights, isoelectric points, and Western immunoblots, the methyl-14C-labeled proteins were identified as actin, ??-tubulin, and neurofilament L. Indirect immunofluorescence studies indicated that without the addition of methionine to the culture, localization of actin and ??-tubulin in the basal cytoplasm did not occur and these neuroepithelial cells lost their columnar morphology.

Moephuli, Shadrack R.; Klein, Norman W.; Baldwin, Michael T.; Krider, Hallie M.

1997-01-01

165

Epidemiologic Aspects of Neural Tube Defects in the United States: Changing Concepts and Their Importance for Screening and Prenatal Diagnostic Programs.  

National Technical Information Service (NTIS)

This report considers several major epidemiologic aspects of neural tube defects (NTDs). After examining briefly the approaches and goals of epidemiology the traditional epidemiologic concepts of NTDs are reviewed and new interpretations of the epidemiolo...

L. E. Sever M. A. Strassburg

1983-01-01

166

Dieting to Lose Weight and Occurrence of Neural Tube Defects in Offspring of Mexican–American Women  

Microsoft Academic Search

Lowered maternal weight gain and reduction in early pregnancy have been associated with risk of neural tube defects (NTDs)\\u000a in offspring. We examined the association of self-reported maternal dieting behaviors on the occurrence of NTDs. We conducted\\u000a a population based case–control study among Mexican–American women who were residents of the 14 Texas counties bordering Mexico.\\u000a Case women had an NTD-affected

Lucina Suarez; Marilyn Felkner; Jean D. Brender; Mark A. Canfield

167

A Second Common Mutation in the Methylenetetrahydrofolate Reductase Gene: An Additional Risk Factor for Neural-Tube Defects?  

Microsoft Academic Search

Summary Recently, we showed that homozygosity for the common 677(CrT) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, causing thermolability of the enzyme, is a risk factor for neural-tube defects (NTDs). We now report on another mutation in the same gene, the 1298(ArC) mutation, which changes a glutamate into an alanine residue. This mutation destroys anMboII recognition site and has an

Fons Gabreëls; Erik M. B. Stevens; Jan A. M. Smeitink; Frans J. M. Trijbels; Tom K. A. B. Eskes; Lambert P. van den Heuvel; Henk J. Blom

1998-01-01

168

Folate supplementation, MTHFR gene polymorphism and neural tube defects: a community based case control study in North India  

Microsoft Academic Search

The present study analyses the potential role of MTHFR gene polymorphism, folate supplementation and dietary pattern among\\u000a the mothers of NTD neonates and controls in heterogeneous populations of North India, with the special focus on their ethnic\\u000a labels. Results indicated significant increased risk for neural tube defects with respect to low folic acid supplementation\\u000a and vegetarian diet in univariate and

Roumi Deb; Jyoti Arora; Sanjenbam Yaiphaba Meitei; Sangeeta Gupta; Vanita Verma; Kallur Nava Saraswathy; Sunil Saran; Aloke Kumar Kalla

169

The thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) is not a major risk factor for neural tube defect in American Caucasians  

Microsoft Academic Search

Mutations in the gene for methylenetetrahydrofolate reductase (MTHFR) have been implicated as a risk factor in the formation\\u000a of neural tube defects. We investigated this gene in a series of 65 sporadic American Caucasians patients with lumbosacral\\u000a NTD and their unaffected parents, using both case-control design and assessment of linkage disequilibrium. We found no evidence\\u000a to support mutations in MTHFR

Marcy C. Speer; Gordon Worley; Joanne F. Mackey; Elizabeth Melvin; W. Jerry Oakes; Timothy M. George

1997-01-01

170

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

SciTech Connect

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

Shalat, S.L.; Walker, D.B.; Finnell, R.H. [Texas A& M Univ., College Station, TX (United States)

1996-10-01

171

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

PubMed Central

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

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

2011-01-01

172

Maternal Dietary Glycemic Intake and the Risk of Neural Tube Defects  

PubMed Central

Both maternal diabetes and obesity have been associated with an increased risk of neural tube defects (NTD), possibly due to a sustained state of hyperglycemia and/or hyperinsulinemia. Data were collected in the Boston University Slone Birth Defects Study (a case-control study) from 1988 to 1998. The authors examined whether high dietary glycemic index (DGI) and high dietary glycemic load (DGL) increased the risk of NTDs in nondiabetic women. Mothers of NTD cases and nonmalformed controls were interviewed in person within 6 months after delivery about diet and other exposures. Odds ratios and 95% confidence intervals were estimated from logistic regression for high DGI (?60) and high DGL (?205), with cutpoints determined by cubic spline. Of 698 case mothers, 25% had high DGI and 4% had high DGL. Of 696 control mothers, 15% had high DGI and 2% had high DGL. After adjustment for sociodemographic factors and other dietary factors, the odds ratio for high DGI was 1.5 (95% confidence interval: 1.1, 2.0); for high DGL, it was 1.8 (95% confidence interval: 0.8, 4.0). Diets with proportionally high DGI or DGL may put the developing fetus at risk of an NTD, adding further evidence that hyperglycemia lies within the pathogenic pathway.

Yazdy, Mahsa M.; Liu, Simin; Mitchell, Allen A.; Werler, Martha M.

2010-01-01

173

Neural tube defects in malaysia: data from the malaysian national neonatal registry.  

PubMed

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. Conclusion: NTDs were common in Malaysia. Mortality was high. Long-term monitoring of NTD prevalence following folic fortification of food is recommended. PMID:23583959

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

2013-04-12

174

Maternal smoking during pregnancy and neural tube defects in offspring: a meta-analysis.  

PubMed

PURPOSE: This study aims to examine the association between maternal smoking during pregnancy and neural tube defects (NTDs) in offspring. METHODS: We retrieved published studies on the association between maternal smoking during pregnancy and NTDs risk in offspring. Meta-analysis was applied to calculate the overall odds ratios (ORs) and their 95 % confidence intervals (CIs). The publication bias was assessed by the Egger's regression asymmetry test and Begg's rank correlation test. RESULTS: The overall effect of maternal smoking during pregnancy on NTDs was 1.03 (OR?=?1.03, 95 % CI?=?0.80-1.33). When subgroup analysis was conducted by geographic regions, the overall effects were 1.39 (OR?=?1.39, 95 % CI?=?1.18-1.64), 0.88 (OR?=?0.88, 95 % CI?=?0.66-1.17) in Europe and USA; when subgroup analysis was conducted by NTDs types, the overall effect was 1.55 (OR?=?1.55, 95 % CI?=?1.06-2.26) for spina bifida. CONCLUSIONS: Women who smoked during pregnancy had mildly elevated risk of having infants with NTDs. PMID:23760473

Wang, Meng; Wang, Zhi-Ping; Gong, Rui; Zhao, Zhong-Tang

2013-06-13

175

Spirulina (arthrospira) protects against valproic acid-induced neural tube defects in mice.  

PubMed

Valproic acid (VPA) is a potent inducer of neural tube defects in human and mouse, its teratogenicity is associated with its potential to generation of free radicals and increase oxidative stress. Furthermore, spirulina (SP) has shown pharmacological properties against teratogenicity, which are attributed to its antioxidant potential. Accordingly, the present study was performed to investigate the influence of SP on the teratogenicity of VPA in imprinting control region mice and the possible mechanisms of action. VPA (sodium valproate) was administered intraperitoneally to mice on gestation day (GD) 8 at a dose of 600 mg/kg. SP was given orally at 125, 250, and 500 mg/kg daily from GD0 through GD18. The most common finding in fetuses with VPA exposure was exencephaly. SP decreased the incidence of this and other malformations and increased levels of superoxide dismutase, catalase, and glutathione peroxidase. In conclusion, these results illustrate the protective action of SP through its antioxidant activity against VPA-induced teratogenicity. PMID:23134463

Escalona-Cardoso, Gerardo N; Paniagua-Castro, Norma; Pérez-Pastén, Ricardo; Chamorro-Cevallos, Germán

2012-11-07

176

Folic acid fortification prevents neural tube defects and may also reduce cancer risks.  

PubMed

The prevalence of neural tube defect (NTD)-affected pregnancies ranges between 0.4 and 2/1000 pregnancies in EU. NTDs result in severe malformations and sometimes miscarriages. Children born with NTD suffer for the rest of their life of disability and chronic healthcare issues, and many women therefore choose termination of pregnancy if NTD is diagnosed prenatally. Women planning for pregnancy are recommended to eat 400??g folic acid/d, whereas average figures across Europe indicate intakes of ?250??g/d for women of fertile age, a gap that could be bridged by implementation of folic acid fortification. The results of mandatory folic acid fortifications introduced in USA and Canada are a decrease between 25 and 45% of NTD pregnancies. Conclusion:? Evidence-based NTD prophylaxis is now practised in more than 60 countries worldwide. EU countries worry over possible cancer risks, but ignore a wealth of studies reporting decreasing cancer risks with folate intakes at recommended levels. Currently, there are indications of a U-shaped relationship, that is, higher cancer risks at low folate intakes (<150??g/day) and highly elevated folate intakes (>1?mg/day), respectively. However neither the global World Cancer Research review nor EU's European Food Safety Authority report present data on increased cancer risk at physiological folate intake levels. Therefore, EU should act to implement folic acid fortification as NTD prophylaxis as soon as possible. PMID:22783992

Jägerstad, Margaretha

2012-07-24

177

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

PubMed Central

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 ?-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.

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

2013-01-01

178

Folate supplementation, MTHFR gene polymorphism and neural tube defects: a community based case control study in North India.  

PubMed

The present study analyses the potential role of MTHFR gene polymorphism, folate supplementation and dietary pattern among the mothers of NTD neonates and controls in heterogeneous populations of North India, with the special focus on their ethnic labels. Results indicated significant increased risk for neural tube defects with respect to low folic acid supplementation and vegetarian diet in univariate and multivariate analyses. There was no significant difference in the genotypic or allelic distribution of MTHFR C677T polymorphism, however, high frequency of CT genotype, as observed, among controls suggests heterozygous advantage probably due to supplementary folate. Among the two communities, Muslim NTD mothers had higher TT genotype showing increased risk for neural tube defects (adjusted OR: 12.9; 95% CI: 1.21-136.8) and lower folic acid supplementation (adjusted OR: 3.5; 95% CI: 1.18-10.22). Whereas, marginal increased risk for NTDs with vegetarian diet was observed among Hindus. Cultural and ethnic variation in the risk factors for neural tube defects is highlighted in the study. PMID:21792640

Deb, Roumi; Arora, Jyoti; Meitei, Sanjenbam Yaiphaba; Gupta, Sangeeta; Verma, Vanita; Saraswathy, Kallur Nava; Saran, Sunil; Kalla, Aloke Kumar

2011-07-27

179

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

PubMed Central

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

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

2012-01-01

180

Maternal Exposure to Ambient Levels of Benzene and Neural Tube Defects among Offspring: Texas, 1999-2004  

PubMed Central

Background Previous studies have reported positive associations between maternal exposure to air pollutants and several adverse birth outcomes. However, there have been no studies assessing the association between environmental levels of hazardous air pollutants, such as benzene, and neural tube defects (NTDs), a common and serious group of congenital malformations. Objective Our goal was to conduct a case–control study assessing the association between ambient air levels of benzene, toluene, ethylbenzene, and xylene (BTEX) and the prevalence of NTDs among offspring. Methods The Texas Birth Defects Registry provided data on NTD cases (spina bifida and anencephaly) delivered between 1999 and 2004. The control group was a random sample of unaffected live births, frequency matched to cases on year of birth. Census tract–level estimates of annual BTEX levels were obtained from the U.S. Environmental Protection Agency 1999 Assessment System for Population Exposure Nationwide. Restricted cubic splines were used in mixed-effects logistic regression models to determine associations between each pollutant and NTD phenotype. Results Mothers living in census tracts with the highest benzene levels were more likely to have offspring with spina bifida than were women living in census tracts with the lowest levels (odds ratio = 2.30; 95% confidence interval, 1.22–4.33). No significant associations were observed between anencephaly and benzene or between any of the NTD phenotypes and toluene, ethylbenzene, or xylene. Conclusion In the first study to assess the relationship between environmental levels of BTEX and NTDs, we found an association between benzene and spina bifida. Our results contribute to the growing body of evidence regarding air pollutant exposure and adverse birth outcomes.

Lupo, Philip J.; Symanski, Elaine; Waller, D. Kim; Chan, Wenyaw; Langlois, Peter H.; Canfield, Mark A.; Mitchell, Laura E.

2011-01-01

181

Analysis of the MTHFD1 promoter and risk of neural tube defects  

PubMed Central

Genetic variants in MTHFD1 (5,10-methylenetetrahydrofolate dehydrogenase/ 5,10-methenyltetrahydrofolate cyclohydrolase/ 10-formyltetrahydrofolate synthetase), an important folate metabolic enzyme, are associated with a number of common diseases, including neural tube defects (NTDs). This study investigates the promoter of the human MTHFD1 gene in a bid to understand how this gene is controlled and regulated. Following a combination of in silico and molecular approaches, we report that MTHFD1 expression is controlled by a TATA-less, Initiator-less promoter and transcription is initiated at multiple start sites over a 126bp region. We confirmed the presence of three database polymorphisms (dbSNP) by direct sequencing of the upstream region (rs1076991 C>T, rs8010584 G>A, rs4243628 G>T), with a fourth (dbSNP rs746488 A>T) not found to be polymorphic in our population and no novel polymorphisms identified. We demonstrate that a common SNP rs1076991 C>T within the window of transcriptional initiation exerts a significant effect on promoter activity in vitro. We investigated this SNP as a potential risk factor for NTDs in a large homogenous Irish population and determined that it is not an independent risk factor, but, it does increase both case (?2 = 11.06, P = 0.001) and maternal (?2 = 6.68, P = 0.01) risk when allele frequencies were analysed in combination with the previously identified disease-associated p.R653Q (c.1958 G>A; dbSNP rs2236225) polymorphism. These results provide the first insight into how MTHFD1 is regulated and further emphasise its importance during embryonic development.

Carroll, Nicola; Pangilinan, Faith; Molloy, Anne M.; Troendle, James; Mills, James L.; Kirke, Peadar N.; Brody, Lawrence C.; Scott, John M.; Parle-McDermott, Anne

2009-01-01

182

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

PubMed

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

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

2013-04-12

183

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

SciTech Connect

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

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

1994-09-01

184

Time trends in neural tube defects prevalence in relation to preventive strategies: an international study  

PubMed Central

OBJECTIVE: To examine time trends in neural tube defects (NTD) prevalence from 1987 to 1996 in relation to the primary prevention policies for folic acid supplementation strategies in different countries. DESIGN: Retrospective time trends analysis of NTD prevalence. SETTING: 11 birth defect registries of congenital malformations participating in the International Clearinghouse for Birth Defects Monitoring System, in the period from 1 July 1987 to 30 June 1996. SUBJECTS: 8207 live births, stillbirths and terminated pregnancies affected by anencephaly or spina bifida registered by the 11 participating centres 1987-1996. OUTCOME MEASURES: Prevalence rate ratios based on the annual rates, using the Poisson regression model. RESULTS: During the study period a significant fall in prevalence rates for all NTD is present in Atlanta (USA), England and Wales, Hungary and Japan, and a significant rise in Norway and South America. After adjusting for the secular trends observed in the earlier years of the study, no significant trend can be attributed to preventive strategies. Data on NTD prevalence are supplemented with information on folate awareness among some of the populations studied. CONCLUSION: There is no evidence that, up to the middle of 1996, any change in time trend was attributable to the introduction of national folate supplementation policies. The possible effectiveness of folate supplementation policies for the reduction of NTD clearly needs to be tried and studied for several more years. Considering that in the Western world about 50% of pregnancies are unplanned, a policy that rests on action taken before conception can only have limited success. Strategies based on food enrichment, such as was introduced in the USA from the beginning of 1998, may prove to be more successful.  

Rosano, A.; Smithells, D.; Cacciani, L.; Botting, B.; Castilla, E.; Cornel, M.; Erickson, D.; Goujard, J.; Irgens, L.; Merlob, P.; Robert, E.; Siffel, C.; Stoll, C.; Sumiyoshi, Y.

1999-01-01

185

The use of a Toolkit for health needs assessment on neural tube defects in Argentina.  

PubMed

Health needs assessment (HNA) is a commonly used process for those working in public health. The PHG Foundation has developed a Toolkit to provide users with a stepwise approach for undertaking a HNA on birth defects. We report the findings from using the Toolkit to examine needs in relation to policies and programs, services, and interventions for neural tube defects (NTDs) in Argentina. The trend over the last few decades is one of decline in infant mortality from nutritional and infectious causes, thus further increasing the relative importance of birth defects. The observed prevalence of NTDs is consistent with that reported internationally. Since 2002 folic acid fortification (FAF) has been mandatory by law, and different studies have shown at least a 50 % decrease in the birth prevalence of NTDs after FAF. In Argentina, there is inequity between the public and non-public health sectors. The birth prevalence of NTDs seems lower in the non-public sector, possibly as a result of better nutritional status of women, higher access to folic acid supplementation, and earlier prenatal diagnosis followed by termination of pregnancy (ToP) in non-public hospitals. Although illegal, ToP is believed to be widespread, with better access for people of higher socioeconomic status. Through the process of HNA, we identified several unmet needs regarding registration of cases, public and professional education, legislation, and organization of care pathways. In our experience, the Toolkit brought together people working on the same issue, and it engaged and motivated experts and stakeholders to work together to tackle the problem. PMID:23055101

Groisman, Boris; Liascovich, Rosa; Barbero, Pablo; Alberg, Corinna; Moorthie, Sowmiya; Nacul, Luis; Sagoo, Gurdeep S

2012-10-04

186

Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects  

PubMed Central

Persistent organic pollutants (POPs) have been associated with a wide range of adverse health effects. Our case–control study was performed to explore the association between placental levels of selected POPs and risks for neural tube defects (NTDs) in a Chinese population with a high prevalence of NTDs. Cases included 80 fetuses or newborns with NTDs, whereas the controls were 50 healthy, nonmalformed newborn infants. Placental concentrations of polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers were analyzed by gas chromatography–mass spectrometry. The medians of PAHs, o,p?-isomers of dichlorodiphenyltrichloroethane (DDT) and metabolites, ?- and ?-hexachlorocyclohexane (HCH), and ?-endosulfan were significantly higher in case placentas than in controls. PAH concentrations above the median were associated with a 4.52-fold [95% confidence interval (CI), 2.10–9.74) increased risk for any NTDs, and 5.84- (95% CI, 2.28–14.96) and 3.71-fold (95% CI, 1.57–8.79) increased risks for anencephaly and spina bifida, respectively. A dose–response relationship was observed between PAH levels and the risk of NTDs, with odds ratios for the second, third, and fourth quartiles, compared with the first, of 1.77- (95% CI, 0.66–4.76), 3.83- (95% CI, 1.37–10.75), and 11.67-fold (95% CI, 3.28–41.49), respectively. A dose–response relationship was observed for anencephaly and spina bifida subtypes. Similar results were observed for o,p?-DDT and metabolites, ?-HCH, ?-HCH, and ?-endosulfan, whereas no dose–response relationship was observed for the last two pollutants. Elevated placental concentrations of PAHs, o,p?-DDT and metabolites, and ?-HCH were associated with increased risks of NTDs in this population.

Ren, Aiguo; Qiu, Xinghua; Jin, Lei; Ma, Jin; Li, Zhiwen; Zhang, Le; Zhu, Huiping; Finnell, Richard H.; Zhu, Tong

2011-01-01

187

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

PubMed

OBJECTIVE: Data on the prevalence of birth defects and neural tube defects (NTD) in Latin America are limited. The present review summarizes NTD prevalence and time trends in Latin American countries and compares pre- and post-fortification periods to assess the impact of folic acid fortification in these countries. DESIGN: We carried out a literature review of studies and institutional reports published between 1990 and 2010 that contained information on NTD prevalence in Latin America. RESULTS: NTD prevalence in Latin American countries varied from 0·2 to 9·6 per 1000 live births and was influenced by methods of ascertainment. Time trends from Bogota, Costa Rica, Dominican Republic, Guatemala City, Mexico and Puerto Rico showed average annual declines of 2·5 % to 21·8 %. Pre- and post-fortification comparisons were available for Argentina, Brazil, Chile, Costa Rica, Puerto Rico and Mexico. The aggregate percentage decline in NTD prevalence ranged from 33 % to 59 %. CONCLUSIONS: The present publication is the first to review data on time trends and the impact of folic acid fortification on NTD prevalence in Latin America. Reported NTD prevalence varied markedly by geographic region and in some areas of Latin America was among the lowest in the world, while in other areas it was among the highest. For countries with available information, time trends showed significant declines in NTD prevalence and these declines were greater in countries where folic acid fortification of staples reached the majority of the population at risk, such as Chile and Costa Rica. PMID:23464652

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

2013-03-01

188

An increase in neural tube defect notifications, South Australia, 2009-2010  

PubMed Central

Introduction In South Australia, reporting of live births, stillbirths of at least 20 weeks or 400 g birth weight, termination of pregnancies and congenital anomalies is mandated. We describe the investigation of an increase in notifications of neural tube defects (NTDs) in South Australia in 2009 and 2010 using data from several surveillance systems. Methods NTD trend data from 1966 to 2010 were reviewed. Comparisons of pregnancies affected by an NTD in 2009 and 2010 were made with pregnancies affected by an NTD in the period 2003–2008 and with all pregnancies in 2009 and 2010. Statistical analysis was undertaken using Poisson regression, ?2 or Fisher’s exact tests. Results The prevalence of NTD-affected pregnancies was 1.95 per 1000 births (39 cases) in 2010 and 1.91 per 1000 births in 2009 (38 cases), the highest annual rates since 1991. Case series comparisons indicated women with NTD-affected pregnancies in 2009 and 2010 were less likely to be Caucasian compared with women who had NTD-affected pregnancies in the period 2003–2008. Women born in the Middle East and African region (n = 7) were significantly more likely to have NTD-affected pregnancies in the years 2009 and 2010 (relative risk: 3.03; 95% confidence interval: 1.39–6.62) compared with women born in the Oceania region. Discussion The increased notifications of NTDs can only be partially explained by the increase in numbers of women from the Middle East and African region, with no other contributory causes revealed. This analysis highlighted areas where prevention efforts should be strengthened and surveillance data improved.

Scheil, Wendy; Nguyen, Anh-Minh; Sage, Leonie; Scott, Joan

2013-01-01

189

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

PubMed

Arsenic, cadmium, lead, and mercury are neurotoxins, and some studies suggest that these elements might also be teratogens. Using a case-control study design, we investigated the relation between exposure to these heavy metals and neural tube defects (NTDs) in offspring of Mexican-American women living in 1 of the 14 Texas counties bordering Mexico. A total of 184 case-women with NTD-affected pregnancies and 225 control-women with normal live births were interviewed about their environmental and occupational exposures during the periconceptional period. Biologic samples for blood lead and urinary arsenic, cadmium, and mercury were also obtained for a subset of these women. Overall, the median levels of these biomarkers for heavy metal exposure did not differ significantly (P > 0.05) between case- and control-women. However, among women in the highest income group, case-women were nine times more likely (95% confidence interval (CI) 1.4-57) than control-women to have a urinary mercury 5.62 microg/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. PMID:16171797

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

2005-09-19

190

Input determination for neural network models in water resources applications. Part 1—background and methodology  

Microsoft Academic Search

The use of artificial neural network (ANN) models in water resources applications has grown considerably over the last decade. However, an important step in the ANN modelling methodology that has received little attention is the selection of appropriate model inputs. This article is the first in a two-part series published in this issue and addresses the lack of a suitable

Gavin J. Bowden; Graeme C. Dandy; Holger R. Maier

2005-01-01

191

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

PubMed

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

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

2012-11-15

192

Maternal and Infant Gene-Folate Interactions and the Risk of Neural Tube Defects  

PubMed Central

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

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

2012-01-01

193

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

PubMed

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

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

2012-08-17

194

Neural network analysis of fin-tube refrigerating heat exchanger with limited experimental data  

Microsoft Academic Search

We consider the problem of accuracy in heat rate estimations from artificial neural network (ANN) models of heat exchangers used for refrigeration applications. Limited experimental measurements from a manufacturer are used to show the capability of the neural network technique in modeling the heat transfer phenomena in these systems. A well-trained network correlates the data with errors of the same

Arturo Pacheco-Vega; Mihir Sen; K. T. Yang; Rodney L. McClain

2001-01-01

195

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

PubMed Central

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

Maddox, Dennis M; Manlapat, Anna; Roon, Penny; Prasad, Puttur; Ganapathy, Vadivel; Smith, Sylvia B

2003-01-01

196

Acoustic characterization and prediction of the cut-off dimensionless frequency of an elastic tube by neural networks.  

PubMed

A neural network is developed to predict cut-off dimensionless frequencies of the antisymmetric circumferential waves (Ai) propagating around an elastic circular cylindrical shell of different radius ratio b/a (a, outer radius; b, inner radius). The useful data to train and test the performances of the model are determinated from calculated trajectories of natural modes of resonances or extracted from time-frequency representations of Wigner-Ville of the acoustic backscattered time signal obtained from a computation. In this work, the studied tubes are made of aluminum or stainless steel. The material density, the radius ratio b/a, the index i of the antisymmetric waves, and the propagation velocities in the tube, are selected like relevant entries of the model of neural network. During the development of the network, several configurations are evaluated. The optimal model selected is a network with two hidden layers. This model is able to predict the cut-off dimensionless frequencies with a mean relative error (MRE) of about 1%, a mean absolute error (MAE) of 3.10(-3) k1a, and a standard error (SE) of 10(-3) k1a (k1a is the dimensionless frequency, k is the wave number in water). PMID:17523570

Dariouchy, Abdelilah; Aassif, El Houcein; Décultot, Dominique; Maze, Gérard

2007-05-01

197

The iron exporter ferroportin 1 is essential for development of the mouse embryo, forebrain patterning and neural tube closure  

PubMed Central

Neural tube defects (NTDs) are some of the most common birth defects observed in humans. The incidence of NTDs can be reduced by peri-conceptional folic acid supplementation alone and reduced even further by supplementation with folic acid plus a multivitamin. Here, we present evidence that iron maybe an important nutrient necessary for normal development of the neural tube. Following implantation of the mouse embryo, ferroportin 1 (Fpn1) is essential for the transport of iron from the mother to the fetus and is expressed in the visceral endoderm, yolk sac and placenta. The flatiron (ffe) mutant mouse line harbors a hypomorphic mutation in Fpn1 and we have created an allelic series of Fpn1 mutations that result in graded developmental defects. A null mutation in the Fpn1 gene is embryonic lethal before gastrulation, hypomorphic Fpn1ffe/ffe mutants exhibit NTDs consisting of exencephaly, spina bifida and forebrain truncations, while Fpn1ffe/KI mutants exhibit even more severe NTDs. We show that Fpn1 is not required in the embryo proper but rather in the extra-embryonic visceral endoderm. Our data indicate that loss of Fpn1 results in abnormal morphogenesis of the anterior visceral endoderm (AVE). Defects in the development of the forebrain in Fpn1 mutants are compounded by defects in multiple signaling centers required for maintenance of the forebrain, including the anterior definitive endoderm (ADE), anterior mesendoderm (AME) and anterior neural ridge (ANR). Finally, we demonstrate that this loss of forebrain maintenance is due in part to the iron deficiency that results from the absence of fully functional Fpn1.

Mao, Jinzhe; McKean, David M.; Warrier, Sunita; Corbin, Joshua G.; Niswander, Lee; Zohn, Irene E.

2010-01-01

198

Severe neural tube defects in the loop-tail mouse result from mutation of Lpp1, a novel gene involved in floor plate specification  

Microsoft Academic Search

Neural tube defects (NTD) are clinically important congenital malformations whose molecular mecha- nisms are poorly understood. The loop-tail ( Lp) mutant mouse provides a model for the most severe NTD, craniorachischisis, in which the brain and spinal cord remain open. During a positional cloning approach, we have identified a mutation in a novel gene, Lpp1, in the Lp mouse, providing

Jennifer N. Murdoch; Kit Doudney; Caroline Paternotte; Andrew J. Copp; Philip Stanier

2001-01-01

199

THE CURLY-TAIL (CT) MOUSE, AN ANIMAL MODEL OF NEURAL TUBE DEFECTS, DISPLAYS ALTERED HOMOCYSTEINE METABOLISM WITHOUT FOLATE RESPONSIVENESS OR A DEFECT IN MTHFR  

Technology Transfer Automated Retrieval System (TEKTRAN)

Maternal mild hyperhomocysteinemia is associated with increased risk for bearing children with neural tube defects (NTD). Folate intake corrects hyperhomocysteinemia and prevents up to 70% of NTD. The curly-tail (ct) mouse, an animal model for NTD, has been suggested to display features that closely...

200

Increased risk of recurrence of pregnancies complicated by fetal neural tube defects in mothers receiving poor diets, and possible benefit of dietary counselling  

Microsoft Academic Search

One hundred and seventy-four women who had previously had a child with a neural-tube defect were assessed retrospectively on the quality of their diets during the first trimester of that pregnancy, between pregnancies, and during the first trimester of other pregnancies. They were then studied prospectively during the first trimester of 186 following pregnancies and the outcome of these was

K M Laurence; N James; M Miller; H Campbell

1980-01-01

201

Genetic basis of neural tube defects: the mouse gene loop-tail maps to a region of chromosome 1 syntenic with human 1q21–q23  

Microsoft Academic Search

A genetic basis for neural tube defects (NTD) is rarely doubted, but the genes involved have not yet been identified. This is partly due to a lack of suitable families on which to perform linkage analysis. An alternative approach is to use the many mouse genes that cause NTD as a means of isolating their human homologues. Loop-tail (Lp) is

Philip Stanier; Jennifer N. Henson; Jane Eddleston; Gudrun E. Moore; Andrew J. Copp

1995-01-01

202

Effects of Folic Acid Public Education on Awareness, Knowledge and Behavior Change in Women of Childbearing Age in Preventing Neural Tube Defects  

Microsoft Academic Search

One goal of Healthy People 2000 is to reduce incidence of spina bifida and other neural tube defects to 3\\/10,000 live births. The US Public Health Service confirms the role of folate hi preventing NTDs by recommending that all women of childbearing age consume at least 400 micrograms of folate per day. NTDs occur before most women realize they are

M. A. McFarland; C. B. Johnson; J. M. Moore; C. D. Pierce; K. T. Robinson; K. M. Smith; W. B. Boone; K. N. Broome

1999-01-01

203

Establishing and Interpreting Graded Sonic Hedgehog Signaling during Vertebrate Neural Tube Patterning: The Role of Negative Feedback  

PubMed Central

The secreted protein Sonic Hedgehog (SHH) acts in graded fashion to pattern the dorsal–ventral axis of the vertebrate neural tube. This is a dynamic process in which increasing concentrations and durations of exposure to SHH generate neurons with successively more ventral identities. Interactions between the receiving cells and the graded signal underpin the mechanism of SHH action. In particular, negative feedback, involving proteins transcriptionally induced or repressed by SHH signaling, plays an essential role in shaping the graded readout. On one hand, negative feedback controls, in a noncell-autonomous manner, the distribution of SHH across the field of receiving cells. On the other, it acts cell-autonomously to convert different concentrations of SHH into distinct durations of intracellular signal transduction. Together, these mechanisms exemplify a strategy for morphogen interpretation, which we have termed temporal adaptation that relies on the continuous processing and refinement of the cellular response to the graded signal.

Ribes, Vanessa; Briscoe, James

2009-01-01

204

Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail.  

PubMed

Neural tube defects (NTDs) such as spina bifida and anencephaly are common congenital malformations in humans (1/1,000 births) that result from failure of the neural tube to close during embryogenesis. The etiology of NTDs is complex, with both genetic and environmental contributions; the genetic component has been extensively studied with mouse models. Loop-tail (Lp) is a semidominant mutation on mouse chromosome 1 (ref. 4). In the two known Lp alleles (Lp, Lpm1Jus), heterozygous mice exhibit a characteristic looped tail, and homozygous embryos show a completely open neural tube in the hindbrain and spinal region, a condition similar to the severe craniorachischisis defect in humans. Morphological and neural patterning studies indicate a role for the Lp gene product in controlling early morphogenesis and patterning of both axial midline structures and the developing neural plate. The 0.6-cM/0.7-megabase (Mb) Lp interval is delineated proximally by D1Mit113/Apoa2/Fcer1g and distally by Fcer1a/D1Mit149/Spna1 and contains a minimum of 17 transcription units. One of these genes, Ltap, encodes a homolog of Drosophila Strabismus/Van Gogh (Stbm/Vang), a component of the frizzled/dishevelled tissue polarity pathway. Ltap is expressed broadly in the neuroectoderm throughout early neurogenesis and is altered in two independent Lp alleles, identifying this gene as a strong candidate for Lp. PMID:11431695

Kibar, Z; Vogan, K J; Groulx, N; Justice, M J; Underhill, D A; Gros, P

2001-07-01

205

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

SciTech Connect

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.

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)]. E-mail: winnl@biology.queensu.ca

2006-03-01

206

Local Protease Signaling Contributes to Neural Tube Closure in the Mouse Embryo  

Microsoft Academic Search

SUMMARY We report an unexpected role for protease signaling inneural tube closureand the formation of thecentral nervous system. Mouse embryos lacking protease- activated receptors 1 and 2 showed defective hind- brain and posterior neuropore closure and devel- oped exencephaly and spina bifida, important human congenital anomalies. Par1 and Par2 were expressed in surface ectoderm, and Par2 was ex- pressed selectively

Eric Camerer; Adrian Barker; Daniel N. Duong; Rajkumar Ganesan; Hiroshi Kataoka; Ivo Cornelissen; Molly R. Darragh; Arif Hussain; Yao-Wu Zheng; Yoga Srinivasan; Christopher Brown; Shan-Mei Xu; Jean B. Regard; Chen-Yong Lin; Charles S. Craik; Daniel Kirchhofer; Shaun R. Coughlin

2010-01-01

207

Pax2\\/5 and Pax6 subdivide the early neural tube into three domains  

Microsoft Academic Search

The nested expression patterns of the paired-box containing transcription factors Pax2\\/5 and Pax6 demarcate the midbrain and forebrain primordium at the neural plate stage. We demonstrate that, in Pax2\\/5 deficient mice, the mesencephalon\\/metencephalon primordium is completely missing, resulting in a fusion of the forebrain to the hindbrain. Morphologically, in the alar plate the deletion is characterized by the substitution of

Martin Schwarz; Gonzalo Alvarez-Bolado; Gregory Dressler; Pavel Urbánek; Meinrad Busslinger; Peter Gruss

1999-01-01

208

Histone modification mapping in human brain reveals aberrant expression of histone H3 lysine 79 dimethylation in neural tube defects.  

PubMed

Neural tube defects (NTDs) are severe, common birth defects that result from failure of neural tube closure, but their pathological mechanisms are not yet fully understood. Histone modifications have an important role in gene regulation during fetal development. We therefore hypothesized that the human NTDs may be partly caused by an imbalance in metabolism, perhaps caused by nutritional deficiencies, that leads to aberrant histone modifications. Here, we report a screen of fetal brain histone modifications using 2D nano-LC strong cation exchange reverse phase (SCX/RP) MS/MS and the identification of 61 unique post-translational modification sites on histones H1, H2a, H2b, H3, and H4. Of these, 38 sites are novel (not already found in the Uniprot database). Furthermore, we compared the histone modification patterns between normal brains and NTD brains special of which maternal folate levels were lower than of normal control. The results showed that histone H3 lysine 79 dimethylation (H3K79me2) and a novel identified site, H2bK5 monomethylation (H2bK5me1), were completely absent in individuals with NTDs. Follow-up Western blotting validated the decreased H3K79me2 expression in brains with NTDs, but the amplified samples experiments displayed that decreased H3K79me2 expression was not suitable for all samples with NTDs. Furthermore, folate-free treated mouse embryonic stem cells induced the decreased H3K79me2 level. Subsequently, our ChIP results in normal fetal brain tissues showed that H3K79me2 binds to SUFU, RARA and ITGA3 which induce NTDs phenotype after knockout in mice, and in NTDs brain tissues the bindings of H3K79me2 to these three genes were significantly altered. Taken together, our study indicated that low folate treatment might attenuate H3K79 dimethylation, further affect its regulate activation on target genes, some of which are NTDs-resulting associated, lastly interrupt early embryo developing. Our study increases the understanding of normal fetal brain histone modifications and provides a platform for investigating histone modifications in neural disease and also has an insight into a potential role of aberrant histone modification in etiology of NTDs. PMID:23376398

Zhang, Qin; Xue, Peng; Li, Huili; Bao, Yihua; Wu, Lihua; Chang, Shaoyan; Niu, Bo; Yang, Fuquan; Zhang, Ting

2013-01-29

209

A high throughput messenger RNA differential display screen identifies discrete domains of gene expression and novel patterning processes along the developing neural tube  

PubMed Central

Background During early development the vertebrate neural tube is broadly organized into the forebrain, midbrain, hindbrain and spinal cord regions. Each of these embryonic zones is patterned by a combination of genetic pathways and the influences of local signaling centres. However, it is clear that much remains to be learned about the complete set of molecular cues that are employed to establish the identity and intrinsic neuronal diversity of these territories. In order to address this, we performed a high-resolution messenger RNA differential display screen to identify molecules whose expression is regionally restricted along the anteroposterior (AP) neuraxis during early chick development, with particular focus on the midbrain and hindbrain vesicles. Results This approach identified 44 different genes, with both known and unknown functions, whose transcription is differentially regulated along the AP axis. The identity and ontological classification of these genes is presented. The wide variety of functional classes of transcripts isolated in this screen reflects the diverse spectrum of known influences operating across these embryonic regions. Of these 44 genes, several have been selected for detailed in situ hybridization analysis to validate the screen and accurately define the expression domains. Many of the identified cDNAs showed no identity to the current databases of known or predicted genes or ESTs. Others represent genes whose embryonic expression has not been previously reported. Expression studies confirmed the predictions of the primary differential display data. Moreover, the nature of identified genes, not previously associated with regionalisation of the brain, identifies novel potential mechanisms in that process. Conclusion This study provides an insight into some of the varied and novel molecular networks that operate during the regionalization of embryonic neural tissue and expands our knowledge of molecular repertoire used during development.

Chambers, David; Mason, Ivor

2006-01-01

210

No association of the polyhistidine tract polymorphism of the ZIC2 gene with neural tube defects in a South American (ECLAMC) population.  

PubMed

The ZIC genes comprise a family of transcriptional factors associated with neural tube defects (NTDs) in mice and with holoprosencephaly in humans. An allelic variant of ZIC2, a CAC repeat within the first exon, was reported in association with an increased risk of non-syndromic NTDs in patients with a Hispanic ethnic background. We investigated whether this 10-residue histidine tract polymorphism of the ZIC2 gene (c.718_720dupCAC) was associated with the risk of NTDs in a sample of 138 patients and their parents from the Latin American Collaborative Study of Congenital Malformations (ECLAMC) hospital network. Analysis with log-linear models of 138 family triads of mother, father and affected child did not provide evidence to support the notion that case (or maternal) 10H/10H or -/10H genotypes were associated with NTDs in this South American population sample, where the 10H variant occurred in 5% of newborns affected with NTDs. We also described the first example of the homozygous state of the 10H allele in a patient with cephalocele, holoprosencephaly and microphthalmia, but did not ascertain whether this polymorphism is associated with the increased risk of a specific subgroup of NTDs, as a normal father of a patient with anencephaly presented the same genotype. PMID:21479430

Costa-Lima, Marcelo A; Meneses, Heloisa N M; El-Jaick, Kenia B; Amorim, Márcia R; Castilla, Eduardo E; Orioli, Iêda M

211

Mechanical properties of micro probe and tube array for neural penetrating devices.  

PubMed

This paper describes the fabrication of Si micro probe and SiO(2) micro tube array and their mechanical properties. The device is successfully fabricated with high-density array. One of the requirements of the penetrating device is to have the enough mechanical strength to be able to penetrate into the tissue. Hence mechanical properties are investigated and discussed using the results on bending obtained by experiments and simulation of finite element method. The device was penetrated by simple in-vitro experiments using a gelatin. PMID:18001918

Takei, Kuniharu; Kawashima, Takahiro; Sawada, Kazuaki; Ishida, Makoto

2007-01-01

212

Disruption of proteoglycans in neural tube fluid by beta-D-xyloside alters brain enlargement in chick embryos.  

PubMed

Following neurulation, the anterior end of the neural tube undergoes a dramatic increase in size due mainly to the enlarging of the brain cavity. This cavity is filled with so-called neural tube fluid (NTF), whose positive pressure has been shown to play a key role in brain morphogenesis. This fluid contains a water-soluble matrix, rich in chondroitin sulfate (CS), which has been proposed as an osmotic regulator of NTF pressure genesis. The purpose of the present study is to observe the influence of CS on NTF osmolality and its relation to NTF hydrostatic pressure and brain expansion. NTF was obtained by means of microaspiration from the mesencephalic cavity of chick embryos. The osmolality of NTF between H.H. stages 20 and 29 was measured on the basis of its cryoscopic point. CS synthesis was disrupted by using beta-D-xyloside and the induced variations in brain volume were measured by means of morphometry. We also measured the variations in NTF osmolality, hydrostatic pressure, and the concentration of CS and sodium induced by means of beta-D-xyloside. Our data reveal that, at the earliest stages of development analyzed, variations in NTF osmolality show a characteristic pattern that coincides with the developmental changes in the previously described fluid pressure. Chick embryos treated with beta-D-xyloside, a chemical that disrupts CS synthesis, displayed a notable increase in brain volume but no other apparent developmental alterations. Morphometric analysis revealed that this increase was due to hyperenlargement of the brain cavity. Beta-D-xyloside brings about specific changes in the biochemical composition of NTF, which entails a large increase in CS concentration, mainly in the form of free chains, and in that of sodium. As a result, the fluid's osmolality and brain intraluminal pressure increased, which could account for the increase in size of the brain anlage. These data support the hypothesis that the intraluminal pressure involved in embryonic brain enlargement is directly dependent on NTF osmolality, and that the concentrations of CS and its associated microions could play a key role in the regulation of this process. PMID:9845201

Alonso, M I; Gato, A; Moro, J A; Barbosa, E

1998-12-01

213

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  

PubMed Central

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 differentially affects the expression levels of the two Ptk7 protein isoforms and, while some Ptk7 protein can still be detected at the membrane, chuzhoi mutants demonstrate a significant reduction in membrane localization of Ptk7 protein. This mutant provides a useful tool to allow future studies aimed at understanding the molecular function of Ptk7.

2010-01-01

214

Frizzled 1 and frizzled 2 genes function in palate, ventricular septum and neural tube closure: general implications for tissue fusion processes  

PubMed Central

The closure of an open anatomical structure by the directed growth and fusion of two tissue masses is a recurrent theme in mammalian embryology, and this process plays an integral role in the development of the palate, ventricular septum, neural tube, urethra, diaphragm and eye. In mice, targeted mutations of the genes encoding frizzled 1 (Fz1) and frizzled 2 (Fz2) show that these highly homologous integral membrane receptors play an essential and partially redundant role in closure of the palate and ventricular septum, and in the correct positioning of the cardiac outflow tract. When combined with a mutant allele of the planar cell polarity gene Vangl2 (Vangl2Lp), Fz1 and/or Fz2 mutations also cause defects in neural tube closure and misorientation of inner ear sensory hair cells. These observations indicate that frizzled signaling is involved in diverse tissue closure processes, defects in which account for some of the most common congenital anomalies in humans.

Yu, Huimin; Smallwood, Philip M.; Wang, Yanshu; Vidaltamayo, Roman; Reed, Randall; Nathans, Jeremy

2010-01-01

215

Crooked tail (Cd) model of human folate-responsive neural tube defects is mutated in Wnt coreceptor lipoprotein receptor-related protein 6  

PubMed Central

A cranial neural tube defect in Crooked tail (Cd) mice is prevented with prenatal dietary folic acid Cd positional cloning reveals a missense mutation of a highly conserved amino acid in the low density lipoprotein receptor-related protein 6 (Lrp6), a coreceptor required for Wnt canonical signaling. Molecular modeling predicts that Lrp6Cd alters a hinge region of the second YWTD ?-propeller domain. Mutant LRP6 binds to Wnt and Dickkopf1 (Dkk1) but not Mesd1, and Dkk1 cannot antagonize Wnt in Cd/Cd cells, resulting in hyperactivity. NIH 3T3 cells transfected with a mutant Lrp6 plasmid resist Dkk1 antagonism much like Cd/+ cells, confirming the significance of the mutation. The Lrp6 mutation in Cd mice provides evidence for a functional connection between Wnt signaling and folate rescue of neural tube defects.

Carter, Michelle; Chen, Xu; Slowinska, Bozena; Minnerath, Sharon; Glickstein, Sara; Shi, Lei; Campagne, Fabien; Weinstein, Harel; Ross, M. Elizabeth

2005-01-01

216

The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse embryonic survival and neural tube closure.  

PubMed

In the nematode Caenorhabditis elegans, the let-7 microRNA (miRNA) controls the timing of key developmental events and terminal differentiation in part by directly regulating lin-41. C. elegans lin-41 mutants display precocious cell cycle exit and terminal differentiation of epidermal skin cells. lin-41 orthologues are found in more complex organisms including both mice and humans, but their roles are not known. We generated Mlin41 mouse mutants to ascertain a functional role for Mlin41. Strong loss of function Mlin41 gene-trap mutants demonstrated a striking neural tube closure defect during development, and embryonic lethality. Like C. elegans lin-41, Mlin41 also appears to be regulated by the let-7 and mir-125 miRNAs. Since Mlin41 is required for neural tube closure and survival it points to human lin-41 (HLIN41/TRIM71) as a potential human development and disease gene. PMID:19098426

Maller Schulman, Betsy R; Liang, Xianping; Stahlhut, Carlos; DelConte, Casey; Stefani, Giovanni; Slack, Frank J

2008-12-13

217

The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse embryonic survival and neural tube closure  

PubMed Central

In the nematode Caenorhabditis elegans, the let-7 microRNA (miRNA) controls the timing of key developmental events and terminal differentiation in part by directly regulating lin-41. C. elegans lin-41 mutants display precocious cell cycle exit and terminal differentiation of epidermal skin cells. lin-41 orthologues are found in more complex organisms including both mice and humans, but their roles are not known. We generated Mlin41 mouse mutants to ascertain a functional role for Mlin41. Strong loss of function Mlin41 gene-trap mutants demonstrated a striking neural tube closure defect during development, and embryonic lethality. Like C. elegans lin-41, Mlin41 also appears to be regulated by the let-7 and mir-125 miRNAs. Since Mlin41 is required for neural tube closure and survival it points to human lin-41 (HLIN41/TRIM71) as a potential human development and disease gene.

Schulman, Betsy R. Maller; Liang, Xianping; Stahlhut, Carlos; DelConte, Casey; Stefani, Giovanni; Slack, Frank J.

2010-01-01

218

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

SciTech Connect

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.

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

1982-01-01

219

Differences in the Neural Mechanisms of Selective Attention in Children from Different Socioeconomic Backgrounds: An Event-Related Brain Potential Study  

ERIC Educational Resources Information Center

|Previous research indicates that children from lower socioeconomic backgrounds show deficits in aspects of attention, including a reduced ability to filter irrelevant information and to suppress prepotent responses. However, less is known about the neural mechanisms of group differences in attention, which could reveal the stages of processing at…

Stevens, Courtney; Lauinger, Brittni; Neville, Helen

2009-01-01

220

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

Microsoft Academic Search

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

Lowell E. Sever

1982-01-01

221

Low erythrocyte folate status and polymorphic variation in folate-related genes are associated with risk of neural tube defect pregnancy  

Microsoft Academic Search

Previous studies have shown conflicting findings in linking polymorphic variation in folate-related genes to the risk of neural tube defect pregnancy. Recent evidence points to maternal genotype being important in determining NTD risk. A case-control study was undertaken in 97 mothers of NTD cases from the northern region of the UK. Pregnant controls (n=190) from a regional DNA bank and

Caroline L Relton; Craig S Wilding; Alison J Laffling; Pat A Jonas; Terry Burgess; Keith Binks; E Janet Tawn; John Burn

2004-01-01

222

Prevention of neural tube defects by loss of function of inducible nitric oxide synthase in fetuses of a mouse model of streptozotocin-induced diabetes  

Microsoft Academic Search

Aims\\/hypothesis  Maternal diabetes during pregnancy increases the risk of congenital malformations such as neural tube defects (NTDs). Although\\u000a the mechanism of this effect is uncertain, it is known that levels of nitric oxide synthase (NOS) and nitric oxide are elevated\\u000a in embryos of a mouse model of diabetes. We postulated that overproduction of nitric oxide causes diabetes-induced congenital\\u000a malformations and that

Y. Sugimura; T. Murase; K. Oyama; A. Uchida; N. Sato; S. Hayasaka; Y. Kano; Y. Takagishi; Y. Hayashi; Y. Oiso; Y. Murata

2009-01-01

223

Analysis of MTHFR 1298A>C in addition to MTHFR 677C>T polymorphism as a risk factor for neural tube defects in the Turkish population  

Microsoft Academic Search

SUMMARY: Boduro?lu K, Alanay Y, Alika?ifo?lu M, Akta? D, Tunçbilek E. Analysis of MTHFR 1298A>C in addition to MTHFR 677C>T polymorphism as a risk factor for neural tube defects in the Turkish population. Turk J Pediatr 2005; 47: 327-333. Maternal folic acid intake in the periconceptional period is strongly related to reduction in recurrence and occurrence of birth defects involving

Yasemin Alanay; Ergül Tunçbilek

2005-01-01

224

Mutations in the COPII vesicle component gene SEC24B are associated with human neural tube defects.  

PubMed

Neural tube defects (NTDs) are severe birth malformations that affect one in 1,000 live births. Recently, mutations in the planar cell polarity (PCP) pathway genes had been implicated in the pathogenesis of NTDs in both the mouse model and in human cohorts. Mouse models indicate that the homozygous disruption of Sec24b, which mediates the ER-to-Golgi transportation of the core PCP gene Vangl2 as a component of the COPII vesicle, will result in craniorachischisis. In this study, we found four rare missense heterozygous SEC24B mutations (p.Phe227Ser, p.Phe682Leu, p.Arg1248Gln, and p.Ala1251Gly) in NTDs cases that were absent in all controls. Among them, p.Phe227Ser and p.Phe682Leu affected its protein stability and physical interaction with VANGL2. Three variants (p.Phe227Ser, p.Arg1248Gln, and p.Ala1251Gly) were demonstrated to affect VANGL2 subcellular localization in cultured cells. Further functional analysis in the zebrafish including overexpression and dosage-dependent rescue study suggested that these four mutations all displayed loss-of-function effects compared with wild-type SEC24B. Our study demonstrated that functional mutations in SEC24B might contribute to the etiology of a subset of human NTDs and further expanded our knowledge of the role of PCP pathway-related genes in the pathogenesis of human NTDs. PMID:23592378

Yang, Xue-Yan; Zhou, Xiang-Yu; Wang, Qing Qing; Li, Hong; Chen, Ying; Lei, Yun-Ping; Ma, Xiao-Hang; Kong, Pan; Shi, Yan; Jin, Li; Zhang, Ting; Wang, Hong-Yan

2013-05-13

225

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

PubMed

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. PMID:19283538

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

2009-03-01

226

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

PubMed

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. PMID:14608380

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

2003-11-09

227

Awareness and intake of folic acid for the prevention of neural tube defects among Lebanese women of childbearing age.  

PubMed

Since the early 1990s, international recommendations have promoted folic acid supplementation during the periconception period as an effective way of preventing neural tube defects (NTDs). However, the adoption of this recommendation remains insufficient. To assess the awareness and actual intake of folic acid among married Lebanese women aged 18-45 years, a cross-sectional study was conducted among 600 women selected from all five administrative districts in Lebanon, using a multistage cluster sampling procedure. An anonymous questionnaire was completed which covered measures of knowledge and use of folate supplements, as well as demographic, socioeconomic and obstetrical factors. Sixty percent of surveyed women (60%; n = 360) had heard about folic acid. Doctors were the most frequent source of information (61.1%) but only 24.7% of women have been told of the correct period during which folic acid supplementation was useful. Overall, only 6.2% had taken folic acid tablets during the adequate period. Younger age, higher education level and stability/sufficiency of income appeared to be significant predictors of awareness among Lebanese women. Actual folic acid intake was significantly associated with younger age, higher number of pregnancies, planning the last pregnancy and having had that last one after 1990. In Lebanon, the level of folic acid awareness and adequate intake remain relatively low. Several approaches should be used to promote folic acid intake including awareness campaigns, and routine counseling by primary health care physicians on folic acid during preconception visits. PMID:21210201

Nasr Hage, Claudine; Jalloul, Maya; Sabbah, Mohamad; Adib, Salim M

2012-01-01

228

The decoupling of Smoothened from G?i proteins has little effect on Gli3 protein processing and Hedgehog-regulated chick neural tube patterning  

PubMed Central

The Hedgehog (Hh) signal is transmitted by two receptor molecules, Patched (Ptc) and Smoothened (Smo). Ptc suppresses Smo activity, while Hh binds Ptc and alleviates the suppression, which results in activation of Hh targets. Smo is a seven-transmembrane protein with a long carboxyl terminal tail. Vertebrate Smo has been previously shown to be coupled to G?i proteins, but the biological significance of the coupling in Hh signal transduction is not clear. Here we show that although inhibition of G?i protein activity appears to significantly reduce Hh pathway activity in Ptc?/? mouse embryonic fibroblasts and the NIH3T3-based Shh-light cells, it fails to derepress Shh- or a Smo agonist-induced inhibition of Gli3 protein processing, a known in vivo indicator of Hh signaling activity. The inhibition of G?i protein activity also cannot block the Sonic Hedgehog (Shh)-dependent specification of neural progenitor cells in the neural tube. Consistent with these results, overexpression of a constitutively active G?i protein, G?i2QL, cannot ectopically specify the neural cell types in the spinal cord, whereas an active Smo, SmoM2, can. Thus, our results indicate that the Smo induced G?i activity plays an insignificant role in the regulation of Gli3 processing and Shh-regulated neural tube patterning.

Low, Wee-Chuang; Wang, Chengbing; Pan, Yong; Huang, Xin-Yun; Chen, James K.; Wang, Baolin

2008-01-01

229

Cloning of zebrafish nkx6.2 and a comprehensive analysis of the conserved transcriptional response to Hedgehog/Gli signaling in the zebrafish neural tube  

PubMed Central

Sonic Hedgehog (Shh) signaling helps pattern the vertebrate neural tube, in part by regulating the dorsal/ventral expression of a number of homeodomain containing transcription factors. These Hh responsive genes have been divided into two classes, with Class II genes being activated by Hh signaling and Class I genes being repressed by Hh signaling. While the transcriptional response to varying Hh levels is well defined in chick and mouse, it is only partially described in zebrafish, despite the fact that zebrafish has emerged as a powerful genetic system for the study of neural patterning. To better characterize the Hh response in the zebrafish neural tube, we cloned the zebrafish Class II Hh target genes nkx2.9 and nkx6.2. We then analyzed the expression of a number of Class I and Class II Hh responsive genes in wild type, Hh mutant, and Hh over-expressing zebrafish embryos. We show that expression of Class I and Class II genes is highly conserved in the vertebrate neural tube. Further, ventral-most Class II gene expression was completely lost in all Hh pathway mutants analyzed, indicating high levels of Hh signaling are blocked in all of these mutants. In contrast, more dorsally expressed genes were variably affected in different Hh pathway mutants, indicating mid-levels of Hh signaling are differentially affected. This comprehensive expression study provides an important tool for the characterization of Hh signaling in zebrafish and provides a sensitive assay for determining the degree to which newly identified zebrafish mutants affect Hh signaling.

Guner, Burcu; Karlstrom, Rolf O.

2007-01-01

230

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

PubMed Central

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

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

2012-01-01

231

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  

PubMed Central

BACKGROUND: It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.). METHODS: A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced 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. RESULTS: 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. CONCLUSION: 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. Birth Defects Research (Part A) 97:444–451, 2013. © 2013 Wiley Periodicals, Inc.

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

2013-01-01

232

Long-term effect of low-dose folic acid intake: potential effect of mandatory fortification on the prevention of neural tube defects123  

PubMed Central

Background: Understanding the full effect of chronic low-dose folic acid is important in interpreting the effect of the mandatory folic acid fortification program in North America. Objective: We aimed to describe the rate of attainment and steady state (plateau) of red blood cell (RBC) folate in response to long-term intake of 140 ?g (designed to mimic fortification) and 400 ?g (recommended dose for the primary prevention of neural tube defects) folic acid/d in reproductive-aged women living in a country with minimal fortification. Design: On the basis of pharmacokinetics principles, it was recently proposed that a steady state should be reached after 40 wk. Thus, 144 women aged 18–40 y were randomly assigned to receive a daily folic acid supplement of 140 (n = 49) or 400 (n = 48) ?g or placebo (n = 47) for 40 wk. RBC folate was measured at baseline and at 6, 12, 29, and 40 wk. Results: After 40 wk, RBC folate did not reach a plateau in either treatment group. Kinetic modeling of the data indicated that RBC folate would approximately double from 779 to 1356 nmol/L in response to 140 ?g folic acid/d with only ?50% of model-estimated steady state conditions achieved at 40 wk. An average RBC folate concentration of 1068 nmol/L after 12 wk of supplementation with 400 ?g folic acid/d was readily achieved at 36 wk after continuous intake of 140 ?g/d. Conclusion: Our model shows the considerable length of time required to attain the full effect of low-dose folic acid, which suggests that 140 ?g folic acid/d could be as effective as 400 ?g folic acid/d taken during the periconceptional period if given sufficient time. This trial is registered at www.anzctr.org.au as ACTRN12609000215224.

Gray, Andrew R; Rose, Meredith C; Miller, Jody C; Hurthouse, Nicola A; Gregory, Jesse F

2011-01-01

233

Genetic Variants in the Folate Pathway and the Risk of Neural Tube Defects: A Meta-Analysis of the Published Literature  

PubMed Central

Background Neural Tube Defects (NTDs) are among the most prevalent and most severe congenital malformations worldwide. Polymorphisms in key genes involving the folate pathway have been reported to be associated with the risk of NTDs. However, the results from these published studies are conflicting. We surveyed the literature (1996–2011) and performed a comprehensive meta-analysis to provide empirical evidence on the association. Methods and Findings We investigated the effects of 5 genetic variants from 47 study populations, for a total of 85 case-control comparisons MTHFR C677T (42 studies; 4374 cases, 7232 controls), MTHFR A1298C (22 studies; 2602 cases, 4070 controls), MTR A2756G (9 studies; 843 cases, 1006 controls), MTRR A66G (8 studies; 703 cases, 1572 controls), and RFC-1 A80G (4 studies; 1107 cases, 1585 controls). We found a convincing evidence of dominant effects of MTHFR C677T (OR 1.23; 95%CI 1.07–1.42) and suggestive evidence of RFC-1 A80G (OR 1.55; 95%CI 1.24–1.92). However, we found no significant effects of MTHFR A1298C, MTR A2756G, MTRR A66G in risk of NTDs in dominant, recessive or in allelic models. Conclusions Our meta-analysis strongly suggested a significant association of the variant MTHFR C677T and a suggestive association of RFC-1 A80G with increased risk of NTDs. However, other variants involved in folate pathway do not demonstrate any evidence for a significant marginal association on susceptibility to NTDs.

Zhang, Ti; Lou, Jiao; Zhong, Rong; Wu, Jing; Zou, Li; Sun, Yu; Lu, Xuzai; Liu, Li; Miao, Xiaoping; Xiong, Guanglian

2013-01-01

234

Gene-gene interaction in folate-related genes and risk of neural tube defects in a UK population  

PubMed Central

Objective: To investigate the contribution of polymorphic variation in genes involved in the folate-dependent homocysteine pathway in the aetiology of neural tube defects (NTD). Design: Case-control association study. Subjects: A total of 530 individuals from families affected by NTD, 645 maternal controls, and 602 healthy newborn controls from the northern UK. Main outcome measures: Seven polymorphisms in six genes coding for proteins in the folate-dependent homocysteine pathway (MTHFR 677C?T, MTHFR 1298A?C, MTRR 66A?G, SHMT 1420C?T, CßS 844ins68, GCPII 1561C?T, RFC-1 80G?A). The impact of each polymorphism and the effect of gene–gene interactions (epistasis) upon risk of NTD were assessed using logistic regression analysis. Results: The MTHFR 677C?T polymorphism was shown to represent a risk factor in NTD cases (CC v CT+TT odds ratio (OR) 2.03 [95% confidence interval (CI) 1.09, 3.79] p = 0.025) and the MTRR 66A?G polymorphism was shown to exert a protective effect in NTD cases (AA v AG+GG OR 0.31 [95% CI 0.10, 0.94] p = 0.04). When statistical tests for interaction were conducted, three genotype combinations in cases (MTRR/GCPII; MTHFR 677/CßS; MTHFR 677/MTRR) and one combination in case mothers (CßS/RFC-1) were shown to elevate NTD risk. Maternal–fetal interaction was also detected when offspring carried the MTHFR 677C?T variant and mothers carried the MTRR 66A?G variant, resulting in a significantly elevated risk of NTD. Conclusion: Both independent genetic effects and gene–gene interaction were observed in relation to NTD risk. Multi-locus rather than single locus analysis might be preferable to gain an accurate assessment of genetic susceptibility to NTD.

Relton, C; Wilding, C; Pearce, M; Laffling, A; Jonas, P; Lynch, S; Tawn, E; Burn, J

2004-01-01

235

Dieting to lose weight and occurrence of neural tube defects in offspring of Mexican-American women.  

PubMed

Lowered maternal weight gain and reduction in early pregnancy have been associated with risk of neural tube defects (NTDs) in offspring. We examined the association of self-reported maternal dieting behaviors on the occurrence of NTDs. We conducted a population based case-control study among Mexican-American women who were residents of the 14 Texas counties bordering Mexico. Case women had an NTD-affected pregnancy identified at birth or prenatally and had deliveries during the years 1995-2000. Control women were those who delivered live born infants without an apparent congenital malformation, randomly selected and frequency-matched to cases by year and facility. One hundred eighty-four case women and 225 control women were asked in person about the use of nutritional supplements, dieting to lose weight, and type of weight reduction supplements used during the 3 months before conception. Women who reported being on a diet to lose weight during the 3 months before conception had an NTD odds ratio (OR) of 1.9 (95% confidence interval (CI) = 1.1, 3.3) compared with those not reporting being on a diet. Neither consuming vitamin drinks (OR = 1.2) nor using diet pills (OR = 1.6) during the 3 months before conception had ORs that were different from the null, when compared to women not reporting those behaviors. The risk effect for dieting did not differ markedly among normal or underweight (OR = 2.0, 95% CI = 0.7, 5.6), overweight (OR = 1.9, 95% CI = 0.7, 5.0), or obese women (OR = 1.5, 95% CI = 0.6, 4.0). No effect was seen among dieting women who were consuming at least 1.0 mg/day of folate (OR = 1.1, CI = 0.3, 4.5). Maternal dieting prior to conception may increase the risk of NTDs in offspring. PMID:21512779

Suarez, Lucina; Felkner, Marilyn; Brender, Jean D; Canfield, Mark A

2012-05-01

236

A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?  

PubMed Central

Recently, we showed that homozygosity for the common 677(C-->T) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, causing thermolability of the enzyme, is a risk factor for neural-tube defects (NTDs). We now report on another mutation in the same gene, the 1298(A-->C) mutation, which changes a glutamate into an alanine residue. This mutation destroys an MboII recognition site and has an allele frequency of .33. This 1298(A-->C) mutation results in decreased MTHFR activity (one-way analysis of variance [ANOVA] P < .0001), which is more pronounced in the homozygous than heterozygous state. Neither the homozygous nor the heterozygous state is associated with higher plasma homocysteine (Hcy) or a lower plasma folate concentration-phenomena that are evident with homozygosity for the 677(C-->T) mutation. However, there appears to be an interaction between these two common mutations. When compared with heterozygosity for either the 677(C-->T) or 1298(A-->C) mutations, the combined heterozygosity for the 1298(A-->C) and 677(C-->T) mutations was associated with reduced MTHFR specific activity (ANOVA P < .0001), higher Hcy, and decreased plasma folate levels (ANOVA P <.03). Thus, combined heterozygosity for both MTHFR mutations results in similar features as observed in homozygotes for the 677(C-->T) mutation. This combined heterozygosity was observed in 28% (n =86) of the NTD patients compared with 20% (n =403) among controls, resulting in an odds ratio of 2.04 (95% confidence interval: .9-4.7). These data suggest that the combined heterozygosity for the two MTHFR common mutations accounts for a proportion of folate-related NTDs, which is not explained by homozygosity for the 677(C-->T) mutation, and can be an additional genetic risk factor for NTDs.

van der Put, N M; Gabreels, F; Stevens, E M; Smeitink, J A; Trijbels, F J; Eskes, T K; van den Heuvel, L P; Blom, H J

1998-01-01

237

A GCH1 haplotype and risk of neural tube defects in the National Birth Defects Prevention Study.  

PubMed

Tetrahydrobiopterin (BH(4)) is an essential cofactor and an important cellular antioxidant. BH(4) deficiency has been associated with diseases whose etiologies stem from excessive oxidative stress. GTP cyclohydrolase I (GCH1) catalyzes the first and rate-limiting step of de novo BH(4) synthesis. A 3-SNP haplotype in GCH1 (rs8007267, rs3783641, and rs10483639) is known to modulate GCH1 gene expression levels and has been suggested as a major determinant of plasma BH(4) bioavailability. As plasma BH(4) bioavailability has been suggested as a mechanism of neural tube defect (NTD) teratogenesis, we evaluated the association between this GCH1 haplotype and the risk of NTDs. Samples were obtained from 760 NTD case-parent triads included in the National Birth Defects Prevention Study (NBDPS). The three SNPs were genotyped using TaqMan® SNP assays. An extension of the log-linear model was used to assess the association between NTDs and both offspring and maternal haplotypes. Offspring carrying two copies of haplotype C-T-C had a significantly increased NTD risk (risk ratio [RR]=3.40, 95% confidence interval [CI]: 1.02-11.50), after adjusting for the effect of the maternal haplotype. Additionally, mothers carrying two copies of haplotype C-T-C had a significantly increased risk of having an NTD-affected offspring (RR=3.46, 95% CI: 1.05-11.00), after adjusting for the effect of the offspring haplotype. These results suggest offspring and maternal variation in the GCH1 gene and altered BH(4) biosynthesis may contribute to NTD risk. PMID:23059057

Lupo, Philip J; Chapa, Claudia; Nousome, Darryl; Duhon, Cody; Canfield, Mark A; Shaw, Gary M; Finnell, Richard H; Zhu, Huiping

2012-09-25

238

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

PubMed

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. PMID:23874236

Safra, Noa; Bassuk, Alexander G; Ferguson, Polly J; Aguilar, Miriam; Coulson, Rochelle L; Thomas, Nicholas; Hitchens, Peta L; Dickinson, Peter J; Vernau, Karen M; Wolf, Zena T; Bannasch, Danika L

2013-07-18

239

Independent mutations in mouse Vangl2 that cause neural tube defects in looptail mice impair interaction with members of the Dishevelled family.  

PubMed

Mammalian Vangl1 and Vangl2 are highly conserved membrane proteins that have evolved from a single ancestral protein Strabismus/Van Gogh found in Drosophila. Mutations in the Vangl2 gene cause a neural tube defect (craniorachischisis) characteristic of the looptail (Lp) mouse. Studies in model organisms indicate that Vangl proteins play a key developmental role in establishing planar cell polarity (PCP) and in regulating convergent extension (CE) movements during embryogenesis. The role of Vangl1 in these processes is virtually unknown, and the molecular function of Vangl1 and Vangl2 in PCP and CE is poorly understood. Using a yeast two-hybrid system, glutathione S-transferase pull-down and co-immunoprecipitation assays, we show that both mouse Vangl1 and Vangl2 physically interact with the three members of the cytoplasmic Dishevelled (Dvl) protein family. This interaction is shown to require both the predicted cytoplasmic C-terminal half of Vangl1/2 and a portion of the Dvl protein containing PDZ and DIX domains. In addition, we show that the two known Vangl2 loss-of-function mutations identified in two independent Lp alleles associated with neural tube defects impair binding to Dvl1, Dvl2, and Dvl3. These findings suggest a molecular mechanism for the neural tube defect seen in Lp mice. Our observations indicate that Vangl1 biochemical properties parallel those of Vangl2 and that Vangl1 might, therefore, participate in PCP and CE either in concert with Vangl2 or independently of Vangl2 in discrete cell types. PMID:15456783

Torban, Elena; Wang, Hui-Jun; Groulx, Normand; Gros, Philippe

2004-09-29

240

[Preparation of mouse KCTD10 antibody and expression analysis of KCTD10 in neuroepithelium of neural tube and dorsal root ganglion].  

PubMed

KCTD10 is a TNF-alpha inducible protein that can interact with the small subunit of DNA polymerase a and PCNA. In order to study the function of KCTD10, we prepared the rabbit anti-mouse KCTD10 polyclonal antibody by using the His-tagged recombinant mouse KCTD10 protein to immune New Zealand white rabbit. Mouse KCTD10 shares significant similarity with PDIP1 (polymerase delta-interacting protein 1) and TNFAIP1 (tumor necrosis factor alpha-induced protein 1) protein,and then KCTD10 polyclonal antiserum possesses cross-reactivity with PDIP1 protein and TNFAIP1 protein. The partially digested fragments of homogeneous proteins PDIP1 and TNFAIP1 were mixed and incubated with anti-KCTD10 antiserum at 4 degrees C for 3 h to deplete unspecific antibodies. Through this method, we removed successfully the cross-reactivity of anti-KCTD10 antibody with PDIP1 and TNFAIP1 and obtained specific anti-KCTD10 antibody. Then, the anti-KCTD10 antibody was used in immunohistochemistry experiments of mouse. The results of immunohistochemistry on whole-mount embryo and paraffin section demonstrated that KCTD10 is highly expressed in neuroepithelium of neural tube and dorsal root ganglion of 12.5 d embryos. These results suggest that KCTD10 may play roles in the development of neuroepithelium of neural tube and dorsal root ganglion. PMID:18257228

Sun, Ji-Kang; Zhang, Bo; Zhang, Jian; Zhou, Jian-Lin

2007-11-01

241

A Polymorphism, R653Q, in the Trifunctional Enzyme Methylenetetrahydrofolate Dehydrogenase\\/Methenyltetrahydrofolate Cyclohydrolase\\/Formyltetrahydrofolate Synthetase Is a Maternal Genetic Risk Factor for Neural Tube Defects: Report of the Birth Defects Research Group  

Microsoft Academic Search

Women who take folic acid periconceptionally reduce their risk of having a child with a neural tube defect (NTD) by 150%. A variant form of methylenetetrahydrofolate reductase (MTHFR) (677CrT) is a known risk factor for NTDs, but the prevalence of the risk genotype explains only a small portion of the protective effect of folic acid. This has prompted the search

Lawrence C. Brody; Mary Conley; Christopher Cox; Peadar N. Kirke; Mary P. McKeever; James L. Mills; Anne M. Molloy; Valerie B. O’Leary; Anne Parle-McDermott; John M. Scott; Deborah A. Swanson

2002-01-01

242

Visual modeling of cathode ray tube displays for finding cross-media corresponding colors based on the natural color system color atlas and neural networks  

NASA Astrophysics Data System (ADS)

A visual method for characterizing cathode ray tube (CRT) displays and finding corresponding colors is presented. The method is motivated by the considerable expense of measuring instruments and the consideration of color appearance factors. In the experiment, a set of color chips in the natural color system (NCS) color atlas, an illuminant, and a CRT are used. 487 sample pairs of RGB (CRT) and HVC, which are the attributes of NCS color chips, are obtained by experimentally comparing softcopies and hardcopies in the office environment in the sense of best color matching to nine observers. Both the spectral data of the color chips and the colorimetric values of the CRT samples are measured. In addition, 12 error back-propagation (BP) neural networks are trained to help the realization of the transformation from HVC to RGB for data generalization. The current results show that the displays on the CRT can match the chips in color perception well.

Chai, Binghua; Zhao, Dazun; Liao, Ningfang; Shao, Yubo

2006-01-01

243

Qualitative and quantitative diagnosis of lethal cranial neural tube defects from the fetal and neonatal human skeleton, with a case study involving taphonomically altered remains.  

PubMed

Cranial neural tube defect, or anencephaly, is the absence of normal brain development because of severe developmental defect in the fetus. While the current incidence of human anencephaly ranges between 1 to 5 per 1000 births, and was higher prior to folic acid supplementation, there is no discussion of anencephaly diagnosis in the forensic literature and only one published example from the archeological record. This article presents both qualitative observations of abnormal cranial elements and an osteometric method to quantitatively determine anencephaly from forensic recovery contexts where taphonomic variables may otherwise mask diagnostic characteristics. Evidence is presented for only the second case of anencephaly diagnosed from a burial context, and the first not involving soft tissue mummification. The initial recognition and accurate prediction of anencephaly is a significant contribution to investigators recovering found human fetal remains. PMID:20384923

Dudar, J Christopher

2010-04-08

244

Epidemiologic aspects of neural tube defects in the United States: changing concepts and their importance for screening and prenatal diagnostic programs  

SciTech Connect

This report considers several major epidemiologic aspects of neural tube defects (NTDs). After examining briefly the approaches and goals of epidemiology the traditional epidemiologic concepts of NTDs are reviewed and new interpretations of the epidemiology of these defects is suggested. Three major topics are addressed: (1) that much of our knowledge of the epidemiology of the NTDs comes from areas or periods of high rates of occurrence and that generalizations based on these data may not be applicable to low incidence situations; (2) that the etiology of these defects is multifactorial, involving interaction between genetic and nongenetic factors which may differ in their relative importance between populations; and (3) that anencephalus and spina bifida may be more epidemiologically and etiologically distinct than is usually appreciated. A final consideration deals with some recent contributions of epidemiology to screening and prenatal diagnosis programs.

Sever, L.E.; Strassburg, M.A.

1983-09-01

245

Neural tube defects on the Texas-Mexico border: what we've learned in the 20 years since the Brownsville cluster.  

PubMed

We reviewed the published findings from the Texas Neural Tube Defect Project, a 6-year case-control study (1995-2000) of neural tube defects (NTDs) on the Texas-Mexico border. In this review, we highlight what was learned about environmental, genetic, and nutritional factors (i.e., those related to the folate and other metabolic pathways) and the novel putative risk factors that emerged from this study of Mexican American women living on the Texas-Mexico border. Our investigations of the micronutrients and metabolic pathways involved confirmed the findings of other researchers that increased folate intake has a protective effect and that low serum B(12) , high serum homocysteine levels, and obesity independently contribute to risk. Studies of this population also have implicated hyperinsulinemia and low ferritin, metabolic risk factors, which require additional study to elucidate their physiologic mechanism. Environmental contaminants such as heavy metals, pesticides, and polychlorinated biphenyls (PCBs), which were of community concern, did little to explain NTD risk. Studies in this folic acid deficit-population also revealed several novel risk factors, namely, diarrhea, stress, fumonisins, and the combination of nitrosatable drug exposure with high nitrate/nitrite intake. In conclusion, the 23 studies among the Mexican American women living along the Texas-Mexico border have demonstrated the multifactorial nature of NTDs and that a population deficient in folic acid will be vulnerable to a variety of insults whether brought on by individual behaviors (e.g., obesity) or through the surrounding environment (e.g., fumonisins). Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc. PMID:22945287

Suarez, Lucina; Felkner, Marilyn; Brender, Jean D; Canfield, Mark; Zhu, Huiping; Hendricks, Katherine A

2012-09-03

246

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

PubMed Central

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

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

2010-01-01

247

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

PubMed

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

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

2012-05-27

248

Genetic background impacts developmental potential of enteric neural crest-derived progenitors in the Sox10Dom model of Hirschsprung disease  

PubMed Central

Abnormalities in the development of enteric neural crest-derived progenitors (ENPs) that generate the enteric nervous system (ENS) can lead to aganglionosis in a variable portion of the distal gastrointestinal tract. Cumulative evidence suggests that variation of aganglionosis is due to gene interactions that modulate the ability of ENPs to populate the intestine; however, the developmental processes underlying this effect are unknown. We hypothesized that differences in enteric ganglion deficits could be attributable to the effects of genetic background on early developmental processes, including migration, proliferation, or lineage divergence. Developmental processes were investigated in congenic Sox10Dom mice, an established Hirschsprung disease (HSCR) model, on distinct inbred backgrounds, C57BL/6J (B6) and C3HeB/FeJ (C3Fe). Immuno-staining on whole-mount fetal gut tissue and dissociated cell suspensions was used to assess migration and proliferation. Flow cytometry utilizing the cell surface markers p75 and HNK-1 was used to isolate live ENPs for analysis of developmental potential. Frequency of ENPs was reduced in Sox10Dom embryos relative to wild-type embryos, but was unaffected by genetic background. Both migration and developmental potential of ENPs in Sox10Dom embryos were altered by inbred strain background with the most highly significant differences seen for developmental potential between strains and genotypes. In vivo imaging of fetal ENPs and postnatal ganglia demonstrates that altered lineage divergence impacts ganglia in the proximal intestine. Our analysis demonstrates that genetic background alters early ENS development and suggests that abnormalities in lineage diversification can shift the proportions of ENP populations and thus may contribute to ENS deficiencies in vivo.

Walters, Lauren C.; Cantrell, V. Ashley; Weller, Kevin P.; Mosher, Jack T.; Southard-Smith, E. Michelle

2010-01-01

249

Improved Heat Transfer Correlation in the Transition Region for a Circular Tube with Three Inlet Configurations Using Artificial Neural Networks  

Microsoft Academic Search

Local forced and mixed heat transfer coefficients were measured by Ghajar and Tam [5] in a horizontal circular straight tube fitted with reentrant, square-edged, and bell-mouth inlets under uniform wall heat flux boundary condition. For the experiments, the Reynolds, Prandtl, and Grashof numbers varied from about 280 to 49000, 4 to 158, and 1000 to 2.5 × 10, respectively. The

AFSHIN J. GHAJAR; LAP MOU TAM; SIK CHUNG TAM

2004-01-01

250

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

PubMed Central

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

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

2011-01-01

251

Amniotic fluid and serum biomarkers from women with neural tube defect-affected pregnancies: a case study for myelomeningocele and anencephaly.  

PubMed

Object The authors sought to identify novel biomarkers for early detection of neural tube defects (NTDs) in human fetuses. Methods Amniotic fluid and serum were drawn from women in the second trimester of pregnancy. The study group included 2 women pregnant with normal fetuses and 4 with fetuses displaying myelomeningocele (n = 1), anencephaly (n = 1), holoprosencephaly (n = 1), or encephalocele (n = 1). Amniotic fluid stem cells (AFSCs) were isolated and cultured. The cells were immunostained for the stem cell markers Oct4, CD133, and Sox2; the epigenetic biomarkers H3K4me2, H3K4me3, H3K27me2, H3K27me3, H3K9Ac, and H3K18Ac; and the histone modifiers KDM6B (a histone H3K27 demethylase) and Gcn5 (a histone acetyltransferase). The levels of 2 markers for neural tube development, bone morphogenetic protein-4 (BMP4) and sonic hedgehog (Shh), were measured in amniotic fluid and serum using an enzyme-linked immunosorbent assay. Results The AFSCs from the woman pregnant with a fetus affected by myelomeningocele had higher levels of H3K4me2, H3K4me3, H3K27me2, and H3K27me3 and lower levels of KDM6B than the AFSCs from the women with healthy fetuses. The levels of H3K9ac, H3K18ac, and Gcn5 were also decreased in the woman with the fetus exhibiting myelomeningocele. In AFSCs from the woman carrying an anencephalic fetus, levels of H3K27me3, along with those of H3K9Ac, H3K18ac, and Gcn5, were increased, while that of KDM6B was decreased. Compared with the normal controls, the levels of BMP4 in amniotic fluid and serum from the woman with a fetus with myelomeningocele were increased, whereas levels of Shh were increased in the woman pregnant with a fetus displaying anencephaly. Conclusions The levels of epigenetic marks, such as H3K4me, H3K27me3, H3K9Ac, and H3K18A, in cultured AFSCs in combination with levels of key developmental proteins, such as BMP4 and Shh, are potential biomarkers for early detection and identification of NTDs in amniotic fluid and maternal serum. PMID:23971635

Tsurubuchi, Takao; Ichi, Shunsuke; Shim, Kyu-Won; Norkett, William; Allender, Elise; Mania-Farnell, Barbara; Tomita, Tadanori; McLone, David G; Ginsberg, Norman; Mayanil, C Shekhar

2013-08-23

252

Comparative Physical and Transcript Maps of ?1 Mb around loop-tail, a Gene for Severe Neural Tube Defects on Distal Mouse Chromosome 1 and Human Chromosome 1q22–q23  

Microsoft Academic Search

The homozygous loop-tail (Lp) mouse has a severe neural tube closure defect, analogous to the craniorachischisis phenotype seen in humans. Linkage analysis and physical mapping have previously localized the Lp locus to a region on mouse chromosome 1 defined by the markers D1Mit113–Tagln2. Here we report the construction of sequence-ready bacterial clone contigs encompassing the Lp critical region in both

Kit Doudney; Jennifer N. Murdoch; Caroline Paternotte; Louise Bentley; Simon Gregory; Andrew J. Copp; Philip Stanier

2001-01-01

253

Association of sociodemographic and nutritional factors with risk of neural tube defects in the North Indian population: a case-control study.  

PubMed

OBJECTIVE: To assess the role of sociodemographic and nutritional factors in the incidence of births affected by neural tube defects (NTD) in the North Indian population. DESIGN: Case-control study. SETTING: Government hospitals of Delhi, India. SUBJECTS: Subjects comprised 284 mothers of NTD children (cases) and 568 mothers of healthy children (controls). RESULTS: Significant differences were found between case and control mothers with respect to maternal age (P = 0·005), type of drinking water (P = 0·03) and consumption of milk (P = 0·01). Univariate and multivariate analysis suggested an association of unpasteurized milk use, low consumption of vegetables, low consumption of fruits and vegetarian dietary habits with NTD births. Further, variation in the risk factors for upper and lower NTD types was also observed, pointing towards phenotypic heterogeneity in the aetiology. CONCLUSIONS: The results of the present study suggest an increased risk of NTD infants in mothers with low consumption of vegetables, fruits and milk and having vegetarian dietary habits. So, in order to reduce these devastating birth defects in future offspring, better nutritional care should be provided to mothers by suggesting dietary modifications and augmenting additional micronutrient supplementation during the periconceptional period. PMID:23340204

Deb, Roumi; Arora, Jyoti; Saraswathy, Kallur N; Kalla, Aloke K

2013-01-23

254

Genetic basis of neural tube defects: The mouse gene loop-tail maps to a region of chromosome 1 syntenic with human 1q21-q23  

SciTech Connect

A genetic basis for neural tube defects (NTD) is rarely doubted, but the genes involved have not yet been identified. This is partly due to a lack of suitable families on which to perform linkage analysis. An alternative approach is to use the many mouse genes that cause NTD as a means of isolating their human homologues. Loop-tail (Lp) is a semidominant mouse gene that, in homozygous mutants, causes the severe NTD phenotype cranio-rachischisis. As a first step toward cloning Lp, we have performed linkage analysis on an intraspecific backcross, using microsatellite and RFLP DNA markers. This study has localized Lp to a region of approximately 1.46 cM on mouse chromosome 1, flanked by the gene for the {alpha} chain of high-affinity Fc receptor for IgE (Fcer1{alpha}) and a microsatellite repeat D1Mit113. Physical mapping data in the region suggest that the interval is likely to be no more than 1.8 Mb in size. The localization is several centimorgans distal to that previously assigned by linkage studies with biochemical and visible markers and suggests that the human homologue of Lp is likely to reside in a region of conserved homology on 1q21-q23. 36 refs., 3 figs., 3 tabs.

Stanier, P.; Moore, G.E. [Institute of Obstetrics and Gynaecology, London (United Kingdom); Henson, J.N. [Univ. of London (United Kingdom)] [and others

1995-04-10

255

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

PubMed Central

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

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

2009-01-01

256

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

SciTech Connect

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.

Sever, L.E.

1982-01-01

257

Gene-environment interactions in the causation of neural tube defects: folate deficiency increases susceptibility conferred by loss of Pax3 function.  

PubMed

Risk of neural tube defects (NTDs) is determined by genetic and environmental factors, among which folate status appears to play a key role. However, the precise nature of the link between low folate status and NTDs is poorly understood, and it remains unclear how folic acid prevents NTDs. We investigated the effect of folate level on risk of NTDs in splotch (Sp(2)(H)) mice, which carry a mutation in Pax3. Dietary folate restriction results in reduced maternal blood folate, elevated plasma homocysteine and reduced embryonic folate content. Folate deficiency does not cause NTDs in wild-type mice, but causes a significant increase in cranial NTDs among Sp(2)(H) embryos, demonstrating a gene-environment interaction. Control treatments, in which intermediate levels of folate are supplied, suggest that NTD risk is related to embryonic folate concentration, not maternal blood folate concentration. Notably, the effect of folate deficiency appears more deleterious in female embryos than males, since defects are not prevented by exogenous folic acid. Folate-deficient embryos exhibit developmental delay and growth retardation. However, folate content normalized to protein content is appropriate for developmental stage, suggesting that folate availability places a tight limit on growth and development. Folate-deficient embryos also exhibit a reduced ratio of s-adenosylmethionine (SAM) to s-adenosylhomocysteine (SAH). This could indicate inhibition of the methylation cycle, but we did not detect any diminution in global DNA methylation, in contrast to embryos in which the methylation cycle was specifically inhibited. Hence, folate deficiency increases the risk of NTDs in genetically predisposed splotch embryos, probably via embryonic growth retardation. PMID:18753144

Burren, Katie A; Savery, Dawn; Massa, Valentina; Kok, Robert M; Scott, John M; Blom, Henk J; Copp, Andrew J; Greene, Nicholas D E

2008-08-26

258

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms resulting in suboptimal oocyte maturation: a discussion of folate status, neural tube defects, schizophrenia, and vasculopathy.  

PubMed

Several conditions apparent at birth, e.g., neural tube defects (NTDs) and cardiac anomalies, are associated with polymorphisms in folate-related genes, such as the 677C --> T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Similar associations have been established for several constitutional chronic diseases in adulthood, such as schizophrenia, cardiovascular diseases, dementia, and even neoplasias in different organ systems. This spectrum of developmental anomalies and constitutional diseases may be linked to high-risk conceptions related to preovulatory overripeness ovopathy (PrOO). Some developmental anomalies, such as NTDs, are to a large extent prevented by supplementation of folic acid before conception, but supplementation does not seem to prevent cardiovascular disease or cognitive decline. These diverging results can be elucidated by introduction of the PrOO concept, as MTHFR polymorphisms and inherent low folate levels induce both non-optimal maturation of the oocyte and unsuccessful DNA methylation and demethylation, i.e. epigenetic mutations. The PrOO concept is testable and predicts in a random population the following: (1) female carriers of specific genetic MTHFR variants exhibit more ovulatory disturbances and inherent subfecundity traits, (2) descendents from a carrier mother, when compared with those from a wild-type mother, are more frequently conceived in PrOO high-risk conditions and, thus, (3) disadvantaged in life expectancy. If so, some MTHFR polymorphisms represent a novel, genetically determined, PrOO high-risk conception category comparable to those which are environmentally and behaviorly influenced. These high-risk conditions may cause developmental anomalies and defective epigenetic reprogramming in progeny. The interaction between genetic and environmental factors is a plausible mechanism of multifactorial inheritance. PMID:18616826

Jongbloet, Piet Hein; Verbeek, André Lm; den Heijer, Martin; Roeleveld, Nel

2008-07-10

259

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms resulting in suboptimal oocyte maturation: a discussion of folate status, neural tube defects, schizophrenia, and vasculopathy  

PubMed Central

Several conditions apparent at birth, e.g., neural tube defects (NTDs) and cardiac anomalies, are associated with polymorphisms in folate-related genes, such as the 677C ? T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Similar associations have been established for several constitutional chronic diseases in adulthood, such as schizophrenia, cardiovascular diseases, dementia, and even neoplasias in different organ systems. This spectrum of developmental anomalies and constitutional diseases may be linked to high-risk conceptions related to preovulatory overripeness ovopathy (PrOO). Some developmental anomalies, such as NTDs, are to a large extent prevented by supplementation of folic acid before conception, but supplementation does not seem to prevent cardiovascular disease or cognitive decline. These diverging results can be elucidated by introduction of the PrOO concept, as MTHFR polymorphisms and inherent low folate levels induce both non-optimal maturation of the oocyte and unsuccessful DNA methylation and demethylation, i.e. epigenetic mutations. The PrOO concept is testable and predicts in a random population the following: (1) female carriers of specific genetic MTHFR variants exhibit more ovulatory disturbances and inherent subfecundity traits, (2) descendents from a carrier mother, when compared with those from a wild-type mother, are more frequently conceived in PrOO high-risk conditions and, thus, (3) disadvantaged in life expectancy. If so, some MTHFR polymorphisms represent a novel, genetically determined, PrOO high-risk conception category comparable to those which are environmentally and behaviorly influenced. These high-risk conditions may cause developmental anomalies and defective epigenetic reprogramming in progeny. The interaction between genetic and environmental factors is a plausible mechanism of multifactorial inheritance.

Jongbloet, Piet Hein; Verbeek, Andre LM; den Heijer, Martin; Roeleveld, Nel

2008-01-01

260

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

SciTech Connect

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

Suzuki, Kenji; Yoshida, Hiroyuki; Naeppi, Janne; Dachman, Abraham H. [Department of Radiology, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637 (United States); Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 75 Blossom Court, Suite 220, Boston, Massachusetts 02114 (United States); Department of Radiology, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637 (United States)

2006-10-15

261

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  

Microsoft Academic Search

Objective  The aims of this study were to elucidate the processes of neuronal differentiation and ventrodorsal patterning in the spinal\\u000a 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\\u000a (ONTD) on these processes.\\u000a \\u000a \\u000a \\u000a \\u000a Method  Expression patterns of neuronal antigens (neuronal nuclear antigen, neurofilament-associated protein (NAP), and

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

2010-01-01

262

Tube support  

DOEpatents

A tube support for supporting horizontal tubes from an inclined vertical support tube passing between the horizontal tubes. A support button is welded to the vertical support tube. Two clamping bars or plates, the lower edges of one bearing on the support button, are removably bolted to the inclined vertical tube. The clamping bars provide upper and lower surface support for the horizontal tubes.

Mullinax, Jerry L. (Green Township, Summit County, OH)

1988-01-01

263

Zebrafish arl6ip1 Is Required for Neural Crest Development during Embryogenesis  

PubMed Central

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

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

2012-01-01

264

TUBE TESTER  

DOEpatents

This patent relates to tube testing, and in particular describes a tube tester for automatic testing of a number of vacuum tubes while in service and as frequently as may be desired. In it broadest aspects the tube tester compares a particular tube with a standard tube tarough a difference amplifier. An unbalanced condition in the circuit of the latter produced by excessive deviation of the tube in its characteristics from standard actuates a switch mechanism stopping the testing cycle and indicating the defective tube.

Gittings, H.T. Jr.; Kalbach, J.F.

1958-01-14

265

Wind Tubes  

NSDL National Science Digital Library

In this activity, learners create and experiment with wind tubes. These tubes are a playful and inventive way to explore the effect that moving air has on objects. Construction uses everyday materials such as a fan and embroidery hoops. Itâs fun to make things fly out of or float in the tubes, and to adjust the tubes to change the way the objects fly. The activity requires a significant amount of time and resources to build and may require adult help in construction. Experimentation with the wind tubes is engaging for a wide age range of learners.

Exploratorium

2012-12-14

266

Comparative physical and transcript maps of approximately 1 Mb around loop-tail, a gene for severe neural tube defects on distal mouse chromosome 1 and human chromosome 1q22-q23.  

PubMed

The homozygous loop-tail (Lp) mouse has a severe neural tube closure defect, analogous to the craniorachischisis phenotype seen in humans. Linkage analysis and physical mapping have previously localized the Lp locus to a region on mouse chromosome 1 defined by the markers D1Mit113-Tagln2. Here we report the construction of sequence-ready bacterial clone contigs encompassing the Lp critical region in both mouse and the orthologous human region (1q22-q23). Twenty-two genes, one EST, and one pseudogene have been identified using a combination of EST database screening, exon amplification, and genomic sequence analysis. The preliminary gene map is Cen-Estm33-AA693056-Ly9-Cd48-Slam-Cd84-Kiaa1215-Nhlh1-Kiaa0253-Copa-Pxf-H326-Pea15-Casq1-Atp1a4-Atp1a2-Estm34-Kcnj9-Kcnj10-Kiaa1355-Tagln2-Nesg1-Crp-Tel. The genes between Slam and Kiaa1355 are positional candidates for Lp. The comparative gene content and order are identical between mouse and human, indicating a high degree of conservation between the two species in this region. Together, the physical and transcript maps described here serve as resources for the identification of the Lp mutation and further define the conservation of this genomic region between mouse and human. PMID:11401431

Doudney, K; Murdoch, J N; Paternotte, C; Bentley, L; Gregory, S; Copp, A J; Stanier, P

2001-03-01

267

Slits affect the timely migration of neural crest cells via Robo receptor.  

PubMed

Background: Neural crest cells emerge by delamination from the dorsal neural tube and give rise to various components of the peripheral nervous system in vertebrate embryos. These cells change from non-motile into highly motile cells migrating to distant areas before further differentiation. Mechanisms controlling delamination and subsequent migration of neural crest cells are not fully understood. Slit2, a chemorepellant for axonal guidance that repels and stimulates motility of trunk neural crest cells away from the gut has recently been suggested to be a tumor suppressor molecule. The goal of this study was to further investigate the role of Slit2 in trunk neural crest cell migration by constitutive expression in neural crest cells. Results: We found that Slit gain-of-function significantly impaired neural crest cell migration while Slit loss-of-function favored migration. In addition, we observed that the distribution of key cytoskeletal markers was disrupted in both gain and loss of function instances. Conclusions: These findings suggest that Slit molecules might be involved in the processes that allow neural crest cells to begin migrating and transitioning to a mesenchymal type. PMID:22689303

Giovannone, Dion; Reyes, Michelle; Reyes, Rachel; Correa, Lisa; Martinez, Darwin; Ra, Hannah; Gomez, Gustavo; Kaiser, Joshua; Ma, Le; Stein, Mary-Pat; de Bellard, Maria Elena

2012-06-23

268

Background Information  

Center for Biologics Evaluation and Research (CBER)

Text VersionPage 1. Background Information ... These have been labeled to remove fluid from patients suffering from volume overload. ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials

269

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

Microsoft Academic Search

BACKGROUND: While the body axis is largely patterned along the anterior-posterior (A-P) axis during gastrulation, the central nervous system (CNS) shows dynamic changes in the expression pattern of Hox genes during neurulation, suggesting that the CNS refines the A-P pattern continuously after neural tube formation. This study aims at clarifying the role of somites in up-regulating Hoxb4 expression to eventually

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

2009-01-01

270

Nasogastric feeding tube  

MedlinePLUS

Feeding - nasogastric tube; NG tube; Bolus feeding; Continuous pump feeding; Gavage tube ... A nasogastric tube, or NG tube, is a special tube that carries food and medicine to the stomach through the nose. ...

271

Hoot Tubes  

NSDL National Science Digital Library

This page, provides an explanation of how hot air rising through an open tube (stove pipe) vibrates to create a sound. It includes instructions on how to perform the demonstration and a Quicktime video illustrating the demonstration.

2010-12-18

272

Multilayer Tube.  

National Technical Information Service (NTIS)

The multilayer tube, including external concrete shell connected by adhesive with the inner core of cast stone is distinguished by the fact that to increase the strength, and the core is made with longitudinal prestressed reinforcement placed uniformly al...

A. E. Shumurnov B. N. Ulyanov V. S. Panasyuk Z. M. Burdenkova

1973-01-01

273

Electron Tubes  

NSDL National Science Digital Library

All About Circuits is a website that âÂÂprovides a series of online textbooks covering electricity and electronics.â Written by Tony R. Kuphaldt, the textbooks available here are wonderful resources for students, teachers, and anyone who is interested in learning more about electronics. This specific section, Electron Tubes, is the thirteenth chapter in Volume II âÂÂAlternating Current. A few of the topics covered in this chapter include: Early tube history; The Triode; The Tetrode; The Pentode; Tube parameters; and Display tubes. Diagrams and detailed descriptions of concepts are included throughout the chapter to provide users with a comprehensive lesson. Visitors to the site are also encouraged to discuss concepts and topics using the All About Circuits discussion forums (registration with the site is required to post materials).

Kuphaldt, Tony R.

2008-07-18

274

Hoot Tubes  

NSDL National Science Digital Library

This demonstration will show how hot air rising through an empty tube (stove pipe) vibrates to create sound. This can be demonstrated by using a Meeker burner or a Bunsen burner; instructions for either method are included in this resource. Note: This demonstration involves open flame. Be sure to have an adult present when performing this demonstration. Wear gloves or some type of hand protection as the metal tube gets very hot.

House, The S.

2010-01-01

275

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

PubMed Central

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

Stottmann, Rolf W.; Klingensmith, John

2011-01-01

276

Multiple tube premixing device  

SciTech Connect

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

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

2012-12-11

277

Multiple tube premixing device  

DOEpatents

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

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

2013-08-13

278

Emergence and migration of trunk neural crest cells in a snake, the California Kingsnake (Lampropeltis getula californiae)  

PubMed Central

Background The neural crest is a group of multipotent cells that emerges after an epithelial-to-mesenchymal transition from the dorsal neural tube early during development. These cells then migrate throughout the embryo, giving rise to a wide variety derivatives including the peripheral nervous system, craniofacial skeleton, pigment cells, and endocrine organs. While much is known about neural crest cells in mammals, birds, amphibians and fish, relatively little is known about their development in non-avian reptiles like snakes and lizards. Results In this study, we show for the first time ever trunk neural crest migration in a snake by labeling it with DiI and immunofluorescence. As in birds and mammals, we find that early migrating trunk neural crest cells use both a ventromedial pathway and an inter-somitic pathway in the snake. However, unlike birds and mammals, we also observed large numbers of late migrating neural crest cells utilizing the inter-somitic pathway in snake. Conclusions We found that while trunk neural crest migration in snakes is very similar to that of other amniotes, the inter-somitic pathway is used more extensively by late-migrating trunk neural crest cells in snake.

2010-01-01

279

Vitamin dificiencies and neural tube defects  

Microsoft Academic Search

Serum folate, red cell folate, white blood cell vitamin C, riboflavin saturation index, and serum vitamin A were determined during the first trimester of pregnancy in over 900 cases. For each of these there was a social classes I + II showed the highest levels which differed significantly from other classes, except for serum folate. In 6 mothers who gave

R. W. Smithells; S Sheppard; C J Schorah

1976-01-01

280

Selective surgical management of neural tube malformations.  

PubMed Central

The physical characteristics of 49 children with spina bifida cystica, survivors of a group subjected to selection for early surgery are compared with 39 children alive from an earlier unselected series, born in the 1960s, and reviewed retrospectively. Sixteen children were also studied in whom the initial decision not to operate had been followed by survival and subsequent treatment. Children selected for initial surgery have a significantly lower mortality than those not selected and their mobility at 5 to 7 years of age is better, although only marginally so compared with the unselected group. Selection does not decrease the need for shunt treatment of the associated hydrocephalus. None of those not initially selected for surgery have normal faecal or urinary continence, whereas 35% of the selected in group have normal continence and urinary tracts. Children treated immediately have significantly higher degrees of intelligence than both the unselectively treated and those whose treatment was delayed but a fifth of the latter group were intellectually normal. There were only small differences in intelligence between children given delayed treatment and those unselectively treated, suggesting that postponing surgery does not necessarily have a deleterious effect on ability.

Evans, R C; Tew, B; Thomas, M D; Ford, J

1985-01-01

281

Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm  

Microsoft Academic Search

The cellular interactions that control the differentiation of dorsal cell types from neural progenitors have been examined in neural plate explants. Certain genes that are expressed in the dorsal neural tube are initially expressed uniformly within the neural plate and appear to achieve their dorsal restriction through a Sonic hedgehog (SHH)-mediated repressive signal from the notochord. The acquisition of definitive

Karel F Liem; Gabi Tremml; Henk Roelink; Thomas M Jessell

1995-01-01

282

Tube Feedings.  

ERIC Educational Resources Information Center

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

Plummer, Nancy

283

Mystery Tubes  

NSDL National Science Digital Library

Learners investigate a pre-constructed mystery tube to determine its interior mechanism. Working in small groups, learners pose explanations (hypotheses) for what they are observing and test their hypotheses. In a possible extension of this activity, learners build their own model to test their hypothesis. This lesson serves as a good introduction to the nature of scientific inquiry.

Paleontology, University O.

2010-01-01

284

Neural Crest Cell Migration  

NSDL National Science Digital Library

This simple FlashTM animation depicts migration of neural crest cells throughout the mesoderm of the neurulating germ disc. For context it opens with a cross section of the germ disc showing the neural crests at the dorsal end of the neural tube. It then turns to a lateral view, which allows users to observe neural crest cells separating from the crests and migrating into the mesoderm along the neural tube or epidermis. A back button allows users to jump to previous scenes, a rate button allows them to toggle between fast and slow modes, and a text button allows them to toggle explanatory text on and off. Instructions for opening animation with Windows system. 1. Double click the icon for the SWF. 2. A dialog box may pop up that begins with the statement "Windows cannot open this file:" If this box does not appear proceed to step 4. If it does choose "Select the program from a list," then click OK. 3. Another dialog box will pop up that lists different programs. Make sure " Internet Explorer" is selected, then click OK. 4. A Window for Internet Explorer will pop up. Beneath the toolbars at the top of the window a yellow bar will appear that reads "To help protect your security, Internet Explorer has restricted this webpage from running scripts or Active X controls that could access your computer. Click here for options..." Pass the cursor over this yellow bar and click the right mouse button. 5. A dialog box will pop up. Left click the option "Allow Blocked Content." 6. Another dialog box will appear labeled "Security Warning" asking you to confirm that you want to run the content. Click "Yes." 7. The Flash animation will appear in the Internet Explorer Window. 8. Left click anywhere in the animation to advance the display. 9. Read instructions provided by the animation for additional controls such as navigation buttons.

PhD Jack D Thatcher (West Virginia School of Osteopathic Medicine Structural Biology)

2010-11-29

285

Electron tube  

SciTech Connect

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.

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

2011-12-20

286

Finned tubing  

US Patent & Trademark Office Database

Finned tubing for use in heat exchangers has tapered helical fins with serrations disposed between connecting webs. The opposed edges of the serrations, interior of the periphery, taper to a relatively sharp edge. Shark-fin like protuberances project outwardly adjacent one leg of each serration with each protuberance having a flange thereon. In one modification, the serrations on adjacent fins are spirally aligned. One method and apparatus of producing the finned tubing subjects a tensioned strip to graduated compression to curl the strip onto a tube to form fins, while simultaneously relieving a portion of the compression at spaced points along the periphery of the strip, resulting in a tearing of the strip to provide the serrations, and the adjacent protuberances. The protuberances are then compressed by rollers to form the flanges. An apparatus for carrying out the method includes a pair of rotary members to taper and curl the strip, with one of the rotary members having a series of recesses. Another method of producing some form of serration uses a raised projection on a rotary member instead of a recess.

1980-10-14

287

Chest tube insertion  

MedlinePLUS

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

288

Tube furnace  

DOEpatents

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

Foster, Kenneth G. (Livermore, CA); Frohwein, Eugene J. (San Ramon, CA); Taylor, Robert W. (Livermore, CA); Bowen, David W. (Livermore, CA)

1991-01-01

289

Tube furnace  

DOEpatents

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

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

1990-12-31

290

Tube furnace  

DOEpatents

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

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

1990-01-01

291

Tapered pulse tube for pulse tube refrigerators  

DOEpatents

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

Swift, Gregory W. (Sante Fe, NM); Olson, Jeffrey R. (San Mateo, CA)

1999-01-01

292

Tube-in-tube thermophotovoltaic generator  

DOEpatents

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

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

1998-06-30

293

Tube-in-tube thermophotovoltaic generator  

DOEpatents

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

Ashcroft, John (Scotia, NY); Campbell, Brian (Scotia, NY); DePoy, David (Clifton Park, NY)

1998-01-01

294

A tube-in-tube thermophotovoltaic generator  

DOEpatents

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

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

1996-12-31

295

Tube Feeding Emergency Kit  

MedlinePLUS

The Tube Feeding Emergency Kit Imagine having fifteen minutes to evacuate before a natural disaster strikes. Or imagine rushing ... of a local community hospital completely unfamiliar with tube-feeding. Having an emergency kit full of tube- ...

296

Eustachian Tube Dysfunction  

MedlinePLUS

MENU Return to Web version Eustachian Tube Dysfunction Overview What is eustachian tube dysfunction? The eustachian tubes are small passageways that connect the upper part of your throat (pharynx) ...

297

Fallopian Tube Cancer  

MedlinePLUS

... Types Fallopian Tube Cancer Share This Page: Fallopian Tube Cancer This section has been reviewed and approved ... Board , 8/2012 Overview Cancer.Net Guide Fallopian Tube Cancer Overview Statistics Medical Illustrations Risk Factors and ...

298

Eustachian Tube Function: A Review.  

National Technical Information Service (NTIS)

The review investigates the anatomy and physiology of the Eustachian tube (ET) and its development, methods of measurement, and the effects of its function and dysfunction on middle ear disorders and hearing loss. The review forms the background to a rese...

S. M. Moss A. M. Martin R. J. Marchbanks

1987-01-01

299

Data analysis for steam generator tubing samples  

SciTech Connect

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.

Dodd, C.V.

1996-07-01

300

Growth hormone in neural tissues of the chick embryo  

Microsoft Academic Search

Growth hormone (GH) gene expression predominantly occurs in the pituitary gland, although it also occurs in many extrapituitary sites, including the brain. The cellular location and ontogeny of neural GH production is, however, largely unknown. This has therefore been determined during chick embryogenesis. In chicks, the brain develops from the neural tube at embryonic day (ED) 3. At this age,

S Harvey; CDM Johnson; E J Sanders

2001-01-01

301

Neural computing  

SciTech Connect

This survey gives a personal view of how the coarse grain of distributed computing in terms of schemas may be integrated with a fine grain approach to neural networks in defining a sixth generation of computers. It shows how biology may inspire the technology of neural computing. According to the author, neural computing defines a lively new subfield of parallel and distributed computing, one which both suggests novel computer architectures - especially those that embody learning principles - and offers challenges to existing architectures in implementing a variety of novel network designs.

Arbib, M.A. (Center for Neural Engineering, Univ. of Southern California, Los Angeles, CA (US))

1989-04-01

302

Magnetic merging in colliding flux tubes  

NASA Astrophysics Data System (ADS)

We develop an analytical theory of reconnection between colliding, twisted magnetic flux tubes. Our analysis is restricted to direct collisions between parallel tubes and is based on the collision dynamics worked out by Bogdan (1984). We show that there is a range of collision velocities for which neutral point reconnection of the Parker-Sweet type can occur, and a smaller range for which reconnection leads to coalescence. Mean velocities within the solar convection zone are probably significantly greater than the upper limit for coalescence. This suggests that the majority of flux tube collisions do not result in merging, unless the frictional coupling of the tubes to the background flow is extremely strong.

Zweibel, Ellen G.; Rhoads, James E.

1995-02-01

303

Neural Networks  

SciTech Connect

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

Smith, Patrick I.

2003-09-23

304

New laser tracheal tube  

NASA Astrophysics Data System (ADS)

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

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

1996-09-01

305

Neural networks for triggering  

SciTech Connect

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

Denby, B. (Fermi National Accelerator Lab., Batavia, IL (USA)); Campbell, M. (Michigan Univ., Ann Arbor, MI (USA)); Bedeschi, F. (Istituto Nazionale di Fisica Nucleare, Pisa (Italy)); Chriss, N.; Bowers, C. (Chicago Univ., IL (USA)); Nesti, F. (Scuola Normale Superiore, Pisa (Italy))

1990-01-01

306

Annexin A6 Modulates Chick Cranial Neural Crest Cell Emigration  

PubMed Central

The vertebrate neural crest is a population of migratory cells that originates in the dorsal aspect of the embryonic neural tube. These cells undergo an epithelial-to-mesencyhmal transition (EMT), delaminate from the neural tube and migrate extensively to generate an array of differentiated cell types. Elucidating the gene regulatory networks involved in neural crest cell induction, migration and differentiation are thus crucial to understanding vertebrate development. To this end, we have identified Annexin A6 as an important regulator of chick midbrain neural crest cell emigration. Annexin proteins comprise a family of calcium-dependent, membrane-binding molecules that mediate a variety of cellular and physiological processes including cell adhesion, migration and invasion. Our data indicate that Annexin A6 is expressed in the proper spatio-temporal pattern in the chick midbrain to play a potential role in neural crest cell ontogeny. To investigate Annexin A6 function, we have depleted or overexpressed Annexin A6 in the developing midbrain neural crest cell population. Our results show that knock-down or overexpression of Annexin A6 reduces or expands the migratory neural crest cell domain, respectively. Importantly, this phenotype is not due to any change in cell proliferation or cell death but can be correlated with changes in the size of the premigratory neural crest cell population and with markers associated with EMT. Taken together, our data indicate that Annexin A6 plays a pivotal role in modulating the formation of cranial migratory neural crest cells during vertebrate development.

Wu, Chyong-Yi; Taneyhill, Lisa A.

2012-01-01

307

Ultrasound Can Accurately Guide Gastrostomy Tube Replacement and Confirm Proper Tube Placement at the Bedside  

Microsoft Academic Search

Background: Malfunctioning or dislodged gastrostomy tubes (G-tubes) often require urgent replacement and reinsertion in the Emergency Department (ED). Few data exist regarding the best technique for bedside catheter replacement and verification, and individual operator preferences vary. Although a few reports have described the use of ultrasound guidance during the initial percutaneous insertion, no data are available concerning its role during

Teresa S. Wu; Stephen J. Leech; Marcy Rosenberg; Charles Huggins; Linda Papa

2009-01-01

308

Condenser tube repairs using tube inserts  

SciTech Connect

It is common knowledge that many heat exchanger (HX) tube failures occur within the first 6 in. (150 mm) of the bundle. Inlet-end erosion, stress corrosion cracking, and crevice corrosion are different types of failure mechanisms that are common in shell-and-tube HX.

Tallman, P.M.

2000-05-01

309

Virtual Lava Tube  

NSDL National Science Digital Library

This interactive resource adapted from The Virtual Lava Tube by Dave Bunnell, presents images of different features found in lava tube caves and includes detailed information on how these features are formed and where they occur.

Foundation, Wgbh E.

2005-10-21

310

Bourdon Tube Gauge  

NSDL National Science Digital Library

A Bourdon tube gauge animation. The objective is to describe how a Bourdon Tube Gauge measures vacuum. This simulation is from Module 101 of the vacuum technology and gas control cluster of the MATEC Module Library (MML).

2011-07-14

311

Eustachian tube (image)  

MedlinePLUS

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

312

Embryology of the neural crest: its inductive role in the neurocutaneous syndromes.  

PubMed

Neural crest cells are first recognized at the lateral margin of the neural placode shortly after gastrulation, although they are not committed to their diverse fates until later. After dorsal closure of the neural tube, neural crest cells separate and migrate throughout the embryo to form many structures of ectodermal origin (eg, dorsal root and autonomic ganglia, peripheral nerve sheaths) and mesodermal origin (eg, blood vessels, melanocytes, adipose tissue, membranous bone, connective tissue, most of the ocular globe). Terminal differentiation occurs after migration is complete. Three regions of the neural tube generate neural crest: rhombencephalon, mesencephalon, and prosencephalon, each with a different migratory pattern. The most important genes promoting neural crest differentiation and migration are those with a dorsalizing influence in the vertical axis of the neural tube (eg, PAX3, BMP4, ZIC2), some segmentation genes (eg, WNT1), genes that inhibit neural crest (eg, EGR2), and neural crest-specific differentiating genes (eg, SLUG, SOX10). In the neurocutaneous syndromes, diverse features result from abnormal neural crest differentiation, providing a more encompassing embryologic basis for these disorders than the traditional view that these syndromes are somehow related to skin and brain because both are ectodermal derivatives. Abnormal angiogenesis, areas of abnormal pigmentation that sometimes follow the lines of Blashko, nerve sheath proliferations, disorders of chromaffin tissue, lipomes and benign and malignant tumors are frequent features. Many defective genes in neurocutaneous syndromes have an additional function as tumor suppressors. Interactions between genes associated with these disorders and others essential to neural crest formation, migration, and differentiation, are a likely molecular genetic basis for these diseases. The craniofacial abnormalities associated with many cerebral malformations and cutaneous lesions in some neurocutaneous syndromes emphasize an important inductive role of the neural tube in the development of non-neural tissues, mediated through neural crest. PMID:16225807

Sarnat, Harvey B; Flores-Sarnat, Laura

2005-08-01

313

VACUETTE EDTA K2 tube; VACUETTE EDTA K3 tube  

Center for Biologics Evaluation and Research (CBER)

... VACUETTE EDTA K2 tube; VACUETTE EDTA K3 tube. Applicant: Sienna Partners. ... Product: VACUETTE EDTA K2 Tube VACUETTE EDTA K3 Tube. ... More results from www.fda.gov/biologicsbloodvaccines/bloodbloodproducts/approvedproducts

314

CORONA STABILIZER TUBE  

Microsoft Academic Search

garian) Various types of corona stabilizing tubes were prepared in the ; Nuclear Research Institute on the basis of previously published data resulting in ; a broad experience in the fields of application of the tube. Of the types used ; the 1-cm diameter cathode and 1-mm dismeter anode tubes were found to be the most ; satisfactory ones. The

Csongor

1961-01-01

315

Extragalactic Background Radiation  

NASA Astrophysics Data System (ADS)

Contents; Preface; List of participants; 1. Introduction P. J. E. Peebles; 2. Extragalactic gamma-ray background N. Gehrels and C. Cheung; 3. The X-ray background (observations) G. Zamorani; 4. Extragalactic ultraviolet background radiation R. C. Henry and J. Murthy; 5. Ultraviolet background (theory) P. Jakobsen; 6. The optical extragalactic background radiation J. A. Tyson; 7. Infrared background (observations) M. G. Hauser; 8. The infrared background (theory) C. J. Lonsdale; 9. Microwave background radiation (observations) J. C. Mather; 10. Detection of degree scale anisotropy P. M. Lubin; 11. Cosmic microwave background anisotropies and structure formation in the universe N. Vittorio; The radio background emission - the long and short of it M. S. Longair; 13. The radio background: radio-loud galaxies at high and low redshifts J. A. Peacock; 14. Conference summary M. J. Rees.

Calzetti, Daniela; Livio, Mario; Madau, Piero

1995-01-01

316

Migration of cardiac neural crest cells in Splotch embryos.  

PubMed

Pax3 encodes a transcription factor expressed during mid-gestation in the region of the dorsal neural tube that gives rise to migrating neural crest populations. In the absence of Pax3, both humans and mice develop with neural crest defects. Homozygous Splotch embryos that lack Pax3 die by embryonic day 13.5 with cardiac defects that resemble those induced by neural crest ablation in chick models. This has led to the hypothesis that Pax3 is required for cardiac neural crest migration. However, cardiac derivatives of Pax3-expressing precursor cells have not been previously defined, and Pax3-expressing cells within the heart have not been well demonstrated. Hence, the precise role of Pax3 during cardiac development remains unclear. Here, we use a Cre-lox method to fate map Pax3-expressing neural crest precursors to the cardiac outflow tract. We show that although Pax3 itself is extinguished prior to neural crest populating the heart, derivatives of these precursors contribute to the aorticopulmonary septum. We further show that neural crest cells are found in the outflow tract of Splotch embryos, albeit in reduced numbers. This indicates that contrary to prior reports, Pax3 is not required for cardiac neural crest migration. Using a neural tube explant culture assay, we demonstrate that neural crest cells from Splotch embryos show normal rates of proliferation but altered migratory characteristics. These studies suggest that Pax3 is required for fine tuning the migratory behavior of the cardiac neural crest cells while it is not essential for neural crest migration. PMID:10751175

Epstein, J A; Li, J; Lang, D; Chen, F; Brown, C B; Jin, F; Lu, M M; Thomas, M; Liu, E; Wessels, A; Lo, C W

2000-05-01

317

Real-Time Decision Fusion for Multimodal Neural Prosthetic Devices  

Microsoft Academic Search

BackgroundThe field of neural prosthetics aims to develop prosthetic limbs with a brain-computer interface (BCI) through which neural activity is decoded into movements. A natural extension of current research is the incorporation of neural activity from multiple modalities to more accurately estimate the user's intent. The challenge remains how to appropriately combine this information in real-time for a neural prosthetic

James Robert White; Todd Levy; William Bishop; James D. Beaty; Joel M. Schnur

2010-01-01

318

Pulse Tube Refrigerators  

NASA Astrophysics Data System (ADS)

Interest in the pulse tube comes from its potential for high reliability and low level of induced vibration. A numerical model has been developed to provide a tool for practical design. It has been successfully validated against the experimental results obtained with a single stage double inlet pulse tube which has achieved a temperature of 28 K at a frequency of a few Hz. Further developments have demonstrated the capability of operating a pulse tube at higher frequencies in association with a Stirling pressure oscillator. Current projects include coaxial geometry for miniature pulse tubes with linear resonant pressure oscillators. A 4K multistaged pulse tube is also in development.

Ravex, A.; Duband, L.; Rolland, P.

1995-10-01

319

Neural Communication  

NSDL National Science Digital Library

First you will explore the neuron. Then how neurons communicate with each other by exploring action potentials and neural transmission. Let's start with the neuron. Explore the neuron and fill out the worksheet by labeling each part of the neuron and giving a brief description of what it does. Structure of the Neuron (Upon entering the site go through each link at the top of the page from intro to terminal buttons) Now take a look ...

Johnson, Mrs.

2010-06-22

320

Neural Networks  

Microsoft Academic Search

\\u000a Neural networks are networks of nerve cells in the brains of humans and animals. The human brain has about 100 billion nerve\\u000a cells. We humans owe our intelligence and our ability to learn various motor skills and intellectual capabilities to the brain’s\\u000a complex relays and adaptivity. The nerve cells and their connections are responsible for awareness, associations, thoughts,\\u000a consciousness and

Wolfgang Ertel

321

Pulse Tube Refrigerator  

NASA Astrophysics Data System (ADS)

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

Matsubara, Yoichi

322

Pediatric cuffed endotracheal tubes  

PubMed Central

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 H2O 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.

Bhardwaj, Neerja

2013-01-01

323

Pediatric cuffed endotracheal tubes.  

PubMed

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 H2O 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. PMID:23492803

Bhardwaj, Neerja

2013-01-01

324

Acetaminophen: Background and Overview  

Center for Biologics Evaluation and Research (CBER)

Text Version1 Acetaminophen: Background and Overview Gerald J. Dal Pan, MD, MHS ... Page 86. 86 Background 1953 NDA 08-717 (acetaminophen tablet) ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials

325

IR Background Suppression Studies.  

National Technical Information Service (NTIS)

A brief description of the background suppression scheme is described, and results obtained using the defocussing technique are presented. It has been demonstrated that a background suppression ratio of two orders of magnitudes can be obtained.

O. Shepherd W. P. Reidy T. F. Zehnpfennig G. A. Vanasse A. T. Stair

1977-01-01

326

Gametophytic pollen tube guidance  

Microsoft Academic Search

The concept of a pollen tube attractant was proposed in the late nineteenth century when pollen tubes were found to grow toward\\u000a excised pistil tissues on medium. Since then, for about 140 years, plant biologists have tried to identify the pollen tube\\u000a attractants. However, no molecule has been convincingly demonstrated to be the true attractant that actually controls the\\u000a navigation of

Tetsuya Higashiyama; Yuki Hamamura

2008-01-01

327

Photomultiplier tube saturation indicator  

DOEpatents

A photomultiplier tube saturation indicator is formed by supplying a supplemental light source, typically a light emitting diode (LED), adjacent to the photomultiplier tube. A switch allows the light source to be activated. The light is forwarded to the photomultiplier tube by an optical fiber. If the probe is properly light tight, then a meter attached to the indicator will register the light from the LED. If the probe is no longer light tight, and the saturation indicator is saturated, no signal will be registered when the LED is activated. This photomultiplier tube is used with alpha contamination probes.

Ruch, J.F.; Urban, D.J.

1995-12-31

328

Wound tube heat exchanger  

DOEpatents

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

Ecker, Amir L. (Duncanville, TX)

1983-01-01

329

Sapphire tube pressure vessel  

SciTech Connect

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

Outwater, J.O.

2000-05-23

330

Simulation of night sky background for HAGAR  

NASA Astrophysics Data System (ADS)

For experiments like HAGAR, based on atmospheric Cherenkov technique, performance of the experiment depends strongly on the level of night sky background (NSB) at the observation site. Proper modeling of NSB in simulations is important to get the realistic estimate of the performance parameters. Here we present the Monte Carlo simulation of NSB and its comparison with experimental data. Effect of after-pulsing in photo-multiplier tubes is also modeled in present simulations.

Saha, Lab; Hagar Collaboration

331

Essential Role for Sphingosine Kinases in Neural and Vascular Development  

Microsoft Academic Search

Sphingosine-1-phosphate (S1P), an important sphingolipid metabolite, regulates diverse cellular processes, including cell survival, growth, and differentiation. Here we show that S1P signaling is critical for neural and vascular development. Sphingosine kinase-null mice exhibited a deficiency of S1P which severely disturbed neurogenesis, including neural tube closure, and angiogenesis and caused embryonic lethality. A dramatic increase in apoptosis and a decrease in

Kiyomi Mizugishi; Tadashi Yamashita; Ana Olivera; Georgina F. Miller; Sarah Spiegel; Richard L. Proia

2005-01-01

332

FGF and Shh Signals Control Dopaminergic and Serotonergic Cell Fate in the Anterior Neural Plate  

Microsoft Academic Search

During development, distinct classes of neurons are specified in precise locations along the dorso–ventral and anterior–posterior axes of the neural tube. We provide evidence that intersections of Shh, which is expressed along the ventral neural tube, and FGF8, which is locally produced at the mid\\/hindbrain boundary and in the rostral forebrain, create induction sites for dopaminergic neurons in the midbrain

Weilan Ye; Kenji Shimamura; John L. R Rubenstein; Mary A Hynes; Arnon Rosenthal

1998-01-01

333

Acoustic streaming in pulse tube refrigerators: tapered pulse tubes  

Microsoft Academic Search

Acoustic streaming is investigated in tapered tubes with axially varying temperature, in the boundary layer limit. By appropriately shaping the tube, the streaming can be eliminated. Experimental data demonstrate that an orifice pulse tube refrigerator with a conical pulse tube whose cone angle eliminates streaming has more cooling power than one with either a cylindrical pulse tube or a conical

J. R. Olson; G. W. Swift

1997-01-01

334

The Cosmic Background Explorer.  

ERIC Educational Resources Information Center

|Outlines the Cosmic Background Explorer (COBE) mission to measure celestial radiation. Describes the instruments used and experiments involving differential microwave radiometers, and a far infrared absolute spectrophotometer. (YP)|

Gulkis, Samuel; And Others

1990-01-01

335

The Cosmic Background Explorer.  

ERIC Educational Resources Information Center

Outlines the Cosmic Background Explorer (COBE) mission to measure celestial radiation. Describes the instruments used and experiments involving differential microwave radiometers, and a far infrared absolute spectrophotometer. (YP)

Gulkis, Samuel; And Others

1990-01-01

336

Genetics of neural crest and neurocutaneous syndromes.  

PubMed

Neural crest progenitor cells are identified at the lateral margins of the neural placode at the time of gastrulation. With folding of the placode, these precursors are brought to the dorsal midline of the neural tube at the site of closure, become committed to neural crest lineage and almost immediately migrate peripherally to various predetermined sites in the body and then differentiate as a variety of cellular types in all three of the traditional "germ layers." All of these processes of migration and differentiation of neural crest are precisely genetically programed, temporally and spatially, by a variety of genes. Primary neurocutaneous syndromes are all very different diseases with different genetic mutations, but the unifying factor amongst them is that all are neurocristopathies and can be explained as such, including the tumor-suppressor function of several of these genes, especially those of neurofibromatosis 1 and 2 and tuberous sclerosis. This chapter reviews the principal genes that program neural crest development and also are documented, implicated, or suspected in the pathogenesis of neurocutaneous syndromes. Recent genetic discoveries are noted in epidermal nevus syndrome, including Proteus syndrome and their association with hemimegalencephaly and congenital infiltrating lipomatosis of the face. PMID:23622181

Sarnat, Harvey B; Flores-Sarnat, Laura

2013-01-01

337

Traveling-Wave Tube.  

National Technical Information Service (NTIS)

In monograph is expounded theory of traveling-wave tube. Basic attention is allotted to question of interaction of electron stream with traveling wave for large values of amplification factor in application to tubes of medium and high power. In detail is ...

A. M. Kats M. B. Tseytlin

1967-01-01

338

Miniature Pulse Tube Cooler  

Microsoft Academic Search

A high capacity miniature pulse tube cooler for space that is scaled from the High Efficiency Cryocooler (HEC) is being developed. The low mass (1.5 kg) integral pulse tube cryocooler can provide large cooling power over a wide temperature range (e.g., 5 W at 95 K). The cooler is designed to be compatible with the existing HEC flight electronics. A

E. Tward; T. Nguyen; J. Godden; G. Toma

2004-01-01

339

Tracheostomy tube - eating  

MedlinePLUS

Most people with a tracheostomy tube will be able to eat normally. However, swallowing food or liquid may feel differently. ... When you get your tracheostomy tube, or trach, you will not be able ... Instead, you will get nutrients through an IV (a intravenous ...

340

Background stratospheric aerosol layer  

Microsoft Academic Search

Balloonborne aerosol particle counter measurements are used in studying the stratospheric sulfate layer at Laramie, Wyoming, during 1978 and 1979, a 2-year volcanically quiescent period in which the layer appears to have been in a near equilibrium background state. Subtracting the background aerosol concentration from data obtained during an earlier volcanically active period indicates that the actual decay rate of

D. J. Hofmann; J. M. Rosen

1981-01-01

341

GLAST Background Model.  

National Technical Information Service (NTIS)

In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles tha...

E. Grove F. Longo J. F. Ormes T. Burnett W. Atwood

2007-01-01

342

Evacuated tube transport  

US Patent & Trademark Office Database

An evacuated tube transport (ETT) system comprises: Evacuated tubes (200) along a travel route (100) for both directions; capsules (300) to transport occupants or cargo within the tubes; equipment (700) providing continuous transfer to tube while preserving vacuum; capsule suspension (400) that substantially eliminates drag; coordinated acceleration device (500); energy recovery braking (600); vibration control structures (820); tube alignment devices (230); automatic capsule switch (650) and synchronization (885); automated operation, inspection, and maintenance (810); methods of construction; redundant data (835), safety and security (880) systems. Low and high technology embodiments are comprehensively disclosed. Possibilities include replacement or augmentation of: vehicles, power lines, energy storage devices, power plants, heaters, air conditioning, water and sewer pipes, and communication cables and satellites. ETT provides continuous, environmentally benign, sustainable, local and international travel. Aerodynamic limitations, weather exposure, and obstacles are essentially eliminated; The system enables a quantum improvement in safety, speed and efficiency.

1999-09-14

343

Correlators in nontrivial backgrounds  

SciTech Connect

Operators in N=4 super Yang-Mills theory with an R-charge of O(N{sup 2}) are dual to backgrounds which are asymtotically AdS{sub 5}xS{sup 5}. In this article we develop efficient techniques that allow the computation of correlation functions in these backgrounds. We find that (i) contractions between fields in the string words and fields in the operator creating the background are the field theory accounting of the new geometry, (ii) correlation functions of probes in these backgrounds are given by the free field theory contractions but with rescaled propagators and (iii) in these backgrounds there are no open string excitations with their special end point interactions; we have only closed string excitations.

Mello Koch, Robert de [National Institute for Theoretical Physics, Department of Physics and Centre for Theoretical Physics, University of the Witwatersrand, Wits, 2050 (South Africa); Stellenbosch Institute for Advanced Studies, Stellenbosch (South Africa); Ives, Norman; Stephanou, Michael [National Institute for Theoretical Physics, Department of Physics and Centre for Theoretical Physics, University of the Witwatersrand, Wits, 2050 (South Africa)

2009-01-15

344

Does lumbosacral spina bifida arise by failure of neural folding or by defective canalisation?  

Microsoft Academic Search

The aim of this study was to determine whether open lumbosacral spina bifida results from an abnormality of neural folding (primary neurulation) or medullary cord canalisation (secondary neurulation). Homozygous curly tail (ct) mouse embryos were studied as a model system for human neural tube defects. The rostral end of the spina bifida was found to lie at the level of

A J Copp; F A Brook

1989-01-01

345

In vitro differentiation of transplantable neural precursors from human embryonic stem cells  

Microsoft Academic Search

The remarkable developmental potential and replicative capacity of human embryonic stem (ES) cells promise an almost unlimited supply of specific cell types for transplantation therapies. Here we describe the in vitro differentiation, enrichment, and transplantation of neural precursor cells from human ES cells. Upon aggregation to embryoid bodies, differentiating ES cells formed large numbers of neural tube–like structures in the

Marius Wernig; Ian D. Duncan; James A. Thomson; Su-Chun Zhang; Oliver Brüstle

2001-01-01

346

Review: The Role of Neural Crest Cells in the Endocrine System  

Microsoft Academic Search

The neural crest is a pluripotent population of cells that arises at the junction of the neural tube and the dorsal ectoderm.\\u000a These highly migratory cells form diverse derivatives including neurons and glia of the sensory, sympathetic, and enteric\\u000a nervous systems, melanocytes, and the bones, cartilage, and connective tissues of the face. The neural crest has long been\\u000a associated with

Meghan Sara Adams; Marianne Bronner-Fraser

2009-01-01

347

Chest tube insertion - series (image)  

MedlinePLUS

... lung can collapse, preventing adequate air exchange. Chest tubes are used to treat conditions that can cause ... Chest tubes are inserted to drain blood, fluid, or air and allow full expansion of the lungs. The tube ...

348

Oxygen tubing lengths and output flows: implications for patient care  

Microsoft Academic Search

Background: Historical wisdom has recommended up to 50 ft (15.24 m) of tubing based on the oxygen cylinder delivery system. Yet, many individuals may store their stationary systems in one area of the home and conduct their activities at distances by adding additional tubing. The aim of this study was to discriminate at what lengths clinically relevant decreases in flow

D L Cullen; J A Koss

2005-01-01

349

Looking Southeast Along Kilauea TEB Tube System  

USGS Multimedia Gallery

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

2010-07-19

350

The GLAST Background Model  

SciTech Connect

In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect.

Ormes, J.F.; /Denver U.; Atwood, W.; /UC, Santa Cruz; Burnett, T.; /Washington U., Seattle; Grove, E.; /Naval Research Lab, Wash., D.C.; Longo, F.; /INFN, Pisa; McEnery, J.; /NASA, Goddard; Mizuno, T.; /Hiroshima U.; Ritz, S.; /NASA, Goddard

2007-10-17

351

The GLAST Background Model  

SciTech Connect

In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect.

Ormes, J. F. [University of Denver (United States); Atwood, W. [University of California at Santa Cruz (United States); Burnett, T. [University of Washington (United States); Grove, E. [Naval Research Laboratory (United States); Longo, F. [Instituto Nazionale di Fisica Nucleare (INFN)-Pisa (Italy); McEnery, J.; Ritz, S. [NASA Goddard Space Flight Center (United States); Mizuno, T. [Hiroshima University (Japan)

2007-07-12

352

Magnetic flux tube models in superstring theory  

Microsoft Academic Search

Superstring models describing curved 4-dimensional magnetic flux tube backgrounds are exactly solvable in terms of free fields. We first consider the simplest model of this type (corresponding to a ‘Kaluza-Klein’ a = ?3 Melvin background). Its 2d action has a flat but topologically non-trivial 10-dimensional target space (there is a mixing of the angular coordinate of the 2-plane with an

J. G. Russo; A. A. Tseytlin

1996-01-01

353

Miniature Pulse Tube Cooler  

NASA Astrophysics Data System (ADS)

A high capacity miniature pulse tube cooler for space that is scaled from the High Efficiency Cryocooler (HEC) is being developed. The low mass (1.5 kg) integral pulse tube cryocooler can provide large cooling power over a wide temperature range (e.g., 5 W at 95 K). The cooler is designed to be compatible with the existing HEC flight electronics. A small back-to-back flexure compressor drives a pulse tube cold head which is integrated with the compressor. The cooler has been tested with both linear and coaxial cold heads. A description of the cooler and its performance in both linear and coaxial cold head versions is presented.

Tward, E.; Nguyen, T.; Godden, J.; Toma, G.

2004-06-01

354

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

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

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

355

Bilateral Myringotomy Tube Placement  

MedlinePLUS Videos and Cool Tools

... Myringotomy Tube Placement You must have Javascript enabled in your web browser. View Program Transcript Click Here to view the OR-Live, Inc. Privacy Policy and Legal Notice © 2010 OR-Live, Inc. All rights reserved.

356

Kinking of medical tubes.  

PubMed

The phenomenon of kinking in medical tubing remains a problem for some applications, particularly critical ones such as transporting gasses or fluids. Design features are described to prevent its occurrence. PMID:15303556

Ingles, David

2004-05-01

357

The Coplanar Electron Tube.  

National Technical Information Service (NTIS)

Coplanar electron tubes consisting of emitting, controlling and collecting electrodes on a single heated plane have been proposed as a method of achieving high temperature and high radiation resistant devices. In order to design these devices, the scaling...

M. H. Zinn

1976-01-01

358

TeacherTube  

NSDL National Science Digital Library

TeacherTube is a professionally vetted site that allows educators to share informative videos with others around the world. The essential interface resembles that of YouTube, and visitors can search for videos by keyword, or they can also look for audio-only resources or helpful documents. Visitors can find a wide variety here including a teacher rapping about perimeters, discussion of the Lenape tribe, and a talk with Benjamin Franklin. This particular resource is compatible with all operating systems.

359

Matching Background Color  

NSDL National Science Digital Library

This chapter introduces an especially important subject in the concealment of animals--countershading. One observes many animals with colors that match the general color of their usual backgrounds. Many leaf-eating insects appear green, for example, making them relatively inconspicuous against their normal background of leaves. The manner of coloration that will provide such a color match is not as obvious as one might imagine. It depends significantly on the nature of the lighting. The inquiry-based activities included in this section effectively illustrate this concept.

Ipsen, David; Gillfillan, Gretchen L.; Judy Diamond (Revised New Edition); Judy Scotchmoor (Revised New Edition); Stebbins, Robert

2008-04-01

360

Fallopian tube catheterization.  

PubMed

The delicate fallopian tube is the anatomic pathway to human reproduction. Simple, inexpensive tools and techniques allow radiologists to access this structure for promoting, and preventing pregnancy. Results from centers worldwide have shown that catheter recanalization is possible in ~90% of women with proximal tubal occlusion using basic angiographic techniques familiar to all interventional radiologists. The American Society for Reproductive Medicine has recommended that patients in whom the hysterosalpingogram (HSG) demonstrates proximal tubal occlusion undergo fallopian tube catheterization with selective salpingography prior to more invasive and more costly infertility treatments. The pregnancy rate following fallopian tube recanalization is as high as 60% when the unblocked tubes are found to be normal and there is no history of tubal disease. In a population where the cause of infertility is less well-defined, tubal catheterization may not only help women conceive, but may also help to better define the underlying tubal abnormality. In the prevention of unwanted pregnancy, numerous materials and devices have been tested for blocking fallopian tubes. The ESSURE coil (Conceptus, Inc., Mountain View, CA) was FDA approved in 2002 for tubal sterilization by hysteroscopic placement. In some locales, radiologists are being asked to assist with this procedure or to place the coils fluoroscopically through fallopian tube catheterization. PMID:21326584

Thurmond, Amy Suzanne

2008-12-01

361

Clearing obstructed feeding tubes.  

PubMed

This is a report of an in vitro study evaluating the ability of six solutions to dissolve clotted enteral feeding, which can cause feeding tube occlusion. The following clotted enteral feeding products were tested: Ensure Plus, Ensure Plus with added protein (Promod 20 g/liter), Osmolite, Enrich, and Pulmocare. Clot dissolution was then tested by adding Adolf's Meat Tenderizer, Viokase, Sprite, Pepsi, Coke, or Mountain Dew. Distilled water served as control. Dissolution score for each mixture was assessed blindly. Best dissolution was observed with Viokase in pH 7.9 solution (p less than 0.01). Similar results were obtained when feeding tube patency was restored in eight in vitro occluded feeding tubes (Dobbhoff, French size 8) by using first Pepsi (two/eight successful) and then Viokase in pH 7.9 (six/six successful). We also report our experience in the first 10 patients with occluded feeding tubes using this Viokase solution injected through a Drum catheter into the feeding tube. In seven patients, this method proved to be successful, and the reasons for failure in three patients include a knotted tube, impacted tablet powder, and a formula clot fo 24 hr duration and 45 cm in length. PMID:2494372

Marcuard, S P; Stegall, K L; Trogdon, S

362

Artificial-neural-network-based failure detection and isolation  

NASA Astrophysics Data System (ADS)

This paper presents the design of a systematic failure detection and isolation system that uses the concept of failure sensitive variables (FSV) and artificial neural networks (ANN). The proposed approach was applied to tube leak detection in a utility boiler system. Results of the experimental testing are presented in the paper.

Sadok, M.; Gharsalli, I.; Alouani, Ali T.

1998-03-01

363

Dynamic tube/support interaction in heat exchanger tubes  

SciTech Connect

The supports for heat exchanger tubes are usually plates with drilled holes; other types of supports also have been used. To facilitate manufacture and to allow for thermal expansion of the tubes, small clearances are used between tubes and tube supports. The dynamics of tube/support interaction in heat exchangers is fairly complicated. Understanding tube dynamics and its effects is important for heat exchangers. This paper summarizes the current state of the art on this subject and to identify future research needs. Specifically, the following topics are discussed: dynamics of loosely supported tubes, tube/support gap dynamics, tube response in flow, tube damage and wear, design considerations, and future research needs. 55 refs., 1 fig.

Chen, S.S.

1991-01-01

364

China: Background Notes Series.  

ERIC Educational Resources Information Center

Concise background information on the People's Republic of China is provided. The publication begins with a profile of the country, outlining the people, geography, economy, and membership in international organizations. The bulk of the document then discusses in more detail China's people, geography, history, government, education, economy, and…

Reams, Joanne Reppert

365

Foregrounding the Background.  

ERIC Educational Resources Information Center

Argues that when introductory activities to the classics begin with background information, it can upstage or confine the life of the story, and shows little faith in the students as readers or in the literature itself. Suggests sometimes letting the literature begin, and then helping students make sense of it. Discusses examples from "To Kill a…

Robbins, Bruce

1998-01-01

366

Building Background Knowledge  

ERIC Educational Resources Information Center

|Too often, students enter our classrooms with insufficient knowledge of physical science. As a result, they have a difficult time understanding content in texts, lectures, and laboratory activities. This lack of background knowledge can have an impact on their ability to ask questions and wonder--both key components of inquiry. In this article,…

Fisher, Douglas; Ross, Donna; Grant, Maria

2010-01-01

367

Taiwan: Background Notes Series.  

ERIC Educational Resources Information Center

|Concise background information on Taiwan is provided. The publication begins with a profile of Taiwan, discussing the people, geography, political establishment, and economy. A map of the country is provided. The bulk of the publication then provides more detailed information on Taiwan's people, geography, history, administration, political…

Reams, Joanne Reppert

368

Background Level Care  

Microsoft Academic Search

The framework enabled by the International Caries Detection and Assessment System to allow appropriate, patient-centred caries management includes a frequently encountered scenario in which a comprehensive assessment of the teeth and the patient reveals no lesions in need of active preventive or operative care. The issue addressed here is: what background care is appropriate for patients attending a dental practice

N. B. Pitts

2009-01-01

369

Cosmic background radiation  

Microsoft Academic Search

We summarise the current status of cosmic microwave background spectrum and\\u000aanisotropy measurements, and their theoretical interpretation. This is the\\u000aupdate of the mini-review for the 1997 web-version of the Review of Particle\\u000aProperties.

George Smoot; Douglas Scott

2000-01-01

370

Diffuse UV Background  

NASA Astrophysics Data System (ADS)

We propose a LEGACY project, with the aim of characterizing the diffuse ultraviolet background radiation. In order to achieve maximum impact, we propose to observe exclusively targets for which we already have in hand Voyager diffuse - background spectra (shortward of Lyman alpha). Our Voyager spectroscopy will allow powerful insight into the interpretation and meaning of the deep GALEX images longward of Lyman alpha that we propose (here) to obtain. There is good evidence that a substantial portion of the diffuse UV background at moderate and high Galactic latitudes is exotic in its origin - that is, that the radiation is not simply diffuse galactic light plus the integrated light of distant galaxies. We propose to find clues to the nature and physical origin of the diffuse ultraviolet background radiation in as comprehensive a manner as can be accomplished using GALEX. But in the course of carrying out the proposed work, we will also be creating a permanent GALEX archive of well-chosen deep images that are supported by spectroscopy - images valuable for a wide range of purposes beyond those that we propose. To speed this broader use, we waive all data rights.

Henry, Richard

371

PRESSURE TUBE-CALANDRIA TUBE THERMAL CONTACT CONDUCTANCE  

Microsoft Academic Search

CANDU reactors are of the heavy water moderated, pressure tube type. The core consists of several hundred horizontal fuel channels surrounded by a heavy water moderator. Fuel channels consist of a Zircaloy-2.5%Nb pressure tube enclosed within a Zircaloy-2 calandria tube. There is an annulus gas gap between the pressure tube and the calandria tube. Under extreme accident conditions such as

Adam Cziraky

2009-01-01

372

Neural tube defects in New South Wales, Australia  

PubMed Central

Cases of spina bifida cystica, encephalocele, and anencephaly occurring over a 9-year period, 1965 to 1973, in New South Wales, Australia, were identified. A low frequency of 1·1 for spina bifida and encephalocele (SB) and 0·9 for anencephaly (A) was found. Secular trends parallel to those observed in the northern hemisphere were noted. Detailed analysis of 1575 cases showed an excess of births in spring, corresponding with conception in the summer months, after correction for shorter gestation in anencephalus, which varies from the peak of spring conceptions observed in British studies. An excess of female cases for each abnormality and a social class effect with a deficit of cases in classes I and II and an excess in classes IV and V and ex-nuptial births were apparent. The first birth rank for younger mothers did not show a significantly increased risk; however, the effect of high birth rank and older maternal age was more significant. Migration studies showed that in migrating from areas of high incidence these parents maintain a higher risk than the Australian population. The highest risk group was that in which both parents were born in the UK, and the next highest that in which an English-born mother was married to an Australian father. Mothers from Malta, and either or both parents from Lebanon, Egypt, and Austria were also at high risk. Part-aboriginal children had a higher risk rate for ASB than white Australian children. The proportion of older sibs affected was 4·12% of sibs of both sexes of an index case of spina bifida, and 3·19% of an index case of anencephaly. The abnormalities alternate or recur in families. An increased perinatal mortality rate in sibs was shown. Twin studies showed a higher concordance rate for monochorionic pairs. A sequential interaction in an excess of opposite sex sib before an index case was apparent. The results of this study support a multifactorial aetiology for ASB resulting from genetic environmental interaction. New South Wales is the eastern coastal state of Australia, with an area of 309 433 square miles and a population of 4 640 800 at the 1971 Census. The continent is geographically isolated with a large migrant population, seasonal reversal, and a hot climate.

Field, Barbara

1978-01-01

373

Ethical Problems of Screening for Neural Tube Defects.  

ERIC Educational Resources Information Center

|Among the ethical problems in screening for severe spina bifida in a fetus are deciding who should be screened; whether the procedure, which has medical risks, is justified; and how to deal with the only known solution--abortion. Journal availability: see EC 114 865. (PHR)|

Habgood, J. S.

1978-01-01

374

Parental Recreational Drug Use and Risk for Neural Tube Defects  

Microsoft Academic Search

0.43-0.95) or preconceptional use of alcohol as <1 drink\\/day (OR = 0.80, 95% Cl 0.62-1.0) or ^1 dnnk\\/day (OR = 0.69, 95% Cl 0.42-1.2) or of cigarettes as <1 pack\\/day (OR = 0.90, 95% Cl 0.65-1.2) or &1 pack\\/day (OR = 0.59, 95% Cl 0.36-0.96) did not increase the risk for delivering NTD-affected offspring. Risks were not substantially altered after

Gary M. Shaw; Ellen M. Velie; Kimberly B. Morland

375

Ethical Problems of Screening for Neural Tube Defects.  

ERIC Educational Resources Information Center

Among the ethical problems in screening for severe spina bifida in a fetus are deciding who should be screened; whether the procedure, which has medical risks, is justified; and how to deal with the only known solution--abortion. Journal availability: see EC 114 865. (PHR)

Habgood, J. S.

1978-01-01

376

PE on YouTube--Investigating Participation in Physical Education Practice  

ERIC Educational Resources Information Center

|Background: In this article, students' diverse ways of participating in physical education (PE) practice shown in clips on YouTube were investigated. YouTube is the largest user-generated video-sharing website on the Internet, where different video content is presented. The clips on YouTube, as used in this paper, can be seen as a user-generated…

Quennerstedt, Mikael

2013-01-01

377

PE on YouTube--Investigating Participation in Physical Education Practice  

ERIC Educational Resources Information Center

Background: In this article, students' diverse ways of participating in physical education (PE) practice shown in clips on YouTube were investigated. YouTube is the largest user-generated video-sharing website on the Internet, where different video content is presented. The clips on YouTube, as used in this paper, can be seen as a user-generated…

Quennerstedt, Mikael

2013-01-01

378

Callose plug deposition patterns vary in pollen tubes of Arabidopsis thaliana ecotypes and in tomato species  

Technology Transfer Automated Retrieval System (TEKTRAN)

Background The pollen grain contains the male gametophyte that extends a pollen tube that grows through female tissues in order to deliver sperm to the embryo sac for double fertilization. Growing pollen tubes form periodic callose plugs that are thought to block off the older parts of the tube and ...

379

Wavelets and Neural Networks.  

National Technical Information Service (NTIS)

During our previous work, we had established a very dose connection between polynomial approximation and approximation by neural networks. In fact, we had developed a unified theory of the approximation properties of neural networks, radial basis function...

H. N. Mhaskar

1999-01-01

380

27 CFR 40.352 - Cigarette tubes.  

Code of Federal Regulations, 2013 CFR

...AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes § 40.352 Cigarette tubes. Cigarette tubes are taxed...thereof, of the length of each as one cigarette tube. * Tax rate for less than 50 tubes is the...

2013-04-01

381

Neural Crest Cell Plasticity  

Microsoft Academic Search

Patterning and morphogenesis of neural crest-derived tissues within a developing vertebrate embryo rely on a complex balance\\u000a between signals acquired by neural crest cells in the neuroepithelium during their formation and signals from the tissues\\u000a that the neural crest cells contact during their migration. Axial identity of hindbrain neural crest is controlled by a combinatorial\\u000a pattern of Hox gene expression.

Lisa L. Sandell; Paul Trainor

382

Neural Stem Cells  

Microsoft Academic Search

This article is concerned with the idea that neural precursor cells in vertebrates can self-renew and give rise to all cell types within the nervous system. Supportive evidence for this notion of neural stem cells comes from clonal analyses undertaken both in vivo and in vitro. Neural stem cells also give rise to other cells in the body, including skin

Mark Murphy; Kate Reid; Renée Dutton; Gordon Brooker; Perry F Bartlett

1997-01-01

383

The H1 neural network trigger project  

NASA Astrophysics Data System (ADS)

We present a short overview of neuromorphic hardware and some of the physics projects making use of such devices. As a concrete example we describe an innovative project within the H1-Experiment at the electron-proton collider HERA, instrumenting hardwired neural networks as pattern recognition machines to discriminate between wanted physics and uninteresting background at the trigger level. The decision time of the system is less than 20 microseconds, typical for a modern second level trigger. The neural trigger has been successfully running for the past four years and has turned out new physics results from H1 unobtainable so far with other triggering schemes. We describe the concepts and the technical realization of the neural network trigger system, present the most important physics results, and motivate an upgrade of the system for the future high luminosity running at HERA. The upgrade concentrates on ``intelligent preprocessing'' of the neural inputs which help to strongly improve the networks' discrimination power. .

Kiesling, C.; Denby, B.; Fent, J.; Fröchtenicht, W.; Garda, P.; Granado, B.; Grindhammer, G.; Haberer, W.; Janauschek, L.; Kobler, T.; Koblitz, B.; Nellen, G.; Prevotet, J.-C.; Schmidt, S.; Tzamariudaki, E.; Udluft, S.

2001-08-01

384

Mapping of neural crest pathways in Xenopus laevis using inter- and intra-specific cell markers.  

PubMed

This study examines the pathways of migration followed by neural crest cells in Xenopus embryos using two recently described cell marking techniques. The first is an interspecific chimera created by grafting Xenopus borealis cells into Xenopus laevis hosts. The cells of these closely related species can be distinguished by their nuclear dimorphism. The second type of marker is created by microinjection of lysinated dextrans into fertilized eggs which can then be used for intraspecific grafting. These recently developed fluorescent dyes are fixable and identifiable in both living and fixed embryos. After grafting labeled donor neural tubes into unlabeled host embryos, the distribution of neural crest cells at various stages after grafting was used to define the pathways of neural crest migration. To control for possible grafting artifacts, fluorescent lysinated dextran was injected into a single blastomere which gives rise to a large number of neural crest cells, thereby labeling the neural crest without grafting. By all three techniques, Xenopus neural crest cells were observed along two predominant pathways in the trunk. The majority of neural crest cells were observed along a "ventral" route, between the neural tube and somite, the notochord and somite, and along the dorsal mesentery. A second group of neural crest cells was observed "dorsally" where they populated the dorsal fin. A third minor "lateral" pathway was observed primarily in borealis/laevis chimerae and in blastomere-injected embryos; some neural crest cells were observed underneath the ectoderm lateral to the neural tube. Along the rostrocaudal axis, neural crest cells were not continuously distributed but were primarily located across from the caudal two-thirds of the somite. Fewer than 3% of the neural crest cells were observed across from the rostral third of each somite. When grafted to ventral locations, neural crest cells were not able to migrate dorsally but migrated laterally along the dorsal mesentery. Labeled neural crest cells gave rise to cells of the spinal, sympathetic, and enteric ganglia as well as to adrenal chromaffin cells, Schwann cells, pigment cells, mesenchymal cells of the dorsal fin, and some cells in the integuments and in the region of the pronephros. These results show that the neural crest migratory pathways in Xenopus differ from those in the avian embryo. In avians NC cells migrate as a closely associated sheet of cells while in Xenopus they migrate as individual cells. Both species exhibit a metamerism in the neural crest cell distribution pattern along the rostrocaudal axis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2452101

Krotoski, D M; Fraser, S E; Bronner-Fraser, M

1988-05-01

385

PRODUCTION OF URANIUM TUBING  

DOEpatents

The manufacture of thin-walled uranium tubing by the hot-piercing techique is described. Uranium billets are preheated to a temperature above 780 d C. The heated billet is fed to a station where it is engaged on its external surface by three convex-surfaced rotating rollers which are set at an angle to the axis of the billet to produce a surface friction force in one direction to force the billet over a piercing mandrel. While being formed around the mandrel and before losing the desired shape, the tube thus formed is cooled by a water spray.

Creutz, E.C.

1958-04-15

386

Does Feeding Tube Insertion and its Timing Improve Survival?  

PubMed Central

Background/Objectives The objective of this study was to examine survival with and without a percutaneous endoscopic gastrostomy (PEG) feeding tube using rigorous methods to account for selection bias. A second objective was to examine whether the timing of feeding tube insertion affected survival. Design Prospective cohort study Setting All U.S. Nursing Homes Participants 36,492 nursing home residents with advanced cognitive impairment from dementia and new problems eating studied between 1999–2007. Measurements Survival following the development of the need for eating assistance and feeding tube insertion. Results Of the 36,492 nursing home (NH) residents (88.4% white, mean age 84.9, 87.4% with one feeding tube risk factor), 1,957 (5.4%) had a feeding tube inserted within 1 year of developing eating problems. After multivariate analysis correcting for selection bias with propensity score weights, no difference was found in the survival of the 2 groups (AHR 1.03, 95% CI 0.94–1.13). Among residents who were tube-fed, the timing of PEG tube insertion relative to the onset of eating problems was not associated with improved survival post feeding tube insertion (AHR 1.01, 95% CI 0.86–1.20) comparing those persons with a PEG inserted within a month of developing an eating problem compared to later (4 months) insertion. Conclusion This national study confirms that neither insertion of PEG feeding tubes nor the timing of the insertion improve survival.

Teno, Joan M.; Gozalo, Pedro L.; Mitchell, Susan L.; Kuo, Sylvia; Rhodes, Ramona L.; Bynum, Julie P.W.; Mor, Vincent

2012-01-01

387

Mechanistic insights from a quantitative analysis of pollen tube guidance  

PubMed Central

Background Plant biologists have long speculated about the mechanisms that guide pollen tubes to ovules. Although there is now evidence that ovules emit a diffusible attractant, little is known about how this attractant mediates interactions between the pollen tube and the ovules. Results We employ a semi-in vitro assay, in which ovules dissected from Arabidopsis thaliana are arranged around a cut style on artificial medium, to elucidate how ovules release the attractant and how pollen tubes respond to it. Analysis of microscopy images of the semi-in vitro system shows that pollen tubes are more attracted to ovules that are incubated on the medium for longer times before pollen tubes emerge from the cut style. The responses of tubes are consistent with their sensing a gradient of an attractant at 100-150 ?m, farther than previously reported. Our microscopy images also show that pollen tubes slow their growth near the micropyles of functional ovules with a spatial range that depends on ovule incubation time. Conclusions We propose a stochastic model that captures these dynamics. In the model, a pollen tube senses a difference in the fraction of receptors bound to an attractant and changes its direction of growth in response; the attractant is continuously released from ovules and spreads isotropically on the medium. The model suggests that the observed slowing greatly enhances the ability of pollen tubes to successfully target ovules. The relation of the results to guidance in vivo is discussed.

2010-01-01

388

Cosmic microwave background polarization  

NASA Astrophysics Data System (ADS)

Cosmic microwave background (CMB) anisotropy is our richest source of cosmological information; the standard cosmological model was largely established thanks to study of the temperature anisotropies. By the end of the decade, the Planck satellite will close this important chapter and move us deeper into the new frontier of polarization measurements. Numerous ground-based and balloon-borne experiments are already forging into this new territory. Besides providing new and independent information on the primordial density perturbations and cosmological parameters, polarization measurements offer the potential to detect primordial gravity waves, constrain dark energy and measure the neutrino mass scale. A vigorous experimental program is underway worldwide and heading towards a new satellite mission dedicated to CMB polarization.

Bartlett, James G.

2006-05-01

389

Earth's Background Free Oscillations  

NASA Astrophysics Data System (ADS)

Earth's background free oscillations, known as Earth's hum, were discovered in 1998. Excited modes of the oscillations are almost exclusively fundamental spheroidal and toroidal modes from 2 to 20 mHz. Seasonal variations in the source distribution suggest that the dominant sources are ocean infragravity waves in the shallow and deep oceans. A probable excitation mechanism is random shear traction acting on the sea bottom owing to linear topographic coupling of the infragravity waves. Excitation by pressure sources on Earth's surface is also significant for a frequency below 5 mHz. A possible pressure source is atmospheric turbulence, which can cause observed resonant oscillations between the solid modes and atmospheric acoustic modes.

Nishida, Kiwamu

2013-05-01

390

Cosmic microwave background theory.  

PubMed

A long-standing goal of theorists has been to constrain cosmological parameters that define the structure formation theory from cosmic microwave background (CMB) anisotropy experiments and large-scale structure (LSS) observations. The status and future promise of this enterprise is described. Current band-powers in -space are consistent with a DeltaT flat in frequency and broadly follow inflation-based expectations. That the levels are approximately (10(-5))2 provides strong support for the gravitational instability theory, while the Far Infrared Absolute Spectrophotometer (FIRAS) constraints on energy injection rule out cosmic explosions as a dominant source of LSS. Band-powers at 100 suggest that the universe could not have re-ionized too early. To get the LSS of Cosmic Background Explorer (COBE)-normalized fluctuations right provides encouraging support that the initial fluctuation spectrum was not far off the scale invariant form that inflation models prefer: e.g., for tilted Lambda cold dark matter sequences of fixed 13-Gyr age (with the Hubble constant H0 marginalized), ns = 1.17 +/- 0.3 for Differential Microwave Radiometer (DMR) only; 1.15 +/- 0.08 for DMR plus the SK95 experiment; 1.00 +/- 0.04 for DMR plus all smaller angle experiments; 1.00 +/- 0.05 when LSS constraints are included as well. The CMB alone currently gives weak constraints on Lambda and moderate constraints on Omegatot, but theoretical forecasts of future long duration balloon and satellite experiments are shown which predict percent-level accuracy among a large fraction of the 10+ parameters characterizing the cosmic structure formation theory, at least if it is an inflation variant. PMID:9419321

Bond, J R

1998-01-01

391

Genes, lineages and the neural crest: a speculative review.  

PubMed Central

Sensory and sympathetic neurons are generated from the trunk neural crest. The prevailing view has been that these two classes of neurons are derived from a common neural crest-derived progenitor that chooses between neuronal fates only after migrating to sites of peripheral ganglion formation. Here I reconsider this view in the light of new molecular and genetic data on the differentiation of sensory and autonomic neurons. These data raise several paradoxes when taken in the context of classical studies of the timing and spatial patterning of sensory and autonomic ganglion formation. These paradoxes can be most easily resolved by assuming that the restriction of neural crest cells to either sensory or autonomic lineages occurs at a very early stage, either before and/or shortly after they exit the neural tube.

Anderson, D J

2000-01-01

392

Flux Tube Model  

NASA Astrophysics Data System (ADS)

This Fortran code computes magnetohydrostatic flux tubes and sheets according to the method of Steiner, Pneuman, & Stenflo (1986) A&A 170, 126-137. The code has many parameters contained in one input file that are easily modified. Extensive documentation is provided in README files.

Steiner, O.

2011-05-01

393

Lighted Guidance Tube Evaluation  

National Technical Information Service (NTIS)

This report summarized the use of 3M-TM Lighted Guidance Tube (LGT) at the Pali Highway hairpin curve site and at the westbound H-1 Freeway off ramp to the Honolulu International Airport site to delineate the change in alignment of the road for the motori...

D. Sakai G. Masatsugu

2003-01-01

394

Rebuilding cathode ray tubes  

Microsoft Academic Search

Results from the evaluation of rebuilt tubes as supplied by several CRT rebuilders are summarized. The sample size was not sufficient to conclude that CRT vendors could be qualified to rebuild special CRT's. Perhaps the most useful result of the investigation and testing was the information obtained relative to commercial television CRT improvements to the FAA CRT rebuilding experiments.

J. W. Aschenbach

1977-01-01

395

Extrusion of a tube  

NSDL National Science Digital Library

For flow through a seamless tube extruder, use simplifying assumptions to reduce the appropriate form of the Navier-Stokes equations as much as possible, sketch the expected flow profile for three rheology types, and discuss microstructure changes during the extrusion process.

Powell, Adam C., IV

2005-05-02

396

Neutron generator tube  

Microsoft Academic Search

This patent describes a neutron generator tube. It comprises: a hermetically sealed housing containing an ionizable gas; an axial recess in one end of the housing adapted to receive a magnet; a ring anode axially oriented within the housing adjacent to the recessed end for accepting the magnet; an axially oriented thermal conductor cathode penetrating through the other end of

Ethridge

1991-01-01

397

Subsea tubing hanger  

SciTech Connect

A packoff assembly for sealing the walls of an annulus between the outside surface of a tubing hanger and the internal bore of a subsea wellhead is described comprising: a packoff sleeve insertable in the annulus and having a seal assembly disposed around its lower periphery; means for actuating the seal assembly into sealing engagement with the walls of the annulus; releasable locking means disposed on the packoff sleeve and engageable with the tubing hanger for releasably locking the packoff assembly to the tubing hanger; axially movable release sleeve means mounted on the packoff sleeve and engagable with the relesable locking means for actuating the releasable locking means into released position and freeing the packoff assembly from the tubing hanger upon the axial movement of the release sleeve means with respect to the packoff sleeve. The releasable locking means includes a circumferential shoulder around the internal bore of the packoff sleeve onto which the expansion ring expands upon sufficient downward axial movement of the packoff sleeve into the annulus, and dogs disposed in circumferentially spaced apart, radially extending openings in the packoff sleeve and radially slidable on the shoulder. The radially inner surface of the dogs being engageable with the expansion ring when the ring expands onto the shoulder; and the release sleeve means including a ramp surface engageable with the radially outer surface of the dogs for camming the dogs radially inwardly upon upward movement of the release sleeve means with respect to the dogs.

Ahistone, A.G.

1988-04-12

398

Downhole pulse tube refrigerators  

SciTech Connect

This report summarizes a preliminary design study to explore the plausibility of using pulse tube refrigeration to cool instruments in a hot down-hole environment. The original motivation was to maintain Dave Reagor`s high-temperature superconducting electronics at 75 K, but the study has evolved to include three target design criteria: cooling at 30 C in a 300 C environment, cooling at 75 K in a 50 C environment, cooling at both 75 K and 30 C in a 250 C environment. These specific temperatures were chosen arbitrarily, as representative of what is possible. The primary goals are low cost, reliability, and small package diameter. Pulse-tube refrigeration is a rapidly growing sub-field of cryogenic refrigeration. The pulse tube refrigerator has recently become the simplest, cheapest, most rugged and reliable low-power cryocooler. The authors expect this technology will be applicable downhole because of the ratio of hot to cold temperatures (in absolute units, such as Kelvin) of interest in deep drilling is comparable to the ratios routinely achieved with cryogenic pulse-tube refrigerators.

Swift, G.; Gardner, D. [Los Alamos National Lab., NM (United States). Condensed Matter and Thermal Physics Group

1997-12-01

399

Biological aerosol background characterization  

NASA Astrophysics Data System (ADS)

To provide useful information during military operations, or as part of other security situations, a biological aerosol detector has to respond within seconds or minutes to an attack by virulent biological agents, and with low false alarms. Within this time frame, measuring virulence of a known microorganism is extremely difficult, especially if the microorganism is of unknown antigenic or nucleic acid properties. Measuring "live" characteristics of an organism directly is not generally an option, yet only viable organisms are potentially infectious. Fluorescence based instruments have been designed to optically determine if aerosol particles have viability characteristics. Still, such commercially available biological aerosol detection equipment needs to be improved for their use in military and civil applications. Air has an endogenous population of microorganisms that may interfere with alarm software technologies. To design robust algorithms, a comprehensive knowledge of the airborne biological background content is essential. For this reason, there is a need to study ambient live bacterial populations in as many locations as possible. Doing so will permit collection of data to define diverse biological characteristics that in turn can be used to fine tune alarm algorithms. To avoid false alarms, improving software technologies for biological detectors is a crucial feature requiring considerations of various parameters that can be applied to suppress alarm triggers. This NATO Task Group will aim for developing reference methods for monitoring biological aerosol characteristics to improve alarm algorithms for biological detection. Additionally, they will focus on developing reference standard methodology for monitoring biological aerosol characteristics to reduce false alarm rates.

Blatny, Janet; Fountain, Augustus W., III

2011-05-01

400

Cosmic Microwave Background  

NASA Astrophysics Data System (ADS)

Large plasma redshifts of photons in hot, sparse plasma are given by ln ( 1+z )=3.326ot 10-25ot int_0^R N_eot dx., provided the wavelength ? ? ?_0.5 =3.185ot 10-6ot ( 1+1.296ot 10^5ot B^2/Ne )ot ? N_e/T cm, where Ne is the electron density in cm-3, T the temperature in K, R the distance in cm to the emitter, and B the magnetic field in Gauss. The cut-off at ? _0.5 means that the redshift is 50% of its full value. The theory is based on an overlooked interaction of photons with hot sparse electron plasma. It has been overlooked, because the necessary conditions (high temperature and low densities over extended dimensions) cannot be created in the laboratory. The plasma redshifts help explain: the heating of the transition to the corona, the coronal heating, solar redshifts (which invalidate the equivalence principle), galactic redshifts, the heating of galactic corona, the redshifts of white dwarfs and quasars, the cosmological redshifts, and the recently discovered dimming of distant super nova. This presentation will show how plasma redshift also helps explain the cosmic microwave background.

Brynjolfsson, Ari

2003-04-01

401

Vanadium tube processing and analysis  

SciTech Connect

Vanadium tubing obtained from Century Tubes, a custom tubing manufacturer, was studied to determine as-received quality and fabricability. Applications for this tubing involve crimping and sealing operations at Pantex Plant requiring very high levels of leak-tightness (leak rates less than 10{sup {minus}8} atm-cc He/sec). The as-received material had poor OD and ID surface finish and cleanliness that needed to be improved before use in component fabrication. Savannah River Technical Center (SRTC) personnel developed a cleaning procedure to make this tubing acceptable for crimping and sealing operations. After suitably cleaning the tubing, we tested several tube sealing techniques and all showed some degree of success. Pantex Plant personnel are now implementing a tube sealing process very similar to one of the techniques studied, a mechanical crimp followed by seal welding.

Kautz, D.D.; Tanaka, G.J.

1993-08-11

402

From Test Tube To Patient  

Center for Drug Evaluation (CDER)

Text VersionPage 1. FDA Home Page | Search FDA Site | FDA AZ Index | Contact FDA From Test Tube To Patient From Test Tube To ... More results from www.fda.gov/downloads/drugs/developmentapprovalprocess

403

Ear tube insertion - series (image)  

MedlinePLUS

Ear tube insertion is recommended for: fluid in the middle ear (present for more than 12 weeks) recurrent ear ... the accumulated fluid is suctioned out. A small tube is inserted through the incised eardrum in order ...

404

Neural decoding based on probabilistic neural network.  

PubMed

Brain-machine interface (BMI) has been developed due to its possibility to cure severe body paralysis. This technology has been used to realize the direct control of prosthetic devices, such as robot arms, computer cursors, and paralyzed muscles. A variety of neural decoding algorithms have been designed to explore relationships between neural activities and movements of the limbs. In this paper, two novel neural decoding methods based on probabilistic neural network (PNN) in rats were introduced, the PNN decoder and the modified PNN (MPNN) decoder. In the experiment, rats were trained to obtain water by pressing a lever over a pressure threshold. Microelectrode array was implanted in the motor cortex to record neural activity, and pressure was recorded by a pressure sensor synchronously. After training, the pressure values were estimated from the neural signals by PNN and MPNN decoders. Their performances were evaluated by a correlation coefficient (CC) and a mean square error (MSE). The results show that the MPNN decoder, with a CC of 0.8657 and an MSE of 0.2563, outperformed the traditionally-used Wiener filter (WF) and Kalman filter (KF) decoders. It was also observed that the discretization level did not affect the MPNN performance, indicating that the MPNN decoder can handle different tasks in BMI system, including the detection of movement states and estimation of continuous kinematic parameters. PMID:20349527

Yu, Yi; Zhang, Shao-min; Zhang, Huai-jian; Liu, Xiao-chun; Zhang, Qiao-sheng; Zheng, Xiao-xiang; Dai, Jian-hua

2010-04-01

405

Neural decoding based on probabilistic neural network*  

PubMed Central

Brain-machine interface (BMI) has been developed due to its possibility to cure severe body paralysis. This technology has been used to realize the direct control of prosthetic devices, such as robot arms, computer cursors, and paralyzed muscles. A variety of neural decoding algorithms have been designed to explore relationships between neural activities and movements of the limbs. In this paper, two novel neural decoding methods based on probabilistic neural network (PNN) in rats were introduced, the PNN decoder and the modified PNN (MPNN) decoder. In the experiment, rats were trained to obtain water by pressing a lever over a pressure threshold. Microelectrode array was implanted in the motor cortex to record neural activity, and pressure was recorded by a pressure sensor synchronously. After training, the pressure values were estimated from the neural signals by PNN and MPNN decoders. Their performances were evaluated by a correlation coefficient (CC) and a mean square error (MSE). The results show that the MPNN decoder, with a CC of 0.8657 and an MSE of 0.2563, outperformed the traditionally-used Wiener filter (WF) and Kalman filter (KF) decoders. It was also observed that the discretization level did not affect the MPNN performance, indicating that the MPNN decoder can handle different tasks in BMI system, including the detection of movement states and estimation of continuous kinematic parameters.

Yu, Yi; Zhang, Shao-min; Zhang, Huai-jian; Liu, Xiao-chun; Zhang, Qiao-sheng; Zheng, Xiao-xiang; Dai, Jian-hua

2010-01-01

406

Does the Cranial Mesenchyme Contribute to Neural Fold Elevation During Neurulation?  

PubMed Central

The central nervous system is derived from the neural plate that undergoes a series of complex morphogenetic events resulting in formation of the neural tube in a process known as neurulation. The cellular behaviors driving neurulation in the cranial region involve forces generated by the neural tissue itself as well as the surrounding epithelium and mesenchyme. Of interest, the cranial mesenchyme underlying the neural plate undergoes stereotypical rearrangements hypothesized to drive elevation of the neural folds. As the neural folds rise, the hyaluronate-rich extracellular matrix greatly expands resulting in increased space between individual cranial mesenchyme cells. Based on inhibitor studies, expansion of the extracellular matrix has been implicated in driving neural fold elevation; however, since the surrounding neural and epidermal ectoderm were also affected by inhibitor exposure, these studies are inconclusive. Similarly, treatment of neurulating embryos with teratogenic doses of retinoic acid results in altered organization of the cranial mesenchyme but alterations in surrounding tissues are also observed. The strongest evidence for a critical role for the cranial mesenchyme in neural fold elevation comes from studies of genes expressed exclusively in the cranial mesenchyme that when mutated result in exencephaly associated with abnormal organization of the cranial mesenchyme. Twist is the best studied of these and is expressed in both the paraxial mesoderm and neural crest derived cranial mesenchyme. Here we review the evidence implicating the cranial mesenchyme in providing a driving force for neural fold elevation to evaluate whether there is sufficient data to support this hypothesis.

Zohn, Irene E.; Sarkar, Anjali A.

2012-01-01

407

Aluminum foil lined composite tubing  

Microsoft Academic Search

This paper describes the development of lightweight aluminum foil lined polymer matrix composite tubing for applications ranging from heat pipe construction to fluid transport tubing and tankage structure for future spacecraft. The metal lining is completely hermetic and endows the tubing with metal like characteristics without compromising its lightweight or strength advantages. It consists of one wrap of 0.076 mm

Nelson J. Gernert; David B. Sarraf; Douglas L. Armstrong; Scott A. Blood

1996-01-01

408

Single Loose Tube Cable Designs.  

National Technical Information Service (NTIS)

Single loose buffer tube cable designs consist of a single tube placed in the center and parallel to tension elements and external sheathing. By comparison, traditional low fiber count loose buffer tube cable designs generally consist of one fiber per tub...

Y. Simons K. Morita J. De Angeles J. Owen

1986-01-01

409

Enteral Tube Feeding and Pneumonia  

ERIC Educational Resources Information Center

|To determine the effects of enteral tube feeding on the incidence of pneumonia, we performed a retrospective review of all clients at our institution who had gastrostomy or jejunostomy tubes placed over a 10-year period. Ninety-three subjects had a history of pneumonia before feeding tube insertion. Eighty had gastrostomy and 13, jejunostomy…

Gray, David Sheridan; Kimmel, David

2006-01-01

410

Boiler tube failure reduction program  

Microsoft Academic Search

Boiler tube failures are generally recognized as the major cause of forced outages of fossil power generating units for US electric utilities. In almost all cases of serious availability losses, the boiler tube failures are repeat in nature and result in multiple forced outages. Primary factors influencing repeat, rather than random, tube failures are usually found to result from not

G. A. Lamping; O. Jonas; R. J. Niebo

1991-01-01

411

Plug for heat exchanger tubes  

Microsoft Academic Search

A heat exchanger tube plug is described for sealing the ends of heat exchanger tubes, comprising a cylindrical housing member sized for insertion within the end portion of one of the heat exchanger tubes, the housing member having a longitudinal blind bore comprising a smooth portion communicating with a threaded portion. An eccentric locking means is mounted on the housing

Epstein

1987-01-01

412

Adaptive Temporal Encoding Leads to a Background Insensitive Cortical Representation of Speech  

PubMed Central

Speech recognition is remarkably robust to the listening background, even when the energy of background sounds strongly overlaps with that of speech. How the brain transforms the corrupted acoustic signal into a reliable neural representation suitable for speech recognition, however, remains elusive. Here, we hypothesize that this transformation is performed at the level of auditory cortex through adaptive neural encoding, and we test the hypothesis by recording, using magnetoencephalography (MEG), the neural responses of human subjects listening to a narrated story. Spectrally matched stationary noise, which has maximal acoustic overlap with the speech, is mixed in at various intensity levels. Despite the severe acoustic interference caused by this noise, it is here demonstrated that low-frequency auditory cortical activity is reliably synchronized to the slow temporal modulations of speech, even when the noise is twice as strong as the speech. Such a reliable neural representation is maintained by intensity contrast gain control, and by adaptive processing of temporal modulations at different time scales, corresponding to the neural delta and theta bands. Critically, the precision of this neural synchronization predicts how well a listener can recognize speech in noise, indicating that the precision of the auditory cortical representation limits the performance of speech recognition in noise. Taken together, these results suggest that, in a complex listening environment, auditory cortex can selectively encode a speech stream in a background insensitive manner, and this stable neural representation of speech provides a plausible basis for background-invariant recognition of speech.

Ding, Nai; Simon, Jonathan Z.

2013-01-01

413

Estimation of neural energy in microelectrode signals  

NASA Astrophysics Data System (ADS)

We considered the problem of determining the neural contribution to the signal recorded by an intracortical electrode. We developed a linear least-squares approach to determine the energy fraction of a signal attributable to an arbitrary number of autocorrelation-defined signals buried in noise. Application of the method requires estimation of autocorrelation functions Rap(tgr) characterizing the action potential (AP) waveforms and Rn(tgr) characterizing background noise. This method was applied to the analysis of chronically implanted microelectrode signals from motor cortex of rat. We found that neural (AP) energy consisted of a large-signal component which grows linearly with the number of threshold-detected neural events and a small-signal component unrelated to the count of threshold-detected AP signals. The addition of pseudorandom noise to electrode signals demonstrated the algorithm's effectiveness for a wide range of noise-to-signal energy ratios (0.08 to 39). We suggest, therefore, that the method could be of use in providing a measure of neural response in situations where clearly identified spike waveforms cannot be isolated, or in providing an additional 'background' measure of microelectrode neural activity to supplement the traditional AP spike count.

Gaumond, R. P.; Clement, R.; Silva, R.; Sander, D.

2004-09-01

414

Neural-specific Sox2 input and differential Gli-binding affinity provide context and positional information in Shh-directed neural patterning.  

PubMed

In the vertebrate neural tube, regional Sonic hedgehog (Shh) signaling invokes a time- and concentration-dependent induction of six different cell populations mediated through Gli transcriptional regulators. Elsewhere in the embryo, Shh/Gli responses invoke different tissue-appropriate regulatory programs. A genome-scale analysis of DNA binding by Gli1 and Sox2, a pan-neural determinant, identified a set of shared regulatory regions associated with key factors central to cell fate determination and neural tube patterning. Functional analysis in transgenic mice validates core enhancers for each of these factors and demonstrates the dual requirement for Gli1 and Sox2 inputs for neural enhancer activity. Furthermore, through an unbiased determination of Gli-binding site preferences and analysis of binding site variants in the developing mammalian CNS, we demonstrate that differential Gli-binding affinity underlies threshold-level activator responses to Shh input. In summary, our results highlight Sox2 input as a context-specific determinant of the neural-specific Shh response and differential Gli-binding site affinity as an important cis-regulatory property critical for interpreting Shh morphogen action in the mammalian neural tube. PMID:23249739

Peterson, Kevin A; Nishi, Yuichi; Ma, Wenxiu; Vedenko, Anastasia; Shokri, Leila; Zhang, Xiaoxiao; McFarlane, Matthew; Baizabal, José-Manuel; Junker, Jan Philipp; van Oudenaarden, Alexander; Mikkelsen, Tarjei; Bernstein, Bradley E; Bailey, Timothy L; Bulyk, Martha L; Wong, Wing H; McMahon, Andrew P

2012-12-15

415

Neural-specific Sox2 input and differential Gli-binding affinity provide context and positional information in Shh-directed neural patterning  

PubMed Central

In the vertebrate neural tube, regional Sonic hedgehog (Shh) signaling invokes a time- and concentration-dependent induction of six different cell populations mediated through Gli transcriptional regulators. Elsewhere in the embryo, Shh/Gli responses invoke different tissue-appropriate regulatory programs. A genome-scale analysis of DNA binding by Gli1 and Sox2, a pan-neural determinant, identified a set of shared regulatory regions associated with key factors central to cell fate determination and neural tube patterning. Functional analysis in transgenic mice validates core enhancers for each of these factors and demonstrates the dual requirement for Gli1 and Sox2 inputs for neural enhancer activity. Furthermore, through an unbiased determination of Gli-binding site preferences and analysis of binding site variants in the developing mammalian CNS, we demonstrate that differential Gli-binding affinity underlies threshold-level activator responses to Shh input. In summary, our results highlight Sox2 input as a context-specific determinant of the neural-specific Shh response and differential Gli-binding site affinity as an important cis-regulatory property critical for interpreting Shh morphogen action in the mammalian neural tube.

Peterson, Kevin A.; Nishi, Yuichi; Ma, Wenxiu; Vedenko, Anastasia; Shokri, Leila; Zhang, Xiaoxiao; McFarlane, Matthew; Baizabal, Jose-Manuel; Junker, Jan Philipp; van Oudenaarden, Alexander; Mikkelsen, Tarjei; Bernstein, Bradley E.; Bailey, Timothy L.; Bulyk, Martha L.; Wong, Wing H.; McMahon, Andrew P.

2012-01-01

416

Modeling pollen tube growth  

PubMed Central

The frequency and amplitude of oscillatory pollen tube growth can be altered by changing the osmotic value of the surrounding medium. This has motivated the proposition that the periodic change in growth velocity is caused by changes in turgor pressure. Using mathematical modeling we recently demonstrated that the oscillatory pollen tube growth does not require turgor to change but that this behavior can be explained with a mechanism that relies on changes in the mechanical properties of the cell wall which in turn are caused by temporal variations in the secretion of cell wall precursors. The model also explains why turgor and growth rate are correlated for oscillatory growth with long growth cycles while they seem uncorrelated for oscillatory growth with short growth cycles. The predictions made by the model are testifiable by experimental data and therefore represent an important step towards understanding the dynamics of the growth behavior in walled cells.

Kroeger, Jens; Geitmann, Anja

2011-01-01

417

Joined concentric tubes  

SciTech Connect

Tubular objects having two or more concentric layers that have different properties are joined to one another during their manufacture primarily by compressive and friction forces generated by shrinkage during sintering and possibly mechanical interlocking. It is not necessary for the concentric tubes to display adhesive-, chemical- or sinter-bonding to each other in order to achieve a strong bond. This facilitates joining of dissimilar materials, such as ceramics and metals.

DeJonghe, Lutgard; Jacobson, Craig; Tucker, Michael; Visco, Steven

2013-01-01

418

Pulse Tube Cryocoolers  

Microsoft Academic Search

\\u000a This paper presents a review of the pulse tube refrigerator from its inception in the mid-1960s up to the present. Various\\u000a factors are discussed which brought it from a laboratory curiosity to the point where it is now the most efficient of all\\u000a cryocoolers (cryogenic refrigerator) for temperatures between about 60 and 120 K, and it is reliable enough to

Ray Radebaugh

419

The LILARTI neural network system  

SciTech Connect

The material of this Technical Memorandum is intended to provide the reader with conceptual and technical background information on the LILARTI neural network system of detail sufficient to confer an understanding of the LILARTI method as it is presently allied and to facilitate application of the method to problems beyond the scope of this document. Of particular importance in this regard are the descriptive sections and the Appendices which include operating instructions, partial listings of program output and data files, and network construction information.

Allen, J.D. Jr.; Schell, F.M.; Dodd, C.V.

1992-10-01

420

TUBE SHEARING VALVE  

DOEpatents

Explosive operated valves can be used to join two or more containers in fluid flow relationship, one such container being a sealed reservoir. The valve is most simply disposed by mounting it on the reservoir so thst a tube extends from the interior of the reservoir through the valve body, terminating at the bottom of the bore in a closed end; other containers may be similarly connected or may be open connected, as desired. The piston of the valve has a cutting edge at its lower end which shears off the closed tube ends and a recess above the cutting edge to provide a flow channel. Intermixing of the fluid being transferred with the explosion gases is prevented by a copper ring at the top of the piston which is force fitted into the bore at the beginning of the stroke. Although designed to avoid backing up of the piston at pressures up to 10,000 psi in the transferred fluid, proper operation is independent of piston position, once the tube ends were sheared.

Wilner, L.B.

1960-05-24

421

Concentric tube support assembly  

SciTech Connect

An assembly (45) includes a plurality of separate pie-shaped segments (72) forming a disk (70) around a central region (48) for retaining a plurality of tubes (46) in a concentrically spaced apart configuration. Each segment includes a support member (94) radially extending along an upstream face (96) of the segment and a plurality of annularly curved support arms (98) transversely attached to the support member and radially spaced apart from one another away from the central region for receiving respective upstream end portions of the tubes in arc-shaped spaces (100) between the arms. Each segment also includes a radial passageway (102) formed in the support member for receiving a fluid segment portion (106) and a plurality of annular passageways (104) formed in the support arms for receiving respective arm portions (108) of the fluid segment portion from the radial passageway and for conducting the respective arm portions into corresponding annular spaces (47) formed between the tubes retained by the disk.

Rubio, Mark F.; Glessner, John C.

2012-09-04

422

Clogging of feeding tubes.  

PubMed

This is a report of an in vitro study evaluating clotting ability of some formulas with intact protein and hydrolyzed protein sources in a series of buffers ranging from a pH of 1 thru 10. The following 10 products were tested: Ensure Plus, Ensure, Enrich, Osmolite, Pulmocare, Citrotein, Resource, Vivonex TEN, Vital, and Hepatic Acid II. Protein (10 and 20 g/liter) was added to Citrotein and Ensure Plus. All formulas were tested at full and some at half strength. Clotting occurred only in premixed intact protein formulas (Pulmocare, Ensure Plus, Osmolite, Enrich, Ensure) and in Resource. No clotting was observed for Citrotein (intact protein formula in powder form), Vital, Vivonex TEN, and Hepatic Aid II. Adding protein did not cause or increase clotting. In summary, clotting of some liquid formula diet appears to be an important factor causing possible gastric feeding tube occlusion. The following measures may help in preventing this problem: flushing before and after aspirating for gastric residuals to eliminate acid precipitation of formula in the feeding tube, advance the nasogastric feeding tube into the duodenum if possible, and avoid mixing these products with liquid medications having a pH value of 5.0 or less. PMID:3138452

Marcuard, S P; Perkins, A M

423

Computing with Neural Synchrony  

PubMed Central

Neurons communicate primarily with spikes, but most theories of neural computation are based on firing rates. Yet, many experimental observations suggest that the temporal coordination of spikes plays a role in sensory processing. Among potential spike-based codes, synchrony appears as a good candidate because neural firing and plasticity are sensitive to fine input correlations. However, it is unclear what role synchrony may play in neural computation, and what functional advantage it may provide. With a theoretical approach, I show that the computational interest of neural synchrony appears when neurons have heterogeneous properties. In this context, the relationship between stimuli and neural synchrony is captured by the concept of synchrony receptive field, the set of stimuli which induce synchronous responses in a group of neurons. In a heterogeneous neural population, it appears that synchrony patterns represent structure or sensory invariants in stimuli, which can then be detected by postsynaptic neurons. The required neural circuitry can spontaneously emerge with spike-timing-dependent plasticity. Using examples in different sensory modalities, I show that this allows simple neural circuits to extract relevant information from realistic sensory stimuli, for example to identify a fluctuating odor in the presence of distractors. This theory of synchrony-based computation shows that relative spike timing may indeed have computational relevance, and suggests new types of neural network models for sensory processing with appealing computational properties.

Brette, Romain

2012-01-01

424

27 CFR 41.35 - Cigarette tubes.  

Code of Federal Regulations, 2013 CFR

...IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Taxes Tax Rates § 41.35 Cigarette tubes. Cigarette tubes...the length of each as one cigarette tube. * Tax rate for less than 50...

2013-04-01

425

Photomultiplier tube characterization for MiniCLEAN  

NASA Astrophysics Data System (ADS)

MiniCLEAN is a single-phase dark matter experiment which uses liquid argon (87 K) or neon (27 K) as an active medium. Photomultiplier tubes (PMTs) submerged in the cryogen detect light emitted by tetraphenyl butadiene, which fluoresces at short optical wavelengths when excited by the primary ultraviolet scintillation of the argon or neon. The collaboration has chosen to use 8'' Hamamatsu R5912-02MOD PMTs, the low-temperature successor of the R1408-R5912 lineage. The bialkali photocathode of the R5912-02MOD has a platinum underlay which increases electron mobility, enabling operation at temperatures lower than 150 K where traditional bialkali cathodes fail. The number of dynodes in the tube has also been increased to 14, which lowers the bias required to attain reasonable gain and saves heat load in the voltage divider chain of the base. This talk describes characterization of the tube and base for use in MiniCLEAN. I present gain and dark rate measurements as a function of temperature, considerations that inform the base design, and implications of using this tube in a low-background experiment.

Jaditz, Stephen

2011-10-01

426

Hybrid endotracheal tubes  

NASA Astrophysics Data System (ADS)

Intubation involves the placement of a tube into the tracheal lumen and is prescribed in any setting in which the airway must be stabilized or the patient anesthetized. The purpose of the endotracheal tube in these procedures is to maintain a viable airway, facilitate mechanical ventilation, allow the administration of anesthetics, and prevent the reflux of vomitus into the lungs. In order to satisfy these requirements a nearly airtight seal must be maintained between the tube and the tracheal lining. Most conventional endotracheal tubes provide this seal by employing a cuff that is inflated once the tube is in place. However, the design of this cuff and properties of the material are a source of irritation and injury to the tracheal tissues. In fact, the complication rate for endotracheal intubation is reported to be between 10 and 60%, with manifestations ranging from severe sore throat to erosion through the tracheal wall. These complications are caused by a combination of the materials employed and the forces exerted by the cuff on the tracheal tissues. In particular, the abrasive action of the cuff shears cells from the lining, epithelium adhering to the cuff is removed during extubation, and normal forces exerted on the basement tissues disrupt the blood supply and cause pressure necrosis. The complications associated with tracheal intubation may be reduced or eliminated by employing airway devices constructed from hydrogel materials. Hydrogels are a class of crosslinked polymers which swell in the presence of moisture, and may contain more than 95% water by weight. For the current study, several prototype airway devices were constructed from hydrogel materials including poly(vinyl alcohol), poly(hydroxyethyl methacrylate), and poly(vinyl pyrrolidone). The raw hydrogel materials from this group were subjected to tensile, swelling, and biocompatibility testing, while the finished devices were subjected to extensive mechanical simulation and animal trials. During the course of these experiments it was discovered that reduced water content hydrogel materials generally exhibited superior mechanical properties, but performed more poorly during simulation and biocompatibility studies. Conversely, higher water content materials exhibited lower mechanical performance but superior simulation and biocompatibility results.

Sakezles, Christopher Thomas

427

June 29, 2012: Background Materials  

Center for Biologics Evaluation and Research (CBER)

... Drug Administration. -. June 29, 2012: Background Materials. -. June 29, 2012: Background Information Memo. -. -. -. Page Last ... More results from www.fda.gov/advisorycommittees/committeesmeetingmaterials/riskcommunicationadvisorycommittee

428

Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure.  

PubMed

The aim of this study was the development of an alternative testing method based on human embryonic stem cells for prenatal developmental toxicity with particular emphasis on early neural development. To this purpose, we designed an in vitro protocol based on the generation of neural rosettes, representing the in vitro counterpart of the developing neural plate and neural tube, and we challenged this complex cell model with retinoic acid (RA), a well-known teratogenic agent. The cells were exposed to different concentrations of RA during the process of rosettes formation. Morphological and molecular parameters were evaluated in treated as compared with untreated cells to detect both cytotoxicity and specific neural toxicity. Transcriptomic analysis was performed with microarray Affymetrix platform and validated by quantitative real-time PCR for genes relevant to early neural development such as HoxA1, HoxA3, HoxB1, HoxB4, FoxA2, FoxC1, Otx2, and Pax7. The results obtained demonstrated that neural rosette forming cells respond to RA with clear concentration-dependent morphological, and gene expression changes remarkably similar to those induced in vivo, in the developing neural tube, by RA exposure. This strict correspondence indicates that the neural rosette protocol described is capable of detecting specific teratogenic mechanisms causing perturbations of early neural development and therefore represents a promising alternative test for human prenatal developmental toxicity. PMID:21934132

Colleoni, Silvia; Galli, Cesare; Gaspar, John Antony; Meganathan, Kesavan; Jagtap, Smita; Hescheler, Jurgen; Sachinidis, Agapios; Lazzari, Giovanna

2011-09-20

429

Real-Time Decision Fusion for Multimodal Neural Prosthetic Devices  

PubMed Central

Background The field of neural prosthetics aims to develop prosthetic limbs with a brain-computer interface (BCI) through which neural activity is decoded into movements. A natural extension of current research is the incorporation of neural activity from multiple modalities to more accurately estimate the user's intent. The challenge remains how to appropriately combine this information in real-time for a neural prosthetic device. Methodology/Principal Findings Here we propose a framework based on decision fusion, i.e., fusing predictions from several single-modality decoders to produce a more accurate device state estimate. We examine two algorithms for continuous variable decision fusion: the Kalman filter and artificial neural networks (ANNs). Using simulated cortical neural spike signals, we implemented several successful individual neural decoding algorithms, and tested the capabilities of each fusion method in the context of decoding 2-dimensional endpoint trajectories of a neural prosthetic arm. Extensively testing these methods on random trajectories, we find that on average both the Kalman filter and ANNs successfully fuse the individual decoder estimates to produce more accurate predictions. Conclusions Our results reveal that a fusion-based approach has the potential to improve prediction accuracy over individual decoders of varying quality, and we hope that this work will encourage multimodal neural prosthetics experiments in the future.

White, James Robert; Levy, Todd; Bishop, William; Beaty, James D.

2010-01-01

430

Audio Environment Classication for Hearing Aids using Artificial Neural Networks with Windowed Input  

Microsoft Academic Search

Excessive background noise is one of the most common complaints from hearing aid users. Background noise classification systems can be used in hearing aids to adjust the response based on the noise environment. This paper examines and compares two promising classification techniques, non-windowed artificial neural networks (ANN) and hidden Markov models (HMM), with an artificial neural network using windowed input.

G. Freeman; R. D. Dony; S. M. Areibi

2007-01-01

431

Neural Crest and Olfactory System: New Prospective  

PubMed Central

Sensory neurons in vertebrates are derived from two embryonic transient cell sources: neural crest (NC) and ectodermal placodes. The placodes are thickenings of ectodermal tissue that are responsible for the formation of cranial ganglia as well as complex sensory organs that include the lens, inner ear, and olfactory epithelium. The NC cells have been indicated to arise at the edges of the neural plate/dorsal neural tube, from both the neural plate and the epidermis in response to reciprocal interactions Moury and Jacobson (Dev Biol 141:243–253, 1990). NC cells migrate throughout the organism and give rise to a multitude of cell types that include melanocytes, cartilage and connective tissue of the head, components of the cranial nerves, the dorsal root ganglia, and Schwann cells. The embryonic definition of these two transient populations and their relative contribution to the formation of sensory organs has been investigated and debated for several decades (Basch and Bronner-Fraser, Adv Exp Med Biol 589:24–31, 2006; Basch et al., Nature 441:218–222, 2006) review (Baker and Bronner-Fraser, Dev Biol 232:1–61, 2001). Historically, all placodes have been described as exclusively derived from non-neural ectodermal progenitors. Recent genetic fate-mapping studies suggested a NC contribution to the olfactory placodes (OP) as well as the otic (auditory) placodes in rodents (Murdoch and Roskams, J NeurosciOff J Soc Neurosci 28:4271–4282, 2008; Murdoch et al., J Neurosci 30:9523–9532, 2010; Forni et al., J Neurosci Off J Soc Neurosci 31:6915–6927, 2011b; Freyer et al., Development 138:5403–5414, 2011; Katoh et al., Mol Brain 4:34, 2011). This review analyzes and discusses some recent developmental studies on the OP, placodal derivatives, and olfactory system.

Forni, Paolo E.

2013-01-01

432

Cognitive neural prosthetics  

Microsoft Academic Search

Research on neural prosthetics has focused largely on using activity related to hand trajectories recorded from motor cortical areas. An interesting question revolves around what other signals might be read out from the brain and used for neural prosthetic applications. Recent studies indicate that goals and expected value are among the high-level cognitive signals that can be used and will

Richard A. Andersen; J. W. Burdick; S. Musallam; B. Pesaran; J. G. Cham

2004-01-01

433

Quantum neural networks  

Microsoft Academic Search

This chapter outlines the research, development and perspectives of quantum neural networks - a burgeoning new field which integrates classical neurocomputing with quantum computation (1). It is argued that the study of quantum neural networks may give us both new undestanding of brain function as well as unprecedented possibilities in creating new systems for information processing, including solving classically intractable

Alexandr A. Ezhov; Dan Ventura

434

Neural Assembly Computing  

Microsoft Academic Search

Spiking neurons can realize several computational operations when firing cooperatively. This is a prevalent notion, although the mechanisms are not yet understood. A way by which neural assemblies compute is proposed in this paper. It is shown how neural coalitions represent things (and world states), memorize them, and control their hierarchical relations in order to perform algorithms. It is described

João Ranhel

2012-01-01

435

On Quantum Neural Computing  

Microsoft Academic Search

This paper examines the notion of quantum neural computing in thecontext of several new directions in neural network research. In particular,we consider new neuron and network models that lead to rapidtraining; chaotic dynamics in neuron assemblies; models of attention andawareness; cytoskeletal microtubule information processing; and quantummodels. Recent discoveries in neuroscience that cannot be placed in the reductionistmodels of biological information

Subhash C. Kak

1995-01-01

436

Falling Test Tubes  

NSDL National Science Digital Library

How can inverted test tubes inserted into one another apparently move upwards against gravity? This material is part of a series of hands-on science activities designed to arouse student interest. Here students investigate the cohesive and adhesive forces of water and glass. The activity includes a description, a list of the science process skills and complex reasoning strategies being used, and a compilation of applicable K-12 national science education standards. Also provided are content topics, a list of necessary supplies, instructions, and presentation techniques. The content of the activity is explained, and assessment suggestions are provided.

Mid-continent Research for Education and Learning (McREL); Jacobs, Steve

2004-01-01

437

Insights from the amphioxus genome on the origin of vertebrate neural crest  

PubMed Central

The emergence of the neural crest has been proposed to play a key role in early vertebrate evolution by remodeling the chordate head into a “new head” that enabled early vertebrates to shift from filter feeding to active predation. Here we show that the genome of the basal chordate, amphioxus, contains homologs of most vertebrate genes implicated in a putative neural crest gene regulatory network (NC-GRN) for neural crest development. Our survey of gene expression shows that early inducing signals, neural plate border patterning genes, and melanocyte differentiation genes appear conserved. Furthermore, exogenous BMP affects expression of amphioxus neural plate border genes as in vertebrates, suggesting that conserved signals specify the neural plate border throughout chordates. In contrast to this core conservation, many neural crest specifier genes are not expressed at the amphioxus <