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1

Neural Tube Defects  

MedlinePLUS

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

2

Opioid Use and Neural Tube Defects  

MedlinePLUS

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

3

Epidemiology of neural tube defects  

PubMed Central

Objectives: To find the prevalence of neural tube defects (NTDs), and compare the findings with local and international data, and highlight the important role of folic acid supplementation and flour fortification with folic acid in preventing NTDs. Methods: This is a retrospective study of data retrieved from the medical records of live newborn infants admitted to the Neonatal Intensive Care Unit (NICU), Security Forces Hospital (SFH), Riyadh, Saudi Arabia with NTDs spanning 14 years (1996-2009). All pregnant women on their first antenatal visit to the primary care clinic were prescribed folic acid 0.5 mg daily, or 5 mg if there is a family history of NTD. The pre-fortification prevalence is compared to post-fortification, before and after excluding syndromic, genetic, and chromosomal causes. The results were compared with reports from other parts of Saudi Arabia and internationally, through a literature search using MEDLINE. Results: The prevalence of NTDs during the period was 1.2 per 1000 live births. The pre-fortification of flour with folic acid prevalence was 1.46 per 1000 live births. The post-fortification prevalence was 1.05 (p=0.103). After excluding syndromic, genetic, and chromosomal causes from calculation of the prevalence, there was a significant reduction in the prevalence, from 1.46 to 0.81 per 1000 live births (p=0.0088). Syndromic, genetic, and chromosomal causes were identified in 20 cases (19.4%). Only 2% of mothers received preconception folic acid, and only 10% of them received it during the first 4 weeks of gestation. Conclusion: Despite the implementation of fortification of flour with folic acid since 2001, the prevalence of NTDs in the Kingdom of Saudi Arabia is still high. This is due to the impact of genetic, syndromic, and chromosomal causes of NTD not preventable by folic acid. Other factors like unplanned pregnancy and lack of awareness of the role of folic acid in preventing nonsyndromic causes, play a significant role. PMID:25551108

Seidahmed, Mohammed Z.; Abdelbasit, Omar B.; Shaheed, Meeralebbae M.; Alhussein, Khalid A.; Miqdad, Abeer M.; Khalil, Mohamed I.; Al-Enazy, Naif M.; Salih, Mustafa A.

2014-01-01

4

Are There Disorders or Conditions Associated with Neural Tube Defects?  

MedlinePLUS

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

5

Spondylocostal dysplasia and neural tube defects.  

PubMed Central

Spondylocostal dysplasia (Jarcho-Levin syndrome) comprises multiple malformations of the vertebrae and ribs coupled with a characteristic clinical picture of short neck, scoliosis, short trunk, and deformity of the rib cage. We describe a patient with the syndrome who also had spina bifida and diastematomyelia. We surmise that this association is not coincidental. Additional evidence is needed to support the hypothesis that spondylocostal dysplasia and neural tube defects are aetiologically related. Images PMID:1999834

Giacoia, G P; Say, B

1991-01-01

6

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. PMID:24048206

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

2013-01-01

7

Neural Tube Defects, Such as Spina Bifida, on The Decline: CDC  

MedlinePLUS

... page, please enable JavaScript. Neural Tube Defects, Such as Spina Bifida, on the Decline: CDC Experts cite ... are born annually with neural tube defects such as spina bifida, the most common neural tube defect ...

8

Neural Tube Defects, Folate, and Immune Modulation  

PubMed Central

Periconceptional supplementation with folic acid has led to a significant worldwide reduction in the incidence of neural tube defects (NTDs). However, despite increasing awareness of the benefits of folic acid supplementation and the implementation of food fortification programs in many countries, NTDs continue to be a leading cause of perinatal morbidity and mortality worldwide. Furthermore, there exists a significant subgroup of women who appear to be resistant to the protective effects of folic acid supplementation. The following review addresses emerging clinical and experimental evidence for a role of the immune system in the etiopathogenesis of NTDs, with the aim of developing novel preventative strategies to further reduce the incidence of NTD-affected pregnancies. In particular, recent studies demonstrating novel roles and interactions between innate immune factors such as the complement cascade, neurulation, and folate metabolism are explored. PMID:24078477

Fathe, Kristin; Finnell, Richard H.; Taylor, Stephen M.; Woodruff, Trent M.

2014-01-01

9

Deficits in early neural tube identity found in CHARGE syndrome  

PubMed Central

Long predicted from studies of model vertebrates, the first human example of abnormal patterning of the early neural tube leading to underdevelopment of the cerebellum has been demonstrated. PMID:24368735

2013-01-01

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? Skip sharing on ... AFP, as well as high levels of acetylcholinesterase; health care providers might conduct this test to confirm high ...

11

Homocysteine metabolism in pregnancies complicated by neural-tube defects  

Microsoft Academic Search

Folic acid taken around the time of conception can prevent many neural-tube defects. Women with low-normal vitamin B12 values may also be at increased risk. We considered whether homocysteine metabolism via the enzyme methionine synthase, which requires both folate and B12, could be the critical defect in folate-related neural tube defects. Blood was obtained during pregnancies that produced 81 infants

J. L. Mills; Y. J. Lee; M. R. Conley; P. N. Kirke; J. M. McPartlin; D. G. Weir; J. M. Scott

1995-01-01

12

Neural tube defects: from a proteomic standpoint.  

PubMed

Neural tube defects (NTDs) are congenital birth defects classified according to their resulting morphological characteristics in newborn patients. Current diagnosis of NTDs relies largely on the structural evaluation of fetuses using ultrasound imaging, with biochemical characterization used as secondary screening tools. The multigene etiology of NTDs has been aided by genetic studies, which have discovered panels of genes mutated in these diseases that encode receptors and cytoplasmic signaling molecules with poorly defined functions. Animal models ranging from flies to mice have been used to determine the function of these genes and identify their associated molecular cascades. More emphasis is now being placed on the identification of biochemical markers from clinical samples and model systems based on mass spectrometry, which open novel avenues in the understanding of NTDs at protein, metabolic and molecular levels. This article reviews how the use of proteomics can push forward the identification of novel biomarkers and molecular networks implicated in NTDs, an indispensable step in the improvement of patient management. PMID:25789708

Puvirajesinghe, Tania M; Borg, Jean-Paul

2015-01-01

13

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

Microsoft Academic Search

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

Jin-Feng Wang; Xin Liu; George Christakos; Yi-Lan Liao; Xue Gu; Xiao-Ying Zheng

2010-01-01

14

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

PubMed Central

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

Kinoshita, Nagatoki; Sasai, Noriaki; Misaki, Kazuyo

2008-01-01

15

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

16

Neural tube defects in Jamaica following Hurricane Gilbert.  

PubMed Central

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

Duff, E M; Cooper, E S

1994-01-01

17

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

18

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.

19

Classification, clinical features, and genetics of neural tube defects  

PubMed Central

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

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

2014-01-01

20

Neural tube defects – recent advances, unsolved questions and controversies  

PubMed Central

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

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

2014-01-01

21

Neural Tube Defects: Review of Experimental Evidence on Stem Cell Therapy and Newer Treatment Options  

Microsoft Academic Search

The failure of closure of the neural tube during development leads to malformations called neural tube defects (NTDs). The most common neural malformations in humans include anencephaly, encephalocele, exencephaly, craniorachischisis spina bifida with or without myelomeningocele, lipomyeloschisis, lipomyelomeningocele, meningocele and myelocystocele. Current preventive strategies are mainly based on pharmacologic\\/folic acid supplementation. However, stem cell-based and other combination approaches may emerge

Dhara B. Dhaulakhandi; Seema Rohilla; Kamal Nain Rattan

2010-01-01

22

Histological Evaluation of Acute Covering of an Experimental Neural Tube Defect with Biomatrices in Fetal Sheep  

Microsoft Academic Search

Objective: The aim of the study was to determine the histological effect on the neural tissue of in utero covering of an experimental neural tube defect in fetal lambs, with the use of two different biomatrices. Materials and Methods: In 23 fetal sheep, surgery was performed at 79 days’ gestation. In 19 of these, a neural tube defect was created,

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

2006-01-01

23

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

PubMed Central

Objective To determine an optimal population red blood cell (RBC) folate concentration for the prevention of neural tube birth defects. Design Bayesian model. Setting Data from two population based studies in China. Participants 247?831 participants in a prospective community intervention project in China (1993-95) to prevent neural tube defects with 400 ?g/day folic acid supplementation and 1194 participants in a population based randomized trial (2003-05) to evaluate the effect of folic acid supplementation on blood folate concentration among Chinese women of reproductive age. Intervention Folic acid supplementation (400 ?g/day). Main outcome measures Estimated RBC folate concentration at time of neural tube closure (day 28 of gestation) and risk of neural tube defects. Results Risk of neural tube defects was high at the lowest estimated RBC folate concentrations (for example, 25.4 (95% uncertainty interval 20.8 to 31.2) neural tube defects per 10?000 births at 500 nmol/L) and decreased as estimated RBC folate concentration increased. Risk of neural tube defects was substantially attenuated at estimated RBC folate concentrations above about 1000 nmol/L (for example, 6 neural tube defects per 10?000 births at 1180 (1050 to 1340) nmol/L). The modeled dose-response relation was consistent with the existing literature. In addition, neural tube defect risk estimates developed using the proposed model and population level RBC information were consistent with the prevalence of neural tube defects in the US population before and after food fortification with folic acid. Conclusions A threshold for “optimal” population RBC folate concentration for the prevention of neural tube defects could be defined (for example, approximately 1000 nmol/L). Population based RBC folate concentrations, as a biomarker for risk of neural tube defects, can be used to facilitate evaluation of prevention programs as well as to identify subpopulations at elevated risk for a neural tube defect affected pregnancy due to folate insufficiency. PMID:25073783

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

2014-01-01

24

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

SciTech Connect

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

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

2013-05-01

25

Professor John Scott, folate and neural tube defects.  

PubMed

John Scott (1940-2013) was born in Dublin where he was to spend the rest of his career, both as an undergraduate and subsequently Professor of Biochemistry and Nutrition at Trinity College. His research with the talented group of scientists and clinicians that he led has had a substantial impact on our understanding of folate metabolism, mechanisms of its catabolism and deficiency. His research established the leading theory of folate involvement with vitamin B12 in the pathogenesis of vitamin B12 neuropathy. He helped to establish the normal daily intake of folate and the increased requirements needed either in food or as a supplement before and during pregnancy to prevent neural tube defects. He also suggested a dietary supplement of vitamin B12 before and during pregnancy to reduce the risk of neural tube defects. It would be an appropriate epitaph if fortification of food with folic acid became mandatory in the UK and Ireland, as it is in over 70 other countries. PMID:24224721

Hoffbrand, A Victor

2014-02-01

26

Epidemiology of neural tube defects in Saudi Arabia  

PubMed Central

Objective: To evaluate the distribution and pattern of neural tube defects in Saudi Arabia by creating a hospital based registry. Methods: All cases registered in the King Faisal Specialist Hospital and Research Center (KFSH&RC) neural tube defect (NTD) registry since it was established in October 2000 until December 2012 were studied through active surveillance comprising a registrar who collects NTD information by reviewing the patient’s medical records, and interviewing patient’s families. Results: The total number of patients registered from October 2000 to December 2012 was 718 patients. There were more females (417, 58%) than males (301, 42%). Of 620 mothers who underwent antenatal ultrasonography; 392 (63%) were diagnosed at birth, and 204 (33%) were diagnosed with antenatal hydrocephalus. In our registry sample, most mothers (95%) did not take folic acid 3 months prior to pregnancy, and 76% did not take folic acid during the 3 months after conception with the affected child. Only 5% received folic acid prior to conception. Conclusions: The KFSH&RC-NTD registry has met its objectives as a source of data that may significantly contribute to the prevention of NTDs, and improving quality of care for NTD patients through active publication of registry findings and management approaches. PMID:25551116

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

2014-01-01

27

Contribution of VANGL2 mutations to isolated neural tube defects.  

PubMed

Vangl2 was identified as the gene defective in the Looptail (Lp) mouse model for neural tube defects (NTDs). This gene forms part of the planar cell polarity (PCP) 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 seven 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. PMID:20738329

Kibar, Z; Salem, S; Bosoi, C M; Pauwels, E; De Marco, P; Merello, E; Bassuk, A G; Capra, V; Gros, P

2011-07-01

28

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. PMID:20738329

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

2010-01-01

29

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

PubMed Central

Background In the last two decades, India has witnessed a substantial decrease in infant mortality attributed to infectious disease and malnutrition. However, the mortality attributed to birth defects remains constant. Studies on the prevalence of birth defects such as neural tube defects and orofacial clefts in India have reported inconsistent results. Therefore, we conducted a systematic review of observational studies to document the birth prevalence of neural tube defects and orofacial clefts. Methods A comprehensive literature search for observational studies was conducted in MEDLINE and EMBASE databases using key MeSH terms (neural tube defects OR cleft lip OR cleft palate AND Prevalence AND India). Two reviewers independently reviewed the retrieved studies, and studies satisfying the eligibility were included. The quality of included studies was assessed using selected criteria from STROBE statement. Results The overall pooled birth prevalence (random effect) of neural tube defects in India is 4.5 per 1000 total births (95% CI 4.2 to 4.9). The overall pooled birth prevalence (random effect) of orofacial clefts is 1.3 per 1000 total births (95% CI 1.1 to 1.5). Subgroup analyses were performed by region, time period, consanguinity, and gender of newborn. Conclusion The overall prevalence of neural tube defects from India is high compared to other regions of the world, while that of orofacial clefts is similar to other countries. The majority of studies included in the review were hospital based. The quality of these studies ranged from low to moderate. Further well-designed, high quality community-based observational studies are needed to accurately estimate the burden of neural tube defects and orofacial clefts in India. PMID:25768737

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

2015-01-01

30

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

Code of Federal Regulations, 2011 CFR

...neural tube forms and closes during early pregnancy, the defect may occur before a woman...of recurrence of a neural tube defect pregnancy who consumed a supplement containing...conception and continuing into early pregnancy had a reduced risk of having...

2011-04-01

31

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

Code of Federal Regulations, 2014 CFR

...neural tube forms and closes during early pregnancy, the defect may occur before a woman...of recurrence of a neural tube defect pregnancy who consumed a supplement containing...conception and continuing into early pregnancy had a reduced risk of having...

2014-04-01

32

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

Code of Federal Regulations, 2013 CFR

...neural tube forms and closes during early pregnancy, the defect may occur before a woman...of recurrence of a neural tube defect pregnancy who consumed a supplement containing...conception and continuing into early pregnancy had a reduced risk of having...

2013-04-01

33

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

Code of Federal Regulations, 2012 CFR

...neural tube forms and closes during early pregnancy, the defect may occur before a woman...of recurrence of a neural tube defect pregnancy who consumed a supplement containing...conception and continuing into early pregnancy had a reduced risk of having...

2012-04-01

34

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

MedlinePLUS

Folic Acid for the Prevention of Infant Neural Tube Defects: U.S. Preventive Services Task Force Recommendation Summaries for Patients ... modern medicine. The full reports are titled “Folic Acid for the Prevention of Neural Tube Defects: U.S. ...

35

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. PMID:23400307

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

2012-01-01

36

In utero Repair of an Experimental Neural Tube Defect in a Chronic Sheep Model Using Biomatrices  

Microsoft Academic Search

Objective: Persistent exposure of the unprotected spinal cord to amniotic fluid and the uterine wall can lead to progressive damage of neural tissue in case of a myelomeningocele (two-hit hypothesis). The aim of this study was to evaluate whether in utero repair of an experimental neural tube defect in a fetal lamb could protect neural tissue from secondary injury and

A. J. Eggink; L. A. J. Roelofs; W. F. J. Feitz; R. M. H. Wijnen; R. A. Mullaart; J. A. Grotenhuis; T. H. van Kuppevelt; M. M. Y. Lammens; A. J. Crevels; A. Hanssen; P. P. van den Berg

2005-01-01

37

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

PubMed Central

Closure of the neural tube during embryogenesis is a crucial step in development of the central nervous system. Failure of this process results in neural tube defects, including spina bifida and anencephaly, which are among the most common birth defects worldwide. Maternal use of folic acid supplements reduces risk of neural tube defects but a proportion of cases are not preventable. Folic acid is thought to act through folate one-carbon metabolism, which transfers one-carbon units for methylation reactions and nucleotide biosynthesis. Hence suboptimal performance of the intervening reactions could limit the efficacy of folic acid. We hypothesized that direct supplementation with nucleotides, downstream of folate metabolism, has the potential to support neural tube closure. Therefore, in a mouse model that exhibits folic acid-resistant neural tube defects, we tested the effect of specific combinations of pyrimidine and purine nucleotide precursors and observed a significant protective effect. Labelling in whole embryo culture showed that nucleotides are taken up by the neurulating embryo and incorporated into genomic DNA. Furthermore, the mitotic index was elevated in neural folds and hindgut of treated embryos, consistent with a proposed mechanism of neural tube defect prevention through stimulation of cellular proliferation. These findings may provide an impetus for future investigations of supplemental nucleotides as a means to prevent a greater proportion of human neural tube defects than can be achieved by folic acid alone. PMID:23935126

Leung, Kit-Yi; De Castro, Sandra C.P.; Savery, Dawn; Copp, Andrew J.

2013-01-01

38

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

PubMed

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

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

2014-12-01

39

Epidemiology, prenatal management, and prevention of neural tube defects  

PubMed Central

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

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

2014-01-01

40

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

41

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. PMID:20544799

Murdoch, Jennifer N.; Copp, Andrew J.

2013-01-01

42

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

PubMed Central

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

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

2008-01-01

43

Investigations into arsenate-induced neural tube defects in a mouse model  

E-print Network

arsenate) in a normal inbred mouse strain, LM/Bc/Fnn, that is sensitive to arsenate-induced exencephaly. We investigated arsenate induced gene expression changes using DNA microarrays of embryonic anterior neural tube tissue, as well as monitoring...

Hill, Denise Suzanne

2009-05-15

44

Protein kinase A deficiency causes axially localized neural tube defects in mice.  

PubMed

We have studied the function of protein kinase A (PKA) during embryonic development using a PKA-deficient mouse that retains only one functional catalytic subunit allele, either Calpha or Cbeta, of PKA. The reduced PKA activity results in neural tube defects that are specifically localized posterior to the forelimb buds and lead to spina bifida. The affected neural tube has closed appropriately but exhibits an enlarged lumen and abnormal neuroepithelium. Decreased PKA activity causes dorsal expansion of Sonic hedgehog signal response in the thoracic to sacral regions correlating with the regions of morphological abnormalities. Other regions of the neural tube appear normal. The regional sensitivity to changes in PKA activity indicates that downstream signaling pathways differ along the anterior-posterior axis and suggests a functional role for PKA activation in neural tube development. PMID:11886853

Huang, Yongzhao; Roelink, Henk; McKnight, G Stanley

2002-05-31

45

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

Code of Federal Regulations, 2010 CFR

...Populations at risk. Prevalence rates for neural tube defects have been reported to vary with a wide range of factors including genetics, geography, socioeconomic status, maternal birth cohort, month of conception, race, nutrition, and maternal...

2010-04-01

46

Folate pathway gene alterations in patients with neural tube defects.  

PubMed

Periconceptional folate supplementation reduces the recurrence and occurrence risk of neural tube defects (NTD) by as much as 70%, yet the protective mechanism remains unknown. Inborn errors of folate and homocysteine metabolism may be involved in the aetiology of NTDs. Previous studies have demonstrated that both homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, and combined heterozygosity for the C677T and for another mutation in the same gene, the A1298C polymorphism, represent genetic risk factors for NTDs. In an attempt to identify additional folate related genes that contribute to NTD pathogenesis, we performed molecular genetic analysis of folate receptors (FRs). We identified 4 unrelated patients out of 50 with de novo insertions of pseudogene (PS)-specific mutations in exon 7 and 3'UTR of the FRalpha gene, arising by microconversion events. All of the substitutions affect the carboxy-terminal amino acid membrane tail, or the GPI anchor region of the nascent protein. Furthermore, among 150 control individuals, we also identified one infant with a gene conversion event within the FRalpha coding region. This study, though preliminary, provides the first genetic association between molecular variations of the FRalpha gene and NTDs and suggests that this gene can act as a risk factor for human NTD. PMID:11102926

De Marco, P; Moroni, A; Merello, E; de Franchis, R; Andreussi, L; Finnell, R H; Barber, R C; Cama, A; Capra, V

2000-11-27

47

Genetic, chromosomal, and syndromic causes of neural tube defects  

PubMed Central

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

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

2014-01-01

48

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. PMID:20549630

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

2010-01-01

49

Split cord malformation associated with spinal open neural tube defect  

PubMed Central

Objective: To illustrate the clinical and radiological findings of split cord malformation (SCM) in patients with spinal open neural tube defect (SONTD), and report the outcome of their treatment. Methods: A retrospective study of the clinical and radiological findings of 11 patients diagnosed with SCM, identified among 83 patients with SONTD at King Khalid University Hospital, in Riyadh, Saudi Arabia between 1995 and 2010. Results: There were 6 girls and 5 boys; their age ranged from less than a year to 9 years (mean 4.2 years). Six patients had type I SCM, and 5 patients type II SCM. The CT and MRI imaging showed characteristic bony, cartilaginous, or fibrous septum, and other SONTD-associated anomalies. Seven patients were graded A & B according to the Frankel grading score, and none of them required surgery, while worsening neurology led to surgical intervention in 3 patients, with clinical improvement after surgery, and one patient that underwent cord untethering remained stable. Conclusion: Split cord malformation is not uncommon among patients with SONTD. It tends to involve mainly the lumbar spine, and female predominance is more remarkable in type I. Neurological manifestations of SCM may be superimposed with SONTD. Surgery is effective for symptomatic patients, and not indicated in the severely disabled. PMID:25551111

Elgamal, Essam A.; Hassan, Hamdy H.; Elwatidy, Sherif M.; Altwijri, Ikhllas; Alhabib, Amro F.; Jamjoom, Zain B.; Murshid, Waleed R.; Salih, Mustafa A.

2014-01-01

50

Signaling by Sonic hedgehog (Shh) controls important developmental processes, including dorsoventral neural tube  

E-print Network

dorsoventral neural tube patterning, neural stem cell proliferation, and neuronal and glial cell survival. Shh differentiation of neuronal and non-neuronal cell types. One such example is the proliferative response of cerebellar granule cell neurons to Shh [17­19] (Figure 1). Shh also regulates the proliferation and survival

Quake, Stephen R.

51

Regional differences in the expression of laminin isoforms during mouse neural tube development  

PubMed Central

Many significant human birth defects originate around the time of neural tube closure or early during post-closure nervous system development. For example, failure of the neural tube to close generates anencephaly and spina bifida, faulty cell cycle progression is implicated in primary microcephaly, while defective migration of neuroblasts can lead to neuronal migration disorders such as lissencephaly. At the stage of neural tube closure, basement membranes are becoming organised around the neuroepithelium, and beneath the adjacent non-neural surface ectoderm. While there is circumstantial evidence to implicate basement membrane dynamics in neural tube and surface ectodermal development, we have an incomplete understanding of the molecular composition of basement membranes at this stage. In the present study, we examined the developing basement membranes of the mouse embryo at mid-gestation (embryonic day 9.5), with particular reference to laminin composition. We performed in situ hybridization to detect the mRNAs of all eleven individual laminin chains, and immunohistochemistry to identify which laminin chains are present in the basement membranes. From this information, we inferred the likely laminin variants and their tissues of origin: that is, whether a given basement membrane laminin is contributed by epithelium, mesenchyme, or both. Our findings reveal major differences in basement composition along the body axis, with the rostral neural tube (at mandibular arch and heart levels) exhibiting many distinct laminin variants, while the lumbar level where the neural tube is just closing shows a much simpler laminin profile. Moreover, there appears to be a marked difference in the extent to which the mesenchyme contributes laminin variants to the basement membrane, with potential contribution of several laminins rostrally, but no contribution caudally. This information paves the way towards a mechanistic analysis of basement membrane laminin function during early neural tube development in mammals. PMID:21524702

Copp, Andrew J.; Carvalho, Rita; Wallace, Adam; Sorokin, Lydia; Sasaki, Takako; Greene, Nicholas D.E.; Ybot-Gonzalez, Patricia

2013-01-01

52

Missing Genetic Risk in Neural Tube Defects: Can Exome Sequencing Yield an Insight?  

PubMed Central

Background Neural tube defects (NTD) have a strong genetic component, with up to 70% of variance in human prevalence determined by heritable factors. Although the identification of causal DNA variants by sequencing candidate genes from functionally relevant pathways and model organisms has provided some success, alternative approaches are demanded. Methods Next generation sequencing platforms are facilitating the production of massive amounts of sequencing data, primarily from the protein coding regions of the genome, at a faster rate and cheaper cost than has previously been possible. These platforms are permitting the identification of variants (de novo, rare, and common) that are drivers of NYTD etiology, and the cost of the approach allows for the screening of increased numbers of affected and unaffected individuals from NTD families and in simplex cases. Conclusion The next generation sequencing platforms represent a powerful tool in the armory of the genetics researcher to identify the causal genetic basis of NTDs. PMID:25044326

Krupp, Deidre R.; Soldano, Karen L.; Garrett, Melanie E.; Cope, Heidi; Ashley-Koch, Allison E.; Gregory, Simon G.

2014-01-01

53

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

PubMed Central

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

Kappen, Claudia

2014-01-01

54

The role of primary cilia in the pathophysiology of neural tube defects.  

PubMed

Neural tube defects (NTDs) are a set of disorders that occur from perturbation of normal neural development. They occur in open or closed forms anywhere along the craniospinal axis and often result from a complex interaction between environmental and genetic factors. One burgeoning area of genetics research is the effect of cilia signaling on the developing neural tube and how the disruption of primary cilia leads to the development of NTDs. Recent progress has implicated the hedgehog (Hh), wingless-type integration site family (Wnt), and planar cell polarity (PCP) pathways in primary cilia as involved in normal neural tube patterning. A set of disorders involving cilia function, known as ciliopathies, offers insight into abnormal neural development. In this article, the authors discuss the common ciliopathies, such as Meckel-Gruber and Joubert syndromes, that are associated with NTDs, and review cilia-related signaling cascades responsible for mammalian neural tube development. Understanding the contribution of cilia in the formation of NTDs may provide greater insight into this common set of pediatric neurological disorders. PMID:23025443

Vogel, Timothy W; Carter, Calvin S; Abode-Iyamah, Kingsley; Zhang, Qihong; Robinson, Shenandoah

2012-10-01

55

An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure.  

PubMed

The number of mouse mutants and strains with neural tube defects (NTDs) now exceeds 240, including 205 representing specific genes, 30 for unidentified genes, and 9 multifactorial strains. These mutants identify genes needed for embryonic neural tube closure. Reports of 50 new NTD mutants since our 2007 review (Harris and Juriloff, 2007) were considered in relation to the previously reviewed mutants to obtain new insights into mechanisms of NTD etiology. In addition to null mutations, some are hypomorphs or conditional mutants. Some mutations do not cause NTDs on their own, but do so in digenic, trigenic, and oligogenic combinations, an etiology that likely parallels the nature of genetic etiology of human NTDs. Mutants that have only exencephaly are fourfold more frequent than those that have spina bifida aperta with or without exencephaly. Many diverse cellular functions and biochemical pathways are involved; the NTD mutants draw new attention to chromatin modification (epigenetics), the protease-activated receptor cascade, and the ciliopathies. Few mutants directly involve folate metabolism. Prevention of NTDs by maternal folate supplementation has been tested in 13 mutants and reduces NTD frequency in six diverse mutants. Inositol reduces spina bifida aperta frequency in the curly tail mutant, and three new mutants involve inositol metabolism. The many NTD mutants are the foundation for a future complete genetic understanding of the processes of neural fold elevation and fusion along mechanistically distinct cranial-caudal segments of the neural tube, and they point to several candidate processes for study in human NTD etiology. PMID:20740593

Harris, Muriel J; Juriloff, Diana M

2010-08-01

56

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. PMID:23733478

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

57

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

PubMed Central

Neural tube defects (NTDs) are among the commonest and most severe forms of developmental defect, characterized by disruption of the early embryonic events of central nervous system formation. NTDs have long been known to exhibit a strong genetic dependence, yet the identity of the genetic determinants remains largely undiscovered. Initiation of neural tube closure is disrupted in mice homozygous for mutations in planar cell polarity (PCP) pathway genes, providing a strong link between NTDs and PCP signaling. Recently, missense gene variants have been identified in PCP genes in humans with NTDs, although the range of phenotypes is greater than in the mouse mutants. In addition, the sequence variants detected in affected humans are heterozygous, and can often be detected in unaffected individuals. It has been suggested that interactions between multiple heterozygous gene mutations cause the NTDs in humans. To determine the phenotypes produced in double heterozygotes, we bred mice with all three pairwise combinations of Vangl2Lp, ScribCrc and Celsr1Crsh mutations, the most intensively studied PCP mutants. The majority of double-mutant embryos had open NTDs, with the range of phenotypes including anencephaly and spina bifida, therefore reflecting the defects observed in humans. Strikingly, even on a uniform genetic background, variability in the penetrance and severity of the mutant phenotypes was observed between the different double-heterozygote combinations. Phenotypically, Celsr1Crsh;Vangl2Lp;ScribCrc triply heterozygous mutants were no more severe than doubly heterozygous or singly homozygous mutants. We propose that some of the variation between double-mutant phenotypes could be attributed to the nature of the protein disruption in each allele: whereas ScribCrc is a null mutant and produces no Scrib protein, Celsr1Crsh and Vangl2Lp homozygotes both express mutant proteins, consistent with dominant effects. The variable outcomes of these genetic interactions are of direct relevance to human patients and emphasize the importance of performing comprehensive genetic screens in humans. PMID:25128525

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

2014-01-01

58

Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects.  

PubMed

BackgroundNeural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population.MethodsReplication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case¿control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case¿control models and NTD groupings in white, African American and Hispanic cohorts from NYS.ResultsOf the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans.ConclusionsWe report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis. PMID:25293959

Pangilinan, Faith; Molloy, Anne M; Mills, James L; Troendle, James F; Parle-McDermott, Anne; Kay, Denise M; Browne, Marilyn L; McGrath, Emily C; Abaan, Hatice; Sutton, Marie; Kirke, Peadar N; Caggana, Michele; Shane, Barry; Scott, John M; Brody, Lawrence C

2014-10-01

59

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

PubMed

A recent study from a research group from Quebec showed a strong decrease in the number of births affected by a neural tube defect since folic acid fortification was introduced in Canada. The prevalence decreased from 1.58 neural tube defects per 1000 births before the introduction of folic acid fortification to 0.86 per 1000 births in the period of complete fortification. Although folic acid fortification of staple food is probably the most effective way to decrease the incidence of neural tube defects, more knowledge about possible health risks should be obtained before fortification is introduced. More research is needed to determine which population groups are at risk of possible negative effects of folic acid fortification and at which level of fortification. Until then, it is important to generate more attention and publicity in order to increase awareness and knowledge concerning folic acid and to promote its use before and after conception. PMID:18320941

Brouwer, I A

2008-01-26

60

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

PubMed Central

Syndecan 4 (Sdc4) is a cell-surface heparan sulfate proteoglycan (HSPG) that regulates gastrulation, neural tube closure and directed neural crest migration in Xenopus development. To determine whether Sdc4 participates in Wnt/PCP signaling during mouse development, we evaluated a possible interaction between a null mutation of Sdc4 and the loop-tail allele of Vangl2. Sdc4 is expressed in multiple tissues, but particularly in the non-neural ectoderm, hindgut and otic vesicles. Sdc4;Vangl2Lp compound mutant mice have defective spinal neural tube closure, disrupted orientation of the stereocilia bundles in the cochlea and delayed wound healing, demonstrating a strong genetic interaction. In Xenopus, co-injection of suboptimal amounts of Sdc4 and Vangl2 morpholinos resulted in a significantly greater proportion of embryos with defective neural tube closure than each individual morpholino alone. To probe the mechanism of this interaction, we overexpressed or knocked down Vangl2 function in HEK293 cells. The Sdc4 and Vangl2 proteins colocalize, and Vangl2, particularly the Vangl2Lp mutant form, diminishes Sdc4 protein levels. Conversely, Vangl2 knockdown enhances Sdc4 protein levels. Overall HSPG steady-state levels were regulated by Vangl2, suggesting a molecular mechanism for the genetic interaction in which Vangl2Lp/+ enhances the Sdc4-null phenotype. This could be mediated via heparan sulfate residues, as Vangl2Lp/+ embryos fail to initiate neural tube closure and develop craniorachischisis (usually seen only in Vangl2Lp/Lp) when cultured in the presence of chlorate, a sulfation inhibitor. These results demonstrate that Sdc4 can participate in the Wnt/PCP pathway, unveiling its importance during neural tube closure in mammalian embryos. PMID:23760952

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

2013-01-01

61

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

2013-07-01

62

?-catenin regulates Pax3 and Cdx2 for caudal neural tube closure and elongation  

PubMed Central

Non-canonical Wnt/planar cell polarity (PCP) signaling plays a primary role in the convergent extension that drives neural tube closure and body axis elongation. PCP signaling gene mutations cause severe neural tube defects (NTDs). However, the role of canonical Wnt/?-catenin signaling in neural tube closure and NTDs remains poorly understood. This study shows that conditional gene targeting of ?-catenin in the dorsal neural folds of mouse embryos represses the expression of the homeobox-containing genes Pax3 and Cdx2 at the dorsal posterior neuropore (PNP), and subsequently diminishes the expression of the Wnt/?-catenin signaling target genes T, Tbx6 and Fgf8 at the tail bud, leading to spina bifida aperta, caudal axis bending and tail truncation. We demonstrate that Pax3 and Cdx2 are novel downstream targets of Wnt/?-catenin signaling. Transgenic activation of Pax3 cDNA can rescue the closure defect in the ?-catenin mutants, suggesting that Pax3 is a key downstream effector of ?-catenin signaling in the PNP closure process. Cdx2 is known to be crucial in posterior axis elongation and in neural tube closure. We found that Cdx2 expression is also repressed in the dorsal PNPs of Pax3-null embryos. However, the ectopically activated Pax3 in the ?-catenin mutants cannot restore Cdx2 mRNA in the dorsal PNP, suggesting that the presence of both ?-catenin and Pax3 is required for regional Cdx2 expression. Thus, ?-catenin signaling is required for caudal neural tube closure and elongation, acting through the transcriptional regulation of key target genes in the PNP. PMID:24284205

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

2014-01-01

63

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

64

Maternal fumonisin exposure as a risk factor for neural tube defects  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

65

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

66

Placental and neural tube defects after maternal fumonisin or FRY720 exposure  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

67

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

68

Spatial analysis of neural tube defects in a rural coal mining area  

Microsoft Academic Search

Shanxi province in northern China has one of the highest reported prevalence rates of neural tube defects (NTDs) in the world. The current study selected Heshun, the county with the highest rate of NTDs in Shanxi, as a study area and tested whether residence in a coal mining area was a contributing factor. A NTD cluster was detected in an

Yilan Liao; Jinfeng Wang; Jilei Wu; Luke Driskell; Wuyi Wang; Ting Zhang; Gu Xue; Xiaoying Zheng

2010-01-01

69

Neural networks for cost estimation of shell and tube heat exchangers  

Microsoft Academic Search

The objective of this paper is to develop and test a model of cost estimating for the shell and tube heat exchangers in the early design phase via the application of artiflcial neural networks (ANN). An ANN model can help the designers to make decisions at the early phases of the design process. With an ANN model, it is possible

Orlando Duran; Nibaldo Rodríguez; Luiz Airton Consalter

2009-01-01

70

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

71

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

PubMed

Exposure to environmental toxic chemicals in utero during the neural tube development period can cause developmental disorders. To evaluate the disruption of neural tube development programming, the murine neural tube defects (NTDs) model was induced by interrupting folate metabolism using methotrexate in our previous study. The present study aimed to examine the effects of dNTP deficiency induced by hydroxyurea (HU), a specific ribonucleotide reductase (RNR) inhibitor, during murine neural tube development. Pregnant C57BL/6J mice were intraperitoneally injected with various doses of HU on gestation day (GD) 7.5, and the embryos were checked on GD 11.5. RNR activity and deoxynucleoside triphosphate (dNTP) levels were measured in the optimal dose. Additionally, DNA damage was examined by comet analysis and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. Cellular behaviors in NTDs embryos were evaluated with phosphorylation of histone H3 (PH-3) and caspase-3 using immunohistochemistry and western blot analysis. The results showed that NTDs were observed mostly with HU treatment at an optimal dose of 225mg/kg b/w. RNR activity was inhibited and dNTP levels were decreased in HU-treated embryos with NTDs. Additionally, increased DNA damage, decreased proliferation, and increased caspase-3 were significant in NTDs embryos compared to the controls. Results indicated that HU induced murine NTDs model by disturbing dNTP metabolism and further led to the abnormal cell balance between proliferation and apoptosis. PMID:25527867

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

2015-02-01

72

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. PMID:24098141

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

2013-01-01

73

The emerging role of epigenetic mechanisms in the etiology of neural tube defects  

PubMed Central

The molecular requirements for neural tube closure are complex. This is illustrated by the occurrence of neural tube defects (NTDs) in many genetic mouse mutants, which implicate a variety of genes, pathways and cellular functions. NTDs are also prevalent birth defects in humans, affecting around 1 per 1,000 pregnancies worldwide. In humans the causation is thought to involve the interplay of fetal genes and the effect of environmental factors. Recent studies on the etiology of human NTDs, as well as analysis of mouse models, have raised the question of the possible involvement of epigenetic factors in determining susceptibility. A consideration of potential causative factors in human NTDs must now include both alterations in the regulation of gene expression, through mutation of promoter or regulatory elements and the additional analysis of epigenetic regulation. Alterations in the epigenetic status can be directly modified by various environmental insults or maternal dietary factors. PMID:21613818

Greene, Nicholas DE; Stanier, Philip

2011-01-01

74

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

75

The LIM domain-only protein LMO4 is required for neural tube closure.  

PubMed

Nuclear LIM domain-only proteins (LMOs), which consist of two closely spaced 50 amino acid Zn2+-finger protein interaction modules mediate interactions between several classes of transcription factors important for development. LMO2 is necessary for development of the entire hematopoietic system and overexpression of LMO1 or LMO2 results in human acute T cell leukemia. LMO4 is the most widely expressed LMO but its normal function is unknown. During development, LMO4 is expressed in dividing neuroepithelial cells within the ventricular zone along the entire rostrocaudal axis of the nervous system. In telencephalic and spinal cord regions of the CNS, LMO4 is highly expressed in ventral but is low in dorsal proliferating neuroepithelial cells. To understand the role of LMO4 during mouse development, we generated a homozygous null mutation in the gene. We found that LMO4 is required for proper closure of the anterior neural tube. In the absence of LMO4, elevation, bending, and proliferation of the ventral neural epithelium and consequent fusion of the prospective dorsal ends of the neural tube do not occur. LMO4 mutant mice die embryonically and exhibit exencephaly, which is associated with abnormal patterns of cell proliferation and with high levels of apoptotic cell death within the neuroepithelium. LMO4 is thus essential for normal patterns of proliferation and for survival of neural epithelial cells in the rostral neural tube. LMO4 is also expressed in Schwann cell progenitors after these contact neurites, a process mediated in part by neuregulin (Nrg). PMID:15691703

Lee, Soo-Kyung; Jurata, Linda W; Nowak, Roberta; Lettieri, Karen; Kenny, Daryn A; Pfaff, Samuel L; Gill, Gordon N

2005-02-01

76

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

PubMed

Neural tube defects (NTDs) are common congenital malformations. Mitogen-activated protein kinases (MAPKs) pathway is involved in many physiological processes. HMGB1 has been showed closely associated with neurulation and NTDs induced by hyperthermia and could activate MAPKs pathway. Since hyperthermia caused increased activation of MAPKs in many systems, the present study aims to investigate whether HMGB1 contributes to hyperthermia induced NTDs through MAPKs pathway. The mRNA levels of MAPKs and HMGB1 between embryonic day 8.5 and 10 (E8.5-10) in hyperthermia induced defective neural tube were detected by real-time quantitative polymerase chain reaction (qPCR). By immunofluorescence and western blotting, the expressions of HMGB1 and phosphorylated MAPKs (ERK1/2, JNK and p38) in neural tubes after hyperthermia were studied. The mRNA levels of MAPKs and HMGB1, as well as the expressions of HMGB1 along with phosphorylated JNK, p38 and ERK, were downregulated in NTDs groups induced by hyperthermia compared with control. The findings suggested that HMGB1 may contribute to hyperthermia induced NTDs formation through decreased cell proliferation due to inhibited phosphorylated ERK1/2 MAPK. PMID:25818329

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

2015-05-01

77

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

PubMed Central

DNA methylation is thought to be involved in the etiology of neural tube defects (NTDs). However, the exact mechanism between DNA methylation and NTDs remains unclear. Herein, we investigated the change of methylation in mouse model of NTDs associated with folate dysmetabolism by use of ultraperformance liquid chromatography tandem mass spectrometry (UPLC/MS/MS), liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS), microarray, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and Real time quantitative PCR. Results showed that NTD neural tube tissues had lower concentrations of 5-methyltetrahydrofolate (5-MeTHF, P = 0.005), 5-formyltetrahydrofolate (5-FoTHF, P = 0.040), S-adenosylmethionine (SAM, P = 0.004) and higher concentrations of folic acid (P = 0.041), homocysteine (Hcy, P = 0.006) and S-adenosylhomocysteine (SAH, P = 0.045) compared to control. Methylation levels of genomic DNA decreased significantly in the embryonic neural tube tissue of NTD samples. 132 differentially methylated regions (35 low methylated regions and 97 high methylated regions) were selected by microarray. Two genes (Siah1b, Prkx) in Wnt signal pathway demonstrated lower methylated regions (peak) and higher expression in NTDs (P<0.05; P<0.05). Results suggest that DNA hypomethylation was one of the possible epigenetic variations correlated with the occurrence of NTDs induced by folate dysmetabolism and that Siah1b, Prkx in Wnt pathway may be candidate genes for NTDs. PMID:25822193

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

2015-01-01

78

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

PubMed

Neural tube defects are congenital malformations that occur during initial fetal development, leading to anencephaly and spina bifida; folic acid deficiency is the most important risk factor identified to date. Brazil has one of the world's highest neural tube defect rates. Food consumption surveys among pregnant Brazilian women showed a high rate of inadequate folic acid intake (< 0.6 mg/day). In 2004, the National Health Surveillance Agency (ANVISA) mandated the fortification of corn meal and wheat flour with folic acid (0.15 mg/100g). The National Family Budget Survey estimated the average amount of bread/flour products available in households as 106.1g/day (contributing with 0.16 mg folic acid/day). However, while in the South of the country the supply was 144 g/day, in the North and Central West it barely reached 70 g/day. Folic acid food fortification is mandatory in some 40 countries, but only four have assessed this strategy. The existing studies have all shown a significant impact, ranging from 19 to 78%. Folic acid fortification is an undeniably important intervention for primary prevention, and neural tube defects can now be considered a preventable epidemic. PMID:17187100

Santos, Leonor Maria Pacheco; Pereira, Michelle Zanon

2007-01-01

79

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

PubMed Central

Summary We report an unexpected role for protease signaling in neural tube closure and formation of the central nervous system. Mouse embryos lacking protease-activated receptor 1 and 2 showed defective hindbrain and posterior neuropore closure and developed exencephaly and spina bifida, important human congenital anomalies. Par1 and Par2 were expressed in surface ectoderm, Par2 selectively along the line of closure. Ablation of Gi/z and Rac1 function in these Par2-expressing cells disrupted neural tube closure, further implicating G protein-coupled receptors and identifying a likely effector pathway. Cluster analysis of protease and Par2 expression patterns revealed a group of membrane-tethered proteases often co-expressed with Par2. Among these, matriptase activated Par2 with picomolar potency, and hepsin and prostasin activated matriptase. Together, our results suggest a role for protease-activated receptor signaling in neural tube closure and identify a local protease network that may trigger Par2 signaling and monitor and regulate epithelial integrity in this context. PMID:20152175

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

2009-01-01

80

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

PubMed Central

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

Liu, Zhizhen; Xie, Jun; Luo, Tian’e; Zhang, Tao; Zhao, Xia; Zhao, Hong; Li, Peizhen

2012-01-01

81

Association of the 677C-->T mutation on the methylenetetrahydrofolate reductase gene in Turkish patients with neural tube defects.  

PubMed

We report the analysis of the 677C-->T mutation on the 5, 10-methylenetetrahydrofolate reductase gene in Turkish controls and cases of neural tube defects. Mutation analysis of 91 patients with neural tube defects, 72 mothers, 63 fathers, and 93 healthy controls has been made by polymerase chain reaction and allele specific restriction digestion with Hinf I. We did not find a significant difference in the 677C-->T allele and genotype distribution among the patients with neural tube defects, their parents, and the control group. This result suggests that another mutation in the folate-related enzyme genes could be responsible for neural tube defects in Turkey. None of the mothers of patients with neural tube defects was advised to use folic acid as recommended to prevent neural tube defects. An immediate attempt to establish an education program for healthcare providers and women of childbearing age is crucial in Turkey. Furthermore, fortification of foods with folate would be a better approach. PMID:10190266

Boduro?lu, K; Alika?ifo?lu, M; Anar, B; Tunçbilek, E

1999-03-01

82

Sonic hedgehog induces the differentiation of ventral forebrain neurons: A common signal for ventral patterning within the neural tube  

Microsoft Academic Search

The vertebrate hedgehog-related gene Sonic hedge-hog (Shh) is expressed in ventral domains along the entire rostrocaudal length of the neural tube, including the forebrain. We show here that SHH induces the differentiation of ventral neuronal cell types in explants derived from prospective forebrain regions of the neural plate. Neurons induced in explants derived from both diencephalic and telencephalic levels of

J Ericson; J Muhr; M Placzek; T Lints; T. M Jessel; T Edlund

1995-01-01

83

FKBP8 cell-autonomously controls neural tube patterning through a Gli2- and Kif3a-dependent mechanism  

Microsoft Academic Search

Signaling by Sonic hedgehog (Shh) represents an important process by which many types of neural progenitor cells become properly organized along the dorsal–ventral axis of the vertebrate neural tube in a concentration-dependent manner. However, the mechanism by which Shh signals are transduced with high fidelity and the relationship between the Shh signaling pathway and other patterning systems remain unclear. Here

Ahryon Cho; Hyuk W. Ko; Jonathan T. Eggenschwiler

2008-01-01

84

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

85

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. PMID:23134640

2012-01-01

86

IS LOW IRON STATUS A RISK FACTOR FOR NEURAL TUBE DEFECTS?  

PubMed Central

Background Folic acid supplements can protect against neural tube defects (NTDs). Low folate and low vitamin B12 status may be maternal risk factors for having an NTD affected pregnancy. However, not all NTDs are preventable by having an adequate folate/ B12 status and other potentially modifiable factors may be involved. Folate and vitamin B12 status have important links to iron metabolism. Animal studies support an association between poor iron status and NTDs but human data are scarce. We examined the relevance of low iron status in a nested NTD case-control study of women within a pregnant population-based cohort. Methods Pregnant women were recruited between 1986 and 1990, when vitamin or iron supplementation in early pregnancy was rare. Blood samples, taken at an average of 14 weeks gestation, were used to measure ferritin and hemoglobin in 64 women during an NTD affected pregnancy and 207 women with unaffected pregnancies. Results No significant differences in maternal ferritin or hemoglobin concentrations were observed between NTD affected and non-affected pregnancies (case median ferritin 16.8?g/L and hemoglobin 12.4g/dL versus 15.4?g/L and 12.3g/dL in controls). As reported previously, red cell folate and vitamin B12 concentrations were significantly lower in cases. Furthermore, there was no significant association of iron status with type of NTD lesion (anencephaly or spina bifida) Conclusions We conclude that low maternal iron status during early pregnancy is not an independent risk factor for NTDs. Adding iron to folic acid for periconceptional use may improve iron status but is not likely to prevent NTDs. PMID:24535840

Molloy, Anne M; Einri, Caitriona Nic; Jain, Divyanshu; Laird, Eamon; Fan, Ruzong; Wang, Yifan; Shane, Barry; Brody, Lawrence C; Kirke, Peadar N; Mills, James L

2014-01-01

87

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

SciTech Connect

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

Hill, Denise S.; Wlodarczyk, Bogdan J. [Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, TX 77030 (United States); Mitchell, Laura E. [Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, TX 77030 (United States); Center for Environmental and Rural Health Texas A and M University, College Station, TX 77843 (United States); Finnell, Richard H. [Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, TX 77030 (United States); Interdisciplinary Faculty of Toxicology, Texas A and M University, College Station, TX 77843 (United States); Center for Environmental and Rural Health Texas A and M University, College Station, TX 77843 (United States)], E-mail: rfinnell@ibt.tamhsc.edu

2009-08-15

88

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. PMID:20122256

2010-01-01

89

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

PubMed Central

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

Lo, Annie; Polšek, Dora; Sidhu, Simrita

2014-01-01

90

Neurulation abnormalities secondary to altered gene expression in neural tube defect susceptible Splotch embryos.  

PubMed

The murine mutant Splotch (Sp) is a well-established model for studying neural tube closure defects. In the current investigation, the progression through neural tube closure (NTC) as well as the expression patterns of 12 developmentally regulated genes were examined in the neural tissue of wildtype (+/+), Splotch heterozygous (Sp/+), and Splotch homozygous (Sp/Sp) embryos during neurulation. The overall growth of the embryos, as measured by the number of somite pairs, did not differ significantly between the three genotypes at any of the collection time-points. There was, however, a significant delay in the progression through NTC for both the Sp/+ and Sp/Sp embryos. A univariate analysis on the expression of the 12 candidate genes (bcl-2, FBP-2, Hmx-2, Msx-3, N-cam, N-cad, noggin, p53, Pax-3, Shh, Wee-1, wnt-1) revealed that although 11 were statistically altered, across time or by genotype, there were no significant interactions between gestation age and genotype for any of these genes during NTC. However, a multivariate statistical analysis on the simultaneous expression of these genes revealed interactions at both gestation day (GD) 8:12 (day:hour) and 9:00 among Pax-3, N-cam, N-cad, bcl-2, p53, and Wee-1 that could potentially explain the aberrant NTC. The data from these studies suggest that a disruption in the genes that govern the cell cycle or extracellular matrices of the developing neural tube might play a critical role in the occurrence of the NTDs observed in Splotch embryos. PMID:9516748

Bennett, G D; An, J; Craig, J C; Gefrides, L A; Calvin, J A; Finnell, R H

1998-01-01

91

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

PubMed Central

Hox genes are classically ascribed to function in patterning the anterior-posterior axis of bilaterian animals; however, their role in directing molecular mechanisms underlying morphogenesis at the cellular level remains largely unstudied. We unveil a non-classical role for the zebrafish hoxb1b gene, which shares ancestral functions with mammalian Hoxa1, in controlling progenitor cell shape and oriented cell division during zebrafish anterior hindbrain neural tube morphogenesis. This is likely distinct from its role in cell fate acquisition and segment boundary formation. We show that, without affecting major components of apico-basal or planar cell polarity, Hoxb1b regulates mitotic spindle rotation during the oriented neural keel symmetric mitoses that are required for normal neural tube lumen formation in the zebrafish. This function correlates with a non-cell-autonomous requirement for Hoxb1b in regulating microtubule plus-end dynamics in progenitor cells in interphase. We propose that Hox genes can influence global tissue morphogenesis by control of microtubule dynamics in individual cells in vivo. PMID:24449840

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

2014-01-01

92

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

93

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. PMID:23462473

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

2013-01-01

94

Nitrosatable Drug Exposure During Early Pregnancy and Neural Tube Defects in Offspring  

PubMed Central

Nitrosatable drugs, such as secondary or tertiary amines and amides, form N-nitroso compounds in the presence of nitrite. Various N-nitroso compounds have been associated with neural tube defects in animal models. Using data from the National Birth Defects Prevention Study, the authors examined nitrosatable drug exposure 1 month before and 1 month after conception in 1,223 case mothers with neural tube defect-affected pregnancies and 6,807 control mothers who delivered babies without major congenital anomalies from 1997 to 2005. Nitrite intakes were estimated from mothers’ responses to a food frequency questionnaire. After adjustment for maternal race/ethnicity, educational level, and folic acid supplementation, case women were more likely than were control women to have taken tertiary amines (odds ratio = 1.60, 95% confidence interval (CI): 1.31, 1.95). This association was strongest with anencephalic births (odds ratio = 1.96, 95% CI: 1.40, 2.73); odds ratios associated with tertiary amines from the lowest tertile of nitrite intake to the highest tertile were 1.16 (95% CI: 0.59, 2.29), 2.19 (95% CI: 1.25, 3.86), and 2.51 (95% CI: 1.45, 4.37), respectively. Odds ratios for anencephaly with nitrosatable drug exposure were reduced among women who also took daily vitamin supplements that contained vitamin C. Prenatal exposure to nitrosatable drugs may increase the risk of neural tube defects, especially in conjunction with a mother’s higher dietary intake of nitrites, but vitamin C might modulate this association. PMID:22047825

Brender, Jean D.; Werler, Martha M.; Kelley, Katherine E.; Vuong, Ann M.; Shinde, Mayura U.; Zheng, Qi; Huber, John C.; Sharkey, Joseph R.; Griesenbeck, John S.; Romitti, Paul A.; Langlois, Peter H.; Suarez, Lucina; Canfield, Mark A.

2011-01-01

95

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

2011-02-01

96

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

PubMed Central

Systems Biology involves the study of the interactions of biological systems and ultimately their functions. Down's syndrome (DS) is one of the most common genetic disorders which are caused by complete, or occasionally partial, triplication of chromosome 21, characterized by cognitive and language dysfunction coupled with sensory and neuromotor deficits. Neural Tube Disorders (NTDs) are a group of congenital malformations of the central nervous system and neighboring structures related to defective neural tube closure during the first trimester of pregnancy usually occurring between days 18-29 of gestation. Several studies in the past have provided considerable evidence that abnormal folate and methyl metabolism are associated with onset of DS & NTDs. There is a possible common etiological pathway for both NTDs and Down's syndrome. But, various research studies over the years have indicated very little evidence for familial link between the two disorders. Our research aimed at the gene expression profiling of microarray datasets pertaining to the two disorders to identify genes whose expression levels are significantly altered in these conditions. The genes which were 1.5 fold unregulated and having a p-value <0.05 were filtered out and gene interaction network were constructed for both NTDs and DS. The top ranked dense clique for both the disorders were recognized and over representation analysis was carried out for each of the constituent genes. The comprehensive manual analysis of these genes yields a hypothetical understanding of the lack of familial link between DS and NTDs. There were no genes involved with folic acid present in the dense cliques. Only – CBL, EGFR genes were commonly present, which makes the allelic variants of these genes – good candidates for future studies regarding the familial link between DS and NTDs. Abbreviations NTD - Neural Tube Disorders, DS - Down's Syndrome, MTHFR - Methylenetetrahydrofolate reductase, MTRR– 5 - methyltetrahydrofolate-homocysteine methyltransferase reductase. PMID:23904737

Ragunath, PK; Abhinand, PA

2013-01-01

97

Ribonucleotide reductase subunit R1: a gene conferring sensitivity to valproic acid-induced neural tube defects in mice.  

PubMed

Neural tube defects (NTDs), although prevalent and easily diagnosed, are etiologically heterogeneous, rendering mechanistic interpretation problematic. To date, there is evidence that mammalian neural tube closure (NTC) initiates and fuses intermittently at four discrete locations. Disruption of this process at any of these four sites may lead to a region-specific NTDs, possibly arising through closure site-specific genetic mechanisms. Although recent efforts have focused on elucidating the genetic components of NTDs, a void persists regarding gene identification in closure site-specific neural tissue. To this end, experiments were conducted to identify neural tube closure site-specific genes that might confer regional sensitivity to teratogen-induced NTDs. Using an inbred mouse strain (SWV/Fnn) with a high susceptibility to VPA- induced NTDs that specifically targets and disrupts NTC between the prosencephalon and mesencephalon region (future fore/midbrain; neural tube closure site II), we identified a VPA-sensitive closure site II-specific clone. Sequencing of this clone from an SWV neural tube cDNA library confirmed that it encodes the r1 subunit of the cell cycle enzyme ribonucleotide reductase (RNR). The abundance of rnr-r1 mRNA was significantly increased in response to VPA drug treatment. This upregulated expression was accompanied by a significant decrease in cellular proliferation in the closure site II neural tube region of the embryos, as determined by ELISA cellular proliferation assays performed on BrdU-pulsed neuroepithelial cells in vivo. We hypothesize that rnr-r1 plays a critical role in the development of VPA-induced exencephaly. PMID:10716750

Craig, J C; Bennett, G D; Miranda, R C; Mackler, S A; Finnell, R H

2000-04-01

98

Detection of Copy Number Variants Reveals Association of Cilia Genes with Neural Tube Defects  

PubMed Central

Background Neural tube defects (NTDs) are one of the most common birth defects caused by a combination of genetic and environmental factors. Currently, little is known about the genetic basis of NTDs although up to 70% of human NTDs were reported to be attributed to genetic factors. Here we performed genome-wide copy number variants (CNVs) detection in a cohort of Chinese NTD patients in order to exam the potential role of CNVs in the pathogenesis of NTDs. Methods The genomic DNA from eighty-five NTD cases and seventy-five matched normal controls were subjected for whole genome CNVs analysis. Non-DGV (the Database of Genomic Variants) CNVs from each group were further analyzed for their associations with NTDs. Gene content in non-DGV CNVs as well as participating pathways were examined. Results Fifty-five and twenty-six non-DGV CNVs were detected in cases and controls respectively. Among them, forty and nineteen CNVs involve genes (genic CNV). Significantly more non-DGV CNVs and non-DGV genic CNVs were detected in NTD patients than in control (41.2% vs. 25.3%, p<0.05 and 37.6% vs. 20%, p<0.05). Non-DGV genic CNVs are associated with a 2.65-fold increased risk for NTDs (95% CI: 1.24–5.87). Interestingly, there are 41 cilia genes involved in non-DGV CNVs from NTD patients which is significantly enriched in cases compared with that in controls (24.7% vs. 9.3%, p<0.05), corresponding with a 3.19-fold increased risk for NTDs (95% CI: 1.27–8.01). Pathway analyses further suggested that two ciliogenesis pathways, tight junction and protein kinase A signaling, are top canonical pathways implicated in NTD-specific CNVs, and these two novel pathways interact with known NTD pathways. Conclusions Evidence from the genome-wide CNV study suggests that genic CNVs, particularly ciliogenic CNVs are associated with NTDs and two ciliogenesis pathways, tight junction and protein kinase A signaling, are potential pathways involved in NTD pathogenesis. PMID:23349908

Gao, Yonghui; Zhao, Huizhi; Sheng, Xiaoming; Zou, Jizhen; Lip, Va; Xie, Hua; Guo, Jin; Shao, Hong; Bao, Yihua; Shen, Jianliang; Niu, Bo; Gusella, James F.; Wu, Bai-Lin; Zhang, Ting

2013-01-01

99

Prevalence of neural tube defects in South Australia, 1966-91: effectiveness and impact of prenatal diagnosis.  

PubMed

The authors sought to determine trends in total prevalence of neural tube defects in South Australia during the period 1966 through 1991, the impact of prenatal diagnosis on birth prevalence, and the effectiveness of prenatal screening for neural tube defects during the period 1986 through 1991. The authors studied 1058 births and terminations of pregnancy affected by neural tube defects during 1966-1991. Data on births and terminations and information on prenatal screening came from the South Australian perinatal and abortion statistics collections, birth defects registers, and the state maternal serum alpha fetoprotein screening program. Main outcome measures of the study were total prevalence and birth prevalence of individual and all neural tube defects and the proportion of screened cases detected prenatally. Total prevalence of neural tube defects during the period 1066-1991 was 2.01/1000 births with no upward or downward trend. However, birth prevalence fell significantly (by 5.1% a year) with an 84% reduction from 2.29/1000 births in 1966 to 0.35/1000 in 1991 (relative risk = 0.16, 95% confidence interval 0.07-0.34). The fall was 96% for anencephaly and 82% for spina bifida. 85% of defects, both open and closed, were detected before 28 weeks gestation in women screened by serum alpha fetoprotein or midtrimester ultrasonography, or both, in 1986-1991 (99.0% for anencephaly and 75.7% for spina bifida). While the total prevalence of neural tube defects in South Australia remained stable, the prenatal diagnosis and termination of pregnancy resulted in an 84% fail in birth prevalence during 1966-1991. Screening detected over four-fifths of the cases during 1986-1991. PMID:8401091

Chan, A; Robertson, E F; Haan, E A; Keane, R J; Ranieri, E; Carney, A

1993-09-18

100

Applying Bayesian Neural Networks to Separate Neutrino Events from Backgrounds in Reactor Neutrino Experiments  

E-print Network

A toy detector has been designed to simulate central detectors in reactor neutrino experiments in the paper. The samples of neutrino events and three major backgrounds from the Monte-Carlo simulation of the toy detector are generated in the signal region. The Bayesian Neural Networks(BNN) are applied to separate neutrino events from backgrounds in reactor neutrino experiments. As a result, the most neutrino events and uncorrelated background events in the signal region can be identified with BNN, and the part events each of the fast neutron and $^{8}$He/$^{9}$Li backgrounds in the signal region can be identified with BNN. Then, the signal to noise ratio in the signal region is enhanced with BNN. The neutrino discrimination increases with the increase of the neutrino rate in the training sample. However, the background discriminations decrease with the decrease of the background rate in the training sample.

Ye Xu; Yixiong Meng; Weiwei Xu

2008-08-02

101

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

102

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

2013-01-01

103

Heat transfer analysis of phase change process in a finned-tube thermal energy storage system using artificial neural network  

Microsoft Academic Search

In this study, a feed-forward back-propagation artificial neural network (ANN) algorithm is proposed for heat transfer analysis of phase change process in a finned-tube, latent heat thermal energy storage system. Heat storage through phase change material (PCM) around the finned tube is experimentally studied. A numerical study is performed to investigate the effect of fin and flow parameter by the

Kemal Ermis; Aytunc Erek; Ibrahim Dincer

2007-01-01

104

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

105

Mutation of Celsr1 Disrupts Planar Polarity of Inner Ear Hair Cells and Causes Severe Neural Tube Defects in the Mouse  

Microsoft Academic Search

We identified two novel mouse mutants with abnormal head-shaking behavior and neural tube defects during the course of independent ENU mutagenesis experiments. The heterozygous and homozygous mutants exhibit defects in the orientation of sensory hair cells in the organ of Corti, indicating a defect in planar cell polarity. The homozygous mutants exhibit severe neural tube defects as a result of

John A. Curtin; Elizabeth Quint; Vicky Tsipouri; Ruth M. Arkell; Bruce Cattanach; Andrew J. Copp; Deborah J. Henderson; Nigel Spurr; Philip Stanier; Elizabeth M. Fisher; Patrick M. Nolan; Karen P. Steel; Steve D. M. Brown; Ian C. Gray; Jennifer N. Murdoch

2003-01-01

106

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

PubMed Central

A relatively small number of signals are responsible for the variety and pattern of cell types generated in developing embryos. In part this is achieved by exploiting differences in the concentration or duration of signaling to increase cellular diversity. In addition, however, changes in cellular competence—temporal shifts in the response of cells to a signal—contribute to the array of cell types generated. Here we investigate how these two mechanisms are combined in the vertebrate neural tube to increase the range of cell types and deliver spatial control over their location. We provide evidence that FGF signaling emanating from the posterior of the embryo controls a change in competence of neural progenitors to Shh and BMP, the two morphogens that are responsible for patterning the ventral and dorsal regions of the neural tube, respectively. Newly generated neural progenitors are exposed to FGF signaling, and this maintains the expression of the Nk1-class transcription factor Nkx1.2. Ventrally, this acts in combination with the Shh-induced transcription factor FoxA2 to specify floor plate cells and dorsally in combination with BMP signaling to induce neural crest cells. As development progresses, the intersection of FGF with BMP and Shh signals is interrupted by axis elongation, resulting in the loss of Nkx1.2 expression and allowing the induction of ventral and dorsal interneuron progenitors by Shh and BMP signaling to supervene. Hence a similar mechanism increases cell type diversity at both dorsal and ventral poles of the neural tube. Together these data reveal that tissue morphogenesis produces changes in the coincidence of signals acting along orthogonal axes of the neural tube and this is used to define spatial and temporal transitions in the competence of cells to interpret morphogen signaling. PMID:25026549

Sasai, Noriaki; Kutejova, Eva; Briscoe, James

2014-01-01

107

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

PubMed Central

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

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

2014-01-01

108

[Prevalence and spatial distribution of neural tube defects in São Paulo State, Brazil, before and after folic acid flour fortification].  

PubMed

This cross-sectional study analyzed the prevalence and spatial distribution of neural tube defects before and after folic acid flour fortification. The study used the Information System on Live Births (SINASC) and presented prevalence rates according to maternal characteristics with odds ratios (OR) and 95% confidence intervals (95%CI). Polynomial regression was used in time trend analysis and empirical Bayesian smoothed maps for spatial analysis. Total prevalence of neural tube defects decreased by 35%, from 0.57/1,000 to 0.37/1,000 live births after fortification (OR = 0.65; 95%CI: 0.59-0.72). There was a reduction among newborns of mothers with the following characteristics: all age groups (except < 15 years), more than three years of schooling, and seven or more prenatal visits. There was a reduction over time and in most of São Paulo State, except in a few municipalities (counties) located in the western region of the State. Other factors may have contributed to the observed decline, but the results corroborate flour fortification as an important measure to prevent neural tube defects. Further research is needed to elucidate the lack of a decline in neural tube defects in the western part of São Paulo State. PMID:23370034

Fujimori, Elizabeth; Baldino, Camila Florido; Sato, Ana Paula Sayuri; Borges, Ana Luiza Vilela; Gomes, Murilo Novaes

2013-01-01

109

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

110

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

111

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

112

Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD1 mice  

Microsoft Academic Search

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

Jennifer E. Dawson; Angela M. Raymond; Louise M.. Winn

2006-01-01

113

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

114

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

ERIC Educational Resources Information Center

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

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

2011-01-01

115

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

Technology Transfer Automated Retrieval System (TEKTRAN)

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides that is found in corn-based foods and is possibly a risk factor for neural tube defects (NTD). The mechanism(s) underlying NTD induction by FB1 in the sensitive LM/Bc mouse model is not well understood, however, there is evidenc...

116

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 ...

117

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 ...

118

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

119

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...

120

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

PubMed Central

ABSTRACT Neural tube closure is a critical developmental event that relies on actomyosin contractility to facilitate specific processes such as apical constriction, tissue bending, and directional cell rearrangements. These complicated processes require the coordinated activities of Rho-Kinase (Rock), to regulate cytoskeletal dynamics and actomyosin contractility, and the Planar Cell Polarity (PCP) pathway, to direct the polarized cellular behaviors that drive convergent extension (CE) movements. Here we investigate the role of Shroom3 as a direct linker between PCP and actomyosin contractility during mouse neural tube morphogenesis. In embryos, simultaneous depletion of Shroom3 and the PCP components Vangl2 or Wnt5a results in an increased liability to NTDs and CE failure. We further show that these pathways intersect at Dishevelled, as Shroom3 and Dishevelled 2 co-distribute and form a physical complex in cells. We observed that multiple components of the Shroom3 pathway are planar polarized along mediolateral cell junctions in the neural plate of E8.5 embryos in a Shroom3 and PCP-dependent manner. Finally, we demonstrate that Shroom3 mutant embryos exhibit defects in planar cell arrangement during neural tube closure, suggesting a role for Shroom3 activity in CE. These findings support a model in which the Shroom3 and PCP pathways interact to control CE and polarized bending of the neural plate and provide a clear illustration of the complex genetic basis of NTDs. PMID:25596276

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

2015-01-01

121

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

PubMed

Fetuses with neural tube defects (NTDs) may be associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization ( Ds )-like human malformations, isolated hemihyperplasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling. PMID:18400576

Chen, Chih-Ping

2008-03-01

122

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

PubMed Central

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

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

1991-01-01

123

Valproic acid-induced neural tube defects: reduction by folinic acid in the mouse.  

PubMed

Neural tube defects were induced dose-dependently by single injections of the anticonvulsant drug valproic acid (VPA) as sodium salt in mice on gestational day 8. Folinic acid (5-CHO-THF) coadministration by i.p. injection or by a constant rate infusion via osmotic minipumps, implanted s.c., significantly reduced the exencephaly rates using a randomized double-blind experimental procedure. 5-CHO-THF supplementation cut the exencephaly rates into half even at high maternal plasma levels of VPA (p less than 0.005, chi 2-test); resorption rates were not affected. The VPA plasma kinetics were not changed by any of the application regimens of 5-CHO-THF. The investigation of the folate metabolite pattern (determined by HPLC) showed that 5-CHO-THF and 5-methyl-tetrahydrofolic acid (5-CH3-THF) were the main metabolites in untreated mice. After supplementation with 5-CHO-THF, only the concentrations of this folate vitamer were increased in the plasma from 0.3 microgram/ml (normal) to 0.6 or 1.9 micrograms/ml (after injection of 3 x 1 mg/kg or 3 X 4 mg/kg) and to 4.2 micrograms/ml (after infusion via osmotic minipumps). Our results indicate that VPA-induced exencephaly in mice combined with the investigation of the plasma levels of VPA and the different folate metabolites could be an appropriate animal model to study protective effects of folates on the occurrence of neural tube defects. PMID:3110521

Trotz, M; Wegner, C; Nau, H

1987-07-01

124

Genetic Association Analyses of Nitric Oxide Synthase Genes and Neural Tube Defects Vary by Phenotype  

PubMed Central

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

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

2014-01-01

125

Neural tube defects in costa rica, 1987-2012: origins and development of birth defect surveillance and folic Acid fortification.  

PubMed

Our aim was to provide a descriptive overview of how the birth defects surveillance and folic acid fortification programs were implemented in Costa Rica-through the establishment of the Registry Center for Congenital Anomalies (Centro de Registro de Enfermedades Congénitas-CREC), and fortification legislation mandates. We estimated the overall prevalence of neural tube defects (i.e., spina bifida, anencephaly and encephalocele) before and after fortification captured by CREC. Prevalence was calculated by dividing the total number of infants born with neural tube defects by the total number of live births in the country (1987-2012).A total of 1,170 newborns with neural tube defects were identified from 1987 to 2012 (1992-1995 data excluded); 628 were identified during the baseline pre-fortification period (1987-1991; 1996-1998); 191 during the fortification period (1999-2002); and 351 during the post-fortification time period (2003-2012). The overall prevalence of neural tube defects decreased from 9.8 per 10,000 live-births (95 % CI 9.1-10.5) for the pre-fortification period to 4.8 per 10,000 live births (95 % CI 4.3-5.3) for the post-fortification period. Results indicate a statistically significant (P < 0.05) decrease of 51 % in the prevalence of neural tube defects from the pre-fortification period to the post-fortification period. Folic acid fortification via several basic food sources has shown to be a successful public health intervention for Costa Rica. Costa Rica's experience can serve as an example for other countries seeking to develop and strengthen both their birth defects surveillance and fortification programs. PMID:24952876

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

2015-03-01

126

Lack of endothelial cell survivin causes embryonic defects in angiogenesis, cardiogenesis, and neural tube closure  

PubMed Central

We explored the physiologic role of endothelial cell apoptosis during development by generating mouse embryos lacking the inhibitor of apoptosis protein (IAP) survivin in endothelium. This was accomplished by intercrossing survivinlox/lox mice with mice expressing cre recombinase under the control of the endothelial cell specific tie1 promoter (tie1-cre mice). Lack of endothelial cell survivin resulted in embryonic lethality. Mutant embryos had prominent and diffuse hemorrhages from embryonic day 9.5 (E9.5) and died before E13.5. Heart development was strikingly abnormal. Survivin-null endocardial lineage cells could not support normal epithelial-mesenchymal transformation (EMT), resulting in hypoplastic endocardial cushions and in utero heart failure. In addition, 30% of mutant embryos had neural tube closure defects (NTDs) that were not caused by bleeding or growth retardation, but were likely due to alterations in the release of soluble factors from endothelial cells that otherwise support neural stem cell proliferation and neurulation. Thus, regulation of endothelial cell survival, and maintenance of vascular integrity by survivin are crucial for normal embryonic angiogenesis, cardiogenesis, and neurogenesis. PMID:17299096

Zwerts, Femke; Lupu, Florea; De Vriese, Astrid; Pollefeyt, Saskia; Moons, Lieve; Altura, Rachel A.; Jiang, Yuying; Maxwell, Patrick H.; Hill, Peter; Oh, Hideyasu; Rieker, Claus; Collen, Désiré; Conway, Simon J.

2007-01-01

127

Improving Application of Bayesian Neural Networks to Discriminate Neutrino Events from Backgrounds in Reactor Neutrino Experiments  

E-print Network

The application of Bayesian Neural Networks(BNN) to discriminate neutrino events from backgrounds in reactor neutrino experiments has been described in Ref.\\cite{key-1}. In the paper, BNN are also used to identify neutrino events in reactor neutrino experiments, but the numbers of photoelectrons received by PMTs are used as inputs to BNN in the paper, not the reconstructed energy and position of events. The samples of neutrino events and three major backgrounds from the Monte-Carlo simulation of a toy detector are generated in the signal region. Compared to the BNN method in Ref.\\cite{key-1}, more $^{8}$He/$^{9}$Li background and uncorrelated background in the signal region can be rejected by the BNN method in the paper, but more fast neutron background events in the signal region are unidentified using the BNN method in the paper. The uncorrelated background to signal ratio and the $^{8}$He/$^{9}$Li background to signal ratio are significantly improved using the BNN method in the paper in comparison with the BNN method in Ref.\\cite{key-1}. But the fast neutron background to signal ratio in the signal region is a bit larger than the one in Ref.\\cite{key-1}.

Ye Xu; WeiWei Xu; YiXiong Meng; Bin Wu

2009-01-12

128

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

NASA Astrophysics Data System (ADS)

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

Mekras, N.; Artemakis, I.

2012-09-01

129

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

PubMed

Genetic studies have established that heparan sulphate proteoglycans (HSPGs) are required for signalling by key developmental regulators, including Hedgehog, Wnt/Wg, FGF, and BMP/Dpp. Post-synthetic remodelling of heparan sulphate (HS) by Sulf1 has been shown to modulate these same signalling pathways. Sulf1 codes for an N-acetylglucosamine 6-O-endosulfatase, an enzyme that specifically removes the 6-O sulphate group from glucosamine in highly sulfated regions of HS chains. One striking aspect of Sulf1 expression in all vertebrates is its co-localisation with that of Sonic hedgehog in the floor plate of the neural tube. We show here that Sulf1 is required for normal specification of neural progenitors in the ventral neural tube, a process known to require a gradient of Shh activity. We use single-cell injection of mRNA coding for GFP-tagged Shh in early Xenopus embryos and find that Sulf1 restricts ligand diffusion. Moreover, we find that the endogenous distribution of Shh protein in Sulf1 knockdown embryos is altered, where a less steep ventral to dorsal gradient forms in the absence of Sulf1, resulting in more a diffuse distribution of Shh. These data point to an important role for Sulf1 in the ventral neural tube, and suggests a mechanism whereby Sulf1 activity shapes the Shh morphogen gradient by promoting ventral accumulation of high levels of Shh protein. PMID:24768893

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

2014-07-15

130

Cell migration into neural tube lumen provides evidence for the "fixed cortex" theory of cell motility.  

PubMed

We present a model of cell motility based on emigration of neural crest cells into the neural tube lumen under in vitro conditions (10% fetal calf serum or YIGSR) that inhibit their normal emigration from the base of the neuroepithelium into surrounding extracellular matrix (ECM). Ultrastructural observations reveal that cells lining the lumen are joined by zonulae adherentes (ZA), which are points of strong intercellular attachment, and thereby serve as markers for fixed regions of plasmalemma and cortical actin. Three major observations of the relationship of cells to the ZA support the "fixed cortex" model of mesenchymal cell migration. First, cells extend apical cell processes past the ZA into the lumen. To do this, they must make new apical plasmalemma and actin cortex that the endoplasm slides into. Second, elongated cells are observed in the lumen that are still attached via ZA to the neuroepithelium. This indicates that all of the endoplasm finally slides past the ZA. Third, numerous cytoplasmic pieces, often attached to each other and to the neuroepithelium via ZA, are found at the site where cells appear to have detached from the epithelium after entering the lumen. Since the ZA is fixed in location, the endoplasm must have slid past it into newly manufactured anterior cortex and plasmalemma, with the trailing end of the cell finally snapping off. The "fixed cortex" theory of cell migration agrees with existing data in that it predicts the polarized insertion of new plasmalemma and actin at the leading end of the cell, but it differs significantly from existing theories of mesenchymal cell migration in that it states that the cell surface remains firmly attached to the substratum while the myosin-rich endoplasm slides past it. PMID:2624941

Bilozur, M E; Hay, E D

1989-01-01

131

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

PubMed Central

Low-density lipoprotein receptor related protein 6 (Lrp6) mutational effects on neurulation were examined using gain (Crooked tail, Lrp6Cd) 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 Lrp6Cd/Cd neural tube. Lrp6?/? embryos showed reduced proliferation and subtle patterning changes in the neural folds. Cell polarity defects in both Lrp6Cd/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 Lrp6Cd/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 Lrp6Cd/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 Lrp6Cd 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

2013-01-01

132

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

PubMed

Geminin is a nucleoprotein that can directly bind chromatin regulatory complexes to modulate gene expression during development. Geminin knockout mouse embryos are preimplantation lethal by the 32-cell stage, precluding in vivo study of Geminin's role in neural development. Therefore, here we used a conditional Geminin allele in combination with several Cre-driver lines to define an essential role for Geminin during mammalian neural tube (NT) formation and patterning. Geminin was required in the NT within a critical developmental time window (embryonic day 8.5-10.5), when NT patterning and closure occurs. Geminin excision at these stages resulted in strongly diminished expression of genes that mark and promote dorsal NT identities and decreased differentiation of ventral motor neurons, resulting in completely penetrant NT defects, while excision after embryonic day 10.5 did not result in NT defects. When Geminin was deleted specifically in the spinal NT, both NT defects and axial skeleton defects were observed, but neither defect occurred when Geminin was excised in paraxial mesenchyme, indicating a tissue autonomous requirement for Geminin in developing neuroectoderm. Despite a potential role for Geminin in cell cycle control, we found no evidence of proliferation defects or altered apoptosis. Comparisons of gene expression in the NT of Geminin mutant versus wild-type siblings at embryonic day 10.5 revealed decreased expression of key regulators of neurogenesis, including neurogenic bHLH transcription factors and dorsal interneuron progenitor markers. Together, these data demonstrate a requirement for Geminin for NT patterning and neuronal differentiation during mammalian neurulation in vivo. PMID:24995796

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

2014-09-01

133

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

PubMed Central

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

Mainetti, Matteo; Ascoli, Giorgio A.

2015-01-01

134

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

PubMed

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

Mainetti, Matteo; Ascoli, Giorgio A

2015-03-01

135

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

PubMed

The planar cell polarity (PCP) pathway controls the process of convergent extension (CE) during gastrulation and neural tube closure, and has been implicated in the pathogenesis of neural tube defects (NTDs) in animal models and human cohorts. In this study, we analyzed the role of one core PCP gene PRICKLE1 in these malformations. We screened this gene in 810 unrelated NTD patients and identified seven rare missense heterozygous mutations that were absent in all controls analyzed and predicted to be functionally deleterious using bioinformatics. Functional validation of five PRICKLE1 variants in a zebrafish model demonstrated that one variant, p.Arg682Cys, antagonized the CE phenotype induced by the wild-type zebrafish prickle1a (zpk1a) in a dominant fashion. Our study demonstrates that PRICKLE1 could act as a predisposing factor to human NTDs and further expands our knowledge of the role of PCP genes in the pathogenesis of these malformations. PMID:21901791

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

2011-12-01

136

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

PubMed Central

Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin’s statement: “An ounce of prevention is better than a pound of care”. PMID:24284617

Czeizel, Andrew E.; Dudás, Istvan; Vereczkey, Attila; Bánhidy, Ferenc

2013-01-01

137

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. PMID:9012820

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

1997-01-01

138

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

139

In ovo electroporation of miRNA-based-plasmids to investigate gene function in the developing neural tube.  

PubMed

When studying gene function in vivo during development, gene expression has to be controlled in a precise temporal and spatial manner. Technologies based on RNA interference (RNAi) are well suited for such studies, as they allow for the efficient silencing of a gene of interest. In contrast to challenging and laborious approaches in mammalian systems, the use of RNAi in combination with oviparous animal models allows temporal control of gene silencing in a fast and precise manner. We have developed approaches using RNAi in the chicken embryo to analyze gene function during neural tube development. Here we describe the construction of plasmids that direct the expression of one or two artificial microRNAs (miRNAs) to knock down expression of endogenous protein/s of interest upon electroporation into the spinal cord. The miRNA cassette is directly linked to a fluorescent protein reporter, for the direct visualization of transfected cells. The transcripts are under the control of different promoters/enhancers which drive expression in genetically defined cell subpopulations in the neural tube. Mixing multiple RNAi vectors allows combinatorial knockdowns of two or more genes in different cell types of the spinal cord, thus permitting the analysis of complex cellular and molecular interactions in a fast and precise manner. The technique that we describe can easily be applied to other cell types in the neural tube, or even adapted to other organisms in developmental studies. PMID:24233790

Andermatt, Irwin; Wilson, Nicole; Stoeckli, Esther T

2014-01-01

140

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

PubMed Central

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

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

2014-01-01

141

Agenesis of the corpus callosum associated with spinal open neural tube defect  

PubMed Central

Objective: To ascertain the incidence and clinical implications of agenesis of the corpus callosum (ACC) in spinal open neural tube defects (SONTD). Methods: All cases of SONTD registered at the Spina Bifida Clinic in King Khalid University Hospital, Riyadh, Saudi Arabia between 1995 and 2010 were retrospectively reviewed, and mid-sagittal MRI of the corpus callosum (CC) area was analyzed in each case. Neurodevelopmental outcome was classified as poor in children with seizures, severe neurodevelopmental impairment, or death. Results: Thirty-eight patients (45.8%) with ACC were identified among 83 cases with SONTD. Patients’ age ranged between one and 16 years. Total ACC was found in 10 patients, partial ACC in 25, and in 3 patients, the CC was hypoplastic. Active hydrocephalus was an associated finding in 9 out of 10 patients with total ACC, 22 out of 25 with partial ACC, and in all patients with hypoplasia of the CC. Thirteen patients (34.2%) had normal intellectual function, whereas 24 patients presented with learning disability, epilepsy, or poor intellectual function; and one patient died of respiratory failure. Conclusion: Agenesis of the corpus callosum is found in a significant portion of patients with SONTD. When associated with hydrocephalus, its presence affects neuro-developmental outcome. PMID:25551114

Elgamal, Essam A.; Elwatidy, Sherif M.; Alhabib, Amro F.; Jamjoom, Zain B.; Murshid, Waleed R.; Hassan, Hamdy H.; Salih, Mustafa A.

2014-01-01

142

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

143

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

PubMed

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

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

2015-01-01

144

Association of SMO polymorphisms and neural tube defects in the Chinese population from Shanxi Province  

PubMed Central

Objective: This study aimed to investigate the single nucleotide polymorphisms (SNPs) of SMO and neural tube defects (NTDs) in Chinese population. Method: A total of 113 NTDs cases and 138 healthy controls were used in this study. 10 selected single nucleotide polymorphism (SNP) sites in the SMO gene were analyzed with MassArray high-throughput DNA analyzer with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. A series of statistical methods were carried out to investigate the correlation between the SNPs and the patient susceptibility to NTDs. Results: The C allele of rs3824 increased the risk of spina bifida (OR=2.52; 95% CI: 1.18, 5.38; p=0.026) but not the risk of anencephaly or encephalocele. Significant differences were found between spina bifida and controls when we compared the GG group with the CC+CG group (OR=2.66; 95% CI: 1.26, 5.61; p=0.011). CC+CG genotype was a risk factor for spina bifida. Conclusions: The gene polymorphism loci rs3824 of SMO was closely related to spina bifida in Chinese population from Shanxi. The haplotype GA in rs3824 and rs9706 increased the risk of NTDs particularly spina bifida in women. PMID:24260604

Wang, Zhen; Shangguan, Shaofang; Lu, Xiaolin; Chang, Shaoyan; Li, Rui; Wu, Lihua; Bao, Yihua; Niu, Bo; Wang, Li; Zhang, Ting

2013-01-01

145

Orally Administered Melatonin Prevents Lipopolysaccharide-Induced Neural Tube Defects in Mice  

PubMed Central

Lipopolysaccharide (LPS) has been associated with adverse pregnant outcomes, including fetal demise, intra-uterine growth restriction (IUGR), neural tube defects (NTDs) and preterm delivery in rodent animals. Previous studies demonstrated that melatonin protected against LPS-induced fetal demise, IUGR and preterm delivery. The aim of the present study was to investigate the effects of melatonin on LPS-induced NTDs. All pregnant mice except controls were intraperitoneally injected with LPS (25 µg/kg) daily from gestational day (GD)8 to GD12. Some pregnant mice were orally administered with melatonin (MT, 50 mg/kg) before each LPS injection. A five-day LPS injection resulted in 27.5% of fetuses with anencephaly, exencephaly or encephalomeningocele. Additional experiment showed that maternal LPS exposure significantly down-regulated placental proton-coupled folate transporter (pcft) and disturbed folate transport from maternal circulation through the placentas into the fetus. Interestingly, melatonin significantly attenuated LPS-induced down-regulation of placental pcft. Moreover, melatonin markedly improved the transport of folate from maternal circulation through the placentas into the fetus. Correspondingly, orally administered melatonin reduced the incidence of LPS-induced anencephaly, exencephaly or encephalomeningocele. Taken together, these results suggest that orally administered melatonin prevents LPS-induced NTDs through alleviating LPS-induced disturbance of folate transport from maternal circulation through the placenta into the fetus. PMID:25420102

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

2014-01-01

146

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

SciTech Connect

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

Parlos, A.G.; Chong, K.T. (Texas A and M Univ., College Station (United States)); Atiya, A. (Dynamica, Inc., Houston, TX (United States))

1992-01-01

147

Chronic sorrow and depression in parents of children with neural tube defects.  

PubMed

Chronic sorrow has been described in the caregivers of individuals with myelomeningocele, multiple sclerosis, Parkinson's disease, cancer, and premature infants. Most studies have reported small numbers of fathers for comparison with mothers. One unpublished study compared chronic sorrow and depression. The purpose of the current study was to describe parental chronic sorrow following the birth of a child with neural tube defect and to explore the relationship between chronic sorrow and depression. One hundred and thirty-two parents (63 mother/father pairs and 6 single parents) responded to 3 measures of chronic sorrow and 1 measure of depression. Multivariate analysis of variance demonstrated significant differences between mothers and fathers in chronic sorrow. In addition, a relationship between chronic sorrow and depression was demonstrated. Chronic sorrow is a potential barrier to parental understanding of their child's care and diagnosis. Based on these findings, separate assessments of each parent and timely interventions are warranted. Further research should include more than 1 measure of chronic sorrow and delineate the dimensions being measured. PMID:15115362

Hobdell, Elizabeth

2004-04-01

148

Novel VANGL1 Gene Mutations in 144 Slovakian, Romanian and German Patients with Neural Tube Defects.  

PubMed

Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system occurring at an average rate of 1 per 1,000 human pregnancies worldwide. Numerous genetic and environmental factors are discussed to be relevant in their etiology. In mice, mutants in >200 genes including the planar cell polarity (PCP) pathway are known to cause NTDs, and recently, heterozygous mutations in the human VANGL1 gene have been described in a small subset of patients with NTDs. We performed a VANGL1 mutation analysis in 144 unrelated individuals with NTDs from Slovakia, Romania and Germany and identified 3 heterozygous missense mutations: c.613G>A (p.Gly205Arg) with an open spina bifida (lumbosacral meningomyelocele), c.557G>A (p.Arg186His) with a closed spina bifida (tethered cord and spinal lipoma) and c.518G>A (p.Arg173His) with an unknown NTD. The c.613G>A mutation was also found in a healthy sibling. None of the mutations were described previously. Findings support that heterozygous VANGL1 mutations represent hypomorphs or conditional mutants predisposing to NTDs and occur at a frequency of approximately 2.1% of open and closed spinal NTDs. The mutations (p.Arg173His, p.Arg186His, p.Gly205Arg) modified conserved regions of the VANGL1 protein and shared similarities with previously described mutants, providing further evidence for the presence of mutational hot spots in these patients. PMID:23326252

Bartsch, O; Kirmes, I; Thiede, A; Lechno, S; Gocan, H; Florian, I S; Haaf, T; Zechner, U; Sabova, L; Horn, F

2012-08-01

149

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

PubMed Central

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

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

2015-01-01

150

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

PubMed

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

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

2015-04-01

151

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

PubMed Central

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

2014-01-01

152

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

PubMed Central

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

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

2015-01-01

153

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

PubMed

Recently, the association between methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G1958A polymorphism and neural tube defects (NTD) susceptibility has been widely investigated; however, the results remained inconclusive. Hence, we conducted a meta-analysis to evaluate the effect of MTHFD1 G1958A polymorphism on NTD. The relative literatures were identified by search of the electronic databases PubMed, MEDLINE, and EMBASE. The extracted data were statistically analyzed, and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the association strength using Stata version 11.0 software. Finally, ten studies met our inclusion criteria, including 2,132/4,082 in NTD infants and controls; 1,402/3,136 in mothers with NTD offspring and controls; and 993/2,879 in fathers with NTD offspring and controls. This meta-analysis showed that, compared with the mothers with GG genotype, the women with AA genotype had an increased risk of NTD in their offspring, with OR values and 95 % CI at 1.39 (1.16-1.68), p < 0.001. Interestingly, fathers with AG genotype had a significant decreased risk of NTD offspring (OR = 0.79, 95 % CI = 0.66-0.94, p = 0.009). However, there was no significant association between the MTHFD1 G1958A polymorphism in NTD patients and the risk of NTD. In conclusion, the present meta-analysis provided evidence of the association between maternal MTHFD1 G1958A polymorphism and NTD susceptibility. PMID:25502174

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

2015-04-01

154

Molecular and cellular mechanisms underlying neural tube defects in the loop-tail mutant mouse.  

PubMed

Loop-tail (Lp) mice show a very severe neural tube defect (craniorachischisis) caused by mutations in the Vangl2 gene (D255E, S464N). Mammalian Vangl1 and Vangl2 are membrane proteins that play critical roles in development such as establishment of planar cell polarity (PCP) in epithelial layers and convergent extension movements during neurogenesis and cardiogenesis. Vangl proteins are thought to assemble with other PCP proteins (Dvl, Pk) to form membrane-bound PCP signaling complexes that provide polarity information to the cell. In the present study, we show that Vangl1 is expressed exclusively at the plasma membrane of transfected MDCK cells, where it is targeted to the basolateral membrane. Experiments with an inserted exofacial HA epitope indicate that the segment delimited by the predicted transmembrane domains 1 and 2 is exposed to the extracellular milieu. Comparative studies of the Lp-associated pathogenic mutation D255E indicate that the targeting of the mutant variant at the plasma membrane is greatly reduced; the mutant variant is predominantly retained intracellularly in endoplasmic reticulum (ER) vesicles colocalizing with the ER marker calreticulin. In addition, the D255E variant shows drastically reduced stability with a half-life of approximately 2 h, compared to >9 h for its wild type counterpart and is rapidly degraded in a proteasome-dependent and MG132 sensitive pathway. These findings highlight a critical role for D255 for normal folding and processing of Vangl proteins, with highly conservative substitutions not tolerated at that site. Our study provide an experimental framework for the analysis of human VANGL mutations recently identified in familial and sporadic cases of spina bifida. PMID:20329788

Gravel, Michel; Iliescu, Alexandra; Horth, Cynthia; Apuzzo, Sergio; Gros, Philippe

2010-04-27

155

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. PMID:21768370

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

2011-01-01

156

Homocysteine remethylation enzyme polymorphisms and increased risks for neural tube defects.  

PubMed

Folic acid supplementation can effectively reduce the risk of neural tube defects (NTDs); however, the mechanism underlying this beneficial effect remains unclear. Recent evidence suggests that certain folate pathway genes, as well as those related to homocysteine metabolism might be contributing to this effect. The purpose of this study is to investigate whether gene polymorphisms of methionine synthase (MTR) and methionine synthase reductase (MTRR) are involved in the risk for NTDs, specifically spina bifida. We detected MTR A2756G and MTRR A66G polymorphisms using PCR-RFLP analysis in a group of NTD infants, their mothers and normal controls. We found that infants with the MTRR mutant genotype had a 2.6-fold higher risk of NTDs when compared to the AA genotype (OR = 2.6, 95%CI = 1.3-5.3). Mothers with the MTRR mutant genotype also had a 1.9-fold higher risk of having an NTD baby compared to AA genotype (OR = 1.9, 95%CI = 1.1-3.1). Infants who carry mutant alleles for both MTRR and MTR had exceptionally elevated NTD risks, with odds ratios of 5.1 compared to infants with the wild type genotype at both loci (AA + AA) (OR = 5.1, 95%CI = 1.7-15.4). A comparable result was observed in the mothers of NTD cases (OR = 2.1, 95%CI = 1.0-4.7). Our results indicate that MTRR and MTR genes may interact to increase the infants' NTD risks. These results did not appear to be influenced by maternal periconceptional folic acid intake. However,the sample size of this study was limited, and a larger population study is needed to pursue these initial observations. PMID:12649067

Zhu, Huiping; Wicker, Ned J; Shaw, Gary M; Lammer, Edward J; Hendricks, Kate; Suarez, Lucina; Canfield, Mark; Finnell, Richard H

2003-03-01

157

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

PubMed Central

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

Liu, Zhenjiang; Yuan, Zhengwei; Zhao, Qun

2014-01-01

158

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

PubMed

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

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

2015-01-01

159

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. PMID:24015369

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

2013-01-01

160

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

PubMed

Fumonisins are mycotoxins produced by the fungus F. verticillioides, a common contaminant of maize (corn) worldwide. Maternal consumption of fumonisin B(1)-contaminated maize during early pregnancy has recently been associated with increased risk for neural tube defects (NTDs) in human populations that rely heavily on maize as a dietary staple. Experimental administration of purified fumonisin to mice early in gestation also results in an increased incidence of NTDs in exposed offspring. Fumonisin inhibits the enzyme ceramide synthase in de novo sphingolipid biosynthesis, resulting in an elevation of free sphingoid bases and depletion of downstream glycosphingolipids. Increased sphingoid base metabolites (i.e., sphinganine-1-phosphate) may perturb signaling cascades involved in embryonic morphogenesis by functioning as ligands for sphingosine-1-P (S1P) receptors, a family of G-protein-coupled receptors that regulate key biological processes such as cell survival/proliferation, differentiation and migration. Fumonisin-induced depletion of glycosphingolipids impairs expression and function of the GPI-anchored folate receptor (Folr1), which may also contribute to adverse pregnancy outcomes. NTDs appear to be multifactorial in origin, involving complex gene-nutrient-environment interactions. Vitamin supplements containing folic acid have been shown to reduce the occurrence of NTDs, and may help protect the developing fetus from environmental teratogens. Fumonisins appear to be an environmental risk factor for birth defects, although other aspects of maternal nutrition and genetics play interactive roles in determining pregnancy outcome. Minimizing exposures to mycotoxins through enhanced agricultural practices, identifying biomarkers of exposure, characterizing mechanisms of toxicity, and improving maternal nutrition are all important strategies for reducing the NTD burden in susceptible human populations. PMID:19389609

Gelineau-van Waes, J; Voss, K A; Stevens, V L; Speer, M C; Riley, R T

2009-01-01

161

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

SciTech Connect

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

Gabe V. Garcia

2005-01-03

162

FKBP8 cell-autonomously controls neural tube patterning through a Gli2- and Kif3a-dependent mechanism.  

PubMed

Signaling by Sonic hedgehog (Shh) represents an important process by which many types of neural progenitor cells become properly organized along the dorsal-ventral axis of the vertebrate neural tube in a concentration-dependent manner. However, the mechanism by which Shh signals are transduced with high fidelity and the relationship between the Shh signaling pathway and other patterning systems remain unclear. Here we focus on the role of FK506-binding protein 8 (FKBP8) in controlling neural cell identity through its antagonism of the Shh pathway. Our data indicate that disruption of FKBP8 function activates the Shh signaling pathway cell-autonomously at a step that is independent of the transmembrane protein Smoothened but dependent on the Gli2 transcription factor. This activation is also dependent on the kinesin-2 subunit Kif3a, a component of the intraflagellar transport (IFT) machinery used to generate cilia. Our data also indicate that non-cell-autonomous effects of the Fkbp8 mutation further contribute to the neural patterning phenotype and suggest that FKBP8 plays an indirect role in promoting Bone morphogenetic protein (BMP) signaling through antagonism of the Shh pathway. PMID:18590716

Cho, Ahryon; Ko, Hyuk W; Eggenschwiler, Jonathan T

2008-09-01

163

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

PubMed

Neural tube defects (NTDs) are common birth defects of complex etiology. Though family- and population-based studies have confirmed a genetic component, the responsible genes for NTDs are still largely unknown. Based on the hypothesis that folic acid prevents NTDs by stimulating methylation reactions, epigenetic factors, such as DNA methylation, are predicted to be involved in NTDs. Homeobox (HOX) genes play a role in spinal cord development and are tightly regulated in a spatiotemporal and collinear manner, partly by epigenetic modifications. We have quantified DNA methylation for the different HOX genes by subtracting values from a genome-wide methylation analysis using leukocyte DNA from 10 myelomeningocele (MMC) patients and 6 healthy controls. From the 1575 CpGs profiled for the 4 HOX clusters, 26 CpGs were differentially methylated (P-value < 0.05; ?-difference > 0.05) between MMC patients and controls. Seventy-seven percent of these CpGs were located in the HOXA and HOXB clusters, with the most profound difference for 3 CpGs within the HOXB7 gene body. A validation case-control study including 83 MMC patients and 30 unrelated healthy controls confirmed a significant association between MMC and HOXB7 hypomethylation (-14.4%; 95% CI: 11.9-16.9%; P-value < 0.0001) independent of the MTHFR 667C>T genotype. Significant HOXB7 hypomethylation was also present in 12 unaffected siblings, each related to a MMC patient, suggestive of an epigenetic change induced by the mother. The inclusion of a neural tube formation model using zebrafish showed that Hoxb7a overexpression but not depletion resulted in deformed body axes with dysmorphic neural tube formation. Our results implicate HOXB7 hypomethylation as risk factor for NTDs and highlight the importance for future genome-wide DNA methylation analyses without preselecting candidate pathways. PMID:25565354

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

2015-01-01

164

Maternal-Fetal Metabolic Gene-Gene Interactions and Risk of Neural Tube Defects  

PubMed Central

Single-gene analyses indicate that maternal genes associated with metabolic conditions (e.g., obesity) may influence the risk of neural tube defects (NTDs). However, to our knowledge, there have been no assessments of maternal-fetal metabolic gene-gene interactions and NTDs. We investigated 23 single nucleotide polymorphisms among 7 maternal metabolic genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, and TCF7L2) and 2 fetal metabolic genes (SLC2A2 and UCP2). Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study for birth years 1999–2007. We used a 2-step approach to evaluate maternal-fetal gene-gene interactions. First, a case-only approach was applied to screen all potential maternal and fetal interactions (n=76), as this design provides greater power in the assessment of gene-gene interactions compared to other approaches. Specifically, ordinal logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for each maternal-fetal gene-gene interaction, assuming a log-additive model of inheritance. Due to the number of comparisons, we calculated a corrected p-value (q-value) using the false discovery rate. Second, we confirmed all statistically significant interactions (q<0.05) using a log-linear approach among case-parent triads. In step 1, there were 5 maternal-fetal gene-gene interactions with q<0.05. The “top hit” was an interaction between maternal ENPP1 rs1044498 and fetal SLC2A2 rs6785233 (interaction OR=3.65, 95% CI: 2.32–5.74, p=2.09×10?8, q=0.001), which was confirmed in step 2 (p=0.00004). Our findings suggest that maternal metabolic genes associated with hyperglycemia and insulin resistance and fetal metabolic genes involved in glucose homeostasis may interact to increase the risk of NTDs. PMID:24332798

Lupo, Philip J.; Mitchell, Laura E.; Canfield, Mark A.; Shaw, Gary M.; Olshan, Andrew F.; Finnell, Richard H.; Zhu, Huiping

2013-01-01

165

Maternal-fetal metabolic gene-gene interactions and risk of neural tube defects.  

PubMed

Single-gene analyses indicate that maternal genes associated with metabolic conditions (e.g., obesity) may influence the risk of neural tube defects (NTDs). However, to our knowledge, there have been no assessments of maternal-fetal metabolic gene-gene interactions and NTDs. We investigated 23 single nucleotide polymorphisms among 7 maternal metabolic genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, and TCF7L2) and 2 fetal metabolic genes (SLC2A2 and UCP2). Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study for birth years 1999-2007. We used a 2-step approach to evaluate maternal-fetal gene-gene interactions. First, a case-only approach was applied to screen all potential maternal and fetal interactions (n = 76), as this design provides greater power in the assessment of gene-gene interactions compared to other approaches. Specifically, ordinal logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for each maternal-fetal gene-gene interaction, assuming a log-additive model of inheritance. Due to the number of comparisons, we calculated a corrected p-value (q-value) using the false discovery rate. Second, we confirmed all statistically significant interactions (q < 0.05) using a log-linear approach among case-parent triads. In step 1, there were 5 maternal-fetal gene-gene interactions with q < 0.05. The "top hit" was an interaction between maternal ENPP1 rs1044498 and fetal SLC2A2 rs6785233 (interaction OR = 3.65, 95% CI: 2.32-5.74, p = 2.09×10(-8), q=0.001), which was confirmed in step 2 (p = 0.00004). Our findings suggest that maternal metabolic genes associated with hyperglycemia and insulin resistance and fetal metabolic genes involved in glucose homeostasis may interact to increase the risk of NTDs. PMID:24332798

Lupo, Philip J; Mitchell, Laura E; Canfield, Mark A; Shaw, Gary M; Olshan, Andrew F; Finnell, Richard H; Zhu, Huiping

2014-01-01

166

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

2012-10-01

167

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

168

Sept6 Is Required for Ciliogenesis in Kupffer's Vesicle, the Pronephros, and the Neural Tube during Early Embryonic Development  

PubMed Central

Septins are conserved filament-forming GTP-binding proteins that act as cellular scaffolds or diffusion barriers in a number of cellular processes. However, the role of septins in vertebrate development remains relatively obscure. Here, we show that zebrafish septin 6 (sept6) is first expressed in the notochord and then in nearly all of the ciliary organs, including Kupffer's vesicle (KV), the pronephros, eye, olfactory bulb, and neural tube. Knockdown of sept6 in zebrafish embryos results in reduced numbers and length of cilia in KV. Consequently, cilium-related functions, such as the left-right patterning of internal organs and nodal/spaw signaling, are compromised. Knockdown of sept6 also results in aberrant cilium formation in the pronephros and neural tube, leading to cilium-related defects in pronephros development and Sonic hedgehog (Shh) signaling. We further demonstrate that SEPT6 associates with acetylated ?-tubulin in vivo and localizes along the axoneme in the cilia of zebrafish pronephric duct cells as well as cultured ZF4 cells. Our study reveals a novel role of sept6 in ciliogenesis during early embryonic development in zebrafish. PMID:24469395

Zhai, Gang; Gu, Qilin; He, Jiangyan; Lou, Qiyong; Chen, Xiaowen; Jin, Xia

2014-01-01

169

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

PubMed

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

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

2015-01-16

170

Background  

E-print Network

Efficiency of the EMDR procedure is based on a presumption of neuropsychological changes in therapeutic process.The aim of the investigation is to scann and give evidence of electroactivity changes, during the process of EMDR procedure and after finishing it. Materials and methods We have recorded a continual polygraph EEG, before, during and after EMDR therapy, in patient with combat-related PTSD. Results Before the treatment, EEG recorded basic activity of low voltage (attenuation) of 20 ?V, frequency of beta range (17-26 Hz), bioccipital, with no pathologic activity. Patient had prominent vegetative symptoms (anxiety, heart rate 100/min). Background activity immediately

Grozdanko Grbesa; Maja Simonovic; Dorjanka Jankovic

171

CBP/p300 and associated transcriptional co-activators exhibit distinct expression patterns during murine craniofacial and neural tube development.  

PubMed

Mutations in each of the transcriptional co-activator genes - CBP, p300, Cited2, Cart1 and Carm1 - result in neural tube defects in mice. The present study thus furnishes a complete and comparative temporal and spatial expression map of CBP/p300 and associated transcriptional co-activators, Cited2, Cart1 and Carm1 during the period of murine neural tube development (embryonic days 8.5 to 10.5). Each co-activator except Cart1 was expressed in the dorsal neural folds on E8.5. Although CBP and p300 are functionally interchangeable in vitro, their respective expression patterns diverge during embryogenesis before neural fold fusion is complete. CBP gene expression was lost from the neural folds by E8.75 and was thereafter weakly expressed in the maxillary region and limb buds, while p300 exhibited strong expression in the first branchial arch, limb bud and telencephalic regions on E9.5. Cart1 exhibited strong expression in the forebrain mesenchyme from E9.0 through E10.5. Although CBP, p300, Carm1 and Cited2 share temporal expression on E8.5, these co-activators have different spatial expression in mesenchyme and/or the neuroepithelium. Nevertheless, co-localization to the dorsal neural folds on E8.5 suggests a functional role in elevation and/or fusion of the neural folds. Target genes, and pathways that promote cranial neural tube fusion that are activated by CBP/p300/Carm1/Cited2/Cart1-containing transcriptional complexes await elucidation. PMID:19598128

Bhattacherjee, Vasker; Horn, Kristin H; Singh, Saurabh; Webb, Cynthia L; Pisano, M Michele; Greene, Robert M

2009-01-01

172

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

173

A new approach for the prediction of the heat transfer rate of the wire-on-tube type heat exchanger––use of an artificial neural network model  

Microsoft Academic Search

This study presents an application of artificial neural networks (ANNs) to predict the heat transfer rate of the wire-on-tube type heat exchanger. A back propagation algorithm, the most common learning method for ANNs, is used in the training and testing of the network. To solve this algorithm, a computer program was developed by using C++ programming language. The consistence between

Yasar Islamoglu

2003-01-01

174

Neural tube defects in Mexican-Americans living on the US-Mexico border: The effects of folic acid and dietary folate  

Microsoft Academic Search

Neural tube defects (NTDs) are malformations of the developing brain and spinal cord; the most common are anencephaly and spina bifida. Evidence from many populations suggests that 50% of NTDs can be prevented through daily consumption of folic acid. A recent study has reported that folic acid may not protect populations of Mexican descent. This finding has serious implications for

Lucina Suarez; Katherine A. Hendricks; Sharon P. Cooper; Anne M. Sweeney; Robert J. Hardy; Russell D. Larsen

1998-01-01

175

Identification of sensitivity genes involved in teratogen-induced neural tube defects  

E-print Network

RNA from Lm/Bc mouse neural tissue, reverse transcribing the RNA into cDNA and PCR amplifying the cDNA using a radioactively end labeled primer in order to visualize the amplified fragment. The labeled cDNA fragment is then loaded onto a denaturing...

Hayes, Blaine G

2013-02-22

176

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

177

MR-Based Morphometry of the Posterior Fossa in Fetuses with Neural Tube Defects of the Spine  

PubMed Central

Objectives In cases of “spina bifida,” a detailed prenatal imaging assessment of the exact morphology of neural tube defects (NTD) is often limited. Due to the diverse clinical prognosis and prenatal treatment options, imaging parameters that support the prenatal differentiation between open and closed neural tube defects (ONTDs and CNTDs) are required. This fetal MR study aims to evaluate the clivus-supraocciput angle (CSA) and the maximum transverse diameter of the posterior fossa (TDPF) as morphometric parameters to aid in the reliable diagnosis of either ONTDs or CNTDs. Methods The TDPF and the CSA of 238 fetuses (20–37 GW, mean: 28.36 GW) with a normal central nervous system, 44 with ONTDS, and 13 with CNTDs (18–37 GW, mean: 24.3 GW) were retrospectively measured using T2-weighted 1.5 Tesla MR -sequences. Results Normal fetuses showed a significant increase in the TDPF (r?=?.956; p<.001) and CSA (r?=?.714; p<.001) with gestational age. In ONTDs the CSA was significantly smaller (p<.001) than in normal controls and CNTDs, whereas in CNTDs the CSA was not significantly smaller than in controls (p?=?.160). In both ONTDs and in CNTDs the TDPF was significantly different from controls (p<.001). Conclusions The skull base morphology in fetuses with ONTDs differs significantly from cases with CNTDs and normal controls. This is the first study to show that the CSA changes during gestation and that it is a reliable imaging biomarker to distinguish between ONTDs and CNTDs, independent of the morphology of the spinal defect. PMID:25393279

Woitek, Ramona; Dvorak, Anton; Weber, Michael; Seidl, Rainer; Bettelheim, Dieter; Schöpf, Veronika; Amann, Gabriele; Brugger, Peter C.; Furtner, Julia; Asenbaum, Ulrika; Prayer, Daniela; Kasprian, Gregor

2014-01-01

178

Background  

E-print Network

Background: Although the outcomes of caustic ingestion differ between children and adults, it is unclear whether such outcomes differ among adults as a function of their age. This retrospective study was performed to ascertain whether the clinical outcomes of caustic ingestion differ significantly between elderly and non-elderly adults. Methods: Medical records of patients hospitalized for caustic ingestion between June 1999 and July 2009 were reviewed retrospectively. Three hundred eighty nine patients between the ages of 17 and 107 years were divided into two groups: non-elderly (ingestion, substance ingested, systemic and gastrointestinal complications, psychological and systemic comorbidities, severity of mucosal injury, and time to expiration. Results: The incidence of psychological comorbidities was higher for the non-elderly group. By contrast, the incidence of systemic comorbidities, the grade of severity of mucosal damage, and the incidence of systemic complications were higher for the elderly group. The percentages of ICU admissions and deaths in the ICU were higher and the cumulative survival rate was lower for the elderly group. Elderly subjects, those with systemic complications had the greatest mortality risk due to caustic ingestion. Conclusions: Caustic ingestion by subjects ?65 years of age is associated with poorer clinical outcomes as compared to subjects < 65 years of age; elderly subjects with systemic complications have the poorest clinical outcomes. The severity of gastrointestinal tract injury appears to have no impact on the survival of elderly subjects.

Jui-min Chang; Nai-jen Liu; Betty Chien-jung Pai; Yun-hen Liu; Ming-hung Tsai; Ching-song Lee; Yin-yi Chu; Chih-chuan Lin; Cheng-tang Chiu; Hao-tsai Cheng

179

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

180

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

PubMed Central

Summary Inducing organogenesis in 3D culture is an important aspect of stem cell research. Anterior neural structures have been produced from large embryonic stem cell (ESC) aggregates, but the steps involved in patterning such complex structures have been ill defined, as embryoid bodies typically contained many cell types. Here we show that single mouse ESCs directly embedded in Matrigel or defined synthetic matrices under neural induction conditions can clonally form neuroepithelial cysts containing a single lumen in 3D. Untreated cysts were uniformly dorsal and could be ventralized to floor plate (FP). Retinoic acid posteriorized cysts to cervical levels and induced localize FP formation yielding full patterning along the dorsal/ventral (DV) axis. Correct spatial organization of motor neurons, interneurons, and dorsal interneurons along the DV axis was observed. This system serves as a valuable tool for studying morphogen action in 3D and as a source of patterned spinal cord tissue. PMID:25454634

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

2014-01-01

181

3D reconstitution of the patterned neural tube from embryonic stem cells.  

PubMed

Inducing organogenesis in 3D culture is an important aspect of stem cell research. Anterior neural structures have been produced from large embryonic stem cell (ESC) aggregates, but the steps involved in patterning such complex structures have been ill defined, as embryoid bodies typically contained many cell types. Here we show that single mouse ESCs directly embedded in Matrigel or defined synthetic matrices under neural induction conditions can clonally form neuroepithelial cysts containing a single lumen in 3D. Untreated cysts were uniformly dorsal and could be ventralized to floor plate (FP). Retinoic acid posteriorized cysts to cervical levels and induced localize FP formation yielding full patterning along the dorsal/ventral (DV) axis. Correct spatial organization of motor neurons, interneurons, and dorsal interneurons along the DV axis was observed. This system serves as a valuable tool for studying morphogen action in 3D and as a source of patterned spinal cord tissue. PMID:25454634

Meinhardt, Andrea; Eberle, Dominic; Tazaki, Akira; Ranga, Adrian; Niesche, Marco; Wilsch-Bräuninger, Michaela; Stec, Agnieszka; Schackert, Gabriele; Lutolf, Matthias; Tanaka, Elly M

2014-12-01

182

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

PubMed Central

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

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

2014-01-01

183

Detection of foreign matter in transfusion solution based on Gaussian background modeling and an optimized BP neural network.  

PubMed

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

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

2014-01-01

184

2014. Published by The Company of Biologists Ltd | Disease Models & Mechanisms (2014) 7, 1153-1163 doi:10.1242/dmm.016758 Neural tube defects (NTDs) are among the commonest and most  

E-print Network

the identity of the genetic determinants remains largely undiscovered. Initiation of neural tube closure link between NTDs and PCP signaling. Recently, missense gene variants have been identified in PCP genes

Chittka, Lars

2014-01-01

185

Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: world health organization guidelines.  

PubMed

Neural tube defects (NTDs) such as spina bifida, anencephaly, and encephalocele are serious birth defects of the brain and spine that occur during the first month of pregnancy when the neural tube fails to close completely. Randomized controlled trials and observational studies have shown that adequate daily consumption of folic acid before and during early pregnancy considerably reduces the risk for NTDs. The U.S. Public Health Service recommends that women capable of becoming pregnant consume 400 µg of folic acid daily for NTD prevention. Furthermore, fortification of staple foods (e.g., wheat flour) with folic acid has decreased folate-sensitive NTD prevalence in multiple settings and is a highly cost-effective intervention. PMID:25905896

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

2015-04-24

186

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

187

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

PubMed Central

Objective: A significant decline in the prevalence of neural tube defects (NTD) through food fortification has been reported. Questions remain, however, about the effectiveness of this intervention in reducing the gap in prevalence across socioeconomic status (SES). Study Design: Using health number and through record linkage, children born in Ontario hospitals between 1994 and 2009 were followed for the diagnosis of congenital anomalies. SES quintiles were assigned to each child using census information at the time of birth. Adjusted rates and multivariate models were used to compare trends among children born in different SES groups. Results: Children born in low SES areas had significantly higher rates of NTDs (RR = 1.25, CI: 1.14–1.37). Prevalence of NTDs among children born in low and high SES areas declined since food fortification began in 1999 although has started rising again since 2006. While the crude decline was greater in low SES areas, after adjustment for maternal age, the slope of decline and SES gap in prevalence rates remained unchanged overtime. Conclusions: While food fortification is successful in reducing the prevalence of NTDs, it was not associated with removing the gap between high and low SES groups. PMID:23538728

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

2013-01-01

188

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. PMID:23056169

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

2012-01-01

189

Detection of neural tube defect in the first and second trimester of pregnancy by ultrasound in Imam Hospital, Ahwaz between December 2008-2010  

PubMed Central

Background: Central nervous system malformations are the second most common congenital malformations after congenital heart diseases. These malformations are associated with many instances of morbidity and mortality which underline the importance of prevention and their early diagnosis. Objective: The objective of this study is the diagnosis of neural tube defect (NTDs) in the first trimester and its comparison to second trimester diagnoses in order to reduce the complications associated with late pregnancy terminations and its costs. Materials and Methods: This study was a trans-sectional study. A total number of 1074 patients who referred to Imam Khomeini Hospital were enrolled in this study. During the 11th-13th (+6 days) gestational week the patients were screened sonographically; subsequently they were re-scanned for fetal anomalies during 18th-20th gestational week, and we followed the babies after birth. Considering that Intracranial Translucency (IT) was introduced in the newer researches, it was, too, measured in 125 of the cases. Results: In a total number of 1074 patients we had one patient with an anencephalous fetus whom was diagnosed in the first trimester of pregnancy. In the second trimester, we detected one case of myelomenigocele; when we referred to this patient’s first trimester sonography, there was no visible IT. In the 125 cases in whom the IT length was measured, it was normal; the 2nd trimester sonographies in these patients were also normal. Conclusion: It must be noted that the diagnosis of NTD is more accurate in the second trimester of pregnancy. Consequently it is recommended that in high risk patients, the second trimester sonography be performed transvaginally, and in an earlier gestational age (14th-16th gestational weeks). PMID:25246925

Masihi, Sara; Barati, Mojgan; Marfu, Javad; Eskandari, Zahra

2012-01-01

190

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. PMID:23873812

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

2013-01-01

191

Forkheadbox N4 (FoxN4) triggers context-dependent differentiation in the developing chick retina and neural tube.  

PubMed

FoxN4, a forkhead box transcription factor, is expressed in the chicken eye field and in retinal progenitor cells (RPCs) throughout development. FoxN4 labelling overlapped with that of Pax6 and Sox2, two crucial transcription factors for RPCs. Later, during neurogenesis in the retina, some cells were intensely and transiently labelled for FoxN4. These cells co-labelled for Lim1, a transcription factor expressed in early-born horizontal cells. The result suggests that high levels of FoxN4 combined with expression of Lim1 define a population of RPCs committed to the horizontal cell fate prior to their last apical mitosis. As these prospective horizontal cells develop, their FoxN4 expression is down-regulated. Previous results suggested that FoxN4 is important for the generation of horizontal and amacrine cells but that it is not sufficient for the generation of horizontal cells (Li et al., 2004). We found that over-expression of FoxN4 in embryonic day 3 chicken retina could activate horizontal cell markers Prox1 and Lim1, and that it generated numerous and ectopically located horizontal cells of both main subtypes. However, genes expressed in photoreceptors, amacrine and ganglion cells were also activated, indicating that FoxN4 triggered the expression of several differentiation factors. This effect was not exclusive for the retina but was also seen when FoxN4 was over-expressed in the mesencephalic neural tube. Combining the results from over-expression and wild-type expression data we suggest a model where a low level of FoxN4 is maintained in RPCs and that increased levels during a restricted period trigger neurogenesis and commitment of RPCs to the horizontal cell fate. PMID:23314287

Boije, H; Shirazi Fard, S; Ring, H; Hallböök, F

2013-01-01

192

PAX genes and human neural tube defects: an amino acid substitution in PAX1 in a patient with spina bifida.  

PubMed Central

From studies in the mouse and from the clinical and molecular analysis of patients with type 1 Waardenburg syndrome, particular members of the PAX gene family are suspected factors in the aetiology of human neural tube defects (NTD). To investigate the role of PAX1, PAX3, PAX7, and PAX9, allelic association studies were performed in 79 sporadic and 38 familial NTD patients from the Dutch population. Sequence variation was studied by SSC analysis of the paired domain regions of the PAX1, PAX7, and PAX9 genes and of the complete PAX3 gene. In one patient with spina bifida, a mutation in the PAX1 gene was detected changing the conserved amino acid Gln to His at position 42 in the paired domain of the protein. The mutation was inherited through the maternal line from the unaffected grandmother and was not detected in 300 controls. In the PAX3 gene, variation was detected at several sites including a Thr/Lys amino acid substitution in exon 6. All alleles were present among patients and controls in about the same frequencies. However, an increased frequency of the rare allele of a silent polymorphism in exon 2 was found in NTD patients, but no significant association was observed (p = 0.06). No sequence variation was observed in the paired domain of the PAX7 and PAX9 genes. Our findings so far do not support a major role of the PAX genes examined in the aetiology of NTD. However, the detection of a mutation in PAX1 suggests that, in principle, this gene can act as a risk factor for human NTD. Images PMID:8863157

Hol, F A; Geurds, M P; Chatkupt, S; Shugart, Y Y; Balling, R; Schrander-Stumpel, C T; Johnson, W G; Hamel, B C; Mariman, E C

1996-01-01

193

Diabetes and obesity-related genes and the risk of neural tube defects in the national birth defects prevention study.  

PubMed

Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999-2007. Log-linear models were used to evaluate maternal and offspring genetic effects. After application of the false discovery rate, there were 5 significant maternal genetic effects. The less common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI): 0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR = 0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)). Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among obese women. These findings indicate that maternal genetic variants associated with glucose homeostasis may modify the risk of having an NTD-affected pregnancy. PMID:23132673

Lupo, Philip J; Canfield, Mark A; Chapa, Claudia; Lu, Wei; Agopian, A J; Mitchell, Laura E; Shaw, Gary M; Waller, D Kim; Olshan, Andrew F; Finnell, Richard H; Zhu, Huiping

2012-12-15

194

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

PubMed Central

Objectives The methylenetetrahydrofolate dehydrogenase (MTHFD1) gene, as one of the key genes involved in the folate pathway, has been reported to play a critical role in the pathogenesis of neural tube defects (NTDs). However, the results of published studies are contradictory and inconclusive. Thus, this meta-analysis aimed to evaluate the effect of the common polymorphism in the MTHFD1 gene, the G1958A (R653Q, dbSNP ID: rs2236225) variant, on the risk of NTDs in all eligible studies. Methods Relevant literature published before January 3, 2014 was retrieved from the MEDLINE, EMBASE, Cochrane Library, and CBM databases. Pooled crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between the MTHFD1 G1958A polymorphism and NTDs risk. Results We performed a meta-analysis of nine studies with a total of 4,302 NTDs patients and 4,238 healthy controls. Our results demonstrated a significant correlation between the MTHFD1 G1958A polymorphism and NTDs in an overall meta-analysis. For family-based studies, the study subjects were classified as NTD cases, mothers with NTDs offspring, and fathers with NTDs offspring. We found no association between any of the fathers’ genotypes and NTDs, whereas there was a clear excess of the 1958A allele in the mothers of children with NTDs compared with controls individuals. Conclusions In summary, our meta-analysis strongly suggests that the MTHFD1 G1958A polymorphism might be associated with maternal risk for NTDs in Caucasian populations. However, the evidence of this association should be interpreted with caution due to the selective nature of publication of genetic association studies. PMID:24977710

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

2014-01-01

195

Adverse reproductive outcomes among pregnancies of aunts and (spouses of) uncles in Irish families with neural tube defects.  

PubMed

Adverse pregnancy outcomes may be more frequent among sibs of individuals with neural tube defects (NTDs), and transmission of risk in families with an NTD may be more frequent among maternal relatives. In a study designed to evaluate matrilineal risk for NTDs, we compared adverse pregnancy outcomes among maternal and paternal first cousin pregnancies. Pregnancy histories were obtained by interview with 288 uncles and aunts (parents of the first cousin pregnancies) in 48 Irish NTD families. We analyzed pregnancy outcomes (preterm deliveries, stillbirths, and miscarriages) among 1,033 singleton first cousin pregnancies and compared risk among maternal versus paternal relatives. Maternal first cousin pregnancies were more likely to end adversely when compared to paternal first cousin pregnancies (17.4% vs. 11.7%, P = 0.01). In a logistic regression analysis of pregnancies unaffected by birth defects, maternal line remained independently associated with adverse outcomes (odds ratio (OR) = 1.55, 95% confidence interval (CI) 1.06, 2.27) after controlling for NTD type, maternal age, maternal smoking during pregnancy, first cousin pregnancy's year of birth. The excess risk with maternal line related mainly to spina bifida occulta families (OR = 42.4; CI 2.64, 681; P = 0.008); risk in open spina bifida families was 1.24 (CI 0.82, 1.87; P = 0.3). These results support the hypothesis of excess risk for adverse pregnancy outcomes among maternal relatives in NTD families. Further work is needed, epidemiological as well as clinical and molecular, not only to confirm these findings, but also to define the underlying biological mechanisms linking adverse reproductive outcomes, excess maternal risk and occurrence of NTDs. PMID:16333827

Byrne, Julianne; Carolan, Susan

2006-01-01

196

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

PubMed Central

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

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

2015-01-01

197

Epidemiologic characteristics of phenotypically distinct neural tube defects among 0.7 million California births, 1983-1987.  

PubMed

Isolated neural tube defects (NTDs) appear to have different risk factors compared to nonisolated NTDs. To extend those observations, we explored routinely collected child and parental characteristics as possible risk factors among isolated versus nonisolated NTD cases, among high versus low spina bifida cases, and among open versus skin-covered spina bifida case. Fetuses and liveborn infants with anencephaly or spina bifida among the 1983-87 cohort of births and fetal deaths (n = 712,863) were ascertained by the California Birth Defects Monitoring Program. One hundred and ninety-three anencephalic cases and 272 spina bifida cases were compared to a random sample of 5,000 liveborn infants. Among anencephalic cases, 55% were livebirths and 85% were isolated. The proportion of males was similar to females across all subgroups. Increased risks were found for Hispanic whites, with risk estimates highest for nonisolated cases (odds ratio = 4.0, 95% confidence interval [1.5, 10.5]). Among spina bifida cases, 92% were livebirths, 81% isolated, 82% open, and 86% were low. More males were found among the group with isolated high open defects, and fewer males were found among the group of all closed defects. The proportion of males was similar to females in all other subgroups. Cases were more likely to be Hispanic with risks largest for high open defects (odds ratio = 2.9, [1.2,6.6]), particularly for nonisolated cases. This study provides some evidence that further classifications of NTDs may reveal subgroupings of cases with different etiologies. PMID:8016745

Shaw, G M; Jensvold, N G; Wasserman, C R; Lammer, E J

1994-02-01

198

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

PubMed

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

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

2015-02-01

199

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

200

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 Central

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.

2013-01-01

201

Use of Natural Neural Scaffolds Consisting of Engineered Vascular Endothelial Growth Factor Immobilized on Ordered Collagen Fibers Filled in a Collagen Tube for Peripheral Nerve Regeneration in Rats  

PubMed Central

The search for effective strategies for peripheral nerve regeneration has attracted much attention in recent years. In this study, ordered collagen fibers were used as intraluminal fibers after nerve injury in rats. Vascular endothelial growth factor (VEGF) plays an important role in nerve regeneration, but its very fast initial burst of activity within a short time has largely limited its clinical use. For the stable binding of VEGF to ordered collagen fibers, we fused a collagen-binding domain (CBD) to VEGF through recombinant DNA technology. Then, we filled the ordered collagen fibers-CBD-VEGF targeting delivery system in a collagen tube to construct natural neural scaffolds, which were then used to bridge transected nerve stumps in a rat sciatic nerve transection model. After transplantation, the natural neural scaffolds showed minimal foreign body reactions and good integration into the host tissue. Oriented collagen fibers in the collagen tube could guide regenerating axons in an oriented manner to the distal, degenerating nerve segment, maximizing the chance of target reinnervation. Functional and histological analyses indicated that the recovery of nerve function in the natural neural scaffolds-treated group was superior to the other grafted groups. The guiding of oriented axonal regeneration and effective delivery systems surmounting the otherwise rapid and short-lived diffusion of growth factors in body fluids are two important strategies in promoting peripheral nerve regeneration. The natural neural scaffolds described take advantage of these two aspects and may produce synergistic effects. These properties qualified the artificial nerve conduits as a putative candidate system for the fabrication of peripheral nerve reconstruction devices. PMID:25322152

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

2014-01-01

202

Use of natural neural scaffolds consisting of engineered vascular endothelial growth factor immobilized on ordered collagen fibers filled in a collagen tube for peripheral nerve regeneration in rats.  

PubMed

The search for effective strategies for peripheral nerve regeneration has attracted much attention in recent years. In this study, ordered collagen fibers were used as intraluminal fibers after nerve injury in rats. Vascular endothelial growth factor (VEGF) plays an important role in nerve regeneration, but its very fast initial burst of activity within a short time has largely limited its clinical use. For the stable binding of VEGF to ordered collagen fibers, we fused a collagen-binding domain (CBD) to VEGF through recombinant DNA technology. Then, we filled the ordered collagen fibers-CBD-VEGF targeting delivery system in a collagen tube to construct natural neural scaffolds, which were then used to bridge transected nerve stumps in a rat sciatic nerve transection model. After transplantation, the natural neural scaffolds showed minimal foreign body reactions and good integration into the host tissue. Oriented collagen fibers in the collagen tube could guide regenerating axons in an oriented manner to the distal, degenerating nerve segment, maximizing the chance of target reinnervation. Functional and histological analyses indicated that the recovery of nerve function in the natural neural scaffolds-treated group was superior to the other grafted groups. The guiding of oriented axonal regeneration and effective delivery systems surmounting the otherwise rapid and short-lived diffusion of growth factors in body fluids are two important strategies in promoting peripheral nerve regeneration. The natural neural scaffolds described take advantage of these two aspects and may produce synergistic effects. These properties qualified the artificial nerve conduits as a putative candidate system for the fabrication of peripheral nerve reconstruction devices. PMID:25322152

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

2014-01-01

203

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

PubMed

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

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

2014-04-01

204

Neural Tube Defects  

MedlinePLUS

... Lasting disabilities for children with encephalocele can include: Intellectual disabilities. These happen in about 75 percent of children ... blood vessels and tissue. They do not cause intellectual disabilities or learning problems. Using ultrasound, a health care ...

205

Mutations in PTF1A are not a common cause for human VATER/VACTERL association or neural tube defects mirroring Danforth's short tail mouse.  

PubMed

Danforth's short tail (Sd) mutant mice exhibit defects of the neural tube and other abnormalities, which are similar to the human vertebral anomalies, anal atresia, cardiac defects, tracheosophageal fistula and/or esophageal atresia, renal and radial abnormalities, and limb defects (VATER/VACTERL) association, including defects of the hindgut. Sd has been shown to underlie ectopic gene expression of murine Ptf1a, which encodes pancreas?specific transcription factor 1A, due to the insertion of a retrotansposon in its 5' regulatory domain. In order to investigate the possible involvement of this gene in human VATER/VACTERL association and human neural tube defects (NTDs), a sequence analysis was performed. DNA samples from 103 patients with VATER/VACTERL and VATER/VACTERL?like association, all presenting with anorectal malformations, and 72 fetuses with NTDs, where termination of pregnancy had been performed, were included in the current study. The complete PTF1A coding region, splice sites and 1.5 kb of the 5' flanking promotor region was sequenced. However, no pathogenic alterations were detected. The results of the present study do not support the hypothesis that high penetrant mutations in these regions of PTF1A are involved in the development of human VATER/VACTERL association or NTDs, although rare mutations may be detectable in larger patient samples. PMID:25775927

Gurung, Nirmala; Grosse, Greta; Draaken, Markus; Hilger, Alina C; Nauman, Nuzhat; Müller, Andreas; Gembruch, Ulrich; Merz, Waltraut M; Reutter, Heiko; Ludwig, Michael

2015-07-01

206

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. PMID:20940229

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

2010-01-01

207

Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice  

PubMed Central

Summary Hypomorphic mutations in the human SPINT2 gene cause a broad spectrum of abnormalities in organogenesis, including organ and digit duplications, atresia, fistulas, hypertelorism, cleft palate and hamartoma. SPINT2 encodes the transmembrane serine protease inhibitor HAI2 (placental bikunin), and the severe developmental effects of decreased HAI2 activity can be hypothesized to be a consequence of excess pericellular proteolytic activity. Indeed, we show here that HAI2 is a potent regulator of protease-guided cellular responses, including motogenic activity and transepithelial resistance of epithelial monolayers. Furthermore, we show that inhibition of the transmembrane serine protease matriptase (encoded by St14) is an essential function of HAI2 during tissue morphogenesis. Genetic inactivation of the mouse Spint2 gene led to defects in neural tube closure, abnormal placental labyrinth development associated with loss of epithelial cell polarity, and embryonic demise. Developmental defects observed in HAI2-deficient mice were caused by unregulated matriptase activity, as both placental development and embryonic survival in HAI2-deficient embryos were completely restored by the simultaneous genetic inactivation of matriptase. However, neural tube defects were detected in HAI2-deficient mice even in the absence of matriptase, although at lower frequency, indicating that the inhibition of additional serine protease(s) by HAI2 is required to complete neural development. Finally, by genetic complementation analysis, we uncovered a unique and complex functional interaction between HAI2 and the related HAI1 in the regulation of matriptase activity during development. This study indicates that unregulated matriptase-dependent cell surface proteolysis can cause a diverse array of abnormalities in mammalian development. PMID:19592578

Szabo, Roman; Hobson, John P.; Christoph, Kristina; Kosa, Peter; List, Karin; Bugge, Thomas H.

2009-01-01

208

Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice.  

PubMed

Hypomorphic mutations in the human SPINT2 gene cause a broad spectrum of abnormalities in organogenesis, including organ and digit duplications, atresia, fistulas, hypertelorism, cleft palate and hamartoma. SPINT2 encodes the transmembrane serine protease inhibitor HAI2 (placental bikunin), and the severe developmental effects of decreased HAI2 activity can be hypothesized to be a consequence of excess pericellular proteolytic activity. Indeed, we show here that HAI2 is a potent regulator of protease-guided cellular responses, including motogenic activity and transepithelial resistance of epithelial monolayers. Furthermore, we show that inhibition of the transmembrane serine protease matriptase (encoded by St14) is an essential function of HAI2 during tissue morphogenesis. Genetic inactivation of the mouse Spint2 gene led to defects in neural tube closure, abnormal placental labyrinth development associated with loss of epithelial cell polarity, and embryonic demise. Developmental defects observed in HAI2-deficient mice were caused by unregulated matriptase activity, as both placental development and embryonic survival in HAI2-deficient embryos were completely restored by the simultaneous genetic inactivation of matriptase. However, neural tube defects were detected in HAI2-deficient mice even in the absence of matriptase, although at lower frequency, indicating that the inhibition of additional serine protease(s) by HAI2 is required to complete neural development. Finally, by genetic complementation analysis, we uncovered a unique and complex functional interaction between HAI2 and the related HAI1 in the regulation of matriptase activity during development. This study indicates that unregulated matriptase-dependent cell surface proteolysis can cause a diverse array of abnormalities in mammalian development. PMID:19592578

Szabo, Roman; Hobson, John P; Christoph, Kristina; Kosa, Peter; List, Karin; Bugge, Thomas H

2009-08-01

209

NEWS & VIEWS NATURE|Vol 439|26 January 2006 consequence, the edges of the neural tube  

E-print Network

extend neural connections to specialized neurons called granule cells, and to the inferior olive nucleus the inferior olive nucleus5,9 . Additionally, the ratio of these precursor pools within the rhombic lip

Tabin, Cliff

210

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

PubMed Central

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

Wang, Jiancai; Xu, Ronghua; Liu, Aizhong

2014-01-01

211

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

PubMed

Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism. PMID:24737468

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

2014-01-01

212

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

SciTech Connect

Recent studies have implicated folic acid as an important determinant of normal human growth, development, and function. Insufficient folate levels appear to be a risk factor for neural tube defects (NTD), as well as for several chronic diseases of adulthood. However, relatively little is known about the factors that influence folate status in the general population. To estimate the relative contribution of genetic and nongenetic factors to variation in folate, we have evaluated red blood cell (RBC) folate levels in 440 pairs of MZ twins and in 331 pairs of DZ twins. The data were best described by a model in which 46% of the variance in RBC folate was attributable to additive genetic effects, 16% of the variance was due to measured phenotypic covariates, and 38% of the variance was due to random environmental effects. Moreover, the correlations for RBC folate in MZ co-twins (r = .46) and in repeat measures from the same individual (r = .51) were very similar, indicating that virtually all repeatable variation in RBC folate is attributable to genetic factors. On the basis of these results, it would seem reasonable to initiate a search for the specific genes that influence RBC folate levels in the general population. Such genes ultimately may be used to identify individuals at increased risk for NTD and other folate-related diseases. 23 refs., 1 tab.

Mitchell, L.E. [Children`s Hospital of Philadelphia, PA (United States); Duffy, P.; Bellingham, G. [Prince Charles Hospital, Brisbane (Australia)] [and others

1997-02-01

213

Neural tube derived Wnt signals cooperate with FGF signaling in the formation and differentiation of the trigeminal placodes  

Microsoft Academic Search

BACKGROUND: Neurogenic placodes are focal thickenings of the embryonic ectoderm that form in the vertebrate head. It is within these structures that the precursors of the majority of the sensory neurons of the cranial ganglia are specified. The trigeminal placodes, the ophthalmic and maxillomandibular, form close to the midbrain-hindbrain boundary and many lines of evidence have shown that signals emanating

Claire A Canning; Lily Lee; Sarah Xinwei Luo; Anthony Graham; C Michael Jones

2008-01-01

214

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

PubMed

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

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

2015-01-16

215

Novel mutations in Lrp6 orthologs in mouse and human neural tube defects affect a highly dosage-sensitive Wnt non-canonical planar cell polarity pathway  

PubMed Central

Wnt signaling has been classified as canonical Wnt/?-catenin-dependent or non-canonical planar cell polarity (PCP) pathway. Misregulation of either pathway is linked mainly to cancer or neural tube defects (NTDs), respectively. Both pathways seem to antagonize each other, and recent studies have implicated a number of molecular switches that activate one pathway while simultaneously inhibiting the other thereby partially mediating this antagonism. The lipoprotein receptor–related protein Lrp6 is crucial for the activation of the Wnt/?-catenin pathway, but its function in Wnt/PCP signaling remains largely unknown. In this study, we investigate the role of Lrp6 as a molecular switch between both Wnt pathways in a novel ENU mouse mutant of Lrp6 (Skax26m1Jus) and in human NTDs. We demonstrate that Skax26m1Jus represents a hypermorphic allele of Lrp6 with increased Wnt canonical and abolished PCP-induced JNK activities. We also show that Lrp6Skax26-Jus genetically interacts with a PCP mutant (Vangl2Lp) where double heterozygotes showed an increased frequency of NTDs and defects in cochlear hair cells’ polarity. Importantly, our study also demonstrates the association of rare and novel missense mutations in LRP6 that is an inhibitor rather than an activator of the PCP pathway with human NTDs. We show that three LRP6 mutations in NTDs led to a reduced Wnt canonical activity and enhanced PCP signaling. Our data confirm an inhibitory role of Lrp6 in PCP signaling in neurulation and indicate the importance of a tightly regulated and highly dosage-sensitive antagonism between both Wnt pathways in this process. PMID:24203697

Allache, Redouane; Lachance, Stéphanie; Guyot, Marie Claude; De Marco, Patrizia; Merello, Elisa; Justice, Monica J.; Capra, Valeria; Kibar, Zoha

2014-01-01

216

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

217

The Maternal ITPK1 Gene Polymorphism Is Associated with Neural Tube Defects in a High-Risk Chinese Population  

PubMed Central

Background Epidemiological surveys and animal studies have revealed that inositol metabolism is associated with NTDs, but the mechanisms are not clear. Inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) is a pivotal regulatory enzyme in inositol metabolic pathway. The objective was to assess the potential impact of the maternal ITPK1 genotypes on the inositol parameter and on the NTD risk in a NTD high-risk area in China. Methodology/Results A case-control study of pregnant women affected with NTDs (n?=?200) and controls (n?=?320) was carried out. 13 tag SNPs of ITPK1 were selected and genotyped by the Sequenom MassArray system. We found that 4 tag SNPs were statistically significant in spina bifida group (P<0.05). MACH was used to impute the un-genotyped SNPs in ITPK1 locus and showed that 3 meaningful SNPs in the non-coding regions were significant. We also predicted the binding capacity of transcription factors in the positive SNPs using the bioinformatics method and found that only rs3783903 was located in the conserved sequence of activator protein-1 (AP-1). To further study the association between biochemical values and genotypes, maternal plasma inositol hexakisphosphate (IP6) levels were also assessed using LC-MS. The maternal plasma IP6 concentrations in the spina bifida subgroup were 7.1% lower than control (136.67 vs. 147.05 ng mL?1, P<0.05), and significantly lower in rs3783903 GG genotype than others (P<0.05). EMSA showed a different allelic binding capacity of AP-1 in rs3783903, which was affected by an A?G exchange. The RT-PCR suggested the ITPK1 expression was decreased significantly in mutant-type of rs3783903 compared with wild-type in the 60 healthy pregnancies (P<0.05). Conclusions/Significance These results suggested that the maternal rs3783903 of ITPK1 might be associated with spina bifida, and the allele G of rs3783903 might affect the binding of AP-1 and the decrease of maternal plasma IP6 concentration in this Chinese population. PMID:24465924

Guo, Jin; Wang, Fang; Wang, Xiuwei; Li, Guannan; Xie, Qiu; Han, Xu; Niu, Bo; Zhang, Ting

2014-01-01

218

Ear Tubes  

MedlinePLUS

Ear Tubes Ear Tubes Patient Health Information News media interested in covering the latest from AAO-HNS/ ... and throat specialist) may be considered. What are ear tubes? Ear tubes are tiny cylinders placed through ...

219

Artificial Neural Networks Single Layer Networks Multi Layer Networks Generalization Artificial Neural Networks  

E-print Network

Artificial Neural Networks Single Layer Networks Multi Layer Networks Generalization Artificial Neural Networks #12;Artificial Neural Networks Single Layer Networks Multi Layer Networks Generalization 1 Artificial Neural Networks Properties Applications Classical Examples Biological Background 2

Kjellström, Hedvig

220

Artificial Neural Networks Single Layer Networks Multi Layer Networks Generalization Artificial Neural Networks  

E-print Network

Artificial Neural Networks Single Layer Networks Multi Layer Networks Generalization Artificial Neural Networks Artificial Neural Networks Single Layer Networks Multi Layer Networks Generalization 1 Artificial Neural Networks Properties Applications Classical Examples Biological Background 2 Single Layer

Kjellström, Hedvig

221

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

222

Neural induction and factors that stabilize a neural fate  

PubMed Central

The neural ectoderm of vertebrates forms when the BMP signaling pathway is suppressed. Herein we review the molecules that directly antagonize extracellular BMP and the signaling pathways that further contribute to reduce BMP activity in the neural ectoderm. Downstream of neural induction, a large number of “neural fate stabilizing” (NFS) transcription factors are expressed in the presumptive neural ectoderm, developing neural tube, and ultimately in neural stem cells. Herein we review what is known about their activities during normal development to maintain a neural fate and regulate neural differentiation. Further elucidation of how the NFS genes interact to regulate neural specification and differentiation should ultimately prove useful for regulating the expansion and differentiation of neural stem and progenitor cells. PMID:19750523

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

2009-01-01

223

What Are Neural Tube Defects?  

MedlinePLUS

... normal intelligence, but some will have learning or intellectual disabilities . 1 There are several common types of spina ... disabilities. Some infants born with myelomeningocele have severe intellectual disabilities . 2 Anencephaly Anencephaly (pronounced an-en-SEF-uh- ...

224

apo B gene knockout in mice results in embryonic lethality in homozygotes and neural tube defects, male infertility, and reduced HDL cholesterol ester and apo A-I transport rates in heterozygotes.  

PubMed Central

apo B is a structural constituent of several classes of lipoprotein particles, including chylomicrons, VLDL, and LDL. To better understand the role of apo B in the body, we have used gene targeting in embryonic stem cells to create a null apo B allele in the mouse. Homozygous apo B deficiency led to embryonic lethality, with resorption of all embryos by gestational day 9. Heterozygotes showed an increased tendency to intrauterine death with some fetuses having incomplete neural tube closure and some live-born heterozygotes developing hydrocephalus. The majority of male heterozygotes were sterile, although the genitourinary system and sperm were grossly normal. Viable heterozygotes had normal triglycerides, but total, LDL, and HDL cholesterol levels were decreased by 37, 37, and 39%, respectively. Hepatic and intestinal apo B mRNA levels were decreased in heterozygotes, presumably contributing to the decreased LDL levels through decreased synthesis of apo B-containing lipoproteins. Kinetic studies indicated that heterozygotes had decreased transport rates of HDL cholesterol ester and apo A-I. As liver and intestinal apo A-I mRNA levels were unchanged, the mechanism for decreased apo A-I transport must be posttranscriptional. Heterozygotes also had normal cholesterol absorption and a normal response of the plasma lipoprotein pattern to chronic consumption of a high fat, high cholesterol, Western-type diet. In summary, we report a mouse model for apo B deficiency with several phenotypic features that were unexpected based on clinical studies of apo B-deficient humans, such as embryonic lethality in homozygotes and neural tube closure defects, male infertility, and a major defect in HDL production in heterozygotes. This model presents an opportunity to study the mechanisms underlying these phenotypic changes. Images PMID:7593600

Huang, L S; Voyiaziakis, E; Markenson, D F; Sokol, K A; Hayek, T; Breslow, J L

1995-01-01

225

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. It’s 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

226

Tracheostomy tubes.  

PubMed

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

Hess, Dean R; Altobelli, Neila P

2014-06-01

227

Null mutation of the Lmo4 gene or a combined null mutation of the Lmo1/Lmo3 genes causes perinatal lethality, and Lmo4 controls neural tube development in mice.  

PubMed

The LIM-only family of proteins comprises four members; two of these (LMO1 and LMO2) are involved in human T-cell leukemia via chromosomal translocations, and LMO2 is a master regulator of hematopoiesis. We have carried out gene targeting of the other members of the LIM-only family, viz., genes Lmo1, Lmo3 and Lmo4, to investigate their role in mouse development. None of these genes has an obligatory role in lymphopoiesis. In addition, while null mutations of Lmo1 or Lmo3 have no discernible phenotype, null mutation of Lmo4 alone causes perinatal lethality due to a severe neural tube defect which occurs in the form of anencephaly or exencephaly. Since the Lmo1 and Lmo3 gene sequences are highly related and have partly overlapping expression domains, we assessed the effect of compound Lmo1/Lmo3 null mutations. Although no anatomical defects were apparent in compound null pups, these animals also die within 24 h of birth, suggesting that a compensation between the related Lmo1 and 3 proteins can occur during embryogenesis to negate the individual loss of these genes. Our results complete the gene targeting of the LIM-only family in mice and suggest that all four members of this family are important in regulators of distinct developmental pathways. PMID:14966285

Tse, E; Smith, A J H; Hunt, S; Lavenir, I; Forster, A; Warren, A J; Grutz, G; Foroni, L; Carlton, M B L; Colledge, W H; Boehm, T; Rabbitts, T H

2004-03-01

228

Gastrostomy Tube (G-Tube)  

MedlinePLUS

... and into the stomach to guide the doctor's positioning of the G-tube. The laparascopic technique is ... TOPIC Finding Your Way in the Health Care System Managing Home Health Care Preparing Your Child for ...

229

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

2012-12-11

230

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

231

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. PMID:20482793

2010-01-01

232

Diffusion tube  

NASA Technical Reports Server (NTRS)

The diffusion tube was designed to operate below about 0.25 percent of water supersaturation. It is simply a long tube lined on the inside with a damp chamois cloth, and heated isothermally to a few degrees centigrade above the incoming air. The diffusion coefficient for water vapor is slightly larger than that for heat, making it possible to supersaturate the airflow. This is the same principle by which transient supersaturations may occur in parallel plate cloud chambers. Only the diffusion of vapor and heat from the walls into the moving air are considered.

Leaitch, R.; Megaw, W. J.

1981-01-01

233

Tube Zither  

NSDL National Science Digital Library

In this activity, learners explore sound by constructing tube zithers, stringed instruments from Southeast Asia and the South Pacific. Use this activity to demonstrate principles of sound including vibration, pitch, tone, frequency, and volume. Note: this activity requires the use of a drill, not included in the cost of materials.

Oakland Discovery Centers

2012-01-01

234

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.

University of California Museum of Paleontology

2010-01-01

235

Hormonal Pregnancy Tests and Neural Tube Malformations  

Microsoft Academic Search

IN 1967 Gal, Kirman and Stern1 reported a possible relationship between pregnancy tests using pills containing synthetic oestrogenic and progesterogenic hormones and the birth of a child with spina bifida. Of the 100 mothers of children with spina bifida, nineteen gave a history of pregnancy diagnosis by this means; only four of the 100 matched control mothers gave such a

Michael Laurence; Mary Miller; MARY VOWLES; KATHLEEN EVANS; CEDRIC CARTER

1971-01-01

236

Fetal surgery for neural tube defects.  

PubMed

A recently completed randomized, controlled, prospective multicenter trial, the Management of Myelomeningocele Study (MOMS), demonstrated that maternal-fetal surgery for myelomeningocele (MMC) before 26 weeks of gestation decreases the need for ventriculoperitoneal shunting, decreases hindbrain herniation, and preserves neurological function. However, the study also found that fetal MMC surgery is not without significant risks, such as premature delivery or maternal complications. The primary objective of this review is to provide a critical overview of the rationale for in-utero intervention for MMC in the context of pathological observations, animal models, initial clinical experience with human fetal MMC surgery, and the results of the randomized trial. The secondary objective is to briefly discuss our approach to fetal MMC. Finally, the ongoing clinical research and the recent developments of potential alternative fetal surgical techniques will be highlighted. PMID:24120287

Danzer, Enrico; Johnson, Mark P

2014-02-01

237

Folic Acid Helps Prevent Neural Tube Defects  

MedlinePLUS

... Stages & Populations Travelers' Health Workplace Safety & Health Features Media Sign up for Features Get Email Updates To ... live longer, healthier and more productive lives. Features Media Sign up for Features Get Email Updates To ...

238

Fetal surgery for neural tube defects  

PubMed Central

Open spina bifida remains a major source of disability despite an overall decrease in incidence. It is frequently diagnosed prenatally and can thus -- potentially -- be treated by fetal surgery. Animal studies and preliminary human studies strongly suggest that at least a portion of the neurological abnormalities seen in these patients are secondary, and occur in mid-gestation. It is estimated that approximately 400 fetal operations have now been performed for myelomeningocele world wide. Despite this large experience, the technique remains of unproven benefit. Preliminary results suggest that fetal surgery results in reversal of hindbrain herniation (the Chiari II malformation), a decrease in shunt-dependent hydrocephalus, and possibly improvement in leg function, but these findings might be explained by selection bias and changing management indications. A randomized prospective trial (the MOMS trial) is currently being conducted by three centers in the United States, and is estimated to be completed in 2009. PMID:17714997

Sutton, Leslie N.

2008-01-01

239

Multisite neural tube closure in humans.  

PubMed

We present evidence for multisite NT closure in humans with representative examples of types of NTDs that would be expected if NT closure in humans is similar to experimental mice models. We determine that the majority of NTDs can be classified by the multisite closure model. Further evidence for multisite closure of the NT is apparent in previous epidemiological studies, recognized monogenic disorders, and environmental and teratogenic exposures. Previous reliance on the single-site closure model has resulted in grouping of anomalies, obscuring evidence for multisite NT closure, etiological heterogeneity, varying recurrence risks, and site-specific effects of environmental factors. The NTDs have been previously referred to as being multifactorial, due to multiple genes and environmental factors. Etiological heterogeneity has been demonstrated previously as well. Classification of NTDs by closure site will be beneficial in better defining etiologies and environmental susceptibilities. Similarly, it is apparent to us that genetic variations in closure sequence, rate, and location are most likely monogenic and result in affected embryos being more susceptible to specific environmental factors, such as the effect of folic acid deficiency. Individual closure sites are most likely under the control of specific embryonically expressed genes, whose monogenic nature may not be apparent postnatally. For the disorders such as Meckel-Gruber syndrome and Walker-Warburg syndrome, the monogenic etiology for NTDs in affected individuals is apparent because of associated malformations. There are three important implications of this study: The first is that monogenic mouse models will be helpful in investigating the pathogenesis of NTDs in humans. The homologies between the mouse and human genome may allow linkage studies to be done in some families who have recurrence of NTDs. Second, in order to have useful results from studies of NTDs, NT anomalies need to be accurately described, either by the classical nomenclature (eg, meroacranium) or by referring to the corresponding closure site involvement (eg, closure 2 defect). Special attention needs to be addressed to those NTDs that do not appear to fit into a discrete closure site (eg, midthoracic spina bifida cystica) or laterally displaced NTDs, since they may be due to other etiologies. With improved nutrition, particularly folic acid treatment, specific etiologies for the remaining NTDs may become more apparent. Finally, recurrence risks for NTDs may vary between families based on the closure site affected, and whether or not associated anomalies are present. PMID:9125329

Van Allen, M I

1996-01-01

240

Electron tube  

DOEpatents

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

241

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

242

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

243

Hierarchical Part-Based Detection of 3D Flexible Tubes: Application to CT Colonoscopy  

E-print Network

Artificial Neural Network (MTANN) to distin- guish between polyps and rectal tubes, which raises questionsHierarchical Part-Based Detection of 3D Flexible Tubes: Application to CT Colonoscopy Adrian Barbu1 of 3D free-form tubular structures, such as the rectal tubes in CT colonoscopy. This method can be used

Barbu, Adrian

244

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

245

Transmural migration of gastrostomy tube retention discs  

Microsoft Academic Search

Background Accidental dislodgment is one of the most frequent causes of avoidable cost and consternation related to gastrostomy tubes. The Sacks–Vine gastrostomy tube, inserted in an antegrade fashion by a percutaneous technique, is extremely stable due to the construction of its disc retention device. However, transmural migration of the retention disc is a known severe delayed complication associated with this

AnneMarie Cahill; Kevin M. Baskin; Robin D. Kaye; Charles R. Fitz; Richard B. Towbin

2004-01-01

246

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

247

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

248

Emission Tube Apparatus  

NSDL National Science Digital Library

This is an image of an emission tube apparatus with tube in place. When plugged in and turned on the gas in the tube will become excited and emit a specific color of light depending upon the type of gas.

Dr. Charles Ward

249

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

250

Neural crest contributions to the lamprey head  

NASA Technical Reports Server (NTRS)

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

McCauley, David W.; Bronner-Fraser, Marianne

2003-01-01

251

Neural patterning in the vertebrate embryo  

Microsoft Academic Search

The embryonic central nervous system (CNS) is patterned along its antero-posterior, dorsal-ventral, and left-right axes. Along the dorsal-ventral axis, cell fate determination occurs during and following neural tube closure and involves the action of two opposing signaling pathways: SHH ventrally from the notochord and BMP\\/GDF dorsally from the boundary of neural and nonneural ectoderm and later from the roof plate.

Curtis R. Altmann; Ali H. Brivanlou

2001-01-01

252

Compact tubing testing unit  

Microsoft Academic Search

A mobile unit is described for use in testing tubing joints as the tubing is being made up and run into an oil well. The mobile unit includes a framework compactly receiving an engine driving a hydraulic pump, a drawworks, high pressure hydraulically actuated pump for pressuring the tubing joint to be tested, and tubing tongs for use in making

Matherne

1974-01-01

253

RDP Neural Network RDP Neural Network Construction Principle  

E-print Network

RDP Neural Network RDP Neural Network Construction Principle Linear Separability Methods for building RDP Neural Networks Geometrical Approaches for Artificial Neural Networks David Elizondo Centre Elizondo Geometrical Approaches for Artificial Neural Networks #12;RDP Neural Network RDP Neural Network

Gorban, Alexander N.

254

Torsion Tests of Tubes  

NASA Technical Reports Server (NTRS)

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

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

1937-01-01

255

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

256

Molecular regulation of neural crest development.  

PubMed

The neural crest is a transient embryonic structure that gives rise to a multitude of different cell types in the vertebrate. As such, it is an ideal model to study the processes of vertebrate differentiation and development. This review focuses on two major questions related to neural crest development. The first question concerns the degree and time of commitment of the neural crest cells to different cell lineages and the emerging role of the homeobox containing genes in regulating this process. Evidence from the cephalic crest suggests that the commitment process does start before the neural crest cells migrate away from the neural tube and gene ablation experiments suggest that different homeobox genes are required for the development of neural and mesenchymal tissue derivatives. However, clonal analysis of neural crest cells before migration suggests that many of the cells remain multi-potential indicating that the final determinative steps occur progressively during migration and in association with environmental influences. The second question concerns the nature of the environmental factors that determine the differentiation of neural crest cells into discrete lineages. Evidence is provided, mainly from in vitro experiments, that purified growth factors selectively promote the differentiation of neural crest cells down either sympathetic, adrenal, sensory, or melanocytic cell lineages. PMID:8103990

Murphy, M; Bartlett, P F

1993-01-01

257

Evolvable synthetic neural system  

NASA Technical Reports Server (NTRS)

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

Curtis, Steven A. (Inventor)

2009-01-01

258

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).

259

Chest Tube Thoracostomy  

MedlinePLUS

... breathe. ? Chest Surgery— Sometimes a chest tube is left in place after surgery. The surgeon can usually tell you if it will be needed and how long it may need to stay in. Risks of Chest Tube Insertion: Below ...

260

Foundations of Artificial Intelligence Neural Networks  

E-print Network

Foundations of Artificial Intelligence Neural Networks Building Artificial Brains #12;Background of observed examples (training data). #12;Neural Networks Objectives Show how the human brain works Introduction The Human Brain (How a neuron works) Building Artificial Neurons Network Architecture and Learning

Qu, Rong

261

Microscale shock tube  

Microsoft Academic Search

This project aims at the simulation, design, fabrication and testing of a microscale shock tube. A step by step procedure has been followed to develop the different components of the microscale shock tube and then combine them together to realize the final device. The document reports on the numerical simulation of flows in a microscale shock tube, the experimental study

Gholamreza Mirshekari

2008-01-01

262

Microhole Tubing Bending Report  

DOE Data Explorer

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

Oglesby, Ken

263

Well tubing handling apparatus  

Microsoft Academic Search

Well tubing handling apparatus is described useful for running and pulling tubing in a well bore and drilling a well bore including a main frame assembly, a pulling and snubbing assembly, a ladder assembly, and a work platform assembly. The apparatus is quickly assembled and torn down. The main frame assembly includes a base, telescoping non-load bearing guide tubes, a

P. S. Sizer

1981-01-01

264

Morphogenesis of the mouse neural plate depends on distinct roles of cofilin 1 in apical and basal epithelial domains.  

PubMed

The genetic control of mammalian epithelial polarity and dynamics can be studied in vivo at cellular resolution during morphogenesis of the mouse neural tube. The mouse neural plate is a simple epithelium that is transformed into a columnar pseudostratified tube over the course of ?24?h. Apical F-actin is known to be important for neural tube closure, but the precise roles of actin dynamics in the neural epithelium are not known. To determine how the organization of the neural epithelium and neural tube closure are affected when actin dynamics are blocked, we examined the cellular basis of the neural tube closure defect in mouse mutants that lack the actin-severing protein cofilin 1 (CFL1). Although apical localization of the adherens junctions, the Par complex, the Crumbs complex and SHROOM3 is normal in the mutants, CFL1 has at least two distinct functions in the apical and basal domains of the neural plate. Apically, in the absence of CFL1 myosin light chain does not become phosphorylated, indicating that CFL1 is required for the activation of apical actomyosin required for neural tube closure. On the basal side of the neural plate, loss of CFL1 has the opposite effect on myosin: excess F-actin and myosin accumulate and the ectopic myosin light chain is phosphorylated. The basal accumulation of F-actin is associated with the assembly of ectopic basal tight junctions and focal disruptions of the basement membrane, which eventually lead to a breakdown of epithelial organization. PMID:25742799

Grego-Bessa, Joaquim; Hildebrand, Jeffrey; Anderson, Kathryn V

2015-04-01

265

Inertance Tube Optimization for Pulse Tube Refrigerators  

NASA Astrophysics Data System (ADS)

The efficiency of regenerative refrigerators is generally maximized when the pressure and flow are in phase near the midpoint of the regenerator. Such a phase relationship minimizes the amplitude of the mass flow for a given acoustic power flow through the regenerator. To achieve this phase relationship in a pulse tube refrigerator requires that the flow at the warm end of the pulse tube lag the pressure by about 60 degrees. The inertance tube allows for the flow to lag the pressure, but such a large phase shift is only possible with relatively large acoustic power flows. In small pulse tube cryocoolers the efficiency is improved by maximizing the phase shift in the inertance tube. This paper describes a simple transmission line model of the inertance tube, which is used to find the maximum phase shift and the corresponding diameter and length of the optimized inertance tube. Acoustic power flows between 1 and 100 W are considered in this study, though the model may be valid for larger systems as well. For large systems the model can be used to find the minimum reservoir volume that in combination with the inertance tube provides a phase shift of 60 degrees. This transmission line model is compared with some experimental results on a small-diameter inertance tube and found to agree quite well provided some heat transfer is taken into account. Design graphs for a frequency of 60 Hz and an average pressure of 2.5 MPa are presented for different pressure ratios and for both adiabatic and isothermal conditions.

Radebaugh, Ray; Lewis, M.; Luo, E.; Pfotenhauer, J. M.; Nellis, G. F.; Schunk, L. A.

2006-04-01

266

21 CFR 868.5800 - Tracheostomy tube and tube cuff.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Tracheostomy tube and tube cuff. 868.5800 Section 868.5800 Food...868.5800 Tracheostomy tube and tube cuff. (a) Identification. A tracheostomy tube and tube cuff is a device intended to be placed...

2011-04-01

267

21 CFR 868.5800 - Tracheostomy tube and tube cuff.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Tracheostomy tube and tube cuff. 868.5800 Section 868.5800 Food...868.5800 Tracheostomy tube and tube cuff. (a) Identification. A tracheostomy tube and tube cuff is a device intended to be placed...

2010-04-01

268

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

269

EFFECTS OF TOXICANTS ON NEURAL DIFFERENTIATION  

EPA Science Inventory

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

270

OPTIMAL DESIGN AND ASSESSMENT OF HIGH PERFORMANCE MICRO BARE-TUBE HEAT EXCHANGERS  

Microsoft Academic Search

An optimal design methodology is proposed for micro bare-tube heat exchangers. A simulated annealing method is employed with a trained neural network representing the heat transfer and pressure drop characteristics of a specified tube bank. A commercial CFD code, FLUENT5, is used to obtain the heat transfer and pressure drop data sets for in-line tube bundles, which are then used

Nobuhide Kasagi; Yuji Suzuki; Naoki Shikazono; Tomohisa Oku

2003-01-01

271

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

272

A new perspective on behavioral inconsistency and neural noise in aging: compensatory speeding of neural communication  

PubMed Central

This paper seeks to present a new perspective on the aging brain. Here, we make connections between two key phenomena of brain aging: (1) increased neural noise or random background activity; and (2) slowing of brain activity. Our perspective proposes the possibility that the slowing of neural processing due to decreasing nerve conduction velocities leads to a compensatory speeding of neuron firing rates. These increased firing rates lead to a broader distribution of power in the frequency spectrum of neural oscillations, which we propose, can just as easily be interpreted as neural noise. Compensatory speeding of neural activity, as we present, is constrained by the: (A) availability of metabolic energy sources; and (B) competition for frequency bandwidth needed for neural communication. We propose that these constraints lead to the eventual inability to compensate for age-related declines in neural function that are manifested clinically as deficits in cognition, affect, and motor behavior. PMID:23055970

Hong, S. Lee; Rebec, George V.

2012-01-01

273

Tube Thoracostomy: Complications and Its Management  

PubMed Central

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

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

2012-01-01

274

Postdoctoral Fellow Neural Cardiovascular Physiology  

E-print Network

Postdoctoral Fellow Neural Cardiovascular Physiology Job Description A postdoctoral position and physiological roles of new components of the renin-angiotensin system in the regulation of cardiovascular with a strong background in molecular biology and cardiovascular physiology. Expertise in sympathetic nerve

Collett Jr., Jeffrey L.

275

Retrograde Gastrojejunostomy Tube Migration  

PubMed Central

Percutaneous enteral feeding tubes are placed about 250,000 times each year in the United States. Although they are relatively safe, their placement may be complicated by perforation, infection, bleeding, vomiting, dislodgment, and obstruction. There have been numerous reports of antegrade migration of gastrojejunostomy (G-J) tubes. We report a case of G-J tube regurgitation following protracted vomiting and discuss the management of this very rare entity. PMID:25614839

Adesina, Adeleke; Rammohan, Guhan

2014-01-01

276

Virtual Lava Tube  

NSDL National Science Digital Library

Lava tubes are cave formations found where volcanoes generate surface flows in the western United States, Japan, Italy, Australia, and other areas. They vary in size and complexity, from short, straight formations to multi-leveled labyrinths that extend for miles. The largest and most extensive lava tubes discovered to date are in Hawaii, where lava flows can travel more than 80 kilometers (50 miles) from their source. This interactive feature offers a visual tour of lava tubes and various features formed by flowing, splashing, or dripping lava. Viewers can click on a cross-section of a lava tube and see photos and explanations for the formation of the features.

277

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

278

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

279

Geiger-Mueller Tube Virtual Lab  

NSDL National Science Digital Library

This virtual lab simulates the traditional GM tube labs, complete with background radiation. In one lab, students can explore how different barriers affect alpha, beta, and gamma radiation, then apply their knowledge to identify an unknown source. In the other, students measure the half-life of a simulated Ba-137m source. Printable lab guides are included for both activities.

2014-04-03

280

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....

281

Steam generator tube failures  

SciTech Connect

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

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

1996-04-01

282

Hologram recording tubes  

NASA Technical Reports Server (NTRS)

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

Rajchman, J. H.

1973-01-01

283

Pyrotechnic Tubing Connector  

NASA Technical Reports Server (NTRS)

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

Graves, Thomas J.; Yang, Robert A.

1988-01-01

284

Fallopian Tube Catheterization  

PubMed Central

Fallopian tube catheterization is used for treatment of infertility caused by proximal tubal occlusion, and has replaced surgical treatment for this condition. More recently, fallopian tube catheterization has been used for tubal sterilization. Interventional radiologists tested numerous methods for tubal occlusion using the rabbit as an animal model. As a result, a tubal device has recently been Food and Drug Administration approved for permanent sterilization using hysteroscopic guidance; it can also be placed fluoroscopically by fallopian tube catheterization as an “off-label” procedure. This is a 5-year continuation and update on a procedure that has been done by interventional radiologists for 25 years; history of the development of fallopian tube catheterization in women has been published in detail in this journal. Highlighted in this article will be description of the basic components needed for fallopian tube catheterization. PMID:24436565

Thurmond, Amy Suzanne

2013-01-01

285

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 ...

Mrs. Johnson

2010-06-22

286

Differentiation state determines neural effects on microvascular endothelial cells  

SciTech Connect

Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. Black-Right-Pointing-Pointer Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell production of nitric oxide. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons have different secretory profiles for angiogenic mediators.

Muffley, Lara A., E-mail: muffley@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Pan, Shin-Chen, E-mail: pansc@mail.ncku.edu.tw [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)] [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Smith, Andria N., E-mail: gnaunderwater@gmail.com [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Ga, Maricar, E-mail: marga16@uw.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)] [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Hocking, Anne M., E-mail: ahocking@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Gibran, Nicole S., E-mail: nicoleg@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)

2012-10-01

287

The tight junction scaffolding protein cingulin regulates neural crest cell migration  

PubMed Central

Neural crest cells give rise to a diverse range of structures during vertebrate development. These cells initially exist in the dorsal neuroepithelium and subsequently acquire the capacity to migrate. Although studies have documented the importance of adherens junctions in regulating neural crest cell migration, little attention has been paid to tight junctions during this process. We now identify the tight junction protein cingulin as a key regulator of neural crest migration. Cingulin knock-down increases the migratory neural crest cell domain, which is correlated with a disruption of the neural tube basal lamina. Overexpression of cingulin also augments neural crest cell migration and is associated with similar basal lamina changes and an expansion of the premigratory neural crest population. Cingulin overexpression causes aberrant ventrolateral neuroepithelial cell delamination, which is linked to laminin loss and a decrease in RhoA. Together, our results highlight a novel function for cingulin in the neural crest. PMID:21905165

Wu, Chyong-Yi; Jhingory, Sharon; Taneyhill, Lisa A.

2011-01-01

288

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

289

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.

290

Travelling-wave tubes  

Microsoft Academic Search

`Travelling-wave tubes' is the name of a recently developed class of electron tubes, operating in the microwave range of frequencies, which amplify by virtue of continuous interaction between an electron stream and a slow-travelling electromagnetic wave. The wave may be propagated along a retarding structure such as a helix or a corrugated waveguide, or it may be a space-charge wave

R. Kompfner

1952-01-01

291

Tubing crimping pliers  

DOEpatents

The disclosure relates to pliers and more particularly to pliers for crimping two or more pieces of copper tubing together prior to their being permanently joined by brazing, soldering or the like. A die containing spring-loaded pins rotates within a cammed ring in the head of the pliers. As the die rotates, the pins force a crimp on tubing held within the pliers.

Lindholm, G.T.

1981-02-27

292

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

1989-01-01

293

Recurrent Neural Networks Neural Computation : Lecture 12  

E-print Network

non-linear dynamical system can be approximated to any accuracy by a recurrent neural network Neural Network Architectures 2. State Space Models and Dynamical Systems 3. Backpropagation Through Time association/prediction). The architectures of recurrent neural networks can take many different forms

Bullinaria, John

294

Coiled tubing operations and services  

SciTech Connect

Coiled tubing offers many advantages over conventional jointed tubing used for drilling in oil fields, including time savings, pumping flexibility, fluid placement, reduced formation damage and safety. The article gives an overview of coiled tubing history and development. Operating concepts are explained, along with descriptions of the major equipment and components associated with coiled tubing use in the oil field today.

Jaworsky, A.S. II (Conoco Inc., Houston, TX (US))

1991-11-01

295

Microwave Background, Backgrounds Hierarchy - Polyphony of Universe  

E-print Network

We discuss the structure, physical nature, dynamic genesis of clearly detected diffuse backgrounds (radiations) in the Universe. From the point of view of Wave Universe concept it is shown, that observed Backgrounds Hierarchy (Polyphony of Universe) is close connected and causely determined by the sound velocity Hierarchy of the physical medium, cosmic (polycomponent) plasma. The well-known Microwave Background (Cosmic Background Radiation - CBR) corresponds to the F[3] Background, that is characterized by the calculated sound velocity C*[3]=11.483 km/s, by the calculated temperature T*[3]=2.9 grad.K and by wavelength of the radiation intensity maximum lambda*[3]=1 mm.

A. M. Chechelnitsky

2001-05-18

296

Microscale shock tube  

NASA Astrophysics Data System (ADS)

This project aims at the simulation, design, fabrication and testing of a microscale shock tube. A step by step procedure has been followed to develop the different components of the microscale shock tube and then combine them together to realize the final device. The document reports on the numerical simulation of flows in a microscale shock tube, the experimental study of gas flow in microchannels, the design, microfabrication, and the test of a microscale shock tube. In the first step, a one-dimensional numerical model for simulation of transport effects at small-scale, appeared in low Reynolds number shock tubes is developed. The conservation equations have been integrated in the lateral directions and three-dimensional effects have been introduced as carefully controlled sources of mass, momentum and energy, into the one-dimensional model. The unsteady flow of gas behind the shock wave is reduced to a quasi-steady laminar flow solution, similar to the Blasius solution. The resulting one-dimensional equations are solved numerically and the simulations are performed for previously reported low Reynolds number shock tube experiments. Good agreement between the shock structure simulation and the attenuation due to the boundary layers has been observed. The simulation for predicting the performance of a microscale shock tube shows the large attenuation of shock wave at low pressure ratios. In the next step the steady flow inside microchannels has been experimentally studied. A set of microchannels with different geometries were fabricated. These microchannels have been used to measure the pressure drop as a function of flow rate in a steady compressible flow. The results of the experiments confirm that the flow inside the microscale shock tube follows the laminar model over the experiment's range of Knudsen number. The microscale shock tube is fabricated by deposition and patterning of different thin layers of selected materials on the silicon substrate. The direct sensing piezoelectric sensors were fabricated and integrated with microchannels patterned on the substrate. The channels were then covered with another substrate. This shock tube is 2000 mum long and it has a 2000 mum wide and 17 mum high rectangular cross section equipped with 5 piezoelectric sensors along the tube. The packaged microscale shock tube was installed in an ordinary shock tube and shock waves with different Mach numbers were directed into the channel. A one-dimensional inviscid calculation as well as viscous simulation using the one-dimensional model have also been performed for the above mentioned geometry. The comparison of results with those of the same geometry for an inviscid flow shows the considerable attenuation of shock strength and deceleration of the shock wave for both incident and reflected shock waves in the channel. The comparison of results with numerically generated results with the one-dimensional model presents good agreement for incident shock waves. Keywords. Shock wave, Shock tube, MEMS, Microfluidic, Piezoelectric sensor, Microchannel, Transport phenomena.

Mirshekari, Gholamreza

297

Coiled tubing working life prediction  

SciTech Connect

Failure of coiled tubing, due to the repeated bending and plastic deformation of coiled tubing on and off the reel and gooseneck, is of great concern in coiled tubing operations. This paper discusses the coiled tubing working life based on one of the coiled tubing life models published in the literature, and compares the results with other models. Certain agreements are found among these models. A group of curves is presented to illustrate the coiled tubing working life affected by coiled tubing size and wall thickness, internal pressure, yield strength, reel diameter, gooseneck radius, operation condition (corrosion) and butt-welded connection (stress concentration). The results show that coiled tubing life can be greatly increased by increasing CT wall thickness and CT strength, while the coiled tubing working life decreases under high internal pressure, corrosion, and butt-weld conditions. These curves can be easily used in estimating coiled tubing life for the field use.

Wu, J.

1995-12-31

298

Notch Signaling Maintains Neural Rosette Polarity  

PubMed Central

Formation of the metazoan body plan requires a complex interplay of morphological changes and patterning, and central to these processes is the establishment of apical/basal cell polarity. In the developing nervous system, apical/basal cell polarity is essential for neural tube closure and maintenance of the neural stem cell population. In this report we explore how a signaling pathway important for nervous system development, Notch signaling, impacts on apical/basal cell polarity in neural differentiation. CSL?/? mouse embryos, which are devoid of canonical Notch signaling, demonstrated a neural tube phenotype consistent with cell polarity and convergent extension defects, including deficiencies in the restricted expression of apical polarity markers in the neuroepithelium. CSL?/? mouse embryonic stem (ES) cells, cultured at low density, behaved as wild-type in the establishment of neural progenitors and apical specification, though progression through rosette formation, an in vitro correlate of neurulation, required CSL for correct maintenance of rosette structure and regulation of neuronal differentiation. Similarly, acute pharmacological inhibition of Notch signaling led to the breakdown of neural rosettes and accelerated neuronal differentiation. In addition to functional Notch signaling, rosette integrity was found to require actin polymerization and Rho kinase (ROCK) activity. Disruption of rosettes through inhibition of actin polymerization or ROCK activity, however, had no effect on neuronal differentiation, indicating that rosette maintenance is not a prerequisite for normal neuronal differentiation. In conclusion, our data indicate that Notch signaling plays a role not only in differentiation, but also in organization and maintenance of polarity during development of the early nervous system. PMID:23675446

Main, Heather; Radenkovic, Jelena; Jin, Shao-bo; Lendahl, Urban; Andersson, Emma R.

2013-01-01

299

Set separation Neural Network paradigms  

E-print Network

Neural Net The inputs Set separation Neural Network paradigms Designing a neural network for forecasting financial time series 29 f´evrier 2008 Designing a neural network for forecasting financial time series #12;Neural Net The inputs Set separation Neural Network paradigms What a Neural Network is ? Each

Chen, Yiling

300

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

PubMed Central

Neural tube defects (NTDs) are the second most common birth defect in humans. Despite many advances in the understanding of NTDs and the identification of many genes related to NTDs, the fundamental etiology for the majority of cases of NTDs remains unclear. Planar cell polarity (PCP) signaling pathway, which is important for polarized cell movement (such as cell migration) and organ morphogenesis through the activation of cytoskeletal pathways, has been shown to play multiple roles during neural tube closure. The disrupted function of PCP pathway is connected with some NTDs. Here, we summarize our current understanding of how PCP factors affect the pathogenesis of NTDs. PMID:21864354

2011-01-01

301

Electronic Neural Networks  

NASA Technical Reports Server (NTRS)

Viewgraphs on electronic neural networks for space station are presented. Topics covered include: electronic neural networks; electronic implementations; VLSI/thin film hybrid hardware for neurocomputing; computations with analog parallel processing; features of neuroprocessors; applications of neuroprocessors; neural network hardware for terrain trafficability determination; a dedicated processor for path planning; neural network system interface; neural network for robotic control; error backpropagation algorithm for learning; resource allocation matrix; global optimization neuroprocessor; and electrically programmable read only thin-film synaptic array.

Thakoor, Anil

1990-01-01

302

Zebrafish Zic2a and Zic2b regulate neural crest and craniofacial development  

PubMed Central

Holoprosencephaly (HPE), the most common malformation of the human forebrain, is associated with defects of the craniofacial skeleton. ZIC2, a zinc-finger transcription factor, is strongly linked to HPE and to a characteristic set of dysmorphic facial features in humans. We have previously identified important functions for zebrafish Zic2 in the developing forebrain. Here, we demonstrate that ZIC2 orthologs zic2a and zic2b also regulate the forming zebrafish craniofacial skeleton, including the jaw and neurocranial cartilages, and use the zebrafish to study Zic2-regulated processes that may contribute to the complex etiology of HPE. Using temporally controlled Zic2a overexpression, we show that the developing craniofacial cartilages are sensitive to Zic2 elevation prior to 24hpf. This window of sensitivity overlaps the critical expansion and migration of the neural crest (NC) cells, which migrate from the developing neural tube to populate vertebrate craniofacial structures. We demonstrate that zic2b influences the induction of NC at the neural plate border, while both zic2a and zic2b regulate NC migratory onset and strongly contribute to chromatophore development. Both Zic2 depletion and early ectopic Zic2 expression cause moderate, incompletely penetrant mispatterning of the NC-derived jaw precursors at 24hpf, yet by 2dpf these changes in Zic2 expression result in profoundly mispatterned chondrogenic condensations. We attribute this discrepancy to an additional role for Zic2a and Zic2b in patterning the forebrain primordium, an important signaling source during craniofacial development. This hypothesis is supported by evidence that transplanted Zic2-deficient cells can contribute to craniofacial cartilages in a wild-type background. Collectively, these data suggest that zebrafish Zic2 plays a dual role during craniofacial development, contributing to two disparate aspects of craniofacial morphogenesis: (1) Neural crest induction and migration, and (2) early patterning of tissues adjacent to craniofacial chondrogenic condensations. PMID:23665173

TeSlaa, Jessica J.; Keller, Abigail N.; Nyholm, Molly K.; Grinblat, Yevgenya

2013-01-01

303

Arsenic-induced alterations in embryonic transcription factor gene expression: implications for abnormal neural development.  

PubMed

We examined the morphological and molecular consequences of acute in utero exposure to teratogenic concentrations of arsenate. The treatment produced a dose-related increase in neural tube defects, along with a significant alteration in the pattern of gene expression for several transcription factors (creb, Hox 3.1, Pax3, and Emx-1) that were examined using in situ transcription and antisense RNA amplification procedures. On gestational day 9:0, there was a significant delay in the embryos progression through neural tube closure, accompanied by a significant downregulation of Hox 3.1 expression and a significant upregulation of Pax3, Emx-1, and creb. As both Hox 3.1 and Pax3 serve to regulate N-CAM expression, it is possible that abnormalities associated with N-CAM may compromise neural crest cell migration and normal neural tube closure. PMID:8754282

Wlodraczyk, B; Bennett, G D; Calvin, J A; Craig, J C; Finnell, R H

1996-01-01

304

Intelligent Space Tube Optimization for speeding ground water remedial design.  

PubMed

An innovative Intelligent Space Tube Optimization (ISTO) two-stage approach facilitates solving complex nonlinear flow and contaminant transport management problems. It reduces computational effort of designing optimal ground water remediation systems and strategies for an assumed set of wells. ISTO's stage 1 defines an adaptive mobile space tube that lengthens toward the optimal solution. The space tube has overlapping multidimensional subspaces. Stage 1 generates several strategies within the space tube, trains neural surrogate simulators (NSS) using the limited space tube data, and optimizes using an advanced genetic algorithm (AGA) with NSS. Stage 1 speeds evaluating assumed well locations and combinations. For a large complex plume of solvents and explosives, ISTO stage 1 reaches within 10% of the optimal solution 25% faster than an efficient AGA coupled with comprehensive tabu search (AGCT) does by itself. ISTO input parameters include space tube radius and number of strategies used to train NSS per cycle. Larger radii can speed convergence to optimality for optimizations that achieve it but might increase the number of optimizations reaching it. ISTO stage 2 automatically refines the NSS-AGA stage 1 optimal strategy using heuristic optimization (we used AGCT), without using NSS surrogates. Stage 2 explores the entire solution space. ISTO is applicable for many heuristic optimization settings in which the numerical simulator is computationally intensive, and one would like to reduce that burden. PMID:18754799

Kalwij, Ineke M; Peralta, Richard C

2008-01-01

305

Calibration-Tube Dewar  

NASA Technical Reports Server (NTRS)

Container maintains reference material for gas chromatography at constant temperature for extended periods. Developed for holding peroxyacetylnitrate (PAN), material unstable at room temperature but stable at 0 degree C. Keeps vial of PAN at this temperature by immersing in mixture of water and ice. Perforated tube surrounds vial, protects from damage by ice but allows cold water to circulate around. Plug with handle removable so ice added through filler tube. O-rings seal joints around removable parts. Substances undergoing phase changes at other temperatures substituted for ice and water if different reference materials and storage temperatures used. Used on research aircraft collecting and analyzing air samples in troposphere and stratosphere.

Herlth, Donald B.; Ohara, Dean P.

1989-01-01

306

Biologically Inspired Neural Architectures of Voluntary Movement1  

E-print Network

states. The modules are developed using much of what is known about the human brain and its functional. The domain is rapidly growing, involving researchers with backgrounds ranging from psychology and cellular simulations with biologically inspired neural models. The general aim is to explore the neural mechanisms

Kouroupetroglou, Georgios

307

Introduction to the modified probabilistic neural network for general signal processing applications  

Microsoft Academic Search

This paper introduces a practical and easy-to-understand network for signal processing called the modified probabilistic neural network (MPNN). It begins with a short introduction to the application of artificial neural networks to signal processing followed by a background and review of the MPNN theory. The MPNN is a regression technique similar to Specht's (1991) general regression neural network, which is

Anthony Zaknich

1998-01-01

308

Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns  

NASA Technical Reports Server (NTRS)

The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However, migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.

Meulemans, Daniel; Bronner-Fraser, Marianne

2002-01-01

309

Uronephrological outcomes of patients with neural tube defects  

PubMed Central

Objectives: To review the uronephrological outcomes of myelomeningocele (MMC) patients attending a Spina Bifida Clinic. Methods: We retrospectively reviewed the medical records of all patients from the combined Spina Bifida Clinic, at King Khalid University Hospital, Riyadh, Saudi Arabia between 1999 and 2009 who had at least one year of follow-up with us. We examined their demographic data, uronephrological status at presentation, most recent follow-up, and the rate of surgical intervention. Results: During the 10-year period, 188 patients were actively followed-up. The mean age at presentation was 5.3 years ± 3.6 SD. At their last follow-up, 109 patients (58%) were using clean intermittent catheterization, 44 (23%) had received Botox® injections, and 26 (14%) had undergone bladder reconstruction. Most (66%) patients were older than 3 years when they presented to us; this group had a significantly higher rate of surgical intervention (Botox® or reconstruction) compared with those who came to us earlier (p=0.003 for patients receiving Botox® injections, and p=0.025 for patients undergoing bladder reconstruction). Conclusion: Our multidisciplinary Spina Bifida Clinic is an integral part of MCC management to reach a safe urological outcome. Early presentations to our clinic resulted in a lesser need for surgical intercession compared with those who presented at more than 3 years old. PMID:25551115

Al-Hazmi, Hamdan H.; Trbay, Mahmoud S.; Gomha, Abdulmonem B.; Elderwy, Ahmad A.; Khatab, Amenah J.; Neel, Khalid F.

2014-01-01

310

Cats, Frogs, and Snakes: Early Concepts of Neural Tube Defects  

Microsoft Academic Search

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

Michael Obladen

2011-01-01

311

Introduction Anteroposterior (AP) patterning of the developing neural tube  

E-print Network

members of the WNT and FGF growth factor families, retinoic acid receptors, and HOX genes. We have of the nervous system (Eyal-Giladi, 1954; Nieuwkoop, 1952). The major components of the activation signal are FGF and WNT signals that act before gastrulation to induce the organizer to secrete inhibitors of BMP and WNT

Blumberg, Bruce

312

What Are the Treatments for Neural Tube Defects?  

MedlinePLUS

... Director’s testimony Advisory Groups Councils, committees, task forces & boards that help guide activities Staff Directory Searchable directory, ... NIH Scientists Combine Efforts to Advance Birth Defects Research It’s in the DNA: Animal Models Offer Clues to Human Development How Can ...

313

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

314

Heat-shrink plastic tubing seals joints in glass tubing  

NASA Technical Reports Server (NTRS)

Small units of standard glass apparatus held together by short lengths of transparent heat-shrinkable polyolefin tubing. The tubing is shrunk over glass O-ring type connectors having O-rings but no lubricant.

Del Duca, B.; Downey, A.

1968-01-01

315

Shock Tube Design  

E-print Network

the diaphragms which allows a single person to change the diaphragm in a timely manner. The entire tube is supported on an I-beam to maintain the rigidity of the system while inclined. To accommodate a variable inclination, a hybrid winch support system...

Koppenberger, Peter K.

2010-07-14

316

Marshmallow Puff Tube  

NSDL National Science Digital Library

In this demonstration/activity, learners observe as a regular size marshmallow is blown through a tube made from a manila file folder. The result is spectacular, and the process provides a great illustration of Newton's 2nd Law, F=ma.

2012-06-26

317

Well tube scraping tool  

Microsoft Academic Search

In order to remove the accumulation of solidified paraffin, sulfates, and carbonates, it has been a conventional practice in the oil and gas industry to utilize tools which may be pumped through the tubing associated with the wells which are generally known as TFL or through flowline tools. A piston section of a TFL tool having an elastic substantially spherical

W. A. Jr

1971-01-01

318

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

319

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

320

Resonance tube igniter  

NASA Technical Reports Server (NTRS)

Reasonance induced in stoichiometric mixtures of gaseous hydrogen-oxygen produces temperatures /over 1100 deg F/ high enough to cause ignition. Resonance tube phenomenon occurs when high pressure gas is forced through sonic or supersonic nozzle into short cavity. Various applications for the phenomenon are discussed.

Conrad, E. W.; Pavli, A. J.; Phillips, B. R.

1970-01-01

321

Overnight nasogastric tube feeding.  

PubMed

Overnight nasogastric tube feeding allows the patient freedom for normal daytime activities and exercise, essential components of rehabilitation. In order to avoid disturbed nights through frequent micturition we have kept the volume of feed to a minimum. Two types of feed have been used: 1. A supplementary isosmolar feed containing 1000 kCals in 1 litre. 2. A concentrated low volume (404 mosm/kg) feed supplying 1800 kCals including 60 g of nitrogen in 1 litre. Both were delivered via a fine bore tube (internal diameter 1 mm) by continuous infusion from a 1-1.5 litre reservoir using a rotary pump. Feed 1 was given to 64 undernourished elderly female patients (group 1) with fractured neck of femur, the tube being tolerated by 78%; 47 patients in this group were fed for more than 5 days. Feed 2 was given to 10 patients in hospital (group 2) and 8 patients at home (group 3). Few side effects were encountered, the hyperosmolar feed causing no diarrhoea, nausea or hyperglycaemia, emphasising the importance of osmoles per unit time rather than per unit volume. Voluntary oral intake was neither impaired nor increased during the period of tube feeding in group 1, in whom anorexia and thinness were longstanding. In group 2, with recent onset of anorexia and weight loss, tube feeding disinhibited appetite, resulting in a doubling of voluntary oral intake. Improvement in anthropometric and biochemical nutritional parameters was seen in all patients. Clinical improvements e.g. closure of fistulae were also observed. This paper describes the results of our trial of both these options in patients treated in hospital or at home. PMID:16831697

Bastow, D; Rawlings, J; Allison, S P

1985-02-01

322

Nasogastric and Enteral Feeding Tubes GI/GU Nasogastric Tubes  

E-print Network

. and 10 FR. Nasogastric and Enteral Feeding Tubes Lucile Packard Children's Hospital Heart Center reduces the risk of exposure to gastric contents. Anderson tube with Anti-Reflux Valve designed double lumen gastric sump tube: The principal green-colored channel is connected to a suction apparatus

Kay, Mark A.

323

Environmental test report for the WX-32335 SEC camera tube. [for International Ultraviolet Explorer  

NASA Technical Reports Server (NTRS)

The environmental testing activity on the WX-32335 was carried out to determine if this tube type could withstand the environmental requirements established for the International Ultraviolet Explorer (IUE) camera tube (WX-32224). The results of the tests led to the following conclusions: (1) The WX-32335 as processed with a CsTe photocathode surface can withstand the temperature extremes established for the IUE camera tube without damage to the photocathode surface or without introducing background signal in the tube after one hour of dark integration. (2) The WX-32335 built with a WX-32224 type target support structure can withstand the sinusoidal vibration requirements established for the IUE camera tube. (3) Although the vibration test of the WX-32335 type tubes built with the flat target ring structure could not be completed, there was no indication that these tubes could not withstand the sinusoidal vibration requirements established for the IUE camera tube.

Malanoski, R. J.

1973-01-01

324

Multiple test tubes stirred mechanically  

NASA Technical Reports Server (NTRS)

Mechanical device simultaneously stirs multiple test tubes under controlled laboratory conditions. The invention provides a variable stirring rate, minimal amount of contamination of tube contents, unattended and simple operation, and easy maintenance and cleaning.

Leon, H. J.; Strong, I. J.

1965-01-01

325

Steam generator tube vibration measurement  

SciTech Connect

There are many steam generator tube problems in world wide nuclear power plants. In order to investigate flow-induced vibration problem of steam generator tubes, investigation of their support conditions in the field units is exceedingly important. MHI has developed a ``Steam Generator Tube Vibration Measurement System`` for this purpose, which is applicable to steam generator tubes in the field during plant-shutdown. The system has an ECT-type probe which can be inserted into the steam generator tubes by using an ECT probe pusher-puller; hence the system can access any tube. Using this system, the tube natural vibration frequency can be measured. This system has already been applied to many operating units where top tube-support-plate support conditions were investigated.

Kusakabe, T. [Mitsubishi Heavy Industries, Ltd., Kobe (Japan); Nakamura, T. [Mitsubishi Heavy Industries, Ltd., Takasago (Japan)

1995-08-01

326

Quarter-wave pulse tube  

NASA Astrophysics Data System (ADS)

In high-power pulse-tube refrigerators, the pulse tube itself can be very long without too much dissipation of acoustic power on its walls. The pressure amplitude, the volume-flow-rate amplitude, and the time phase between them evolve significantly along a pulse tube that is about a quarter-wavelength long. Proper choice of length and area makes the oscillations at the ambient end of the long pulse tube optimal for driving a second, smaller pulse-tube refrigerator, thereby utilizing the acoustic power that would typically have been dissipated in the first pulse-tube refrigerator's orifice. Experiments show that little heat is carried from the ambient heat exchanger to the cold heat exchanger in such a long pulse tube, even though the oscillations are turbulent and even when the tube is compactly coiled.

Swift, G. W.; Gardner, D. L.; Backhaus, S. N.

2011-10-01

327

Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells.  

PubMed

The classical view of neural plate development held that it arises from the ectoderm, after its separation from the mesodermal and endodermal lineages. However, recent cell-lineage-tracing experiments indicate that the caudal neural plate and paraxial mesoderm are generated from common bipotential axial stem cells originating from the caudal lateral epiblast. Tbx6 null mutant mouse embryos which produce ectopic neural tubes at the expense of paraxial mesoderm must provide a clue to the regulatory mechanism underlying this neural versus mesodermal fate choice. Here we demonstrate that Tbx6-dependent regulation of Sox2 determines the fate of axial stem cells. In wild-type embryos, enhancer N1 of the neural primordial gene Sox2 is activated in the caudal lateral epiblast, and the cells staying in the superficial layer sustain N1 activity and activate Sox2 expression in the neural plate. In contrast, the cells destined to become mesoderm activate Tbx6 and turn off enhancer N1 before migrating into the paraxial mesoderm compartment. In Tbx6 mutant embryos, however, enhancer N1 activity persists in the paraxial mesoderm compartment, eliciting ectopic Sox2 activation and transforming the paraxial mesoderm into neural tubes. An enhancer-N1-specific deletion mutation introduced into Tbx6 mutant embryos prevented this Sox2 activation in the mesodermal compartment and subsequent development of ectopic neural tubes, indicating that Tbx6 regulates Sox2 via enhancer N1. Tbx6-dependent repression of Wnt3a in the paraxial mesodermal compartment is implicated in this regulatory process. Paraxial mesoderm-specific misexpression of a Sox2 transgene in wild-type embryos resulted in ectopic neural tube development. Thus, Tbx6 represses Sox2 by inactivating enhancer N1 to inhibit neural development, and this is an essential step for the specification of paraxial mesoderm from the axial stem cells. PMID:21331042

Takemoto, Tatsuya; Uchikawa, Masanori; Yoshida, Megumi; Bell, Donald M; Lovell-Badge, Robin; Papaioannou, Virginia E; Kondoh, Hisato

2011-02-17

328

Tbx6-dependent Sox2 regulation determines neural vs mesodermal fate in axial stem cells  

PubMed Central

The classical view of neural plate development held that it arises from the ectoderm, after its separation from the mesodermal and endodermal lineages. However, recent cell lineage tracing experiments indicate that the caudal neural plate and paraxial mesoderm are generated from common bipotential axial stem cells originating from the caudal lateral epiblast (CLE)1,2. Tbx6 null mutant mouse embryos which produce ectopic neural tubes at the expense of paraxial mesoderm3 must provide a clue to the regulatory mechanism underlying this neural versus mesodermal fate choice. Here we demonstrate that Tbx6-dependent regulation of Sox2 determines the fate of axial stem cells. In wild-type embryos, enhancer N1 of the neural primordial gene Sox2 is activated in the CLE, and the cells staying in the superficial layer sustain N1 activity and activate Sox2 expression in the neural plate4-6. In contrast, the cells destined to become mesoderm activate Tbx6 and turn off enhancer N1 before migrating into the paraxial mesoderm compartment. In Tbx6 mutant embryos, however, enhancer N1 activity persists in the paraxial mesoderm compartment, eliciting ectopic Sox2 activation and transforming the paraxial mesoderm into neural tubes. An enhancer N1-specific deletion mutation introduced into Tbx6 mutant embryos prevented this Sox2 activation in the mesodermal compartment and subsequent development of ectopic neural tubes, indicating that Tbx6 regulates Sox2 via enhancer N1. Tbx6-dependent repression of Wnt3a in the paraxial mesodermal compartment is implicated in this regulatory process. Paraxial mesoderm-specific misexpression of a Sox2 transgene in wild type embryos resulted in ectopic neural tube development. Thus, Tbx6 represses Sox2 by inactivating enhancer N1 to inhibit neural development, and this is an essential step for the specification of paraxial mesoderm from the axial stem cells. PMID:21331042

Takemoto, Tatsuya; Uchikawa, Masanori; Yoshida, Megumi; Bell, Donald M.; Lovell-Badge, Robin; Papaioannou, Virginia E.; Kondoh, Hisato

2010-01-01

329

Reduction of Endotracheal Tube Biofilms Using Antimicrobial Photodynamic Therapy  

PubMed Central

Background Ventilator-associated pneumonia (VAP) is reported to occur in 12 to 25% of patients who require mechanical ventilation with a mortality rate of 24 to 71%. The endotracheal (ET) tube has long been recognized as a major factor in the development of VAP since biofilm harbored within the ET tube become dislodged during mechanical ventilation and have direct access to the lungs. The objective of this study was to demonstrate the safety and effectiveness of a non-invasive antimicrobial photodynamic therapy (aPDT) treatment method of eradicating antibiotic resistant biofilms from ET tubes in an in vitro model. Methods Antibiotic resistant polymicrobial biofilms of Pseudomonas aerugenosa and MRSA were grown in ET tubes and treated, under standard ventilator conditions, with a methylene blue (MB) photosensitizer and 664nm non-thermal activating light. Cultures of the lumen of the ET tube were obtained before and after light treatment to determine efficacy of biofilm reduction. Results The in vitro ET tube biofilm study demonstrated that aPDT reduced the ET tube polymicrobial biofilm by >99.9% (p<0.05%) after a single treatment. Conclusions MB aPDT can effectively treat polymicrobial antibiotic resistant biofilms in an ET tube. PMID:21987599

Biel, Merrill A.; Sievert, Chet; Usacheva, Marina; Teichert, Matthew; Wedell, Eric; Loebel, Nicolas; Rose, Andreas; Zimmermann, Ron

2011-01-01

330

Evaluation of a large format image tube camera for the shuttle sortie mission  

NASA Technical Reports Server (NTRS)

A large format image tube camera of a type under consideration for use on the Space Shuttle Sortie Missions is evaluated. The evaluation covers the following subjects: (1) resolving power of the system (2) geometrical characteristics of the system (distortion etc.) (3) shear characteristics of the fiber optic coupling (4) background effects in the tube (5) uniformity of response of the tube (as a function of wavelength) (6) detective quantum efficiency of the system (7) astronomical applications of the system. It must be noted that many of these characteristics are quantitatively unique to the particular tube under discussion and serve primarily to suggest what is possible with this type of tube.

Tifft, W. C.

1976-01-01

331

NEI You Tube Videos: Amblyopia  

MedlinePLUS

... NEI Education Programs Training and Jobs NEI YouTube Videos YouTube Videos Home Age-Related Macular Degeneration Amblyopia ... of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Amblyopia Your browser does not support iframes please ...

332

180 Wrapped Tubes Herbert Edelsbrunner  

E-print Network

180 Wrapped Tubes Herbert Edelsbrunner Department of Computer Science, Duke University, Durham, NC of Hermann's current age. That ratio will go down and we expect it to approach zero. Each tube is defined of the hole through the middle. To determine the sign, we see whether the tube curls towards the middle

Edelsbrunner, Herbert

333

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

334

Collapse pressure of coiled tubing  

SciTech Connect

The collapse pressure is a measure of an external force required to collapse a tube in the absence of internal pressure. It is defined as the minimum pressure required to yield the tube in the absence of internal pressure. Coiled tubing is sometimes used in high-pressure wells. If the external pressure becomes too high, the coiled tubing will collapse. This could not only lead to serious well-control problems, but may result in extensive fishing operations. A reliable safety criterion of collapse pressure for the coiled tubing is needed by the coiled tubing operators. Theoretical models of collapse pressure are well developed for perfectly round coiled tubing but not for oval coiled tubing. Coiled tubing is initially manufactured with nearly perfect roundness, sometimes having a small ovality (typically {le} 0.5%). Perfectly round CT becomes oval owing to the plastic mechanical deformation of the coiled tubing as it spooled on and off the reel and over the gooseneck. As the cycling continues, the ovality usually increases. This ovality significantly decreases the collapse failure pressure as compared to perfectly round tubing. In this paper, an analytical model of collapse pressure for oval tubing under axial tension or compression is developed based on elastic instability theory and the von Mises criterion. The theoretical model shows satisfactory agreement with experimental data.

Yang, Y.S. [Precision Tube Technology, Inc., Houston, TX (United States)

1996-09-01

335

78 FR 48416 - Light-Walled Rectangular Pipe and Tube From the People's Republic of China: Final Results of the...  

Federal Register 2010, 2011, 2012, 2013, 2014

...Trade Administration [C-570-915] Light-Walled Rectangular Pipe and Tube From...review of the countervailing duty order on light-walled rectangular pipe and tube from...Background The countervailing duty order on light-walled rectangular pipe and tube...

2013-08-08

336

Overview of artificial neural networks.  

PubMed

The artificial neural network (ANN), or simply neural network, is a machine learning method evolved from the idea of simulating the human brain. The data explosion in modem drug discovery research requires sophisticated analysis methods to uncover the hidden causal relationships between single or multiple responses and a large set of properties. The ANN is one of many versatile tools to meet the demand in drug discovery modeling. Compared to a traditional regression approach, the ANN is capable of modeling complex nonlinear relationships. The ANN also has excellent fault tolerance and is fast and highly scalable with parallel processing. This chapter introduces the background of ANN development and outlines the basic concepts crucially important for understanding more sophisticated ANN. Several commonly used learning methods and network setups are discussed briefly at the end of the chapter. PMID:19065803

Zou, Jinming; Han, Yi; So, Sung-Sau

2008-01-01

337

Using Neural Networks  

E-print Network

A neural network approach is employed for estimating key efficiency parameters in a gas turbine engine. The concept is demonstrated within a limited operating region for a given engine. The neural network is developed to estimate certain...

Gabel, S.

338

Parallel Consensual Neural Networks  

NASA Technical Reports Server (NTRS)

A new neural network architecture is proposed and applied in classification of remote sensing/geographic data from multiple sources. The new architecture is called the parallel consensual neural network and its relation to hierarchical and ensemble neural networks is discussed. The parallel consensual neural network architecture is based on statistical consensus theory. The input data are transformed several times and the different transformed data are applied as if they were independent inputs and are classified using stage neural networks. Finally, the outputs from the stage networks are then weighted and combined to make a decision. Experimental results based on remote sensing data and geographic data are given. The performance of the consensual neural network architecture is compared to that of a two-layer (one hidden layer) conjugate-gradient backpropagation neural network. The results with the proposed neural network architecture compare favorably in terms of classification accuracy to the backpropagation method.

Benediktsson, J. A.; Sveinsson, J. R.; Ersoy, O. K.; Swain, P. H.

1993-01-01

339

Induction plasma tube  

DOEpatents

An induction plasma tube having a segmented, fluid-cooled internal radiation shield is disclosed. The individual segments are thick in cross-section such that the shield occupies a substantial fraction of the internal volume of the plasma enclosure, resulting in improved performance and higher sustainable plasma temperatures. The individual segments of the shield are preferably cooled by means of a counterflow fluid cooling system wherein each segment includes a central bore and a fluid supply tube extending into the bore. The counterflow cooling system results in improved cooling of the individual segments and also permits use of relatively larger shield segments which permit improved electromagnetic coupling between the induction coil and a plasma located inside the shield. Four embodiments of the invention, each having particular advantages, are disclosed.

Hull, Donald E. (Los Alamos, NM)

1984-01-01

340

Induction plasma tube  

DOEpatents

An induction plasma tube having a segmented, fluid-cooled internal radiation shield is disclosed. The individual segments are thick in cross-section such that the shield occupies a substantial fraction of the internal volume of the plasma enclosure, resulting in improved performance and higher sustainable plasma temperatures. The individual segments of the shield are preferably cooled by means of a counterflow fluid cooling system wherein each segment includes a central bore and a fluid supply tube extending into the bore. The counterflow cooling system results in improved cooling of the individual segments and also permits use of relatively larger shield segments which permit improved electromagnetic coupling between the induction coil and a plasma located inside the shield. Four embodiments of the invention, each having particular advantages, are disclosed.

Hull, D.E.

1982-07-02

341

Downhole pulse tube refrigerators  

Microsoft Academic Search

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

G. Swift; D. Gardner

1997-01-01

342

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

343

Joined concentric tubes  

DOEpatents

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

344

Optical Neural Interfaces  

PubMed Central

Genetically encoded optical actuators and indicators have changed the landscape of neuroscience, enabling targetable control and readout of specific components of intact neural circuits in behaving animals. Here, we review the development of optical neural interfaces, focusing on hardware designed for optical control of neural activity, integrated optical control and electrical readout, and optical readout of population and single-cell neural activity in freely moving mammals. PMID:25014785

Warden, Melissa R.; Cardin, Jessica A.; Deisseroth, Karl

2014-01-01

345

27 CFR 41.35 - Cigarette tubes.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Cigarette tubes. 41.35 Section 41...IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED... Taxes Tax Rates § 41.35 Cigarette tubes. Cigarette tubes...

2014-04-01

346

27 CFR 41.35 - Cigarette tubes.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Cigarette tubes. 41.35 Section 41...IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED... Taxes Tax Rates § 41.35 Cigarette tubes. Cigarette tubes...

2013-04-01

347

27 CFR 41.35 - Cigarette tubes.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2011-04-01 true Cigarette tubes. 41.35 Section 41...IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED... Taxes Tax Rates § 41.35 Cigarette tubes. Cigarette tubes...

2012-04-01

348

27 CFR 41.35 - Cigarette tubes.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Cigarette tubes. 41.35 Section 41...IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED... Taxes Tax Rates § 41.35 Cigarette tubes. Cigarette tubes...

2010-04-01

349

27 CFR 41.35 - Cigarette tubes.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Cigarette tubes. 41.35 Section 41...IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED... Taxes Tax Rates § 41.35 Cigarette tubes. Cigarette tubes...

2011-04-01

350

IDENTIFICATION AND CONTROL METHODS FOR HIGH POWER ELECTRON BEAM-DRIVEN MICROWAVE TUBES  

E-print Network

concepts to the field of high power microwave (HPM) tubes. These concepts are well known to the control systems community, but have not yet been fully exploited within the HPM community. The simpler is extremely fast to warrant the inclusion of dynamical effects, and that a static, neural network model

351

Traveling-Wave Tubes  

NASA Technical Reports Server (NTRS)

The traveling-wave tube (TWT) is a vacuum device invented in the early 1940's used for amplification at microwave frequencies. Amplification is attained by surrendering kinetic energy from an electron beam to a radio frequency (RF) electromagnetic wave. The demand for vacuum devices has been decreased largely by the advent of solid-state devices. However, although solid state devices have replaced vacuum devices in many areas, there are still many applications such as radar, electronic countermeasures and satellite communications, that require operating characteristics such as high power (Watts to Megawatts), high frequency (below 1 GHz to over 100 GHz) and large bandwidth that only vacuum devices can provide. Vacuum devices are also deemed irreplaceable in the music industry where musicians treasure their tube-based amplifiers claiming that the solid-state and digital counterparts could never provide the same "warmth" (3). The term traveling-wave tube includes both fast-wave and slow-wave devices. This article will concentrate on slow-wave devices as the vast majority of TWTs in operation fall into this category.

Kory, Carol L.

1998-01-01

352

Enhanced expression of FNDC5 in human embryonic stem cell-derived neural cells along with relevant embryonic neural tissues.  

PubMed

Availability of human embryonic stem cells (hESCs) has enhanced the capability of basic and clinical research in the context of human neural differentiation. Derivation of neural progenitor (NP) cells from hESCs facilitates the process of human embryonic development through the generation of neuronal subtypes. We have recently indicated that fibronectin type III domain containing 5 protein (FNDC5) expression is required for appropriate neural differentiation of mouse embryonic stem cells (mESCs). Bioinformatics analyses have shown the presence of three isoforms for human FNDC5 mRNA. To differentiate which isoform of FNDC5 is involved in the process of human neural differentiation, we have used hESCs as an in vitro model for neural differentiation by retinoic acid (RA) induction. The hESC line, Royan H5, was differentiated into a neural lineage in defined adherent culture treated by RA and basic fibroblast growth factor (bFGF). We collected all cell types that included hESCs, rosette structures, and neural cells in an attempt to assess the expression of FNDC5 isoforms. There was a contiguous increase in all three FNDC5 isoforms during the neural differentiation process. Furthermore, the highest level of expression of the isoforms was significantly observed in neural cells compared to hESCs and the rosette structures known as neural precursor cells (NPCs). High expression levels of FNDC5 in human fetal brain and spinal cord tissues have suggested the involvement of this gene in neural tube development. Additional research is necessary to determine the major function of FDNC5 in this process. PMID:25497839

Ghahrizjani, Fatemeh Ahmadi; Ghaedi, Kamran; Salamian, Ahmad; Tanhaei, Somayeh; Nejati, Alireza Shoaraye; Salehi, Hossein; Nabiuni, Mohammad; Baharvand, Hossein; Nasr-Esfahani, Mohammad Hossein

2015-02-25

353

RESEARCH Open Access Acupuncture modulates temporal neural  

E-print Network

RESEARCH Open Access Acupuncture modulates temporal neural responses in wide brain networks Background: Accumulating neuroimaging studies in humans have shown that acupuncture can modulate a widely, a striking feature of acupuncture-induced analgesia is found to be associated with its long-last effect

Tian, Jie

354

Step piston pulse tube refrigerator  

NASA Astrophysics Data System (ADS)

In this paper, a numerical simulation is done for a step piston pulse tube refrigerator. The step piston pulse tube refrigerator is a modification of an inertance tube pulse tube refrigerator, which has a step piston compressor. The step piston in a step cylinder forms a compression space which is connected to the after cooler and an expansion space which is connected to the buffer. Numerical simulation shows that it is more effective at higher refrigeration temperature. It also shows there is an optimum swept volume ratio of the expansion space over the compression space, and an optimum diameter and length of the inertance tube for a given refrigerator.

Zhu, Shaowei

2014-11-01

355

Apparatus Splits Glass Tubes Longitudinally  

NASA Technical Reports Server (NTRS)

Tubes split into half cylinders by hot-wire/thermal-shock method. Tube to be cut placed on notched jig in apparatus. Nichrome wire stretched between arms of pivoted carriage and oriented parallel to notch. Wire heated by electrical current while resting on tube. After heating for about 1 minute for each millimeter of thickness of glass, tube quenched in water and split by resulting thermal shock. Apparatus used to split tubes in sizes ranging from 3/8 in. in diameter by 1 in. long to 1 1/2 in. in diameter by 4 in. long.

Shaw, Ernest; Manahan, Robert O'neil

1993-01-01

356

Nested Neural Networks  

NASA Technical Reports Server (NTRS)

Report presents analysis of nested neural networks, consisting of interconnected subnetworks. Analysis based on simplified mathematical models more appropriate for artificial electronic neural networks, partly applicable to biological neural networks. Nested structure allows for retrieval of individual subpatterns. Requires fewer wires and connection devices than fully connected networks, and allows for local reconstruction of damaged subnetworks without rewiring entire network.

Baram, Yoram

1992-01-01

357

Computational Verb Neural Networks  

Microsoft Academic Search

When any attribute value in a conventional neural network is verbified, the result is a computational verb neural network(VNN). We can verbify inputs, outputs, biases, weights and many other attributes of conventional neural networks. In this paper, we reported two types of VNNs. The first one consists of computational verb inputs and numerical output. The second one consists of computational

Tao Yang

2007-01-01

358

Sip1 mediates an E-cadherin-to-N-cadherin switch during cranial neural crest EMT  

PubMed Central

The neural crest, an embryonic stem cell population, initially resides within the dorsal neural tube but subsequently undergoes an epithelial-to-mesenchymal transition (EMT) to commence migration. Although neural crest and cancer EMTs are morphologically similar, little is known regarding conservation of their underlying molecular mechanisms. We report that Sip1, which is involved in cancer EMT, plays a critical role in promoting the neural crest cell transition to a mesenchymal state. Sip1 transcripts are expressed in premigratory/migrating crest cells. After Sip1 loss, the neural crest specifier gene FoxD3 was abnormally retained in the dorsal neuroepithelium, whereas Sox10, which is normally required for emigration, was diminished. Subsequently, clumps of adherent neural crest cells remained adjacent to the neural tube and aberrantly expressed E-cadherin while lacking N-cadherin. These findings demonstrate two distinct phases of neural crest EMT, detachment and mesenchymalization, with the latter involving a novel requirement for Sip1 in regulation of cadherin expression during completion of neural crest EMT. PMID:24297751

Rogers, Crystal D.; Saxena, Ankur

2013-01-01

359

Elastocapillary flows in flexible tubes  

NASA Astrophysics Data System (ADS)

Interactions between capillary and elastic effects are relevant to a variety of applications from micro- and nano-scale manufacturing to biological systems. In this work, we investigate capillary flows in flexible, millimeter-scale cylindrical elastic tubes. We demonstrate that surface tension can cause sufficiently flexible tubes to collapse and coalesce spontaneously through non-axisymmetric buckling, and develop criteria for the initial deformation and complete collapse of a circular tube. Experimental results for capillary rise and evaporation of a liquid in a flexible tube are presented, and several regimes are seen for the equilibrium state of a flexible tube deforming under capillary pressure. Deformations of the tube walls are measured in different regimes and compared with a shell theory model. Analysis and experimental results show that despite the complex and non-axisymmetric deformed shapes of cylindrical structures, the elastocapillary length used in previous literature for flat plates and sheets can be used to predict the behavior of flexible tubes.

Hoberg, Theresa B.; Verneuil, Emilie; Hosoi, A. E.

2014-12-01

360

Background sources at PEP  

SciTech Connect

Important sources of background for PEP experiments are studied. Background particles originate from high-energy electrons and positrons which have been lost from stable orbits, ..gamma..-rays emitted by the primary beams through bremsstrahlung in the residual gas, and synchrotron radiation x-rays. The effect of these processes on the beam lifetime are calculated and estimates of background rates at the interaction region are given. Recommendations for the PEP design, aimed at minimizing background are presented. 7 figs., 4 tabs.

Lynch, H.; Schwitters, R.F.; Toner, W.T.

1988-01-01

361

Stochastic perturbations in vortex-tube dynamics.  

PubMed

A dual lattice vortex formulation of homogeneous turbulence is developed, within the Martin-Siggia-Rose field theoretical approach. It consists of a generalization of the usual dipole version of the Navier-Stokes equations, known to hold in the limit of vanishing external forcing. We investigate, as a straightforward application of our formalism, the dynamics of closed vortex tubes, randomly stirred at large length scales by Gaussian stochastic forces. We find that besides the usual self-induced propagation, the vortex tube evolution may be effectively modeled through the introduction of an additional white-noise correlated velocity field background. The resulting phenomenological picture is closely related to observations previously reported from a wavelet decomposition analysis of turbulent flow configurations. PMID:15600755

Moriconi, L; Nobre, F A S

2004-11-01

362

Building Background Knowledge  

ERIC Educational Resources Information Center

This article make a case for the importance of background knowledge in children's comprehension. It suggests that differences in background knowledge may account for differences in understanding text for low- and middle-income children. It then describes strategies for building background knowledge in the age of common core standards.

Neuman, Susan B.; Kaefer, Tanya; Pinkham, Ashley

2014-01-01

363

Shielding and background reduction  

Microsoft Academic Search

The background spectrum in a Low Background intrinsic germanium detector was analysed. Different possible sources of background and the influence of the materials used as well as the thickness of shielding was studied. Lead, copper, nylon, delrin and teflon of different thicknessewere used. Too much shielding material could induce some gamma rays from neutron production in the shielding due to

R. Núñez-Lagos; A. Virto

1996-01-01

364

Liquid-Nitrogen Test for Blocked Tubes  

NASA Technical Reports Server (NTRS)

Nondestructive test identifies obstructed tube in array of parallel tubes. Trickle of liquid nitrogen allowed to flow through tube array until array accumulates substantial formation of frost from moisture in air. Flow stopped and warm air introduced into inlet manifold to heat tubes in array. Tubes still frosted after others defrosted identified as obstructed tubes. Applications include inspection of flow systems having parallel legs.

Wagner, W. R.

1984-01-01

365

The development of the neural crest in the human  

PubMed Central

The first systematic account of the neural crest in the human has been prepared after an investigation of 185 serially sectioned staged embryos, aided by graphic reconstructions. As many as fourteen named topographical subdivisions of the crest were identified and eight of them give origin to ganglia (Table 2). Significant findings in the human include the following. (1) An indication of mesencephalic neural crest is discernible already at stage 9, and trigeminal, facial, and postotic components can be detected at stage 10. (2) Crest was not observed at the level of diencephalon 2. Although pre-otic crest from the neural folds is at first continuous (stage 10), crest-free zones are soon observable (stage 11) in Rh.1, 3, and 5. (3) Emigration of cranial neural crest from the neural folds at the neurosomatic junction begins before closure of the rostral neuropore, and later crest cells do not accumulate above the neural tube. (4) The trigeminal, facial, glossopharyngeal and vagal ganglia, which develop from crest that emigrates before the neural folds have fused, continue to receive contributions from the roof plate of the neural tube after fusion of the folds. (5) The nasal crest and the terminalis-vomeronasal complex are the last components of the cranial crest to appear (at stage 13) and they persist longer. (6) The optic, mesencephalic, isthmic, accessory, and hypoglossal crest do not form ganglia. Cervical ganglion 1 is separated early from the neural crest and is not a Froriep ganglion. (7) The cranial ganglia derived from neural crest show a specific relationship to individual neuromeres, and rhombomeres are better landmarks than the otic primordium, which descends during stages 9–14. (8) Epipharyngeal placodes of the pharyngeal arches contribute to cranial ganglia, although that of arch 1 is not typical. (9) The neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there rostrad to the truncus arteriosus at stage 12 is identified here, for the first time in the human, as the cardiac crest. (10) The hypoglossal crest provides cells that accompany those of myotomes 1–4 and form the hypoglossal cell cord at stages 13 and 14. (11) The occipital crest, which is related to somites 1–4 in the human, differs from the spinal mainly in that it does not develop ganglia. (12) The occipital and spinal portions of the crest migrate dorsoventrad and appear to traverse the sclerotomes before the differentiation into loose and dense zones in the latter. (13) Embryonic examples of synophthalmia and anencephaly are cited to emphasize the role of the neural crest in the development of cranial ganglia and the skull. PMID:17848161

O’Rahilly, Ronan; Müller, Fabiola

2007-01-01

366

Tube thoracostomy; chest tube implantation and follow up  

PubMed Central

Pneumothorax is an urgent medical situation that requires urgent treatment. We can divide this entity based on the etiology to primary and secondary. Chest tube implantation can be performed either in the upper chest wall or lower. Both thoracic surgeons and pulmonary physicians can place a chest tube with minimal invasive techniques. In our current work, we will demonstrate chest tube implantation to locations, methodology and tools. PMID:25337405

Kuhajda, Ivan; Zarogoulidis, Konstantinos; Kougioumtzi, Ioanna; Huang, Haidong; Li, Qiang; Dryllis, Georgios; Kioumis, Ioannis; Pitsiou, Georgia; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Papaiwannou, Antonis; Lampaki, Sofia; Papaiwannou, Antonis; Zaric, Bojan; Branislav, Perin; Porpodis, Konstantinos

2014-01-01

367

Tube thoracostomy; chest tube implantation and follow up.  

PubMed

Pneumothorax is an urgent medical situation that requires urgent treatment. We can divide this entity based on the etiology to primary and secondary. Chest tube implantation can be performed either in the upper chest wall or lower. Both thoracic surgeons and pulmonary physicians can place a chest tube with minimal invasive techniques. In our current work, we will demonstrate chest tube implantation to locations, methodology and tools. PMID:25337405

Kuhajda, Ivan; Zarogoulidis, Konstantinos; Kougioumtzi, Ioanna; Huang, Haidong; Li, Qiang; Dryllis, Georgios; Kioumis, Ioannis; Pitsiou, Georgia; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Papaiwannou, Antonis; Lampaki, Sofia; Papaiwannou, Antonis; Zaric, Bojan; Branislav, Perin; Porpodis, Konstantinos; Zarogoulidis, Paul

2014-10-01

368

Gyrotron transmitting tube  

NASA Technical Reports Server (NTRS)

An RF transmitting tube for the 20 GHz to 500 GHz range comprises a gyrotron and a multistage depressed collector. A winding provides a magnetic field which acts on spent, spinning or orbiting electrons changing their motion to substantially forward linear motion in a downstream direction. The spent electrons then pass through a focusser into the collector. Nearly all of the electrons injected into the collector will remain within an imaginary envelope as they travel forward toward the end collector plate. The apertures in the collector plates are at least as large in diameter as the envelope at any particular axial position.

Kosmahl, H. G. (inventor)

1983-01-01

369

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

370

High voltage capacitors for low background experiments  

NASA Astrophysics Data System (ADS)

Low background experiments place stringent constraints on amount of radioactive impurities in the materials used for their assembly. Often these are in conflict with the constraints placed on the materials by their roles in the experiment. This is especially true for certain electronic components. A high value, high voltage capacitor for use in low background experiments has been developed from specially selected radiopure materials. Electroformed copper foils are separated by polyethylene napthalate (PEN) foils and supported within a PTFE teflon spiral coil tube. The electrical performance as well as radiopurity are scrutinized here. With some minor modifications to tune the performance for the application, this capacitor can be well suited for a variety of applications in low background experiments. Here the use of the capacitor for high voltage (HV) decoupling in the operation of high purity germanium (HPGe) detectors is demonstrated.

O'Shaughnessy, C.; Andreotti, E.; Budjáš, D.; Caldwell, A.; Gangapshev, A.; Gusev, K.; Hult, M.; Lubashevskiy, A.; Majorovits, B.; Schönert, S.; Smolnikov, A.

2013-05-01

371

Free compression tube. Applications  

NASA Astrophysics Data System (ADS)

During the flight of vehicles, their propulsion energy must overcome gravity, to ensure the displacement of air masses on vehicle trajectory, to cover both energy losses from the friction between a solid surface and the air and also the kinetic energy of reflected air masses due to the impact with the flying vehicle. The flight optimization by increasing speed and reducing fuel consumption has directed research in the aerodynamics field. The flying vehicles shapes obtained through studies in the wind tunnel provide the optimization of the impact with the air masses and the airflow along the vehicle. By energy balance studies for vehicles in flight, the author Ioan Rusu directed his research in reducing the energy lost at vehicle impact with air masses. In this respect as compared to classical solutions for building flight vehicles aerodynamic surfaces which reduce the impact and friction with air masses, Ioan Rusu has invented a device which he named free compression tube for rockets, registered with the State Office for Inventions and Trademarks of Romania, OSIM, deposit f 2011 0352. Mounted in front of flight vehicles it eliminates significantly the impact and friction of air masses with the vehicle solid. The air masses come into contact with the air inside the free compression tube and the air-solid friction is eliminated and replaced by air to air friction.

Rusu, Ioan

2012-11-01

372

Cosmological String Backgrounds  

E-print Network

Talk given at the ``4th Hellenic School on Elementary Particle Physics", Corfu, 2-20 September 1992: The propagation of strings in cosmological space-time backgrounds is reviewed. We show the relation of a special class of cosmological backgrounds to exact conformal field theory. Particular emphasis is put on the singularity structure of the cosmological space-time and on the discrete duality symmetries of the string background.

Dieter Luest

1993-03-31

373

Resolving time and space constraints during neural crest formation and delamination.  

PubMed

A striking feature of neural crest development in vertebrates is that all the specification, delamination, migration, and differentiation steps occur consecutively in distinct areas of the embryo and at different timings of development. The significance and consequences of this partition into clearly separated events are not fully understood yet, but it ought to be related to the necessity of controlling precisely and independently each step, given the wide array of cell types and tissues derived from the neural crest and the long duration of their development spanning almost the entire embryonic life. In this chapter, using the examples of early neural crest induction and delamination, we discuss how time and space constraints influence their development and describe the molecular and cellular responses that are employed by cells to adapt. In the first example, we analyze how cell sorting and cell movements cooperate to allow nascent neural crest cells, which are initially mingled with other neurectodermal progenitors after induction, to segregate from the neural tube and ectoderm populations and settle at the apex of the neural tube prior to migration. In the second example, we examine how cadherins drive the entire process of neural crest segregation from the rest of the neurectoderm by their dual role in mediating first cell sorting and cohesion during specification and later in promoting their delamination. In the third example, we describe how the expression and activity of the transcription factors known to drive epithelium-to-mesenchyme transition (EMT) are regulated timely and spatially by the cellular machinery so that they can alternatively and successively regulate neural crest specification and delamination. In the last example, we briefly tackle the problem of how factors triggering EMT may elicit different cell responses in neural tube and neural crest progenitors. PMID:25662257

Duband, Jean-Loup; Dady, Alwyn; Fleury, Vincent

2015-01-01

374

YouTube Sharathon Crackerbarrel  

NASA Astrophysics Data System (ADS)

This year at the AAPT Summer Meeting in Philadelphia, there was a session called "YouTube Sharathon Crackerbarrel." The session allowed many teachers to share their YouTube videos and explain how they use YouTube in their classroom. Unfortunately, I had a conflicting meeting and had to miss this session. Dean Baird was the originator of the session and also served as host. In addition, he forwarded a few of the best videos to me.

2012-10-01

375

Tubing for augmented heat transfer  

SciTech Connect

The objectives of the program reported were: to determine the heat transfer and friction characteristics on the outside of spiral fluted tubing in single phase flow of water, and to assess the relative cost of a heat exchanger constructed with spiral fluted tubing with one using conventional smooth tubing. An application is examined where an isolation water/water heat exchanger was used to transfer the heat from a gaseous diffusion plant to an external system for energy recovery. (LEW)

Yampolsky, J.S.; Pavlics, P.

1983-08-01

376

YouTube Sharathon Crackerbarrel  

NASA Astrophysics Data System (ADS)

This year at the AAPT Summer Meeting in Philadelphia, there was a session called ``YouTube Sharathon Crackerbarrel.'' The session allowed many teachers to share their YouTube videos and explain how they use YouTube in their classroom. Unfortunately, I had a conflicting meeting and had to miss this session. Dean Baird was the originator of the session and also served as host. In addition, he forwarded a few of the best videos to me.

Riendeau, Diane

2012-10-01

377

Diffusion in a Curved Tube  

E-print Network

The diffusion of particles in confining walls forming a tube is discussed. Such a transport phenomenon is observed in biological cells and porous media. We consider the case in which the tube is winding with curvature and torsion, and the thickness of the tube is sufficiently small compared with its curvature radius. We discuss how geomerical quantities appear in a quasi-one-dimensional diffusion equation.

Naohisa Ogawa

2013-03-01

378

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

379

Selective migration of neuralized embryonic stem cells to stem cell factor and media conditioned by glioma cell lines  

Microsoft Academic Search

BACKGROUND: Pluripotent mouse embryonic stem (ES) cells can be induced in vitro to become neural progenitors. Upon transplantation, neural progenitors migrate toward areas of damage and inflammation in the CNS. We tested whether undifferentiated and neuralized mouse ES cells migrate toward media conditioned by glioma cell lines (C6, U87 & N1321) or Stem Cell Factor (SCF). RESULTS: Cell migration assays

Peter Serfozo; Maggie S Schlarman; Chris Pierret; Bernard L Maria; Mark D Kirk

2006-01-01

380

An early requirement for FGF signalling in the acquisition of neural cell fate in the chick embryo  

Microsoft Academic Search

Background: In Xenopus embryos, fibroblast growth factors (FGFs) and secreted inhibitors of bone morphogenetic protein (BMP)-mediated signalling have been implicated in neural induction. The precise roles, if any, that these factors play in neural induction in amniotes remains to be established.Results: To monitor the initial steps of neural induction in the chick embryo, we developed an in vitro assay of

Sara I Wilson; Enrique Graziano; Richard Harland; Thomas M Jessell; Thomas Edlund

2000-01-01

381

Evolvable Neural Software System  

NASA Technical Reports Server (NTRS)

The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

Curtis, Steven A.

2009-01-01

382

Reduced-vibration tube array  

DOEpatents

A reduced-vibration tube array is disclosed. The array includes a plurality of tubes in a fixed arrangement and a plurality of damping members positioned within the tubes. The damping members include contoured interface regions characterized by bracing points that selectively contact the inner surface of an associated tube. Each interface region is sized and shaped in accordance with the associated tube, so that the damping member bracing points are spaced apart a vibration-reducing distance from the associated tube inner surfaces at equilibrium. During operation, mechanical interaction between the bracing points and the tube inner surfaces reduces vibration by a damage-reducing degree. In one embodiment, the interface regions are serpentine shaped. In another embodiment, the interface regions are helical in shape. The interface regions may be simultaneously helical and serpentine in shape. The damping members may be fixed within the associated tubes, and damping member may be customized several interference regions having attributes chosen in accordance with desired flow characteristics and associated tube properties.

Bruck, Gerald J.; Bartolomeo, Daniel R.

2004-07-20

383

Coiled tubing; Operations and services  

SciTech Connect

This paper reports on coiled tubing units which are used for many types of remedial well operations, including sand plugbacks, cement squeezes, fill cleanouts, underreaming, acid stimulations, and fishing. Fishing operations include removal of inflatable bridge plugs, lock mandrels stuck in profile nipples, coiled tubing, coiled tubing bottomhole assemblies (BHAs) and wireline. Recommended guidelines for selecting candidates, proper tool string configuration and operational techniques are presented here to assist coiled tubing supervisors and company representatives in the planning and implementation of efficient and effective fishing operations. Treatment of these areas are not intended to be exhaustive, but rather generally representative of common applications. Each fishing operation requires individualized analysis and planning.

Welch, J.L.; Stephens, R.K. (BP Exploration (US))

1992-09-01

384

Coiled tubing. operations and services  

SciTech Connect

Coiled tubing is being used with increasing frequency in conventional or traditional production operations. Demand for coiled pipe in these types of applications is expected to experience rapid growth as standard 2 (3/8) and 2 (7/8)-in. OD tubing sizes and units equipped to run larger pipe become more readily available. This paper reports on a recent market survey which indicated that coiled tubing used for velocity strings and standard production tubing installations are two areas with the most potential for immediate and near-term expansion. Other applications include: well casing and liners, gravel packing, artificial lift, flowlines and pipelines.

Hightower, C.M. (Arco Exploration and Production Technology, Plano, TX (United States))

1992-11-01

385

Method for producing a tube  

DOEpatents

A method is described for producing tubular substrates having parallel spaced concentric rings of electrical conductors that can be used as the drift tube of an Ion Mobility Spectrometer (IMS). The invention comprises providing electrodes on the inside of a tube that are electrically connected to the outside of the tube through conductors that extend between adjacent plies of substrate that are combined to form the tube. Tubular substrates are formed from flexible polymeric printed wiring board materials, ceramic materials and material compositions of glass and ceramic, commonly known as Low Temperature Co-Fired Ceramic (LTCC). The adjacent plies are sealed together around the electrode.

Peterson, Kenneth A. (Albuquerque, NM); Rohde, Steven B. (Corrales, NM); Pfeifer, Kent B. (Los Lunas, NM); Turner, Timothy S. (Rio Rancho, NM)

2007-01-02

386

Primary Fallopian Tube Carcinoma Arising in the Setting of Chronic Pelvic Inflammatory Disease  

PubMed Central

Primary fallopian tube cancer (PFTC) is a rare gynaecological malignancy, clinically often mistaken for pelvic inflammatory disease or ovarian cancer. Three primary fallopian tube carcinomas, arising in a background of chronic pelvic inflammatory disease (PID), are presented. The possible association between chronic PID and PFTC is discussed and a hypothesies linking these cancers with chronic inflammation is proposed. PMID:24527040

Zardawi, Ibrahim M.

2014-01-01

387

How easily do topical antibiotics pass through tympanostomy tubes?—an in vitro study  

Microsoft Academic Search

Background: Despite potential ototoxicity, eardrops containing aminoglycosides remain in widespread use in the presence of indwelling tympanostomy tubes (grommets). It is unclear how readily they pass into the middle ear during administration, nor whether this is affected by middle ear secretions. Materials and methods: The trans-tympanic pressure required to force antibiotic solutions through a tympanostomy tube in an artificial middle

M. W Saunders; P. J Robinson

1999-01-01

388

A Simple Method for DNA Isolation from Clotted Blood Extricated Rapidly from Serum Separator Tubes  

Microsoft Academic Search

Background: After clinical laboratory tests have been performed, it can be difficult to obtain DNA without further patient involvement. Although the blood clot remaining within the serum-separation tube after serum collection is a source of DNA, recovery of the clot from the tube is a significant challenge. Method: We devised a method to efficiently remove clotted blood from the serum-separation

Steven Se; Fum Wong; Jeffrey J. Kuei; Naina Prasad; Gustavo A. Mendoza; Trevor J. Pemberton

389

Id expression in amphioxus and lamprey highlights the role of gene cooption during neural crest evolution  

NASA Technical Reports Server (NTRS)

Neural crest cells are unique to vertebrates and generate many of the adult structures that differentiate them from their closest invertebrate relatives, the cephalochordates. Id genes are robust markers of neural crest cells at all stages of development. We compared Id gene expression in amphioxus and lamprey to ask if cephalochordates deploy Id genes at the neural plate border and dorsal neural tube in a manner similar to vertebrates. Furthermore, we examined whether Id expression in these cells is a basal vertebrate trait or a derived feature of gnathostomes. We found that while expression of Id genes in the mesoderm and endoderm is conserved between amphioxus and vertebrates, expression in the lateral neural plate border and dorsal neural tube is a vertebrate novelty. Furthermore, expression of lamprey Id implies that recruitment of Id genes to these cells occurred very early in the vertebrate lineage. Based on expression in amphioxus we postulate that Id cooption conferred sensory cell progenitor-like properties upon the lateral neurectoderm, and pharyngeal mesoderm-like properties upon cranial neural crest. Amphioxus Id expression is also consistent with homology between the anterior neurectoderm of amphioxus and the presumptive placodal ectoderm of vertebrates. These observations support the idea that neural crest evolution was driven in large part by cooption of multipurpose transcriptional regulators from other tissues and cell types.

Meulemans, Daniel; McCauley, David; Bronner-Fraser, Marianne

2003-01-01

390

The Cosmic Microwave Background  

E-print Network

This set of lectures provides an overview of the basic theory and phenomenology of the cosmic microwave background. Topics include a brief historical review; the physics of temperature and polarization fluctuations; acoustic oscillations of the primordial plasma; the space of inflationary cosmological models; current and potential constraints on these models from the microwave background; and constraints on inflation.

Arthur Kosowsky

2001-02-23

391

The feasibility of using neural networks to obtain cross sections from electron swarm data  

SciTech Connect

This paper reports that although still more a curiosity than an accepted technique in computational modeling, the very new field of neural computing is beginning to find applications in physics. Presented in some background on neural computing and a discussion on the use of neural networks to obtain electron-impact cross sections from measured drift velocities, characteristic energies, and other swarm data. This is what is known as an inverse problem, a class of problems for which neural networks may be frequently superior to other numerical algorithms. Momentum transfer cross sections obtained for a model problem and for xenon using a neural network are presented.

Morgan, W.L. (Kinema Research Monument, CO (US))

1991-04-01

392

Angiogenesis in the developing spinal cord: blood vessel exclusion from neural progenitor region is mediated by VEGF and its antagonists.  

PubMed

Blood vessels in the central nervous system supply a considerable amount of oxygen via intricate vascular networks. We studied how the initial vasculature of the spinal cord is formed in avian (chicken and quail) embryos. Vascular formation in the spinal cord starts by the ingression of intra-neural vascular plexus (INVP) from the peri-neural vascular plexus (PNVP) that envelops the neural tube. At the ventral region of the PNVP, the INVP grows dorsally in the neural tube, and we observed that these vessels followed the defined path at the interface between the medially positioned and undifferentiated neural progenitor zone and the laterally positioned differentiated zone. When the interface between these two zones was experimentally displaced, INVP faithfully followed a newly formed interface, suggesting that the growth path of the INVP is determined by surrounding neural cells. The progenitor zone expressed mRNA of vascular endothelial growth factor-A whereas its receptor VEGFR2 and FLT-1 (VEGFR1), a decoy for VEGF, were expressed in INVP. By manipulating the neural tube with either VEGF or the soluble form of FLT-1, we found that INVP grew in a VEGF-dependent manner, where VEGF signals appear to be fine-tuned by counteractions with anti-angiogenic activities including FLT-1 and possibly semaphorins. These results suggest that the stereotypic patterning of early INVP is achieved by interactions between these vessels and their surrounding neural cells, where VEGF and its antagonists play important roles. PMID:25585380

Takahashi, Teruaki; Takase, Yuta; Yoshino, Takashi; Saito, Daisuke; Tadokoro, Ryosuke; Takahashi, Yoshiko

2015-01-01

393

Angiogenesis in the Developing Spinal Cord: Blood Vessel Exclusion from Neural Progenitor Region Is Mediated by VEGF and Its Antagonists  

PubMed Central

Blood vessels in the central nervous system supply a considerable amount of oxygen via intricate vascular networks. We studied how the initial vasculature of the spinal cord is formed in avian (chicken and quail) embryos. Vascular formation in the spinal cord starts by the ingression of intra-neural vascular plexus (INVP) from the peri-neural vascular plexus (PNVP) that envelops the neural tube. At the ventral region of the PNVP, the INVP grows dorsally in the neural tube, and we observed that these vessels followed the defined path at the interface between the medially positioned and undifferentiated neural progenitor zone and the laterally positioned differentiated zone. When the interface between these two zones was experimentally displaced, INVP faithfully followed a newly formed interface, suggesting that the growth path of the INVP is determined by surrounding neural cells. The progenitor zone expressed mRNA of vascular endothelial growth factor-A whereas its receptor VEGFR2 and FLT-1 (VEGFR1), a decoy for VEGF, were expressed in INVP. By manipulating the neural tube with either VEGF or the soluble form of FLT-1, we found that INVP grew in a VEGF-dependent manner, where VEGF signals appear to be fine-tuned by counteractions with anti-angiogenic activities including FLT-1 and possibly semaphorins. These results suggest that the stereotypic patterning of early INVP is achieved by interactions between these vessels and their surrounding neural cells, where VEGF and its antagonists play important roles. PMID:25585380

Takahashi, Teruaki; Takase, Yuta; Yoshino, Takashi; Saito, Daisuke; Tadokoro, Ryosuke; Takahashi, Yoshiko

2015-01-01

394

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

395

A comparison of conventional tube and EndoFlex tube for tracheal intubation in patients with a cervical spine immobilisation  

PubMed Central

Background The EndoFlex is a new type of tracheal tube with an adjustable distal tip that can be bent without the use of a stylet. The aim of this study was to compare a standard endotracheal tube with the EndoFlex tracheal tube for intubation in patients with simulated cervical spine injury. Methods A group of 60 patients without any kind of the cervical spine injury, classified as the ASA physiological scale I or II and qualified for elective surgery procedures were intubated with the use of classical Macintosh laryngoscope, and either a standard endotracheal tube with the intubation stylet in it or EndoFlex tube without stylet. The subjects were randomized into two subgroups. All patients have had the cervical collar placed on their neck for the simulation of intubation procedure in case of the spinal injury. Results The intubation procedure was performed by 16 anesthetists with different experience (5-19 yrs). Time of intubation with the use of EndoFlex tube was similar to that with a the use of standard endotracheal tube and intubation stylet: Me (median) 19.5 s [IQR (interquatile range) 18-50] vs. Me 20 s [IQR 17-60] respectively (p?=?0.9705). No significant additional maneuvers were necessary during intubation with the use of EndoFlex tube in comparison with standard endotracheal tube (70% vs. 56.6%) (p?=?0.4220). Subjective assessment of the usability of both tubes revealed that more anesthesiologists found intubations with the use of EndoFlex more demanding than intubation with conventional tracheal tube and intubation stylet. The assessment of usability: very easy 3.3% vs. 20%, easy 83.4% vs. 56.7%, difficult 10% vs. 20% and very difficult 3.3% vs. 3.3% for standard endotracheal tube with stylet and EndoFlex, respectively. Conclusion In conclusion we asses, that the EndoFlex tube does not improve intubation success rate, in fact it requires more maneuvers facilitating intubation and was found to be more difficult to use. PMID:24267640

2013-01-01

396

Semiconductor Nanomembrane Tubes: Three-Dimensional Confinement for Controlled Neurite Outgrowth  

PubMed Central

In many neural culture studies, neurite migration on a flat, open surface does not reflect the three-dimensional (3D) microenvironment in vivo. With that in mind, we fabricated arrays of semiconductor tubes using strained silicon (Si) and germanium (Ge) nanomembranes and employed them as a cell culture substrate for primary cortical neurons. Our experiments show that the SiGe substrate and the tube fabrication process are biologically viable for neuron cells. We also observe that neurons are attracted by the tube topography, even in the absence of adhesion factors, and can be guided to pass through the tubes during outgrowth. Coupled with selective seeding of individual neurons close to the tube opening, growth within a tube can be limited to a single axon. Furthermore, the tube feature resembles the natural myelin, both physically and electrically, and it is possible to control the tube diameter to be close to that of an axon, providing a confined 3D contact with the axon membrane and potentially insulating it from the extracellular solution. PMID:21366271

Yu, Minrui; Huang, Yu; Ballweg, Jason; Shin, Hyuncheol; Huang, Minghuang; Savage, Donald E.; Lagally, Max G.; Dent, Erik W.; Blick, Robert H.; Williams, Justin C.

2013-01-01

397

Traveling wave tube circuit  

NASA Technical Reports Server (NTRS)

A traveling wave tube (TWT) has a slow wave structure (SWS) which is severed into two or more sections. A signal path, connects the end of an SWS section to the beginning of the following SWS section. The signal path comprises an impedance matching coupler (IMC), followed by an isolator, a variable phase shifter, and a second IMC. The aggregate band pass characteristic of the components in the signal path is chosen to reject, or strongly attenuate, all frequencies outside the desired operating frequency range of the TWT and yet pass, with minimal attenuation in the forward direction, all frequencies within the desired operating frequency range. The isolator is chosen to reject, or strongly attenuate, waves, of all frequencies, which propagate in the backward direction. The aggregate phase shift characteristic of the components in the signal path is chosen to apply signal power to the beginning of the following SWS section with the phase angle yielding maximum efficiency.

Connolly, D. J. (inventor)

1978-01-01

398

Equations determine coiled tubing collapse pressure  

SciTech Connect

A set of equations has been developed for calculating pipe collapse pressure for oval tubing such as coiled tubing. When coiled tubing is placed onto a reel, the tubing is forced into an oval shape and never again returns to perfect roundness because the coiling process exceeds the plasticity limits of the tubing. Straightening the tubing for the trip into the well does not restore roundness. The consequence of this physical property is that all coiled tubing collapse pressure calculations should be made considering oval tubing, not round tubing. Tubing collapse can occur when formation pressure against the coiled tubing exceeds the collapse resistance inherent in the coiled tubing. As coiled tubing becomes more oval in shape, it becomes more oval in shape, it becomes more susceptible to collapse from outside pressure.

Avakov, V.; Taliaferro, W. [Halliburton Energy Services, Duncan, OK (United States)

1995-07-24

399

Delusion of Test-Tube Pregnancy in a Sexually Abused Girl  

Microsoft Academic Search

We report the case of a patient who presented with catatonic features and delusion of test-tube pregnancy in the background of previous sexual abuse. The reported case illustrates the importance of contemporary themes in the evolution of psychopathology.

P. N. Manoj; John P. John; Ashu Gandhi; Madhu Kewalramani; Pratima Murthy; Santosh K. Chaturvedi; Mohan K. Isaac

2004-01-01

400

Fuzzy and neural control  

NASA Technical Reports Server (NTRS)

Fuzzy logic and neural networks provide new methods for designing control systems. Fuzzy logic controllers do not require a complete analytical model of a dynamic system and can provide knowledge-based heuristic controllers for ill-defined and complex systems. Neural networks can be used for learning control. In this chapter, we discuss hybrid methods using fuzzy logic and neural networks which can start with an approximate control knowledge base and refine it through reinforcement learning.

Berenji, Hamid R.

1992-01-01

401

Quantum neural network  

Microsoft Academic Search

In the neural network theory content-addressable memories are defined by patterns that are attractors of the dynamical rule\\u000a of the system. This paper develops a quantum neural network starting from a classical neural network Hamiltonian and using\\u000a a Schrödinger-like equation. It then shows that such a system exhibits probabilistic memory storage characteristics analogous\\u000a to those of the dynamical attractors of

G. Bonnell; G. Papini

1997-01-01

402

Dual-Purpose Gastric Decompression and Enteral Feeding Tubes Rationale and Design of Novel Nasogastric and Nasogastrojejunal Tubes.  

PubMed

Background: The importance of early postoperative nutrition in surgical patients and early institution of enteral nutrition in intensive care unit (ICU) patients have recently been highlighted. Unfortunately, institution of enteral feeding in both groups of patients often has to be postponed due to delayed gastric emptying and the need for gastric decompression. The design of current polyvinylchloride (PVC) gastric decompression tubes (Salem Sump [Covidien, Mansfield, MA] in the United States; Ryles [Penine Health Care Ltd, Derby, UK] in the United Kingdom and Europe) make them unsuitable for their subsequent use as either nasogastric enteral feeding tubes or for continued gastric decompression during postpyloric enteral feeding. To overcome these problems, we have designed a range of polyurethane (PU) dual-purpose gastric decompression and enteral feeding tubes that include 2 nasogastric tubes (double lumen to replace Salem Sump; single lumen to replace Ryles). Two novel multilumen nasogastrojejunal tubes (triple lumen for the United States; double lumen for the United Kingdom and Europe) complete the range. By using PU, a given internal diameter (ID) and flow area can be incorporated into a lower outside diameter (OD) compared with that achieved with PVC. The ID and lumen and flow area of an 18Fr (OD 6.7 mm) PVC Salem Sump can be incorporated into a 14Fr (OD 4.7 mm) PU tube. The design of aspiration/infusion ports of current PVC and PU tubes invites occlusion by gastrointestinal mucosa and clogging by mucus and enteral feed. To overcome this, we have designed long, single, widened, smooth, and curved edge ports with no "dead space" to trap mucus or curdled diet. Involving up to 214° of the circumference, these ports have up to 11 times the flow areas of the aspiration ports of current PVC tubes. Conclusion: The proposed designs will lead to the development of dual-purpose nasogastric and nasojejunal tubes that will significantly improve the clinical and nutrition care of postoperative and ICU patients. PMID:25261414

Silk, David B A; Quinn, David G

2014-09-26

403

Neural assembly computing.  

PubMed

Spiking neurons can realize several computational operations when firing cooperatively. This is a prevalent notion, although the mechanisms are not yet understood. A way by which neural assemblies compute is proposed in this paper. It is shown how neural coalitions represent things (and world states), memorize them, and control their hierarchical relations in order to perform algorithms. It is described how neural groups perform statistic logic functions as they form assemblies. Neural coalitions can reverberate, becoming bistable loops. Such bistable neural assemblies become short- or long-term memories that represent the event that triggers them. In addition, assemblies can branch and dismantle other neural groups generating new events that trigger other coalitions. Hence, such capabilities and the interaction among assemblies allow neural networks to create and control hierarchical cascades of causal activities, giving rise to parallel algorithms. Computing and algorithms are used here as in a nonstandard computation approach. In this sense, neural assembly computing (NAC) can be seen as a new class of spiking neural network machines. NAC can explain the following points: 1) how neuron groups represent things and states; 2) how they retain binary states in memories that do not require any plasticity mechanism; and 3) how branching, disbanding, and interaction among assemblies may result in algorithms and behavioral responses. Simulations were carried out and the results are in agreement with the hypothesis presented. A MATLAB code is available as a supplementary material. PMID:24806763

Ranhel, João

2012-06-01

404

Neural-Network Simulator  

NASA Technical Reports Server (NTRS)

F77NNS (FORTRAN 77 Neural Network Simulator) computer program simulates popular back-error-propagation neural network. Designed to take advantage of vectorization when used on computers having this capability, also used on any computer equipped with ANSI-77 FORTRAN Compiler. Problems involving matching of patterns or mathematical modeling of systems fit class of problems F77NNS designed to solve. Program has restart capability so neural network solved in stages suitable to user's resources and desires. Enables user to customize patterns of connections between layers of network. Size of neural network F77NNS applied to limited only by amount of random-access memory available to user.

Mitchell, Paul H.

1991-01-01

405

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. PMID:22719243

Brette, Romain

2012-01-01

406

ROTARY ELONGATION OF URANIUM TUBING  

Microsoft Academic Search

One hundred twenty-eight U tubes were rotary elongated successfully on a ; No. 1 Witter mill. The test was performed on a small, shell-rolling mill which ; utilized the same three-roll rolling principle now in use in the Asseltype ; seamless tube mill. Feed stock for the test was supplied by extrusion and by ; centrifugal casting. Billets were preheated

R. B. Steck; H. W. Hesselbrock

1963-01-01

407

Tubes at Glen Canyon Dam  

USGS Multimedia Gallery

The river outlet tubes at Glen Canyon Dam on the Colorado River in Arizona. At noon Monday, Nov. 19, U.S. Interior Secretary Ken Salazar will open the dam's river outlet tubes, releasing controlled flows larger than the usual 8,000-25,000 cubic feet per second that flows through the turbines of...

408

ATLAS Muon Drift Tube Electronics  

Microsoft Academic Search

This paper describes the electronics used for the ATLAS monitored drift tube (MDT) chambers. These chambers are the main component of the precision tracking system in the ATLAS muon spectrometer. The MDT detector system consists of 1,150 chambers containing a total of 354,000 drift tubes. It is capable of measuring the sagitta of muon tracks to an accuracy of 60

Y. Arai; B. Ball; M. Beretta; H. Boterenbrood; G. W. Brandenburg; F. Ceradini; J. W. Chapman; T. Dai; C. Ferretti; T. Fries; J. Gregory; J. Guimarães da Costa; S. Harder; E. Hazen; J. Huth; P. P. M. Jansweijer; L. E. Kirsch; A. C. König; A. Lanza; G. Mikenberg; J. Oliver; C. Posch; R. Richter; W. Riegler; E. Spiriti; F. E. Taylor; J. C. Vermeulen; B. Wadsworth; T. A. M. Wijnen

2008-01-01

409

Coiled tubing - Operations and services  

SciTech Connect

Drilling with a continuous (rather than jointed) drill string is an old concept that is gaining new attention as a result of recent advances made in coiled tubing and drilling technology. The development of larger diameter, reliable, high-strength coiled tubing and smaller diameter, positive displacement motors, orienting tools, surveying systems and fixed cutting drill bits have given drilling with a continuous drill string a capability that was previously unattainable. Like its many other uses, (e.g., squeeze cementing, wellbore cleanouts, flow initiation, logging) the continuity of coiled tubing gives it several advantages over conventional drill strings. These include: drilling underbalanced safely, significantly reduced trip time, continuous circulation, smaller surface requirements. Coiled tubing drilling operations have smaller surface lease requirements than most conventional rigs due to the smaller footprint of the coiled tubing unit and associated equipment. Current coiled tubing drilling operations have the following limitations: conventional rig assistance is required for well preparation; conventional rigs must assist in running long protective and production casing strings or liners; hole sizes are smaller; working depth capabilities are shallower, coiled tubing life is less. This paper goes on to discuss the history of continuous drill strings and includes information on tubing units, circulating systems, drilling fluids, well control systems, downhole tools, orientation tools, and bottomhole assemblies. It then gives a cost comparison and an application of this type of drilling.

Gronseth, J.M. (Imperial Oil Resources Ltd., Calgary, Alberta (Canada))

1993-04-01

410

Background stratospheric aerosol layer  

SciTech Connect

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 volcanic aerosol is over 30% faster than one would obtain without this correction. At background, the aerosol size distribution is found to remain remarkably constant between the tropopause and an altitude of approx.25 km, with a sudden transition to a distribution dominated by smaller particles above this altitude. The observations, in some respects, compare favorably with equilibrium one-dimensional stratospheric aerosol models and thus to some extent support the concept of relatively inert tropospheric sulfurous gases, such as carbonyl sulfide and carbon disulfide, as the main background stratospheric aerosol sulfur source. Models which incorporate sulfur chemistry are apparently not able to predict the observed variation of particle size with altitude. The 2-year background period is not long enough in itself to establish long-term trends. The eruption of Mt. St. Helens in May 1980 has considerably disrupted the background stratospheric aerosol which will probably not recover for several years. A comparison of the 1978--79 observations with Junge's original measurements made some 20 years earlier, also during a period void of volcanic perturbations, does not preclude a long-term increase in the background stratospheric aerosol level.

Hofmann, D.J.; Rosen, J.M.

1981-01-01

411

Calculation of the Pitot tube correction factor for Newtonian and non-Newtonian fluids.  

PubMed

This paper presents the numerical investigation performed to calculate the correction factor for Pitot tubes. The purely viscous non-Newtonian fluids with the power-law model constitutive equation were considered. It was shown that the power-law index, the Reynolds number, and the distance between the impact and static tubes have a major influence on the Pitot tube correction factor. The problem was solved for a wide range of these parameters. It was shown that employing Bernoulli's equation could lead to large errors, which depend on the magnitude of the kinetic energy and energy friction loss terms. A neural network model was used to correlate the correction factor of a Pitot tube as a function of these three parameters. This correlation is valid for most Newtonian, pseudoplastic, and dilatant fluids at low Reynolds number. PMID:14582876

Etemad, S Gh; Thibault, J; Hashemabadi, S H

2003-10-01

412

The Cosmic Background Radiation  

E-print Network

We summarise the current status of cosmic microwave background spectrum and anisotropy measurements, and their theoretical interpretation. This is the update of the mini-review for the 1997 web-version of the Review of Particle Properties.

George Smoot; Douglas Scott

1997-11-08

413

Building Background Knowledge  

NSDL National Science Digital Library

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

Donna Ross

2010-01-01

414

Introduction Biological Background  

E-print Network

@mail.sdsu.eduUBC Biomath Seminar -- (1/39) #12;Introduction Biological Background Mathematical Models Conclusions Tunicate ­ Ciona intestinalis Ciona intestinalis ­ Tunicate ­ Sea Squirt Joseph M. Mahaffy, jmahaffy

Mahaffy, Joseph M.

415

Introduction 1 Background 1  

E-print Network

squirrel (Sciurus carolinensis). The grey squirrel was introduced to Britain in the late 19 th century populations in Northern Ireland. Background The red squirrel (Sciurus vulgaris) was once ubiquitous

416

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

417

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

418

The Cosmic Microwave Background  

E-print Network

I review the discovery of the temperature fluctuations in the cosmic microwave background radiation. The underlying theory and the implications for cosmology are reviewed, and I describe the prospects for future progress.

Joseph Silk

2002-12-12

419

K(3)EDTA Vacuum Tubes Validation for Routine Hematological Testing.  

PubMed

Background and Objective. Some in vitro diagnostic devices (e.g, blood collection vacuum tubes and syringes for blood analyses) are not validated before the quality laboratory managers decide to start using or to change the brand. Frequently, the laboratory or hospital managers select the vacuum tubes for blood collection based on cost considerations or on relevance of a brand. The aim of this study was to validate two dry K(3)EDTA vacuum tubes of different brands for routine hematological testing. Methods. Blood specimens from 100 volunteers in two different K(3)EDTA vacuum tubes were collected by a single, expert phlebotomist. The routine hematological testing was done on Advia 2120i hematology system. The significance of the differences between samples was assessed by paired Student's t-test after checking for normality. The level of statistical significance was set at P < 0.05. Results and Conclusions. Different brand's tubes evaluated can represent a clinically relevant source of variations only on mean platelet volume (MPV) and platelet distribution width (PDW). Basically, our validation will permit the laboratory or hospital managers to select the brand's vacuum tubes validated according to him/her technical or economical reasons for routine hematological tests. PMID:22888448

Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Montagnana, Martina; Poli, Giovanni; Solero, Giovanni Pietro; Picheth, Geraldo; Guidi, Gian Cesare

2012-01-01

420

K3EDTA Vacuum Tubes Validation for Routine Hematological Testing  

PubMed Central

Background and Objective. Some in vitro diagnostic devices (e.g, blood collection vacuum tubes and syringes for blood analyses) are not validated before the quality laboratory managers decide to start using or to change the brand. Frequently, the laboratory or hospital managers select the vacuum tubes for blood collection based on cost considerations or on relevance of a brand. The aim of this study was to validate two dry K3EDTA vacuum tubes of different brands for routine hematological testing. Methods. Blood specimens from 100 volunteers in two different K3EDTA vacuum tubes were collected by a single, expert phlebotomist. The routine hematological testing was done on Advia 2120i hematology system. The significance of the differences between samples was assessed by paired Student's t-test after checking for normality. The level of statistical significance was set at P < 0.05. Results and Conclusions. Different brand's tubes evaluated can represent a clinically relevant source of variations only on mean platelet volume (MPV) and platelet distribution width (PDW). Basically, our validation will permit the laboratory or hospital managers to select the brand's vacuum tubes validated according to him/her technical or economical reasons for routine hematological tests. PMID:22888448

Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Montagnana, Martina; Poli, Giovanni; Solero, Giovanni Pietro; Picheth, Geraldo; Guidi, Gian Cesare

2012-01-01

421

Tube Cholecystostomy Before Cholecystectomy for the Treatment of Acute Cholecystitis  

PubMed Central

Background and Objectives: Percutaneous cholecystostomy is currently indicated for patients with cholecystitis who might be poor candidates for operative cholecystectomy. We performed a study to evaluate the long-term outcome of patients undergoing emergent tube cholecystostomy. Methods: This study was a retrospective chart review of patients who underwent tube cholecystostomy from July 1, 2005, to July 1, 2012. Results: During the study period, 82 patients underwent 125 cholecystostomy tube placements. Four patients (5%) died during the year after tube placement. The mean hospital length of stay for survivors was 8.8 days (range, 1–59 days). Twenty-eight patients (34%) required at least 1 additional percutaneous procedure (range, 1–6) for gallbladder drainage. Twenty-nine patients (34%) ultimately underwent cholecystectomy. Surgery was performed a mean of 7 weeks after cholecystostomy tube placement. Laparoscopic cholecystectomy was attempted in 25 operative patients but required conversion to an open approach in 8 cases (32%). In another 4 cases, planned open cholecystectomy was performed. Major postoperative complications were limited to 2 patients with postoperative common bile duct obstruction requiring endoscopic retrograde cholangiopancreatography, 1 patient requiring a return to the operating room for hemoperitoneum, and 2 patients with bile leak from the cystic duct stump. Conclusions: In high-risk patients receiving cholecystostomy tubes for acute cholecystitis, only about one third will undergo surgical cholecystectomy. Laparoscopic cholecystectomy performed in this circumstance has a higher rate of conversion to open surgery and higher hepatobiliary morbidity rate.

Suzuki, Kei; Bower, Margaret; Cassaro, Sebastiano; Patel, Rajesh I.; Karpeh, Martin S.

2015-01-01

422

Characterization of domestic and foreign image intensifier tubes  

NASA Astrophysics Data System (ADS)

The market for military-use Generation 2 and Generation 3 image intensifier (I2) tubes has become truly global, with major manufacturers and customers spanning five continents. This worldwide market is becoming increasingly important to U.S. manufacturers, with the majority of U.S. Army intensifier fielding having been completed in 2012. Given this keen global competition, it is not surprising that the advertised tube performance of a given source is often discounted by competitors, and the customers have no objective "honest broker" to determine the relative accuracy of these claims. To help fill this void, the U.S. Army RDECOM CERDEC NVESD recently measured a number of domestic and foreign image intensifier tubes, using consistent test equipment/procedures with which the U.S. industry must correlate for Army tube deliveries. Data and analysis will be presented for the major tube parameters of luminance gain, equivalent background input (EBI), signal-to-noise ratio (SNR), limiting resolution, halo, and modulation transfer function (MTF). The bright-light resolution provided by various auto-gated and non-gated tubes will also be addressed, since this area has been an important factor in the international market. RDECOM CERDEC NVESD measurement data will be compared to the corresponding manufacturer specifications whenever possible.

Bender, Edward J.; Wood, Michael V.; Hosek, Daniel J.; Hart, Steve D.

2013-06-01

423

Arbitrary background picture segmentation  

Microsoft Academic Search

In this paper, we present a new method for real time arbitrary background picture segmentation. We consider the following picture conditions: color picture, noisy picture, scene light changes, and still image arbitrary background. They are typical for many applications, e.g. for video security system, videophone, videoconference, V-commerce, etc. A set-theoretic approach has been used for picture model creation, adaptive picture

S. Itzikowitz; S. Sheraizin

2002-01-01

424

49 CFR 230.61 - Arch tubes, water bar tubes, circulators and thermic siphons.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 false Arch tubes, water bar tubes, circulators and thermic siphons...Boilers § 230.61 Arch tubes, water bar tubes, circulators and thermic siphons...the boiler is washed, arch tubes and water bar tubes shall thoroughly be cleaned...

2010-10-01

425

Anticipatory Anxiety Disrupts Neural Valuation during Risky Choice.  

PubMed

Incidental negative emotions unrelated to the current task, such as background anxiety, can strongly influence decisions. This is most evident in psychiatric disorders associated with generalized emotional disturbances. However, the neural mechanisms by which incidental emotions may affect choices remain poorly understood. Here we study the effects of incidental anxiety on human risky decision making, focusing on both behavioral preferences and their underlying neural processes. Although observable choices remained stable across affective contexts with high and low incidental anxiety, we found a clear change in neural valuation signals: during high incidental anxiety, activity in ventromedial prefrontal cortex and ventral striatum showed a marked reduction in (1) neural coding of the expected subjective value (ESV) of risky options, (2) prediction of observed choices, (3) functional coupling with other areas of the valuation system, and (4) baseline activity. At the same time, activity in the anterior insula showed an increase in coding the negative ESV of risky lotteries, and this neural activity predicted whether the risky lotteries would be rejected. This pattern of results suggests that incidental anxiety can shift the focus of neural valuation from possible positive consequences to anticipated negative consequences of choice options. Moreover, our findings show that these changes in neural value coding can occur in the absence of changes in overt behavior. This suggest a possible pathway by which background anxiety may lead to the development of chronic reward desensitization and a maladaptive focus on negative cognitions, as prevalent in affective and anxiety disorders. PMID:25698745

Engelmann, Jan B; Meyer, Friederike; Fehr, Ernst; Ruff, Christian C

2015-02-18

426

27 CFR 40.352 - Cigarette tubes.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Cigarette tubes. 40.352 Section 40.352... MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes §...

2010-04-01

427

27 CFR 40.352 - Cigarette tubes.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Cigarette tubes. 40.352 Section 40.352... MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes §...

2013-04-01

428

27 CFR 40.352 - Cigarette tubes.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Cigarette tubes. 40.352 Section 40.352... MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes §...

2011-04-01

429

27 CFR 40.352 - Cigarette tubes.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2011-04-01 true Cigarette tubes. 40.352 Section 40.352... MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes §...

2012-04-01

430

27 CFR 40.352 - Cigarette tubes.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Cigarette tubes. 40.352 Section 40.352... MANUFACTURE OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND PROCESSED TOBACCO Manufacture of Cigarette Papers and Tubes Taxes §...

2014-04-01

431

Water-storage-tube systems. Final report  

SciTech Connect

Passive solar collection/storage/distribution systems were surveyed, designed, fabricated, and mechanically and thermally tested. The types studied were clear and opaque fiberglass tubes, metal tubes with plastic liners, and thermosyphoning tubes. (MHR)

Hemker, P.

1981-12-24

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

Critical Branching Neural Networks  

ERIC Educational Resources Information Center

It is now well-established that intrinsic variations in human neural and behavioral activity tend to exhibit scaling laws in their fluctuations and distributions. The meaning of these scaling laws is an ongoing matter of debate between isolable causes versus pervasive causes. A spiking neural network model is presented that self-tunes to critical…

Kello, Christopher T.

2013-01-01

434

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

435

Use of Microcuff® endotracheal tubes in paediatric laparoscopic surgeries  

PubMed Central

Background and Aims: Traditionally, uncuffed endotracheal tubes have been used in children. Cuffed tubes may be useful in special situations like laparoscopy. Microcuff® endotracheal tube is a specifically designed cuffed endotracheal tube for the paediatric airway. We studied the appropriateness of Microcuff® tube size selection, efficacy of ventilation, and complications, in children undergoing laparoscopy. Methods: In a prospective, observational study, 100 children undergoing elective laparoscopy were intubated with Microcuff® tube as per recommended size. We studied appropriateness of size selection, sealing pressure, ability to ventilate with low flow, quality of capnography and post-extubation laryngospasm or stridor. Results: Mean age of the patients was 5.44 years (range 8 months 5 days–9 years 11 months). There was no resistance for tube passage during intubation in any patient. Leak on intermittent positive pressure ventilation at airway pressure ?20 cm H2O was present in all patients. Mean sealing pressure was 11.72 (1.9 standard deviation [SD]) cm H2 O. With the creation of pnemoperitoneum, mean intracuff pressure increased to 12.48 (3.12 SD) cm H2 O. With head low positioning, mean cuff pressure recorded was 13.32 (2.92 SD). Ventilation at low flow (mean flow 1 L/min), plateau-type capnography was noted in all patients. Mean duration of intubation was 83.50 min. Coughing at extubation occurred in 6 patients. Partial laryngospasm occurred in 4 patients, which responded to continuous positive airway pressure via face mask. Severe laryngospasm or stridor was not seen in any patient. Conclusion: Microcuff® tubes can be safely used in children if size selection recommendations are followed and cuff pressure is strictly monitored. Advantages are better airway seal and effective ventilation, permitting use of low flows. PMID:25788740

Mhamane, Rameshwar; Dave, Nandini; Garasia, Madhu

2015-01-01

436

Differentiation between non-neural and neural contributors to ankle joint stiffness in cerebral palsy  

PubMed Central

Background Spastic paresis in cerebral palsy (CP) is characterized by increased joint stiffness that may be of neural origin, i.e. improper muscle activation caused by e.g. hyperreflexia or non-neural origin, i.e. altered tissue viscoelastic properties (clinically: “spasticity” vs. “contracture”). Differentiation between these components is hard to achieve by common manual tests. We applied an assessment instrument to obtain quantitative measures of neural and non-neural contributions to ankle joint stiffness in CP. Methods Twenty-three adolescents with CP and eleven healthy subjects were seated with their foot fixated to an electrically powered single axis footplate. Passive ramp-and-hold rotations were applied over full ankle range of motion (RoM) at low and high velocities. Subject specific tissue stiffness, viscosity and reflexive torque were estimated from ankle angle, torque and triceps surae EMG activity using a neuromuscular model. Results In CP, triceps surae reflexive torque was on average 5.7 times larger (p?=?.002) and tissue stiffness 2.1 times larger (p?=?.018) compared to controls. High tissue stiffness was associated with reduced RoM (p?neural and non-neural contributors varied substantially within adolescents with CP. Significant associations of SPAT (spasticity test) score with both tissue stiffness and reflexive torque show agreement with clinical phenotype. Conclusions Using an instrumented and model based approach, increased joint stiffness in CP could be mainly attributed to higher reflexive torque compared to control subjects. Ratios between contributors varied substantially within adolescents with CP. Quantitative differentiation of neural and non-neural stiffness contributors in CP allows for assessment of individual patient characteristics and tailoring of therapy. PMID:23880287

2013-01-01

437

Rijke tube with flexible walls  

NASA Astrophysics Data System (ADS)

Sound is excited spontaneously in a Rijke tube because the small temperature perturbations in an acoustic field interact with heat transfer from a heat source in the tube. The air particles near the heat source undergo a thermodynamic cyle converting heat to mechanical energy, which is heard as the sound emanating from the Rijke tube. This principle of energy conversion is used in thermoacoustic engines, and the main objective of this study is to improve their performance. The acoustic oscillations in the Rijke tube regulate the thermodynamic cycle, just as in conventional engines the cycle is controlled by the motion of a piston and the action of inlet and exit valves. The acoustic regulation in the Rijke tube, however, does not allow arbitrary control of the cycle in thermodynamic phase space. In this presentation, we introduce a new way of overcoming this limitation, one by using Rijke tubes with flexible walls. We will discuss how this modification allows for more general thermodynamic cycles to be executed by the air particles in the tube. This possibility, when used in thermoacoustic engines, opens a channel for further improving the engine performance.

Mandre, Shreyas; Nguyen, Bao-Nhat; Li, Marvin

2011-11-01

438

Tube wall temperature monitoring technique  

SciTech Connect

In 1977, Monsanto and Conoco undertook the construction of a new, modern technology ethylene plant at Chocolate Bayou, near Alvin, Texas. This plant included high severity cracking furnaces with potential tube wall temperatures considerably higher than any we had previously experienced. Furnace on-stream time between decokes, a factor in the economics of plant operation, was limited by tube wall temperature, thus requiring its accurate knowledge. Earlier work with other ethylene furnaces had also demonstrated our lack of knowledge concerning high temperature measurements in a furnace firebox environment. This had to change. An outside consultant was called upon to provide a threeday workshop on radiant tube temperature sensing. The workshop consisted of two days of formal training in the theory and practice of temperature measurement and one day of field training. This workshop was conducted at a site away from the plant. Approximately 20 engineers (manufacturing and technical groups) attended. The major topics covered by this workshop are as follows: radiant tube temperature sensing, radiation situation of radiant tubes, g.a. method: sample calculations, noncontact sensors: methods of specifying and purchasing, thermal imager strategies, calibration of noncontact sensors, avoiding problems with noncontact sensors, optical aids to radiant tube viewing, tube temperature management and its environmental implications, and contact temperature sensors.

Granton, R.L.

1985-07-01

439

Sieve Tubes in Action  

PubMed Central

Abstract A method was designed for in vivo observation of sieve element/companion complexes by using confocal laser scanning microscopy. A leaf attached to an intact fava bean plant was mounted upside down on the stage of a confocal microscope. Two shallow paradermal cortical cuts were made in the major vein. The basal cortical window allowed us to observe the phloem intact. The apical window at 3 cm from the site of observation was used to apply phloem-mobile fluorochromes, which identified living sieve elements at the observation site. In intact sieve tubes, the sieve plates did not present a barrier to mass flow, because the translocation of fluorochromes appeared to be unhindered. Two major occlusion mechanisms were distinguished. In response to intense laser light, the parietal proteins detached from the plasma membrane and formed a network of minute strands and clustered material that aggregated and pressed against the sieve plate. In response to mechanical damage, the evenly distributed P plastids exploded, giving rise to the formation of a massive plug against the sieve plate. In case of mechanical damage, the parietal proteins transformed into elastic threads (strands) that extended throughout the sieve element lumen. Our observations cover the phenomena encountered in previous microscopic and electron microscopic studies and provide a temporal disentanglement of the events giving rise to the confusing mass of structures observed thus far.

Knoblauch, M.; van Bel, A. J. E.

1998-01-01