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Sample records for neural crest migration

  1. Modelling collective cell migration of neural crest.

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    Szabó, András; Mayor, Roberto

    2016-10-01

    Collective cell migration has emerged in the recent decade as an important phenomenon in cell and developmental biology and can be defined as the coordinated and cooperative movement of groups of cells. Most studies concentrate on tightly connected epithelial tissues, even though collective migration does not require a constant physical contact. Movement of mesenchymal cells is more independent, making their emergent collective behaviour less intuitive and therefore lending importance to computational modelling. Here we focus on such modelling efforts that aim to understand the collective migration of neural crest cells, a mesenchymal embryonic population that migrates large distances as a group during early vertebrate development. By comparing different models of neural crest migration, we emphasize the similarity and complementary nature of these approaches and suggest a future direction for the field. The principles derived from neural crest modelling could aid understanding the collective migration of other mesenchymal cell types. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The neural crest migrating into the 21st century

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    Bronner, Marianne E.; Simões-Costa, Marcos

    2016-01-01

    From the initial discovery of the neural crest over 150 years ago to the seminal studies of Le Douarin and colleagues in the latter part of the 20th century, understanding of the neural crest has moved from the descriptive to the experimental. Now, in the 21st century, neural crest research has migrated into the genomic age. Here we reflect upon the major advances in neural crest biology and the open questions that will continue to make research on this incredible vertebrate cell type an important subject in developmental biology for the century to come. PMID:26970616

  3. Role of the extracellular matrix during neural crest cell migration.

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    Perris, R; Perissinotto, D

    2000-07-01

    Once specified to become neural crest (NC), cells occupying the dorsal portion of the neural tube disrupt their cadherin-mediated cell-cell contacts, acquire motile properties, and embark upon an extensive migration through the embryo to reach their ultimate phenotype-specific sites. The understanding of how this movement is regulated is still rather fragmentary due to the complexity of the cellular and molecular interactions involved. An additional intricate aspect of the regulation of NC cell movement is that the timings, modes and patterns of NC cell migration are intimately associated with the concomitant phenotypic diversification that cells undergo during their migratory phase and the fact that these changes modulate the way that moving cells interact with their microenvironment. To date, two interplaying mechanisms appear central for the guidance of the migrating NC cells through the embryo: one involves secreted signalling molecules acting through their cognate protein kinase/phosphatase-type receptors and the other is contributed by the multivalent interactions of the cells with their surrounding extracellular matrix (ECM). The latter ones seem fundamental in light of the central morphogenetic role played by the intracellular signals transduced through the cytoskeleton upon integrin ligation, and the convergence of these signalling cascades with those triggered by cadherins, survival/growth factor receptors, gap junctional communications, and stretch-activated calcium channels. The elucidation of the importance of the ECM during NC cell movement is presently favoured by the augmenting knowledge about the macromolecular structure of the specific ECM assembled during NC development and the functional assaying of its individual constituents via molecular and genetic manipulations. Collectively, these data propose that NC cell migration may be governed by time- and space-dependent alterations in the expression of inhibitory ECM components; the relative ratio

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

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    Meulemans, Daniel; Bronner-Fraser, Marianne

    2002-01-01

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

  5. Embryonic cell-cell adhesion: a key player in collective neural crest migration.

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    Barriga, Elias H; Mayor, Roberto

    2015-01-01

    Cell migration is essential for morphogenesis, adult tissue remodeling, wound healing, and cancer cell migration. Cells can migrate as individuals or groups. When cells migrate in groups, cell-cell interactions are crucial in order to promote the coordinated behavior, essential for collective migration. Interestingly, recent evidence has shown that cell-cell interactions are also important for establishing and maintaining the directionality of these migratory events. We focus on neural crest cells, as they possess extraordinary migratory capabilities that allow them to migrate and colonize tissues all over the embryo. Neural crest cells undergo an epithelial-to-mesenchymal transition at the same time than perform directional collective migration. Cell-cell adhesion has been shown to be an important source of planar cell polarity and cell coordination during collective movement. We also review molecular mechanisms underlying cadherin turnover, showing how the modulation and dynamics of cell-cell adhesions are crucial in order to maintain tissue integrity and collective migration in vivo. We conclude that cell-cell adhesion during embryo development cannot be considered as simple passive resistance to force, but rather participates in signaling events that determine important cell behaviors required for cell migration. © 2015 Elsevier Inc. All rights reserved.

  6. Leader Cells Define Directionality of Trunk, but Not Cranial, Neural Crest Cell Migration

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    Jo Richardson

    2016-05-01

    Full Text Available Collective cell migration is fundamental for life and a hallmark of cancer. Neural crest (NC cells migrate collectively, but the mechanisms governing this process remain controversial. Previous analyses in Xenopus indicate that cranial NC (CNC cells are a homogeneous population relying on cell-cell interactions for directional migration, while chick embryo analyses suggest a heterogeneous population with leader cells instructing directionality. Our data in chick and zebrafish embryos show that CNC cells do not require leader cells for migration and all cells present similar migratory capacities. In contrast, laser ablation of trunk NC (TNC cells shows that leader cells direct movement and cell-cell contacts are required for migration. Moreover, leader and follower identities are acquired before the initiation of migration and remain fixed thereafter. Thus, two distinct mechanisms establish the directionality of CNC cells and TNC cells. This implies the existence of multiple molecular mechanisms for collective cell migration.

  7. A role for chemokine signaling in neural crest cell migration and craniofacial development

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    Killian, Eugenia C. Olesnicky; Birkholz, Denise A.; Artinger, Kristin Bruk

    2009-01-01

    Neural crest cells (NCCs) are a unique population of multipotent cells that migrate along defined pathways throughout the embryo and give rise to many diverse cell types including pigment cells, craniofacial cartilage and the peripheral nervous system (PNS). Aberrant migration of NCCs results in a wide variety of congenital birth defects including craniofacial abnormalities. The chemokine Sdf1 and its receptors, Cxcr4 and Cxcr7, have been identified as key components in the regulation of cell migration in a variety of tissues. Here we describe a novel role for the zebrafish chemokine receptor Cxcr4a in the development and migration of cranial NCCs (CNCCs). We find that loss of Cxcr4a, but not Cxcr7b results in aberrant CNCC migration, defects in the neurocranium, as well as cranial ganglia dismorphogenesis. Moreover, overexpression of either Sdf1b or Cxcr4a causes aberrant CNCC migration and results in ectopic craniofacial cartilages. We propose a model in which Sdf1b signaling from the pharyngeal arch endoderm and optic stalk to Cxcr4a expressing CNCCs is important for both the proper condensation of the CNCCs into pharyngeal arches and the subsequent patterning and morphogenesis of the neural crest derived tissues. PMID:19576198

  8. PDGF controls contact inhibition of locomotion by regulating N-cadherin during neural crest migration.

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    Bahm, Isabel; Barriga, Elias H; Frolov, Antonina; Theveneau, Eric; Frankel, Paul; Mayor, Roberto

    2017-07-01

    A fundamental property of neural crest (NC) migration is contact inhibition of locomotion (CIL), a process by which cells change their direction of migration upon cell contact. CIL has been proven to be essential for NC migration in amphibians and zebrafish by controlling cell polarity in a cell contact-dependent manner. Cell contact during CIL requires the participation of the cell adhesion molecule N-cadherin, which starts to be expressed by NC cells as a consequence of the switch between E- and N-cadherins during epithelial-to-mesenchymal transition (EMT). However, the mechanism that controls the upregulation of N-cadherin remains unknown. Here, we show that platelet-derived growth factor receptor alpha (PDGFRα) and its ligand platelet-derived growth factor A (PDGF-A) are co-expressed in migrating cranial NC. Inhibition of PDGF-A/PDGFRα blocks NC migration by inhibiting N-cadherin and, consequently, impairing CIL. Moreover, we identify phosphatidylinositol-3-kinase (PI3K)/AKT as a downstream effector of the PDGFRα cellular response during CIL. Our results lead us to propose PDGF-A/PDGFRα signalling as a tissue-autonomous regulator of CIL by controlling N-cadherin upregulation during EMT. Finally, we show that once NC cells have undergone EMT, the same PDGF-A/PDGFRα works as an NC chemoattractant, guiding their directional migration. © 2017. Published by The Company of Biologists Ltd.

  9. E-cadherin is required for cranial neural crest migration in Xenopus laevis.

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    Huang, Chaolie; Kratzer, Marie-Claire; Wedlich, Doris; Kashef, Jubin

    2016-03-15

    The cranial neural crest (CNC) is a highly motile and multipotent embryonic cell population, which migrates directionally on defined routes throughout the embryo, contributing to facial structures including cartilage, bone and ganglia. Cadherin-mediated cell-cell adhesion is known to play a crucial role in the directional migration of CNC cells. However, migrating CNC co-express different cadherin subtypes, and their individual roles have yet to be fully explored. In previous studies, the expression of individual cadherin subtypes has been analysed using different methods with varying sensitivities, preventing the direct comparison of expression levels. Here, we provide the first comprehensive and comparative analysis of the expression of six cadherin superfamily members during different phases of CNC cell migration in Xenopus. By applying a quantitative RT-qPCR approach, we can determine the copy number and abundance of each expressed cadherin through different phases of CNC migration. Using this approach, we show for the first time expression of E-cadherin and XB/C-cadherin in CNC cells, adding them as two new members of cadherins co-expressed during CNC migration. Cadherin co-expression during CNC migration in Xenopus, in particular the constant expression of E-cadherin, contradicts the classical epithelial-mesenchymal transition (EMT) model postulating a switch in cadherin expression. Loss-of-function experiments further show that E-cadherin is required for proper CNC cell migration in vivo and also for cell protrusion formation in vitro. Knockdown of E-cadherin is not rescued by co-injection of other classical cadherins, pointing to a specific function of E-cadherin in mediating CNC cell migration. Finally, through reconstitution experiments with different E-cadherin deletion mutants in E-cadherin morphant embryos, we demonstrate that the extracellular domain, but not the cytoplasmic domain, of E-cadherin is sufficient to rescue CNC cell migration in vivo

  10. Neural crest contributions to the lamprey head

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    McCauley, David W.; Bronner-Fraser, Marianne

    2003-01-01

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

  11. Insights into neural crest development from studies of avian embryos

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    Gandhi, Shashank; Bronner, Marianne E.

    2018-01-01

    The neural crest is a multipotent and highly migratory cell type that contributes to many of the defining features of vertebrates, including the skeleton of the head and most of the peripheral nervous system. 150 years after the discovery of the neural crest, avian embryos remain one of the most important model organisms for studying neural crest development. In this review, we describe aspects of neural crest induction, migration and axial level differences, highlighting what is known about ...

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

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    Bernd Willems

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

  13. Novel migrating mouse neural crest cell assay system utilizing P0-Cre/EGFP fluorescent time-lapse imaging

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    Kawakami Minoru

    2011-11-01

    Full Text Available Abstract Background Neural crest cells (NCCs are embryonic, multipotent stem cells. Their long-range and precision-guided migration is one of their most striking characteristics. We previously reported that P0-Cre/CAG-CAT-lacZ double-transgenic mice showed significant lacZ expression in tissues derived from NCCs. Results In this study, by embedding a P0-Cre/CAG-CAT-EGFP embryo at E9.5 in collagen gel inside a culture glass slide, we were able to keep the embryo developing ex vivo for more than 24 hours; this development was with enough NCC fluorescent signal intensity to enable single-cell resolution analysis, with the accompanying NCC migration potential intact and with the appropriate NCC response to the extracellular signal maintained. By implantation of beads with absorbed platelet-derived growth factor-AA (PDGF-AA, we demonstrated that PDGF-AA acts as an NCC-attractant in embryos. We also performed assays with NCCs isolated from P0-Cre/CAG-CAT-EGFP embryos on culture plates. The neuromediator 5-hydroxytryptamine (5-HT has been known to regulate NCC migration. We newly demonstrated that dopamine, in addition to 5-HT, stimulated NCC migration in vitro. Two NCC populations, with different axial levels of origins, showed unique distribution patterns regarding migration velocity and different dose-response patterns to both 5-HT and dopamine. Conclusions Although avian species predominated over the other species in the NCC study, our novel system should enable us to use mice to assay many different aspects of NCCs in embryos or on culture plates, such as migration, division, differentiation, and apoptosis.

  14. AKT signaling displays multifaceted functions in neural crest development.

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    Sittewelle, Méghane; Monsoro-Burq, Anne H

    2018-05-31

    AKT signaling is an essential intracellular pathway controlling cell homeostasis, cell proliferation and survival, as well as cell migration and differentiation in adults. Alterations impacting the AKT pathway are involved in many pathological conditions in human disease. Similarly, during development, multiple transmembrane molecules, such as FGF receptors, PDGF receptors or integrins, activate AKT to control embryonic cell proliferation, migration, differentiation, and also cell fate decisions. While many studies in mouse embryos have clearly implicated AKT signaling in the differentiation of several neural crest derivatives, information on AKT functions during the earliest steps of neural crest development had remained relatively scarce until recently. However, recent studies on known and novel regulators of AKT signaling demonstrate that this pathway plays critical roles throughout the development of neural crest progenitors. Non-mammalian models such as fish and frog embryos have been instrumental to our understanding of AKT functions in neural crest development, both in neural crest progenitors and in the neighboring tissues. This review combines current knowledge acquired from all these different vertebrate animal models to describe the various roles of AKT signaling related to neural crest development in vivo. We first describe the importance of AKT signaling in patterning the tissues involved in neural crest induction, namely the dorsal mesoderm and the ectoderm. We then focus on AKT signaling functions in neural crest migration and differentiation. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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    BORIC BRENET, KATICA ANDREA; BORIC BRENET, KATICA ANDREA

    2012-01-01

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

  16. Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells.

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    Xu, Xin; Francis, Richard; Wei, Chih Jen; Linask, Kaari L; Lo, Cecilia W

    2006-09-01

    Connexin 43 knockout (Cx43alpha1KO) mice have conotruncal heart defects that are associated with a reduction in the abundance of cardiac neural crest cells (CNCs) targeted to the heart. In this study, we show CNCs can respond to changing fibronectin matrix density by adjusting their migratory behavior, with directionality increasing and speed decreasing with increasing fibronectin density. However, compared with wild-type CNCs, Cx43alpha1KO CNCs show reduced directionality and speed, while CNCs overexpressing Cx43alpha1 from the CMV43 transgenic mice show increased directionality and speed. Altered integrin signaling was indicated by changes in the distribution of vinculin containing focal contacts, and altered temporal response of Cx43alpha1KO and CMV43 CNCs to beta1 integrin function blocking antibody treatment. High resolution motion analysis showed Cx43alpha1KO CNCs have increased cell protrusive activity accompanied by the loss of polarized cell movement. They exhibited an unusual polygonal arrangement of actin stress fibers that indicated a profound change in cytoskeletal organization. Semaphorin 3A, a chemorepellent known to inhibit integrin activation, was found to inhibit CNC motility, but in the Cx43alpha1KO and CMV43 CNCs, cell processes failed to retract with semaphorin 3A treatment. Immunohistochemical and biochemical analyses suggested close interactions between Cx43alpha1, vinculin and other actin-binding proteins. However, dye coupling analysis showed no correlation between gap junction communication level and fibronectin plating density. Overall, these findings indicate Cx43alpha1 may have a novel function in mediating crosstalk with cell signaling pathways that regulate polarized cell movement essential for the directional migration of CNCs.

  17. Recycling signals in the neural crest

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    Taneyhill, Lisa A.; Bronner-Fraser, Marianne E.

    2006-01-01

    Vertebrate neural crest cells are multipotent and differentiate into structures that include cartilage and the bones of the face, as well as much of the peripheral nervous system. Understanding how different model vertebrates utilize signaling pathways reiteratively during various stages of neural crest formation and differentiation lends insight into human disorders associated with the neural crest.

  18. Recycling signals in the neural crest.

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    Taneyhill, Lisa A; Bronner-Fraser, Marianne

    2005-01-01

    Vertebrate neural crest cells are multipotent and differentiate into structures that include cartilage and the bones of the face, as well as much of the peripheral nervous system. Understanding how different model vertebrates utilize signaling pathways reiteratively during various stages of neural crest formation and differentiation lends insight into human disorders associated with the neural crest.

  19. ADAM13 function is required in the 3 dimensional context of the embryo during cranial neural crest cell migration in Xenopus laevis

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    Cousin, Hélène; Abbruzzese, Genevieve; McCusker, Catherine; Alfandari, Dominique

    2012-01-01

    The cranial neural crest (CNC) is a population of cells that arises from the lateral part of the developing brain, migrates ventrally and coordinates the entire craniofacial development of vertebrates. Many molecules are involved in CNC migration including the transmembrane metalloproteases ADAM13 and 19. We have previously shown that these ADAMs cleave a number of extracellular proteins and modify the transcription of a number of genes, and that both of these activities are important for cell migration. Here we show that the knock down of ADAM13 inhibits CNC migration in vivo but not in vitro, indicating that ADAM13 function is required in the 3-dimentional context of the embryo. We further show that the migration of CNC that do not express ADAM13 and ADAM19 can be rescued in vivo by co-grafting wild type CNC. Furthermore, the migration of CNC lacking ADAM13 can be rescued by mechanically separating the CNC from the surrounding ectoderm and mesoderm. Finally, we show that ADAM13 function is autonomous to CNC tissue, as the migration of morphant CNC can only be rescued by ADAM13 expression in the CNC and not the surrounding tissues. Together our results suggest that ADAM13 changes CNC interaction with the extracellular environment and that this change is necessary for their migration in vivo. PMID:22683825

  20. DNA methyltransferase 3b is dispensable for mouse neural crest development.

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    Bridget T Jacques-Fricke

    Full Text Available The neural crest is a population of multipotent cells that migrates extensively throughout vertebrate embryos to form diverse structures. Mice mutant for the de novo DNA methyltransferase DNMT3b exhibit defects in two neural crest derivatives, the craniofacial skeleton and cardiac ventricular septum, suggesting that DNMT3b activity is necessary for neural crest development. Nevertheless, the requirement for DNMT3b specifically in neural crest cells, as opposed to interacting cell types, has not been determined. Using a conditional DNMT3b allele crossed to the neural crest cre drivers Wnt1-cre and Sox10-cre, neural crest DNMT3b mutants were generated. In both neural crest-specific and fully DNMT3b-mutant embryos, cranial neural crest cells exhibited only subtle migration defects, with increased numbers of dispersed cells trailing organized streams in the head. In spite of this, the resulting cranial ganglia, craniofacial skeleton, and heart developed normally when neural crest cells lacked DNMT3b. This indicates that DNTM3b is not necessary in cranial neural crest cells for their development. We conclude that defects in neural crest derivatives in DNMT3b mutant mice reflect a requirement for DNMT3b in lineages such as the branchial arch mesendoderm or the cardiac mesoderm that interact with neural crest cells during formation of these structures.

  1. The ectodomain of cadherin-11 binds to erbB2 and stimulates Akt phosphorylation to promote cranial neural crest cell migration.

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    Ketan Mathavan

    Full Text Available During development, a multi-potent group of cells known as the cranial neural crest (CNC migrate to form craniofacial structures. Proper migration of these cells requires proteolysis of cell adhesion molecules, such as cadherins. In Xenopus laevis, preventing extracellular cleavage of cadherin-11 impairs CNC migration. However, overexpression of the soluble cleavage product (EC1-3 is capable of rescuing this phenotype. The mechanism by which EC1-3 promotes CNC migration has not been investigated until now. Here we show that EC1-3 stimulates phosphorylation of Akt, a target of PI3K, in X.laevis CNC. Through immunoprecipitation experiments, we determined that EC1-3 interacts with all ErbB receptors, PDGFRα, and FGFR1. Of these receptors, only ErbB2 was able to produce an increase in Akt phosphorylation upon treatment with a recombinant EC1-3. This increase was abrogated by mubritinib, an inhibitor of ErbB2. We were able to recapitulate this decrease in Akt phosphorylation in vivo by knocking down ErbB2 in CNC cells. Knockdown of the receptor also significantly reduced CNC migration in vivo. We confirmed the importance of ErbB2 and ErbB receptor signaling in CNC migration using mubritinib and canertinib, respectively. Mubritinib and the PI3K inhibitor LY294002 significantly decreased cell migration while canertinib nearly prevented it altogether. These data show that ErbB2 and Akt are important for CNC migration and implicate other ErbB receptors and Akt-independent signaling pathways. Our findings provide the first example of a functional interaction between the extracellular domain of a type II classical cadherin and growth factor receptors.

  2. Decreased proliferative, migrative and neuro-differentiative potential of postnatal rat enteric neural crest-derived cells during culture in vitro

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    Yu, Hui; Pan, Wei-Kang; Zheng, Bai-Jun; Wang, Huai-Jie; Chen, Xin-Lin; Liu, Yong; Gao, Ya

    2016-01-01

    A growing body of evidence supports the potential use of enteric neural crest-derived cells (ENCCs) as a cell replacement therapy for Hirschsprung's disease. Based on previous observations of robust propagation of primary ENCCs, as opposed to their progeny, it is suggested that their therapeutic potential after in vitro expansion may be restricted. We therefore examined the growth and differentiation activities and phenotypic characteristics of continuous ENCC cultures. ENCCs were isolated from the intestines of postnatal rats and were identified using an immunocytochemical approach. During continuous ENCC culture expansion, proliferation, migration, apoptosis, and differentiation potentials were monitored. The Cell Counting Kit-8 was used for assessment of ENCC vitality, Transwell inserts for cell migration, immunocytochemistry for cell counts and identification, and flow cytometry for apoptosis. Over six continuous generations, ENCC proliferation potency was reduced and with prolonged culture, the ratio of migratory ENCCs was decreased. The percentage of apoptosis showed an upward trend with prolonged intragenerational culture, but showed a downward trend with prolonged culture of combined generations. Furthermore, the percentage of peripherin"+ cells decreased whilst the percentage of GFAP"+ cells increased with age. The results demonstrated that alterations in ENCC growth characteristics occur with increased culture time, which may partially account for the poor results of proposed cell therapies. - Highlights: • Differences were identified between primary and daughter ENCCs. • Daughter ENCCs had reduced proliferation, migration and differentiation. • Daughter ENCCs also had increased apoptosis. • These altered characteristics warrant further investigation.

  3. Decreased proliferative, migrative and neuro-differentiative potential of postnatal rat enteric neural crest-derived cells during culture in vitro

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    Yu, Hui [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Pan, Wei-Kang; Zheng, Bai-Jun; Wang, Huai-Jie [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Chen, Xin-Lin; Liu, Yong [Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Gao, Ya, E-mail: ygao@mail.xjtu.edu.cn [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China)

    2016-05-01

    A growing body of evidence supports the potential use of enteric neural crest-derived cells (ENCCs) as a cell replacement therapy for Hirschsprung's disease. Based on previous observations of robust propagation of primary ENCCs, as opposed to their progeny, it is suggested that their therapeutic potential after in vitro expansion may be restricted. We therefore examined the growth and differentiation activities and phenotypic characteristics of continuous ENCC cultures. ENCCs were isolated from the intestines of postnatal rats and were identified using an immunocytochemical approach. During continuous ENCC culture expansion, proliferation, migration, apoptosis, and differentiation potentials were monitored. The Cell Counting Kit-8 was used for assessment of ENCC vitality, Transwell inserts for cell migration, immunocytochemistry for cell counts and identification, and flow cytometry for apoptosis. Over six continuous generations, ENCC proliferation potency was reduced and with prolonged culture, the ratio of migratory ENCCs was decreased. The percentage of apoptosis showed an upward trend with prolonged intragenerational culture, but showed a downward trend with prolonged culture of combined generations. Furthermore, the percentage of peripherin{sup +} cells decreased whilst the percentage of GFAP{sup +} cells increased with age. The results demonstrated that alterations in ENCC growth characteristics occur with increased culture time, which may partially account for the poor results of proposed cell therapies. - Highlights: • Differences were identified between primary and daughter ENCCs. • Daughter ENCCs had reduced proliferation, migration and differentiation. • Daughter ENCCs also had increased apoptosis. • These altered characteristics warrant further investigation.

  4. Musculocontractural Ehlers–Danlos syndrome and neurocristopathies: dermatan sulfate is required for Xenopus neural crest cells to migrate and adhere to fibronectin

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    Nadège Gouignard

    2016-06-01

    Full Text Available Of all live births with congenital anomalies, approximately one-third exhibit deformities of the head and face. Most craniofacial disorders are associated with defects in a migratory stem and progenitor cell population, which is designated the neural crest (NC. Musculocontractural Ehlers–Danlos syndrome (MCEDS is a heritable connective tissue disorder with distinct craniofacial features; this syndrome comprises multiple congenital malformations that are caused by dysfunction of dermatan sulfate (DS biosynthetic enzymes, including DS epimerase-1 (DS-epi1; also known as DSE. Studies in mice have extended our understanding of DS-epi1 in connective tissue maintenance; however, its role in fetal development is not understood. We demonstrate that DS-epi1 is important for the generation of isolated iduronic acid residues in chondroitin sulfate (CS/DS proteoglycans in early Xenopus embryos. The knockdown of DS-epi1 does not affect the formation of early NC progenitors; however, it impairs the correct activation of transcription factors involved in the epithelial–mesenchymal transition (EMT and reduces the extent of NC cell migration, which leads to a decrease in NC-derived craniofacial skeleton, melanocytes and dorsal fin structures. Transplantation experiments demonstrate a tissue-autonomous role for DS-epi1 in cranial NC cell migration in vivo. Cranial NC explant and single-cell cultures indicate a requirement of DS-epi1 in cell adhesion, spreading and extension of polarized cell processes on fibronectin. Thus, our work indicates a functional link between DS and NC cell migration. We conclude that NC defects in the EMT and cell migration might account for the craniofacial anomalies and other congenital malformations in MCEDS, which might facilitate the diagnosis and development of therapies for this distressing condition. Moreover, the presented correlations between human DS-epi1 expression and gene sets of mesenchymal character, invasion and

  5. Aebp2 as an epigenetic regulator for neural crest cells.

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    Hana Kim

    Full Text Available Aebp2 is a potential targeting protein for the mammalian Polycomb Repression Complex 2 (PRC2. We generated a mutant mouse line disrupting the transcription of Aebp2 to investigate its in vivo roles. Aebp2-mutant homozygotes were embryonic lethal while heterozygotes survived to adulthood with fertility. In developing mouse embryos, Aebp2 is expressed mainly within cells of neural crest origin. In addition, many heterozygotes display a set of phenotypes, enlarged colon and hypopigmentation, similar to those observed in human patients with Hirschsprung's disease and Waardenburg syndrome. These phenotypes are usually caused by the absence of the neural crest-derived ganglia in hindguts and melanocytes. ChIP analyses demonstrated that the majority of the genes involved in the migration and development process of neural crest cells are downstream target genes of AEBP2 and PRC2. Furthermore, expression analyses confirmed that some of these genes are indeed affected in the Aebp2 heterozygotes. Taken together, these results suggest that Aebp2 may regulate the migration and development of the neural crest cells through the PRC2-mediated epigenetic mechanism.

  6. Musculocontractural Ehlers-Danlos syndrome and neurocristopathies: dermatan sulfate is required for Xenopus neural crest cells to migrate and adhere to fibronectin.

    Science.gov (United States)

    Gouignard, Nadège; Maccarana, Marco; Strate, Ina; von Stedingk, Kristoffer; Malmström, Anders; Pera, Edgar M

    2016-06-01

    Of all live births with congenital anomalies, approximately one-third exhibit deformities of the head and face. Most craniofacial disorders are associated with defects in a migratory stem and progenitor cell population, which is designated the neural crest (NC). Musculocontractural Ehlers-Danlos syndrome (MCEDS) is a heritable connective tissue disorder with distinct craniofacial features; this syndrome comprises multiple congenital malformations that are caused by dysfunction of dermatan sulfate (DS) biosynthetic enzymes, including DS epimerase-1 (DS-epi1; also known as DSE). Studies in mice have extended our understanding of DS-epi1 in connective tissue maintenance; however, its role in fetal development is not understood. We demonstrate that DS-epi1 is important for the generation of isolated iduronic acid residues in chondroitin sulfate (CS)/DS proteoglycans in early Xenopus embryos. The knockdown of DS-epi1 does not affect the formation of early NC progenitors; however, it impairs the correct activation of transcription factors involved in the epithelial-mesenchymal transition (EMT) and reduces the extent of NC cell migration, which leads to a decrease in NC-derived craniofacial skeleton, melanocytes and dorsal fin structures. Transplantation experiments demonstrate a tissue-autonomous role for DS-epi1 in cranial NC cell migration in vivo Cranial NC explant and single-cell cultures indicate a requirement of DS-epi1 in cell adhesion, spreading and extension of polarized cell processes on fibronectin. Thus, our work indicates a functional link between DS and NC cell migration. We conclude that NC defects in the EMT and cell migration might account for the craniofacial anomalies and other congenital malformations in MCEDS, which might facilitate the diagnosis and development of therapies for this distressing condition. Moreover, the presented correlations between human DS-epi1 expression and gene sets of mesenchymal character, invasion and metastasis in

  7. Neural crest cells: from developmental biology to clinical interventions.

    Science.gov (United States)

    Noisa, Parinya; Raivio, Taneli

    2014-09-01

    Neural crest cells are multipotent cells, which are specified in embryonic ectoderm in the border of neural plate and epiderm during early development by interconnection of extrinsic stimuli and intrinsic factors. Neural crest cells are capable of differentiating into various somatic cell types, including melanocytes, craniofacial cartilage and bone, smooth muscle, and peripheral nervous cells, which supports their promise for cell therapy. In this work, we provide a comprehensive review of wide aspects of neural crest cells from their developmental biology to applicability in medical research. We provide a simplified model of neural crest cell development and highlight the key external stimuli and intrinsic regulators that determine the neural crest cell fate. Defects of neural crest cell development leading to several human disorders are also mentioned, with the emphasis of using human induced pluripotent stem cells to model neurocristopathic syndromes. © 2014 Wiley Periodicals, Inc.

  8. Pax7 lineage contributions to the mammalian neural crest.

    Directory of Open Access Journals (Sweden)

    Barbara Murdoch

    Full Text Available Neural crest cells are vertebrate-specific multipotent cells that contribute to a variety of tissues including the peripheral nervous system, melanocytes, and craniofacial bones and cartilage. Abnormal development of the neural crest is associated with several human maladies including cleft/lip palate, aggressive cancers such as melanoma and neuroblastoma, and rare syndromes, like Waardenburg syndrome, a complex disorder involving hearing loss and pigment defects. We previously identified the transcription factor Pax7 as an early marker, and required component for neural crest development in chick embryos. In mammals, Pax7 is also thought to play a role in neural crest development, yet the precise contribution of Pax7 progenitors to the neural crest lineage has not been determined.Here we use Cre/loxP technology in double transgenic mice to fate map the Pax7 lineage in neural crest derivates. We find that Pax7 descendants contribute to multiple tissues including the cranial, cardiac and trunk neural crest, which in the cranial cartilage form a distinct regional pattern. The Pax7 lineage, like the Pax3 lineage, is additionally detected in some non-neural crest tissues, including a subset of the epithelial cells in specific organs.These results demonstrate a previously unappreciated widespread distribution of Pax7 descendants within and beyond the neural crest. They shed light regarding the regionally distinct phenotypes observed in Pax3 and Pax7 mutants, and provide a unique perspective into the potential roles of Pax7 during disease and development.

  9. Retinoic acid temporally orchestrates colonization of the gut by vagal neural crest cells.

    Science.gov (United States)

    Uribe, Rosa A; Hong, Stephanie S; Bronner, Marianne E

    2018-01-01

    The enteric nervous system arises from neural crest cells that migrate as chains into and along the primitive gut, subsequently differentiating into enteric neurons and glia. Little is known about the mechanisms governing neural crest migration en route to and along the gut in vivo. Here, we report that Retinoic Acid (RA) temporally controls zebrafish enteric neural crest cell chain migration. In vivo imaging reveals that RA loss severely compromises the integrity and migration of the chain of neural crest cells during the window of time window when they are moving along the foregut. After loss of RA, enteric progenitors accumulate in the foregut and differentiate into enteric neurons, but subsequently undergo apoptosis resulting in a striking neuronal deficit. Moreover, ectopic expression of the transcription factor meis3 and/or the receptor ret, partially rescues enteric neuron colonization after RA attenuation. Collectively, our findings suggest that retinoic acid plays a critical temporal role in promoting enteric neural crest chain migration and neuronal survival upstream of Meis3 and RET in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Xenopus reduced folate carrier regulates neural crest development epigenetically.

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    Jiejing Li

    Full Text Available Folic acid deficiency during pregnancy causes birth neurocristopathic malformations resulting from aberrant development of neural crest cells. The Reduced folate carrier (RFC is a membrane-bound receptor for facilitating transfer of reduced folate into the cells. RFC knockout mice are embryonic lethal and develop multiple malformations, including neurocristopathies. Here we show that XRFC is specifically expressed in neural crest tissues in Xenopus embryos and knockdown of XRFC by specific morpholino results in severe neurocristopathies. Inhibition of RFC blocked the expression of a series of neural crest marker genes while overexpression of RFC or injection of 5-methyltetrahydrofolate expanded the neural crest territories. In animal cap assays, knockdown of RFC dramatically reduced the mono- and trimethyl-Histone3-K4 levels and co-injection of the lysine methyltransferase hMLL1 largely rescued the XRFC morpholino phenotype. Our data revealed that the RFC mediated folate metabolic pathway likely potentiates neural crest gene expression through epigenetic modifications.

  11. Characterization of Pax3 and Sox10 transgenic Xenopus laevis embryos as tools to study neural crest development.

    Science.gov (United States)

    Alkobtawi, Mansour; Ray, Heather; Barriga, Elias H; Moreno, Mauricio; Kerney, Ryan; Monsoro-Burq, Anne-Helene; Saint-Jeannet, Jean-Pierre; Mayor, Roberto

    2018-03-06

    The neural crest is a multipotent population of cells that originates a variety of cell types. Many animal models are used to study neural crest induction, migration and differentiation, with amphibians and birds being the most widely used systems. A major technological advance to study neural crest development in mouse, chick and zebrafish has been the generation of transgenic animals in which neural crest specific enhancers/promoters drive the expression of either fluorescent proteins for use as lineage tracers, or modified genes for use in functional studies. Unfortunately, no such transgenic animals currently exist for the amphibians Xenopus laevis and tropicalis, key model systems for studying neural crest development. Here we describe the generation and characterization of two transgenic Xenopus laevis lines, Pax3-GFP and Sox10-GFP, in which GFP is expressed in the pre-migratory and migratory neural crest, respectively. We show that Pax3-GFP could be a powerful tool to study neural crest induction, whereas Sox10-GFP could be used in the study of neural crest migration in living embryos. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Neural crest stem cell population in craniomaxillofacial development and tissue repair

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    M La Noce

    2014-10-01

    Full Text Available Neural crest cells, delaminating from the neural tube during migration, undergo an epithelial-mesenchymal transition and differentiate into several cell types strongly reinforcing the mesoderm of the craniofacial body area – giving rise to bone, cartilage and other tissues and cells of this human body area. Recent studies on craniomaxillofacial neural crest-derived cells have provided evidence for the tremendous plasticity of these cells. Actually, neural crest cells can respond and adapt to the environment in which they migrate and the cranial mesoderm plays an important role toward patterning the identity of the migrating neural crest cells. In our experience, neural crest-derived stem cells, such as dental pulp stem cells, can actively proliferate, repair bone and give rise to other tissues and cytotypes, including blood vessels, smooth muscle, adipocytes and melanocytes, highlighting that their use in tissue engineering is successful. In this review, we provide an overview of the main pathways involved in neural crest formation, delamination, migration and differentiation; and, in particular, we concentrate our attention on the translatability of the latest scientific progress. Here we try to suggest new ideas and strategies that are needed to fully develop the clinical use of these cells. This effort should involve both researchers/clinicians and improvements in good manufacturing practice procedures. It is important to address studies towards clinical application or take into consideration that studies must have an effective therapeutic prospect for humans. New approaches and ideas must be concentrated also toward stem cell recruitment and activation within the human body, overcoming the classical grafting.

  13. Influence and timing of arrival of murine neural crest on pancreatic beta cell development and maturation.

    Science.gov (United States)

    Plank, Jennifer L; Mundell, Nathan A; Frist, Audrey Y; LeGrone, Alison W; Kim, Thomas; Musser, Melissa A; Walter, Teagan J; Labosky, Patricia A

    2011-01-15

    Interactions between cells from the ectoderm and mesoderm influence development of the endodermally-derived pancreas. While much is known about how mesoderm regulates pancreatic development, relatively little is understood about how and when the ectodermally-derived neural crest regulates pancreatic development and specifically, beta cell maturation. A previous study demonstrated that signals from the neural crest regulate beta cell proliferation and ultimately, beta cell mass. Here, we expand on that work to describe timing of neural crest arrival at the developing pancreatic bud and extend our knowledge of the non-cell autonomous role for neural crest derivatives in the process of beta cell maturation. We demonstrated that murine neural crest entered the pancreatic mesenchyme between the 26 and 27 somite stages (approximately 10.0 dpc) and became intermingled with pancreatic progenitors as the epithelium branched into the surrounding mesenchyme. Using a neural crest-specific deletion of the Forkhead transcription factor Foxd3, we ablated neural crest cells that migrate to the pancreatic primordium. Consistent with previous data, in the absence of Foxd3, and therefore the absence of neural crest cells, proliferation of insulin-expressing cells and insulin-positive area are increased. Analysis of endocrine cell gene expression in the absence of neural crest demonstrated that, although the number of insulin-expressing cells was increased, beta cell maturation was significantly impaired. Decreased MafA and Pdx1 expression illustrated the defect in beta cell maturation; we discovered that without neural crest, there was a reduction in the percentage of insulin-positive cells that co-expressed Glut2 and Pdx1 compared to controls. In addition, transmission electron microscopy analyses revealed decreased numbers of characteristic insulin granules and the presence of abnormal granules in insulin-expressing cells from mutant embryos. Together, these data demonstrate that

  14. Robo signaling regulates the production of cranial neural crest cells.

    Science.gov (United States)

    Li, Yan; Zhang, Xiao-Tan; Wang, Xiao-Yu; Wang, Guang; Chuai, Manli; Münsterberg, Andrea; Yang, Xuesong

    2017-12-01

    Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1 + cranial neural crest cells in early chick embryo development after knock-down (KD) of Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2α, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robo1 KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development. Copyright © 2017. Published by Elsevier Inc.

  15. Epithelial–Mesenchymal Transitions during Neural Crest and Somite Development

    Directory of Open Access Journals (Sweden)

    Chaya Kalcheim

    2015-12-01

    Full Text Available Epithelial-to-mesenchymal transition (EMT is a central process during embryonic development that affects selected progenitor cells of all three germ layers. In addition to driving the onset of cellular migrations and subsequent tissue morphogenesis, the dynamic conversions of epithelium into mesenchyme and vice-versa are intimately associated with the segregation of homogeneous precursors into distinct fates. The neural crest and somites, progenitors of the peripheral nervous system and of skeletal tissues, respectively, beautifully illustrate the significance of EMT to the above processes. Ongoing studies progressively elucidate the gene networks underlying EMT in each system, highlighting the similarities and differences between them. Knowledge of the mechanistic logic of this normal ontogenetic process should provide important insights to the understanding of pathological conditions such as cancer metastasis, which shares some common molecular themes.

  16. Migration flyway of the Mediterranean breeding Lesser Crested Tern ...

    African Journals Online (AJOL)

    The Lesser Crested Tern Thalasseus bengalensis emigratus breeding population in the Mediterranean is found exclusively in Libya, on the two coastal islands of Gara and Elba and one wetland on the mainland coast at Benghazi. In order to improve knowledge of the species migration to wintering quarters in West Africa, ...

  17. The hypoxia factor Hif-1α controls neural crest chemotaxis and epithelial to mesenchymal transition

    Science.gov (United States)

    Barriga, Elias H.; Maxwell, Patrick H.

    2013-01-01

    One of the most important mechanisms that promotes metastasis is the stabilization of Hif-1 (hypoxia-inducible transcription factor 1). We decided to test whether Hif-1α also was required for early embryonic development. We focused our attention on the development of the neural crest, a highly migratory embryonic cell population whose behavior has been likened to cancer metastasis. Inhibition of Hif-1α by antisense morpholinos in Xenopus laevis or zebrafish embryos led to complete inhibition of neural crest migration. We show that Hif-1α controls the expression of Twist, which in turn represses E-cadherin during epithelial to mesenchymal transition (EMT) of neural crest cells. Thus, Hif-1α allows cells to initiate migration by promoting the release of cell–cell adhesions. Additionally, Hif-1α controls chemotaxis toward the chemokine SDF-1 by regulating expression of its receptor Cxcr4. Our results point to Hif-1α as a novel and key regulator that integrates EMT and chemotaxis during migration of neural crest cells. PMID:23712262

  18. Evolution of neural crest and placodes: amphioxus as a model for the ancestral vertebrate?

    Science.gov (United States)

    Holland, L. Z.; Holland, N. D.

    2001-01-01

    Recent studies of protochordates (ascidian tunicates and amphioxus) have given insights into possible ancestors of 2 of the characteristic features of the vertebrate head: neural crest and placodes. The neural crest probably evolved from cells on either side of the neural plate-epidermis boundary in a protochordate ancestral to the vertebrates. In amphioxus, homologues of several vertebrate neural crest marker genes (BMP2/4, Pax3/7, Msx, Dll and Snail) are expressed at the edges of the neural plate and/or adjacent nonneural ectoderm. Some of these markers are also similarly expressed in tunicates. In protochordates, however, these cells, unlike vertebrate neural crest, neither migrate as individuals through embryonic tissues nor differentiate into a wide spectrum of cell types. Therefore, while the protochordate ancestor of the vertebrates probably had the beginnings of a genetic programme for neural crest formation, this programme was augmented in the earliest vertebrates to attain definitive neural crest. Clear homologues of vertebrate placodes are lacking in protochordates. However, both amphioxus and tunicates have ectodermal sensory cells. In tunicates these are all primary neurons, sending axons to the central nervous system, while in amphioxus, the ectodermal sensory cells include both primary neurons and secondary neurons lacking axons. Comparisons of developmental gene expression suggest that the anterior ectoderm in amphioxus may be homologous to the vertebrate olfactory placode, the only vertebrate placode with primary, not secondary, neurons. Similarly, biochemical, morphological and gene expression data suggest that amphioxus and tunicates also have homologues of the adenohypophysis, one of the few vertebrate structures derived from nonneurogenic placodes. In contrast, the origin of the other vertebrate placodes is very uncertain.

  19. Establishing neural crest identity: a gene regulatory recipe

    Science.gov (United States)

    Simões-Costa, Marcos; Bronner, Marianne E.

    2015-01-01

    The neural crest is a stem/progenitor cell population that contributes to a wide variety of derivatives, including sensory and autonomic ganglia, cartilage and bone of the face and pigment cells of the skin. Unique to vertebrate embryos, it has served as an excellent model system for the study of cell behavior and identity owing to its multipotency, motility and ability to form a broad array of cell types. Neural crest development is thought to be controlled by a suite of transcriptional and epigenetic inputs arranged hierarchically in a gene regulatory network. Here, we examine neural crest development from a gene regulatory perspective and discuss how the underlying genetic circuitry results in the features that define this unique cell population. PMID:25564621

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

    Science.gov (United States)

    Pla, Patrick; Monsoro-Burq, Anne H

    2018-05-28

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

  1. Utility of Phox2b immunohistochemical stain in neural crest tumours and non-neural crest tumours in paediatric patients.

    Science.gov (United States)

    Warren, Mikako; Matsuno, Ryosuke; Tran, Henry; Shimada, Hiroyuki

    2018-03-01

    This study evaluated the utility of Phox2b in paediatric tumours. Previously, tyrosine hydroxylase (TH) was the most widely utilised sympathoadrenal marker specific for neural crest tumours with neuronal/neuroendocrine differentiation. However, its sensitivity is insufficient. Recently Phox2b has emerged as another specific marker for this entity. Phox2b immunohistochemistry (IHC) was performed on 159 paediatric tumours, including (group 1) 65 neural crest tumours with neuronal differentiation [peripheral neuroblastic tumours (pNT)]: 15 neuroblastoma undifferentiated (NB-UD), 10 NB poorly differentiated (NB-PD), 10 NB differentiating (NB-D), 10 ganglioneuroblastoma intermixed (GNBi), 10 GNB nodular (GNBn) and 10 ganglioneuroma (GN); (group 2) 23 neural crest tumours with neuroendocrine differentiation [pheochromocytoma/paraganglioma (PCC/PG)]; (group 3) 27 other neural crest tumours including one composite rhabdomyosarcoma/neuroblastoma; and (group 4) 44 non-neural crest tumours. TH IHC was performed on groups 1, 2 and 3. Phox2b was expressed diffusely in pNT (n = 65 of 65), strongly in NB-UD and NB-PD and with less intensity in NB-D, GNB and GN. Diffuse TH was seen in all NB-PD, NB-D, GNB and GN, but nine of 15 NB-UD and a nodule in GNBn did not express TH (n = 55 of 65). PCC/PG expressed diffuse Phox2b (n = 23 of 23) and diffuse TH, except for one tumour (n = 22 of 23). In composite rhabdomyosarcoma, TH was expressed only in neuroblastic cells and Phox2b was diffusely positive in neuroblastic cells and focally in rhabdomyosarcoma. All other tumours were negative for Phox2b (n = none of 44). Phox2b was a specific and sensitive marker for pNT and PCC/PG, especially useful for identifying NB-UD often lacking TH. Our study also presented a composite rhabdomyosarcoma/neuroblastoma of neural crest origin. © 2017 John Wiley & Sons Ltd.

  2. Cut loose and run: The complex role of ADAM proteases during neural crest cell development.

    Science.gov (United States)

    Alfandari, Dominique; Taneyhill, Lisa A

    2018-02-24

    ADAM metalloproteases have been shown to play critical roles during development. In this review, we will describe functional evidence that implicates ADAM proteins during the genesis, migration and differentiation of neural crest cells. We will restrict our analysis to the transmembrane ADAMs as other reviews have addressed the role of extracellular metalloproteases (Christian et al. [2013] Critical Reviews in Biochemistry and Molecular Biology 48:544-560). This review will describe advances that have been obtained mainly through the use of two vertebrate model systems, the frog, and avian embryos. The role of the principal substrates of ADAMs, the cadherins, has been extensively described in other reviews, most recently in (Cousin [1997] Mechanisms of Development 148:79-88; Taneyhill and Schiffmacher [2017] Genesis, 55). The function of ADAMs in the migration of other cell types, including the immune system, wound healing and cancer has been described previously in (Dreymueller et al. [2017] Mediators of Inflammation 2017: 9621724). Our goal is to illustrate both the importance of ADAMs in controlling neural crest behavior and how neural crest cells have helped us understand the molecular interactions, substrates, and functions of ADAM proteins in vivo. © 2018 Wiley Periodicals, Inc.

  3. Applications of Mesenchymal Stem Cells and Neural Crest Cells in Craniofacial Skeletal Research

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    Satoru Morikawa

    2016-01-01

    Full Text Available Craniofacial skeletal tissues are composed of tooth and bone, together with nerves and blood vessels. This composite material is mainly derived from neural crest cells (NCCs. The neural crest is transient embryonic tissue present during neural tube formation whose cells have high potential for migration and differentiation. Thus, NCCs are promising candidates for craniofacial tissue regeneration; however, the clinical application of NCCs is hindered by their limited accessibility. In contrast, mesenchymal stem cells (MSCs are easily accessible in adults, have similar potential for self-renewal, and can differentiate into skeletal tissues, including bones and cartilage. Therefore, MSCs may represent good sources of stem cells for clinical use. MSCs are classically identified under adherent culture conditions, leading to contamination with other cell lineages. Previous studies have identified mouse- and human-specific MSC subsets using cell surface markers. Additionally, some studies have shown that a subset of MSCs is closely related to neural crest derivatives and endothelial cells. These MSCs may be promising candidates for regeneration of craniofacial tissues from the perspective of developmental fate. Here, we review the fundamental biology of MSCs in craniofacial research.

  4. The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in Xenopus laevis

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    Hartley Rebecca S

    2010-01-01

    Full Text Available Abstract Background The neural crest is a unique population of cells that arise in the vertebrate ectoderm at the neural plate border after which they migrate extensively throughout the embryo, giving rise to a wide range of derivatives. A number of proteins involved in neural crest development have dynamic expression patterns, and it is becoming clear that ubiquitin-mediated protein degradation is partly responsible for this. Results Here we demonstrate a novel role for the F-box protein Cdc4/Fbxw7 in neural crest development. Two isoforms of Xenopus laevis Cdc4 were identified, and designated xCdc4α and xCdc4β. These are highly conserved with vertebrate Cdc4 orthologs, and the Xenopus proteins are functionally equivalent in terms of their ability to degrade Cyclin E, an established vertebrate Cdc4 target. Blocking xCdc4 function specifically inhibited neural crest development at an early stage, prior to expression of c-Myc, Snail2 and Snail. Conclusions We demonstrate that Cdc4, an ubiquitin E3 ligase subunit previously identified as targeting primarily cell cycle regulators for proteolysis, has additional roles in control of formation of the neural crest. Hence, we identify Cdc4 as a protein with separable but complementary functions in control of cell proliferation and differentiation.

  5. Regeneration of neural crest derivatives in the Xenopus tadpole tail

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    Slack Jonathan MW

    2007-05-01

    Full Text Available Abstract Background After amputation of the Xenopus tadpole tail, a functionally competent new tail is regenerated. It contains spinal cord, notochord and muscle, each of which has previously been shown to derive from the corresponding tissue in the stump. The regeneration of the neural crest derivatives has not previously been examined and is described in this paper. Results Labelling of the spinal cord by electroporation, or by orthotopic grafting of transgenic tissue expressing GFP, shows that no cells emigrate from the spinal cord in the course of regeneration. There is very limited regeneration of the spinal ganglia, but new neurons as well as fibre tracts do appear in the regenerated spinal cord and the regenerated tail also contains abundant peripheral innervation. The regenerated tail contains a normal density of melanophores. Cell labelling experiments show that melanophores do not arise from the spinal cord during regeneration, nor from the mesenchymal tissues of the skin, but they do arise by activation and proliferation of pre-existing melanophore precursors. If tails are prepared lacking melanophores, then the regenerates also lack them. Conclusion On regeneration there is no induction of a new neural crest similar to that seen in embryonic development. However there is some regeneration of neural crest derivatives. Abundant melanophores are regenerated from unpigmented precursors, and, although spinal ganglia are not regenerated, sufficient sensory systems are produced to enable essential functions to continue.

  6. Development of teeth in chick embryos after mouse neural crest transplantations

    OpenAIRE

    Mitsiadis, Thimios A.; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

    2003-01-01

    Teeth were lost in birds 70–80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick ...

  7. Development of teeth in chick embryos after mouse neural crest transplantations.

    Science.gov (United States)

    Mitsiadis, Thimios A; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

    2003-05-27

    Teeth were lost in birds 70-80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick chimeras obtained show evidence of tooth formation showing that avian oral epithelium is able to induce a nonavian developmental program in mouse neural crest-derived mesenchymal cells.

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

    Science.gov (United States)

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

    2012-06-02

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

  9. A negative modulatory role for rho and rho-associated kinase signaling in delamination of neural crest cells

    Directory of Open Access Journals (Sweden)

    Kalcheim Chaya

    2008-10-01

    Full Text Available Abstract Background Neural crest progenitors arise as epithelial cells and then undergo a process of epithelial to mesenchymal transition that precedes the generation of cellular motility and subsequent migration. We aim at understanding the underlying molecular network. Along this line, possible roles of Rho GTPases that act as molecular switches to control a variety of signal transduction pathways remain virtually unexplored, as are putative interactions between Rho proteins and additional known components of this cascade. Results We investigated the role of Rho/Rock signaling in neural crest delamination. Active RhoA and RhoB are expressed in the membrane of epithelial progenitors and are downregulated upon delamination. In vivo loss-of-function of RhoA or RhoB or of overall Rho signaling by C3 transferase enhanced and/or triggered premature crest delamination yet had no effect on cell specification. Consistently, treatment of explanted neural primordia with membrane-permeable C3 or with the Rock inhibitor Y27632 both accelerated and enhanced crest emigration without affecting cell proliferation. These treatments altered neural crest morphology by reducing stress fibers, focal adhesions and downregulating membrane-bound N-cadherin. Reciprocally, activation of endogenous Rho by lysophosphatidic acid inhibited emigration while enhancing the above. Since delamination is triggered by BMP and requires G1/S transition, we examined their relationship with Rho. Blocking Rho/Rock function rescued crest emigration upon treatment with noggin or with the G1/S inhibitor mimosine. In the latter condition, cells emigrated while arrested at G1. Conversely, BMP4 was unable to rescue cell emigration when endogenous Rho activity was enhanced by lysophosphatidic acid. Conclusion Rho-GTPases, through Rock, act downstream of BMP and of G1/S transition to negatively regulate crest delamination by modifying cytoskeleton assembly and intercellular adhesion.

  10. Adrenergic innervation of the developing chick heart: neural crest ablations to produce sympathetically aneural hearts

    International Nuclear Information System (INIS)

    Kirby, M.; Stewart, D.

    1984-01-01

    Ablation of various regions of premigratory trunk neural crest which gives rise to the sympathetic trunks was used to remove sympathetic cardiac innervation. Neuronal uptake of [ 3 H]-norepinephrine was used as an index of neuronal development in the chick atrium. Following ablation of neural crest over somites 10-15 or 15-20, uptake was significantly decreased in the atrium at 16 and 17 days of development. Ablation of neural crest over somites 5-10 and 20-25 caused no decrease in [ 3 H]-norepinephrine uptake. Removal of neural crest over somites 5-25 or 10-20 caused approximately equal depletions of [ 3 H]-norepinephrine uptake in the atrium. Cardiac norepinephrine concentration was significantly depressed following ablation of neural crest over somites 5-25 but not over somites 10-20. Light-microscopic and histofluorescent preparations confirmed the absence of sympathetic trunks in the region of the normal origin of the sympathetic cardiac nerves following neural crest ablation over somites 10-20. The neural tube and dorsal root ganglia were damaged in the area of the neural-crest ablation; however, all of these structures were normal cranial and caudal to the lesioned area. Development of most of the embryos as well as the morphology of all of the hearts was normal following the lesion. These results indicate that it is possible to produce sympathetically aneural hearts by neural-crest ablation; however, sympathetic cardiac nerves account for an insignificant amount of cardiac norepinephrine

  11. Inca: a novel p21-activated kinase-associated protein required for cranial neural crest development.

    Science.gov (United States)

    Luo, Ting; Xu, Yanhua; Hoffman, Trevor L; Zhang, Tailin; Schilling, Thomas; Sargent, Thomas D

    2007-04-01

    Inca (induced in neural crest by AP2) is a novel protein discovered in a microarray screen for genes that are upregulated in Xenopus embryos by the transcriptional activator protein Tfap2a. It has no significant similarity to any known protein, but is conserved among vertebrates. In Xenopus, zebrafish and mouse embryos, Inca is expressed predominantly in the premigratory and migrating neural crest (NC). Knockdown experiments in frog and fish using antisense morpholinos reveal essential functions for Inca in a subset of NC cells that form craniofacial cartilage. Cells lacking Inca migrate successfully but fail to condense into skeletal primordia. Overexpression of Inca disrupts cortical actin and prevents formation of actin "purse strings", which are required for wound healing in Xenopus embryos. We show that Inca physically interacts with p21-activated kinase 5 (PAK5), a known regulator of the actin cytoskeleton that is co-expressed with Inca in embryonic ectoderm, including in the NC. These results suggest that Inca and PAK5 cooperate in restructuring cytoskeletal organization and in the regulation of cell adhesion in the early embryo and in NC cells during craniofacial development.

  12. Imidacloprid Exposure Suppresses Neural Crest Cells Generation during Early Chick Embryo Development.

    Science.gov (United States)

    Wang, Chao-Jie; Wang, Guang; Wang, Xiao-Yu; Liu, Meng; Chuai, Manli; Lee, Kenneth Ka Ho; He, Xiao-Song; Lu, Da-Xiang; Yang, Xuesong

    2016-06-15

    Imidacloprid is a neonicotinoid pesticide that is widely used in the control pests found on crops and fleas on pets. However, it is still unclear whether imidacloprid exposure could affect early embryo development-despite some studies having been conducted on the gametes. In this study, we demonstrated that imidacloprid exposure could lead to abnormal craniofacial osteogenesis in the developing chick embryo. Cranial neural crest cells (NCCs) are the progenitor cells of the chick cranial skull. We found that the imidacloprid exposure retards the development of gastrulating chick embryos. HNK-1, PAX7, and Ap-2α immunohistological stainings indicated that cranial NCCs generation was inhibited after imidacloprid exposure. Double immunofluorescent staining (Ap-2α and PHIS3 or PAX7 and c-Caspase3) revealed that imidacloprid exposure inhibited both NCC proliferation and apoptosis. In addition, it inhibited NCCs production by repressing Msx1 and BMP4 expression in the developing neural tube and by altering expression of EMT-related adhesion molecules (Cad6B, E-Cadherin, and N-cadherin) in the developing neural crests. We also determined that imidacloprid exposure suppressed cranial NCCs migration and their ability to differentiate. In sum, we have provided experimental evidence that imidacloprid exposure during embryogenesis disrupts NCCs development, which in turn causes defective cranial bone development.

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  1. File list: InP.PSC.50.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. Review: the role of neural crest cells in the endocrine system.

    Science.gov (United States)

    Adams, Meghan Sara; Bronner-Fraser, Marianne

    2009-01-01

    The neural crest is a pluripotent population of cells that arises at the junction of the neural tube and the dorsal ectoderm. These highly migratory cells form diverse derivatives including neurons and glia of the sensory, sympathetic, and enteric nervous systems, melanocytes, and the bones, cartilage, and connective tissues of the face. The neural crest has long been associated with the endocrine system, although not always correctly. According to current understanding, neural crest cells give rise to the chromaffin cells of the adrenal medulla, chief cells of the extra-adrenal paraganglia, and thyroid C cells. The endocrine tumors that correspond to these cell types are pheochromocytomas, extra-adrenal paragangliomas, and medullary thyroid carcinomas. Although controversies concerning embryological origin appear to have mostly been resolved, questions persist concerning the pathobiology of each tumor type and its basis in neural crest embryology. Here we present a brief history of the work on neural crest development, both in general and in application to the endocrine system. In particular, we present findings related to the plasticity and pluripotency of neural crest cells as well as a discussion of several different neural crest tumors in the endocrine system.

  3. Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells

    Directory of Open Access Journals (Sweden)

    Tsutomu Motohashi

    2016-03-01

    Full Text Available Neural crest cells (NC cells are multipotent cells that emerge from the edge of the neural folds and migrate throughout the developing embryo. Although the gene regulatory network for generation of NC cells has been elucidated in detail, it has not been revealed which of the factors in the network are pivotal to directing NC identity. In this study we analyzed the gene expression profile of a pure NC subpopulation isolated from Sox10-IRES-Venus mice and investigated whether these genes played a key role in the direct conversion of Sox10-IRES-Venus mouse embryonic fibroblasts (MEFs into NC cells. The comparative molecular profiles of NC cells and neural tube cells in 9.5-day embryos revealed genes including transcription factors selectively expressed in developing trunk NC cells. Among 25 NC cell-specific transcription factor genes tested, SOX10 and SOX9 were capable of converting MEFs into SOX10-positive (SOX10+ cells. The SOX10+ cells were then shown to differentiate into neurons, glial cells, smooth muscle cells, adipocytes and osteoblasts. These SOX10+ cells also showed limited self-renewal ability, suggesting that SOX10 and SOX9 directly converted MEFs into NC cells. Conversely, the remaining transcription factors, including well-known NC cell specifiers, were unable to convert MEFs into SOX10+ NC cells. These results suggest that SOX10 and SOX9 are the key factors necessary for the direct conversion of MEFs into NC cells.

  4. Fluorescence-Activated Cell Sorting of EGFP-Labeled Neural Crest Cells From Murine Embryonic Craniofacial Tissue

    Directory of Open Access Journals (Sweden)

    Saurabh Singh

    2005-01-01

    Full Text Available During the early stages of embryogenesis, pluripotent neural crest cells (NCC are known to migrate from the neural folds to populate multiple target sites in the embryo where they differentiate into various derivatives, including cartilage, bone, connective tissue, melanocytes, glia, and neurons of the peripheral nervous system. The ability to obtain pure NCC populations is essential to enable molecular analyses of neural crest induction, migration, and/or differentiation. Crossing Wnt1-Cre and Z/EG transgenic mouse lines resulted in offspring in which the Wnt1-Cre transgene activated permanent EGFP expression only in NCC. The present report demonstrates a flow cytometric method to sort and isolate populations of EGFP-labeled NCC. The identity of the sorted neural crest cells was confirmed by assaying expression of known marker genes by TaqMan Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR. The molecular strategy described in this report provides a means to extract intact RNA from a pure population of NCC thus enabling analysis of gene expression in a defined population of embryonic precursor cells critical to development.

  5. Changes in cholinergic parameters associated with failure of conotruncal septation in embryonic chick hearts after neural crest ablation

    International Nuclear Information System (INIS)

    Kirby, M.L.; Aronstam, R.S.; Buccafusco, J.J.

    1985-01-01

    Cells from the neural crest over occipital somites migrate to the heart, where they give rise to parasympathetic postganglionic neurons as well as ectomesenchymal elements which contribute to conotruncal septation. With a microcautery needle, the neural crest over occipital somites was ablated bilaterally in chicken embryos at an early stage of development. Histological examination on incubation day 15 revealed conotruncal malformations, involving malformation or absence of the conotruncal septum in all embryos. Two peaks of embryo mortality were observed. One peak (incubation days 6-8) occurred at the same time as conotruncal septal closure; the second peak (incubation days 11-13) was concurrent with the onset of functional parasympathetic innervation. A disruption of parasympathetic innervation was indicated by: (1) a decrease in acetylcholinesterase staining, (2) a decrease (27%) in the number of ganglion cells in the conotruncus, (3) decreases in the acetylcholine content of atrium (31%) and ventricle (39%), and (4) a decrease (21%) in muscarinic acetylcholine receptor density on incubation day 15. Radiolabeled ligand-binding studies revealed no change in the affinity of cardiac muscarinic receptors for [ 3 H]methylscopolamine (K/sub D/ . 0.17-0.21 nM). Agonist-binding affinity and sensitivity to guanine nucleotides were similarly unaffected. The reasons for the limited extent of the parasympathetic lesion are unclear, but may involve recruitment of precursor cells from other regions of the neural crest, partial regeneration of the neural crest following surgical removal, or an alteration in the contribution of incoming sympathetic or preganglionic parasympathetic elements. No such plasticity was associated with neural crest contributions to the structural development of the conotruncus. Malformations were observed in all lesioned embryos

  6. Neural crest does not contribute to the neck and shoulder in the axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Epperlein, Hans-Henning; Khattak, Shahryar; Knapp, Dunja; Tanaka, Elly M; Malashichev, Yegor B

    2012-01-01

    A major step during the evolution of tetrapods was their transition from water to land. This process involved the reduction or complete loss of the dermal bones that made up connections to the skull and a concomitant enlargement of the endochondral shoulder girdle. In the mouse the latter is derived from three separate embryonic sources: lateral plate mesoderm, somites, and neural crest. The neural crest was suggested to sustain the muscle attachments. How this complex composition of the endochondral shoulder girdle arose during evolution and whether it is shared by all tetrapods is unknown. Salamanders that lack dermal bone within their shoulder girdle were of special interest for a possible contribution of the neural crest to the endochondral elements and muscle attachment sites, and we therefore studied them in this context. We grafted neural crest from GFP+ fluorescent transgenic axolotl (Ambystoma mexicanum) donor embryos into white (d/d) axolotl hosts and followed the presence of neural crest cells within the cartilage of the shoulder girdle and the connective tissue of muscle attachment sites of the neck-shoulder region. Strikingly, neural crest cells did not contribute to any part of the endochondral shoulder girdle or to the connective tissue at muscle attachment sites in axolotl. Our results in axolotl suggest that neural crest does not serve a general function in vertebrate shoulder muscle attachment sites as predicted by the "muscle scaffold theory," and that it is not necessary to maintain connectivity of the endochondral shoulder girdle to the skull. Our data support the possibility that the contribution of the neural crest to the endochondral shoulder girdle, which is observed in the mouse, arose de novo in mammals as a developmental basis for their skeletal synapomorphies. This further supports the hypothesis of an increased neural crest diversification during vertebrate evolution.

  7. Neural crest does not contribute to the neck and shoulder in the axolotl (Ambystoma mexicanum.

    Directory of Open Access Journals (Sweden)

    Hans-Henning Epperlein

    Full Text Available BACKGROUND: A major step during the evolution of tetrapods was their transition from water to land. This process involved the reduction or complete loss of the dermal bones that made up connections to the skull and a concomitant enlargement of the endochondral shoulder girdle. In the mouse the latter is derived from three separate embryonic sources: lateral plate mesoderm, somites, and neural crest. The neural crest was suggested to sustain the muscle attachments. How this complex composition of the endochondral shoulder girdle arose during evolution and whether it is shared by all tetrapods is unknown. Salamanders that lack dermal bone within their shoulder girdle were of special interest for a possible contribution of the neural crest to the endochondral elements and muscle attachment sites, and we therefore studied them in this context. RESULTS: We grafted neural crest from GFP+ fluorescent transgenic axolotl (Ambystoma mexicanum donor embryos into white (d/d axolotl hosts and followed the presence of neural crest cells within the cartilage of the shoulder girdle and the connective tissue of muscle attachment sites of the neck-shoulder region. Strikingly, neural crest cells did not contribute to any part of the endochondral shoulder girdle or to the connective tissue at muscle attachment sites in axolotl. CONCLUSIONS: Our results in axolotl suggest that neural crest does not serve a general function in vertebrate shoulder muscle attachment sites as predicted by the "muscle scaffold theory," and that it is not necessary to maintain connectivity of the endochondral shoulder girdle to the skull. Our data support the possibility that the contribution of the neural crest to the endochondral shoulder girdle, which is observed in the mouse, arose de novo in mammals as a developmental basis for their skeletal synapomorphies. This further supports the hypothesis of an increased neural crest diversification during vertebrate evolution.

  8. Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Sowa

    Full Text Available Recent studies have shown that adipose-derived stromal/stem cells (ASCs contain phenotypically and functionally heterogeneous subpopulations of cells, but their developmental origin and their relative differentiation potential remain elusive. In the present study, we aimed at investigating how and to what extent the neural crest contributes to ASCs using Cre-loxP-mediated fate mapping. ASCs harvested from subcutaneous fat depots of either adult P0-Cre/or Wnt1-Cre/Floxed-reporter mice contained a few neural crest-derived ASCs (NCDASCs. This subpopulation of cells was successfully expanded in vitro under standard culture conditions and their growth rate was comparable to non-neural crest derivatives. Although NCDASCs were positive for several mesenchymal stem cell markers as non-neural crest derivatives, they exhibited a unique bipolar or multipolar morphology with higher expression of markers for both neural crest progenitors (p75NTR, Nestin, and Sox2 and preadipocytes (CD24, CD34, S100, Pref-1, GATA2, and C/EBP-delta. NCDASCs were able to differentiate into adipocytes with high efficiency but their osteogenic and chondrogenic potential was markedly attenuated, indicating their commitment to adipogenesis. In vivo, a very small proportion of adipocytes were originated from the neural crest. In addition, p75NTR-positive neural crest-derived cells were identified along the vessels within the subcutaneous adipose tissue, but they were negative for mural and endothelial markers. These results demonstrate that ASCs contain neural crest-derived adipocyte-restricted progenitors whose phenotype is distinct from that of non-neural crest derivatives.

  9. The neural crest, a multifaceted structure of the vertebrates.

    Science.gov (United States)

    Dupin, Elisabeth; Le Douarin, Nicole M

    2014-09-01

    In this review, several features of the cells originating from the lateral borders of the primitive neural anlagen, the neural crest (NC) are considered. Among them, their multipotentiality, which together with their migratory properties, leads them to colonize the developing body and to participate in the development of many tissues and organs. The in vitro analysis of the developmental capacities of single NC cells (NCC) showed that they present several analogies with the hematopoietic cells whose differentiation involves the activity of stem cells endowed with different arrays of developmental potentialities. The permanence of such NC stem cells in the adult organism raises the problem of their role at that stage of life. The NC has appeared during evolution in the vertebrate phylum and is absent in their Protocordates ancestors. The major role of the NCC in the development of the vertebrate head points to a critical role for this structure in the remarkable diversification and radiation of this group of animals. © 2014 Wiley Periodicals, Inc.

  10. Animal models for studying neural crest development: is the mouse different?

    Science.gov (United States)

    Barriga, Elias H; Trainor, Paul A; Bronner, Marianne; Mayor, Roberto

    2015-05-01

    The neural crest is a uniquely vertebrate cell type and has been well studied in a number of model systems. Zebrafish, Xenopus and chick embryos largely show consistent requirements for specific genes in early steps of neural crest development. By contrast, knockouts of homologous genes in the mouse often do not exhibit comparable early neural crest phenotypes. In this Spotlight article, we discuss these species-specific differences, suggest possible explanations for the divergent phenotypes in mouse and urge the community to consider these issues and the need for further research in complementary systems. © 2015. Published by The Company of Biologists Ltd.

  11. Germ layers, the neural crest and emergent organization in development and evolution.

    Science.gov (United States)

    Hall, Brian K

    2018-04-10

    Discovered in chick embryos by Wilhelm His in 1868 and named the neural crest by Arthur Milnes Marshall in 1879, the neural crest cells that arise from the neural folds have since been shown to differentiate into almost two dozen vertebrate cell types and to have played major roles in the evolution of such vertebrate features as bone, jaws, teeth, visceral (pharyngeal) arches, and sense organs. I discuss the discovery that ectodermal neural crest gave rise to mesenchyme and the controversy generated by that finding; the germ layer theory maintained that only mesoderm could give rise to mesenchyme. A second topic of discussion is germ layers (including the neural crest) as emergent levels of organization in animal development and evolution that facilitated major developmental and evolutionary change. The third topic is gene networks, gene co-option, and the evolution of gene-signaling pathways as key to developmental and evolutionary transitions associated with the origin and evolution of the neural crest and neural crest cells. © 2018 Wiley Periodicals, Inc.

  12. Dicer activity in neural crest cells is essential for craniofacial organogenesis and pharyngeal arch artery morphogenesis

    Science.gov (United States)

    Nie, Xuguang; Wang, Qin; Jiao, Kai

    2014-01-01

    MicroRNAs (miRNAs) play important roles in regulating gene expression during numerous biological/pathological processes. Dicer encodes an RNase III endonuclease that is essential for generating most, if not all, functional miRNAs. In this work, we applied a conditional gene inactivation approach to examine the function of Dicer during neural crest cell (NCC) development. Mice with NCC-specific inactivation of Dicer died perinatally. Cranial and cardiac NCC migration into target tissues was not affected by Dicer disruption, but their subsequent development was disturbed. NCC derivatives and their associated mesoderm-derived cells displayed massive apoptosis, leading to severe abnormalities during craniofacial morphogenesis and organogenesis. In addition, the 4th pharyngeal arch artery (PAA) remodeling was affected, resulting in interrupted aortic arch artery type B (IAA-B) in mutant animals. Taken together, our results show that Dicer activity in NCCs is essential for craniofacial development and pharyngeal arch artery morphogenesis. PMID:21256960

  13. Lack of beta1 integrins in enteric neural crest cells leads to a Hirschsprung-like phenotype

    DEFF Research Database (Denmark)

    Breau, Marie A; Pietri, Thomas; Eder, Olivier

    2006-01-01

    The enteric nervous system arises mainly from vagal and sacral neural crest cells that colonise the gut between 9.5 and 14 days of development in mice. Using the Cre-LoxP system, we removed beta1 integrins in the neural crest cells when they emerge from the neural tube. beta1-null enteric neural...

  14. Requirement for Foxd3 in the maintenance of neural crest progenitors.

    Science.gov (United States)

    Teng, Lu; Mundell, Nathan A; Frist, Audrey Y; Wang, Qiaohong; Labosky, Patricia A

    2008-05-01

    Understanding the molecular mechanisms of stem cell maintenance is crucial for the ultimate goal of manipulating stem cells for the treatment of disease. Foxd3 is required early in mouse embryogenesis; Foxd3(-/-) embryos fail around the time of implantation, cells of the inner cell mass cannot be maintained in vitro, and blastocyst-derived stem cell lines cannot be established. Here, we report that Foxd3 is required for maintenance of the multipotent mammalian neural crest. Using tissue-specific deletion of Foxd3 in the neural crest, we show that Foxd3(flox/-); Wnt1-Cre mice die perinatally with a catastrophic loss of neural crest-derived structures. Cranial neural crest tissues are either missing or severely reduced in size, the peripheral nervous system consists of reduced dorsal root ganglia and cranial nerves, and the entire gastrointestinal tract is devoid of neural crest derivatives. These results demonstrate a global role for this transcriptional repressor in all aspects of neural crest maintenance along the anterior-posterior axis, and establish an unprecedented molecular link between multiple divergent progenitor lineages of the mammalian embryo.

  15. Anosmin-1 is essential for neural crest and cranial placodes formation in Xenopus.

    Science.gov (United States)

    Bae, Chang-Joon; Hong, Chang-Soo; Saint-Jeannet, Jean-Pierre

    2018-01-15

    During embryogenesis vertebrates develop a complex craniofacial skeleton associated with sensory organs. These structures are primarily derived from two embryonic cell populations the neural crest and cranial placodes, respectively. Neural crest cells and cranial placodes are specified through the integrated action of several families of signaling molecules, and the subsequent activation of a complex network of transcription factors. Here we describe the expression and function of Anosmin-1 (Anos1), an extracellular matrix protein, during neural crest and cranial placodes development in Xenopus laevis. Anos1 was identified as a target of Pax3 and Zic1, two transcription factors necessary and sufficient to generate neural crest and cranial placodes. Anos1 is expressed in cranial neural crest progenitors at early neurula stage and in cranial placode derivatives later in development. We show that Anos1 function is required for neural crest and sensory organs development in Xenopus, consistent with the defects observed in Kallmann syndrome patients carrying a mutation in ANOS1. These findings indicate that anos1 has a conserved function in the development of craniofacial structures, and indicate that anos1-depleted Xenopus embryos represent a useful model to analyze the pathogenesis of Kallmann syndrome. Copyright © 2017. Published by Elsevier Inc.

  16. Enteric neural crest cells regulate vertebrate stomach patterning and differentiation.

    Science.gov (United States)

    Faure, Sandrine; McKey, Jennifer; Sagnol, Sébastien; de Santa Barbara, Pascal

    2015-01-15

    In vertebrates, the digestive tract develops from a uniform structure where reciprocal epithelial-mesenchymal interactions pattern this complex organ into regions with specific morphologies and functions. Concomitant with these early patterning events, the primitive GI tract is colonized by the vagal enteric neural crest cells (vENCCs), a population of cells that will give rise to the enteric nervous system (ENS), the intrinsic innervation of the GI tract. The influence of vENCCs on early patterning and differentiation of the GI tract has never been evaluated. In this study, we report that a crucial number of vENCCs is required for proper chick stomach development, patterning and differentiation. We show that reducing the number of vENCCs by performing vENCC ablations induces sustained activation of the BMP and Notch pathways in the stomach mesenchyme and impairs smooth muscle development. A reduction in vENCCs also leads to the transdifferentiation of the stomach into a stomach-intestinal mixed phenotype. In addition, sustained Notch signaling activity in the stomach mesenchyme phenocopies the defects observed in vENCC-ablated stomachs, indicating that inhibition of the Notch signaling pathway is essential for stomach patterning and differentiation. Finally, we report that a crucial number of vENCCs is also required for maintenance of stomach identity and differentiation through inhibition of the Notch signaling pathway. Altogether, our data reveal that, through the regulation of mesenchyme identity, vENCCs act as a new mediator in the mesenchymal-epithelial interactions that control stomach development. © 2015. Published by The Company of Biologists Ltd.

  17. Modeling initiation of Ewing sarcoma in human neural crest cells.

    Directory of Open Access Journals (Sweden)

    Cornelia von Levetzow

    2011-04-01

    Full Text Available Ewing sarcoma family tumors (ESFT are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC and/or neural crest (NCSC stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCSC (hNCSC. Ectopic expression of EWS-FLI1 in undifferentiated hNCSC and their neuro-mesenchymal stem cell (hNC-MSC progeny was readily tolerated and led to altered expression of both well established as well as novel EWS-FLI1 target genes. Importantly, whole genome expression profiling studies revealed that the molecular signature of established ESFT is more similar to hNCSC than any other normal tissue, including MSC, indicating that maintenance or reactivation of the NCSC program is a feature of ESFT pathogenesis. Consistent with this hypothesis, EWS-FLI1 induced hNCSC genes as well as the polycomb proteins BMI-1 and EZH2 in hNC-MSC. In addition, up-regulation of BMI-1 was associated with avoidance of cellular senescence and reversible silencing of p16. Together these studies confirm that, unlike terminally differentiated cells but consistent with bone marrow-derived MSC, NCSC tolerate expression of EWS-FLI1 and ectopic expression of the oncogene initiates transition to an ESFT-like state. In addition, to our knowledge this is the first demonstration that EWS-FLI1-mediated induction of BMI-1 and epigenetic silencing of p16 might be critical early initiating events in ESFT tumorigenesis.

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

    Directory of Open Access Journals (Sweden)

    Erika Kague

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

  19. Regulation of Msx genes by a Bmp gradient is essential for neural crest specification.

    Science.gov (United States)

    Tribulo, Celeste; Aybar, Manuel J; Nguyen, Vu H; Mullins, Mary C; Mayor, Roberto

    2003-12-01

    There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification. As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region. In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail, slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest

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    Lifescience Database Archive (English)

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  1. File list: ALL.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

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  8. Tcf7l1 protects the anterior neural fold from adopting the neural crest fate

    Czech Academy of Sciences Publication Activity Database

    Mašek, Jan; Machoň, Ondřej; Kořínek, Vladimír; Taketo, M.M.; Kozmik, Zbyněk

    2016-01-01

    Roč. 143, č. 12 (2016), s. 2206-2216 ISSN 0950-1991 R&D Projects: GA ČR GAP305/12/2042; GA ČR(CZ) GA14-33952S; GA MŠk(CZ) LK11214; GA MŠk LO1419; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : Tcf/Lef * Wnt dignaling * neural crest * forebrain * mouse * zebrafish Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.843, year: 2016

  9. Hepatocyte growth factor/scatter factor-MET signaling in neural crest-derived melanocyte development.

    Science.gov (United States)

    Kos, L; Aronzon, A; Takayama, H; Maina, F; Ponzetto, C; Merlino, G; Pavan, W

    1999-02-01

    The mechanisms governing development of neural crest-derived melanocytes, and how alterations in these pathways lead to hypopigmentation disorders, are not completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling through the tyrosine-kinase receptor, MET, is capable of promoting the proliferation, increasing the motility, and maintaining high tyrosinase activity and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and leptomenigenes and develop melanomas. To investigate whether HGF/ SF-MET signaling is involved in the development of neural crest-derived melanocytes, transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF transgenic embryos, the distribution of melanoblasts along the characteristic migratory pathway was not affected. However, additional ectopically localized melanoblasts were also observed in the dorsal root ganglia and neural tube, as early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest culture assay to further explore the role of HGF/SF-MET signaling in neural crest development. HGF/SF added to neural crest cultures increased melanoblast number, permitted differentiation into pigmented melanocytes, promoted melanoblast survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant cultures. To examine whether HGF/SF-MET signaling is required for the proper development of melanocytes, embryos with a targeted Met null mutation (Met-/-) were analysed. In Met-/- embryos, melanoblast number and location were not overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET signaling influences, but is not required for, the initial development of neural crest-derived melanocytes in vivo and in vitro.

  10. Neuropilin-1 interacts with the second branchial arch microenvironment to mediate chick neural crest cell dynamics

    Science.gov (United States)

    McLennan, Rebecca; Kulesa, Paul M.

    2011-01-01

    Cranial neural crest cells (NCCs) require neuropilin signaling to reach and invade the branchial arches. Here, we use an in vivo chick model to investigate whether the neuropilin-1 knockdown phenotype is specific to the second branchial arch (ba2), changes in NCC behaviors and phenotypic consequences, and whether neuropilins work together to facilitate entry into and invasion of ba2. We find that cranial NCCs with reduced neuropilin-1 expression displayed shorter protrusions and decreased cell body and nuclear length-to-width ratios characteristic of a loss in polarity and motility, after specific interaction with ba2. Directed NCC migration was rescued by transplantation of transfected cells into rhombomere 4 of younger hosts. Lastly, reduction of neuropilin-2 expression by shRNA either solely or with reduction of neuropilin-1 expression did not lead to a stronger head phenotype. Thus, NCCs, independent of rhombomere origin, require neuropilin-1, but not neuropilin-2 to maintain polarity and directed migration into ba2. PMID:20503363

  11. Expression of cardiac neural crest and heart genes isolated by modified differential display.

    Science.gov (United States)

    Martinsen, Brad J; Groebner, Nathan J; Frasier, Allison J; Lohr, Jamie L

    2003-08-01

    The invasion of the cardiac neural crest (CNC) into the outflow tract (OFT) and subsequent outflow tract septation are critical events during vertebrate heart development. We have performed four modified differential display screens in the chick embryo to identify genes that may be involved in CNC, OFT, secondary heart field, and heart development. The screens included differential display of RNA isolated from three different axial segments containing premigratory cranial neural crest cells; of RNA from distal outflow tract, proximal outflow tract, and atrioventricular tissue of embryonic chick hearts; and of RNA isolated from left and right cranial tissues, including the early heart fields. These screens have resulted in the identification of the five cDNA clones presented here, which are expressed in the cardiac neural crest, outflow tract and developing heart in patterns that are unique in heart development.

  12. Apoptosis in neural crest cells by functional loss of APC tumor suppressor gene

    Science.gov (United States)

    Hasegawa, Sumitaka; Sato, Tomoyuki; Akazawa, Hiroshi; Okada, Hitoshi; Maeno, Akiteru; Ito, Masaki; Sugitani, Yoshinobu; Shibata, Hiroyuki; Miyazaki, Jun-ichi; Katsuki, Motoya; Yamauchi, Yasutaka; Yamamura, Ken-ichi; Katamine, Shigeru; Noda, Tetsuo

    2002-01-01

    Apc is a gene associated with familial adenomatous polyposis coli (FAP) and its inactivation is a critical step in colorectal tumor formation. The protein product, adenomatous polyposis coli (APC), acts to down-regulate intracellular levels of β-catenin, a key signal transducer in the Wnt signaling. Conditional targeting of Apc in the neural crest of mice caused massive apoptosis of cephalic and cardiac neural crest cells at about 11.5 days post coitum, resulting in craniofacial and cardiac anomalies at birth. Notably, the apoptotic cells localized in the regions where β-catenin had accumulated. In contrast to its role in colorectal epithelial cells, inactivation of APC leads to dysregulation of β-catenin/Wnt signaling with resultant apoptosis in certain tissues including neural crest cells. PMID:11756652

  13. Effects of epidermal growth factor on neural crest cells in tissue culture

    International Nuclear Information System (INIS)

    Erickson, C.A.; Turley, E.A.

    1987-01-01

    Epidermal growth factor (EGF) stimulates the release of hyaluronic acid (HA) and chondroitin sulfate proteoglycan (CSPG) from quail trunk neural crest cultures in a dose-dependent fashion. It also promotes the expression of cell-associated heparan sulfate proteoglycan (HSPG) as detected by immunofluorescence and immunoprecipitation of the 3 H-labeled proteoglycan. Furthermore, EGF stimulates [ 3 H]thymidine incorporation into total cell DNA. These results raise the possibility that EGF or an analogous growth factor is involved in regulation of neural crest cell morphogenesis

  14. In vivo transplantation of enteric neural crest cells into mouse gut; Engraftment, functional integration and long-term safety

    NARCIS (Netherlands)

    J.E. Cooper (Julie E.); C. Mccann; D. Natarajan (Dipa); S. Choudhury; W. Boesmans (Werend); J.-M. Delalande (Jean-Marie); P.V. Berghe (Pieter Vanden); A.J. Burns (Alan); N. Thapar (Nikhil)

    2016-01-01

    textabstractObjectives: Enteric neuropathies are severe gastrointestinal disorders with unsatisfactory outcomes. We aimed to investigate the potential of enteric neural stem cell therapy approaches for such disorders by transplanting mouse enteric neural crest cells (ENCCs) into ganglionic and

  15. Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates.

    Science.gov (United States)

    Mundell, Nathan A; Labosky, Patricia A

    2011-02-01

    Neural crest (NC) progenitors generate a wide array of cell types, yet molecules controlling NC multipotency and self-renewal and factors mediating cell-intrinsic distinctions between multipotent versus fate-restricted progenitors are poorly understood. Our earlier work demonstrated that Foxd3 is required for maintenance of NC progenitors in the embryo. Here, we show that Foxd3 mediates a fate restriction choice for multipotent NC progenitors with loss of Foxd3 biasing NC toward a mesenchymal fate. Neural derivatives of NC were lost in Foxd3 mutant mouse embryos, whereas abnormally fated NC-derived vascular smooth muscle cells were ectopically located in the aorta. Cranial NC defects were associated with precocious differentiation towards osteoblast and chondrocyte cell fates, and individual mutant NC from different anteroposterior regions underwent fate changes, losing neural and increasing myofibroblast potential. Our results demonstrate that neural potential can be separated from NC multipotency by the action of a single gene, and establish novel parallels between NC and other progenitor populations that depend on this functionally conserved stem cell protein to regulate self-renewal and multipotency.

  16. Diprosopia revisited in light of the recognized role of neural crest cells in facial development.

    Science.gov (United States)

    Carles, D; Weichhold, W; Alberti, E M; Léger, F; Pigeau, F; Horovitz, J

    1995-01-01

    The aim of this study is to compare the theory of embryogenesis of the face with human diprosopia. This peculiar form of conjoined twinning is of great interest because 1) only the facial structures are duplicated and 2) almost all cases have a rather monomorphic pattern. The hypothesis is that an initial duplication of the notochord leads to two neural plates and subsequently duplicated neural crests. In those conditions, derivatives of the neural crests will be partially or totally duplicated; therefore, in diprosopia, the duplicated facial structures would be considered to be neural crest derivatives. If these structures are identical to those that are experimentally demonstrated to be neural crest derivatives in animals, these findings are an argument to apply this theory of facial embryogenesis in man. Serial horizontal sections of the face of two diprosopic fetuses (11 and 21 weeks gestation) were studied macro- and microscopically to determine the external and internal structures that are duplicated. Complete postmortem examination was performed in search for additional malformations. The face of both fetuses showed a very similar morphologic pattern with duplication of ocular, nasal, and buccal structures. The nasal fossae and the anterior part of the tongue were also duplicated, albeit the posterior part and the pharyngolaryngeal structures were unique. Additional facial clefts were present in both fetuses. Extrafacial anomalies were represented by a craniorachischisis, two fused vertebral columns and, in the older fetus, by a complex cardiac malformation morphologically identical to malformations induced by removal or grafting of additional cardiac neural crest cells in animals. These pathological findings could identify the facial structures that are neural crest derivatives in man. They are similar to those experimentally demonstrated to be neural crest derivatives in animals. In this respect, diprosopia could be considered as the end of a spectrum

  17. Synthesis on accumulation of putative neurotransmitters by cultured neural crest cells

    International Nuclear Information System (INIS)

    Maxwell, G.D.; Sietz, P.D.; Rafford, C.E.

    1982-01-01

    The events mediating the differentiation of embryonic neural crest cells into several types of neurons are incompletely understood. In order to probe one aspect of this differentiation, we have examined the capacity of cultured quail trunk neural crest cells to synthesize, from radioactive precursors, and store several putative neurotransmitter compounds. These neural crest cultures develop the capacity to synthesize and accumulate acetylcholine and the catecholamines norepinephrine and dopamine. In contrast, detectable but relatively little synthesis and accumulation of 5-hydroxytryptamine gamma-aminobutyric acid, or octopamine from the appropriate radiolabeled precursors were observed. The capacity for synthesis and accumulation of radiolabeled acetylcholine and catecholamines is very low or absent at 2 days in vitro. Between 3 and 7 days in vitro, there is a marked rise in both catecholamine and acetylcholine accumulation in the cultures. These findings suggest that, under the particular conditions used in these experiments, the development of neurotransmitter biosynthesis in trunk neural crest cells ijs restricted and resembles, at least partially, the pattern observed in vivo. The development of this capacity to synthesize and store radiolabeled acetylcholine and catecholamines from the appropriate radioactive precursors coincides closely with the development of the activities of the synthetic enzymes choline acetyltransferase and dopamine beta-hydroxylase reported by others

  18. Properties of Neural Crest-Like Cells Differentiated from Human Embryonic Stem Cells

    Czech Academy of Sciences Publication Activity Database

    Křivánek, J.; Švandová, Eva; Králik, J.; Hajda, S.; Fedr, Radek; Vinařský, V.; Jaroš, J.; Souček, Karel

    2014-01-01

    Roč. 60, č. 2014 (2014), s. 30-38 ISSN 0015-5500 R&D Projects: GA ČR(CZ) GAP304/11/1418 Institutional support: RVO:68081707 Keywords : stem cell differentiation * neural crest * odontogenesis Subject RIV: BO - Biophysics; ED - Physiology (UZFG-Y) Impact factor: 1.000, year: 2014

  19. Modeling Cerebrovascular Pathophysiology in Amyloid-β Metabolism using Neural-Crest-Derived Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Christine Cheung

    2014-10-01

    Full Text Available Summary: There is growing recognition of cerebrovascular contributions to neurodegenerative diseases. In the walls of cerebral arteries, amyloid-beta (Aβ accumulation is evident in a majority of aged people and patients with cerebral amyloid angiopathy. Here, we leverage human pluripotent stem cells to generate vascular smooth muscle cells (SMCs from neural crest progenitors, recapitulating brain-vasculature-specific attributes of Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural-crest-derived SMCs to mediate Aβ uptake and intracellular lysosomal degradation. Hypoxia significantly compromises the contribution of SMCs to Aβ clearance by suppressing LRP1 expression. This enabled us to develop an assay of Aβ uptake by using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high-throughput format, demonstrating the value of stem-cell-based phenotypic screening for novel therapeutics and drug repurposing, aimed at alleviating amyloid burden. : The contribution of blood vessel pathologies to neurodegenerative disorders is relatively neglected, partly due to inadequate human tissues for research. By using human stem cells, Cheung et al. establish a method of generating vascular smooth muscle cells (SMCs from neural crest progenitors, the primary precursors that give rise to brain blood vessels. These stem-cell-derived SMCs display defective amyloid processing under chronic hypoxia, a phenomenon well documented in the cerebral vasculatures of aged people and patients with Alzheimer’s disease.

  20. Meis2 is essential for cranial and cardiac neural crest development

    Czech Academy of Sciences Publication Activity Database

    Machoň, Ondřej; Mašek, Jan; Machoňová, Olga; Krauss, S.; Kozmik, Zbyněk

    2015-01-01

    Roč. 15, Nov 6 (2015) ISSN 1471-213X R&D Projects: GA ČR GAP305/12/2042; GA MŠk(CZ) LK11214 Institutional support: RVO:68378050 Keywords : Meis2 * Persistent truncus arteriosus * Neural crest * Craniofacial skeleton * Cranial nerves Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.096, year: 2015

  1. Fibronectin promotes differentiation of neural crest progenitors endowed with smooth muscle cell potential

    International Nuclear Information System (INIS)

    Costa-Silva, Bruno; Coelho da Costa, Meline; Melo, Fernanda Rosene; Neves, Cynara Mendes; Alvarez-Silva, Marcio; Calloni, Giordano Wosgrau; Trentin, Andrea Goncalves

    2009-01-01

    The neural crest (NC) is a model system used to investigate multipotency during vertebrate development. Environmental factors control NC cell fate decisions. Despite the well-known influence of extracellular matrix molecules in NC cell migration, the issue of whether they also influence NC cell differentiation has not been addressed at the single cell level. By analyzing mass and clonal cultures of mouse cephalic and quail trunk NC cells, we show for the first time that fibronectin (FN) promotes differentiation into the smooth muscle cell phenotype without affecting differentiation into glia, neurons, and melanocytes. Time course analysis indicated that the FN-induced effect was not related to massive cell death or proliferation of smooth muscle cells. Finally, by comparing clonal cultures of quail trunk NC cells grown on FN and collagen type IV (CLIV), we found that FN strongly increased both NC cell survival and the proportion of unipotent and oligopotent NC progenitors endowed with smooth muscle potential. In contrast, melanocytic progenitors were prominent in clonogenic NC cells grown on CLIV. Taken together, these results show that FN promotes NC cell differentiation along the smooth muscle lineage, and therefore plays an important role in fate decisions of NC progenitor cells

  2. The SWI/SNF BAF-A complex is essential for neural crest development.

    Science.gov (United States)

    Chandler, Ronald L; Magnuson, Terry

    2016-03-01

    Growing evidence indicates that chromatin remodeler mutations underlie the pathogenesis of human neurocristopathies or disorders that affect neural crest cells (NCCs). However, causal relationships among chromatin remodeler subunit mutations and NCC defects remain poorly understood. Here we show that homozygous loss of ARID1A-containing, SWI/SNF chromatin remodeling complexes (BAF-A) in NCCs results in embryonic lethality in mice, with mutant embryos succumbing to heart defects. Strikingly, monoallelic loss of ARID1A in NCCs led to craniofacial defects in adult mice, including shortened snouts and low set ears, and these defects were more pronounced following homozygous loss of ARID1A, with the ventral cranial bones being greatly reduced in size. Early NCC specification and expression of the BRG1 NCC target gene, PLEXINA2, occurred normally in the absence of ARID1A. Nonetheless, mutant embryos displayed incomplete conotruncal septation of the cardiac outflow tract and defects in the posterior pharyngeal arteries, culminating in persistent truncus arteriosus and agenesis of the ductus arteriosus. Consistent with this, migrating cardiac NCCs underwent apoptosis within the circumpharyngeal ridge. Our data support the notion that multiple, distinct chromatin remodeling complexes govern genetically separable events in NCC development and highlight a potential pathogenic role for NCCs in the human BAF complex disorder, Coffin-Siris Syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

    OpenAIRE

    Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

    2010-01-01

    The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identif...

  4. Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis.

    Science.gov (United States)

    Milstone, Zachary J; Lawson, Grace; Trivedi, Chinmay M

    2017-12-01

    Craniofacial anomalies involve defective pharyngeal arch development and neural crest function. Copy number variation at 1p35, containing histone deacetylase 1 (Hdac1), or 6q21-22, containing Hdac2, are implicated in patients with craniofacial defects, suggesting an important role in guiding neural crest development. However, the roles of Hdac1 and Hdac2 within neural crest cells remain unknown. The neural crest and its derivatives express both Hdac1 and Hdac2 during early murine development. Ablation of Hdac1 and Hdac2 within murine neural crest progenitor cells cause severe hemorrhage, atrophic pharyngeal arches, defective head morphogenesis, and complete embryonic lethality. Embryos lacking Hdac1 and Hdac2 in the neural crest exhibit decreased proliferation and increased apoptosis in both the neural tube and the first pharyngeal arch. Mechanistically, loss of Hdac1 and Hdac2 upregulates cyclin-dependent kinase inhibitors Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, Cdkn2c, and Tp53 within the first pharyngeal arch. Our results show that Hdac1 and Hdac2 function redundantly within the neural crest to regulate proliferation and the development of the pharyngeal arches by means of repression of cyclin-dependent kinase inhibitors. Developmental Dynamics 246:1015-1026, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Role of cranial neural crest cells in visceral arch muscle positioning and morphogenesis in the Mexican axolotl, Ambystoma mexicanum.

    Science.gov (United States)

    Ericsson, Rolf; Cerny, Robert; Falck, Pierre; Olsson, Lennart

    2004-10-01

    The role of cranial neural crest cells in the formation of visceral arch musculature was investigated in the Mexican axolotl, Ambystoma mexicanum. DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine, perchlorate) labeling and green fluorescent protein (GFP) mRNA injections combined with unilateral transplantations of neural folds showed that neural crest cells contribute to the connective tissues but not the myofibers of developing visceral arch muscles in the mandibular, hyoid, and branchial arches. Extirpations of individual cranial neural crest streams demonstrated that neural crest cells are necessary for correct morphogenesis of visceral arch muscles. These do, however, initially develop in their proper positions also in the absence of cranial neural crest. Visceral arch muscles forming in the absence of neural crest cells start to differentiate at their origins but fail to extend toward their insertions and may have a frayed appearance. Our data indicate that visceral arch muscle positioning is controlled by factors that do not have a neural crest origin. We suggest that the cranial neural crest-derived connective tissues provide directional guidance important for the proper extension of the cranial muscles and the subsequent attachment to the insertion on the correct cartilage. In a comparative context, our data from the Mexican axolotl support the view that the cranial neural crest plays a fundamental role in the development of not only the skeleton of the vertebrate head but also in the morphogenesis of the cranial muscles and that this might be a primitive feature of cranial development in vertebrates. 2004 Wiley-Liss, Inc.

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

    Science.gov (United States)

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

    2017-09-01

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

  7. Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds.

    Science.gov (United States)

    Liu, Hong-Xiang; Komatsu, Yoshihiro; Mishina, Yuji; Mistretta, Charlotte M

    2012-08-15

    The epithelium of mammalian tongue hosts most of the taste buds that transduce gustatory stimuli into neural signals. In the field of taste biology, taste bud cells have been described as arising from "local epithelium", in distinction from many other receptor organs that are derived from neurogenic ectoderm including neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme in the developing tongue is not fully understood. In the present study we used two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express Cre recombinase in a NC-specific manner, in combination with two Cre reporter mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to both tongue mesenchyme and epithelium including taste papillae and taste buds. In tongue mesenchyme, distribution of NC-derived cells is in close association with taste papillae. In tongue epithelium, labeled cells are observed in an initial scattered distribution and progress to a clustered pattern between papillae, and within papillae and early taste buds. This provides evidence for a contribution of NC to lingual epithelium. Together with previous reports for the origin of taste bud cells from local epithelium in postnatal mouse, we propose that NC cells migrate into and reside in the epithelium of the tongue primordium at an early embryonic stage, acquire epithelial cell phenotypes, and undergo cell proliferation and differentiation that is involved in the development of taste papillae and taste buds. Our findings lead to a new concept about derivation of taste bud cells that include a NC origin. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Neural Crest-Derived Mesenchymal Cells Require Wnt Signaling for Their Development and Drive Invagination of the Telencephalic Midline

    Science.gov (United States)

    Choe, Youngshik; Zarbalis, Konstantinos S.; Pleasure, Samuel J.

    2014-01-01

    Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs) leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis. PMID:24516524

  9. Neural crest-derived mesenchymal cells require Wnt signaling for their development and drive invagination of the telencephalic midline.

    Directory of Open Access Journals (Sweden)

    Youngshik Choe

    Full Text Available Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.

  10. Bmps and id2a act upstream of Twist1 to restrict ectomesenchyme potential of the cranial neural crest.

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    Ankita Das

    Full Text Available Cranial neural crest cells (CNCCs have the remarkable capacity to generate both the non-ectomesenchyme derivatives of the peripheral nervous system and the ectomesenchyme precursors of the vertebrate head skeleton, yet how these divergent lineages are specified is not well understood. Whereas studies in mouse have indicated that the Twist1 transcription factor is important for ectomesenchyme development, its role and regulation during CNCC lineage decisions have remained unclear. Here we show that two Twist1 genes play an essential role in promoting ectomesenchyme at the expense of non-ectomesenchyme gene expression in zebrafish. Twist1 does so by promoting Fgf signaling, as well as potentially directly activating fli1a expression through a conserved ectomesenchyme-specific enhancer. We also show that Id2a restricts Twist1 activity to the ectomesenchyme lineage, with Bmp activity preferentially inducing id2a expression in non-ectomesenchyme precursors. We therefore propose that the ventral migration of CNCCs away from a source of Bmps in the dorsal ectoderm promotes ectomesenchyme development by relieving Id2a-dependent repression of Twist1 function. Together our model shows how the integration of Bmp inhibition at its origin and Fgf activation along its migratory route would confer temporal and spatial specificity to the generation of ectomesenchyme from the neural crest.

  11. Neural Crest Cells Isolated from the Bone Marrow of Transgenic Mice Express JCV T-Antigen.

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    Jennifer Gordon

    Full Text Available JC virus (JCV, a common human polyomavirus, is the etiological agent of the demyelinating disease, progressive multifocal leukoencephalopathy (PML. In addition to its role in PML, studies have demonstrated the transforming ability of the JCV early protein, T-antigen, and its association with some human cancers. JCV infection occurs in childhood and latent virus is thought to be maintained within the bone marrow, which harbors cells of hematopoietic and non-hematopoietic lineages. Here we show that non-hematopoietic mesenchymal stem cells (MSCs isolated from the bone marrow of JCV T-antigen transgenic mice give rise to JCV T-antigen positive cells when cultured under neural conditions. JCV T-antigen positive cells exhibited neural crest characteristics and demonstrated p75, SOX-10 and nestin positivity. When cultured in conditions typical for mesenchymal cells, a population of T-antigen negative cells, which did not express neural crest markers arose from the MSCs. JCV T-antigen positive cells could be cultured long-term while maintaining their neural crest characteristics. When these cells were induced to differentiate into neural crest derivatives, JCV T-antigen was downregulated in cells differentiating into bone and maintained in glial cells expressing GFAP and S100. We conclude that JCV T-antigen can be stably expressed within a fraction of bone marrow cells differentiating along the neural crest/glial lineage when cultured in vitro. These findings identify a cell population within the bone marrow permissible for JCV early gene expression suggesting the possibility that these cells could support persistent viral infection and thus provide clues toward understanding the role of the bone marrow in JCV latency and reactivation. Further, our data provides an excellent experimental model system for studying the cell-type specificity of JCV T-antigen expression, the role of bone marrow-derived stem cells in the pathogenesis of JCV-related diseases

  12. SOX10-Nano-Lantern Reporter Human iPS Cells; A Versatile Tool for Neural Crest Research.

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    Tomoko Horikiri

    Full Text Available The neural crest is a source to produce multipotent neural crest stem cells that have a potential to differentiate into diverse cell types. The transcription factor SOX10 is expressed through early neural crest progenitors and stem cells in vertebrates. Here we report the generation of SOX10-Nano-lantern (NL reporter human induced pluripotent stem cells (hiPS by using CRISPR/Cas9 systems, that are beneficial to investigate the generation and maintenance of neural crest progenitor cells. SOX10-NL positive cells are produced transiently from hiPS cells by treatment with TGFβ inhibitor SB431542 and GSK3 inhibitor CHIR99021. We found that all SOX10-NL-positive cells expressed an early neural crest marker NGFR, however SOX10-NL-positive cells purified from differentiated hiPS cells progressively attenuate their NL-expression under proliferation. We therefore attempted to maintain SOX10-NL-positive cells with additional signaling on the plane and sphere culture conditions. These SOX10-NL cells provide us to investigate mass culture with neural crest cells for stem cell research.

  13. Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve.

    Science.gov (United States)

    Odelin, Gaëlle; Faure, Emilie; Coulpier, Fanny; Di Bonito, Maria; Bajolle, Fanny; Studer, Michèle; Avierinos, Jean-François; Charnay, Patrick; Topilko, Piotr; Zaffran, Stéphane

    2018-01-03

    Although cardiac neural crest cells are required at early stages of arterial valve development, their contribution during valvular leaflet maturation remains poorly understood. Here, we show in mouse that neural crest cells from pre-otic and post-otic regions make distinct contributions to the arterial valve leaflets. Genetic fate-mapping analysis of Krox20-expressing neural crest cells shows a large contribution to the borders and the interleaflet triangles of the arterial valves. Loss of Krox20 function results in hyperplastic aortic valve and partially penetrant bicuspid aortic valve formation. Similar defects are observed in neural crest Krox20 -deficient embryos. Genetic lineage tracing in Krox20 -/- mutant mice shows that endothelial-derived cells are normal, whereas neural crest-derived cells are abnormally increased in number and misplaced in the valve leaflets. In contrast, genetic ablation of Krox20 -expressing cells is not sufficient to cause an aortic valve defect, suggesting that adjacent cells can compensate this depletion. Our findings demonstrate a crucial role for Krox20 in arterial valve development and reveal that an excess of neural crest cells may be associated with bicuspid aortic valve. © 2018. Published by The Company of Biologists Ltd.

  14. Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1

    DEFF Research Database (Denmark)

    Fuchs, Sebastian; Herzog, Dominik; Sumara, Grzegorz

    2009-01-01

    -renewal and proliferation of later stage, but not early migratory NCSCs. This stage-specific requirement for small Rho GTPases is due to changes in NCSCs that, during development, acquire responsiveness to mitogenic EGF acting upstream of both Cdc42 and Rac1. Thus, our data reveal distinct mechanisms for growth control......The neural crest (NC) generates a variety of neural and non-neural tissues during vertebrate development. Both migratory NC cells and their target structures contain cells with stem cell features. Here we show that these populations of neural crest-derived stem cells (NCSCs) are differentially...

  15. Twist1 Controls a Cell-Specification Switch Governing Cell Fate Decisions within the Cardiac Neural Crest

    Science.gov (United States)

    Vincentz, Joshua W.; Firulli, Beth A.; Lin, Andrea; Spicer, Douglas B.; Howard, Marthe J.; Firulli, Anthony B.

    2013-01-01

    Neural crest cells are multipotent progenitor cells that can generate both ectodermal cell types, such as neurons, and mesodermal cell types, such as smooth muscle. The mechanisms controlling this cell fate choice are not known. The basic Helix-loop-Helix (bHLH) transcription factor Twist1 is expressed throughout the migratory and post-migratory cardiac neural crest. Twist1 ablation or mutation of the Twist-box causes differentiation of ectopic neuronal cells, which molecularly resemble sympathetic ganglia, in the cardiac outflow tract. Twist1 interacts with the pro-neural factor Sox10 via its Twist-box domain and binds to the Phox2b promoter to repress transcriptional activity. Mesodermal cardiac neural crest trans-differentiation into ectodermal sympathetic ganglia-like neurons is dependent upon Phox2b function. Ectopic Twist1 expression in neural crest precursors disrupts sympathetic neurogenesis. These data demonstrate that Twist1 functions in post-migratory neural crest cells to repress pro-neural factors and thereby regulate cell fate determination between ectodermal and mesodermal lineages. PMID:23555309

  16. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

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    Sophie R. Miller

    2017-03-01

    Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

  17. Impaired Cellular Immunity in the Murine Neural Crest Conditional Deletion of Endothelin Receptor-B Model of Hirschsprung's Disease.

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    Ankush Gosain

    Full Text Available Hirschsprung's disease (HSCR is characterized by aganglionosis from failure of neural crest cell (NCC migration to the distal hindgut. Up to 40% of HSCR patients suffer Hirschsprung's-associated enterocolitis (HAEC, with an incidence that is unchanged from the pre-operative to the post-operative state. Recent reports indicate that signaling pathways involved in NCC migration may also be involved in the development of secondary lymphoid organs. We hypothesize that gastrointestinal (GI mucosal immune defects occur in HSCR that may contribute to enterocolitis. EdnrB was deleted from the neural crest (EdnrBNCC-/- resulting in mutants with defective NCC migration, distal colonic aganglionosis and the development of enterocolitis. The mucosal immune apparatus of these mice was interrogated at post-natal day (P 21-24, prior to histological signs of enterocolitis. We found that EdnrBNCC-/- display lymphopenia of their Peyer's Patches, the major inductive site of GI mucosal immunity. EdnrBNCC-/- Peyer's Patches demonstrate decreased B-lymphocytes, specifically IgM+IgDhi (Mature B-lymphocytes, which are normally activated and produce IgA following antigen presentation. EdnrBNCC-/- animals demonstrate decreased small intestinal secretory IgA, but unchanged nasal and bronchial airway secretory IgA, indicating a gut-specific defect in IgA production or secretion. In the spleen, which is the primary source of IgA-producing Mature B-lymphocytes, EdnrBNCC-/- animals display decreased B-lymphocytes, but an increase in Mature B-lymphocytes. EdnrBNCC-/- spleens are also small and show altered architecture, with decreased red pulp and a paucity of B-lymphocytes in the germinal centers and marginal zone. Taken together, these findings suggest impaired GI mucosal immunity in EdnrBNCC-/- animals, with the spleen as a potential site of the defect. These findings build upon the growing body of literature that suggests that intestinal defects in HSCR are not restricted

  18. ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

    Science.gov (United States)

    Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

    2010-01-01

    SUMMARY The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction. PMID:20708595

  19. In vivo impact of Dlx3 conditional inactivation in Neural Crest-Derived Craniofacial Bones

    Science.gov (United States)

    Duverger, Olivier; Isaac, Juliane; Zah, Angela; Hwang, Joonsung; Berdal, Ariane; Lian, Jane B.; Morasso, Maria I.

    2012-01-01

    Mutations in DLX3 in humans lead to defects in craniofacial and appendicular bones, yet the in vivo activity related to Dlx3 function during normal skeletal development have not been fully elucidated. Here we used a conditional knockout approach to analyze the effects of neural crest deletion of Dlx3 on craniofacial bones development. At birth, mutant mice exhibit a normal overall positioning of the skull bones, but a change in the shape of the calvaria was observed. Molecular analysis of the genes affected in the frontal bones and mandibles from these mice identified several bone markers known to affect bone development, with a strong prediction for increased bone formation and mineralization in vivo. Interestingly, while a subset of these genes were similarly affected in frontal bones and mandibles (Sost, Mepe, Bglap, Alp, Ibsp, Agt), several genes, including Lect1 and Calca, were specifically affected in frontal bones. Consistent with these molecular alterations, cells isolated from the frontal bone of mutant mice exhibited increased differentiation and mineralization capacities ex vivo, supporting cell autonomous defects in neural crest cells. However, adult mutant animals exhibited decreased bone mineral density in both mandibles and calvaria, as well as a significant increase in bone porosity. Together, these observations suggest that mature osteoblasts in the adult respond to signals that regulate adult bone mass and remodeling. This study provides new downstream targets for Dlx3 in craniofacial bone, and gives additional evidence of the complex regulation of bone formation and homeostasis in the adult skeleton. PMID:22886599

  20. I131-meta-iodobenzylguanidine in the diagnosis and treatment of neural crest tumours

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.; Hartog Jager, F.C.A. den; Taal, B.G.; Engelsman, E.; Kraker, J. de; Voute, P.A.

    1988-01-01

    Iodine-131-meta-iodobenzylguanidine (I-131-MIBG) was used for scintigraphic detection and therapy of neural crest tumours. The methodology of both techniques is described. Based upon experience with I-131-MIBG-scintigraphy in 170 patients with neural crest tumours, of whom 46 received multiple therapeutic doses of I-131-MIBG, and upon the cumulative reports in the literature, the role of I-131-MIBG in diagnosis and treatment of each of these diseases is indicated. I-131-MIBG-scintigraphy is one of the most sensitive and specific techniques for the diagnosis, staging and follow-up of phaeochromocytoma and neuroblastoma and I-131-MIBG-therapy may induce remission in a number of these patients. In carcinoid and medullary thyroid carcinoma the diagnostic sensitivity is less; however, once the diagnosis has been made, it is useful to establish that the tumour concentrates I-131-MIBG, to see if the patients at some point in time may be amenable to I-131-MIBG-therapy

  1. ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com; Wu, Yong, E-mail: wyonger@gmail.com; Wang, Bo, E-mail: wb228@126.com; Jiang, Ning, E-mail: 179639060@qq.com; Nie, Ping, E-mail: nieping1011@sina.com; Cao, Haifeng, E-mail: 0412chf@163.com; Yang, Zhi, E-mail: wcums1981@163.com; Fang, Bing, E-mail: fangbing@sjtu.edu.cn

    2016-07-08

    Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.

  2. ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

    International Nuclear Information System (INIS)

    Tan, Yu; Fu, Runqing; Liu, Jiaqiang; Wu, Yong; Wang, Bo; Jiang, Ning; Nie, Ping; Cao, Haifeng; Yang, Zhi; Fang, Bing

    2016-01-01

    Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.

  3. Expression of the capacity to release [3H]norepinephrine by neural crest cultures

    International Nuclear Information System (INIS)

    Maxwell, G.D.; Sietz, P.D.

    1983-01-01

    Cultures of trunk neural crest cells from quail embryos were tested for their ability to release [ 3 H]norepinephrine [( 3 H]NE) in response to depolarization. After 7 days in vitro, exposure of the cultures to either the alkaloid veratridine or 40 mM K+ results in the evoked release of [ 3 H]NE. The release evoked by veratridine is blocked in the presence of tetrodotoxin. The release evoked by increased K+ is blocked by the calcium antagonist cobalt. Release in response to the nicotinic cholinergic agonist 1,1-dimethyl-4-phenylpiperazine was also observed. The amount of evoked release is highly correlated with the number of histochemically demonstrable catecholamine-containing cells in a given culture. Autoradiography reveals that the radioactivity taken up by these cultures is located in a subpopulation of cells whose morphology resembles that of the histochemically detectable catecholamine-containing cell population. Whereas capacity for the release of [ 3 H] NE is readily detectable after 7 days in vitro, it is detectable only with difficulty after 4 days in vitro. There is a greater than 6-fold increase in uptake capacity over the period of 4 to 7 days in vitro. These results demonstrate that neural crest cultures grown without their normal synaptic inputs or targets can exhibit the capacity for stimulus secretion coupling characteristic of synaptic neurotransmitter release

  4. Dental anomalies in different cleft groups related to neural crest developmental fields contributes to the understanding of cleft aetiology

    DEFF Research Database (Denmark)

    Riis, Louise Claudius; Kjær, Inger; Mølsted, Kirsten

    2014-01-01

    OBJECTIVE: To analyze dental deviations in three cleft groups and relate findings to embryological neural crest fields (frontonasal, maxillary, and palatal). The overall purpose was to evaluate how fields are involved in different cleft types. DESIGN: Retrospective audit of clinical photographs...

  5. The lamprey: a jawless vertebrate model system for examining origin of the neural crest and other vertebrate traits.

    Science.gov (United States)

    Green, Stephen A; Bronner, Marianne E

    2014-01-01

    Lampreys are a group of jawless fishes that serve as an important point of comparison for studies of vertebrate evolution. Lampreys and hagfishes are agnathan fishes, the cyclostomes, which sit at a crucial phylogenetic position as the only living sister group of the jawed vertebrates. Comparisons between cyclostomes and jawed vertebrates can help identify shared derived (i.e. synapomorphic) traits that might have been inherited from ancestral early vertebrates, if unlikely to have arisen convergently by chance. One example of a uniquely vertebrate trait is the neural crest, an embryonic tissue that produces many cell types crucial to vertebrate features, such as the craniofacial skeleton, pigmentation of the skin, and much of the peripheral nervous system (Gans and Northcutt, 1983). Invertebrate chordates arguably lack unambiguous neural crest homologs, yet have cells with some similarities, making comparisons with lampreys and jawed vertebrates essential for inferring characteristics of development in early vertebrates, and how they may have evolved from nonvertebrate chordates. Here we review recent research on cyclostome neural crest development, including research on lamprey gene regulatory networks and differentiated neural crest fates. Copyright © 2014 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  6. Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation.

    Science.gov (United States)

    Pünzeler, Sebastian; Link, Stephanie; Wagner, Gabriele; Keilhauer, Eva C; Kronbeck, Nina; Spitzer, Ramona Mm; Leidescher, Susanne; Markaki, Yolanda; Mentele, Edith; Regnard, Catherine; Schneider, Katrin; Takahashi, Daisuke; Kusakabe, Masayuki; Vardabasso, Chiara; Zink, Lisa M; Straub, Tobias; Bernstein, Emily; Harata, Masahiko; Leonhardt, Heinrich; Mann, Matthias; Rupp, Ralph Aw; Hake, Sandra B

    2017-08-01

    Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a functionally uncharacterized, vertebrate-specific protein that binds very tightly to chromatin through a concerted multivalent binding mode. Two internal protein regions mediate H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain exhibits direct DNA binding. Genome-wide mapping reveals that PWWP2A binds selectively to H2A.Z-containing nucleosomes with strong preference for promoters of highly transcribed genes. In human cells, its depletion affects gene expression and impairs proliferation via a mitotic delay. While PWWP2A does not influence H2A.Z occupancy, the C-terminal tail of H2A.Z is one important mediator to recruit PWWP2A to chromatin. Knockdown of PWWP2A in Xenopus results in severe cranial facial defects, arising from neural crest cell differentiation and migration problems. Thus, PWWP2A is a novel H2A.Z-specific multivalent chromatin binder providing a surprising link between H2A.Z, chromosome segregation, and organ development. © 2017 The Authors.

  7. The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.

    Science.gov (United States)

    Isern, Joan; García-García, Andrés; Martín, Ana M; Arranz, Lorena; Martín-Pérez, Daniel; Torroja, Carlos; Sánchez-Cabo, Fátima; Méndez-Ferrer, Simón

    2014-09-25

    Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. In this study, we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin(-) MSCs participate in fetal skeletogenesis and lose MSC activity soon after birth. In contrast, quiescent neural crest-derived nestin(+) cells preserve MSC activity, but do not generate fetal chondrocytes. Instead, they differentiate into HSC niche-forming MSCs, helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP(+) Pdgfrα(-) cell population also contains Schwann cell precursors, but does not comprise mature Schwann cells. Thus, in the developing bone marrow HSC niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, and ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation.

  8. Postotic and preotic cranial neural crest cells differently contribute to thyroid development.

    Science.gov (United States)

    Maeda, Kazuhiro; Asai, Rieko; Maruyama, Kazuaki; Kurihara, Yukiko; Nakanishi, Toshio; Kurihara, Hiroki; Miyagawa-Tomita, Sachiko

    2016-01-01

    Thyroid development and formation vary among species, but in most species the thyroid morphogenesis consists of five stages: specification, budding, descent, bilobation and folliculogenesis. The detailed mechanisms of these stages have not been fully clarified. During early development, the cranial neural crest (CNC) contributes to the thyroid gland. The removal of the postotic CNC (corresponding to rhombomeres 6, 7 and 8, also known as the cardiac neural crest) results in abnormalities of the cardiovascular system, thymus, parathyroid glands, and thyroid gland. To investigate the influence of the CNC on thyroid bilobation process, we divided the CNC into two regions, the postotic CNC and the preotic CNC (from the mesencephalon to rhombomere 5) regions and examined. We found that preotic CNC-ablated embryos had a unilateral thyroid lobe, and confirmed the presence of a single lobe or the absence of lobes in postotic CNC-ablated chick embryos. The thyroid anlage in each region-ablated embryos was of a normal size at the descent stage, but at a later stage, the thyroid in preotic CNC-ablated embryos was of a normal size, conflicting with a previous report in which the thyroid was reduced in size in the postotic CNC-ablated embryos. The postotic CNC cells differentiated into connective tissues of the thyroid in quail-to-chick chimeras. In contrast, the preotic CNC cells did not differentiate into connective tissues of the thyroid. We found that preotic CNC cells encompassed the thyroid anlage from the specification stage to the descent stage. Finally, we found that endothelin-1 and endothelin type A receptor-knockout mice and bosentan (endothelin receptor antagonist)-treated chick embryos showed bilobation anomalies that included single-lobe formation. Therefore, not only the postotic CNC, but also the preotic CNC plays an important role in thyroid morphogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. SOXE neofunctionalization and elaboration of the neural crest during chordate evolution

    Science.gov (United States)

    Tai, Andrew; Cheung, Martin; Huang, Yong-Heng; Jauch, Ralf; Bronner, Marianne E.; Cheah, Kathryn S. E.

    2016-01-01

    During chordate evolution, two genome-wide duplications facilitated acquisition of vertebrate traits, including emergence of neural crest cells (NCCs), in which neofunctionalization of the duplicated genes are thought to have facilitated development of craniofacial structures and the peripheral nervous system. How these duplicated genes evolve and acquire the ability to specify NC and their derivatives are largely unknown. Vertebrate SoxE paralogues, most notably Sox9/10, are essential for NC induction, delamination and lineage specification. In contrast, the basal chordate, amphioxus, has a single SoxE gene and lacks NC-like cells. Here, we test the hypothesis that duplication and divergence of an ancestral SoxE gene may have facilitated elaboration of NC lineages. By using an in vivo expression assay to compare effects of AmphiSoxE and vertebrate Sox9 on NC development, we demonstrate that all SOXE proteins possess similar DNA binding and homodimerization properties and can induce NCCs. However, AmphiSOXE is less efficient than SOX9 in transactivation activity and in the ability to preferentially promote glial over neuronal fate, a difference that lies within the combined properties of amino terminal and transactivation domains. We propose that acquisition of AmphiSoxE expression in the neural plate border led to NCC emergence while duplication and divergence produced advantageous mutations in vertebrate homologues, promoting elaboration of NC traits. PMID:27734831

  10. Stephen L. Gans Distinguished Overseas Lecture. The neural crest in pediatric surgery.

    Science.gov (United States)

    Tovar, Juan A

    2007-06-01

    This review highlights the relevance of the neural crest (NC) as a developmental control mechanism involved in several pediatric surgical conditions and the investigative interest of following some of its known signaling pathways. The participation of the NC in facial clefts, ear defects, branchial fistulae and cysts, heart outflow tract and aortic arch anomalies, pigmentary disorders, abnormal enteric innervation, neural tumors, hemangiomas, and vascular anomalies is briefly reviewed. Then, the literature on clinical and experimental esophageal atresia-tracheoesophageal fistula (EA-TEF) and congenital diaphragmatic hernia (CDH) is reviewed for the presence of associated NC defects. Finally, some of the molecular signaling pathways involved in both conditions (sonic hedgehog, Hox genes, and retinoids) are summarized. The association of facial, cardiovascular, thymic, parathyroid, and C-cell defects together with anomalies of extrinsic and intrinsic esophageal innervation in babies and/or animals with both EA-TEF and CDH strongly supports the hypothesis that NC is involved in the pathogenesis of these malformative clusters. On the other hand, both EA-TEF and CDH are observed in mice mutant for genes involved in the previously mentioned signaling pathways. The investigation of NC-related molecular pathogenic pathways involved in malformative associations like EA-TEF and CDH that are induced by chromosomal anomalies, chemical teratogens, and engineered mutations is a promising way of clarifying why and how some pediatric surgical conditions occur. Pediatric surgeons should be actively involved in these investigations.

  11. Enteric neurospheres are not specific to neural crest cultures : Implications for neural stem cell therapies

    NARCIS (Netherlands)

    Binder, E. (Ellen); D. Natarajan (Dipa); J.E. Cooper (Julie E.); Kronfli, R. (Rania); Cananzi, M. (Mara); J.-M. Delalande (Jean-Marie); C. Mccann; A.J. Burns (Alan); N. Thapar (Nikhil)

    2015-01-01

    textabstractObjectives Enteric neural stem cells provide hope of curative treatment for enteric neuropathies. Current protocols for their harvesting from humans focus on the generation of 'neurospheres' from cultures of dissociated gut tissue. The study aims to better understand the derivation,

  12. Dissecting CNBP, a zinc-finger protein required for neural crest development, in its structural and functional domains.

    Science.gov (United States)

    Armas, Pablo; Agüero, Tristán H; Borgognone, Mariana; Aybar, Manuel J; Calcaterra, Nora B

    2008-10-17

    Cellular nucleic-acid-binding protein (CNBP) plays an essential role in forebrain and craniofacial development by controlling cell proliferation and survival to mediate neural crest expansion. CNBP binds to single-stranded nucleic acids and displays nucleic acid chaperone activity in vitro. The CNBP family shows a conserved modular organization of seven Zn knuckles and an arginine-glycine-glycine (RGG) box between the first and second Zn knuckles. The participation of these structural motifs in CNBP biochemical activities has still not been addressed. Here, we describe the generation of CNBP mutants that dissect the protein into regions with structurally and functionally distinct properties. Mutagenesis approaches were followed to generate: (i) an amino acid replacement that disrupted the fifth Zn knuckle; (ii) N-terminal deletions that removed the first Zn knuckle and the RGG box, or the RGG box alone; and (iii) a C-terminal deletion that eliminated the three last Zn knuckles. Mutant proteins were overexpressed in Escherichia coli, purified, and used to analyze their biochemical features in vitro, or overexpressed in Xenopus laevis embryos to study their function in vivo during neural crest cell development. We found that the Zn knuckles are required, but not individually essential, for CNBP biochemical activities, whereas the RGG box is essential for RNA-protein binding and nucleic acid chaperone activity. Removal of the RGG box allowed CNBP to preserve a weak single-stranded-DNA-binding capability. A mutant mimicking the natural N-terminal proteolytic CNBP form behaved as the RGG-deleted mutant. By gain-of-function and loss-of-function experiments in Xenopus embryos, we confirmed the participation of CNBP in neural crest development, and we demonstrated that the CNBP mutants lacking the N-terminal region or the RGG box alone may act as dominant negatives in vivo. Based on these data, we speculate about the existence of a specific proteolytic mechanism for the

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

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    Brenda L Bohnsack

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

  14. The Melanocyte Fate in Neural Crest is Triggered by Myb Proteins through Activation of c-kit

    Czech Academy of Sciences Publication Activity Database

    Karafiát, Vít; Dvořáková, Marta; Pajer, Petr; Čermák, Vladimír; Dvořák, Michal

    2007-01-01

    Roč. 64, č. 21 (2007), s. 2975-2984 ISSN 1420-682X R&D Projects: GA MŠk(CZ) LC06061; GA ČR GA204/06/1728 Institutional research plan: CEZ:AV0Z50520514 Keywords : c-myb proto-oncogene * v-mybAMV oncogene * neural crest * cell fate determination * melanocytes * c-kit signal Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.239, year: 2007

  15. Specific and spatial labeling of P0-Cre versus Wnt1-Cre in cranial neural crest in early mouse embryos.

    Science.gov (United States)

    Chen, Guiqian; Ishan, Mohamed; Yang, Jingwen; Kishigami, Satoshi; Fukuda, Tomokazu; Scott, Greg; Ray, Manas K; Sun, Chenming; Chen, Shi-You; Komatsu, Yoshihiro; Mishina, Yuji; Liu, Hong-Xiang

    2017-06-01

    P0-Cre and Wnt1-Cre mouse lines have been widely used in combination with loxP-flanked mice to label and genetically modify neural crest (NC) cells and their derivatives. Wnt1-Cre has been regarded as the gold standard and there have been concerns about the specificity of P0-Cre because it is not clear about the timing and spatial distribution of the P0-Cre transgene in labeling NC cells at early embryonic stages. We re-visited P0-Cre and Wnt1-Cre models in the labeling of NC cells in early mouse embryos with a focus on cranial NC. We found that R26-lacZ Cre reporter responded to Cre activity more reliably than CAAG-lacZ Cre reporter during early embryogenesis. Cre immunosignals in P0-Cre and reporter (lacZ and RFP) activity in P0-Cre/R26-lacZ and P0-Cre/R26-RFP embryos was detected in the cranial NC and notochord regions in E8.0-9.5 (4-19 somites) embryos. P0-Cre transgene expression was observed in migrating NC cells and was more extensive in the forebrain and hindbrain but not apparent in the midbrain. Differences in the Cre distribution patterns of P0-Cre and Wnt1-Cre were profound in the midbrain and hindbrain regions, that is, extensive in the midbrain of Wnt1-Cre and in the hindbrain of P0-Cre embryos. The difference between P0-Cre and Wnt1-Cre in labeling cranial NC may provide a better explanation of the differential distributions of their NC derivatives and of the phenotypes caused by Cre-driven genetic modifications. © 2017 Wiley Periodicals, Inc.

  16. Differentiation of neural crest stem cells from nasal mucosa into motor neuron-like cells.

    Science.gov (United States)

    Bagher, Zohreh; Kamrava, Seyed Kamran; Alizadeh, Rafieh; Farhadi, Mohammad; Absalan, Moloud; Falah, Masoumeh; Faghihi, Faezeh; Zare-Sadeghi, Arash; Komeili, Ali

    2018-05-25

    Cell transplantation is a potential therapeutic approach for repairing neuropathological and neurodegenerative disorders of central nervous system by replacing the degenerated cells with new ones. Among a variety of stem cell candidates to provide these new cells, olfactory ectomesenchymal stem cells (OE-MSCs) have attracted a great attention due to their neural crest origin, easy harvest, high proliferation, and autologous transplantation. Since there is no report on differentiation potential of these cells into motor neuron-like cells, we evaluated this potential using Real-time PCR, flowcytometry and immunocytochemistry after the treatment with differentiation cocktail containing retinoic acid and Sonic Hedgehog. Immunocytochemistry staining of the isolated OE-MSCs demonstrated their capability to express nestin and vimentin, as the two markers of primitive neuroectoderm. The motor neuron differentiation of OE-MSCs resulted in changing their morphology into bipolar cells with high expression of motor neuron markers of ChAT, Hb-9 and Islet-1 at the level of mRNA and protein. Consequently, we believe that the OE-MSCs have great potential to differentiate into motor neuron-like cells and can be an ideal stem cell source for the treatment of motor neuron-related disorders of central nervous system. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Directory of Open Access Journals (Sweden)

    Cécile eCoste

    2015-06-01

    Full Text Available Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL12-abundant reticular (CAR cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs, which have been recently identified as neural crest-derived cells (NCSCs. Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-to-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  18. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Science.gov (United States)

    Coste, Cécile; Neirinckx, Virginie; Gothot, André; Wislet, Sabine; Rogister, Bernard

    2015-01-01

    Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC) function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL) 12-abundant reticular (CAR) cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs), which have been recently identified as neural crest-derived cells (NCSCs). Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  19. Temporally Regulated Neural Crest Transcription Factors Distinguish Neuroectodermal Tumors of Varying Malignancy and Differentiation

    Directory of Open Access Journals (Sweden)

    Timothy R. Gershon

    2005-06-01

    Full Text Available Neuroectodermal tumor cells, like neural crest (NC cells, are pluripotent, proliferative, and migratory. We tested the hypothesis that genetic programs essential to NC development are activated in neuroectodermal tumors. We examined the expression of transcription factors PAX3, PAX7, AP-2α, and SOX10 in human embryos and neuroectodermal tumors: neurofibroma, schwannoma, neuroblastoma, malignant nerve sheath tumor, melanoma, medulloblastoma, supratentorial primitive neuroectodermal tumor, and Ewing's sarcoma. We also examined the expression of P0, ERBB3, and STX, targets of SOX10, AP-2α, and PAX3, respectively. PAX3, AP-2α, and SOX10 were expressed sequentially in human NC development, whereas PAX7 was restricted to mesoderm. Tumors expressed PAX3, AP-2α, SOX10, and PAX7 in specific combinations. SOX10 and AP-2α were expressed in relatively differentiated neoplasms. The early NC marker, PAX3, and its homologue, PAX7, were detected in poorly differentiated tumors and tumors with malignant potential. Expression of NC transcription factors and target genes correlated. Transcription factors essential to NC development are thus present in neuroectodermal tumors. Correlation of specific NC transcription factors with phenotype, and with expression of specific downstream genes, provides evidence that these transcription factors actively influence gene expression and tumor behavior. These findings suggest that PAX3, PAX7, AP-2α, and SOX10 are potential markers of prognosis and targets for therapeutic intervention.

  20. Climate Forcing of Ripple Migration and Crest Alignment in the Last 400 kyr in Meridiani Planum, Mars

    Science.gov (United States)

    Fenton, Lori K.; Carson, Helen C.; Michaels, Timothy I.

    2018-04-01

    The plains ripples of Meridiani Planum are the first paleo-aeolian bedforms on Mars to have had their last migration episode constrained in time (to 50-200 ka). Here we test how variations in orbital configuration, air pressure, and atmospheric dust loading over the past 400 kyr affect bedform mobility and crest alignment. Using the National Aeronautics and Space Administration Ames Mars Global Climate Model, we ran a series of sensitivity tests under a number of different conditions, seeking changes in wind patterns relative to those modeled for present-day conditions. Results indicate that enhanced sand drift potential in Meridiani Planum correlates with (1) high axial obliquity, (2) a longitude of perihelion (Lp) near southern summer solstice, and (3) a greater air pressure. The last pulse of westward plains ripple migration likely occurred during the most recent obliquity (relative) maximum, from 111 to 86 ka. At Lp coinciding with southern summer solstice, the Mars Global Climate Model produced a westward resultant drift direction, consistent with the observed north-south plains ripple crest alignment. However, smaller superposed ripples, aligned NNE-SSW, are consistent with a strengthened northern summer Hadley return flow, occurring when Lp coincided with northern summer solstice. The superposed NNE-SSW ripples likely formed as the axial obliquity decreased during the last relative maximum and Lp swung toward northern summer, from 86 to 72 ka. The timeline of bedform activity supports the proposed sequence of CO2 sequestration in the south polar residual cap over the past 400 kyr.

  1. Occipital cephalocele with neural crest remnants? Radiological and pathological findings in a newborn boy.

    Science.gov (United States)

    Arishima, Hidetaka; Neishi, Hiroyuki; Kikuta, Ken-Ichiro

    2016-06-01

    A cephalocele is a congenital anomaly involving the herniation of intracranial tissue from a skull defect. The sac containing the central nervous system (CNS) with the ventricle system is called the encephalocystocele. An atretic cephalocele is thought to be an abortive form of cephalocele, and the essential nature is still controversial. Here, we report the case of a newborn boy with an occipital cephalocele containing a small cystic component which was composed of ependymal cells and the immature CNS tissue. A newborn boy was admitted to our hospital because of an occipital mass, which was about 2.5 cm in diameter, located at the posterior midline, and covered with alopetic skin without CSF leakage. He had a cleft palate. Magnetic resonance imaging (MRI) clearly showed an occipital cephalocele with a tiny cystic component connecting to the subarachnoid space. MRI also showed mild hydrocephalus, hypoplasia of the corpus callosum and tentorium cerebelli, dropping down of the bilateral occipital lobes and vermicular agenesis. We performed the extirpation of the subscalp module under general anesthesia and histologically examined the resected mass. On immunohistopathological examination, most part of the subscalp module was fibrous tissue with numerous vessels and meningeal origin cells. In a small part of the innermost layer, we found a small island consisting of CNS tissue and a tiny cyst lined with a single layer of ependymal cells. Based on radiological and immunohistopathological findings, we speculate that the cystic component at the base of the nodule seems to correspond to neural crest remnants but not to true herniation of the brain and cerebral ventricles.

  2. Derivation of corneal endothelial cell-like cells from rat neural crest cells in vitro.

    Directory of Open Access Journals (Sweden)

    Chengqun Ju

    Full Text Available The aim of this study was to investigate the feasibility of inducing rat neural crest cells (NCC to differentiate to functional corneal endothelial cell (CEC-like cells in vitro. Rat NCC were induced with adult CEC-derived conditioned medium. Immunofluorescence, flow cytometry and real time RT-PCR assay were used to detect expression of the corneal endothelium differentiation marker N-cadherin and transcription factors FoxC1 and Pitx2. CFDA SE-labeled CEC-like cells were transplanted to the corneal endothelium of a rat corneal endothelium deficiency model, and an eye-down position was maintained for 24 hours to allow cell attachment. The animals were observed for as long as 2 months after surgery and underwent clinical and histological examination. Spindle-like NCC turned to polygonal CEC-like after induction and expressed N-cadherin, FoxC1, Pitx2, zonula occludens-1 and sodium-potassium pump Na(+/K(+ ATPase. The corneas of the experimental group were much clearer than those of the control group and the mean corneal thickness in the experimental group was significantly less than in the control group7, 14, 21 and 28 days after surgery. Confocal microscopy through focusing and histological analysis confirmed that green fluorescence-positive CEC-like cells formed a monolayer covering the Descemet's membrane in the experimental group. In conclusion, CEC-like cells derived from NCCs displayed characters of native CEC, and the induction protocol provides guidance for future human CEC induction from NCC.

  3. Stem cell property of postmigratory cranial neural crest cells and their utility in alveolar bone regeneration and tooth development.

    Science.gov (United States)

    Chung, Il-Hyuk; Yamaza, Takayoshi; Zhao, Hu; Choung, Pill-Hoon; Shi, Songtao; Chai, Yang

    2009-04-01

    The vertebrate neural crest is a multipotent cell population that gives rise to a variety of different cell types. We have discovered that postmigratory cranial neural crest cells (CNCCs) maintain mesenchymal stem cell characteristics and show potential utility for the regeneration of craniofacial structures. We are able to induce the osteogenic differentiation of postmigratory CNCCs, and this differentiation is regulated by bone morphogenetic protein (BMP) and transforming growth factor-beta signaling pathways. After transplantation into a host animal, postmigratory CNCCs form bone matrix. CNCC-formed bones are distinct from bones regenerated by bone marrow mesenchymal stem cells. In addition, CNCCs support tooth germ survival via BMP signaling in our CNCC-tooth germ cotransplantation system. Thus, we conclude that postmigratory CNCCs preserve stem cell features, contribute to craniofacial bone formation, and play a fundamental role in supporting tooth organ development. These findings reveal a novel function for postmigratory CNCCs in organ development, and demonstrate the utility of these CNCCs in regenerating craniofacial structures.

  4. Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves

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    Jiao Jiao

    2016-08-01

    Full Text Available Individuals with bicuspid aortic valves (BAV are at a higher risk of developing thoracic aortic aneurysms (TAA than patients with trileaflet aortic valves (TAV. The aneurysms associated with BAV most commonly involve the ascending aorta and spare the descending aorta. Smooth muscle cells (SMCs in the ascending and descending aorta arise from neural crest (NC and paraxial mesoderm (PM, respectively. We hypothesized defective differentiation of the neural crest stem cells (NCSCs-derived SMCs but not paraxial mesoderm cells (PMCs-derived SMCs contributes to the aortopathy associated with BAV. When induced pluripotent stem cells (iPSCs from BAV/TAA patients were differentiated into NCSC-derived SMCs, these cells demonstrated significantly decreased expression of marker of SMC differentiation (MYH11 and impaired contraction compared to normal control. In contrast, the PMC-derived SMCs were similar to control cells in these aspects. The NCSC-SMCs from the BAV/TAA also showed decreased TGF-β signaling based on phosphorylation of SMAD2, and increased mTOR signaling. Inhibition of mTOR pathway using rapamycin rescued the aberrant differentiation. Our data demonstrates that decreased differentiation and contraction of patient's NCSC-derived SMCs may contribute to that aortopathy associated with BAV.

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

    Science.gov (United States)

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

    2013-01-01

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

  6. Neuronal regeneration in injured rat spinal cord after human dental pulp derived neural crest stem cell transplantation.

    Science.gov (United States)

    Kabatas, S; Demir, C S; Civelek, E; Yilmaz, I; Kircelli, A; Yilmaz, C; Akyuva, Y; Karaoz, E

    2018-01-01

    This study aimed to analyze the effect of human Dental Pulp-Neural Crest Stem Cells (hDP-NCSCs) delivery on lesion site after spinal cord injury (SCI), and to observe the functional recovery after transplantation. Neural Crest Stem Cells (NCSCs) were isolated from human Dental Pulp (hDP). The experimental rat population was divided into four groups (n = 6/24). Their behavioral motility was scored regularly. After 4-weeks, rats were sacrificed, and their spinal cords were examined for Green Fluorescent Protein (GFP) labeled hDP-NCSCs by immunofluorescence (IF) staining. In early post-injury (p.i) period, the ultrastructure of spinal cord tissue was preserved in Group 4. The majority of cells forming the ependymal region around the central canal were found to be hDP-NCSCs. While the grey-and-white-matter around the ependymal region was composed of e.g. GFP cells, with astrocytic-like appearance. The scores showed significant motor recovery in hind limb functions in Group 4. However, no obvious change was observed in other groups. Cells e.g., mesenchymal (Vimentin+) which express GFP+ cells in the gray-and-white-matter around the ependymal region could indicate the potential to self-renewal and plasticity. Thus, transplantation of hDP-NCSCs might be an effective strategy to improve functional recovery following spinal cord trauma (Fig. 10, Ref. 32).

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

    Directory of Open Access Journals (Sweden)

    Myron S Ignatius

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

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

    Science.gov (United States)

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

    2006-06-15

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

  9. Gene expression profiling analysis of the effects of low-intensity pulsed ultrasound on induced pluripotent stem cell-derived neural crest stem cells.

    Science.gov (United States)

    Xia, Bin; Zou, Yang; Xu, Zhiling; Lv, Yonggang

    2017-11-01

    Low-intensity pulsed ultrasound (LIPUS) is a noninvasive technique that has been shown to affect cell proliferation, migration, and differentiation and promote the regeneration of damaged peripheral nerve. Our previous studies had proved that LIPUS can significantly promote the neural differentiation of induced pluripotent stem cell-derived neural crest stem cells (iPSCs-NCSCs) and enhance the repair of rat-transected sciatic nerve. To further explore the underlying mechanisms of LIPUS treatment of iPSCs-NCSCs, this study reported the gene expression profiling analysis of iPSCs-NCSCs before and after LIPUS treatment using the RNA-sequencing (RNA-Seq) method. It was found that expression of 76 genes of iPSCs-NCSCs cultured in a serum-free neural induction medium and expression of 21 genes of iPSCs-NCSCs cultured in a neuronal differentiation medium were significantly changed by LIPUS treatment. The differentially expressed genes are related to angiogenesis, nervous system activity and functions, cell activities, and so on. The RNA-seq results were further verified by a quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). High correlation was observed between the results obtained from qRT-PCR and RNA-Seq. This study presented new information on the global gene expression patterns of iPSCs-NCSCs after LIPUS treatment and may expand the understanding of the complex molecular mechanism of LIPUS treatment of iPSCs-NCSCs. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  10. Search for the Missing lncs: Gene Regulatory Networks in Neural Crest Development and Long Non-coding RNA Biomarkers of Hirschsprung's Disease

    Science.gov (United States)

    Hirschsprung’s disease (HSCR), a birth defect characterized by variable aganglionosis of the gut, affects about 1 in 5000 births, and is a consequence of abnormal development of neural crest cells, from which enteric ganglia derive. In the companion article in this issue (Shen et...

  11. Prediction and characterisation of a highly conserved, remote and cAMP responsive enhancer that regulates Msx1 gene expression in cardiac neural crest and outflow tract.

    Science.gov (United States)

    Miller, Kerry Ann; Davidson, Scott; Liaros, Angela; Barrow, John; Lear, Marissa; Heine, Danielle; Hoppler, Stefan; MacKenzie, Alasdair

    2008-05-15

    Double knockouts of the Msx1 and Msx2 genes in the mouse result in severe cardiac outflow tract malformations similar to those frequently found in newborn infants. Despite the known role of the Msx genes in cardiac formation little is known of the regulatory systems (ligand receptor, signal transduction and protein-DNA interactions) that regulate the tissue-specific expression of the Msx genes in mammals during the formation of the outflow tract. In the present study we have used a combination of multi-species comparative genomics, mouse transgenic analysis and in-situ hybridisation to predict and validate the existence of a remote ultra-conserved enhancer that supports the expression of the Msx1 gene in migrating mouse cardiac neural crest and the outflow tract primordia. Furthermore, culturing of embryonic explants derived from transgenic lines with agonists of the PKC and PKA signal transduction systems demonstrates that this remote enhancer is influenced by PKA but not PKC dependent gene regulatory systems. These studies demonstrate the efficacy of combining comparative genomics and transgenic analyses and provide a platform for the study of the possible roles of Msx gene mis-regulation in the aetiology of congenital heart malformation.

  12. Combination of exogenous cell transplantation and 5-HT4 receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model.

    Science.gov (United States)

    Yu, Hui; Zheng, Bai-Jun; Pan, Wei-Kang; Wang, Huai-Jie; Xie, Chong; Zhao, Yu-Ying; Chen, Xin-Lin; Liu, Yong; Gao, Ya

    2017-02-01

    Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT 4 receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT 4 receptor agonist/antagonist. The labeled ENCCs were then transplanted into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75 NTR and peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT 4 receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells.

    Directory of Open Access Journals (Sweden)

    Allyson E Kennedy

    Full Text Available Since electronic cigarette (ECIG introduction to American markets in 2007, vaping has surged in popularity. Many, including women of reproductive age, also believe that ECIG use is safer than traditional tobacco cigarettes and is not hazardous when pregnant. However, there are few studies investigating the effects of ECIG exposure on the developing embryo and nothing is known about potential effects on craniofacial development. Therefore, we have tested the effects of several aerosolized e-cigarette liquids (e-cigAM in an in vivo craniofacial model, Xenopus laevis, as well as a mammalian neural crest cell line. Results demonstrate that e-cigAM exposure during embryonic development induces a variety of defects, including median facial clefts and midface hypoplasia in two of e-cigAMs tested e-cigAMs. Detailed quantitative analyses of the facial morphology revealed that nicotine is not the main factor in inducing craniofacial defects, but can exacerbate the effects of the other e-liquid components. Additionally, while two different e-cigAMs can have very similar consequences on facial appearances, there are subtle differences that could be due to the differences in e-cigAM components. Further assessment of embryos exposed to these particular e-cigAMs revealed cranial cartilage and muscle defects and a reduction in the blood supply to the face. Finally, the expression of markers for vascular and cartilage differentiation was reduced in a mammalian neural crest cell line corroborating the in vivo effects. Our work is the first to show that ECIG use could pose a potential hazard to the developing embryo and cause craniofacial birth defects. This emphasizes the need for more testing and regulation of this new popular product.

  14. E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells.

    Science.gov (United States)

    Kennedy, Allyson E; Kandalam, Suraj; Olivares-Navarrete, Rene; Dickinson, Amanda J G

    2017-01-01

    Since electronic cigarette (ECIG) introduction to American markets in 2007, vaping has surged in popularity. Many, including women of reproductive age, also believe that ECIG use is safer than traditional tobacco cigarettes and is not hazardous when pregnant. However, there are few studies investigating the effects of ECIG exposure on the developing embryo and nothing is known about potential effects on craniofacial development. Therefore, we have tested the effects of several aerosolized e-cigarette liquids (e-cigAM) in an in vivo craniofacial model, Xenopus laevis, as well as a mammalian neural crest cell line. Results demonstrate that e-cigAM exposure during embryonic development induces a variety of defects, including median facial clefts and midface hypoplasia in two of e-cigAMs tested e-cigAMs. Detailed quantitative analyses of the facial morphology revealed that nicotine is not the main factor in inducing craniofacial defects, but can exacerbate the effects of the other e-liquid components. Additionally, while two different e-cigAMs can have very similar consequences on facial appearances, there are subtle differences that could be due to the differences in e-cigAM components. Further assessment of embryos exposed to these particular e-cigAMs revealed cranial cartilage and muscle defects and a reduction in the blood supply to the face. Finally, the expression of markers for vascular and cartilage differentiation was reduced in a mammalian neural crest cell line corroborating the in vivo effects. Our work is the first to show that ECIG use could pose a potential hazard to the developing embryo and cause craniofacial birth defects. This emphasizes the need for more testing and regulation of this new popular product.

  15. In Vivo Transplantation of Enteric Neural Crest Cells into Mouse Gut; Engraftment, Functional Integration and Long-Term Safety.

    Directory of Open Access Journals (Sweden)

    Julie E Cooper

    Full Text Available Enteric neuropathies are severe gastrointestinal disorders with unsatisfactory outcomes. We aimed to investigate the potential of enteric neural stem cell therapy approaches for such disorders by transplanting mouse enteric neural crest cells (ENCCs into ganglionic and aganglionic mouse gut in vivo and analysing functional integration and long-term safety.Neurospheres generated from yellow fluorescent protein (YFP expressing ENCCs selected from postnatal Wnt1-cre;R26R-YFP/YFP murine gut were transplanted into ganglionic hindgut of wild-type littermates or aganglionic hindgut of Ednrbtm1Ywa mice (lacking functional endothelin receptor type-B. Intestines were then assessed for ENCC integration and differentiation using immunohistochemistry, cell function using calcium imaging, and long-term safety using PCR to detect off-target YFP expression.YFP+ ENCCs engrafted, proliferated and differentiated into enteric neurons and glia within recipient ganglionic gut. Transplanted cells and their projections spread along the endogenous myenteric plexus to form branching networks. Electrical point stimulation of endogenous nerve fibres resulted in calcium transients (F/F0 = 1.16 ± 0.01;43 cells, n = 6 in YFP+ transplanted ENCCs (abolished with TTX. Long-term follow-up (24 months showed transplanted ENCCs did not give rise to tumours or spread to other organs (PCR negative in extraintestinal sites. In aganglionic gut ENCCs similarly spread and differentiated to form neuronal and glial networks with projections closely associated with endogenous neural networks of the transition zone.Transplanted ENCCs successfully engrafted into recipient ganglionic and aganglionic gut showing appropriate spread, localisation and, importantly, functional integration without any long-term safety issues. This study provides key support for the development and use of enteric neural stem cell therapies.

  16. A key role for poly(ADP-ribose polymerase 3 in ectodermal specification and neural crest development.

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    Michèle Rouleau

    2011-01-01

    Full Text Available The PARP family member poly(ADP-ribose polymerase 3 (PARP3 is structurally related to the well characterized PARP1 that orchestrates cellular responses to DNA strand breaks and cell death by the synthesis of poly(ADP-ribose. In contrast to PARP1 and PARP2, the functions of PARP3 are undefined. Here, we reveal critical functions for PARP3 during vertebrate development.We have used several in vitro and in vivo approaches to examine the possible functions of PARP3 as a transcriptional regulator, a function suggested from its previously reported association with several Polycomb group (PcG proteins. We demonstrate that PARP3 gene occupancy in the human neuroblastoma cell line SK-N-SH occurs preferentially with developmental genes regulating cell fate specification, tissue patterning, craniofacial development and neurogenesis. Addressing the significance of this association during zebrafish development, we show that morpholino oligonucleotide-directed inhibition of parp3 expression in zebrafish impairs the expression of the neural crest cell specifier sox9a and of dlx3b/dlx4b, the formation of cranial sensory placodes, inner ears and pectoral fins. It delays pigmentation and severely impedes the development of the median fin fold and tail bud.Our findings demonstrate that Parp3 is crucial in the early stages of zebrafish development, possibly by exerting its transcriptional regulatory functions as early as during the specification of the neural plate border.

  17. The neural crest and neural crest cells

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    papers and independent studies in the 1920s and '30s by. Landacre ..... Four possibilities, which are not mutually exclusive, could explain evolutionary changes in gene function: .... description of the results of the chief course of events in the.

  18. Sonic Hedgehog promotes the survival of neural crest cells by limiting apoptosis induced by the dependence receptor CDON during branchial arch development.

    Science.gov (United States)

    Delloye-Bourgeois, Céline; Rama, Nicolas; Brito, José; Le Douarin, Nicole; Mehlen, Patrick

    2014-09-26

    Cell-adhesion molecule-related/Downregulated by Oncogenes (CDO or CDON) was identified as a receptor for the classic morphogen Sonic Hedgehog (SHH). It has been shown that, in cell culture, CDO also behaves as a SHH dependence receptor: CDO actively triggers apoptosis in absence of SHH via a proteolytic cleavage in CDO intracellular domain. We present evidence that CDO is also pro-apoptotic in the developing neural tube where SHH is known to act as a survival factor. SHH, produced by the ventral foregut endoderm, was shown to promote survival of facial neural crest cells (NCCs) that colonize the first branchial arch (BA1). We show here that the survival activity of SHH on neural crest cells is due to SHH-mediated inhibition of CDO pro-apoptotic activity. Silencing of CDO rescued NCCs from apoptosis observed upon SHH inhibition in the ventral foregut endoderm. Thus, the pair SHH/dependence receptor CDO may play an important role in neural crest cell survival during the formation of the first branchial arch. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. PSA-NCAM-Negative Neural Crest Cells Emerging during Neural Induction of Pluripotent Stem Cells Cause Mesodermal Tumors and Unwanted Grafts

    Science.gov (United States)

    Lee, Dongjin R.; Yoo, Jeong-Eun; Lee, Jae Souk; Park, Sanghyun; Lee, Junwon; Park, Chul-Yong; Ji, Eunhyun; Kim, Han-Soo; Hwang, Dong-Youn; Kim, Dae-Sung; Kim, Dong-Wook

    2015-01-01

    Summary Tumorigenic potential of human pluripotent stem cells (hPSCs) is an important issue in clinical applications. Despite many efforts, PSC-derived neural precursor cells (NPCs) have repeatedly induced tumors in animal models even though pluripotent cells were not detected. We found that polysialic acid-neural cell adhesion molecule (PSA-NCAM)− cells among the early NPCs caused tumors, whereas PSA-NCAM+ cells were nontumorigenic. Molecular profiling, global gene analysis, and multilineage differentiation of PSA-NCAM− cells confirm that they are multipotent neural crest stem cells (NCSCs) that could differentiate into both ectodermal and mesodermal lineages. Transplantation of PSA-NCAM− cells in a gradient manner mixed with PSA-NCAM+ cells proportionally increased mesodermal tumor formation and unwanted grafts such as PERIPHERIN+ cells or pigmented cells in the rat brain. Therefore, we suggest that NCSCs are a critical target for tumor prevention in hPSC-derived NPCs, and removal of PSA-NCAM− cells eliminates the tumorigenic potential originating from NCSCs after transplantation. PMID:25937368

  20. Transcrition factor c-Myb is involved in the regulation of the epithelial-mesenchymal transition in the avian neural crest

    Czech Academy of Sciences Publication Activity Database

    Karafiát, Vít; Dvořáková, Marta; Krejčí, E.; Králová, Jarmila; Pajer, Petr; Šnajdr, P.; Mandíková, Sonja; Bartůněk, Petr; Grim, M.; Dvořák, Michal

    2005-01-01

    Roč. 62, č. 21 (2005), s. 2516-2525 ISSN 1420-682X R&D Projects: GA ČR GA304/03/0463; GA AV ČR IAA5052309 Institutional research plan: CEZ:AV0Z50520514 Keywords : c-myb gene * epithelial-mesenchymal transition * neural crest Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.582, year: 2005

  1. Conditional deletion of AP-2β in mouse cranial neural crest results in anterior segment dysgenesis and early-onset glaucoma

    Directory of Open Access Journals (Sweden)

    Vanessa B. Martino

    2016-08-01

    Full Text Available Anterior segment dysgenesis (ASD encompasses a group of developmental disorders in which a closed angle phenotype in the anterior chamber of the eye can occur and 50% of patients develop glaucoma. Many ASDs are thought to involve an inappropriate patterning and migration of the periocular mesenchyme (POM, which is derived from cranial neural crest cells (NCCs and mesoderm. Although, the mechanism of this disruption is not well understood, a number of transcriptional regulatory molecules have previously been implicated in ASDs. Here, we investigate the function of the transcription factor AP-2β, encoded by Tfap2b, which is expressed in NCCs and their derivatives. Wnt1-Cre-mediated conditional deletion of Tfap2b in NCCs resulted in post-natal ocular defects typified by opacity. Histological data revealed that the conditional AP-2β NCC knockout (KO mutants exhibited dysgenesis of multiple structures in the anterior segment of the eye including defects in the corneal endothelium, corneal stroma, ciliary body and disruption in the iridocorneal angle with adherence of the iris to the cornea. We further show that this phenotype leads to a significant increase in intraocular pressure and a subsequent loss of retinal ganglion cells and optic nerve degeneration, features indicative of glaucoma. Overall, our findings demonstrate that AP-2β is required in the POM for normal development of the anterior segment of the eye and that the AP-2β NCC KO mice might serve as a new and exciting model of ASD and glaucoma that is fully penetrant and with early post-natal onset.

  2. Combination of exogenous cell transplantation and 5-HT{sub 4} receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Hui [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Zheng, Bai-Jun; Pan, Wei-Kang; Wang, Huai-Jie; Xie, Chong; Zhao, Yu-Ying [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Chen, Xin-Lin; Liu, Yong [Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Gao, Ya, E-mail: ygao@mail.xjtu.edu.cn [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China)

    2017-02-01

    Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT{sub 4} receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT{sub 4} receptor agonist/antagonist. The labeled ENCCs were then transplanted into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75{sup NTR} and peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT{sub 4} receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model. - Highlights: • Survival and differentiation of exogenous ENCCs in treated colons. • With longer times post-intervention, the number of ENCCs and their progeny cells gradually increased. • Exogenous ENCCs combined with the 5-HT4 receptor agonist ffectively induced ENCCs proliferation and differentiation.

  3. Combination of exogenous cell transplantation and 5-HT4 receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model

    International Nuclear Information System (INIS)

    Yu, Hui; Zheng, Bai-Jun; Pan, Wei-Kang; Wang, Huai-Jie; Xie, Chong; Zhao, Yu-Ying; Chen, Xin-Lin; Liu, Yong; Gao, Ya

    2017-01-01

    Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT 4 receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT 4 receptor agonist/antagonist. The labeled ENCCs were then transplanted into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75 NTR and peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT 4 receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model. - Highlights: • Survival and differentiation of exogenous ENCCs in treated colons. • With longer times post-intervention, the number of ENCCs and their progeny cells gradually increased. • Exogenous ENCCs combined with the 5-HT4 receptor agonist ffectively induced ENCCs proliferation and differentiation.

  4. A Human Neural Crest Stem Cell-Derived Dopaminergic Neuronal Model Recapitulates Biochemical Abnormalities in GBA1 Mutation Carriers

    Directory of Open Access Journals (Sweden)

    Shi-Yu Yang

    2017-03-01

    Full Text Available Numerically the most important risk factor for the development of Parkinson's disease (PD is the presence of mutations in the glucocerebrosidase GBA1 gene. In vitro and in vivo studies show that GBA1 mutations reduce glucocerebrosidase (GCase activity and are associated with increased α-synuclein levels, reflecting similar changes seen in idiopathic PD brain. We have developed a neural crest stem cell-derived dopaminergic neuronal model that recapitulates biochemical abnormalities in GBA1 mutation-associated PD. Cells showed reduced GCase protein and activity, impaired macroautophagy, and increased α-synuclein levels. Advantages of this approach include easy access to stem cells, no requirement to reprogram, and retention of the intact host genome. Treatment with a GCase chaperone increased GCase protein levels and activity, rescued the autophagic defects, and decreased α-synuclein levels. These results provide the basis for further investigation of GCase chaperones or similar drugs to slow the progression of PD.

  5. Augmented Indian hedgehog signaling in cranial neural crest cells leads to craniofacial abnormalities and dysplastic temporomandibular joint in mice.

    Science.gov (United States)

    Yang, Ling; Gu, Shuping; Ye, Wenduo; Song, Yingnan; Chen, YiPing

    2016-04-01

    Extensive studies have pinpointed the crucial role of Indian hedgehog (Ihh) signaling in the development of the appendicular skeleton and the essential function of Ihh in the formation of the temporomandibular joint (TMJ). In this study, we have investigated the effect of augmented Ihh signaling in TMJ development. We took a transgenic gain-of-function approach by overexpressing Ihh in the cranial neural crest (CNC) cells using a conditional Ihh transgenic allele and the Wnt1-Cre allele. We found that Wnt1-Cre-mediated tissue-specific overexpression of Ihh in the CNC lineage caused severe craniofacial abnormalities, including cleft lip/palate, encephalocele, anophthalmos, micrognathia, and defective TMJ development. In the mutant TMJ, the glenoid fossa was completely absent, whereas the condyle and the articular disc appeared relatively normal with slightly delayed chondrocyte differentiation. Our findings thus demonstrate that augmented Ihh signaling is detrimental to craniofacial development, and that finely tuned Ihh signaling is critical for TMJ formation. Our results also provide additional evidence that the development of the condyle and articular disc is independent of the glenoid fossa.

  6. Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation.

    Directory of Open Access Journals (Sweden)

    Lu Li

    Full Text Available The importance of BMP receptor Ia (BMPRIa mediated signaling in the development of craniofacial organs, including the tooth and palate, has been well illuminated in several mouse models of loss of function, and by its mutations associated with juvenile polyposis syndrome and facial defects in humans. In this study, we took a gain-of-function approach to further address the role of BMPR-IA-mediated signaling in the mesenchymal compartment during tooth and palate development. We generated transgenic mice expressing a constitutively active form of BmprIa (caBmprIa in cranial neural crest (CNC cells that contributes to the dental and palatal mesenchyme. Mice bearing enhanced BMPRIa-mediated signaling in CNC cells exhibit complete cleft palate and delayed odontogenic differentiation. We showed that the cleft palate defect in the transgenic animals is attributed to an altered cell proliferation rate in the anterior palatal mesenchyme and to the delayed palatal elevation in the posterior portion associated with ectopic cartilage formation. Despite enhanced activity of BMP signaling in the dental mesenchyme, tooth development and patterning in transgenic mice appeared normal except delayed odontogenic differentiation. These data support the hypothesis that a finely tuned level of BMPRIa-mediated signaling is essential for normal palate and tooth development.

  7. Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2.

    Science.gov (United States)

    Rabadán, M Angeles; Herrera, Antonio; Fanlo, Lucia; Usieto, Susana; Carmona-Fontaine, Carlos; Barriga, Elias H; Mayor, Roberto; Pons, Sebastián; Martí, Elisa

    2016-06-15

    Delamination of neural crest (NC) cells is a bona fide physiological model of epithelial-to-mesenchymal transition (EMT), a process that is influenced by Wnt/β-catenin signalling. Using two in vivo models, we show that Wnt/β-catenin signalling is transiently inhibited at the time of NC delamination. In attempting to define the mechanism underlying this inhibition, we found that the scaffold proteins Dact1 and Dact2, which are expressed in pre-migratory NC cells, are required for NC delamination in Xenopus and chick embryos, whereas they do not affect the motile properties of migratory NC cells. Dact1/2 inhibit Wnt/β-catenin signalling upstream of the transcriptional activity of T cell factor (TCF), which is required for EMT to proceed. Dact1/2 regulate the subcellular distribution of β-catenin, preventing β-catenin from acting as a transcriptional co-activator to TCF, yet without affecting its stability. Together, these data identify a novel yet important regulatory element that inhibits β-catenin signalling, which then affects NC delamination. © 2016. Published by The Company of Biologists Ltd.

  8. Interaction of adult human neural crest-derived stem cells with a nanoporous titanium surface is sufficient to induce their osteogenic differentiation

    Directory of Open Access Journals (Sweden)

    Matthias Schürmann

    2014-07-01

    Full Text Available Osteogenic differentiation of various adult stem cell populations such as neural crest-derived stem cells is of great interest in the context of bone regeneration. Ideally, exogenous differentiation should mimic an endogenous differentiation process, which is partly mediated by topological cues. To elucidate the osteoinductive potential of porous substrates with different pore diameters (30 nm, 100 nm, human neural crest-derived stem cells isolated from the inferior nasal turbinate were cultivated on the surface of nanoporous titanium covered membranes without additional chemical or biological osteoinductive cues. As controls, flat titanium without any topological features and osteogenic medium was used. Cultivation of human neural crest-derived stem cells on 30 nm pores resulted in osteogenic differentiation as demonstrated by alkaline phosphatase activity after seven days as well as by calcium deposition after 3 weeks of cultivation. In contrast, cultivation on flat titanium and on membranes equipped with 100 nm pores was not sufficient to induce osteogenic differentiation. Moreover, we demonstrate an increase of osteogenic transcripts including Osterix, Osteocalcin and up-regulation of Integrin β1 and α2 in the 30 nm pore approach only. Thus, transplantation of stem cells pre-cultivated on nanostructured implants might improve the clinical outcome by support of the graft adherence and acceleration of the regeneration process.

  9. Pa2G4 is a novel Six1 co-factor that is required for neural crest and otic development☆

    Science.gov (United States)

    Neilson, Karen M.; Abbruzzesse, Genevieve; Kenyon, Kristy; Bartolo, Vanessa; Krohn, Patrick; Alfandari, Dominique; Moody, Sally A.

    2016-01-01

    Mutations in SIX1 and in its co-factor, EYA1, underlie Branchiootorenal Spectrum disorder (BOS), which is characterized by variable branchial arch, otic and kidney malformations. However, mutations in these two genes are identified in only half of patients. We screened for other potential co-factors, and herein characterize one of them, Pa2G4 (aka Ebp1/Plfap). In human embryonic kidney cells, Pa2G4 binds to Six1 and interferes with the Six1-Eya1 complex. In Xenopus embryos, knock-down of Pa2G4 leads to down-regulation of neural border zone, neural crest and cranial placode genes, and concomitant expansion of neural plate genes. Gain-of-function leads to a broader neural border zone, expanded neural crest and altered cranial placode domains. In loss-of-function assays, the later developing otocyst is reduced in size, which impacts gene expression. In contrast, the size of the otocyst in gain-of-function assays is not changed but the expression domains of several otocyst genes are reduced. Together these findings establish an interaction between Pa2G4 and Six1, and demonstrate that it has an important role in the development of tissues affected in BOS. Thereby, we suggest that pa2g4 is a potential candidate gene for BOS. PMID:27940157

  10. The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage.

    Science.gov (United States)

    Wrage, Philip C; Tran, Thi; To, Khai; Keefer, Edward W; Ruhn, Kelly A; Hong, John; Hattangadi, Supriya; Treviño, Isaac; Tansey, Malú G

    2008-01-16

    We investigated whether adipose-derived adult stromal (ADAS) are of neural crest origin and the extent to which Notch 1 regulates their growth and differentiation. Mouse ADAS cells cultured in media formulated for neural stem cells (NSC) displayed limited capacity for self-renewal, clonogenicity, and neurosphere formation compared to NSC from the subventricular zone in the hippocampus. Although ADAS cells expressed Nestin, GFAP, NSE and Tuj1 in vitro, exposure to NSC differentiation supplements did not induce mature neuronal marker expression. In contrast, in mesenchymal stem cell (MSC) media, ADAS cells retained their ability to proliferate and differentiate beyond 20 passages and expressed high levels of Nestin. In neuritizing cocktails, ADAS cells extended processes, downregulated Nestin expression, and displayed depolarization-induced Ca(2+) transients but no spontaneous or evoked neural network activity on Multi-Electrode Arrays. Deletion of Notch 1 in ADAS cell cultures grown in NSC proliferation medium did not significantly alter their proliferative potential in vitro or the differentiation-induced downregulation of Nestin. Co-culture of ADAS cells with fibroblasts that stably expressed the Notch ligand Jagged 1 or overexpression of the Notch intracellular domain (NICD) did not alter ADAS cell growth, morphology, or cellular marker expression. ADAS cells did not display robust expression of neural crest transcription factors or genes (Sox, CRABP2, and TH); and lineage tracing analyses using Wnt1-Cre;Rosa26R-lacZ or -EYFP reporter mice confirmed that fewer than 2% of the ADAS cell population derived from a Wnt1-positive population during development. In summary, although media formulations optimized for MSCs or NSCs enable expansion of mouse ADAS cells in vitro, we find no evidence that these cells are of neural crest origin, that they can undergo robust terminal differentiation into functionally mature neurons, and that Notch 1 is likely to be a key

  11. CREST Revealed

    DEFF Research Database (Denmark)

    Rapp, Hermann; Parisi, Cristiana; Bridgeman, Alfia

    This report covers the period from 1993 when the CREST project was initiated, to its launch in 1996, and considers the environment that prompted its instigation. The report looks at the massive cooperation of Government, industry and a range of different service providers that all came together......, under the central control of the CREST project team. It proposes five reasons why the CREST project was successful and examines why the CREST system continues to be at the heart of UK settlement, 20 years on....

  12. Transplanted Dental Pulp Stem Cells Migrate to Injured Area and Express Neural Markers in a Rat Model of Cerebral Ischemia.

    Science.gov (United States)

    Zhang, Xuemei; Zhou, Yinglian; Li, Hulun; Wang, Rui; Yang, Dan; Li, Bing; Cao, Xiaofang; Fu, Jin

    2018-01-01

    Ischemic stroke is a major cause of disability and mortality worldwide, while effective restorative treatments are limited at present. Stem cell transplantation holds therapeutic potential for ischemic vascular diseases and may provide an opportunity for neural regeneration. Dental pulp stem cells (DPSCs) origin from neural crest and have neuro-ectodermal features including proliferation and multilineage differentiation potentials. The rat model of middle cerebral artery occlusion (MCAO) was used to evaluate whether intravenous administration of DPSCs can reduce infarct size and to estimate the migration and trans-differentiation into neuron-like cells in focal cerebral ischemia models. Brain tissues were collected at 4 weeks following cell transplantation and analyzed with immunofluorescence, immunohistochemistry and real-time polymerase chain reaction (RT-PCR) methods. Intravenously administration of rat-derived DPSCs were found to migrate into the boundary of ischemic areas and expressed neural specific markers, reducing infarct volume and cerebral edema. These results suggest that DPSCs treatment may serve as a potential therapy for clinical stroke patients in the future. © 2018 The Author(s). Published by S. Karger AG, Basel.

  13. Mef2c-F10N enhancer driven β-galactosidase (LacZ) and Cre recombinase mice facilitate analyses of gene function and lineage fate in neural crest cells.

    Science.gov (United States)

    Aoto, Kazushi; Sandell, Lisa L; Butler Tjaden, Naomi E; Yuen, Kobe C; Watt, Kristin E Noack; Black, Brian L; Durnin, Michael; Trainor, Paul A

    2015-06-01

    Neural crest cells (NCC) comprise a multipotent, migratory stem cell and progenitor population that gives rise to numerous cell and tissue types within a developing embryo, including craniofacial bone and cartilage, neurons and glia of the peripheral nervous system, and melanocytes within the skin. Here we describe two novel stable transgenic mouse lines suitable for lineage tracing and analysis of gene function in NCC. Firstly, using the F10N enhancer of the Mef2c gene (Mef2c-F10N) linked to LacZ, we generated transgenic mice (Mef2c-F10N-LacZ) that express LacZ in the majority, if not all migrating NCC that delaminate from the neural tube. Mef2c-F10N-LacZ then continues to be expressed primarily in neurogenic, gliogenic and melanocytic NCC and their derivatives, but not in ectomesenchymal derivatives. Secondly, we used the same Mef2c-F10N enhancer together with Cre recombinase to generate transgenic mice (Mef2c-F10N-Cre) that can be used to indelibly label, or alter gene function in, migrating NCC and their derivatives. At early stages of development, Mef2c-F10N-LacZ and Mef2c-F10N-Cre label NCC in a pattern similar to Wnt1-Cre mice, with the exception that Mef2c-F10N-LacZ and Mef2c-F10N-Cre specifically label NCC that have delaminated from the neural plate, while premigratory NCC are not labeled. Thus, our Mef2c-F10N-LacZ and Mef2c-F10N-Cre transgenic mice provide new resources for tracing migratory NCC and analyzing gene function in migrating and differentiating NCC independently of NCC formation. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. The Effects of Epidermal Neural Crest Stem Cells on Local Inflammation Microenvironment in the Defected Sciatic Nerve of Rats

    Directory of Open Access Journals (Sweden)

    Yue Li

    2017-05-01

    Full Text Available Cell-based therapy is a promising strategy for the repair of peripheral nerve injuries (PNIs. epidermal neural crest stems cells (EPI-NCSCs are thought to be important donor cells for repairing PNI in different animal models. Following PNI, inflammatory response is important to regulate the repair process. However, the effects of EPI-NCSCs on regulation of local inflammation microenviroment have not been investigated extensively. In the present study, these effects were studied by using 10 mm defected sciatic nerve, which was bridged with 15 mm artificial nerve composed of EPI-NCSCs, extracellular matrix (ECM and poly (lactide-co-glycolide (PLGA. Then the expression of pro- and anti-inflammatory cytokines, polarization of macrophages, regulation of fibroblasts and shwann cells (SCs were assessed by western blot, immunohistochemistry, immunofluorescence staining at 1, 3, 7 and 21 days after bridging. The structure and the function of the bridged nerve were determined by observation under light microscope and by examination of right lateral foot retraction time (LFRT, sciatic function index (SFI, gastrocnemius wet weight and electrophysiology at 9 weeks. After bridging with EPI-NCSCs, the expression of anti-inflammatory cytokines (IL-4 and IL-13 was increased, but decreased for pro-inflammatory cytokines (IL-6 and TNF-α compared to the control bridging, which was consistent with increase of M2 macrophages and decrease of M1 macrophages at 7 days after transplantation. Likewise, myelin-formed SCs were significantly increased, but decreased for the activated fibroblasts in their number at 21 days. The recovery of structure and function of nerve bridged with EPI-NCSCs was significantly superior to that of DMEM. These results indicated that EPI-NCSCs could be able to regulate and provide more suitable inflammation microenvironment for the repair of defected sciatic nerve.

  15. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo.

    Science.gov (United States)

    Barriga, Elias H; Franze, Kristian; Charras, Guillaume; Mayor, Roberto

    2018-02-22

    Collective cell migration is essential for morphogenesis, tissue remodelling and cancer invasion. In vivo, groups of cells move in an orchestrated way through tissues. This movement involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in collective cell migration is comparatively well understood, how tissue mechanics influence collective cell migration in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion. We found that, during morphogenesis, the head mesoderm underlying the cephalic neural crest stiffens. This stiffening initiates an epithelial-to-mesenchymal transition in neural crest cells and triggers their collective migration. To detect changes in their mechanical environment, neural crest cells use mechanosensation mediated by the integrin-vinculin-talin complex. By performing mechanical and molecular manipulations, we show that mesoderm stiffening is necessary and sufficient to trigger neural crest migration. Finally, we demonstrate that convergent extension of the mesoderm, which starts during gastrulation, leads to increased mesoderm stiffness by increasing the cell density underneath the neural crest. These results show that convergent extension of the mesoderm has a role as a mechanical coordinator of morphogenesis, and reveal a link between two apparently unconnected processes-gastrulation and neural crest migration-via changes in tissue mechanics. Overall, we demonstrate that changes in substrate stiffness can trigger collective cell migration by promoting epithelial-to-mesenchymal transition in vivo. More broadly, our results raise the idea that tissue mechanics combines with molecular effectors to coordinate morphogenesis.

  16. Crest syndrome

    International Nuclear Information System (INIS)

    Koch, B.; Roedl, W.

    1988-01-01

    If a patient has peri- and intra-articular calcinosis, as well as acro-osteolysis and esophageal hypomotility, and rheumatic symptoms, Crest syndrome should be considered as a manifestation of progressive systemic sclerosis. In connection with relevant symptoms on the skin and visceral involvement, radiological studies offer the possibility of classifying progressive systemic sclerosis more accurately. (orig.) [de

  17. Progress of research on cytoskeleton and neural cell migration obstacle induced by ionizing radiation

    International Nuclear Information System (INIS)

    Qiu Jun; Wu Cuiping; Wang Mingming

    2012-01-01

    The dynamic changes of the microtubules and microfilaments provide the main force that drives the normal migration. Biological effects in tissues and cells induced by ionizing radiation are closely correlated with the changes happening to the cytoskeleton. It is that the ionizing radiation can induce the depolymeration of microfilaments and the assembly obstacles of microtubules, and make neural cell incapable of entering the model of migration or abnormally migrate. The effects of relevant changes of the cytoskeleton induced by irradiation on neural cell migration were discussed in this paper. (authors)

  18. Dataset of TWIST1-regulated genes in the cranial mesoderm and a transcriptome comparison of cranial mesoderm and cranial neural crest

    Directory of Open Access Journals (Sweden)

    Heidi Bildsoe

    2016-12-01

    Full Text Available This article contains data related to the research article entitled “Transcriptional targets of TWIST1 in the cranial mesoderm regulate cell-matrix interactions and mesenchyme maintenance” by Bildsoe et al. (2016 [1]. The data presented here are derived from: (1 a microarray-based comparison of sorted cranial mesoderm (CM and cranial neural crest (CNC cells from E9.5 mouse embryos; (2 comparisons of transcription profiles of head tissues from mouse embryos with a CM-specific loss-of-function of Twist1 and control mouse embryos collected at E8.5 and E9.5; (3 ChIP-seq using a TWIST1-specific monoclonal antibody with chromatin extracts from TWIST1-expressing MDCK cells, a model for a TWIST1-dependent mesenchymal state.

  19. In vitro cementoblast-like differentiation of postmigratory neural crest-derived p75{sup +} stem cells with dental follicle cell conditioned medium

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Xiujie; Liu, Luchuan; Deng, Manjing; Liu, Rui; Zhang, Li; Nie, Xin, E-mail: dr.xinnie@gmail.com

    2015-09-10

    Cranial neural crest-derived cells (CNCCs) play important role in epithelial–mesenchymal interactions during tooth morphogenesis. However, the heterogeneity of CNCCs and their tendency to spontaneously differentiate along smooth muscle or osteoblast lineages in vitro limit further understanding of their biological properties. We studied the differentiation properties of isolated rat embryonic postmigratory CNCCs, expressing p75 neurotrophin receptor (p75NTR). These p75NTR positive (p75{sup +}) CNCCs, isolated using fluorescence activated cell sorter, exhibited fibroblast-like morphology and characteristics of mesenchymal stem cells. Incubation of p75{sup +} CNCCs in dental follicle cell conditioned medium (DFCCM) combined with dentin non-collagenous proteins (dNCPs), altered their morphological features to cementoblast-like appearance. These cells also showed low proliferative activity, high ALP activity and significantly increased calcified nodule formation. Markers related to mineralization or specific to cementoblast lineage were highly expressed in dNCPs/DFCCM-treated p75{sup +} cells, suggesting their differentiation along cementoblast-like lineage. p75{sup +} stem cells selected from postmigratory CNCCs represent a pure stem cell population and could be used as a stem cell model for in vitro studies due to their intrinsic ability to differentiate to neuronal cells and transform from neuroectoderm to ectomesenchyme. They can provide a potential stem cell resource for tooth engineering studies and help to further investigate mechanisms of epithelial–mesenchymal interactions in tooth morphogenesis. - Highlights: • Cranial neural crest-derived cells (CNCCs) take part in tooth morphogenesis. • positive (p75{sup +}) CNCCs are fibroblast-like and resemble mesenchymal stem cells. • p75{sup +} CNCCs in dental follicle cell medium (DFCCM/dNCP) appear like cementoblasts. • DFCCM/dNCP-treated p75{sup +} cells express cementoblast specific mineralization

  20. In vitro cementoblast-like differentiation of postmigratory neural crest-derived p75+ stem cells with dental follicle cell conditioned medium

    International Nuclear Information System (INIS)

    Wen, Xiujie; Liu, Luchuan; Deng, Manjing; Liu, Rui; Zhang, Li; Nie, Xin

    2015-01-01

    Cranial neural crest-derived cells (CNCCs) play important role in epithelial–mesenchymal interactions during tooth morphogenesis. However, the heterogeneity of CNCCs and their tendency to spontaneously differentiate along smooth muscle or osteoblast lineages in vitro limit further understanding of their biological properties. We studied the differentiation properties of isolated rat embryonic postmigratory CNCCs, expressing p75 neurotrophin receptor (p75NTR). These p75NTR positive (p75 + ) CNCCs, isolated using fluorescence activated cell sorter, exhibited fibroblast-like morphology and characteristics of mesenchymal stem cells. Incubation of p75 + CNCCs in dental follicle cell conditioned medium (DFCCM) combined with dentin non-collagenous proteins (dNCPs), altered their morphological features to cementoblast-like appearance. These cells also showed low proliferative activity, high ALP activity and significantly increased calcified nodule formation. Markers related to mineralization or specific to cementoblast lineage were highly expressed in dNCPs/DFCCM-treated p75 + cells, suggesting their differentiation along cementoblast-like lineage. p75 + stem cells selected from postmigratory CNCCs represent a pure stem cell population and could be used as a stem cell model for in vitro studies due to their intrinsic ability to differentiate to neuronal cells and transform from neuroectoderm to ectomesenchyme. They can provide a potential stem cell resource for tooth engineering studies and help to further investigate mechanisms of epithelial–mesenchymal interactions in tooth morphogenesis. - Highlights: • Cranial neural crest-derived cells (CNCCs) take part in tooth morphogenesis. • positive (p75 + ) CNCCs are fibroblast-like and resemble mesenchymal stem cells. • p75 + CNCCs in dental follicle cell medium (DFCCM/dNCP) appear like cementoblasts. • DFCCM/dNCP-treated p75 + cells express cementoblast specific mineralization markers. • p75 + cells are pure stem

  1. Correction of Hirschsprung-Associated Mutations in Human Induced Pluripotent Stem Cells Via Clustered Regularly Interspaced Short Palindromic Repeats/Cas9, Restores Neural Crest Cell Function.

    Science.gov (United States)

    Lai, Frank Pui-Ling; Lau, Sin-Ting; Wong, John Kwong-Leong; Gui, Hongsheng; Wang, Reeson Xu; Zhou, Tingwen; Lai, Wing Hon; Tse, Hung-Fat; Tam, Paul Kwong-Hang; Garcia-Barcelo, Maria-Mercedes; Ngan, Elly Sau-Wai

    2017-07-01

    Hirschsprung disease is caused by failure of enteric neural crest cells (ENCCs) to fully colonize the bowel, leading to bowel obstruction and megacolon. Heterozygous mutations in the coding region of the RET gene cause a severe form of Hirschsprung disease (total colonic aganglionosis). However, 80% of HSCR patients have short-segment Hirschsprung disease (S-HSCR), which has not been associated with genetic factors. We sought to identify mutations associated with S-HSCR, and used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system to determine how mutations affect ENCC function. We created induced pluripotent stem cell (iPSC) lines from 1 patient with total colonic aganglionosis (with the G731del mutation in RET) and from 2 patients with S-HSCR (without a RET mutation), as well as RET +/- and RET -/- iPSCs. IMR90-iPSC cells were used as the control cell line. Migration and differentiation capacities of iPSC-derived ENCCs were analyzed in differentiation and migration assays. We searched for mutation(s) associated with S-HSCR by combining genetic and transcriptome data from patient blood- and iPSC-derived ENCCs, respectively. Mutations in the iPSCs were corrected using the CRISPR/Cas9 system. ENCCs derived from all iPSC lines, but not control iPSCs, had defects in migration and neuronal lineage differentiation. RET mutations were associated with differentiation and migration defects of ENCCs in vitro. Genetic and transcriptome analyses associated a mutation in the vinculin gene (VCL M209L) with S-HSCR. CRISPR/Cas9 correction of the RET G731del and VCL M209L mutations in iPSCs restored the differentiation and migration capacities of ENCCs. We identified mutations in VCL associated with S-HSCR. Correction of this mutation in iPSC using CRISPR/Cas9 editing, as well as the RET G731del mutation that causes Hirschsprung disease with total colonic aganglionosis, restored ENCC function. Our study demonstrates how human iPSCs can

  2. EGF–FGF{sub 2} stimulates the proliferation and improves the neuronal commitment of mouse epidermal neural crest stem cells (EPI-NCSCs)

    Energy Technology Data Exchange (ETDEWEB)

    Bressan, Raul Bardini; Melo, Fernanda Rosene; Almeida, Patricia Alves; Bittencourt, Denise Avani; Visoni, Silvia; Jeremias, Talita Silva [Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário – Trindade, 88040-900 Florianópolis SC (Brazil); Costa, Ana Paula; Leal, Rodrigo Bainy [Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário – Trindade, 88040-900 Florianópolis SC (Brazil); Trentin, Andrea Gonçalves, E-mail: andrea.trentin@ufsc.br [Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário – Trindade, 88040-900 Florianópolis SC (Brazil)

    2014-09-10

    Epidermal neural crest stem cells (EPI-NCSCs), which reside in the bulge of hair follicles, are attractive candidates for several applications in cell therapy, drug screening and tissue engineering. As suggested remnants of the embryonic neural crest (NC) in an adult location, EPI-NCSCs are able to generate a wide variety of cell types and are readily accessible by a minimally invasive procedure. Since the combination of epidermal growth factor (EGF) and fibroblast growth factor type 2 (FGF{sub 2}) is mitogenic and promotes the neuronal commitment of various stem cell populations, we examined its effects in the proliferation and neuronal potential of mouse EPI-NCSCs. By using a recognized culture protocol of bulge whiskers follicles, we were able to isolate a population of EPI-NCSCs, characterized by the migratory potential, cell morphology and expression of phenotypic markers of NC cells. EPI-NCSCs expressed neuronal, glial and smooth muscle markers and exhibited the NC-like fibroblastic morphology. The treatment with the combination EGF and FGF{sub 2}, however, increased their proliferation rate and promoted the acquisition of a neuronal-like morphology accompanied by reorganization of neural cytoskeletal proteins βIII-tubulin and nestin, as well as upregulation of the pan neuronal marker βIII-tubulin and down regulation of the undifferentiated NC, glial and smooth muscle cell markers. Moreover, the treatment enhanced the response of EPI-NCSCs to neurogenic stimulation, as evidenced by induction of GAP43, and increased expression of Mash-1 in neuron-like cell, both neuronal-specific proteins. Together, the results suggest that the combination of EGF–FGF2 stimulates the proliferation and improves the neuronal potential of EPI-NCSCs similarly to embryonic NC cells, ES cells and neural progenitor/stem cells of the central nervous system and highlights the advantage of using EGF–FGF{sub 2} in neuronal differentiation protocols. - Highlights: • EPI

  3. EGF–FGF2 stimulates the proliferation and improves the neuronal commitment of mouse epidermal neural crest stem cells (EPI-NCSCs)

    International Nuclear Information System (INIS)

    Bressan, Raul Bardini; Melo, Fernanda Rosene; Almeida, Patricia Alves; Bittencourt, Denise Avani; Visoni, Silvia; Jeremias, Talita Silva; Costa, Ana Paula; Leal, Rodrigo Bainy; Trentin, Andrea Gonçalves

    2014-01-01

    Epidermal neural crest stem cells (EPI-NCSCs), which reside in the bulge of hair follicles, are attractive candidates for several applications in cell therapy, drug screening and tissue engineering. As suggested remnants of the embryonic neural crest (NC) in an adult location, EPI-NCSCs are able to generate a wide variety of cell types and are readily accessible by a minimally invasive procedure. Since the combination of epidermal growth factor (EGF) and fibroblast growth factor type 2 (FGF 2 ) is mitogenic and promotes the neuronal commitment of various stem cell populations, we examined its effects in the proliferation and neuronal potential of mouse EPI-NCSCs. By using a recognized culture protocol of bulge whiskers follicles, we were able to isolate a population of EPI-NCSCs, characterized by the migratory potential, cell morphology and expression of phenotypic markers of NC cells. EPI-NCSCs expressed neuronal, glial and smooth muscle markers and exhibited the NC-like fibroblastic morphology. The treatment with the combination EGF and FGF 2 , however, increased their proliferation rate and promoted the acquisition of a neuronal-like morphology accompanied by reorganization of neural cytoskeletal proteins βIII-tubulin and nestin, as well as upregulation of the pan neuronal marker βIII-tubulin and down regulation of the undifferentiated NC, glial and smooth muscle cell markers. Moreover, the treatment enhanced the response of EPI-NCSCs to neurogenic stimulation, as evidenced by induction of GAP43, and increased expression of Mash-1 in neuron-like cell, both neuronal-specific proteins. Together, the results suggest that the combination of EGF–FGF2 stimulates the proliferation and improves the neuronal potential of EPI-NCSCs similarly to embryonic NC cells, ES cells and neural progenitor/stem cells of the central nervous system and highlights the advantage of using EGF–FGF 2 in neuronal differentiation protocols. - Highlights: • EPI-NCSCs express

  4. ERK-dependent and -independent pathways trigger human neural progenitor cell migration

    International Nuclear Information System (INIS)

    Moors, Michaela; Cline, Jason E.; Abel, Josef; Fritsche, Ellen

    2007-01-01

    Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2 phosphorylation and inhibited cell migration. We identified protein kinase C (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases governing ERK1/2 activation, thereby controlling NHNP cell migration. Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways

  5. Effect of low dose 131I-MIBG therapy in metastatic neural crest tumors: Evaluation by RECIST and quality of life questionnaire

    International Nuclear Information System (INIS)

    Basu, S.; Joseph, J.K.

    2004-01-01

    Full text: The primary aim of 131I-MIBG therapy in advanced metastatic or recurrent neural crest tumors is palliation i.e. disease control and improvement of health related quality of life. No clear guidelines regarding the dosage and schedule of 131I-MIBG therapy in neural crest tumors exist at present. In general, a fixed dose of 100-300 mCi has been suggested for each therapy. We share our experience of 131I-MIBG therapy in various subgroups of neural crest tumors and discuss the response assessed by the RECIST and the quality of life questionnaire. A total number of 14 patients were treated with indigenously produced 131I-MIBG, which was administered as continuous intravenous infusion over a period of 2-4 hours. Patient isolation according to guidelines set by the national regulatory authority and thyroid blockade with Lugol's iodide were strictly adhered to. Antihypertensive measures were undertaken in case of pheochromocytoma and paraganglioma to prevent effects of catecholamine release during or following 131I-MIBG infusion. The primaries included neuroblastoma (n=7), pheochromocytoma (n=5) and paraganglioma (n=2). The cases of neuroblastoma included patients with progressive disease where the conventional chemotherapy had failed, while those of pheochromocytoma and paraganglioma were cases with recurrent / metastatic disease following surgery. In cases of multiple therapies, the minimum interval between two consecutive therapies was 12 weeks. Regular renal and haematological profiles were monitored in all the cases. Response to therapy was assessed by RECIST. The findings of 131I-MIBG scintigraphy were incorporated with CT scan in assessing the target lesions. Biochemical response was evaluated by 24 hours urinary VMA estimation. The quality of life status was evaluated by the conventional questionnaire. A total of 27 therapies were administered in 14 patients. In five treated cases of pheochromocytoma, three received multiple therapies. Follow up results

  6. Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects

    Science.gov (United States)

    Nie, Xuguang; Deng, Chu-xia; Wang, Qin; Jiao, Kai

    2008-01-01

    TGFβ/BMP signaling pathways are essential for normal development of neural crest cells (NCCs). Smad4 encodes the only common Smad protein in mammals, which is a critical nuclear mediator of TGFβ/BMP signaling. In this work, we sought to investigate the roles of Smad4 for development of NCCs. To overcome the early embryonic lethality of Smad4 null mice, we specifically disrupted Smad4 in NCCs using a Cre/loxP system. The mutant mice died at mid-gestation with defects in facial primordia, pharyngeal arches, outflow tract and cardiac ventricles. Further examination revealed that mutant embryos displayed severe molecular defects starting from E9.5. Expression of multiple genes, including Msx1, 2, Ap-2α, Pax3, and Sox9, which play critical roles for NCC development, was downregulated by NCC disruption of Smad4. Moreover, increased cell death was observed in pharyngeal arches from E10.5. However, the cell proliferation rate in these areas was not substantially altered. Taken together, these findings provide compelling genetic evidence that Smad4-mediated activities of TGFβ/BMP signals are essential for appropriate NCC development. PMID:18334251

  7. FGF8 signaling sustains progenitor status and multipotency of cranial neural crest-derived mesenchymal cells in vivo and in vitro

    Science.gov (United States)

    Shao, Meiying; Liu, Chao; Song, Yingnan; Ye, Wenduo; He, Wei; Yuan, Guohua; Gu, Shuping; Lin, Congxin; Ma, Liang; Zhang, Yanding; Tian, Weidong; Hu, Tao; Chen, YiPing

    2015-01-01

    The cranial neural crest (CNC) cells play a vital role in craniofacial development and regeneration. They are multi-potent progenitors, being able to differentiate into various types of tissues. Both pre-migratory and post-migratory CNC cells are plastic, taking on diverse fates by responding to different inductive signals. However, what sustains the multipotency of CNC cells and derivatives remains largely unknown. In this study, we present evidence that FGF8 signaling is able to sustain progenitor status and multipotency of CNC-derived mesenchymal cells both in vivo and in vitro. We show that augmented FGF8 signaling in pre-migratory CNC cells prevents cell differentiation and organogenesis in the craniofacial region by maintaining their progenitor status. CNC-derived mesenchymal cells with Fgf8 overexpression or control cells in the presence of exogenous FGF8 exhibit prolonged survival, proliferation, and multi-potent differentiation capability in cell cultures. Remarkably, exogenous FGF8 also sustains the capability of CNC-derived mesenchymal cells to participate in organogenesis such as odontogenesis. Furthermore, FGF8-mediated signaling strongly promotes adipogenesis but inhibits osteogenesis of CNC-derived mesenchymal cells in vitro. Our results reveal a specific role for FGF8 in the maintenance of progenitor status and in fate determination of CNC cells, implicating a potential application in expansion and fate manipulation of CNC-derived cells in stem cell-based craniofacial regeneration. PMID:26243590

  8. Lack of the central nervous system- and neural crest-expressed forkhead gene Foxs1 affects motor function and body weight.

    Science.gov (United States)

    Heglind, Mikael; Cederberg, Anna; Aquino, Jorge; Lucas, Guilherme; Ernfors, Patrik; Enerbäck, Sven

    2005-07-01

    To gain insight into the expression pattern and functional importance of the forkhead transcription factor Foxs1, we constructed a Foxs1-beta-galactosidase reporter gene "knock-in" (Foxs1beta-gal/beta-gal) mouse, in which the wild-type (wt) Foxs1 allele has been inactivated and replaced by a beta-galactosidase reporter gene. Staining for beta-galactosidase activity reveals an expression pattern encompassing neural crest-derived cells, e.g., cranial and dorsal root ganglia as well as several other cell populations in the central nervous system (CNS), most prominently the internal granule layer of cerebellum. Other sites of expression include the lachrymal gland, outer nuclear layer of retina, enteric ganglion neurons, and a subset of thalamic and hypothalamic nuclei. In the CNS, blood vessel-associated smooth muscle cells and pericytes stain positive for Foxs1. Foxs1beta-gal/beta-gal mice perform significantly better (P fat diet, and we speculate that dorsomedial hypothalamic neurons, expressing Foxs1, could play a role in regulating body weight via regulation of sympathetic outflow. In support of this, we observed increased levels of uncoupling protein 1 mRNA in Foxs1beta-gal/beta-gal mice. This points toward a role for Foxs1 in the integration and processing of neuronal signals of importance for energy turnover and motor function.

  9. Renal excretion of iodine-131 labelled meta-iodobenzylguanidine and metabolites after therapeutic doses in patients suffering from different neural crest-derived tumours

    International Nuclear Information System (INIS)

    Wafelman, A.R.; Hoefnagel, C.A.; Maessen, H.J.M.; Maes, R.A.A.; Beijnen, J.H.

    1997-01-01

    Iodine-131 labelled meta-iodobenzylguanidine ([ 131 I[MIBG) is used for diagnostic scintigraphy and radionuclide therapy of neural crest-derived tumours. After administration of therapeutic doses of [ 131 I[MIBG (3.1-7.5 GBq) to 17 patients (n=32 courses), aged 2-73 years, 56%±10%, 73%±11%, 80%±10% and 83%±10% of the dose was cumulatively excreted as total radioactivity in urine at t=24 h, 48 h, 72 h and 96 h, respectively. Except for two adult patients, who showed excretion of 14%-18% of [ 131 I[meta-iodohippuric acid ([ 131 I[MIHA), the cumulatively excreted radioactivity consisted of >85% [ 131 I[MIBG, with 6% of the dose excreted as free [ 131 I[iodide, 4% as [ 131 I[MIHA and 2.5% as an unknown iodine-131 labelled metabolite. Cumulative renal excretion rates of total radioactivity and of [ 131 I[MIBG appeared to be higher in neuroblastoma and phaeochromocytoma patients than in carcinoid patients. Based on the excretion of small amounts of [ 131 I[meta-iodobenzoic acid in two patients, a possible metabolic pathway for [ 131 I[MIBG is suggested. The degree of metabolism was not related to the extent of liver uptake of radioactivity. (orig.). With 2 figs., 5 tabs

  10. Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development.

    Science.gov (United States)

    Guerrero-Cazares, Hugo; Lavell, Emily; Chen, Linda; Schiapparelli, Paula; Lara-Velazquez, Montserrat; Capilla-Gonzalez, Vivian; Clements, Anna Christina; Drummond, Gabrielle; Noiman, Liron; Thaler, Katrina; Burke, Anne; Quiñones-Hinojosa, Alfredo

    2017-07-01

    Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860-1865. © 2017 AlphaMed Press.

  11. Artificial neural network models' application for radioactive substances' migration forecasting in soil

    International Nuclear Information System (INIS)

    Kovalenko, V.I.; Khil'ko, O.S.; Kundas, S.P.

    2009-01-01

    The work is indicated to the use of artificial neural network (ANN) models in program complex SPS for radioactive substances' migration forecasting in soil. For the problem solution two ANN models are used. One of them forecasts radioactive substances' migration, another carries out forecasting of physical and chemical soil properties. Program complex SPS allows to achieve a low error of forecasting (no more than 5 %) and high training speed. (authors)

  12. MRI visualization of endogenous neural progenitor cell migration along the RMS in the adult mouse brain

    DEFF Research Database (Denmark)

    Vreys, Ruth; Vande Velde, Greetje; Krylychkina, Olga

    2010-01-01

    The adult rodent brain contains neural progenitor cells (NPCs), generated in the subventricular zone (SVZ), which migrate along the rostral migratory stream (RMS) towards the olfactory bulb (OB) where they differentiate into neurons. The aim of this study was to visualize endogenous NPC migration...... by a longitudinal MRI study and validated with histology. Here, we visualized endogenous NPC migration in the mouse brain by in vivo MRI and demonstrated accumulation of MPIO-labeled NPCs in the OB over time with ex vivo MRI. Furthermore, we investigated the influence of in situ injection of MPIOs on adult...

  13. Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media.

    Directory of Open Access Journals (Sweden)

    Makoto Fukuta

    Full Text Available Neural crest cells (NCCs are an embryonic migratory cell population with the ability to differentiate into a wide variety of cell types that contribute to the craniofacial skeleton, cornea, peripheral nervous system, and skin pigmentation. This ability suggests the promising role of NCCs as a source for cell-based therapy. Although several methods have been used to induce human NCCs (hNCCs from human pluripotent stem cells (hPSCs, such as embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs, further modifications are required to improve the robustness, efficacy, and simplicity of these methods. Chemically defined medium (CDM was used as the basal medium in the induction and maintenance steps. By optimizing the culture conditions, the combination of the GSK3β inhibitor and TGFβ inhibitor with a minimum growth factor (insulin very efficiently induced hNCCs (70-80% from hPSCs. The induced hNCCs expressed cranial NCC-related genes and stably proliferated in CDM supplemented with EGF and FGF2 up to at least 10 passages without changes being observed in the major gene expression profiles. Differentiation properties were confirmed for peripheral neurons, glia, melanocytes, and corneal endothelial cells. In addition, cells with differentiation characteristics similar to multipotent mesenchymal stromal cells (MSCs were induced from hNCCs using CDM specific for human MSCs. Our simple and robust induction protocol using small molecule compounds with defined media enabled the generation of hNCCs as an intermediate material producing terminally differentiated cells for cell-based innovative medicine.

  14. Hyperexpressed netrin-1promoted neural stem cells migration in mice after focal cerebral ischemia

    OpenAIRE

    Haiyan Lu; Xiaoyan Song; Feng Wang; Guodong Wang; Yuncheng Wu; Qiaoshu Wang; Yongting Wang; Guoyuan Yang; Zhijun Zhang

    2016-01-01

    Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explored whether NT-1 can be steadily overexpressed by adeno-associated virus (AAV) and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with AAV carrying NT-1 gene (AAV-NT-1). Mice underwent ...

  15. MANF Promotes Differentiation and Migration of Neural Progenitor Cells with Potential Neural Regenerative Effects in Stroke

    DEFF Research Database (Denmark)

    Tseng, Kuan-Yin; Anttila, Jenni E; Khodosevich, Konstantin

    2018-01-01

    die shortly after injury or are unable to arrive at the infarct boundary. In this study, we demonstrate for the first time that endogenous mesencephalic astrocyte-derived neurotrophic factor (MANF) protects NSCs against oxygen-glucose-deprivation-induced injury and has a crucial role in regulating NPC...... migration. In NSC cultures, MANF protein administration did not affect growth of cells but triggered neuronal and glial differentiation, followed by activation of STAT3. In SVZ explants, MANF overexpression facilitated cell migration and activated the STAT3 and ERK1/2 pathway. Using a rat model of cortical...... stroke, intracerebroventricular injections of MANF did not affect cell proliferation in the SVZ, but promoted migration of doublecortin (DCX)+ cells toward the corpus callosum and infarct boundary on day 14 post-stroke. Long-term infusion of MANF into the peri-infarct zone increased the recruitment...

  16. Global detection of live virtual machine migration based on cellular neural networks.

    Science.gov (United States)

    Xie, Kang; Yang, Yixian; Zhang, Ling; Jing, Maohua; Xin, Yang; Li, Zhongxian

    2014-01-01

    In order to meet the demands of operation monitoring of large scale, autoscaling, and heterogeneous virtual resources in the existing cloud computing, a new method of live virtual machine (VM) migration detection algorithm based on the cellular neural networks (CNNs), is presented. Through analyzing the detection process, the parameter relationship of CNN is mapped as an optimization problem, in which improved particle swarm optimization algorithm based on bubble sort is used to solve the problem. Experimental results demonstrate that the proposed method can display the VM migration processing intuitively. Compared with the best fit heuristic algorithm, this approach reduces the processing time, and emerging evidence has indicated that this new approach is affordable to parallelism and analog very large scale integration (VLSI) implementation allowing the VM migration detection to be performed better.

  17. Global Detection of Live Virtual Machine Migration Based on Cellular Neural Networks

    Directory of Open Access Journals (Sweden)

    Kang Xie

    2014-01-01

    Full Text Available In order to meet the demands of operation monitoring of large scale, autoscaling, and heterogeneous virtual resources in the existing cloud computing, a new method of live virtual machine (VM migration detection algorithm based on the cellular neural networks (CNNs, is presented. Through analyzing the detection process, the parameter relationship of CNN is mapped as an optimization problem, in which improved particle swarm optimization algorithm based on bubble sort is used to solve the problem. Experimental results demonstrate that the proposed method can display the VM migration processing intuitively. Compared with the best fit heuristic algorithm, this approach reduces the processing time, and emerging evidence has indicated that this new approach is affordable to parallelism and analog very large scale integration (VLSI implementation allowing the VM migration detection to be performed better.

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

    Directory of Open Access Journals (Sweden)

    I-Chen Li

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

  19. Lesion-induced increase in survival and migration of human neural progenitor cells releasing GDNF

    Science.gov (United States)

    Behrstock, Soshana; Ebert, Allison D.; Klein, Sandra; Schmitt, Melanie; Moore, Jeannette M.; Svendsen, Clive N.

    2009-01-01

    The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson’s and Huntington’s disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line derived neurotrophic factor (hNPCGDNF) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington’s model) with indirect lesions of the dopamine system (Parkinson’s model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases. PMID:19044202

  20. Adult subependymal neural precursors, but not differentiated cells, undergo rapid cathodal migration in the presence of direct current electric fields.

    Directory of Open Access Journals (Sweden)

    Robart Babona-Pilipos

    Full Text Available BACKGROUND: The existence of neural stem and progenitor cells (together termed neural precursor cells in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke. METHODS AND FINDINGS: With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour. CONCLUSIONS: These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma.

  1. A career at the interface of cell and developmental biology: a view from the crest.

    Science.gov (United States)

    Bronner, Marianne E

    2012-11-01

    Just as neural crest cells migrate great distances through the embryo, my journey has taken me from a childhood in a distant land to a career as a biologist. My mentoring relationships have shaped not only the careers of my trainees, but also the trajectory of my own science. One of the most satisfying aspects of mentoring comes from helping to empower the next generation of scientists to do more tomorrow than is possible today. This, together with a passion for discovery and learning new things, motivates me and makes science such a rewarding career.

  2. EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex.

    Science.gov (United States)

    Kanemitsu, Michiko; Tsupykov, Oleg; Potter, Gaël; Boitard, Michael; Salmon, Patrick; Zgraggen, Eloisa; Gascon, Eduardo; Skibo, Galina; Dayer, Alexandre G; Kiss, Jozsef Z

    2017-11-01

    Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system. We found that EMMPRIN-transduced progenitors exhibited enhanced MMP-2 activity in vitro and showed improved motility in 3D collagen gel as well as in cortical slices. Using a rat model of neonatal ischemia, we showed that EMMPRIN overexpressing SVZ cells invade the injured cortical tissue more efficiently than controls. Our results suggest that EMMPRIN overexpression could be suitable approach to improve capacities of endogenous or transplanted progenitors to invade the injured cortex. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Multidisciplinary approaches to understanding collective cell migration in developmental biology.

    Science.gov (United States)

    Schumacher, Linus J; Kulesa, Paul M; McLennan, Rebecca; Baker, Ruth E; Maini, Philip K

    2016-06-01

    Mathematical models are becoming increasingly integrated with experimental efforts in the study of biological systems. Collective cell migration in developmental biology is a particularly fruitful application area for the development of theoretical models to predict the behaviour of complex multicellular systems with many interacting parts. In this context, mathematical models provide a tool to assess the consistency of experimental observations with testable mechanistic hypotheses. In this review, we showcase examples from recent years of multidisciplinary investigations of neural crest cell migration. The neural crest model system has been used to study how collective migration of cell populations is shaped by cell-cell interactions, cell-environmental interactions and heterogeneity between cells. The wide range of emergent behaviours exhibited by neural crest cells in different embryonal locations and in different organisms helps us chart out the spectrum of collective cell migration. At the same time, this diversity in migratory characteristics highlights the need to reconcile or unify the array of currently hypothesized mechanisms through the next generation of experimental data and generalized theoretical descriptions. © 2016 The Authors.

  4. Upregulation of the Nr2f1-A830082K12Rik gene pair in murine neural crest cells results in a complex phenotype reminiscent of Waardenburg syndrome type 4.

    Science.gov (United States)

    Bergeron, Karl-F; Nguyen, Chloé M A; Cardinal, Tatiana; Charrier, Baptiste; Silversides, David W; Pilon, Nicolas

    2016-11-01

    Waardenburg syndrome is a neurocristopathy characterized by a combination of skin and hair depigmentation, and inner ear defects. In the type 4 form, these defects show comorbidity with Hirschsprung disease, a disorder marked by an absence of neural ganglia in the distal colon, triggering functional intestinal obstruction. Here, we report that the Spot mouse line - obtained through an insertional mutagenesis screen for genes involved in neural crest cell (NCC) development - is a model for Waardenburg syndrome type 4. We found that the Spot insertional mutation causes overexpression of an overlapping gene pair composed of the transcription-factor-encoding Nr2f1 and the antisense long non-coding RNA A830082K12Rik in NCCs through a mechanism involving relief of repression of these genes. Consistent with the previously described role of Nr2f1 in promoting gliogenesis in the central nervous system, we further found that NCC-derived progenitors of the enteric nervous system fail to fully colonize Spot embryonic guts owing to their premature differentiation in glial cells. Taken together, our data thus identify silencer elements of the Nr2f1-A830082K12Rik gene pair as new candidate loci for Waardenburg syndrome type 4. © 2016. Published by The Company of Biologists Ltd.

  5. Upregulation of the Nr2f1-A830082K12Rik gene pair in murine neural crest cells results in a complex phenotype reminiscent of Waardenburg syndrome type 4

    Directory of Open Access Journals (Sweden)

    Karl-F. Bergeron

    2016-11-01

    Full Text Available Waardenburg syndrome is a neurocristopathy characterized by a combination of skin and hair depigmentation, and inner ear defects. In the type 4 form, these defects show comorbidity with Hirschsprung disease, a disorder marked by an absence of neural ganglia in the distal colon, triggering functional intestinal obstruction. Here, we report that the Spot mouse line – obtained through an insertional mutagenesis screen for genes involved in neural crest cell (NCC development – is a model for Waardenburg syndrome type 4. We found that the Spot insertional mutation causes overexpression of an overlapping gene pair composed of the transcription-factor-encoding Nr2f1 and the antisense long non-coding RNA A830082K12Rik in NCCs through a mechanism involving relief of repression of these genes. Consistent with the previously described role of Nr2f1 in promoting gliogenesis in the central nervous system, we further found that NCC-derived progenitors of the enteric nervous system fail to fully colonize Spot embryonic guts owing to their premature differentiation in glial cells. Taken together, our data thus identify silencer elements of the Nr2f1-A830082K12Rik gene pair as new candidate loci for Waardenburg syndrome type 4.

  6. Targeted deletion of Sox10 by Wnt1-cre defects neuronal migration and projection in the mouse inner ear.

    Directory of Open Access Journals (Sweden)

    YanYan Mao

    Full Text Available Sensory nerves of the brainstem are mostly composed of placode-derived neurons, neural crest-derived neurons and neural crest-derived Schwann cells. This mixed origin of cells has made it difficult to dissect interdependence for fiber guidance. Inner ear-derived neurons are known to connect to the brain after delayed loss of Schwann cells in ErbB2 mutants. However, the ErbB2 mutant related alterations in the ear and the brain compound interpretation of the data. We present here a new model to evaluate exclusively the effect of Schwann cell loss on inner ear innervation. Conditional deletion of the neural crest specific transcription factor, Sox10, using the rhombic lip/neural crest specific Wnt1-cre driver spares Sox10 expression in the ear. We confirm that neural crest-derived cells provide a stop signal for migrating spiral ganglion neurons. In the absence of Schwann cells, spiral ganglion neurons migrate into the center of the cochlea and even out of the ear toward the brain. Spiral ganglion neuron afferent processes reach the organ of Corti, but many afferent fibers bypass the organ of Corti to enter the lateral wall of the cochlea. In contrast to this peripheral disorganization, the central projection to cochlear nuclei is normal. Compared to ErbB2 mutants, conditional Sox10 mutants have limited cell death in spiral ganglion neurons, indicating that the absence of Schwann cells alone contributes little to the embryonic survival of neurons. These data suggest that neural crest-derived cells are dispensable for all central and some peripheral targeting of inner ear neurons. However, Schwann cells provide a stop signal for migratory spiral ganglion neurons and facilitate proper targeting of the organ of Corti by spiral ganglion afferents.

  7. Targeted Deletion of Sox10 by Wnt1-cre Defects Neuronal Migration and Projection in the Mouse Inner Ear

    Science.gov (United States)

    Mao, YanYan; Reiprich, Simone; Wegner, Michael; Fritzsch, Bernd

    2014-01-01

    Sensory nerves of the brainstem are mostly composed of placode-derived neurons, neural crest-derived neurons and neural crest-derived Schwann cells. This mixed origin of cells has made it difficult to dissect interdependence for fiber guidance. Inner ear-derived neurons are known to connect to the brain after delayed loss of Schwann cells in ErbB2 mutants. However, the ErbB2 mutant related alterations in the ear and the brain compound interpretation of the data. We present here a new model to evaluate exclusively the effect of Schwann cell loss on inner ear innervation. Conditional deletion of the neural crest specific transcription factor, Sox10, using the rhombic lip/neural crest specific Wnt1-cre driver spares Sox10 expression in the ear. We confirm that neural crest-derived cells provide a stop signal for migrating spiral ganglion neurons. In the absence of Schwann cells, spiral ganglion neurons migrate into the center of the cochlea and even out of the ear toward the brain. Spiral ganglion neuron afferent processes reach the organ of Corti, but many afferent fibers bypass the organ of Corti to enter the lateral wall of the cochlea. In contrast to this peripheral disorganization, the central projection to cochlear nuclei is normal. Compared to ErbB2 mutants, conditional Sox10 mutants have limited cell death in spiral ganglion neurons, indicating that the absence of Schwann cells alone contributes little to the embryonic survival of neurons. These data suggest that neural crest-derived cells are dispensable for all central and some peripheral targeting of inner ear neurons. However, Schwann cells provide a stop signal for migratory spiral ganglion neurons and facilitate proper targeting of the organ of Corti by spiral ganglion afferents. PMID:24718611

  8. Creative Copper Crests

    Science.gov (United States)

    Knab, Thomas

    2011-01-01

    In this article, the author discusses how to create an art activity that would link the computer-created business cards of fourth-grade students with an upcoming school-wide medieval event. Creating family crests from copper foil would be a great connection, since they, like business cards, are an individual's way to identify themselves to others.…

  9. Cdk1 Activates Pre-Mitotic Nuclear Envelope Dynein Recruitment and Apical Nuclear Migration in Neural Stem cells

    Science.gov (United States)

    Baffet, Alexandre D.; Hu, Daniel J.; Vallee, Richard B.

    2015-01-01

    Summary Dynein recruitment to the nuclear envelope is required for pre-mitotic nucleus-centrosome interactions in nonneuronal cells, and for apical nuclear migration in neural stem cells. In each case, dynein is recruited to the nuclear envelope (NE) specifically during G2, via two nuclear pore-mediated mechanisms involving RanBP2-BicD2 and Nup133-CENP-F. The mechanisms responsible for cell cycle control of this behavior are unknown. We now find that Cdk1 serves as a direct master controller for NE dynein recruitment in neural stem cells and HeLa cells. Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment. Late recruitment is triggered by a Cdk1-induced export of CENP-F from the nucleus. Forced NE targeting of BicD2 overrides Cdk1 inhibition, fully rescuing dynein recruitment and nuclear migration in neural stem cells. These results reveal how NE dynein recruitment is cell cycle regulated, and identify the trigger mechanism for apical nuclear migration in the brain. PMID:26051540

  10. Signaling through three chemokine receptors triggers the migration of transplanted neural precursor cells in a model of multiple sclerosis.

    Science.gov (United States)

    Cohen, Mikhal E; Fainstein, Nina; Lavon, Iris; Ben-Hur, Tamir

    2014-09-01

    Multiple sclerosis (MS) is a multifocal disease, and precursor cells need to migrate into the multiple lesions in order to exert their therapeutic effects. Therefore, cell migration is a crucial element in regenerative processes in MS, dictating the route of delivery, when cell transplantation is considered. We have previously shown that inflammation triggers migration of multi-potential neural precursor cells (NPCs) into the white matter of experimental autoimmune encephalomyelitis (EAE) rodents, a widely used model of MS. Here we investigated the molecular basis of this attraction. NPCs were grown from E13 embryonic mouse brains and transplanted into the lateral cerebral ventricles of EAE mice. Transplanted NPC migration was directed by three tissue-derived chemokines. Stromal cell-derived factor-1α, monocyte chemo-attractant protein-1 and hepatocyte growth factor were expressed in the EAE brain and specifically in microglia and astrocytes. Their cognate receptors, CXCR4, CCR2 or c-Met were constitutively expressed on NPCs. Selective blockage of CXCR4, CCR2 or c-Met partially inhibited NPC migration in EAE brains. Blocking all three receptors had an additive effect and resulted in profound inhibition of NPC migration, as compared to extensive migration of control NPCs. The inflammation-triggered NPC migration into white matter tracts was dependent on a motile NPC phenotype. Specifically, depriving NPCs from epidermal growth factor (EGF) prevented the induction of glial commitment and a motile phenotype (as indicated by an in vitro motility assay), hampering their response to neuroinflammation. In conclusion, signaling via three chemokine systems accounts for most of the inflammation-induced, tissue-derived attraction of transplanted NPCs into white matter tracts during EAE. Copyright © 2014. Published by Elsevier B.V.

  11. IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation.

    Science.gov (United States)

    Wei, Hongen; Zou, Hua; Sheikh, Ashfaq M; Malik, Mazhar; Dobkin, Carl; Brown, W Ted; Li, Xiaohong

    2011-05-19

    Although the cellular mechanisms responsible for the pathogenesis of autism are not understood, a growing number of studies have suggested that localized inflammation of the central nervous system (CNS) may contribute to the development of autism. Recent evidence shows that IL-6 has a crucial role in the development and plasticity of CNS. Immunohistochemistry studies were employed to detect the IL-6 expression in the cerebellum of study subjects. In vitro adenoviral gene delivery approach was used to over-express IL-6 in cultured cerebellar granule cells. Cell adhesion and migration assays, DiI labeling, TO-PRO-3 staining and immunofluorescence were used to examine cell adhesion and migration, dendritic spine morphology, cell apoptosis and synaptic protein expression respectively. In this study, we found that IL-6 was significantly increased in the cerebellum of autistic subjects. We investigated how IL-6 affects neural cell development and function by transfecting cultured mouse cerebellar granule cells with an IL-6 viral expression vector. We demonstrated that IL-6 over-expression in granule cells caused impairments in granule cell adhesion and migration but had little effect on the formation of dendritic spines or granule cell apoptosis. However, IL-6 over-expression stimulated the formation of granule cell excitatory synapses, without affecting inhibitory synapses. Our results provide further evidence that aberrant IL-6 may be associated with autism. In addition, our results suggest that the elevated IL-6 in the autistic brain could alter neural cell adhesion, migration and also cause an imbalance of excitatory and inhibitory circuits. Thus, increased IL-6 expression may be partially responsible for the pathogenesis of autism.

  12. IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation

    Directory of Open Access Journals (Sweden)

    Dobkin Carl

    2011-05-01

    Full Text Available Abstract Background Although the cellular mechanisms responsible for the pathogenesis of autism are not understood, a growing number of studies have suggested that localized inflammation of the central nervous system (CNS may contribute to the development of autism. Recent evidence shows that IL-6 has a crucial role in the development and plasticity of CNS. Methods Immunohistochemistry studies were employed to detect the IL-6 expression in the cerebellum of study subjects. In vitro adenoviral gene delivery approach was used to over-express IL-6 in cultured cerebellar granule cells. Cell adhesion and migration assays, DiI labeling, TO-PRO-3 staining and immunofluorescence were used to examine cell adhesion and migration, dendritic spine morphology, cell apoptosis and synaptic protein expression respectively. Results In this study, we found that IL-6 was significantly increased in the cerebellum of autistic subjects. We investigated how IL-6 affects neural cell development and function by transfecting cultured mouse cerebellar granule cells with an IL-6 viral expression vector. We demonstrated that IL-6 over-expression in granule cells caused impairments in granule cell adhesion and migration but had little effect on the formation of dendritic spines or granule cell apoptosis. However, IL-6 over-expression stimulated the formation of granule cell excitatory synapses, without affecting inhibitory synapses. Conclusions Our results provide further evidence that aberrant IL-6 may be associated with autism. In addition, our results suggest that the elevated IL-6 in the autistic brain could alter neural cell adhesion, migration and also cause an imbalance of excitatory and inhibitory circuits. Thus, increased IL-6 expression may be partially responsible for the pathogenesis of autism.

  13. Chicken HOXA3 Gene: Its Expression Pattern and Role in Branchial Nerve Precursor Cell Migration

    Science.gov (United States)

    Watari-Goshima, Natsuko; Chisaka, Osamu

    2011-01-01

    In vertebrates, the proximal and distal sensory ganglia of the branchial nerves are derived from neural crest cells (NCCs) and placodes, respectively. We previously reported that in Hoxa3 knockout mouse embryos, NCCs and placode-derived cells of the glossopharyngeal nerve were defective in their migration. In this report, to determine the cell-type origin for this Hoxa3 knockout phenotype, we blocked the expression of the gene with antisense morpholino oligonucleotides (MO) specifically in either NCCs/neural tube or placodal cells of chicken embryos. Our results showed that HOXA3 function was required for the migration of the epibranchial placode-derived cells and that HOXA3 regulated this cell migration in both NCCs/neural tube and placodal cells. We also report that the expression pattern of chicken HOXA3 was slightly different from that of mouse Hoxa3. PMID:21278919

  14. Co-culture of neural crest stem cells (NCSC and insulin producing beta-TC6 cells results in cadherin junctions and protection against cytokine-induced beta-cell death.

    Directory of Open Access Journals (Sweden)

    Anongnad Ngamjariyawat

    Full Text Available PURPOSE: Transplantation of pancreatic islets to Type 1 diabetes patients is hampered by inflammatory reactions at the transplantation site leading to dysfunction and death of insulin producing beta-cells. Recently we have shown that co-transplantation of neural crest stem cells (NCSCs together with the islet cells improves transplantation outcome. The aim of the present investigation was to describe in vitro interactions between NCSCs and insulin producing beta-TC6 cells that may mediate protection against cytokine-induced beta-cell death. PROCEDURES: Beta-TC6 and NCSC cells were cultured either alone or together, and either with or without cell culture inserts. The cultures were then exposed to the pro-inflammatory cytokines IL-1β and IFN-γ for 48 hours followed by analysis of cell death rates (flow cytometry, nitrite production (Griess reagent, protein localization (immunofluorescence and protein phosphorylation (flow cytometry. RESULTS: We observed that beta-TC6 cells co-cultured with NCSCs were protected against cytokine-induced cell death, but not when separated by cell culture inserts. This occurred in parallel with (i augmented production of nitrite from beta-TC6 cells, indicating that increased cell survival allows a sustained production of nitric oxide; (ii NCSC-derived laminin production; (iii decreased phospho-FAK staining in beta-TC6 cell focal adhesions, and (iv decreased beta-TC6 cell phosphorylation of ERK(T202/Y204, FAK(Y397 and FAK(Y576. Furthermore, co-culture also resulted in cadherin and beta-catenin accumulations at the NCSC/beta-TC6 cell junctions. Finally, the gap junction inhibitor carbenoxolone did not affect cytokine-induced beta-cell death during co-culture with NCSCs. CONCLUSION: In summary, direct contacts, but not soluble factors, promote improved beta-TC6 viability when co-cultured with NCSCs. We hypothesize that cadherin junctions between NCSC and beta-TC6 cells promote powerful signals that maintain beta

  15. Specific Intensity Direct Current (DC) Electric Field Improves Neural Stem Cell Migration and Enhances Differentiation towards βIII-Tubulin+ Neurons

    Science.gov (United States)

    Zhao, Huiping; Steiger, Amanda; Nohner, Mitch; Ye, Hui

    2015-01-01

    Control of stem cell migration and differentiation is vital for efficient stem cell therapy. Literature reporting electric field–guided migration and differentiation is emerging. However, it is unknown if a field that causes cell migration is also capable of guiding cell differentiation—and the mechanisms for these processes remain unclear. Here, we report that a 115 V/m direct current (DC) electric field can induce directional migration of neural precursor cells (NPCs). Whole cell patching revealed that the cell membrane depolarized in the electric field, and buffering of extracellular calcium via EGTA prevented cell migration under these conditions. Immunocytochemical staining indicated that the same electric intensity could also be used to enhance differentiation and increase the percentage of cell differentiation into neurons, but not astrocytes and oligodendrocytes. The results indicate that DC electric field of this specific intensity is capable of promoting cell directional migration and orchestrating functional differentiation, suggestively mediated by calcium influx during DC field exposure. PMID:26068466

  16. Effects of atelocollagen on neural stem cell function and its migrating capacity into brain in psychiatric disease model.

    Science.gov (United States)

    Yoshinaga, Toshihiro; Hashimoto, Eri; Ukai, Wataru; Ishii, Takao; Shirasaka, Tomohiro; Kigawa, Yoshiyasu; Tateno, Masaru; Kaneta, Hiroo; Watanabe, Kimihiko; Igarashi, Takeshi; Kobayashi, Seiju; Sohma, Hitoshi; Kato, Tadafumi; Saito, Toshikazu

    2013-10-01

    Stem cell therapy is well proposed as a potential method for the improvement of neurodegenerative damage in the brain. Among several different procedures to reach the cells into the injured lesion, the intravenous (IV) injection has benefit as a minimally invasive approach. However, for the brain disease, prompt development of the effective treatment way of cellular biodistribution of stem cells into the brain after IV injection is needed. Atelocollagen has been used as an adjunctive material in a gene, drug and cell delivery system because of its extremely low antigenicity and bioabsorbability to protect these transplants from intrabody environment. However, there is little work about the direct effect of atelocollagen on stem cells, we examined the functional change of survival, proliferation, migration and differentiation of cultured neural stem cells (NSCs) induced by atelocollagen in vitro. By 72-h treatment 0.01-0.05% atelocollagen showed no significant effects on survival, proliferation and migration of NSCs, while 0.03-0.05% atelocollagen induced significant reduction of neuronal differentiation and increase of astrocytic differentiation. Furthermore, IV treated NSCs complexed with atelocollagen (0.02%) could effectively migrate into the brain rather than NSC treated alone using chronic alcohol binge model rat. These experiments suggested that high dose of atelocollagen exerts direct influence on NSC function but under 0.03% of atelocollagen induces beneficial effect on regenerative approach of IV administration of NSCs for CNS disease.

  17. The role of CXC chemokine ligand (CXCL)12-CXC chemokine receptor (CXCR)4 signalling in the migration of neural stem cells towards a brain tumour

    NARCIS (Netherlands)

    van der Meulen, A. A. E.; Biber, K.; Lukovac, S.; Balasubramaniyan, V.; den Dunnen, W. F. A.; Boddeke, H. W. G. M.; Mooij, J. J. A.

    2009-01-01

    Aims: It has been shown that neural stem cells (NSCs) migrate towards areas of brain injury or brain tumours and that NSCs have the capacity to track infiltrating tumour cells. The possible mechanism behind the migratory behaviour of NSCs is not yet completely understood. As chemokines are involved

  18. Abnormal neuronal migration: radiologic-clinic study. Alteraciones en la migracion neural: estudio clinico-radiologico

    Energy Technology Data Exchange (ETDEWEB)

    Martinez Fernandez, M.; Menor Serrano, F.; Bordon Ferre, F.; Garcia Tena, J.; Esteban Hernandez, E.; Sanguesa Nebot, C.; Marti Bonnati, L. (Hospital Infantil La Fe, Valencia (Spain))

    1994-01-01

    We present our experience in 18 pediatric patients with abnormal neuronal migration. Seven cases of heterotopia of the gray matter, 7 agyria-pachygyria complexes, 1 case of polymicrogyria, 2 cases of schizencephaly and 1 case of hemimegalencephaly were diagnosed by means of ultrasonography, computed tomography and magnetic resonance. The clinical picture was reviewed in each case, with special attention to the occurrence of convulsions, psycho motor development and visual changes. In general, the greater the morphological change, the greater the neurological involvement in these patients. However, the two cases of schizencephaly presented mild clinical expression. Magnetic resonance increases the diagnostic yield in neuronal migration disorders. Nevertheless, either ultrasonography or, especially, computed tomography is useful as a first diagnostic approach in these malformative disorders. (Author)

  19. Chondroitin sulfate proteoglycans regulate the growth, differentiation and migration of multipotent neural precursor cells through the integrin signaling pathway

    Directory of Open Access Journals (Sweden)

    Lü He-Zuo

    2009-10-01

    Full Text Available Abstract Background Neural precursor cells (NPCs are defined by their ability to proliferate, self-renew, and retain the potential to differentiate into neurons and glia. Deciphering the factors that regulate their behaviors will greatly aid in their use as potential therapeutic agents or targets. Chondroitin sulfate proteoglycans (CSPGs are prominent components of the extracellular matrix (ECM in the central nervous system (CNS and are assumed to play important roles in controlling neuronal differentiation and development. Results In the present study, we demonstrated that CSPGs were constitutively expressed on the NPCs isolated from the E16 rat embryonic brain. When chondroitinase ABC was used to abolish the function of endogenous CSPGs on NPCs, it induced a series of biological responses including the proliferation, differentiation and migration of NPCs, indicating that CSPGs may play a critical role in NPC development and differentiation. Finally, we provided evidence suggesting that integrin signaling pathway may be involved in the effects of CSPGs on NPCs. Conclusion The present study investigating the influence and mechanisms of CSPGs on the differentiation and migration of NPCs should help us to understand the basic biology of NPCs during CNS development and provide new insights into developing new strategies for the treatment of the neurological disorders in the CNS.

  20. Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Katja M. Piltti

    2015-09-01

    Full Text Available The effect of transplantation dose on the spatiotemporal dynamics of human neural stem cell (hNSC engraftment has not been quantitatively evaluated in the central nervous system. We investigated changes over time in engraftment/survival, proliferation, and migration of multipotent human central nervous system-derived neural stem cells (hCNS-SCns transplanted at doses ranging from 10,000 to 500,000 cells in spinal cord injured immunodeficient mice. Transplant dose was inversely correlated with measures of donor cell proliferation at 2 weeks post-transplant (WPT and dose-normalized engraftment at 16 WPT. Critically, mice receiving the highest cell dose exhibited an engraftment plateau, in which the total number of engrafted human cells never exceeded the initial dose. These data suggest that donor cell expansion was inversely regulated by target niche parameters and/or transplantation density. Investigation of the response of donor cells to the host microenvironment should be a key variable in defining target cell dose in pre-clinical models of CNS disease and injury.

  1. Numerical Simulation of 3-D Wave Crests

    Institute of Scientific and Technical Information of China (English)

    YU Dingyong; ZHANG Hanyuan

    2003-01-01

    A clear definition of 3-D wave crest and a description of the procedures to detect the boundary of wave crest are presented in the paper. By using random wave theory and directional wave spectrum, a MATLAB-platformed program is designed to simulate random wave crests for various directional spectral conditions in deep water. Statistics of wave crests with different directional spreading parameters and different directional functions are obtained and discussed.

  2. Defective neuronal migration and inhibition of bipolar to multipolar transition of migrating neural cells by Mesoderm-Specific Transcript, Mest, in the developing mouse neocortex.

    Science.gov (United States)

    Ji, Liting; Bishayee, Kausik; Sadra, Ali; Choi, Seunghyuk; Choi, Wooyul; Moon, Sungho; Jho, Eek-Hoon; Huh, Sung-Oh

    2017-07-04

    Brain developmental disorders such as lissencephaly can result from faulty neuronal migration and differentiation during the formation of the mammalian neocortex. The cerebral cortex is a modular structure, where developmentally, newborn neurons are generated as a neuro-epithelial sheet and subsequently differentiate, migrate and organize into their final positions in the cerebral cortical plate via a process involving both tangential and radial migration. The specific role of Mest, an imprinted gene, in neuronal migration has not been previously studied. In this work, we reduced expression of Mest with in utero electroporation of neuronal progenitors in the developing embryonic mouse neocortex. Reduction of Mest levels by shRNA significantly reduced the number of neurons migrating to the cortical plate. Also, Mest-knockdown disrupted the transition of bipolar neurons into multipolar neurons migrating out of the sub-ventricular zone region. The migrating neurons also adopted a more tangential migration pattern upon knockdown of the Mest message, losing their potential to attach to radial glia cells, required for radial migration. The differentiation and migration properties of neurons via Wnt-Akt signaling were affected by Mest changes. In addition, miR-335, encoded in a Mest gene intron, was identified as being responsible for blocking the default tangential migration of the neurons. Our results suggest that Mest and its intron product, miR-335, play important roles in neuronal migration with Mest regulating the morphological transition of primary neurons required in the formation of the mammalian neocortex. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Development of the nervus terminalis: origin and migration.

    Science.gov (United States)

    Whitlock, Kathleen E

    2004-09-01

    The origin of the nervus terminalis is one of the least well understood developmental events involved in generating the cranial ganglia of the forebrain in vertebrate animals. This cranial nerve forms at the formidable interface of the anteriormost limits of migrating cranial neural crest cells, the terminal end of the neural tube and the differentiating olfactory and adenohypophyseal placodes. The complex cellular interactions that give rise to the various structures associated with the sensory placode (olfactory) and endocrine placode (adenohypophysis) surround and engulf this enigmatic cranial nerve. The tortured history of nervus terminalis development (see von Bartheld, this issue, pages 13-24) reflects the lack of consensus on the origin (or origins), as well as the experimental difficulties in uncovering the origin, of the nervus terminalis. Recent technical advances have allowed us to make headway in understanding the origin(s) of this nerve. The emergence of the externally fertilized zebrafish embryo as a model system for developmental biology and genetics has shed new light on this century-old problem. Coupled with new developmental models are techniques that allow us to trace lineage, visualize gene expression, and genetically ablate cells, adding to our experimental tools with which to follow up on studies provided by our scientific predecessors. Through these techniques, a picture is emerging in which the origin of at least a subset of the nervus terminalis cells lies in the cranial neural crest. In this review, the data surrounding this finding will be discussed in light of recent findings on neural crest and placode origins. Copyright 2004 Wiley-Liss, Inc.

  4. The effect of pulsed electric fields on the electrotactic migration of human neural progenitor cells through the involvement of intracellular calcium signaling.

    Science.gov (United States)

    Hayashi, Hisamitsu; Edin, Fredrik; Li, Hao; Liu, Wei; Rask-Andersen, Helge

    2016-12-01

    Endogenous electric fields (EFs) are required for the physiological control of the central nervous system development. Application of the direct current EFs to neural stem cells has been studied for the possibility of stem cell transplantation as one of the therapies for brain injury. EFs generated within the nervous system are often associated with action potentials and synaptic activity, apparently resulting in a pulsed current in nature. The aim of this study is to investigate the effect of pulsed EF, which can reduce the cytotoxicity, on the migration of human neural progenitor cells (hNPCs). We applied the mono-directional pulsed EF with a strength of 250mV/mm to hNPCs for 6h. The migration distance of the hNPCs exposed to pulsed EF was significantly greater compared with the control not exposed to the EF. Pulsed EFs, however, had less of an effect on the migration of the differentiated hNPCs. There was no significant change in the survival of hNPCs after exposure to the pulsed EF. To investigate the role of Ca 2+ signaling in electrotactic migration of hNPCs, pharmacological inhibition of Ca 2+ channels in the EF-exposed cells revealed that the electrotactic migration of hNPCs exposed to Ca 2+ channel blockers was significantly lower compared to the control group. The findings suggest that the pulsed EF induced migration of hNPCs is partly influenced by intracellular Ca 2+ signaling. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Multi-cellular logistics of collective cell migration.

    Directory of Open Access Journals (Sweden)

    Masataka Yamao

    Full Text Available During development, the formation of biological networks (such as organs and neuronal networks is controlled by multicellular transportation phenomena based on cell migration. In multi-cellular systems, cellular locomotion is restricted by physical interactions with other cells in a crowded space, similar to passengers pushing others out of their way on a packed train. The motion of individual cells is intrinsically stochastic and may be viewed as a type of random walk. However, this walk takes place in a noisy environment because the cell interacts with its randomly moving neighbors. Despite this randomness and complexity, development is highly orchestrated and precisely regulated, following genetic (and even epigenetic blueprints. Although individual cell migration has long been studied, the manner in which stochasticity affects multi-cellular transportation within the precisely controlled process of development remains largely unknown. To explore the general principles underlying multicellular migration, we focus on the migration of neural crest cells, which migrate collectively and form streams. We introduce a mechanical model of multi-cellular migration. Simulations based on the model show that the migration mode depends on the relative strengths of the noise from migratory and non-migratory cells. Strong noise from migratory cells and weak noise from surrounding cells causes "collective migration," whereas strong noise from non-migratory cells causes "dispersive migration." Moreover, our theoretical analyses reveal that migratory cells attract each other over long distances, even without direct mechanical contacts. This effective interaction depends on the stochasticity of the migratory and non-migratory cells. On the basis of these findings, we propose that stochastic behavior at the single-cell level works effectively and precisely to achieve collective migration in multi-cellular systems.

  6. Whistler wave trapping in a density crest

    International Nuclear Information System (INIS)

    Sugai, H.; Niki, H.; Inutake, M.; Takeda, S.

    1979-11-01

    The linear trapping process of whistler waves in a field-aligned density crest is investigated theoretically and experimentally below ω = ωsub(c)/2 (half gyrofrequency). The conditions of the crest trapping are derived in terms of the frequency ω/ωsub(c), the incident wave-normal angle theta sub(i), and the density ratio n sub(i)/n sub(o), where n sub(i) and n sub(o) denote the density at the incident point and that at the ridge, respectively. The oscillation length of the trapped ray path is calculated for a parabolic density profile. The experiment on antenna-excited whistler wave has been performed in a large magnetized plasma with the density crest. The phase and amplitude profile of the whistler wave is measured along and across the crest. The measurement has verified characteristic behaviors of the crest trapping. (author)

  7. Untangling cell tracks: Quantifying cell migration by time lapse image data analysis.

    Science.gov (United States)

    Svensson, Carl-Magnus; Medyukhina, Anna; Belyaev, Ivan; Al-Zaben, Naim; Figge, Marc Thilo

    2018-03-01

    Automated microscopy has given researchers access to great amounts of live cell imaging data from in vitro and in vivo experiments. Much focus has been put on extracting cell tracks from such data using a plethora of segmentation and tracking algorithms, but further analysis is normally required to draw biologically relevant conclusions. Such relevant conclusions may be whether the migration is directed or not, whether the population has homogeneous or heterogeneous migration patterns. This review focuses on the analysis of cell migration data that are extracted from time lapse images. We discuss a range of measures and models used to analyze cell tracks independent of the biological system or the way the tracks were obtained. For single-cell migration, we focus on measures and models giving examples of biological systems where they have been applied, for example, migration of bacteria, fibroblasts, and immune cells. For collective migration, we describe the model systems wound healing, neural crest migration, and Drosophila gastrulation and discuss methods for cell migration within these systems. We also discuss the role of the extracellular matrix and subsequent differences between track analysis in vitro and in vivo. Besides methods and measures, we are putting special focus on the need for openly available data and code, as well as a lack of common vocabulary in cell track analysis. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  8. Follow-the-leader cell migration requires biased cell-cell contact and local microenvironmental signals

    Science.gov (United States)

    Wynn, Michelle L.; Rupp, Paul; Trainor, Paul A.; Schnell, Santiago; Kulesa, Paul M.

    2013-06-01

    Directed cell migration often involves at least two types of cell motility that include multicellular streaming and chain migration. However, what is unclear is how cell contact dynamics and the distinct microenvironments through which cells travel influence the selection of one migratory mode or the other. The embryonic and highly invasive neural crest (NC) are an excellent model system to study this question since NC cells have been observed in vivo to display both of these types of cell motility. Here, we present data from tissue transplantation experiments in chick and in silico modeling that test our hypothesis that cell contact dynamics with each other and the microenvironment promote and sustain either multicellular stream or chain migration. We show that when premigratory cranial NC cells (at the pre-otic level) are transplanted into a more caudal region in the head (at the post-otic level), cells alter their characteristic stream behavior and migrate in chains. Similarly, post-otic NC cells migrate in streams after transplantation into the pre-otic hindbrain, suggesting that local microenvironmental signals dictate the mode of NC cell migration. Simulations of an agent-based model (ABM) that integrates the NC cell behavioral data predict that chain migration critically depends on the interplay of biased cell-cell contact and local microenvironment signals. Together, this integrated modeling and experimental approach suggests new experiments and offers a powerful tool to examine mechanisms that underlie complex cell migration patterns.

  9. Follow-the-leader cell migration requires biased cell–cell contact and local microenvironmental signals

    International Nuclear Information System (INIS)

    Wynn, Michelle L; Rupp, Paul; Trainor, Paul A; Kulesa, Paul M; Schnell, Santiago

    2013-01-01

    Directed cell migration often involves at least two types of cell motility that include multicellular streaming and chain migration. However, what is unclear is how cell contact dynamics and the distinct microenvironments through which cells travel influence the selection of one migratory mode or the other. The embryonic and highly invasive neural crest (NC) are an excellent model system to study this question since NC cells have been observed in vivo to display both of these types of cell motility. Here, we present data from tissue transplantation experiments in chick and in silico modeling that test our hypothesis that cell contact dynamics with each other and the microenvironment promote and sustain either multicellular stream or chain migration. We show that when premigratory cranial NC cells (at the pre-otic level) are transplanted into a more caudal region in the head (at the post-otic level), cells alter their characteristic stream behavior and migrate in chains. Similarly, post-otic NC cells migrate in streams after transplantation into the pre-otic hindbrain, suggesting that local microenvironmental signals dictate the mode of NC cell migration. Simulations of an agent-based model (ABM) that integrates the NC cell behavioral data predict that chain migration critically depends on the interplay of biased cell–cell contact and local microenvironment signals. Together, this integrated modeling and experimental approach suggests new experiments and offers a powerful tool to examine mechanisms that underlie complex cell migration patterns. (paper)

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

    Science.gov (United States)

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

    1999-04-01

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

  11. Design Guidelines for Low Crested Structures

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Lamberti, Alberto

    2004-01-01

    1998-2002. The Guidelines comprise engineering aspects related to morphological impact and structure stability, biological aspects related to ecological impact, and socio-economical aspects related to the implementation of LCS-schemes. The guidelines are limited to submerged and regularly overtopped......The paper presents an overview of the design guidelines for low crested structures (LCS's) to be applied in coastal protection schemes. The design guidelines are formulated as a part of the research project: Environmental Design of Low Crested Coastal Defence Structures (DELOS) within the EC 5FP...

  12. Sagittal crest formation in great apes and gibbons

    OpenAIRE

    Balolia, K. L.; Soligo, C.; Wood, B.

    2017-01-01

    The frequency of sagittal crest expression and patterns of sagittal crest growth and development have been documented in hominoids, including some extinct hominin taxa, and the more frequent expression of the sagittal crest in males has been traditionally linked with the need for larger-bodied individuals to have enough attachment area for the temporalis muscle. In the present study, we investigate sagittal cresting in a dentally mature sample of four hominoid taxa (Pan troglodytes schweinfur...

  13. Diversification of crested wheatgrass stands in Utah

    Science.gov (United States)

    April Hulet

    2009-01-01

    Agropyron cristatum [L.] Gaertner (crested wheatgrass) continues to be seeded on burned wildlands. Effective control methods need to be developed to convert these seedings to more diverse native plant communities. This research was designed to determine effective ways to control A. cristatum and establish native species while...

  14. Multiscale mechanisms of cell migration during development: theory and experiment.

    Science.gov (United States)

    McLennan, Rebecca; Dyson, Louise; Prather, Katherine W; Morrison, Jason A; Baker, Ruth E; Maini, Philip K; Kulesa, Paul M

    2012-08-01

    Long-distance cell migration is an important feature of embryonic development, adult morphogenesis and cancer, yet the mechanisms that drive subpopulations of cells to distinct targets are poorly understood. Here, we use the embryonic neural crest (NC) in tandem with theoretical studies to evaluate model mechanisms of long-distance cell migration. We find that a simple chemotaxis model is insufficient to explain our experimental data. Instead, model simulations predict that NC cell migration requires leading cells to respond to long-range guidance signals and trailing cells to short-range cues in order to maintain a directed, multicellular stream. Experiments confirm differences in leading versus trailing NC cell subpopulations, manifested in unique cell orientation and gene expression patterns that respond to non-linear tissue growth of the migratory domain. Ablation experiments that delete the trailing NC cell subpopulation reveal that leading NC cells distribute all along the migratory pathway and develop a leading/trailing cellular orientation and gene expression profile that is predicted by model simulations. Transplantation experiments and model predictions that move trailing NC cells to the migratory front, or vice versa, reveal that cells adopt a gene expression profile and cell behaviors corresponding to the new position within the migratory stream. These results offer a mechanistic model in which leading cells create and respond to a cell-induced chemotactic gradient and transmit guidance information to trailing cells that use short-range signals to move in a directional manner.

  15. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.

    Science.gov (United States)

    Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique

    2016-07-15

    The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. Copyright © 2015. Published by Elsevier Inc.

  16. Overflow Characteristic of Cylindrical Shape Crest Weirs Over Horizontal Bed

    OpenAIRE

    Emad4 AbdulGabbar

    2013-01-01

    The most common types of weirs are the broad-crested weir, the sharp-crested weir, the circular crested weir and the ogee crested weir. Advantages of the cylindrical weir shape include the stable overflow pattern, the ease to pass floating debris, the simplicity of design compared to ogee crest design and the associated lower costs. In present study, it was investigated the overflow characteristics of circular weirs in laboratory for various cylinder radii of three sizes (11.4, 9.0, 6.3 cm), ...

  17. Structural Stability Of Detached Low Crested Breakwaters

    DEFF Research Database (Denmark)

    Burcharth, Hans F.; Kramer, Morten; Lamberti, Alberto

    2006-01-01

    The aim of the paper is to describe hydraulic stability of rock-armoured low-crested structures on the basis of new experimental tests and prototype observations. Rock armour stability results from earlier model tests under non-depth-limited long-crested head-on waves are reviewed. Results from new...... determining armour stone size in shallow water conditions is given together with a rule of thumb for the required stone size in depth-limited design waves. Rock toe stability is discussed on the basis of prototype experience, hard bottom 2-D tests in depth-limited waves and an existing hydraulic stability...... formula. Toe damage predicted by the formula is in agreement with experimental results. In field sites, damage at the toe induced by scour or by sinking is observed and the volume of the berm is often insufficient to avoid regressive erosion of the armour layer. Stone sinking and settlement in selected...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-05-01

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

  19. Sagittal crest formation in great apes and gibbons.

    Science.gov (United States)

    Balolia, Katharine L; Soligo, Christophe; Wood, Bernard

    2017-06-01

    The frequency of sagittal crest expression and patterns of sagittal crest growth and development have been documented in hominoids, including some extinct hominin taxa, and the more frequent expression of the sagittal crest in males has been traditionally linked with the need for larger-bodied individuals to have enough attachment area for the temporalis muscle. In the present study, we investigate sagittal cresting in a dentally mature sample of four hominoid taxa (Pan troglodytes schweinfurthii, Gorilla gorilla gorilla, Pongo pygmaeus pygmaeus and Hylobates lar). We investigate whether sagittal crest size increases with age beyond dental maturity in males and females of G. g. gorilla and Po. pyg. pygmaeus, and whether these taxa show sex differences in the timing of sagittal crest development. We evaluate the hypothesis that the larger sagittal crest of males may not be solely due to the requirement for a larger surface area than the un-crested cranial vault can provide for the attachment of the temporalis muscle, and present data on sex differences in temporalis muscle attachment area and sagittal crest size relative to cranial size. Gorilla g. gorilla and Po. pyg. pygmaeus males show significant relationships between tooth wear rank and sagittal crest size, and they show sagittal crest size differences between age groups that are not found in females. The sagittal crest emerges in early adulthood in the majority of G. g. gorilla males, whereas the percentage of G. g. gorilla females possessing a sagittal crest increases more gradually. Pongo pyg. pygmaeus males experience a three-fold increase in the number of specimens exhibiting a sagittal crest in mid-adulthood, consistent with a secondary growth spurt. Gorilla g. gorilla and Po. pyg. pygmaeus show significant sex differences in the size of the temporalis muscle attachment area, relative to cranial size, with males of both taxa showing positive allometry not shown in females. Gorilla g

  20. Expression of MiR-9 promotes proliferation, migration and ...

    African Journals Online (AJOL)

    differentiation of human neural stem cells. Fei Zeng ... Keywords: Neural stem cells, MicroRNA, Mir-9, Migration, Differentiation, Proliferation ... Neural stem cells (NSCs) are basically ..... application of patient-specific pluripotent stem cells. J.

  1. Laboratory Experiments on Low-crested Breakwaters

    DEFF Research Database (Denmark)

    Kramer, Morten; Zanuttigh, B.; van der Meer, J.W.

    2005-01-01

    New unique laboratory experiments on low-crested structures (LCSs) have been performed within the DELOS project. The experiments were carried out in three European laboratories aiming at extending and completing existing available information with respect to a wide range of engineering design...... in a wave channel at small scale, and scale effects regarding wave transmission and reflection were studied in a wave channel at a large scale facility. The paper describes the experiments and associated databank with respect to objectives, test program, set-ups and measurements. Results, guidelines...... and recommendations elaborated from the tests are included in the other companion papers of the Coastal Engineering Special Issue on DELOS....

  2. Hydraulic model tests of an innovative dike crest design

    NARCIS (Netherlands)

    Verhagen, H.J.; Kortenhaus, A.; Bollinger, K.; Dassayanake, D.

    2007-01-01

    Report on laboratory tests on a crest drainage dike; investigation if a channel in the crest of the dike is able to decrease the amount of overtopping over the dike. Chapter 2 provides details about findings from previous studies and the relevance of those findings to this research project.

  3. Degradation processes and the methods of securing wall crests

    Directory of Open Access Journals (Sweden)

    Maciej Trochonowicz

    2017-12-01

    Full Text Available The protection of historical ruins requires solution of doctrinal and technical problems. Technical problems concern above all preservation of walls, which are exposed to the influence of atmospheric factors. The problem that needs to be solved in any historic ruin is securing of wall crests. Form of protection of the wall crests depends on many factors, mainly technical features of the wall and architectural and conservatory vision. The following article presents three aspects important for protection of wall crests. Firstly, analysis of features of the wall as a structure, secondly the characteristics of destructive agents, thirdly forms of protection of wall crests. In the summary of the following article, advantages and disadvantages of each method of preservation of the wall crests were presented.

  4. L-3-n-Butylphthalide Regulates Proliferation, Migration, and Differentiation of Neural Stem Cell In Vitro and Promotes Neurogenesis in APP/PS1 Mouse Model by Regulating BDNF/TrkB/CREB/Akt Pathway.

    Science.gov (United States)

    Lei, Hui; Zhang, Yu; Huang, Longjian; Xu, Shaofeng; Li, Jiang; Yang, Lichao; Wang, Ling; Xing, Changhong; Wang, Xiaoliang; Peng, Ying

    2018-05-04

    Alzheimer's disease (AD) is characterized by extracellular accumulation of β-amyloid peptides (Aβ) and intracellular neurofibrillary tangles, along with cognitive decline and neurodegeneration. The cognitive deficit is considered to be due to the dysfunction of hippocampal neurogenesis. Although L-3-n-butylphthalide (L-NBP) has been shown beneficial effects in multiple AD animal models, the underlying molecular mechanisms are still elusive. In this study, we investigated the effects of L-NBP on neurogenesis both in vitro and in vivo. L-NBP promoted proliferation and migration of neural stem cells and induced neuronal differentiation in vitro. In APP/PS1 mice, L-NBP induced neurogenesis in the dentate gyrus and improved cognitive functions. In addition, L-NBP significantly increased the expressions of BDNF and NGF, tyrosine phosphorylation of its cognate receptor, and phosphorylation of Akt as well as CREB at Ser133 in the hippocampus of APP/PS1 mice. These results indicated that L-NBP might stimulate the proliferation, migration, and differentiation of hippocampal neural stem cells and reversed cognitive deficits in APP/PS1 mice. BDNF/TrkB/CREB/Akt signaling pathway might be involved.

  5. Coronin-1C and RCC2 guide mesenchymal migration by trafficking Rac1 and controlling GEF exposure

    Science.gov (United States)

    Williamson, Rosalind C.; Cowell, Christopher A. M.; Hammond, Christina L.; Bergen, Dylan J. M.; Roper, James A.; Feng, Yi; Rendall, Thomas C. S.; Race, Paul R.; Bass, Mark D.

    2014-01-01

    ABSTRACT Sustained forward migration through a fibrillar extracellular matrix requires localization of protrusive signals. Contact with fibronectin at the tip of a cell protrusion activates Rac1, and for linear migration it is necessary to dampen Rac1 activity in off-axial positions and redistribute Rac1 from non-protrusive membrane to the leading edge. Here, we identify interactions between coronin-1C (Coro1C), RCC2 and Rac1 that focus active Rac1 to a single protrusion. Coro1C mediates release of inactive Rac1 from non-protrusive membrane and is necessary for Rac1 redistribution to a protrusive tip and fibronectin-dependent Rac1 activation. The second component, RCC2, attenuates Rac1 activation outside the protrusive tip by binding to the Rac1 switch regions and competitively inhibiting GEF action, thus preventing off-axial protrusion. Depletion of Coro1C or RCC2 by RNA interference causes loss of cell polarity that results in shunting migration in 1D or 3D culture systems. Furthermore, morpholinos against Coro1C or RCC2, or mutation of any of the binding sites in the Rac1–RCC2–Coro1C complex delays the arrival of neural crest derivatives at the correct location in developing zebrafish, demonstrating the crucial role in migration guidance in vivo. PMID:25074804

  6. Upregulated expression of Nogo-A and NgR in an experimental model of focal microgyria regulates the migration, proliferation and self-renewal of subventricular zone neural progenitors

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Sixun; Shu, Haifeng; Yang, Tao; Huang, Haidong [Department of Neurosurgery, General Hospital of the People' s Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083 (China); Li, Song [Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Zhao, Ziyi [Central Laboratory, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, 610075 (China); Kuang, Yongqin, E-mail: kuangyongqin@163.com [Department of Neurosurgery, General Hospital of the People' s Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083 (China)

    2016-04-29

    Nogo-A and its receptor (NgR) were first described as myelin-associated inhibitors of neuronal regeneration in response to injury. In recent years, knowledge about the important role of the Nogo-A protein in several neuronal pathologies has grown considerably. Here, we employed a neonatal cortex freeze-lesion (NFL) model in neonatal rats and measured the expression of Nogo-A and NgR in the resulting cerebrocortical microdysgenesis 5–75 days after freezing injury. We observed marked upregulation of Nogo-A and NgR in protein levels. Furthermore, the migration of neural precursor cells (NPCs) derived from the subventricular zone (SVZ) toward the sits of injury was perturbed by treatment of NgR antagonist peptide NEP1-40. In vitro analysis showed that the knockdown of NgR by lentivirus-delivered siRNA promoted in axonal regeneration and SVZ-derived neural stem cell/progenitor cell (SVZ-NPCs) adhesion and migration, findings which were similar to the effects of NEP1-40. Taken together, our results indicate an important role for NgR in regulating the physiological processes of SVZ-NPCs. The observation of upregulated Nogo-A/NgR in lesion sites in the NFL model suggest that the effects of the perturbed Nogo-A are a key feature during the development and/or the progression of cortical malformation. - Highlights: • NFL model is an accurate experimental reproduction of focal microgyria of FCD. • The increase of the Nogo-A Levels occurs in response to freeze-induced focal lesioning. • Nogo-A/NgR may play a critical role for in the pathologic progression of FCD. • Nogo-A is associated with the migration, proliferation and self-renewal of SVZ-NPCs.

  7. p75 neurotrophin receptor positive dental pulp stem cells: new hope for patients with neurodegenerative disease and neural injury.

    Science.gov (United States)

    Dai, Jie-wen; Yuan, Hao; Shen, Shun-yao; Lu, Jing-ting; Zhu, Xiao-fang; Yang, Tong; Zhang, Jiang-fei; Shen, Guo-fang

    2013-08-01

    Neurodegenerative diseases and neural injury are 2 of the most feared disorders that afflict humankind by leading to permanent paralysis and loss of sensation. Cell based treatment for these diseases had gained special interest in recent years. Previous studies showed that dental pulp stem cells (DPSCs) could differentiate toward functionally active neurons both in vitro and in vivo, and could promote neuranagenesis through both cell-autonomous and paracrine neuroregenerative activities. Some of these neuroregenerative activities were unique to tooth-derived stem cells and superior to bone marrow stromal cells. However, DPSCs used in most of these studies were mixed and unfractionated dental pulp cells that contain several types of cells, and most were fibroblast cells while just contain a small portion of DPSCs. Thus, there might be weaker ability of neuranagenesis and more side effects from the fibroblast cells that cannot differentiate into neural cells. p75 neurotrophin receptor (p75NTR) positive DPSCs subpopulation was derived from migrating cranial neural crest cells and had been isolated from DPSCs, which had capacity of differentiation into neurons and repairing neural system. In this article, we hypothesize that p75NTR positive DPSCs simultaneously have greater propensity for neuronal differentiation and fewer side effects from fibroblast, and in vivo transptantation of autologous p75NTR positive DPSCs is a novel method for neuranagenesis. This will bring great hope to patients with neurodegenerative disease and neural injury.

  8. Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse

    Science.gov (United States)

    Schill, Ellen Merrick; Lake, Jonathan I.; Tusheva, Olga A.; Nagy, Nandor; Bery, Saya K.; Foster, Lynne; Avetisyan, Marina; Johnson, Stephen L.; Stenson, William F.; Goldstein, Allan M.; Heuckeroth, Robert O.

    2016-01-01

    Hirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-associated mutation is 100% penetrant, suggesting gene-gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, we found that ibuprofen treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active RAC1/CDC42. Additionally, inhibiting ROCK, a RHOA effector and known RAC1 antagonist, reversed ibuprofen effects on migrating mouse ENCDC in culture. Ibuprofen also inhibited colonization of Ret+/− mouse bowel by ENCDC in vivo and dramatically reduced bowel colonization by chick ENCDC in culture. Interestingly, ibuprofen did not affect ENCDC migration until after at least three hours of exposure. Furthermore, mice deficient in Ptgs1 (COX 1) and Ptgs2 (COX 2) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, ibuprofen did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in zebrafish. Thus, ibuprofen inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in zebrafish, mouse and chick, but there are cell type and strain specific responses. These data raise concern that ibuprofen may increase Hirschsprung disease risk in some genetically susceptible children. PMID:26586201

  9. A simple model of bedform migration

    DEFF Research Database (Denmark)

    Bartholdy, Jesper; Ernstsen, Verner Brandbyge; Flemming, Burg W

    2010-01-01

    and width) of naturally-packed bed material on the bedform lee side, qb(crest). The model is simple, built on a rational description of simplified sediment mechanics, and its calibration constant can be explained in accordance with estimated values of the physical constants on which it is based. Predicted......A model linking subaqueous dune migration to the effective (grain related) shear stress is calibrated by means of flume data for bedform dimensions and migration rates. The effective shear stress is calculated on the basis of a new method assuming a near-bed layer above the mean bed level in which...... the current velocity accelerates towards the bedform crest. As a consequence, the effective bed shear stress corresponds to the shear stress acting directly on top of the bedform. The model operates with the critical Shields stress as a function of grain size, and predicts the deposition (volume per unit time...

  10. Cryoglobulinemic vasculitis in a patient with CREST syndrome.

    Science.gov (United States)

    Hurst, Rebecca L; Berianu, Florentina; Ginsburg, William W; Klein, Christopher J; Englestad, Janean K; Kennelly, Kathleen D

    2014-10-01

    Cryoglobulinemic vasculitis is a rare entity. Although it has been reported in diffuse systemic sclerosis, it has not been reported in calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia (CREST) syndrome. We report a patient with cryoglobulinemic vasculitis with CREST syndrome who did not have typical clinical features of vasculitis. This 58-year-old woman presented with mild generalized weakness and a diagnosis of CREST syndrome, which included Raynaud's syndrome, dysphagia and telangiectasias. She was positive for serum cryoglobulins, which led to a sural nerve biopsy. The biopsy results were consistent with cryoglobulinemic vasculitis. Cryoglobulinemic vasculitis has not been previously reported in CREST syndrome to our knowledge. Additionally, the patient also had limited clinical symptoms. Our patient displays the importance of checking for cryoglobulins and obtaining a nerve biopsy when the serum is positive. Both of these diagnostic tests were integral for directing appropriate treatment for this patient. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Lessons learned from the EU project T-CREST

    DEFF Research Database (Denmark)

    Schoeberl, Martin

    2016-01-01

    A three year EU project, such a T-CREST, with partners from all over Europe and with backgrounds from different domains is a challenging endeavor. Successful execution of such a project depends on more factors than simply performing excellent research. Within the three-year project T-CREST eight...... partners from academia and industry developed and evaluated a time-predictable multi-core processor with an accompanying compiler and a worst-case execution time analysis tool. The tight cooperation of the partners and the shared vision of the need of new computer architectures for future real-time systems...... enabled the successful completion of the T-CREST project. The T-CREST platform is now available, with most components in open source, to be used for future real-time systems and as a platform for further research....

  12. Flow structure in front of the broad-crested weir

    Directory of Open Access Journals (Sweden)

    Zachoval Zbyněk

    2015-01-01

    Full Text Available The paper deals with research focused on description of flow structure in front of broad-crested weir. Based on experimental measurement, the flow structure in front of the weir (the recirculation zone of flow and tornado vortices and flow structure on the weir crest has been described. The determined flow character has been simulated using numerical model and based on comparing results the suitable model of turbulence has been recommended.

  13. Degradation processes and the methods of securing wall crests

    OpenAIRE

    Maciej Trochonowicz; Bogusław Szmygin

    2017-01-01

    The protection of historical ruins requires solution of doctrinal and technical problems. Technical problems concern above all preservation of walls, which are exposed to the influence of atmospheric factors. The problem that needs to be solved in any historic ruin is securing of wall crests. Form of protection of the wall crests depends on many factors, mainly technical features of the wall and architectural and conservatory vision. The following article presents three aspects important for ...

  14. Overflow Characteristic of Cylindrical Shape Crest Weirs Over Horizontal Bed

    Directory of Open Access Journals (Sweden)

    Emad4 AbdulGabbar

    2013-05-01

    Full Text Available The most common types of weirs are the broad-crested weir, the sharp-crested weir, the circular crested weir and the ogee crested weir. Advantages of the cylindrical weir shape include the stable overflow pattern, the ease to pass floating debris, the simplicity of design compared to ogee crest design and the associated lower costs. In present study, it was investigated the overflow characteristics of circular weirs in laboratory for various cylinder radii of three sizes (11.4, 9.0, 6.3 cm, and the models fixed on the channel bed vertically to the direction of flow. The result shows that the increase in the ratio of head to weir radius ratio (Hw/R value causes an increase in discharge coefficient (Cd value for the same height of weir. It was observed that the cylinder size (i.e. radius of cylindrical weir (R has an effect on the (Cd. The flow magnification factor (qw/qs increases with an increase in (Hw/R value and values of (qw/qs were always higher than one for all values of (Hw/R, this means that weirs of cylindrical shape performed better than those of sharp crest for any value of weir radius tested in this study.

  15. Interregional income differentials and migration: their interrelationships.

    Science.gov (United States)

    Tabuchi, T

    1988-02-01

    "The major objective of this paper is to demonstrate that interregional income differential is exogenous to interregional net migration, but not conversely. Utilizing Japanese prefectural-based data for 1954-82, we conduct the following three kinds of analyses to confirm this statement. Firstly, a simple comparison of the crests of interregional time-series plots was made to see which occurred first. Secondly, Sims', 1972, test of causality was done to investigate causation between urban/rural income differential and net migration. Finally, per capita income and population share were examined by two-dimensional phase diagram for nine regions." (SUMMARY IN FRE AND GER) excerpt

  16. CREST--classification resources for environmental sequence tags.

    Directory of Open Access Journals (Sweden)

    Anders Lanzén

    Full Text Available Sequencing of taxonomic or phylogenetic markers is becoming a fast and efficient method for studying environmental microbial communities. This has resulted in a steadily growing collection of marker sequences, most notably of the small-subunit (SSU ribosomal RNA gene, and an increased understanding of microbial phylogeny, diversity and community composition patterns. However, to utilize these large datasets together with new sequencing technologies, a reliable and flexible system for taxonomic classification is critical. We developed CREST (Classification Resources for Environmental Sequence Tags, a set of resources and tools for generating and utilizing custom taxonomies and reference datasets for classification of environmental sequences. CREST uses an alignment-based classification method with the lowest common ancestor algorithm. It also uses explicit rank similarity criteria to reduce false positives and identify novel taxa. We implemented this method in a web server, a command line tool and the graphical user interfaced program MEGAN. Further, we provide the SSU rRNA reference database and taxonomy SilvaMod, derived from the publicly available SILVA SSURef, for classification of sequences from bacteria, archaea and eukaryotes. Using cross-validation and environmental datasets, we compared the performance of CREST and SilvaMod to the RDP Classifier. We also utilized Greengenes as a reference database, both with CREST and the RDP Classifier. These analyses indicate that CREST performs better than alignment-free methods with higher recall rate (sensitivity as well as precision, and with the ability to accurately identify most sequences from novel taxa. Classification using SilvaMod performed better than with Greengenes, particularly when applied to environmental sequences. CREST is freely available under a GNU General Public License (v3 from http://apps.cbu.uib.no/crest and http://lcaclassifier.googlecode.com.

  17. Flow characteristics at trapezoidal broad-crested side weir

    Directory of Open Access Journals (Sweden)

    Říha Jaromír

    2015-06-01

    Full Text Available Broad-crested side weirs have been the subject of numerous hydraulic studies; however, the flow field at the weir crest and in front of the weir in the approach channel still has not been fully described. Also, the discharge coefficient of broad-crested side weirs, whether slightly inclined towards the stream or lateral, still has yet to be clearly determined. Experimental research was carried out to describe the flow characteristics at low Froude numbers in the approach flow channel for various combinations of in- and overflow discharges. Three side weir types with different oblique angles were studied. Their flow characteristics and discharge coefficients were analyzed and assessed based on the results obtained from extensive measurements performed on a hydraulic model. The empirical relation between the angle of side weir obliqueness, Froude numbers in the up- and downstream channels, and the coefficient of obliqueness was derived.

  18. Stability of Cubipod Armoured Roundheads in Short Crested Waves

    DEFF Research Database (Denmark)

    Burcharth, Hans F.; Andersen, Thomas Lykke; Medina, Josep R.

    2011-01-01

    The paper presents a comparison of the stability of concrete cube armour and Cubipod armour in a breakwater roundhead with slope 1:1.5, exposed to both 2-D (long-crested) and 3-D (short-crested) waves. The model tests were performed at the Hydraulics and Coastal Engineering Laboratory at Aalborg...... University, Denmark. The model tests showed that Cubipod armour is more stable than cube armour when exposed to longer waves (steepness approx. 0.025) and has equal stability to cubes in shorter waves. The Cubipod armour layer contained due to its high porosity approximately 6-17% less concrete than the cube...

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

    Science.gov (United States)

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

    2017-04-05

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

  20. The CREST reactive-burn model for explosives

    Directory of Open Access Journals (Sweden)

    Maheswaran M-A.

    2011-01-01

    Full Text Available CREST is an innovative reactive-burn model that has been developed at AWE for simulating shock initiation and detonation propagation behaviour in explosives. The model has a different basis from other reactive-burn models in that its reaction rate is independent of local flow variables behind the shock wave e.g. pressure and temperature. The foundation for CREST, based on a detailed analysis of data from particle-velocity gauge experiments, is that the reaction rate depends only on the local shock strength and the time since the shock passed. Since a measure of shock strength is the entropy of the non-reacted explosive, which remains constant behind a shock, CREST uses an entropy-dependent reaction rate. This paper will provide an overview of the CREST model and its predictive capability. In particular, it will be shown that the model can predict a wide range of experimental phenomena for both shock initiation (e.g. the effects of porosity and initial temperature on sustained-shock and thin-flyer initiation and detonation propagation (e.g. the diameter effect curve and detonation failure cones using a single set of coefficients.

  1. Jaccoud's arthropathy and pulmonary fibrosis in CREST syndrome

    International Nuclear Information System (INIS)

    Spinel B, Nestor; Montenegro, Pablo; Rondon Federico; Restrepo, Jose F; Iglesias G, Antonio

    2010-01-01

    We report a case of a 48 years old patient with diagnosis of incomplete CREST syndrome (variant limited systemic sclerosis) in who we documented the presence of Jaccoud's arthropathy of the hands and pulmonary involvement by pulmonary fibrosis type usual interstitial pneumonia, with positivity for rheumatoid factor and anti-cyclic citrullinated peptide antibody.

  2. Long-throated flumes and broad-crested weirs

    NARCIS (Netherlands)

    Bos, M.G.

    1985-01-01

    Vital for water management are structures that can measure the flow in a wide variety of channels. Chapter 1 introduces the long-throated flume and the broad-crested weir; it explains why this family of structures can meet the boundary conditions and hydraulic demands of most measuring

  3. Dlx proteins position the neural plate border and determine adjacent cell fates.

    Science.gov (United States)

    Woda, Juliana M; Pastagia, Julie; Mercola, Mark; Artinger, Kristin Bruk

    2003-01-01

    The lateral border of the neural plate is a major source of signals that induce primary neurons, neural crest cells and cranial placodes as well as provide patterning cues to mesodermal structures such as somites and heart. Whereas secreted BMP, FGF and Wnt proteins influence the differentiation of neural and non-neural ectoderm, we show here that members of the Dlx family of transcription factors position the border between neural and non-neural ectoderm and are required for the specification of adjacent cell fates. Inhibition of endogenous Dlx activity in Xenopus embryos with an EnR-Dlx homeodomain fusion protein expands the neural plate into non-neural ectoderm tissue whereas ectopic activation of Dlx target genes inhibits neural plate differentiation. Importantly, the stereotypic pattern of border cell fates in the adjacent ectoderm is re-established only under conditions where the expanded neural plate abuts Dlx-positive non-neural ectoderm. Experiments in which presumptive neural plate was grafted to ventral ectoderm reiterate induction of neural crest and placodal lineages and also demonstrate that Dlx activity is required in non-neural ectoderm for the production of signals needed for induction of these cells. We propose that Dlx proteins regulate intercellular signaling across the interface between neural and non-neural ectoderm that is critical for inducing and patterning adjacent cell fates.

  4. Hydraulic Evaluation of the Crest Wing Wave Energy Converter

    DEFF Research Database (Denmark)

    Kofoed, Jens Peter; Antonishen, Michael Patrick

    This report presents the results of an experimental study of the wave energy converting abilities of the Crest Wing wave energy converter (WEC). The Crest Wing is a WEC that uses its movement in matching the shape of an oncoming wave to generate power. Model tests have been performed using a scale...... model (length scale 1:30), provided by WaveEnergyFyn, in regular and irregular wave states that can be found in Assessment of Wave Energy Devices. Best Practice as used in Denmark (Frigaard et al., 2008). The tests were carried out at Dept. of Civil Engineering, Aalborg (Frigaard et al., 2008......). The tests were carried out at Dept. of Civil Engineering, Aalborg University (AAU) in the 3D deep water wave tank. The displacement and force applied to a power take off system, provided by WaveEnergyFyn, were measured and used to calculate total power take off....

  5. TeV electron measurement with CREST experiment

    Science.gov (United States)

    Park, Nahee; Anderson, T.; Bower, C.; Coutu, S.; Gennaro, J.; Geske, M.; Muller, D.; Musser, J.; Nutter, S.

    CREST, the Cosmic Ray Electron Synchrotron Telescope is a balloon-borne experiment de-signed to measure the spectrum of multi-TeV electrons by the detection of the x-ray synchrotron photons generated in the magnetic field of the Earth. Electrons in the TeV range are expected to reflect the properties of local sources because fluxes from remote locations are suppressed by radiative losses during propagation. Since CREST needs to intersect only a portion of the kilometers-long trail of photons generated by the high-energy electron, the method yields a larger effective area than the physical size of the detector, boosting detection areas. The in-strument is composed of an array of 1024 BaF2 crystals and a set of scintillating veto counters. A long duration balloon flight in Antarctica is currently planned for the 2010-11 season.

  6. The CREST Simulation Development Process: Training the Next Generation.

    Science.gov (United States)

    Sweet, Robert M

    2017-04-01

    The challenges of training and assessing endourologic skill have driven the development of new training systems. The Center for Research in Education and Simulation Technologies (CREST) has developed a team and a methodology to facilitate this development process. Backwards design principles were applied. A panel of experts first defined desired clinical and educational outcomes. Outcomes were subsequently linked to learning objectives. Gross task deconstruction was performed, and the primary domain was classified as primarily involving decision-making, psychomotor skill, or communication. A more detailed cognitive task analysis was performed to elicit and prioritize relevant anatomy/tissues, metrics, and errors. Reference anatomy was created using a digital anatomist and clinician working off of a clinical data set. Three dimensional printing can facilitate this process. When possible, synthetic or virtual tissue behavior and textures were recreated using data derived from human tissue. Embedded sensors/markers and/or computer-based systems were used to facilitate the collection of objective metrics. A learning Verification and validation occurred throughout the engineering development process. Nine endourology-relevant training systems were created by CREST with this approach. Systems include basic laparoscopic skills (BLUS), vesicourethral anastomosis, pyeloplasty, cystoscopic procedures, stent placement, rigid and flexible ureteroscopy, GreenLight PVP (GL Sim), Percutaneous access with C-arm (CAT), Nephrolithotomy (NLM), and a vascular injury model. Mixed modalities have been used, including "smart" physical models, virtual reality, augmented reality, and video. Substantial validity evidence for training and assessment has been collected on systems. An open source manikin-based modular platform is under development by CREST with the Department of Defense that will unify these and other commercial task trainers through the common physiology engine, learning

  7. MR imaging findings of medial tibial crest friction

    International Nuclear Information System (INIS)

    Klontzas, Michail E.; Akoumianakis, Ioannis D.; Vagios, Ilias; Karantanas, Apostolos H.

    2013-01-01

    Objective: Medial tibial condyle bone marrow edema (BME), associated with soft tissue edema (STe) surrounding the medial collateral ligament, was incidentally observed in MRI examinations of young and athletic individuals. The aim of the present study was to 1. Prospectively investigate the association between these findings and coexistence of localized pain, and 2. Explore the possible contribution of the tibial morphology to its pathogenesis. Methods: The medial tibial condyle crest was evaluated in 632 knee MRI examinations. The angle and depth were measured by two separate evaluators. The presence of STe and BME was recorded. A third evaluator blindly assessed the presence of pain at this site. Results: BME associated with STe was found in 24 patients (with no history of previous trauma, osteoarthritis, tumor or pes anserine bursitis). The mean crest angle was 151.3° (95%CI 147.4–155.3°) compared to 159.4° (95%CI 158.8–160°) in controls (Mann–Whitney test, P < 0.0001). MRI findings were highly predictive of localized pain (sensitivity 92% specificity 99%, Fisher's exact test, P < 0.0001). Conclusion: Friction at the medial tibial condyle crest is a painful syndrome. MRI is a highly specific and sensitive imaging modality for its diagnosis

  8. MR imaging findings of medial tibial crest friction

    Energy Technology Data Exchange (ETDEWEB)

    Klontzas, Michail E., E-mail: miklontzas@gmail.com; Akoumianakis, Ioannis D., E-mail: ioannis.akoumianakis@gmail.com; Vagios, Ilias, E-mail: iliasvagios@gmail.com; Karantanas, Apostolos H., E-mail: akarantanas@gmail.com

    2013-11-01

    Objective: Medial tibial condyle bone marrow edema (BME), associated with soft tissue edema (STe) surrounding the medial collateral ligament, was incidentally observed in MRI examinations of young and athletic individuals. The aim of the present study was to 1. Prospectively investigate the association between these findings and coexistence of localized pain, and 2. Explore the possible contribution of the tibial morphology to its pathogenesis. Methods: The medial tibial condyle crest was evaluated in 632 knee MRI examinations. The angle and depth were measured by two separate evaluators. The presence of STe and BME was recorded. A third evaluator blindly assessed the presence of pain at this site. Results: BME associated with STe was found in 24 patients (with no history of previous trauma, osteoarthritis, tumor or pes anserine bursitis). The mean crest angle was 151.3° (95%CI 147.4–155.3°) compared to 159.4° (95%CI 158.8–160°) in controls (Mann–Whitney test, P < 0.0001). MRI findings were highly predictive of localized pain (sensitivity 92% specificity 99%, Fisher's exact test, P < 0.0001). Conclusion: Friction at the medial tibial condyle crest is a painful syndrome. MRI is a highly specific and sensitive imaging modality for its diagnosis.

  9. Migration chemistry

    International Nuclear Information System (INIS)

    Carlsen, L.

    1992-05-01

    Migration chemistry, the influence of chemical -, biochemical - and physico-chemical reactions on the migration behaviour of pollutants in the environment, is an interplay between the actual natur of the pollutant and the characteristics of the environment, such as pH, redox conditions and organic matter content. The wide selection of possible pollutants in combination with varying geological media, as well as the operation of different chemical -, biochemical - and physico-chemical reactions compleactes the prediction of the influence of these processes on the mobility of pollutants. The report summarizes a wide range of potential pollutants in the terrestrial environment as well as a variety of chemical -, biochemical - and physico-chemical reactions, which can be expected to influence the migration behaviour, comprising diffusion, dispersion, convection, sorption/desorption, precipitation/dissolution, transformations/degradations, biochemical reactions and complex formation. The latter comprises the complexation of metal ions as well as non-polar organics to naturally occurring organic macromolecules. The influence of the single types of processes on the migration process is elucidated based on theoretical studies. The influence of chemical -, biochemical - and physico-chemical reactions on the migration behaviour is unambiguous, as the processes apparently control the transport of pollutants in the terrestrial environment. As the simple, conventional K D concept breaks down, it is suggested that the migration process should be described in terms of the alternative concepts chemical dispersion, average-elution-time and effective retention. (AB) (134 refs.)

  10. On the development of a bedform migration model

    DEFF Research Database (Denmark)

    Bartholdy, Jesper; Ernstsen, V.B.; Flemming, B.W.

    2008-01-01

    A model linking subaqueous dune migration to the effective (grain related) shear stress is calibrated by means of flume data for bedform dimensions and migration rates. The effective shear stress is calculated on the basis of a new method assuming a near-bed layer above the mean bed level in which...... the current velocity accelerates towards the bedform crest. As a consequence, the effective bed shear stress corresponds to the shear stress acting directly on top of the bedform. The model operates with the critical Shields stress as a function of grain size. It predicts the deposition (volume per unit time...

  11. CREST Calcinosis Affecting the Lumbar and Cervical Spine and the Use of Minimally-Invasive Surgery

    OpenAIRE

    Faraj, Kassem; Perez-Cruet, Kristin; Perez-Cruet, Mick

    2017-01-01

    Calcinosis in CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome can affect the spinal and paraspinal areas. We present the first case to our knowledge where a CREST syndrome patient required surgery for spinal calcinosis in both the cervical and lumbar areas.?A 66-year-old female with a history of CREST syndrome presented with right-sided lower extremity radicular pain. A computed tomography (CT) scan showed bilateral lumbar masses (5...

  12. Hydraulic evaluation of the Crest Wing wave energy converter

    Energy Technology Data Exchange (ETDEWEB)

    Kofoed, J.P.; Antonishen, M.

    2008-09-15

    The Crest Wing Wave Energy Converter is currently being developed by Henning Pilgaard, of WaveEnergyFyn, Denmark. It is meant to act like a carpet on the water, conforming to the shape of each wave and using that movement to generate power. The thought of making a WEC that acts like a carpet on top of the waves is not new; ongoing or past projects such as the Pelamis and Cockerel Raft were designed with this thought in mind. The real difference with the Crest Wing is that it has skirt drafts, that extend down into the water and create suction; this increases the effective mass of the WEC while minimizing the material use. Special attention was given to the design of the first and last floaters as they are meant to act as a smooth transition between wave and machine. Their purpose is to make sure that no air gets under the two middle floaters so that suction is not broken and the device continues to function well. In summary the Crest Wing functions and is able to produce power with a good overall efficiency. The configuration with relative reference PTO (Power Take Off) is superior. It has not been proven that the idea of mounting skirts on the floaters is leading to a better performance. Thus, the study leads to the conclusion that the idea of making a simple hinged raft type device is good, and it is likely that the construction cost for a device of this type can be kept down. However, the study also leaves the chance that some limited draft of skirts in combination with inlet/outlet devices, could prove beneficial. In case of further testing on this device, an effort should be made to design and construct a more easily and accurately controlled PTO model in the test setup. This could greatly improve the quality of the output of such tests. (ln)

  13. Multielement analysis of iliac crest bone by neutron activation

    International Nuclear Information System (INIS)

    Aras, N.K.; Yilmaz, G.; Korkusuz, F.; Olmez, I.; Sepici, B.; Eksioglu, F.; Bode, P.

    2000-01-01

    Bone samples from iliac crest were obtained from apparently healthy female (n = 4) and male (n = 8) subjects with ages between 15-50. Cortical and trabecular parts were separated and soft tissues like fat, muscle and blood were removed. Calcium, Mg, Na, Cl, Fe, Zn, Br, Sr, and Cs were determined by instrumental neutron activation analysis and other techniques, and their relations were discussed. Fairly good agreement was obtained with literature data. These values may serve as reference values for subjects from a Turkish population. (author)

  14. A Colonial Conundrum: Boy with Sulphur-Crested Cockatoo

    Directory of Open Access Journals (Sweden)

    Elisabeth Findlay

    2008-12-01

    Full Text Available This paper presents a detailed analysis of the perplexing painting Boy with Sulphur-Crested Cockatoo. Unfortunately, there is little information on the provenance of the portrait, including the identity of the artist, sitter and patron. It will be argued that it is the work of Augustus Earle and that it is a portrait of Daniel Cooper II and was commissioned by his uncle, also named Daniel Cooper. The aim of this article is to start to unravel the ambiguities of the image, and I suggest that the painting is a strong statement on the rights of freed convicts in Australian colonial society

  15. Taxane-induced morphea in a patient with CREST syndrome

    Directory of Open Access Journals (Sweden)

    Susan Michele Bouchard

    2010-07-01

    Full Text Available The taxanes, docetaxel and paclitaxel, are microtubule stabilizing chemotherapeutic agents that have demonstrated antineoplastic effects in a variety of solid tumors. They have been linked to the development of localized cutaneous sclerosis in some patients. We present a case of docetaxel-induced cutaneous sclerosis of the lower extremities in a patient with pre-existing CREST syndrome. We propose that patients with a history of limited or diffuse systemic sclerosis should be given taxane chemotherapy with caution, as these patients may have an immunological predisposition for the development of drug-induced morphea.

  16. Migrating Worker

    DEFF Research Database (Denmark)

    Hansen, Hans

    This is the preliminary report on the results obtained in the Migrating Worker-project. This project was initiated by the Danish Ministry of Finance with the aim of illustrating the effects of the 1408/71 agreement and the bilateral double taxation agreements Denmark has with the countries included...

  17. Dateline Migration.

    Science.gov (United States)

    Tomasi, Lydio E., Ed.

    1995-01-01

    Presents data on international migration and its effects in and between various countries in North America, Europe, and Africa. Discussions include refugee, immigrant, and migrant worker flows; the legal, political, and social problems surrounding immigrants; alien terrorism and law enforcement problems; and migrant effects on education, social…

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-28

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

  20. WAC Bennett Dam - the characterization of a crest sinkhole

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, R.A.; Gaffran, P.C. [British Columbia Hydro, Burnaby, BC (Canada); Watts, B.D. [Klohn-Crippen Consultants Ltd., Richmond, BC (Canada); Sobkowicz, J.C. [Thurber Engineering Ltd., Vancouver, BC (Canada); Kupper, A.G. [AGRA Earth and Environmental, Edmonton, AB (Canada)

    1998-11-01

    In June, 1996, a small hole was discovered in the asphaltic concrete road on the crest of the 183 m high WAC Bennett Dam on the Peace River in northeastern British Columbia. Examination of the hole resulted in a sinkhole on the dam crest. The sinkhole was 2.5 m in diameter and 7 m deep. Speculation was that the cavity was likely associated in some way with a buried survey benchmark tube. An investigation was immediately planned and executed to characterize the sinkhole, to determine the extent of damage and the safety status of this very large dam. British Columbia`s Dam Safety Regulator made the decision to lower the reservoir level. During the reservoir drawdown, various surface geophysical techniques were used to investigate the condition of the dam beyond the sinkholes. Intrusive investigations of the sinkhole were also planned. This involved trial drilling and downhole geophysical surveys in intact portions of the core at locations far from the sinkhole. The objectives and criteria developed for the investigation program are summarized. Scope of key activities at the sinkhole and important lessons learned during the investigation are also described. 9 refs., 15 figs.

  1. Concentration profiling of minerals in iliac crest bone tissue of opium addicted humans using inductively coupled plasma and discriminant analysis techniques.

    Science.gov (United States)

    Mani-Varnosfaderani, Ahmad; Jamshidi, Mahbobeh; Yeganeh, Ali; Mahmoudi, Mani

    2016-02-20

    Opium addiction is one of the main health problems in developing countries and induces serious defects on the human body. In this work, the concentrations of 32 minerals including alkaline, heavy and toxic metals have been determined in the iliac crest bone tissue of 22 opium addicted individuals using inductively coupled plasma-optical emission spectroscopy (ICP-OES). The bone tissues of 30 humans with no physiological and metabolomic diseases were used as the control group. For subsequent analyses, the linear and quadratic discriminant analysis techniques have been used for classification of the data into "addicted" and "non-addicted" groups. Moreover, the counter-propagation artificial neural network (CPANN) has been used for clustering of the data. The results revealed that the CPANN is a robust model and thoroughly classifies the data. The area under the curve for the receiver operating characteristic curve for this model was more than 0.91. Investigation of the results revealed that the opium consumption causes a deficiency in the level of Calcium, Phosphate, Potassium and Sodium in iliac crest bone tissue. Moreover, this type of addiction induces an increment in the level of toxic and heavy metals such as Co, Cr, Mo and Ni in iliac crest tissue. The correlation analysis revealed that there were no significant dependencies between the age of the samples and the mineral content of their iliac crest, in this study. The results of this work suggest that the opium addicted individuals need thorough and restricted dietary and medical care programs after recovery phases, in order to have healthy bones. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. A preference for migration

    OpenAIRE

    Stark, Oded

    2007-01-01

    At least to some extent migration behavior is the outcome of a preference for migration. The pattern of migration as an outcome of a preference for migration depends on two key factors: imitation technology and migration feasibility. We show that these factors jointly determine the outcome of a preference for migration and we provide examples that illustrate how the prevalence and transmission of a migration-forming preference yield distinct migration patterns. In particular, the imitation of...

  3. Is mitochondrial DNA divergence of near easter crested newts, Triturus karelinii group, reflected by differentiation of skull shape

    NARCIS (Netherlands)

    Ivanovic, A.; Uzum, N.; Wielstra, B.M.; Olgun, K.; Litvinchuk, S.N.; Kalezic, M.L.; Arntzen, J.W.

    2013-01-01

    The Eurasian Triturus karelinii group of crested newts comprises three distinct, geographically coherent mitochondrial DNA lineages, designated as the eastern, central and western lineage. These three lineages are genetically as diverged as other, morphologically well-differentiated crested newt

  4. Diet of double-crested cormorants wintering in Texas

    Science.gov (United States)

    Campo, J.J.; Thompson, B.C.; Barron, J.C.; Telfair II, R. C.; Durocher, P.; Gutreuter, S.

    1993-01-01

    The diets of 420 Double-crested Cormorants (Phalacrocorax auritus) were studied during November 1986-March 1987 on eight public reservoirs in Texas. Prey included 29 fish species and the mean live weight of fish per bird was 122 g. Fishes a??415 mm long were ingested, but those a??125 mm accounted for 90% of cormorant food contents by number. Shad (Dorosoma spp.) and sunfishes (Lepomis spp.) accounted for 90% of the total food items by number. Consumption of fishes (percent by weight) was different for male vs. female and adult vs. juvenile cormorants. Total consumption of fish by weight was consistent throughout the period; however, fewer but much larger fish were consumed after 15 February. Cormorants ate fishes that were most abundant in reservoirs. Sport fishes made up a substantial portion of cormorant food by weight, but not by number on some reservoirs. Cormorants ate very few large sport fish, however.

  5. CREST: Center for Renewable Energy Science and Technology

    Energy Technology Data Exchange (ETDEWEB)

    Billo, Richard E. [Univ. of Texas, Arlington, TX (United States); Rajeshwar, Krishnan [Univ. of Texas, Arlington, TX (United States)

    2012-03-20

    The DOE project addressed an approach to the hydrogen economy by researching hydrogen generation from low cost domestic fossil fuel sources. Specifically, the CREST research team developed new processes for extracting hydrogen from southwestern lignite for the production of clean synthetic fuels such as synthetic crude oil that is free of sulfur, carbon dioxide and other pollutants that can be shipped to nearby Texas refineries and power plants for development of transportation fuels and power generation. Research was also undertaken to convert any potential by-products of this process such as CO2 to useful chemicals and gases which may be recycled and used as feedstock to the synthetic fuel process. Finally, to ensure the proposed process is functional beyond bench scale, a detailed design of a pilot plant was completed. The overall project was divided into five tasks including a management task as outlined below.

  6. Medical image of the week: CREST plus ILD

    Directory of Open Access Journals (Sweden)

    Oliva I

    2013-06-01

    Full Text Available A 60 year old female with a history of fibromyalgia presented with dyspnea and skin changes, predominantly on the hands. Physical exam and imaging showed classic findings of limited cutaneous systemic sclerosis (scleroderma CREST syndrome. Calcinosis cutis (Figure 1A, Raynaud’s (not shown but endorsed by the patient, Esophageal dysmotility (Figure 1B, dilated esophagus, Sclerodactyly (Figure 1C, and Teleganectasias (Figure 1D were all present. Ground glass opacities were seen predominantly in the bilateral lower lung zones, associated with increased reticular markings (Figure 2A, and traction bronchiectasis (Figure 2B. Pulmonary involvement is noted in the majority of scleroderma patients. Interstitial lung disease (ILD is common and often portends a poor prognosis.

  7. Generation of Induced Pluripotent Stem Cells from Hair Follicle Bulge Neural Crest Stem Cells

    NARCIS (Netherlands)

    Ma, Ming-San; Czepiel, Marcin; Krause, Tina; Schaefer, Karl-Herbert; Boddeke, Erik; Copray, Sjef

    2014-01-01

    Induced pluripotent stem cells (iPSCs) are promising candidates for the study of disease models as well as for tissue engineering purposes. Part of a strategy to develop safe reprogramming technique is reducing the number of exogenous reprogramming factors. Some cells types are more prone to

  8. The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival.

    Science.gov (United States)

    Dworkin, Sebastian; Boglev, Yeliz; Owens, Harley; Goldie, Stephen J

    2016-08-03

    Craniofacial defects (CFD) are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog ( Shh ), a vertebrate orthologue of Drosophila hedgehog , is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla) and lower jaw (mandible).

  9. The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival

    Directory of Open Access Journals (Sweden)

    Sebastian Dworkin

    2016-08-01

    Full Text Available Craniofacial defects (CFD are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog (Shh, a vertebrate orthologue of Drosophila hedgehog, is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla and lower jaw (mandible.

  10. The hindbrain neural crest and the development of the enteric nervous system

    NARCIS (Netherlands)

    M.J.H. van der Sanden (Marjo)

    1994-01-01

    textabstractThe wonder of things is the beginning of knowledge, as was already stated by Aristotle, the fIrst embryologist known to history. Embryology has remained a source of wonder ever since. It all starts with the fusion of the female egg and the male sperm. Sperm cells were first described by

  11. The 'Unicorn' dinosaur that wasn't: a new reconstruction of the crest of Tsintaosaurus and the early evolution of the lambeosaurine crest and rostrum.

    Directory of Open Access Journals (Sweden)

    Albert Prieto-Márquez

    Full Text Available The lambeosaurine Tsintaosaurus spinorhinus has traditionally been reconstructed with an elevated, hollow, spike-like crest composed entirely of the nasal bones, although this has been disputed. Here, we provide a new reconstruction of the skull of this species based on reexamination and reinterpretation of the morphology and articular relationships of the type and Paratype skulls and a fragmentary crest. We confirm the presence of a supracranial crest composed of the elevated nasal bones, but also including the premaxillae. We hypothesize that the crest is a tall, lobate, hollow structure that projects dorsally and slightly caudally a distance greater than the height of the skull along the quadrate. In our reconstruction, the nasal passage passes through the crest, but enters the skull rostral to the tubular process of the nasals, not through it. Tsintaosaurus spinorhinus is rediagnosed on the basis of a suite of cranial autapomorphies including a circumnarial fossa subdivided into three accessory fossae, prefrontal with ascending rostral process and lateral flange, nasals fused sagittally to form elongate tubular process that rises dorsally from skull roof, each nasal being expanded rostrocaudally into a rhomboid distal process, and medial processes of premaxillae at the summit of the cranial crest inserted between rhomboid processes of nasals. Tsintaosaurus spinorhinus lacks characters that are present in more derived lambeosaurines (parasaurolophins and lambeosaurins, such as rotation of the caudal margin of the crest to an acute angle with the skull roof, lateral processes of the nasals that enclose part of the intracranial cavity and participate in the formation of the walls of the common median chamber, and a smooth narial fossa lacking ridges and accessory fossae. We hypothesize that ancestrally the rostrum of lambeosaurines may have been more similar to that in Saurolophinae, and became subsequently reduced in complexity during

  12. The 'Unicorn' dinosaur that wasn't: a new reconstruction of the crest of Tsintaosaurus and the early evolution of the lambeosaurine crest and rostrum.

    Science.gov (United States)

    Prieto-Márquez, Albert; Wagner, Jonathan R

    2013-01-01

    The lambeosaurine Tsintaosaurus spinorhinus has traditionally been reconstructed with an elevated, hollow, spike-like crest composed entirely of the nasal bones, although this has been disputed. Here, we provide a new reconstruction of the skull of this species based on reexamination and reinterpretation of the morphology and articular relationships of the type and Paratype skulls and a fragmentary crest. We confirm the presence of a supracranial crest composed of the elevated nasal bones, but also including the premaxillae. We hypothesize that the crest is a tall, lobate, hollow structure that projects dorsally and slightly caudally a distance greater than the height of the skull along the quadrate. In our reconstruction, the nasal passage passes through the crest, but enters the skull rostral to the tubular process of the nasals, not through it. Tsintaosaurus spinorhinus is rediagnosed on the basis of a suite of cranial autapomorphies including a circumnarial fossa subdivided into three accessory fossae, prefrontal with ascending rostral process and lateral flange, nasals fused sagittally to form elongate tubular process that rises dorsally from skull roof, each nasal being expanded rostrocaudally into a rhomboid distal process, and medial processes of premaxillae at the summit of the cranial crest inserted between rhomboid processes of nasals. Tsintaosaurus spinorhinus lacks characters that are present in more derived lambeosaurines (parasaurolophins and lambeosaurins), such as rotation of the caudal margin of the crest to an acute angle with the skull roof, lateral processes of the nasals that enclose part of the intracranial cavity and participate in the formation of the walls of the common median chamber, and a smooth narial fossa lacking ridges and accessory fossae. We hypothesize that ancestrally the rostrum of lambeosaurines may have been more similar to that in Saurolophinae, and became subsequently reduced in complexity during evolution of the group.

  13. The ‘Unicorn’ Dinosaur That Wasn’t: A New Reconstruction of the Crest of Tsintaosaurus and the Early Evolution of the Lambeosaurine Crest and Rostrum

    Science.gov (United States)

    Prieto-Márquez, Albert; Wagner, Jonathan R.

    2013-01-01

    The lambeosaurine Tsintaosaurus spinorhinus has traditionally been reconstructed with an elevated, hollow, spike-like crest composed entirely of the nasal bones, although this has been disputed. Here, we provide a new reconstruction of the skull of this species based on reexamination and reinterpretation of the morphology and articular relationships of the type and Paratype skulls and a fragmentary crest. We confirm the presence of a supracranial crest composed of the elevated nasal bones, but also including the premaxillae. We hypothesize that the crest is a tall, lobate, hollow structure that projects dorsally and slightly caudally a distance greater than the height of the skull along the quadrate. In our reconstruction, the nasal passage passes through the crest, but enters the skull rostral to the tubular process of the nasals, not through it. Tsintaosaurus spinorhinus is rediagnosed on the basis of a suite of cranial autapomorphies including a circumnarial fossa subdivided into three accessory fossae, prefrontal with ascending rostral process and lateral flange, nasals fused sagittally to form elongate tubular process that rises dorsally from skull roof, each nasal being expanded rostrocaudally into a rhomboid distal process, and medial processes of premaxillae at the summit of the cranial crest inserted between rhomboid processes of nasals. Tsintaosaurus spinorhinus lacks characters that are present in more derived lambeosaurines (parasaurolophins and lambeosaurins), such as rotation of the caudal margin of the crest to an acute angle with the skull roof, lateral processes of the nasals that enclose part of the intracranial cavity and participate in the formation of the walls of the common median chamber, and a smooth narial fossa lacking ridges and accessory fossae. We hypothesize that ancestrally the rostrum of lambeosaurines may have been more similar to that in Saurolophinae, and became subsequently reduced in complexity during evolution of the group

  14. Neurally Derived Tissues in Xenopus laevis Embryos Exhibit a Consistent Bioelectrical Left-Right Asymmetry

    Directory of Open Access Journals (Sweden)

    Vaibhav P. Pai

    2012-01-01

    Full Text Available Consistent left-right asymmetry in organ morphogenesis is a fascinating aspect of bilaterian development. Although embryonic patterning of asymmetric viscera, heart, and brain is beginning to be understood, less is known about possible subtle asymmetries present in anatomically identical paired structures. We investigated two important developmental events: physiological controls of eye development and specification of neural crest derivatives, in Xenopus laevis embryos. We found that the striking hyperpolarization of transmembrane potential (Vmem demarcating eye induction usually occurs in the right eye field first. This asymmetry is randomized by perturbing visceral left-right patterning, suggesting that eye asymmetry is linked to mechanisms establishing primary laterality. Bilateral misexpression of a depolarizing channel mRNA affects primarily the right eye, revealing an additional functional asymmetry in the control of eye patterning by Vmem. The ATP-sensitive K+ channel subunit transcript, SUR1, is asymmetrically expressed in the eye primordia, thus being a good candidate for the observed physiological asymmetries. Such subtle asymmetries are not only seen in the eye: consistent asymmetry was also observed in the migration of differentiated melanocytes on the left and right sides. These data suggest that even anatomically symmetrical structures may possess subtle but consistent laterality and interact with other developmental left-right patterning pathways.

  15. Quill injury - cause od death of captive indian crested porcupine(Hystrix indica, Kerr, 1792

    Directory of Open Access Journals (Sweden)

    Tanja Švara

    2015-03-01

    Full Text Available Indian crested porcupine (Hystrix indica is a member of the family of Old World porcupines (Hystricidae. Its body is covered with multiple layers of quills, which serve for warning and attack if animal is threatened. However, the literature data on injuries caused by Indian crested porcupine are absent. We describe pathomorphological lesions in an Indian crested porcupine from the Ljubljana Zoo, which died after a fight with a younger male that caused a perforative quill injury of the thoracic wall, followed by septicaemia. Macroscopic, microscopic and bacteriological findings were detailed

  16. Short-crested waves in deep water: a numerical investigation of recent laboratory experiments

    DEFF Research Database (Denmark)

    Fuhrman, David R.; Madsen, Per A.

    2006-01-01

    A numerical study of quasi-steady, doubly-periodic monochromatic short-crested wave patterns in deep water is conducted using a high-order Boussinesq-type model. Simulations using linear wavemaker conditions in the nonlinear model are initially used to approximate conditions from recent laboratory...... experiments. The computed patterns share many features with those observed in wavetanks, including bending (both frontwards and backwards) of the wave crests, dipping at the crest centerlines, and a pronounced long modulation in the direction of propagation. A new and simple explanation for these features...

  17. A Comparative Study of Growth Patterns in Crested Langurs and Vervet Monkeys

    Directory of Open Access Journals (Sweden)

    Debra R. Bolter

    2011-01-01

    Full Text Available The physical growth patterns of crested langurs and vervet monkeys are investigated for several unilinear dimensions. Long bone lengths, trunk height, foot length, epiphyseal fusion of the long bones and the pelvis, and cranial capacity are compared through six dental growth stages in male Trachypithecus cristatus (crested langurs and Cercopithecus aethiops (vervet monkeys. Results show that the body elements of crested langurs mature differently than those of vervets. In some dimensions, langurs and vervets grow comparably, in others vervets attain adult values in advance of crested langurs, and in one feature the langurs are accelerated. Several factors may explain this difference, including phylogeny, diet, ecology, and locomotion. This study proposes that locomotor requirements affect differences in somatic growth between the species.

  18. First report and breeding record of the Chinese Crested Tern Thalasseus bernsteini on the Korean Peninsula

    Directory of Open Access Journals (Sweden)

    Se-Kyu Song

    2017-06-01

    Full Text Available The Chinese Crested Tern Thalasseus bernsteini is a critically endangered species (as designated by the IUCN (International Union for Conservation of Nature and Natural Resources. This report expands the known breeding grounds of these birds eastward. An individual of the Chinese Crested Tern was first observed at an uninhabited island of Jeollanam-do in Korea on April 28, 2016. On May 9, 2016 five Chinese Crested Terns (consisting of 2 breeding pairs and a single bird were observed. Nests from the breeding pairs were found, at a distance of 0.6 m from each other; each pair was observed incubating one egg in the nest. To our knowledge, this is the easternmost record of breeding grounds for the Chinese Crested Tern.

  19. Crest Factor Reduction for OFDM Using Selective Subcarrier Degradation

    Institute of Scientific and Technical Information of China (English)

    R. Neil Braithwaite

    2011-01-01

    This paper describes a crest factor reduction (CFR) method that reduces peaks in the time domain by modifying selected data subcarriers within an OFDM signal. The data subcarriers selected for modification vary with each symbol interval and are limited to those subcarriers whose aata elements are mapped onto the outer boundary of the constellation. In the proposed method, a set of peaks are identified within an OFDM symbol interval. Data subcarriers whose data element has a positive or negative correlation with the set peak are selected. For a subcarrier with an outer element and a significant positive correlation, a bit error (reversal) is intentionally introduced. This moves the data element to the opposite side of the constellation. Outer elements on negatively-correlatea subcarriers are increased in magnitude along the real or imaginary axis. Experimental results show that selecting the correct subcarriers for bit reversals and outward enhancements reduces the peak-to-average power ratio (PAPR) of the OFDM signal to a target value and limits in-band degradation measured by bit error rate (BER) and error vector magnitude (EVM).

  20. Distress prevention by grooming others in crested black macaques.

    Science.gov (United States)

    Aureli, Filippo; Yates, Kerrie

    2010-02-23

    Allogrooming is probably one of the most common and most studied social behaviours in a variety of animals. Whereas the short-term benefits for the groomee have often been investigated, little is known about the effects for the groomer. Our study focused on the short-term effects of grooming another group member in seven adult female crested black macaques (Macaca nigra). We found reductions in self-directed behaviour, an indicator of anxiety, and aggressive tendencies soon after grooming, when compared to matched-control periods. These findings can be interpreted as evidence of distress prevention, possibly mediated by an increase in tolerance. Indeed, a former groomee was more likely to be the nearest neighbour of the former groomer in the 10 min after grooming ended. Thus, the role of grooming in short-term distress alleviation can be applicable to the groomer as well as the groomee. These short-term effects, together with the longer-term effects of large and/or strong grooming networks confirm that grooming, as well as receiving grooming, has great importance for social dynamics.

  1. The Globalisation of migration

    OpenAIRE

    Milan Mesić

    2002-01-01

    The paper demonstrates that contemporary international migration is a constitutive part of the globalisation process. After defining the concepts of globalisation and the globalisation of migration, the author discusses six key themes, linking globalisation and international migration (“global cities”, the scale of migration; diversification of migration flows; globalisation of science and education; international migration and citizenship; emigrant communities and new identities). First, in ...

  2. Enteric Neural Cells From Hirschsprung Disease Patients Form Ganglia in Autologous Aneuronal ColonSummary

    Directory of Open Access Journals (Sweden)

    Benjamin N. Rollo

    2016-01-01

    Full Text Available Background & Aims: Hirschsprung disease (HSCR is caused by failure of cells derived from the neural crest (NC to colonize the distal bowel in early embryogenesis, resulting in absence of the enteric nervous system (ENS and failure of intestinal transit postnatally. Treatment is by distal bowel resection, but neural cell replacement may be an alternative. We tested whether aneuronal (aganglionic colon tissue from patients may be colonized by autologous ENS-derived cells. Methods: Cells were obtained and cryopreserved from 31 HSCR patients from the proximal resection margin of colon, and ENS cells were isolated using flow cytometry for the NC marker p75 (nine patients. Aneuronal colon tissue was obtained from the distal resection margin (23 patients. ENS cells were assessed for NC markers immunohistologically and by quantitative reverse-transcription polymerase chain reaction, and mitosis was detected by ethynyl-2′-deoxyuridine labeling. The ability of human HSCR postnatal ENS-derived cells to colonize the embryonic intestine was demonstrated by organ coculture with avian embryo gut, and the ability of human postnatal HSCR aneuronal colon muscle to support ENS formation was tested by organ coculture with embryonic mouse ENS cells. Finally, the ability of HSCR patient ENS cells to colonize autologous aneuronal colon muscle tissue was assessed. Results: ENS-derived p75-sorted cells from patients expressed multiple NC progenitor and differentiation markers and proliferated in culture under conditions simulating Wnt signaling. In organ culture, patient ENS cells migrated appropriately in aneural quail embryo gut, and mouse embryo ENS cells rapidly spread, differentiated, and extended axons in patient aneuronal colon muscle tissue. Postnatal ENS cells derived from HSCR patients colonized autologous aneuronal colon tissue in cocultures, proliferating and differentiating as neurons and glia. Conclusions: NC-lineage cells can be obtained from HSCR

  3. Marek’s disease in the holland white crested chickens

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    Spalević Ljiljana

    2016-01-01

    Full Text Available Marek’s disease is a viral lymphoproliferative disease of poultry characterized by the creation of lymphoma in muscle, skin, eye or internal organs. Virus maturing into infective forms in follicular epithelium from where enters in the external environment where long time remains infectious. Poultry are infected by dust and remains the holder of the virus throughout their lives. The virus is transmitted vertically. The disease can occur in three forms: nervous, visceral and skin. Affected poultry may have any shape or combination of these. The aim of this study was to determine the cause of the disorder the health status in the flock of holland white crested chickens. Flock had 25 chickens whose ages ranged from 4-16 weeks. Observation, we noticed that the chickens are cachectic, showing signs of sporadic diarrhea and died 3 hens and 2 roosters. Pathoanatomical examination is ascertained changes in certain internal organs. The liver was enlarged with lymphoid proliferate on the surface and in the parenchyma, spleen increased several times and marbled, glandular stomach (proventriculus dilated with petechial hemorrhages on mucose. Changed organs was examination histopathological. In the liver were observed multifocal lymphoid infiltration with subsequent atrophy of the parenchyma, in addition to spleen lymphoid proliferation heterophyllus and histiocytic infiltrates, in proventriculus lymphoblastic infiltration with congestion of capillaries and small haemorrhages. In samples pathologically altered organs PCR method proved the genome of Marek’s disease virus serotype 1 . Based on these results we concluded that the livestock were sick from Marek’s disease, which is expressed in visceral form.

  4. Neural Crossroads in the Hematopoietic Stem Cell Niche.

    Science.gov (United States)

    Agarwala, Sobhika; Tamplin, Owen J

    2018-05-29

    The hematopoietic stem cell (HSC) niche supports steady-state hematopoiesis and responds to changing needs during stress and disease. The nervous system is an important regulator of the niche, and its influence is established early in development when stem cells are specified. Most research has focused on direct innervation of the niche, however recent findings show there are different modes of neural control, including globally by the central nervous system (CNS) and hormone release, locally by neural crest-derived mesenchymal stem cells, and intrinsically by hematopoietic cells that express neural receptors and neurotransmitters. Dysregulation between neural and hematopoietic systems can contribute to disease, however new therapeutic opportunities may be found among neuroregulator drugs repurposed to support hematopoiesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Neural networks

    International Nuclear Information System (INIS)

    Denby, Bruce; Lindsey, Clark; Lyons, Louis

    1992-01-01

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

  6. Inductive differentiation of two neural lineages reconstituted in a microculture system from Xenopus early gastrula cells.

    Science.gov (United States)

    Mitani, S; Okamoto, H

    1991-05-01

    Neural induction of ectoderm cells has been reconstituted and examined in a microculture system derived from dissociated early gastrula cells of Xenopus laevis. We have used monoclonal antibodies as specific markers to monitor cellular differentiation from three distinct ectoderm lineages in culture (N1 for CNS neurons from neural tube, Me1 for melanophores from neural crest and E3 for skin epidermal cells from epidermal lineages). CNS neurons and melanophores differentiate when deep layer cells of the ventral ectoderm (VE, prospective epidermis region; 150 cells/culture) and an appropriate region of the marginal zone (MZ, prospective mesoderm region; 5-150 cells/culture) are co-cultured, but not in cultures of either cell type on their own; VE cells cultured alone yield epidermal cells as we have previously reported. The extent of inductive neural differentiation in the co-culture system strongly depends on the origin and number of MZ cells initially added to culture wells. The potency to induce CNS neurons is highest for dorsal MZ cells and sharply decreases as more ventrally located cells are used. The same dorsoventral distribution of potency is seen in the ability of MZ cells to inhibit epidermal differentiation. In contrast, the ability of MZ cells to induce melanophores shows the reverse polarity, ventral to dorsal. These data indicate that separate developmental mechanisms are used for the induction of neural tube and neural crest lineages. Co-differentiation of CNS neurons or melanophores with epidermal cells can be obtained in a single well of co-cultures of VE cells (150) and a wide range of numbers of MZ cells (5 to 100). Further, reproducible differentiation of both neural lineages requires intimate association between cells from the two gastrula regions; virtually no differentiation is obtained when cells from the VE and MZ are separated in a culture well. These results indicate that the inducing signals from MZ cells for both neural tube and neural

  7. A new fossil dolphin Dilophodelphis fordycei provides insight into the evolution of supraorbital crests in Platanistoidea (Mammalia, Cetacea)

    Science.gov (United States)

    Boersma, Alexandra T.; McCurry, Matthew R.; Pyenson, Nicholas D.

    2017-05-01

    Many odontocete groups have developed enlarged facial crests, although these crests differ in topography, composition and function. The most elaborate crests occur in the South Asian river dolphin (Platanista gangetica), in which they rise dorsally as delicate, pneumatized wings anterior of the facial bones. Their position wrapping around the melon suggests their involvement in sound propagation for echolocation. To better understand the origin of crests in this lineage, we examined facial crests among fossil and living Platanistoidea, including a new taxon, Dilophodelphis fordycei, nov. gen. and sp., described herein, from the Early Miocene Astoria Formation of Oregon, USA. We measured the physical extent and thickness of platanistoid crests, categorized their relative position and used computed tomography scans to examine their internal morphology and relative bone density. Integrating these traits in a phylogenetic context, we determined that the onset of crest elaboration or enlargement and the evolution of crest pneumatization among the platanistoids were separate events, with crest enlargement beginning in the Oligocene. However, we find no evidence for pneumatization until possibly the Early Miocene, although certainly by the Middle Miocene. Such an evolutionary context, including data from the fossil record, should inform modelling efforts that seek to understand the diversity of sound generation morphology in Odontoceti.

  8. Convergent Evolution of Head Crests in Two Domesticated Columbids Is Associated with Different Missense Mutations in EphB2

    Science.gov (United States)

    Vickrey, Anna I.; Domyan, Eric T.; Horvath, Martin P.; Shapiro, Michael D.

    2015-01-01

    Head crests are important display structures in wild bird species and are also common in domesticated lineages. Many breeds of domestic rock pigeon (Columba livia) have crests of reversed occipital feathers, and this recessive trait is associated with a nonsynonymous coding mutation in the intracellular kinase domain of EphB2 (Ephrin receptor B2). The domestic ringneck dove (Streptopelia risoria) also has a recessive crested morph with reversed occipital feathers, and interspecific crosses between crested doves and pigeons produce crested offspring, suggesting a similar genetic basis for this trait in both species. We therefore investigated EphB2 as a candidate for the head crest phenotype of ringneck doves and identified a nonsynonymous coding mutation in the intracellular kinase domain that is significantly associated with the crested morph. This mutation is over 100 amino acid positions away from the crest mutation found in rock pigeons, yet both mutations are predicted to negatively affect the function of ATP-binding pocket. Furthermore, bacterial toxicity assays suggest that “crest” mutations in both species severely impact kinase activity. We conclude that head crests are associated with different mutations in the same functional domain of the same gene in two different columbid species, thereby representing striking evolutionary convergence in morphology and molecules. PMID:26104009

  9. Adenocarcinoma of the third portion of the duodenum in a man with CREST syndrome

    Directory of Open Access Journals (Sweden)

    Fragulidis Georgios

    2008-10-01

    Full Text Available Abstract Background CREST (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasias syndrome has been rarely associated with other malignancies (lung, esophagus.This is the first report of a primary adenocarcinoma of the third portion of the duodenum in a patient with CREST syndrome. Case presentation A 54-year-old male patient with CREST syndrome presented with colicky postprandial pain of the upper abdomen, diminished food uptake and a 6-Kg-body weight loss during the previous 2 months. An ulcerative lesion in the third portion of the duodenum was revealed during duodenoscopy, with a diagnosis of adenocarcinoma on biopsy specimen histology. The patient underwent a partial pancreatoduodenectomy. No adjuvant therapy was instituted and follow-up is negative for local recurrence or metastases 21 months postoperatively. Conclusion CREST syndrome has been associated with colon cancer, gastric polyps, familial adenomatous polyposis (FAP syndrome and Crohn's disease; however, this is the first report of a primary adenocarcinoma of the duodenum in a patient with CREST syndrome. However, any etiologic relationship remains to be further investigated.

  10. A study on ionospheric scintillation near the EIA crest in relation to equatorial electrodynamics

    Science.gov (United States)

    Chatterjee, S.; Chakraborty, S. K.; Veenadhari, B.; Banola, S.

    2014-02-01

    Equatorial electrojet (EEJ) data, which are considered as a proxy index of equatorial electric field, are analyzed in conjunction with equatorial ionosonde, total electron content (TEC) and scintillation data near the equatorial ionization anomaly (EIA) crest for the equinoctial months of high solar activity years (2011-2012) to identify any precursor index of postsunset evolution of equatorial electron density irregularities and subsequent occurrence of scintillation near the northern EIA crest. Only geomagnetically quiet and normal electrojet days are considered. The diurnal profiles of EEJ on the scintillation days exhibit a secondary enhancement in the afternoon to presunset hours following diurnal peaks. A series of electrodynamical processes conducive for generation of irregularities emerge following secondary enhancement of EEJ. Latitudinal profile of TEC exhibits resurgence in EIA structure around the postsunset period. Diurnal TEC profile near the EIA crest resembles postsunset secondary enhancement on the days with afternoon enhancement in EEJ. Occurrence of equatorial spread F and postsunset scintillation near the EIA crest seems to follow the secondary enhancement events in EEJ. Both the magnitude and duration of enhanced EEJ are found to be important for postsunset intensification of EIA structure and subsequent occurrence of equatorial irregularities. A critical value combining the two may be considered an important precursor for postsunset occurrence of scintillation near the EIA crest. The results are validated using archived data for the years 1989-1990 and explained in terms of modulation effects of enhanced equatorial fountain.

  11. Cardiac outflow tract malformations in chick embryos exposed to homocysteine

    NARCIS (Netherlands)

    M.J. Boot (Marit); R.P.M. Steegers-Theunissen (Régine); R.E. Poelmann (Robert); L. van Iperen (Liesbeth); A.C. Gittenberger-De Groot (Adriana)

    2004-01-01

    textabstractIncreased homocysteine concentrations have been associated with cardiac outflow tract defects. It has been hypothesized that cardiac neural crest cells were the target cells in these malformations. Cardiac neural crest cells migrate from the neural tube and contribute to the condensed

  12. Internal wave-mediated shading causes frequent vertical migrations in fishes

    KAUST Repository

    Kaartvedt, Stein

    2012-04-25

    We provide evidence that internal waves cause frequent vertical migrations (FVM) in fishes. Acoustic data from the Benguela Current revealed that pelagic scattering layers of fish below ~140 m moved in opposite phases to internal waves, ascending ~20 m towards the wave trough and descending from the wave crest. At the trough, the downward displacement of upper waters and the upward migration of fish created an overlapping zone. Near-bottom fish correspondingly left the benthic boundary zone at the wave trough, ascending into an acoustic scattering layer likely consisting of zooplankton and then descending to the benthic boundary zone at the wave crest. We suggest that this vertical fish migration is a response to fluctuations in light intensity of 3 to 4 orders of magnitude caused by shading from a turbid surface layer that had chlorophyll a values of 3 to 4 mg m−3 and varied in thickness from ~15 to 50 m at a temporal scale corresponding to the internal wave period (30 min). This migration frequency thus is much higher than that of the common and widespread light-associated diel vertical migration. Vertical movements affect prey encounters, growth, and survival. We hypothesize that FVM increase the likelihood of prey encounters and the time for safe visual foraging among planktivorous fish, thereby contributing to efficient trophic transfer in major upwelling areas.

  13. MANAGING MIGRATION: TURKISH PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    İhsan GÜLAY

    2018-04-01

    Full Text Available Conducting migration studies is of vital importance to Turkey, a country which has been experiencing migration throughout history due to its “open doors policy”. The objective of this study is to evaluate the strategic management of migration in Turkey in order to deal with the issue of migration. The main focus of the study is Syrian migrants who sought refuge in Turkey due to the civil war that broke out in their country in April 2011. This study demonstrates the policies and processes followed by Turkey for Syrian migration flow in terms of the social acceptance and harmonisation of the migrants within a democratic environment. The study addresses some statistical facts and issues related to Syrian migration as it has become an integral part of daily life in Turkey. The study also reviews how human rights are protected in the migration process. The study will provide insights for developing sound strategic management policies for the migration issue.

  14. Migration and revolution

    Directory of Open Access Journals (Sweden)

    Nando Sigona

    2012-06-01

    Full Text Available The Arab Spring has not radically transformed migration patterns in the Mediterranean, and the label ‘migration crisis’ does not do justice to the composite and stratified reality.

  15. Nuchal crest avulsion fracture in 2 horses : a cause of headshaking : clinical communication

    Directory of Open Access Journals (Sweden)

    A. Voigt

    2009-05-01

    Full Text Available The medical records of 2 Thoroughbred horses that developed headshaking after blunt trauma to the occipital region are reviewed. The history, signalment, clinical signs, diagnostic methods, diagnosis and treatment were recorded in each case. Both horses displayed headshaking, while one horse repeatedly lifted its upper lip and pawed excessively at the ground. In both horses, diagnostic imaging of the occipital region revealed avulsion fragments of the nuchal crest and a nuchal desmitis in association with hyperfibrinogenaemia. The presence of an avulsion fragment of the nuchal crest with associated nuchal desmitis should be considered in horses presenting with headshaking and may respond favourably to conservative therapy.

  16. Isolation and characterization of eight novel microsatellite loci in the double-crested cormorant (Phalacrocorax auritus)

    Science.gov (United States)

    Mercer, Dacey; Haig, Susan; Mullins, Thomas

    2010-01-01

    We describe the isolation and characterization of eight microsatellite loci from the double-crested cormorant (Phalacrocorax auritus). Genetic variability was assessed using 60 individuals from three populations. All loci were variable with the number of alleles ranging from two to 17 per locus, and observed heterozygosity varying from 0.05 to 0.89. No loci showed signs of linkage disequilibrium and all loci conformed to Hardy–Weinberg equilibrium frequencies. Further, all loci amplified and were polymorphic in two related Phalacrocorax species. These loci should prove useful for population genetic studies of the double-crested cormorant and other pelecaniform species.

  17. Population, migration and urbanization.

    Science.gov (United States)

    1982-06-01

    Despite recent estimates that natural increase is becoming a more important component of urban growth than rural urban transfer (excess of inmigrants over outmigrants), the share of migration in the total population growth has been consistently increasing in both developed and developing countries. From a demographic perspective, the migration process involves 3 elements: an area of origin which the mover leaves and where he or she is considered an outmigrant; the destination or place of inmigration; and the period over which migration is measured. The 2 basic types of migration are internal and international. Internal migration consists of rural to urban migration, urban to urban migration, rural to rural migration, and urban to rural migration. Among these 4 types of migration various patterns or processes are followed. Migration may be direct when the migrant moves directly from the village to the city and stays there permanently. It can be circular migration, meaning that the migrant moves to the city when it is not planting season and returns to the village when he is needed on the farm. In stage migration the migrant makes a series of moves, each to a city closer to the largest or fastest growing city. Temporary migration may be 1 time or cyclical. The most dominant pattern of internal migration is rural urban. The contribution of migration to urbanization is evident. For example, the rapid urbanization and increase in urban growth from 1960-70 in the Republic of Korea can be attributed to net migration. In Asia the largest component of the population movement consists of individuals and groups moving from 1 rural location to another. Recently, because urban centers could no longer absorb the growing number of migrants from other places, there has been increased interest in the urban to rural population redistribution. This reverse migration also has come about due to slower rates of employment growth in the urban centers and improved economic opportunities

  18. Computer modelling of contaminant migration in natural disperse media

    International Nuclear Information System (INIS)

    Kundas, S.P.; Gishkelyuk, I.A.; Khil'ko, O.S.

    2012-01-01

    The theoretical foundations for modeling of the contaminants migration in natural disperses media taking into account interconnected heat and moisture transport are developed. The calculation of mass transfer parameters based on adsorption isotherms of water and thermodynamic equations in the developed mathematical models. The artificial neural networks use to predict migration of contaminants in natural disperse media is proposed. The developed software package is presented and results of practical application of models and software are discussed. (authors)

  19. The distribution of deformation in parallel fault-related folds with migrating axial surfaces: comparison between fault-propagation and fault-bend folding

    Science.gov (United States)

    Salvini, Francesco; Storti, Fabrizio

    2001-01-01

    In fault-related folds that form by axial surface migration, rocks undergo deformation as they pass through axial surfaces. The distribution and intensity of deformation in these structures has been impacted by the history of axial surface migration. Upon fold initiation, unique dip panels develop, each with a characteristic deformation intensity, depending on their history. During fold growth, rocks that pass through axial surfaces are transported between dip panels and accumulate additional deformation. By tracking the pattern of axial surface migration in model folds, we predict the distribution of relative deformation intensity in simple-step, parallel fault-bend and fault-propagation anticlines. In both cases the deformation is partitioned into unique domains we call deformation panels. For a given rheology of the folded multilayer, deformation intensity will be homogeneously distributed in each deformation panel. Fold limbs are always deformed. The flat crests of fault-propagation anticlines are always undeformed. Two asymmetric deformation panels develop in fault-propagation folds above ramp angles exceeding 29°. For lower ramp angles, an additional, more intensely-deformed panel develops at the transition between the crest and the forelimb. Deformation in the flat crests of fault-bend anticlines occurs when fault displacement exceeds the length of the footwall ramp, but is never found immediately hinterland of the crest to forelimb transition. In environments dominated by brittle deformation, our models may serve as a first-order approximation of the distribution of fractures in fault-related folds.

  20. [Internal migration studies].

    Science.gov (United States)

    Stpiczynski, T

    1986-10-01

    Recent research on internal migration in Poland is reviewed. The basic sources of data, consisting of censuses or surveys, are first described. The author discusses the relationship between migration studies and other sectors of the national economy, and particularly the relationship between migration and income.

  1. The Effect of Iliac Crest Autograft on the Outcome of Fusion in the Setting of Degenerative Spondylolisthesis

    Science.gov (United States)

    Radcliff, Kristen; Hwang, Raymond; Hilibrand, Alan; Smith, Harvey E.; Gruskay, Jordan; Lurie, Jon D.; Zhao, Wenyan; Albert, Todd; Weinstein, James

    2012-01-01

    Background: There is considerable controversy about the long-term morbidity associated with the use of posterior autologous iliac crest bone graft for lumbar spine fusion procedures compared with the use of bone-graft substitutes. The hypothesis of this study was that there is no long-term difference in outcome for patients who had posterior lumbar fusion with or without iliac crest autograft. Methods: The study population includes patients enrolled in the degenerative spondylolisthesis cohort of the Spine Patient Outcomes Research Trial who underwent lumbar spinal fusion. Patients were divided according to whether they had or had not received posterior autologous iliac crest bone graft. Results: There were 108 patients who had fusion with iliac crest autograft and 246 who had fusion without iliac crest autograft. There were no baseline differences between groups in demographic characteristics, comorbidities, or baseline clinical scores. At baseline, the group that received iliac crest bone graft had an increased percentage of patients who had multilevel fusions (32% versus 21%; p = 0.033) and L5-S1 surgery (37% versus 26%; p = 0.031) compared with the group without iliac crest autograft. Operative time was higher in the iliac crest bone-graft group (233.4 versus 200.9 minutes; p case-by-case basis for lumbar spinal fusion. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID:22878599

  2. Incisional Colopexy for Treatment of Chronic, Recurrent Colocloacal Prolapse in a Sulphur-Crested Cockatoo (Cacatua galerita)

    NARCIS (Netherlands)

    van Zeeland, Yvonne; Schoemaker, Nico; van Sluijs, Freek

    2014-01-01

    Objective To report a surgical technique for treatment of chronic, recurrent cloacal prolapse in a sulphur-crested cockatoo (Cacatua galerita). Study Design Clinical report Animals Sulphur-crested cockatoo (n = 1) Methods The bird was admitted with a 2-year history of periodic lethargy, decreased

  3. Differentiation state determines neural effects on microvascular endothelial cells

    International Nuclear Information System (INIS)

    Muffley, Lara A.; Pan, Shin-Chen; Smith, Andria N.; Ga, Maricar; Hocking, Anne M.; Gibran, Nicole S.

    2012-01-01

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

  4. A Native Arbuscular Mycorrhizal Fungus, Acaulospora scrobiculata Stimulated Growth of Mongolian Crested Wheatgrass ( Agropyron cristatum (L. Gaertn.

    Directory of Open Access Journals (Sweden)

    Burenjargal Otgonsuren

    2010-12-01

    Full Text Available Agr opyron cristatum (L. Gaertn. (crested wheatgrass is an endemic plant species, which dominates most area of the Mongolian steppe and forest steppe. In the present study, spores of arbuscular mycorrhizal fungi in the rhizosphere soil of crested wheatgrass were isolated with wet- sieving/decanting methods, and the major species was identifi ed as Acaulospora scrobiculata Trappe. For arbuscular-mycorrhizal resynthesis, the spores of A. scrobiculata were propagated with corn pot-culture technique and inoculated onto the roots of crested wheatgrass seedlings. The inoculated crested wheatgrass seedlings exhibited vigor in growth, and examination of the root structure revealed the occurrence of arbuscules and vesicles in the cortical cells. These results demonstrated that A. scrobiculata could effectively form arbuscular mycorrhizas with crested wheatgrass and promote its growth, which can be used to restore Mongolian grassland.

  5. Neural Networks

    International Nuclear Information System (INIS)

    Smith, Patrick I.

    2003-01-01

    Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing

  6. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

    International Nuclear Information System (INIS)

    Colleoni, Silvia; Galli, Cesare; Giannelli, Serena G.; Armentero, Marie-Therese; Blandini, Fabio; Broccoli, Vania; Lazzari, Giovanna

    2010-01-01

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  7. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

    Energy Technology Data Exchange (ETDEWEB)

    Colleoni, Silvia, E-mail: silviacolleoni@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Galli, Cesare [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Dipartimento Clinico Veterinario, Universita di Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (Italy); Giannelli, Serena G. [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Armentero, Marie-Therese; Blandini, Fabio [Laboratory of Functional Neurochemistry, Interdepartmental Research Center for Parkinson' s Disease, Neurological Institute C. Mondino, Via Mondino 2, 27100 Pavia (Italy); Broccoli, Vania, E-mail: broccoli.vania@hsr.it [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Lazzari, Giovanna, E-mail: giovannalazzari@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy)

    2010-04-15

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  8. Evolvable synthetic neural system

    Science.gov (United States)

    Curtis, Steven A. (Inventor)

    2009-01-01

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

  9. msh/Msx gene family in neural development.

    Science.gov (United States)

    Ramos, Casto; Robert, Benoît

    2005-11-01

    The involvement of Msx homeobox genes in skull and tooth formation has received a great deal of attention. Recent studies also indicate a role for the msh/Msx gene family in development of the nervous system. In this article, we discuss the functions of these transcription factors in neural-tissue organogenesis. We will deal mainly with the interactions of the Drosophila muscle segment homeobox (msh) gene with other homeobox genes and the repressive cascade that leads to neuroectoderm patterning; the role of Msx genes in neural-crest induction, focusing especially on the differences between lower and higher vertebrates; their implication in patterning of the vertebrate neural tube, particularly in diencephalon midline formation. Finally, we will examine the distinct activities of Msx1, Msx2 and Msx3 genes during neurogenesis, taking into account their relationships with signalling molecules such as BMP.

  10. Pelvic instability after bone graft harvesting from posterior iliac crest: report of nine patients

    Energy Technology Data Exchange (ETDEWEB)

    Chan, K.; Pathria, M.; Jacobson, J. [Dept. of Radiology, Univ. of California, San Diego, CA (United States); Resnick, D. [Dept. of Radiology, Veterans Affairs Medical Center, San Diego, CA (United States)

    2001-05-01

    Objective. To report the imaging findings in nine patients who developed pelvic instability after bone graft harvest from the posterior aspect of the iliac crest.Design and patients. A retrospective study was performed of the imaging studies of nine patients who developed pelvic pain after autologous bone graft was harvested from the posterior aspect of the ilium for spinal arthrodesis. Plain films, bone scans, and CT and MR examinations of the pelvis were reviewed. Pertinent aspects of the clinical history of these patients were noted, including age, gender and clinical symptoms.Results. The age of the patients ranged from 52 to 77 years (average 69 years) and all were women. The bone graft had been derived from the posterior aspect of the iliac crest about the sacroiliac joint. All patients subsequently developed subluxation of the pubic symphysis. Eight patients had additional insufficiency fractures of the iliac crest adjacent to the bone graft donor site, and five patients also revealed subluxation of the sacroiliac joint. Two had insufficiency fractures of the sacrum and one had an additional fracture of the pubic ramus.Conclusions. Pelvic instability is a potential complication of bone graft harvesting from the posterior aspect of the iliac crest. The pelvic instability is manifested by insufficiency fractures of the ilium and subluxation of the sacroiliac joints and pubic symphysis. (orig.)

  11. Pelvic instability after bone graft harvesting from posterior iliac crest: report of nine patients

    International Nuclear Information System (INIS)

    Chan, K.; Pathria, M.; Jacobson, J.; Resnick, D.

    2001-01-01

    Objective. To report the imaging findings in nine patients who developed pelvic instability after bone graft harvest from the posterior aspect of the iliac crest.Design and patients. A retrospective study was performed of the imaging studies of nine patients who developed pelvic pain after autologous bone graft was harvested from the posterior aspect of the ilium for spinal arthrodesis. Plain films, bone scans, and CT and MR examinations of the pelvis were reviewed. Pertinent aspects of the clinical history of these patients were noted, including age, gender and clinical symptoms.Results. The age of the patients ranged from 52 to 77 years (average 69 years) and all were women. The bone graft had been derived from the posterior aspect of the iliac crest about the sacroiliac joint. All patients subsequently developed subluxation of the pubic symphysis. Eight patients had additional insufficiency fractures of the iliac crest adjacent to the bone graft donor site, and five patients also revealed subluxation of the sacroiliac joint. Two had insufficiency fractures of the sacrum and one had an additional fracture of the pubic ramus.Conclusions. Pelvic instability is a potential complication of bone graft harvesting from the posterior aspect of the iliac crest. The pelvic instability is manifested by insufficiency fractures of the ilium and subluxation of the sacroiliac joints and pubic symphysis. (orig.)

  12. Unraveling the rapid radiation of crested newts, Triturus cristatus superspecies, using complete mitogenomic sequences

    NARCIS (Netherlands)

    Wielstra, B.M.; Arntzen, J.W.

    2011-01-01

    Background - The rapid radiation of crested newts (Triturus cristatus superspecies) comprises four morphotypes: 1) the T. karelinii group, 2) T. carnifex - T. macedonicus, 3) T. cristatus and 4) T. dobrogicus. These vary in body build and the number of rib-bearing pre-sacral vertebrae (NRBV). The

  13. The evolution of the adult body form of the crested newt (Triturus cristatus superspecies, Caudata, Salamandridae)

    NARCIS (Netherlands)

    Vukov, T.D.; Sotiropoulos, K.; Wielstra, B.M.; Dzukic, G.; Kalezic, M.

    2011-01-01

    We characterized the adult body form of the crested newt (Triturus cristatus superspecies) and explored its evolution. From seven morphometric traits, we determined that body size, interlimb distance and head width define the body form. None of the morphometric traits showed a phylogenetic signal.

  14. 76 FR 15971 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Teleconference

    Science.gov (United States)

    2011-03-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002-CA] Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Teleconference a. Date and Time of Meeting: Friday, April 15, 2011 at 9 a.m. (Pacific Time). b. Place: By copy of this notice we are inviting all...

  15. 76 FR 22699 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Teleconference

    Science.gov (United States)

    2011-04-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002--CA] Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Teleconference a. Date and Time of Meeting: Friday, May 6, 2011 at 1 p.m. (Pacific Time). b. Place: By copy of this notice we are inviting all...

  16. 77 FR 47628 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting...

    Science.gov (United States)

    2012-08-09

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002-CA] Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting Postponement On July 17, 2012, the...), on the Eagle Mountain Pumped Storage Hydroelectric Project. However, the meeting has been postponed...

  17. 76 FR 22393 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Cancellation...

    Science.gov (United States)

    2011-04-21

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002-CA] Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Cancellation of Teleconference On March 15... Mountain Pumped Storage Hydroelectric Project. This meeting has been cancelled. We will reschedule this...

  18. 78 FR 25263 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2013-04-30

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002--CA] Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting With the Bureau of Land Management a... Hydroelectric Project. e. All local, state, and federal agencies, tribes, and interested parties, are hereby...

  19. 77 FR 43280 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2012-07-24

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002-CA] Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With the Bureau of Land Management a... Mountain Pumped Storage Hydroelectric Project. e. All local, state, and federal agencies, tribes, and...

  20. 78 FR 26358 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2013-05-06

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002-CA] Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With the Bureau of Land Management a... Policy and Management Act and the Federal Power Act), on the Eagle Mountain Pumped Storage Hydroelectric...

  1. The detection of great crested newts year round via environmental DNA analysis.

    Science.gov (United States)

    Rees, Helen C; Baker, Claire A; Gardner, David S; Maddison, Ben C; Gough, Kevin C

    2017-07-26

    Analysis of environmental DNA (eDNA) is a method that has been used for the detection of various species within water bodies. The great crested newt (Triturus cristatus) has a short eDNA survey season (mid-April to June). Here we investigate whether this season could be extended into other months using the current methodology as stipulated by Natural England. Here we present data to show that in monthly water samples taken from two ponds (March 2014-February 2015) we were able to detect great crested newt DNA in all months in at least one of the ponds. Similar levels of great crested newt eDNA (i.e. highly positive identification) were detected through the months of March-August, suggesting it may be possible to extend the current survey window. In order to determine how applicable these observations are for ponds throughout the rest of the UK, further work in multiple other ponds over multiple seasons is suggested. Nevertheless, the current work clearly demonstrates, in two ponds, the efficacy and reproducibility of eDNA detection for determining the presence of great crested newts.

  2. Temporary hindlimb paresis following dystocia due to foetal macrosomia in a Celebes crested macaque (Macaca nigra).

    Science.gov (United States)

    Debenham, John James; Bettembourg, Vanessa; Østevik, Liv; Modig, Michaela; Jâderlund, Karin Hultin; Lervik, Andreas

    2017-04-01

    A multiparous Celebes crested macaque presented with dystocia due to foetal macrosomia, causing foetal mortality and hindlimb paresis. After emergency caesarean section, recovery of motor function took 1 month before hindlimbs were weight bearing and 2 months before re-integration with the troop. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Estimation of Overtopping Rates on Slopes in Wave Power Devices and Other Low Crested Structures

    DEFF Research Database (Denmark)

    Kofoed, Jens Peter; Burcharth, Hans Falk

    2002-01-01

    Motivated by questions raised by developers of wave energy devices based on wave overtopping concepts, model tests have been performed to study overtopping of structures with limited draught, low crest freeboards and slope geometries designed to increase overtopping and thereby also the captured...

  4. A numerical study of lowest-order short-crested water wave instabilities

    DEFF Research Database (Denmark)

    Fuhrman, David R.; Madsen, Per A.

    2005-01-01

    This work presents the first numerical simulations of the long-term evolution of doubly-periodic short-crested wave instabilities, which are the simplest cases involving the three-dimensional instability of genuinely three-dimensional progressive water waves. The simulated evolutions reveal quali...

  5. Results of operative treatment of avulsion fractures of the iliac crest apophysis in adolescents.

    Science.gov (United States)

    Li, Xigong; Xu, Sanzhong; Lin, Xiangjin; Wang, Quan; Pan, Jun

    2014-04-01

    Avulsion fracture of the iliac crest apophysis is a rare condition that commonly occurs in adolescent athletes. Conservative treatment for this injury can produce excellent functional outcomes. However, the rehabilitation process requires a rather long immobilisation period. This study aimed to evaluate the use of cannulated screws for fixation of avulsion fractures of iliac crest apophysis. Ten patients with avulsion fractures of iliac crest apophysis were treated by open reduction and internal fixation using cannulated screws. The mean age of patients was 14.6 years (range, 13-15 years). The mean intraoperative blood loss was 14.9 ml (range, 10-25 ml). The mean operative time was 40.3 min (range, 33-52 min). The mean follow-up period was 11.2 months (range, 6-20 months). At the 4-week follow-up, all patients returned to previously normal activity without pain and had no evidence of lower extremity muscle weakness. At the final follow-up, all patients resumed their athletic activity without any complications. Open reduction and internal fixation for the treatment of avulsion fracture of iliac crest apophysis can be recommended for patients requiring rapid rehabilitation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Genotyping-by-sequencing data of 272 crested wheatgrass (Agropyron cristatum genotypes

    Directory of Open Access Journals (Sweden)

    Pingchuan Li

    2017-12-01

    Full Text Available Crested wheatgrass [Agropyron cristatum L. (Gaertn.] is an important cool-season forage grass widely used for early spring grazing. However, the genomic resources for this non-model plant are still lacking. Our goal was to generate the first set of next generation sequencing data using the genotyping-by-sequencing technique. A total of 272 crested wheatgrass plants representing seven breeding lines, five cultivars and five geographically diverse accessions were sequenced with an Illumina MiSeq instrument. These sequence datasets were processed using different bioinformatics tools to generate contigs for diploid and tetraploid plants and SNPs for diploid plants. Together, these genomic resources form a fundamental basis for genomic studies of crested wheatgrass and other wheatgrass species. The raw reads were deposited into Sequence Read Archive (SRA database under NCBI accession SRP115373 (https://www.ncbi.nlm.nih.gov/sra?term=SRP115373 and the supplementary datasets are accessible in Figshare (10.6084/m9.figshare.5345092. Keywords: Crested wheatgrass, Genotyping-by-sequencing, Diploid, Tetraploid, Raw sequence data

  7. Nesting habitat requirements and nestling diet in the Mediterranean populations of Crested Tits Lophophanes cristatus

    NARCIS (Netherlands)

    Atienzar, F.; Barba, E.; Holleman, L.J.M.; Belda, E.J.

    2009-01-01

    Most bird species show specific habitat requirements for breeding and feeding. We studied the pattern of habitat occupation, nestling diet and breeding performance of Crested Tits Lophophanes cristatus in a “typical” (coniferous) and an “atypical” (Holm Oak Quercus ilex) forest in eastern Spain

  8. 50 CFR 21.48 - Depredation order for double-crested cormorants to protect public resources.

    Science.gov (United States)

    2010-10-01

    ..., BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD PERMITS Control of..., wildlife, plants, and their habitats) caused by double-crested cormorants. (b) In what areas can this..., Minnesota, Mississippi, Missouri, New York, North Carolina, Ohio, Oklahoma, South Carolina, Tennessee, Texas...

  9. Variation in sagebrush communities historically seeded with crested wheatgrass in the eastern great basin

    Science.gov (United States)

    Although crested wheatgrass (CWG; Agropyron cristatum [L.] Gaertn.) has been one of the most commonly seeded exotic species in the western United States, long-term successional trajectories of seeded sites are poorly characterized, especially for big sagebrush (Artemisia tridentana Nutt.) ecosystems...

  10. Can microsatellite markers resolve phylogenetic relationships between closely related crested newt species (Triturus cristatus superspecies)?

    Czech Academy of Sciences Publication Activity Database

    Mikulíček, P.; Crnobrnja-Isailović, J.; Piálek, Jaroslav

    2007-01-01

    Roč. 28, č. 4 (2007), s. 467-474 ISSN 0173-5373 R&D Projects: GA ČR GA206/01/0695; GA MŠk LC06073 Institutional research plan: CEZ:AV0Z60930519 Keywords : crested newt * microsatelitte markers Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.929, year: 2007

  11. Ontogeny in the tube-crested dinosaur Parasaurolophus (Hadrosauridae and heterochrony in hadrosaurids

    Directory of Open Access Journals (Sweden)

    Andrew A. Farke

    2013-10-01

    Full Text Available The tube-crested hadrosaurid dinosaur Parasaurolophus is remarkable for its unusual cranial ornamentation, but little is known about its growth and development, particularly relative to well-documented ontogenetic series for lambeosaurin hadrosaurids (such as Corythosaurus, Lambeosaurus, and Hypacrosaurus. The skull and skeleton of a juvenile Parasaurolophus from the late Campanian-aged (∼75.5 Ma Kaiparowits Formation of southern Utah, USA, represents the smallest and most complete specimen yet described for this taxon. The individual was approximately 2.5 m in body length (∼25% maximum adult body length at death, with a skull measuring 246 mm long and a femur 329 mm long. A histological section of the tibia shows well-vascularized, woven and parallel-fibered primary cortical bone typical of juvenile ornithopods. The histological section revealed no lines of arrested growth or annuli, suggesting the animal may have still been in its first year at the time of death. Impressions of the upper rhamphotheca are preserved in association with the skull, showing that the soft tissue component for the beak extended for some distance beyond the limits of the oral margin of the premaxilla. In marked contrast with the lengthy tube-like crest in adult Parasaurolophus, the crest of the juvenile specimen is low and hemicircular in profile, with an open premaxilla-nasal fontanelle. Unlike juvenile lambeosaurins, the nasal passages occupy nearly the entirety of the crest in juvenile Parasaurolophus. Furthermore, Parasaurolophus initiated development of the crest at less than 25% maximum skull size, contrasting with 50% of maximum skull size in hadrosaurs such as Corythosaurus. This early development may correspond with the larger and more derived form of the crest in Parasaurolophus, as well as the close relationship between the crest and the respiratory system. In general, ornithischian dinosaurs formed bony cranial ornamentation at a relatively younger age

  12. Novel structural components of the ventral disc and lateral crest in Giardia intestinalis.

    Directory of Open Access Journals (Sweden)

    Kari D Hagen

    2011-12-01

    Full Text Available Giardia intestinalis is a ubiquitous parasitic protist that is the causative agent of giardiasis, one of the most common protozoan diarrheal diseases in the world. Giardia trophozoites attach to the intestinal epithelium using a specialized and elaborate microtubule structure, the ventral disc. Surrounding the ventral disc is a less characterized putatively contractile structure, the lateral crest, which forms a continuous perimeter seal with the substrate. A better understanding of ventral disc and lateral crest structure, conformational dynamics, and biogenesis is critical for understanding the mechanism of giardial attachment to the host. To determine the components comprising the ventral disc and lateral crest, we used shotgun proteomics to identify proteins in a preparation of isolated ventral discs. Candidate disc-associated proteins, or DAPs, were GFP-tagged using a ligation-independent high-throughput cloning method. Based on disc localization, we identified eighteen novel DAPs, which more than doubles the number of known disc-associated proteins. Ten of the novel DAPs are associated with the lateral crest or outer edge of the disc, and are the first confirmed components of this structure. Using Fluorescence Recovery After Photobleaching (FRAP with representative novel DAP::GFP strains we found that the newly identified DAPs tested did not recover after photobleaching and are therefore structural components of the ventral disc or lateral crest. Functional analyses of the novel DAPs will be central toward understanding the mechanism of ventral disc-mediated attachment and the mechanism of disc biogenesis during cell division. Since attachment of Giardia to the intestine via the ventral disc is essential for pathogenesis, it is possible that some proteins comprising the disc could be potential drug targets if their loss or disruption interfered with disc biogenesis or function, preventing attachment.

  13. Oral Crest Lengthening for Increasing Removable Denture Retention by Means of CO2 Laser

    Directory of Open Access Journals (Sweden)

    Samir Nammour

    2014-01-01

    Full Text Available The loss of teeth and their replacement by artificial denture is associated with many problems. The denture needs a certain amount of ridge height to give it retention and a long-term function. Crest lengthening procedures are performed to provide a better anatomic environment and to create proper supporting structures for more stability and retention of the denture. The purpose of our study is to describe and evaluate the effectiveness of CO2 laser-assisted surgery in patients treated for crest lengthening (vestibular deepening. There have been various surgical techniques described in order to restore alveolar ridge height by pushing muscles attaching of the jaws. Most of these techniques cause postoperative complications such as edemas, hemorrhage, pain, infection, slow healing, and rebound to initial position. Our clinical study describes the treatment planning and clinical steps for the crest lengthening with the use of CO2 laser beam (6–15 Watts in noncontact, energy density range: 84.92–212.31 J/cm2, focus, and continuous mode with a focal point diameter of 0.3 mm. At the end of each surgery, dentures were temporarily relined with a soft material. Patients were asked to mandatorily wear their relined denture for a minimum of 4–6 weeks and to remove it for hygienic purposes. At the end of each surgery, the deepest length of the vestibule was measured by the operator. No sutures were made and bloodless wounds healed in second intention without grafts. Results pointed out the efficiency of the procedure using CO2 laser. At 8 weeks of post-op, the mean of crest lengthening was stable without rebound. Only a loss of 15% was noticed. To conclude, the use of CO2 laser is an effective option for crest lengthening.

  14. Radon depth migration

    International Nuclear Information System (INIS)

    Hildebrand, S.T.; Carroll, R.J.

    1993-01-01

    A depth migration method is presented that used Radon-transformed common-source seismograms as input. It is shown that the Radon depth migration method can be extended to spatially varying velocity depth models by using asymptotic ray theory (ART) to construct wavefield continuation operators. These operators downward continue an incident receiver-array plane wave and an assumed point-source wavefield into the subsurface. The migration velocity model is constrain to have longer characteristic wavelengths than the dominant source wavelength such that the ART approximations for the continuation operators are valid. This method is used successfully to migrate two synthetic data examples: (1) a point diffractor, and (2) a dipping layer and syncline interface model. It is shown that the Radon migration method has a computational advantage over the standard Kirchhoff migration method in that fewer rays are computed in a main memory implementation

  15. Migratory timing, rate, routes and wintering areas of White-crested Elaenia (Elaenia albiceps chilensis, a key seed disperser for Patagonian forest regeneration.

    Directory of Open Access Journals (Sweden)

    Susana Patricia Bravo

    Full Text Available Migratory animals often play key ecological roles within the communities they visit throughout their annual journeys. As a consequence of the links between biomes mediated by migrants, changes in one biome could affect remote areas in unpredictable ways. Migratory routes and timing of most Neotropical austral migrants, which breed at south temperate latitudes of South America and overwinter closer to or within tropical latitudes of South America, have yet to be described in detail. As a result, our understanding about how these birds provide links between South American biomes is almost non-existent. White-crested Elaenia (Elaenia albiceps chilensis is a long-distance austral migrant that breeds in the Patagonian Forest biome and overwinters in tropical South America. Because this small flycatcher plays a key role in the regeneration of this ecosystem, our objective was to describe the annual cycle of White-crested elaenias to evaluate the degree of migratory connectivity between breeding and wintering areas and therefore to determine if there are specific biomes of northern South America linked by elaenias to Patagonian forests. Fifteen individuals were successfully tracked throughout a complete migration cycle using miniature light-level geolocators. All individuals resided and moved through the same general regions. During fall (March-April-May, elaenias were located in the Caatinga and the Atlantic Forest biomes, from Rio de Janeiro to the region near Salvador da Bahia, Brazil. During winter (June-July-Aug., birds were located further inland, within the Cerrado biome. Birds used three different routes during fall migration. Our results indicate that some individuals use a direct route, flying between 500-600 km/day, crossing desert and grasslands, while others took a detour, flying 100-200 km/day through forested areas with refueling opportunities. All birds used the Yunga forest during spring migration, with ten out of 15 individuals

  16. Migration into art

    DEFF Research Database (Denmark)

    Petersen, Anne Ring

    This book addresses a topic of increasing importance to artists, art historians and scholars of cultural studies, migration studies and international relations: migration as a profoundly transforming force that has remodelled artistic and art institutional practices across the world. It explores...... contemporary art's critical engagement with migration and globalisation as a key source for improving our understanding of how these processes transform identities, cultures, institutions and geopolitics. The author explores three interwoven issues of enduring interest: identity and belonging, institutional...

  17. Expression of MiR-9 promotes proliferation, migration and ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of miR-9 on the proliferation, differentiation and migration of human neural stem cells (NSCs). Methods: The expression of miR-9 was investigated by quantitative real-time polymerase chain reaction (RT-PCR). Cell proliferation was assessed by cell counting kit-8 (CCK8) assay, while cell ...

  18. Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

    International Nuclear Information System (INIS)

    Kasalak, Oemer; Glaudemans, Andor W.J.M.; Overbosch, Jelle; Kwee, Thomas C.; Jutte, Paul C.

    2018-01-01

    To determine and compare the value of 18 F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. This retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results. FDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7-98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4-99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere. FDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available. (orig.)

  19. Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

    Energy Technology Data Exchange (ETDEWEB)

    Kasalak, Oemer; Glaudemans, Andor W.J.M.; Overbosch, Jelle; Kwee, Thomas C. [University of Groningen, Department of Radiology, Nuclear Medicine and Molecular Imaging, University Medical Center Groningen (Netherlands); Jutte, Paul C. [University of Groningen, Department of Orthopedics, University Medical Center Groningen (Netherlands)

    2018-03-15

    To determine and compare the value of {sup 18}F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. This retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results. FDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7-98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4-99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere. FDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available. (orig.)

  20. Regional Redistribution and Migration

    DEFF Research Database (Denmark)

    Manasse, Paolo; Schultz, Christian

    We study a model with free migration between a rich and a poor region. Since there is congestion, the rich region has an incentive to give the poor region a transfer in order to reduce immigration. Faced with free migration, the rich region voluntarily chooses a transfer, which turns out...... to be equal to that a social planner would choose. Provided migration occurs in equilibrium, this conclusion holds even in the presence of moderate mobility costs. However, large migration costs will lead to suboptimal transfers in the market solution...

  1. RECONSTRUCTION OF ATROPHIC MAXILLA BY ANTERIOR ILIAC CREST BONE GRAFTING VIA NEUROAXIAL BLOCKADE TECHNIQUE: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Erol CANSIZ

    2017-01-01

    Full Text Available Anterior iliac crest bone grafting is a well-established modality in the treatment of alveolar bone deficiencies. However, this procedure may also have considerable postoperative morbidity which is mostly related to general anesthesia. Postoperative pain-related complications can be managed by neuroaxial blockade techniques which provide adequate surgical analgesia and reduce postoperative pain. This clinical report describes the reconstruction of a severely atrophic maxilla with anterior iliac crest bone grafting using combined spinal epidural anesthesia. Neuroaxial blockade techniques may be a useful alternative to eliminate general anesthesia related challenges of anterior iliac crest bone grafting procedures.

  2. Samtidskunst og migration

    DEFF Research Database (Denmark)

    Petersen, Anne Ring

    2010-01-01

    "Samtidskunst og migration. En oversigt over faglitteraturen" er en forskningsoversigt der gør status over hvad der hidtil er skrevet inden for det kunsthistoriske område om vor tids billedkunst og migration som politisk, socialt og kulturelt fænomen, primært i forbindelse med immigration til...

  3. The Great Migration.

    Science.gov (United States)

    Trotter, Joe William, Jr.

    2002-01-01

    Describes the migration of African Americans in the United States and the reasons why African Americans migrated from the south. Focuses on issues, such as the effect of World War I, the opportunities offered in the north, and the emergence of a black industrial working class. (CMK)

  4. Migrating Art History

    DEFF Research Database (Denmark)

    Ørum, Tania

    2012-01-01

    Review of Hiroko Ikegami, The Great Migrator. Robert Rauschenberg and the Global Rise of American Art. Cambridge Mass., The MIT Press, 2010. 277 pages. ISBN 978-0-262-01425-0.......Review of Hiroko Ikegami, The Great Migrator. Robert Rauschenberg and the Global Rise of American Art. Cambridge Mass., The MIT Press, 2010. 277 pages. ISBN 978-0-262-01425-0....

  5. College Student Migration.

    Science.gov (United States)

    Fenske, Robert H.; And Others

    This study examines the background characteristics of two large national samples of first-time enrolled freshmen who (a) attended college within their state of residence but away from their home community, (b) migrated to a college in an adjacent state, (c) migrated to a college in a distant state, and (d) attended college in their home community.…

  6. Migration, klima og sundhed

    DEFF Research Database (Denmark)

    Tellier, Siri; Carballo, Manuel

    2009-01-01

    Many tentative connections have been postulated between migration and climate. This article points to rural-urban migration, particularly into low elevation urban slums prone to flooding as an issue needing urgent attention by health professionals. It also notes the no-man's land in which environ...

  7. Migration in Burkina Faso

    NARCIS (Netherlands)

    Wouterse, F.S.

    2007-01-01

    Migration plays an important role in development and as a strategy for poverty reduction. A recent World Bank investigation finds a significant positive relationship between international migration and poverty reduction at the country level (Adams and Page 2003). Burkina Faso, whose conditions for

  8. Migration, Narration, Identity

    DEFF Research Database (Denmark)

    Leese, Peter

    (co-editor with Carly McLaughlin and Wladyslaw Witalisz) This book presents articles resulting from joint research on the representations of migration conducted in connection with the Erasmus Intensive Programme entitled «Migration and Narration» taught to groups of international students over...

  9. The Globalisation of migration

    Directory of Open Access Journals (Sweden)

    Milan Mesić

    2002-04-01

    Full Text Available The paper demonstrates that contemporary international migration is a constitutive part of the globalisation process. After defining the concepts of globalisation and the globalisation of migration, the author discusses six key themes, linking globalisation and international migration (“global cities”, the scale of migration; diversification of migration flows; globalisation of science and education; international migration and citizenship; emigrant communities and new identities. First, in accordance with Saskia Sassen’s analysis, the author rejects the wide-spread notion that unqualified migrants have lost an (important role in »global cities«, i.e. in the centres of the new (global economy. Namely, the post-modern service sector cannot function without the support of a wide range of auxiliary unqualified workers. Second, a critical comparison with traditional overseas mass migration to the USA at the turn of the 19th and 20th centuries indicates that present international migration is, perhaps, less extensive – however it is important to take into consideration various limitations that previously did not exist, and thus the present migration potential is in really greater. Third, globalisation is more evident in a diversification of the forms of migration: the source area of migrants to the New World and Europe has expanded to include new regions in the world; new immigration areas have arisen (the Middle East, new industrial countries of the Far East, South Europe; intra-regional migration has intensified. Forth, globalisation is linked to an increased migration of experts and the pessimistic notion of a brain drain has been replaced by the optimistic idea of a brain gain. Fifth, contemporary international migration has been associated with a crisis of the national model of citizenship. Sixth, the interlinking of (migrant cultural communities regardless of distance and the physical proximity of cultural centres (the

  10. Progress towards a measurement of the UHE cosmic ray electron flux using the CREST Instrument

    Science.gov (United States)

    Musser, Jim; Wakely, Scott; Coutu, Stephane; Geske, Matthew; Nutter, Scott; Tarle, Gregory; Park, Nahee; Schubnell, Michael; Gennaro, Joseph; Muller, Dietrich

    2012-07-01

    Electrons of energy beyond about 3 TeV have never been detected in the flux of cosmic rays at Earth despite strong evidence of their presence in a number of supernova remnants (e.g., SN 1006). The detection of high energy electrons at Earth would be extremely significant, yielding information about the spatial distribution of nearby cosmic ray sources. With the Cosmic Ray Electron Synchrotron Telescope (CREST), our collaboration has adopted a novel approach to the detection of electrons of energies between 2 and 50 TeV which results in a substantial increase in the acceptance and sensitivity of the apparatus relative to its physics size. The first LDB flight of the CREST detector took place in January 2012, with a float duration of approximately 10 days. In this paper we describe the flight performance of the instrument, and progress in the analysis of the data obtained in this flight.

  11. Genomic diversity and evolution of the head crest in the rock pigeon.

    Science.gov (United States)

    Shapiro, Michael D; Kronenberg, Zev; Li, Cai; Domyan, Eric T; Pan, Hailin; Campbell, Michael; Tan, Hao; Huff, Chad D; Hu, Haofu; Vickrey, Anna I; Nielsen, Sandra C A; Stringham, Sydney A; Hu, Hao; Willerslev, Eske; Gilbert, M Thomas P; Yandell, Mark; Zhang, Guojie; Wang, Jun

    2013-03-01

    The geographic origins of breeds and the genetic basis of variation within the widely distributed and phenotypically diverse domestic rock pigeon (Columba livia) remain largely unknown. We generated a rock pigeon reference genome and additional genome sequences representing domestic and feral populations. We found evidence for the origins of major breed groups in the Middle East and contributions from a racing breed to North American feral populations. We identified the gene EphB2 as a strong candidate for the derived head crest phenotype shared by numerous breeds, an important trait in mate selection in many avian species. We also found evidence that this trait evolved just once and spread throughout the species, and that the crest originates early in development by the localized molecular reversal of feather bud polarity.

  12. Disproportionately severe calcinosis cutis in an 88-year-old patient with CREST syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Buchowski, J.M.; Ahn, N.U.; Ahn, U.M. [Dept. of Orthopaedic Surgery, Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); McCarthy, E.F. [Dept. of Orthopaedic Surgery, Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Dept. of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Mehta, M.B. [Clinical Associates, Good Samaritan Hospital, Baltimore, MD (United States)

    2001-08-01

    An 88-year-old woman with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) presented with hyperglycemia, intravascular depletion, and atrial fibrillation. The patient was found to have unusually severe calcinosis cutis in both legs extending from the knees to the ankles bilaterally, as well as Raynaud's phenomenon, sclerodactyly, and telangiectasias. The patient was normocalcemic and normophosphatemic. Although subcutaneous calcification is often seen with CREST syndrome, this case is unusual in that the area of involvement was much larger than previously described. Furthermore, the amount of calcinosis was disproportionately severe and was the major cause of symptoms and disability compared with the other components of the syndrome. (orig.)

  13. Spatial correlation of the ionsphere total electron content at the equatorial anomaly crest

    International Nuclear Information System (INIS)

    Huang, Y.

    1984-01-01

    The spatial correlation of the ionospheric total electron content (TEC) at the equatorial anomaly crest was studied by recording Faraday rotation angle of the ETS-II geostationary satellite at Lunping and Kaohsiung whose subionospheric points are located at 23.0 0 N, 121.0 0 N, and 20.9 0 N, 121.1 0 E, respectively, and are about 280 km apart. The results show that the spatial correlation of TEC at the equatorial crest region is smaller than that at other places. The day-to-day variabilities of TEC differences between two subionospheric points are quite large. The day-to-day variabilities of the fountain effect seem to play an important role

  14. Real-Time Audio Processing on the T-CREST Multicore Platform

    DEFF Research Database (Denmark)

    Ausin, Daniel Sanz; Pezzarossa, Luca; Schoeberl, Martin

    2017-01-01

    of the audio signal. This paper presents a real-time multicore audio processing system based on the T-CREST platform. T-CREST is a time-predictable multicore processor for real-time embedded systems. Multiple audio effect tasks have been implemented, which can be connected together in different configurations...... forming sequential and parallel effect chains, and using a network-onchip for intercommunication between processors. The evaluation of the system shows that real-time processing of multiple effect configurations is possible, and that the estimation and control of latency ensures real-time behavior.......Multicore platforms are nowadays widely used for audio processing applications, due to the improvement of computational power that they provide. However, some of these systems are not optimized for temporally constrained environments, which often leads to an undesired increase in the latency...

  15. Malaysia and forced migration

    Directory of Open Access Journals (Sweden)

    Arzura Idris

    2012-06-01

    Full Text Available This paper analyzes the phenomenon of “forced migration” in Malaysia. It examines the nature of forced migration, the challenges faced by Malaysia, the policy responses and their impact on the country and upon the forced migrants. It considers forced migration as an event hosting multifaceted issues related and relevant to forced migrants and suggests that Malaysia has been preoccupied with the issue of forced migration movements. This is largely seen in various responses invoked from Malaysia due to “south-south forced migration movements.” These responses are, however, inadequate in terms of commitment to the international refugee regime. While Malaysia did respond to economic and migration challenges, the paper asserts that such efforts are futile if she ignores issues critical to forced migrants.

  16. Role of SDF1/CXCR4 Interaction in Experimental Hemiplegic Models with Neural Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Noboru Suzuki

    2012-02-01

    Full Text Available Much attention has been focused on neural cell transplantation because of its promising clinical applications. We have reported that embryonic stem (ES cell derived neural stem/progenitor cell transplantation significantly improved motor functions in a hemiplegic mouse model. It is important to understand the molecular mechanisms governing neural regeneration of the damaged motor cortex after the transplantation. Recent investigations disclosed that chemokines participated in the regulation of migration and maturation of neural cell grafts. In this review, we summarize the involvement of inflammatory chemokines including stromal cell derived factor 1 (SDF1 in neural regeneration after ES cell derived neural stem/progenitor cell transplantation in mouse stroke models.

  17. Iliac Crest Donor Site for Children With Cleft Lip and Palate Undergoing Alveolar Bone Grafting: A Long-term Assessment.

    Science.gov (United States)

    Wheeler, Jonathan; Sanders, Megan; Loo, Stanley; Moaveni, Zac; Bartlett, Glenn; Keall, Heather; Pinkerton, Mark

    2016-05-01

    The authors aimed to accurately assess the donor site morbidity from iliac crest bone grafts for secondary bone grafting in patients with cleft lip and palate alveolar defects. Fifty patients between 3 months and 10 years following alveolar bone grafting for cleft lip and palate were entered into the study. Two-thirds of patients had no significant concerns about the donor site. The remaining third had some concerns about the appearance of their hips and less than 10% of patients expressing strong agreement with statements about concerns with shape, appearance, and self-consciousness about the iliac crest donor site. Examination findings showed the average length of scar being 5.4 cm and a third of patients having some minor palpable boney irregularities of the iliac crest. The authors found that the alveolar crest donor site is well tolerated by patients long term but has a measurable morbidity long term.

  18. Crest Level Optimization of the Multi Level Overtopping based Wave Energy Converter Seawave Slot-Cone Generator

    DEFF Research Database (Denmark)

    Kofoed, Jens Peter; Osaland, E.

    2005-01-01

    The paper describes the optimization of the crest levels and geometrical layout of the SSG structure, focusing on maximizing the obtained potential energy in the overtopping water. During wave tank testing at AAU average overtopping rates into the individual reservoirs have been measured. The ini......The paper describes the optimization of the crest levels and geometrical layout of the SSG structure, focusing on maximizing the obtained potential energy in the overtopping water. During wave tank testing at AAU average overtopping rates into the individual reservoirs have been measured....... The initial tests led to an expression describing the derivative of the overtopping rate with respect to the vertical distance. Based on this, numerical optimizations of the crest levels, for a number of combinations of wave conditions, have been performed. The hereby found optimal crest levels have been...

  19. New Results from the NOAA CREST Lidar Network (CLN Observations in the US Eastcoast

    Directory of Open Access Journals (Sweden)

    Moshary Fred

    2016-01-01

    Full Text Available This paper presents coordinated ground-based observations by the NOAA-CREST Lidar Network (CLN for profiling of aerosols, cloud, water vapor, and wind along the US east coast including Caribbean region at Puerto Rico. The instrumentation, methodology and observation capability are reviewed. The applications to continental and intercontinental-scale transport of smoke and dust plumes, and their large scale regional impact are discussed.

  20. Iliac crest autograft versus alternative constructs for anterior cervical spine surgery: Pros, cons, and costs

    Science.gov (United States)

    Epstein, Nancy E.

    2012-01-01

    Background: Grafting choices available for performing anterior cervical diskectomy/fusion (ACDF) procedures have become a major concern for spinal surgeons, and their institutions. The “gold standard”, iliac crest autograft, may still be the best and least expensive grafting option; it deserves to be reassessed along with the pros, cons, and costs for alternative grafts/spacers. Methods: Although single or multilevel ACDF have utilized iliac crest autograft for decades, the implant industry now offers multiple alternative grafting and spacer devices; (allografts, cages, polyether-etherketone (PEEK) amongst others). While most studies have focused on fusion rates and clinical outcomes following ACDF, few have analyzed the “value-added” of these various constructs (e.g. safety/efficacy, risks/complications, costs). Results: The majority of studies document 95%-100% fusion rates when iliac crest autograft is utilized to perform single level ACDF (X-ray or CT confirmed at 6-12 postoperative months). Although many allograft studies similarly quote 90%-100% fusion rates (X-ray alone confirmed at 6-12 postoperative months), a recent “post hoc analysis of data from a prospective multicenter trial” (Riew KD et. al., CSRS Abstract Dec. 2011; unpublished) revealed a much higher delayed fusion rate using allografts at one year 55.7%, 2 years 87%, and four years 92%. Conclusion: Iliac crest autograft utilized for single or multilevel ACDF is associated with the highest fusion, lowest complication rates, and significantly lower costs compared with allograft, cages, PEEK, or other grafts. As spinal surgeons and institutions become more cost conscious, we will have to account for the “value added” of these increasingly expensive graft constructs. PMID:22905321

  1. Breeding Double-crested Cormorants and Wading Birds on Isla Alcatraz, Sonora, México

    Science.gov (United States)

    Jennifer N. Duberstein; Virginia Jimenez-Serrania; Tad A. Pfister; Kirsten E. Lindquist; Lorayne Meltzer

    2005-01-01

    Isla Alcatraz is a small volcanic island in the Eastern Midriff Island region of the Gulf of California, approximately 1.4 km from the fishing community of Bahía de Kino, Sonora, México. The island falls under the protection of the Gulf Island Reserve system for wildlife and migratory birds. Isla Alcatraz is home to one of the largest Double-crested Cormorant (

  2. Computerized determination of 3-D connectivity density in human iliac crest bone biopsies

    DEFF Research Database (Denmark)

    Thomsen, J.S.; Mosekilde, Li.; Barlach, J.

    1996-01-01

    Combining the physical disector principle with an algorithm for automatic non-linear alignment of disector pairs we have developed a software system for direct measurement of 3D connectivity densities in iliac crest bone biopsies. The method was applied to biopsies from 14 non-selected autopsy...... cases: 7 men (age range 20-84 yr) and 7 women (age range 20-86 yr). The study reveals decreases in both trabecular bone mass and connectivity density with age in women....

  3. Donor site complications in bone grafting: comparison of iliac crest, calvarial, and mandibular ramus bone.

    Science.gov (United States)

    Scheerlinck, Laura M E; Muradin, Marvick S M; van der Bilt, Andries; Meijer, Gert J; Koole, Ronald; Van Cann, Ellen M

    2013-01-01

    To compare the donor site complication rate and length of hospital stay following the harvest of bone from the iliac crest, calvarium, or mandibular ramus. Ninety-nine consecutively treated patients were included in this retrospective observational single-center study. Iliac crest bone was harvested in 55 patients, calvarial bone in 26 patients, and mandibular ramus bone in 18 patients. Harvesting of mandibular ramus bone was associated with the lowest percentages of major complications (5.6%), minor complications (22.2%), and total complications (27.8%). Harvesting of iliac crest bone was related to the highest percentages of minor complications (56.4%) and total complications (63.6%), whereas harvesting of calvarial bone induced the highest percentage of major complications (19.2%). The length of the hospital stay was significantly influenced by the choice of donor site (P = .003) and age (P = .009); young patients with the mandibular ramus as the donor site had the shortest hospital stay. Harvesting of mandibular ramus bone was associated with the lowest percentage of complications and the shortest hospital stay. When the amount of bone to be obtained is deemed sufficient, mandibular ramus bone should be the first choice for the reconstruction of maxillofacial defects.

  4. Polyurethane resins derived from castor oil (Ricinus communis) for tibial crest deviation in dogs

    International Nuclear Information System (INIS)

    Maria, P.P.; Padilha Filho, J.G.; Canola, J.C.; Castro, M.B.

    2004-01-01

    Medial patellar luxation is one of the most common orthopedic problems in small breeds of dogs and tibial crest deviation is a frequent accompaining anatomical abnormality. For that reason, the purpose of this study was to evaluate the behavior of castor oil derived polyurethane implants when apllied to experimental defects created on the medial side of the proximal tibia of normal puppies. Twelve dogs were randomly divided in 3 groups of 4 animals and were submitted to the same treatment. Histopathological study was performed respectively at 30 (GI), 60 (GII) and 90 (GIII) days post-surgery. Evaluations methods included clinical assessment, radiology, gross and macroscopic study, tomography and statistical analysis. Clinically, there were no signs of implant rejection. Radiology revealed intense periosteal reaction and new bone formation. On gross examination, there was thickening and lateral deviation of the tibial crest and new bone neoformation. On microscopic examination, there was fibrous tissue around the polyurethane, periosteal proliferation on the medial side of the tibia and no bone proliferation towards the implant. Cat scans reveled lateral deviation of the tibial crest in eleven animals, which was statistically significant (p [pt

  5. Neural Networks

    Directory of Open Access Journals (Sweden)

    Schwindling Jerome

    2010-04-01

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

  6. Migration and AIDS.

    Science.gov (United States)

    1998-01-01

    This article presents the perspectives of UNAIDS and the International Organization for Migration (IOM) on migration and HIV/AIDS. It identifies research and action priorities and policy issues, and describes the current situation in major regions of the world. Migration is a process. Movement is enhanced by air transport, rising international trade, deregulation of trade practices, and opening of borders. Movements are restricted by laws and statutes. Denial to freely circulate and obtain asylum is associated with vulnerability to HIV infections. A UNAIDS policy paper in 1997 and IOM policy guidelines in 1988 affirm that refugees and asylum seekers should not be targeted for special measures due to HIV/AIDS. There is an urgent need to provide primary health services for migrants, voluntary counseling and testing, and more favorable conditions. Research is needed on the role of migration in the spread of HIV, the extent of migration, availability of health services, and options for HIV prevention. Research must be action-oriented and focused on vulnerability to HIV and risk taking behavior. There is substantial mobility in West and Central Africa, economic migration in South Africa, and nonvoluntary migration in Angola. Sex workers in southeast Asia contribute to the spread. The breakup of the USSR led to population shifts. Migrants in Central America and Mexico move north to the US where HIV prevalence is higher.

  7. Gas Migration Processes through the Gas Hydrate Stability Zone at Four-Way Closure Ridge Offshore SW Taiwan

    Science.gov (United States)

    Kunath, P.; Chi, W. C.; Berndt, C.; Liu, C. S.

    2016-12-01

    We have used 3D P-Cable seismic data from Four-Way-Closure Ridge, a NW-SE trending anticlinal ridge within the lower slope domain of accretionary wedge, to investigate the geological constraints influencing the fluid migration pattern in the shallow marine sediments. In the seismic data, fluid migration feature manifests itself as high reflection layers of dipping strata, which originate underneath a bottom simulating reflector (BSR) and extend towards the seafloor. Shoaling of the BSR near fluid migration pathways indicates a focused fluid flux, perturbing the temperature field. Furthermore, seafloor video footage confirmed the presence of recent methane seepage above seismically imaged fluid migration pathways. We plan to test two hypotheses for the occurrence of these fluid migration pathways: 1) the extensional regime under the anticlinal ridge crest caused the initiation of localized fault zones, acting as fluid conduits in the gas hydrate stability zone (GHSZ). 2) sediment deformation induced by focused fluid flow and massive growth and dissolution of gas hydrate, similar to processes controlling the evolution of pockmarks on the Nigerian continental margin. We suggest that these processes may be responsible for the formation of a massive hydrate core in the crest of the anticline, as inferred from other geophysical datasets. Triggering process for fluid migration cannot be clearly defined. However, the existence of blind thrust faults may help to advect deep-seated fluids. This may be augmented by biogenic production of shallow gas underneath the ridge, where the excess of gas enables the coexistence of gas, water, and gas hydrate within the GHSZ. Fluid migration structures may exists because of the buoyancy of gas-bearing fluids. This study shows a potential model on how gas-bearing fluids migrate upward towards structural highs, which might occur in other anticlinal structures around the world. Keywords: P-Cable, gas-hydrate, fluid flow, fault-related fold

  8. CREST-SAFE: Snow LST validation, wetness profiler creation, and depth/SWE product development

    Science.gov (United States)

    Perez Diaz, C. L.; Lakhankar, T.; Romanov, P.; Khanbilvardi, R.; Munoz Barreto, J.; Yu, Y.

    2017-12-01

    CREST-SAFE: Snow LST validation, wetness profiler creation, and depth/SWE product development The Field Snow Research Station (also referred to as Snow Analysis and Field Experiment, SAFE) is operated by the NOAA Center for Earth System Sciences and Remote Sensing Technologies (CREST) in the City University of New York (CUNY). The field station is located within the premises of the Caribou Municipal Airport (46°52'59'' N, 68°01'07'' W) and in close proximity to the National Weather Service (NWS) Regional Forecast Office. The station was established in 2010 to support studies in snow physics and snow remote sensing. The Visible Infrared Imager Radiometer Suite (VIIRS) Land Surface Temperature (LST) Environmental Data Record (EDR) and Moderate Resolution Imaging Spectroradiometer (MODIS) LST product (provided by the Terra and Aqua Earth Observing System satellites) were validated using in situ LST (T-skin) and near-surface air temperature (T-air) observations recorded at CREST-SAFE for the winters of 2013 and 2014. Results indicate that T-air correlates better than T-skin with VIIRS LST data and that the accuracy of nighttime LST retrievals is considerably better than that of daytime. Several trends in the MODIS LST data were observed, including the underestimation of daytime values and night-time values. Results indicate that, although all the data sets showed high correlation with ground measurements, day values yielded slightly higher accuracy ( 1°C). Additionally, we created a liquid water content (LWC)-profiling instrument using time-domain reflectometry (TDR) at CREST-SAFE and tested it during the snow melt period (February-April) immediately after installation in 2014. Results displayed high agreement when compared to LWC estimates obtained using empirical formulas developed in previous studies, and minor improvement over wet snow LWC estimates. Lastly, to improve on global snow cover mapping, a snow product capable of estimating snow depth and snow water

  9. Labor migration in Asia.

    Science.gov (United States)

    Martin, P L

    1991-01-01

    "A recent conference sponsored by the United Nations Center for Regional Development (UNCRD) in Nagoya, Japan examined the growing importance of labor migration for four major Asian labor importers (Japan, Hong Kong, Malaysia, and Singapore) and five major labor exporters (Bangladesh, Korea, Pakistan, Philippines, and Thailand).... The conference concluded that international labor migration would increase within Asia because the tight labor markets and rising wages which have stimulated Japanese investment in other Asian nations, for example, have not been sufficient to eliminate migration push and pull forces...." excerpt

  10. The morphology of the sella turcica in velocardiofacial syndrome suggests involvement of a neural crest developmental field

    DEFF Research Database (Denmark)

    Mølsted, Kirsten; Boers, Maria; Kjaer, Inger

    2010-01-01

    . The deviations were mostly in the posterior part of the dorsum sellae. Individuals with VCFS had increased cranial base angles. The results of this study combined with the information in the literature on the main defects in VCFS (palatal abnormalities, cardiac anomalies, thymic hypoplasia or aplasia......, hypothyroidism, and posterior brain abnormality), suggest involvement of a specific developmental field....

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

    Science.gov (United States)

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

    2018-05-16

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

  12. Osteosynthesis of ununited femoral neck fracture by internal fixation combined with iliac crest bone chips and muscle pedicle bone grafting

    Directory of Open Access Journals (Sweden)

    D D Baksi

    2016-01-01

    Full Text Available Background: Ununited femoral neck fracture is seen commonly in developing countries due to delayed presentation or failure of primary internal fixation. Such fractures, commonly present with partial or total absorption of femoral neck, osteonecrosis of femoral head in 8-30% cases with upward migration of trochanter posing problem for osteosynthesis, especially in younger individuals. Several techniques for treatment of such conditions are described like osteotomies or nonvascularied cortical or cancellous bone grafting provided varying degrees of success in terms of fracture union but unsatisfactory long term results occurred due to varying incidence of avascular necrosis (AVN of femoral head. Moreover, in presence of AVN of femoral head neither free fibular graft nor cancellous bone graft is satisfactory. The vascularied bone grafting by deep circumflex iliac artery based on iliac crest bone grafting, free vascularied fibular grafting and muscle pedicle periosteal grafting showed high incidence of success rate. Osteosynthesis is the preferred treatment of choice in ununited femoral neck fracture in younger individuals. Materials and Methods: Of the 293 patients operated during the period from June 1977 to June 2009, 42 were lost to followup. Seven patients with gluteus medius muscle pedicle bone grafting (MPBG were excluded. Thus, out of 244 patients, 208 (85.3% untreated nonunion and 36 (14.7% following failure of primary internal fixation were available for studies. Time interval between the date of injury and operation in untreated nonunion cases was mean 6.5 months and in failed internal fixation cases was mean 11.2 months. Ages of the patients varied from 16 to 55 years. Seventy patients had partial and 174 had subtotal absorption of the femoral neck. Evidence of avascular necrosis (AVN femoral head was found histologically in 135 (54.3% and radiologically in 48 (19.7% patients. The patients were operated by open reduction of fracture

  13. Neuronal Migration Disorders

    Science.gov (United States)

    ... Understanding Sleep The Life and Death of a Neuron Genes At Work In The Brain Order Publications ... birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. In ...

  14. Migration og etnicitet

    DEFF Research Database (Denmark)

    Christiansen, Connie Carøe

    2004-01-01

    Migration og etnicitet er aktuelle og forbundne fænomener, idet migration øger berøringsfladerne mellem befolkningsgrupper. Etniciteter formes i takt med at grænser drages imellem disse grupper. Imod moderniserings-teoriernes forventning forsvandt etnicitet ikke som en traditionel eller oprindelig...... måde at skabe tilhørsforhold på; globalt set fremstår vor tid istedet som en "migrationens tidsalder", der tilsyneladende også er en tidsalder, hvor kulturelle særtræk, i form af etnicitet, udgør vigtige linjer, hvorefter grupper skilller sig ud fra hinanden. Både migration og etnicitet bringer fokus...... den finder sted i modtagerlandet, men nyere perspektiver på migration, som begreber om medborgerskab, transnationalisme og diaspora er eksponenter for, søger udover den nationalstatslige ramme og inddrager konsekvenserne af migrationen for afsenderlande....

  15. A comparative evaluation of the in vitro penetration performance of the improved Crest complete toothbrush versus the Current Crest complete toothbrush, the Colgate Precision toothbrush and the Oral-B P40 toothbrush.

    Science.gov (United States)

    Volpenhein, D W; Handel, S E; Hughes, T J; Wild, J

    1996-01-01

    Removal of plaque and debris from interproximal surfaces during toothbrushing has generally been difficult to achieve, in large part because traditional flat-bristled toothbrushes do not offer good interproximal penetration. As a result, a number of varying bristle designs have been developed, with the rippled-design brush shown to be particularly effective at removing interproximal plaque. Recently, an existing brush, the original Crest Complete, was modified to offer a more deeply rippled version. This study evaluated the interproximal penetration of four bristle designs: rippled pattern (original Crest Complete), deeper rippled pattern (improved Crest Complete), multi-level (Colgate Precision), and flat-tufted (Oral-B P40). The study used a previously reported in vitro model for determining interproximal penetration of manual toothbrushes (J Clin Dent 5:27-33, 1994). In order to effectively mimic the in-use characteristics of toothbrushing, this model is based on analysis of videotaped consumer brushing habits, tooth morphology, and in vivo plaque tenacity characteristics and uses the three most predominantly used brushing techniques (circular, up-and-down, and back-and-forth, with the brush held at both 45 and 90 degrees to the tooth surface). In addition, the model's brush stroke length, brush force, and brush speed are likewise based on analysis of consumer brushing patterns. The results of the study indicate that the new Crest Complete with deeper rippled bristles provided significantly superior (p Colgate Precision and Oral-B brushes overall and for three of the four brush strokes tested. In addition, the new Crest Complete was found to provide significantly superior interproximal penetration to the original Crest Complete overall and in circular and up-and-down strokes, and the original Crest Complete provided superior overall interproximal penetration to the Colgate and Oral-B brushes.

  16. Indonesia's migration transition.

    Science.gov (United States)

    Hugo, G

    1995-01-01

    This article describes population movements in Indonesia in the context of rapid and marked social and economic change. Foreign investment in Indonesia is increasing, and global mass media is available to many households. Agriculture is being commercialized, and structural shifts are occurring in the economy. Educational levels are increasing, and women's role and status are shifting. Population migration has increased over the decades, both short and long distance, permanent and temporary, legal and illegal, and migration to and between urban areas. This article focuses specifically on rural-to-urban migration and international migration. Population settlements are dense in the agriculturally rich inner areas of Java, Bali, and Madura. Although the rate of growth of the gross domestic product was 6.8% annually during 1969-94, the World Bank ranked Indonesia as a low-income economy in 1992 because of the large population size. Income per capita is US $670. Indonesia is becoming a large exporter of labor to the Middle East, particularly women. The predominance of women as overseas contract workers is changing women's role and status in the family and is controversial due to the cases of mistreatment. Malaysia's high economic growth rate of over 8% per year means an additional 1.3 million foreign workers and technicians are needed. During the 1980s urban growth increased at a very rapid rate. Urban growth tended to occur along corridors and major transportation routes around urban areas. It is posited that most of the urban growth is due to rural-to-urban migration. Data limitations prevent an exact determination of the extent of rural-to-urban migration. More women are estimated to be involved in movements to cities during the 1980s compared to the 1970s. Recruiters and middlemen have played an important role in rural-to-urban migration and international migration.

  17. Repeat migration and disappointment.

    Science.gov (United States)

    Grant, E K; Vanderkamp, J

    1986-01-01

    This article investigates the determinants of repeat migration among the 44 regions of Canada, using information from a large micro-database which spans the period 1968 to 1971. The explanation of repeat migration probabilities is a difficult task, and this attempt is only partly successful. May of the explanatory variables are not significant, and the overall explanatory power of the equations is not high. In the area of personal characteristics, the variables related to age, sex, and marital status are generally significant and with expected signs. The distance variable has a strongly positive effect on onward move probabilities. Variables related to prior migration experience have an important impact that differs between return and onward probabilities. In particular, the occurrence of prior moves has a striking effect on the probability of onward migration. The variable representing disappointment, or relative success of the initial move, plays a significant role in explaining repeat migration probabilities. The disappointment variable represents the ratio of actural versus expected wage income in the year after the initial move, and its effect on both repeat migration probabilities is always negative and almost always highly significant. The repeat probabilities diminish after a year's stay in the destination region, but disappointment in the most recent year still has a bearing on the delayed repeat probabilities. While the quantitative impact of the disappointment variable is not large, it is difficult to draw comparisons since similar estimates are not available elsewhere.

  18. (GAGs) in normal and ethanol-induced chick embryo during neural

    African Journals Online (AJOL)

    Administrator

    2011-09-14

    Sep 14, 2011 ... Alcohol as a teratogenic agent inhibits cell growth, function, proliferation and migration by affecting .... formed along the right and left side of the neural tube .... of neurons by harming the developing brain and also can.

  19. Managing migration: the Brazilian case

    OpenAIRE

    Eduardo L. G. Rios-Neto

    2005-01-01

    The objective of this paper is to present the Brazilian migration experience and its relationship with migration management. The article is divided into three parts. First, it reviews some basic facts regarding Brazilian immigration and emigration processes. Second, it focuses on some policy and legal issues related to migration. Finally, it addresses five issues regarding migration management in Brazil.

  20. Alpha male replacements and delayed dispersal in crested macaques (Macaca nigra).

    Science.gov (United States)

    Marty, Pascal R; Hodges, Keith; Agil, Muhammad; Engelhardt, Antje

    2017-07-01

    In species with a high male reproductive skew, competition between males for the top dominant position is high and escalated fights are common between competitors. As a consequence, challenges incur potentially high costs. Selection should favor males who time an alpha male challenge to maximize chances of a successful outcome minimizing costs. Despite the importance of alpha male replacements for individual males, we know little about the timing of challenges and the condition of the challenger. We investigated the timing and process of alpha male replacements in a species living in multi-male groups with high male reproductive skew, the crested macaque. We studied four wild groups over 6 years in the Tangkoko Reserve, North Sulawesi, Indonesia, during which 16 alpha male replacements occurred. Although unusual for cercopithecines, male crested macaques delayed their natal dispersal until they attained maximum body mass and therefore fighting ability whereupon they emigrated and challenged the alpha male in another group. Accordingly, all observed alpha male replacements were from outside males. Ours is the first report of such a pattern in a primate species living in multi-male groups. Although the majority of alpha male replacements occurred through direct male-male challenges, many also took place opportunistically (i.e., after the alpha male had already been injured or had left the group). Furthermore, alpha male tenures were very short (averaging ca. 12 months). We hypothesize that this unusual pattern of alpha male replacements in crested macaques is related to the species-specific combination of high male reproductive skew with a large number of males per group. Am. J. Primatol. 79:e22448, 2017. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc.

  1. Myocardial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis. Exercise radionuclide evaluation and comparison with diffuse scleroderma

    International Nuclear Information System (INIS)

    Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.; Owens, G.R.; Steen, V.D.; Rodnan, G.P.

    1984-01-01

    Myocardial function and perfusion were evaluated in 22 patients with progressive systemic sclerosis with the CREST syndrome using exercise and radionuclide techniques, pulmonary function testing, and chest roentgenography. The results were compared with a similar study of 26 patients with progressive systemic sclerosis with diffuse scleroderma. The prevalence of thallium perfusion abnormalities was similar in the groups with CREST syndrome and diffuse scleroderma, (64 percent versus 77 percent), but the defects were significantly smaller in the CREST syndrome (p less than 0.01). Reperfusion thallium defects in the absence of extramural coronary artery disease were seen in 38 percent of patients with diffuse scleroderma. This finding was not seen in any of the patients with the CREST syndrome. In diffuse scleroderma, abnormalities of both right and left ventricular function were related to larger thallium perfusion defects. In the CREST syndrome, abnormalities of left ventricular function were minor, were seen only during exercise, and were unrelated to thallium perfusion defects. Abnormal resting right ventricular function was seen in 36 percent of the patients with the CREST syndrome and was associated with an isolated decrease in diffusing capacity of carbon monoxide. It is concluded that the cardiac manifestations of the CREST syndrome are distinct from those found in diffuse scleroderma. Unlike diffuse scleroderma, abnormalities of left ventricular function in the CREST syndrome are minor and are unrelated to abnormalities of coronary perfusion. Right ventricular dysfunction in the CREST syndrome appears to be primarily related to pulmonary vascular disease

  2. The Crest of the Peacock Non-European Roots of Mathematics (Third Edition)

    CERN Document Server

    Joseph, George Gheverghese

    2011-01-01

    From the Ishango Bone of central Africa and the Inca quipu of South America to the dawn of modern mathematics, The Crest of the Peacock makes it clear that human beings everywhere have been capable of advanced and innovative mathematical thinking. George Gheverghese Joseph takes us on a breathtaking multicultural tour of the roots and shoots of non-European mathematics. He shows us the deep influence that the Egyptians and Babylonians had on the Greeks, the Arabs' major creative contributions, and the astounding range of successes of the great civilizations of India and China. The third editio

  3. Evaluation of MODIS Land Surface Temperature with In Situ Snow Surface Temperature from CREST-SAFE

    Science.gov (United States)

    Perez Diaz, C. L.; Lakhankar, T.; Romanov, P.; Munoz, J.; Khanbilvardi, R.; Yu, Y.

    2016-12-01

    This paper presents the procedure and results of a temperature-based validation approach for the Moderate Resolution Imaging Spectroradiometer (MODIS) Land Surface Temperature (LST) product provided by the National Aeronautics and Space Administration (NASA) Terra and Aqua Earth Observing System satellites using in situ LST observations recorded at the Cooperative Remote Sensing Science and Technology Center - Snow Analysis and Field Experiment (CREST-SAFE) during the years of 2013 (January-April) and 2014 (February-April). A total of 314 day and night clear-sky thermal images, acquired by the Terra and Aqua satellites, were processed and compared to ground-truth data from CREST-SAFE with a frequency of one measurement every 3 min. Additionally, this investigation incorporated supplementary analyses using meteorological CREST-SAFE in situ variables (i.e. wind speed, cloud cover, incoming solar radiation) to study their effects on in situ snow surface temperature (T-skin) and T-air. Furthermore, a single pixel (1km2) and several spatially averaged pixels were used for satellite LST validation by increasing the MODIS window size to 5x5, 9x9, and 25x25 windows for comparison. Several trends in the MODIS LST data were observed, including the underestimation of daytime values and nighttime values. Results indicate that, although all the data sets (Terra and Aqua, diurnal and nocturnal) showed high correlation with ground measurements, day values yielded slightly higher accuracy ( 1°C), both suggesting that MODIS LST retrievals are reliable for similar land cover classes and atmospheric conditions. Results from the CREST-SAFE in situ variables' analyses indicate that T-air is commonly higher than T-skin, and that a lack of cloud cover results in: lower T-skin and higher T-air minus T-skin difference (T-diff). Additionally, the study revealed that T-diff is inversely proportional to cloud cover, wind speed, and incoming solar radiation. Increasing the MODIS window size

  4. Development and characterization of polymorphic microsatellitemarkers for the crested caracara, Caracara cheriway

    Science.gov (United States)

    Vaughn, Erin E.; Dwyer, James F.; Morrison, Joan L.; Culver, Melanie

    2015-01-01

    We isolated novel microsatellites from the crested caracara (Caracara cheriway) with a shotgun pyrosequencing approach. We tested 80 loci for polymorphism among 20 individuals from the threatened Florida population. Fourteen loci were polymorphic. The mean number of alleles was 2.21 (range 2–3) and the mean observed heterozygosity was 0.41 (range 0.15–0.65). None of the 14 polymorphic loci exhibited significant linkage disequilibrium nor did they deviate significantly from Hardy–Weinberg expectations. We also report 16 monomorphic loci.

  5. Discharge coefficient of a rectangular sharp-edged broad-crested weir

    OpenAIRE

    Zachoval Zbyněk; Knéblová Michaela; Roušar Ladislav; Rumann Ján; Šulc Jan

    2014-01-01

    his paper is concerned with the determination of the relationship for the calculation of the discharge coefficient at free overflow over a rectangular sharp-edged broad-crested weir without lateral contraction. The determination was made on the basis of new measurement in a range of the relative thickness of the weir from 0.12 to 0.30 and newly in a large range of relative height of the weir extremely from 0.24 to 6.8 which greatly expands the application possibilities of low weirs. In additi...

  6. Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomised controlled trial.

    Science.gov (United States)

    Lal, Brajesh K; Beach, Kirk W; Roubin, Gary S; Lutsep, Helmi L; Moore, Wesley S; Malas, Mahmoud B; Chiu, David; Gonzales, Nicole R; Burke, J Lee; Rinaldi, Michael; Elmore, James R; Weaver, Fred A; Narins, Craig R; Foster, Malcolm; Hodgson, Kim J; Shepard, Alexander D; Meschia, James F; Bergelin, Robert O; Voeks, Jenifer H; Howard, George; Brott, Thomas G

    2012-09-01

    In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion. Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732. 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31

  7. Resurrection of Bronchocela burmana Blanford, 1878 for the Green Crested Lizard (Squamata, Agamidae of southern Myanmar

    Directory of Open Access Journals (Sweden)

    George R. Zug

    2017-02-01

    Full Text Available Recent fieldwork in southern Tanintharyi revealed the presence of a small Green Crested Lizard in the wet evergreen forest. We generated mtDNA sequence data (ND2 that demonstrates that this population’s nearest relative is Bronchocela rayaensis Grismer et al., 2015 of Pulau Langkawi, northwestern Peninsular Malaysia and Phuket Island. Morphologically the Burmese Bronchocela shares many features with B. rayaensis, which potentially would make this recently described Thai-Malay species a synonym of Bronchocela burmana Blanford, 1878; however, we interpret the genetic and morphological differences to reflect evolutionary divergence and recommend the recognition of both species.

  8. T-CREST: Time-predictable multi-core architecture for embedded systems

    DEFF Research Database (Denmark)

    Schoeberl, Martin; Abbaspourseyedi, Sahar; Jordan, Alexander

    2015-01-01

    -core architectures that are optimized for the WCET instead of the average-case execution time. The resulting time-predictable resources (processors, interconnect, memory arbiter, and memory controller) and tools (compiler, WCET analysis) are designed to ease WCET analysis and to optimize WCET performance. Compared...... domain shows that the WCET can be reduced for computation-intensive tasks when distributing the tasks on several cores and using the network-on-chip for communication. With three cores the WCET is improved by a factor of 1.8 and with 15 cores by a factor of 5.7.The T-CREST project is the result...

  9. Prestack depth migration

    International Nuclear Information System (INIS)

    Postma, R.W.

    1991-01-01

    Two lines form the southern North Sea, with known velocity inhomogeneities in the overburden, have been pre-stack depth migrated. The pre-stack depth migrations are compared with conventional processing, one with severe distortions and one with subtle distortions on the conventionally processed sections. The line with subtle distortions is also compared with post-stack depth migration. The results on both lines were very successful. Both have already influenced drilling decisions, and have caused a modification of structural interpretation in the respective areas. Wells have been drilled on each of the lines, and well tops confirm the results. In fact, conventional processing led to incorrect locations for the wells, both of which were dry holes. The depth migrated sections indicate the incorrect placement, and on one line reveals a much better drilling location. This paper reports that even though processing costs are high for pre-stack depth migration, appropriate use can save millions of dollars in dry-hole expense

  10. Migration = cloning; aliasiing

    DEFF Research Database (Denmark)

    Hüttel, Hans; Kleist, Josva; Nestmann, Uwe

    1999-01-01

    In Obliq, a lexically scoped, distributed, object-oriented programming language, object migration was suggested as the creation of a copy of an object’s state at the target site, followed by turning the object itself into an alias, also called surrogate, for the remote copy. We consider the creat......In Obliq, a lexically scoped, distributed, object-oriented programming language, object migration was suggested as the creation of a copy of an object’s state at the target site, followed by turning the object itself into an alias, also called surrogate, for the remote copy. We consider...... the creation of object surrogates as an abstraction of the abovementioned style of migration. We introduce Øjeblik, a distribution-free subset of Obliq, and provide three different configuration-style semantics, which only differ in the respective aliasing model. We show that two of the semantics, one of which...... matches Obliq’s implementation, render migration unsafe, while our new proposal for a third semantics is provably safe. Our work suggests a straightforward repair of Obliq’s aliasing model such that it allows programs to safely migrate objects....

  11. Reconstruction of iliac crest with rib to prevent donor site complications: A prospective study of 26 cases

    Directory of Open Access Journals (Sweden)

    Dave B

    2007-01-01

    Full Text Available Background: The tricortical bone graft from the iliac crest are used to reconstruct the post corpectomy spinal defects. The donor iliac area defect is large and may give rise to pain at donor site, instability of pelvis, fracture of ilium, donor site muscle herniation or abdominal content herniation. Rib removed during thoracotomy was used by us to reconstruct the iliac crest defect. Materials and Methods: Twenty-six patients who underwent thoracotomy for dorsal spine corpectomy or curettage for various spinal pathologies from June 2002 to May 2004 were included in the study. After adequate decompression the spine was reconstructed by tricortical bone graft from iliac crest and reconstruction of the iliac crest was done with the rib removed for exposure during thoracotomy. Results: The mean follow up was 15 months. All patients had good graft incorporation which was evaluated on the basis of local tenderness and radiographs. One patient had graft displacement. Conclusion: The reconstruction of iliac crest by rib is a simple and effective procedure to prevent donor site complications.

  12. En fornemmelse for migration

    DEFF Research Database (Denmark)

    Schütze, Laura Maria

    Afhandlingen undersøger, hvordan sted, museets rolle som aktør og religion er relevante for produktionen af migration på Immigrantmuseet (2012) og i Københavns Museums udstilling At blive københavner (2010). Afhandlingen er baseret på udstillingsanalyse samt interview med relevant museumsfagligt......, anvendes som virkemidler til at nuancere migration og distancere udstillingen fra den offentlige debat om indvandring. Afhandlingen peger på, at produktionen af den nyere danske historie på museum er præget af et fravær af religion. Det skyldes, at de museumsfaglige praksisser og traditioner afspejler en...... identiteter, som vi tager for givet: nationer, byer, kvinder - såvel som migration og religion. Afhandlingen argumenterer følgelig for, at museernes produktion af (materiel) religion er et særdeles relevant, men kun ringe udforsket, genstandsfelt for religionssociologien....

  13. Cell reprogramming by 3D bioprinting of human fibroblasts in polyurethane hydrogel for fabrication of neural-like constructs.

    Science.gov (United States)

    Ho, Lin; Hsu, Shan-Hui

    2018-04-01

    3D bioprinting is a technique which enables the direct printing of biodegradable materials with cells into 3D tissue. So far there is no cell reprogramming in situ performed with the 3D bioprinting process. Forkhead box D3 (FoxD3) is a transcription factor and neural crest marker, which was reported to reprogram human fibroblasts into neural crest stem-like cells. In this study, we synthesized a new biodegradable thermo-responsive waterborne polyurethane (PU) gel as a bioink. FoxD3 plasmids and human fibroblasts were co-extruded with the PU hydrogel through the syringe needle tip for cell reprogramming. The rheological properties of the PU hydrogel including the modulus, gelation time, and shear thinning were optimized for the transfection effect of FoxD3 in situ. The corresponding shear rate and shear stress were examined. Results showed that human fibroblasts could be reprogrammed into neural crest stem-like cells with high cell viability during the extrusion process under an average shear stress ∼190 Pa. We further translated the method to the extrusion-based 3D bioprinting, and demonstrated that human fibroblasts co-printed with FoxD3 in the thermo-responsive PU hydrogel could be reprogrammed and differentiated into a neural-tissue like construct at 14 days after induction. The neural-like tissue construct produced by 3D bioprinting from human fibroblasts may be applied to personalized drug screening or neuroregeneration. There is no study so far on cell reprogramming in situ with 3D bioprinting. In this manuscript, a new thermoresponsive polyurethane bioink was developed and employed to deliver FoxD3 plasmid into human fibroblasts by the extrusion-based bioprinting. When the polyurethane gel was extruded through the syringe tip, the shear stress generated may have caused the transient membrane permeability for transfection. The shear stress was optimized for transfection in situ by 3D bioprinting. We demonstrated that human fibroblasts could be

  14. What's driving migration?

    Science.gov (United States)

    Kane, H

    1995-01-01

    During the 1990s investment in prevention of international or internal migration declined, and crisis intervention increased. The budgets of the UN High Commissioner for Refugees and the UN Development Program remained about the same. The operating assumption is that war, persecution, famine, and environmental and social disintegration are inevitable. Future efforts should be directed to stabilizing populations through investment in sanitation, public health, preventive medicine, land tenure, environmental protection, and literacy. Forces pushing migration are likely to increase in the future. Forces include depletion of natural resources, income disparities, population pressure, and political disruption. The causes of migration are not constant. In the past, migration occurred during conquests, settlement, intermarriage, or religious conversion and was a collective movement. Current migration involves mass movement of individuals and the struggle to survive. There is new pressure to leave poor squatter settlements and the scarcities in land, water, and food. The slave trade between the 1500s and the 1800s linked continents, and only 2-3 million voluntarily crossed national borders. Involuntary migration began in the early 1800s when European feudal systems were in a decline, and people sought freedom. Official refugees, who satisfy the strict 1951 UN definition, increased from 15 million in 1980 to 23 million in 1990 but remained a small proportion of international migrants. Much of the mass movement occurs between developing countries. Migration to developed countries is accompanied by growing intolerance, which is misinformed. China practices a form of "population transfer" in Tibet in order to dilute Tibetan nationalism. Colonization of countries is a new less expensive form of control over territory. Eviction of minorities is another popular strategy in Iraq. Public works projects supported by foreign aid displace millions annually. War and civil conflicts

  15. Unix Application Migration Guide

    CERN Document Server

    Microsoft. Redmond

    2003-01-01

    Drawing on the experience of Microsoft consultants working in the field, as well as external organizations that have migrated from UNIX to Microsoft® Windows®, this guide offers practical, prescriptive guidance on the issues you are likely to face when porting existing UNIX applications to the Windows operating system environment. Senior IT decision makers, network managers, and operations managers will get real-world guidance and best practices on planning and implementation issues to understand the different methods through which migration or co-existence can be accomplished. Also detailing

  16. Migrating for a Profession

    DEFF Research Database (Denmark)

    Olwig, Karen Fog

    2015-01-01

    a strong sense of agency and self-empowerment. In the post-WWII period, numerous Caribbean women trained in nursing at British hospitals that have been described as marred by race and gender related inequality and associated forms of exploitation. Yet, the nurses interviewed about this training emphasised......Youths from the Global South migrating for further education often face various forms of discrimination. This Caribbean case study discusses how conditions in the home country can provide a foundation for educational migration that helps the migrants overcome such obstacles and even develop...... in which it enabled these Caribbean women to stake out a new life for themselves....

  17. Rodent Zic Genes in Neural Network Wiring.

    Science.gov (United States)

    Herrera, Eloísa

    2018-01-01

    The formation of the nervous system is a multistep process that yields a mature brain. Failure in any of the steps of this process may cause brain malfunction. In the early stages of embryonic development, neural progenitors quickly proliferate and then, at a specific moment, differentiate into neurons or glia. Once they become postmitotic neurons, they migrate to their final destinations and begin to extend their axons to connect with other neurons, sometimes located in quite distant regions, to establish different neural circuits. During the last decade, it has become evident that Zic genes, in addition to playing important roles in early development (e.g., gastrulation and neural tube closure), are involved in different processes of late brain development, such as neuronal migration, axon guidance, and refinement of axon terminals. ZIC proteins are therefore essential for the proper wiring and connectivity of the brain. In this chapter, we review our current knowledge of the role of Zic genes in the late stages of neural circuit formation.

  18. In vitro effects of Epidiferphane™ on adult human neural progenitor cells

    Science.gov (United States)

    Neural stem cells have the capacity to respond to their environment, migrate to the injury site and generate functional cell types, and thus they hold great promise for cell therapies. In addition to representing a source for central nervous system (CNS) repair, neural stem and progenitor cells als...

  19. Age-related changes in vertebral and iliac crest 3D bone microstructure-differences and similarities

    DEFF Research Database (Denmark)

    Thomsen, Jesper Skovhus; Jensen, Michael Vinkel; Niklassen, Andreas Steenholt

    2015-01-01

    Summary Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure...... was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes.Introduction The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between...... the bone microstructure at these skeletal sites.Methods Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19–96 years) and 39 men (23–95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified.Results For both women...

  20. A new crested pterosaur from the Early Cretaceous of Spain: the first European tapejarid (Pterodactyloidea: Azhdarchoidea.

    Directory of Open Access Journals (Sweden)

    Romain Vullo

    Full Text Available BACKGROUND: The Tapejaridae is a group of unusual toothless pterosaurs characterized by bizarre cranial crests. From a paleoecological point of view, frugivorous feeding habits have often been suggested for one of its included clades, the Tapejarinae. So far, the presence of these intriguing flying reptiles has been unambiguously documented from Early Cretaceous sites in China and Brazil, where pterosaur fossils are less rare and fragmentary than in similarly-aged European strata. METHODOLOGY/PRINCIPAL FINDINGS: Europejara olcadesorum gen. et sp. nov. is diagnosed by a unique combination of characters including an unusual caudally recurved dentary crest. It represents the oldest known member of Tapejaridae and the oldest known toothless pterosaur. The new taxon documents the earliest stage of the acquisition of this anatomical feature during the evolutionary history of the Pterodactyloidea. This innovation may have been linked to the development of new feeding strategies. CONCLUSION/SIGNIFICANCE: The discovery of Europejara in the Barremian of the Iberian Peninsula reveals an earlier and broader global distribution of tapejarids, suggesting a Eurasian origin of this group. It adds to the poorly known pterosaur fauna of the Las Hoyas locality and contributes to a better understanding of the paleoecology of this Konservat-Lagerstätte. Finally, the significance of a probable contribution of tapejarine tapejarids to the early angiosperm dispersal is discussed.

  1. Can footwall unloading explain late Cenozoic uplift of the Sierra Nevada crest?

    Science.gov (United States)

    Thompson, G.A.; Parsons, T.

    2009-01-01

    Globally, normal-fault displacement bends and warps rift flanks upwards, as adjoining basins drop downwards. Perhaps the most evident manifestations are the flanks of the East African Rift, which cuts across the otherwise minimally deformed continent. Flank uplift was explained by Vening Meinesz (1950, Institut Royal Colonial Belge, Bulletin des Seances, v. 21, p. 539-552), who recognized that isostasy should cause uplift of a normal-faulted footwall and subsidence of its hanging wall. Uplift occurs because slip on a dipping normal fault creates a broader root of less-dense material beneath the footwall, and a narrowed one beneath the hanging wall. In this paper, we investigate the potential influence of this process on the latest stages of Sierra Nevada uplift. Through theoretical calculations and 3D finite element modelling, we find that cumulative slip of about 4km on range-front faults would have produced about 1.3km peak isostatic uplift at the ridge crest. Numerical models suggest that the zone of uplift is narrow, with the width controlled by bending resistance of the seismogenic crust. We conclude that footwall unloading cannot account for the entire elevation of the Sierran crest above sea level, but if range-front faulting initiated in an already elevated plateau like the adjacent Basin and Range Province, then a hybrid model of pre-existing regional uplift and localized footwall unloading can account for the older and newer uplift phases suggested by the geologic record.

  2. Discharge Coefficient of Rectangular Short-Crested Weir with Varying Slope Coefficients

    Directory of Open Access Journals (Sweden)

    Yuejun Chen

    2018-02-01

    Full Text Available Rectangular short-crested weirs are widely used for simple structure and high discharge capacity. As one of the most important and influential factors of discharge capacity, side slope can improve the hydraulic characteristics of weirs at special conditions. In order to systemically study the effects of upstream and downstream slope coefficients S1 and S2 on overflow discharge coefficient in a rectangular short-crested weir the Volume of Fluid (VOF method and the Renormalization Group (RNG κ-ε turbulence model are used. In this study, the slope coefficient ranges from V to 3H:1V and each model corresponds to five total energy heads of H0 ranging from 8.0 to 24.0 cm. Comparisons of discharge coefficients and free surface profiles between simulated and laboratory results display a good agreement. The simulated results show that the difference of discharge coefficients will decrease with upstream slopes and increase with downstream slopes as H0 increases. For a given H0, the discharge coefficient has a convex parabolic relation with S1 and a piecewise linearity relation with S2. The maximum discharge coefficient is always obtained at S2 = 0.8. There exists a difference between upstream and downstream slope coefficients in the influence range of free surface curvatures. Furthermore, a proposed discharge coefficient equation by nonlinear regression is a function of upstream and downstream slope coefficients.

  3. Organochlorine contaminants and reproductive success of double-crested cormorants from Green Bay, Wisconsin, USA

    Science.gov (United States)

    Custer, T.W.; Custer, Christine M.; Hines, R.K.; Gutreuter, S.; Stromborg, K.L.; Allen, P. David; Melancon, M.J.

    1999-01-01

    In 1994 and 1995, nesting success of double-crested cormorants (Phalacrocorax auritus) was measured at Cat Island, in southern Green Bay, Lake Michigan, Wisconsin, USA. Sample eggs at pipping and unhatched eggs were collected and analyzed for organochlorines (including total polychlorinated biphenyls [PCBs] and DDE), hepatic microsomal ethoxyresorufin-O-dealkylase (EROD) activity in embryos, and eggshell thickness. Of 1,570 eggs laid, 32% did not hatch and 0.4% had deformed embryos. Of 632 chicks monitored from hatching to 12 d of age, 9% were missing or found dead; no deformities were observed. The PCB concentrations in sample eggs from clutches with deformed embryos (mean = 10.2 μg/g wet weight) and dead embryos (11.4 μg/g) were not significantly higher than concentrations in sample eggs from nests where all eggs hatched (12.1 μg/g). A logistic regression of hatching success versus DDE, dieldrin, and PCB concentrations in sibling eggs identified DDE and not dieldrin or PCBs as a significant risk factor. A logistic regression of hatching success versus DDE and eggshell thickness implicated DDE and not eggshell thickness as a significant risk factor. Even though the insecticide DDT was banned in the early 1970s, we suggest that DDE concentrations in double-crested cormorant eggs in Green Bay are still having an effect on reproduction in this species.

  4. Clinical effectiveness of 99mTc-diphosphonate scintigraphy of revascularized iliac crest flaps

    International Nuclear Information System (INIS)

    Smeele, L.E.; Hoekstra, O.S.; Winters, H.A.H.; Leemans, C.R.

    1996-01-01

    Clinical assessment of the perfusion of the musculocutaneous portion of composite iliac crest free flaps was compared to 99m Tc-diphosphonate (HDP) uptake in 14 patients who underwent primary oromandibular reconstruction after ablative cancer surgery. Bone scanning was performed on average at the 9-10th postoperative day (range 4-48) 3 h after intravenous injection of 550 MBq 99m Tc-HDP. Eleven patients showed complete concordance between 99m Tc-HDP uptake and soft-tissue status. Two patients showed uptake and viable muscle in spite of necrotic skin. One patient had a viable musculocutaneous flap but a photopenic defect in the bone graft; 6 months later, a small corresponding part of the bone was sequestrated. In this study, bone scanning and clinical assessment of muscle perfusion were 100% accurate in predicting viability of bone graft. Skin viability was a less reliable parameter. It is concluded that bone scanning is not indicated as routine investigation for revascularized iliac crest flaps and that clinical assessment of muscle perfusion is a reliable monitor of the early function of such flaps. (au) 8 refs

  5. Assessment of GPS Multifrequency Signal Characteristics During Periods of Ionospheric Scintillations from an Anomaly Crest Location

    Science.gov (United States)

    Goswami, S.; Paul, K. S.; Paul, A.

    2017-09-01

    Multifrequency GPS transmissions have provided the opportunity for testing the applicability of the principle of frequency diversity for scintillation mitigation. Published results addressing this issue with quantified estimates are not available in literature, at least from the anomaly crest location of the Indian longitude sector. Multifrequency scattering within the same L band is often the attributed cause behind simultaneous decorrelated signal fluctuations. The present paper aims to provide proportion of time during scintillation patches that decorrelations are found across GPS L1, L2, and L5 frequencies associated with high S4, corresponding high values of scattering coefficients, and large receiver position deviations thereby seriously compromising the performance of satellite-based navigation system. Results from the anomaly crest station at Calcutta indicate maximum 40% of scintillation time during February-April 2014 and 33% during August-October 2014 that the signals are decorrelated. It is important to note that it is only during these time intervals that the principle of frequency diversity could be applied for scintillation mitigation.

  6. Reproductive behavior of the Red-crested Finch Coryphospingus cucullatus (Aves: Thraupidae in southeastern Brazil

    Directory of Open Access Journals (Sweden)

    Paulo V.Q. Zima

    Full Text Available ABSTRACT Several behavioral aspects of the Red-crested Finch Coryphospingus cucullatus (Statius Müller, 1776 are poorly studied. Here we provide reproductive information on 16 active nests. This information may be valuable to elucidate the phylogenetic relationships of this bird, and to design plans to manage it. Nesting activities occurred from October to February. Clutches consisted of two to three eggs (2.06 ± 0.25, which were laid on consecutive days. Incubation usually started the morning the females laid their last egg and lasted 11.27 ± 0.47 days. Hatching was synchronous, or happened at a one-day interval. The nestling stage lasted 12 ± 0.89 days. Only females incubated the eggs and they fed the young more often than the males did. Overall nesting success, from incubation to fledging, was 28.2%. Nest architecture and egg color proved to be diagnostic characteristics of Coryphospingus , supporting its maintenance as a distinct genus within the recently proposed sub-family Tachyphoninae. Red-crested Finches showed a preference for certain nesting sites, i.e., forest borders or a Cerrado in late regeneration stage. This information can be useful to programs aiming to release illegally trapped individuals.

  7. 7

    African Journals Online (AJOL)

    abp

    2012-06-04

    Jun 4, 2012 ... (www.afenet.net) ... Malignant melanoma is a tumour arising from the melancytes which are derived from the neural crest, it migrate during the ... to deep palpation of the left hypochondrium, where a masse could be felt.

  8. Migrating the Light

    DEFF Research Database (Denmark)

    Sørensen, Bent

    The migration of Blaga’s universalist, even centralist poems from Romanian of the first third of the 20th C. into American of the first fifth of the 21st C. illustrates the uses of Pierre Joris’s nomadic methods. My translations of Blaga read well for a teenage audience whose only exposure to lit...

  9. Describing migration spatial structure

    NARCIS (Netherlands)

    Rogers, A; Willekens, F; Little, J; Raymer, J

    The age structure of a population is a fundamental concept in demography and is generally depicted in the form of an age pyramid. The spatial structure of an interregional system of origin-destination-specific migration streams is, however, a notion lacking a widely accepted definition. We offer a

  10. Brain Migration Revisited

    Science.gov (United States)

    Vinokur, Annie

    2006-01-01

    The "brain drain/brain gain" debate has been going on for the past 40 years, with irresolvable theoretical disputes and unenforceable policy recommendations that economists commonly ascribe to the lack of reliable empirical data. The recent report of the World Bank, "International migration, remittances and the brain drain", documents the…

  11. Dispersal and migration

    Directory of Open Access Journals (Sweden)

    Schwarz, C.

    2004-06-01

    Full Text Available Ringing of birds unveiled many aspects of avian migration and dispersal movements. However, there is even much more to be explored by the use of ringing and other marks. Dispersal is crucial in understanding the initial phase of migration in migrating birds as it is to understand patterns and processes of distribution and gene flow. So far, the analysis of migration was largely based on analysing spatial and temporal patters of recoveries of ringed birds. However, there are considerable biases and pitfalls in using recoveries due to spatial and temporal variation in reporting probabilities. Novel methods are required for future studies separating the confounding effects of spatial and temporal heterogeneity of recovery data and heterogeneity of the landscape as well. These novel approaches should aim a more intensive and novel use of the existing recovery data by taking advantage of, for instance, dynamic and multistate modeling, should elaborate schemes for future studies, and should also include other marks that allow a more rapid data collection, like telemetry, geolocation and global positioning systems, and chemical and molecular markers. The latter appear to be very useful in the delineating origin of birds and connectivity between breeding and non–breeding grounds. Many studies of migration are purely descriptive. However, King and Brooks (King & Brooks, 2004 examine if movement patterns of dolphins change after the introduction of a gillnet ban. Bayesian methods are an interesting approach to this problem as they provide a meaningful measure of the probability that such a change occurred rather than simple yes/no response that is often the result of classical statistical methods. However, the key difficulty of a general implementation of Bayesian methods is the complexity of the modelling —there is no general userfriendly package that is easily accessible to most scientists. Drake and Alisauskas (Drake & Alisauskas, 2004 examine the

  12. Migration and Africa

    DEFF Research Database (Denmark)

    Zoppi, Marco

    2014-01-01

    European powers imposed the nation-state on Africa through colonialism. But even after African independencies, mainstream discourses and government policies have amplified the idea that sedentariness and the state are the only acceptable mode of modernity. Migration is portrayed as a menace...

  13. Migration as Adventure

    DEFF Research Database (Denmark)

    Olwig, Karen Fog

    2018-01-01

    Narratives of adventure constitute a well-established convention of describing travel experiences, yet the significance of this narrative genre in individuals’ accounts of their migration and life abroad has been little investigated. Drawing on Simmel and Bakhtin, among others, this article...

  14. Digitizing migration heritage

    DEFF Research Database (Denmark)

    Marselis, Randi

    2011-01-01

    Museums are increasingly digitizing their collections and making them available to the public on-line. Creating such digital resources may become means for social inclusion. For museums that acknowledge migration history and cultures of ethnic minority groups as important subjects in multiethnic...

  15. The politicisation of migration

    NARCIS (Netherlands)

    van der Brug, W.; D' Amato, G.; Berkhout, J.; Ruedin, D.

    2015-01-01

    Why are migration policies sometimes heavily contested and high on the political agenda? And why do they, at other moments and in other countries, hardly lead to much public debate? The entrance and settlement of migrants in Western Europe has prompted various political reactions. In some countries

  16. Practical Data Migration

    CERN Document Server

    Morris, Johny

    2012-01-01

    This book is for executives and practitioners tasked with the movement of data from old systems to a new repository. It uses a series of steps guaranteed to get the reader from an empty new system to one that is working and backed by the user population. Using this proven methodology will vastly increase the chances of a successful migration.

  17. Migration pathways in soils

    International Nuclear Information System (INIS)

    Gronow, J.R.

    1986-01-01

    This study looked at diffusive migration through three types of deformation; the projectile pathways, hydraulic fractures of the sediments and faults, and was divided into three experimental areas: autoradiography, the determination of diffusion coefficients and electron microscopy of model projectile pathways in clay. For the autoradiography, unstressed samples were exposed to two separate isotopes, Pm-147 (a possible model for Am behaviour) and the poorly sorbed iodide-125. The results indicated that there was no enhanced migration through deformed kaolin samples nor through fractured Great Meteor East (GME) sediment, although some was evident through the projectile pathways in GME and possibly through the GME sheared samples. The scanning electron microscopy of projectile pathways in clay showed that emplacement of a projectile appeared to have no effect on the orientation of particles at distances greater than two projectile radii from the centre of a projectile pathway. It showed that the particles were not simply aligned with the direction of motion of the projectile but that, the closer to the surface of a particular pathway, the closer the particles lay to their original orientation. This finding was of interest from two points of view: i) the ease of migration of a pollutant along the pathway, and ii) possible mechanisms of hole closure. It was concluded that, provided that there is no advective migration, the transport of radionuclides through sediments containing these defects would not be significantly more rapid than in undeformed sediments. (author)

  18. International Migration of Couples

    DEFF Research Database (Denmark)

    Junge, Martin; Munk, Martin D.; Nikolka, Till

    2018-01-01

    Migrant self-selection is important to labor markets and public finances in both origin and destination countries. We develop a theoretical model regarding the migration of dual-earner couples and test it using population-wide administrative data from Denmark. Our model predicts that the probabil...

  19. Gastrointestinal and external parasites of the white-crested elaenia Elaenia albiceps chilensis (Aves, Tyrannidae in Chile

    Directory of Open Access Journals (Sweden)

    Danny Fuentes

    Full Text Available The objective of this study is to evaluate the ectoparasites and helminths of the white-crested elaenia, Elaenia albiceps chilensis. Feather mites Anisophyllodes elaeniae, Trouessartia elaeniae, and Analges sp. were detected in 51% of birds (n=106, whereas 24% were infected with lice (Tyranniphilopterus delicatulus, Menacanthus cfr. distinctus, and Ricinus cfr. invadens. Helminths Viguiera sp. and Capillaria sp. were found in five of the birds that were necropsied (n=20. With the exception of A. elaeniae, T. elaeniae, and T. delicatulus, all parasites represented new records found for the white-crested elaenia, and therefore for the Chilean repertoire of biodiversity.

  20. Globalization, Migration and Development

    Directory of Open Access Journals (Sweden)

    George, Susan

    2002-01-01

    Full Text Available EnglishMigration may become the most important branch of demography in the earlydecades of the new millennium in a rapidly globalizing world. This paper discusses the causes, costsand benefits of international migration to countries of the South and North, and key issues of commonconcern. International migration is as old as national boundaries, though its nature, volume,direction, causes and consequences have changed. The causes of migration are rooted in the rate ofpopulation growth and the proportion of youth in the population, their education and training,employment opportunities, income differentials in society, communication and transportationfacilities, political freedom and human rights and level of urbanization. Migration benefits the Souththrough remittances of migrants, improves the economic welfare of the population (particularly womenof South countries generally, increases investment, and leads to structural changes in the economy.However, emigration from the South has costs too, be they social or caused by factors such as braindrain. The North also benefits by migration through enhancement of economic growth, development ofnatural resources, improved employment prospects, social development and through exposure toimmigrants' new cultures and lifestyles. Migration also has costs to the North such as of immigrantintegration, a certain amount of destabilization of the economy, illegal immigration, and socialproblems of discrimination and exploitation. Issues common to both North and South include impact onprivate investment, trade, international cooperation, and sustainable development. Both North andSouth face a dilemma in seeking an appropriate balance between importing South's labour or itsproducts and exporting capital and technology from the North.FrenchLa migration est sans doute devenue la partie la plus importante de la démographie des premières décennies du nouveau millénaire dans un monde qui change rapidement. Ce

  1. Migration and Remittances : Recent Developments and Outlook - Transit Migration

    OpenAIRE

    World Bank Group

    2018-01-01

    This Migration and Development Brief reports global trends in migration and remittance flows, as well as developments related to the Global Compact on Migration (GCM), and the Sustainable Development Goal (SDG) indicators for volume of remittances as percentage of gross domestic product (GDP) (SDG indicator 17.3.2), reducing remittance costs (SDG indicator 10.c.1) and recruitment costs (SD...

  2. Arteriovenous fistula of the superior gluteal artery as a complication of posterior iliac crest bone graft harvesting: 3D-CT angiography and arterial embolization

    OpenAIRE

    Kong, Chae-Gwan; Park, Jong-Beom; Won, Yoo-Dong; Riew, K. Daniel

    2009-01-01

    Superior gluteal artery injuries are rare, but potentially serious complications that occur during posterior iliac crest bone graft harvesting. The authors reported an arteriovenous fistula of the superior gluteal artery, which occurred as a complication during posterior iliac crest bone graft harvesting and was diagnosed with 3D-CT angiography, then treated with arterial embolization.

  3. THE ROMANIAN MIGRATIONAL EVOLUTION PHENOMENON

    Directory of Open Access Journals (Sweden)

    Cristian Raluca

    2009-05-01

    Full Text Available In our contemporary democratic society the migration phenomenon meets unknown valences in any previous societies. Free will and right to self-determination, much exploited by the XX century society., raised the possibility of interpretation of migration

  4. International migration and the gender

    OpenAIRE

    Koropecká, Markéta

    2010-01-01

    My bachelor thesis explores the connection between international migration and gender. Gender, defined as a social, not a biological term, has a huge impact on the migration process. Statistics and expert studies that have been gender sensitive since 1970s demonstrate that women form half of the amount of the international migrants depending on the world region and representing a wide range of the kinds of international migration: family formation and reunification, labour migration, illegal ...

  5. The commercialization of migration.

    Science.gov (United States)

    Abrera-mangahas, M A

    1989-01-01

    International migration is not new to the Philippines. In the recent outflow of contract workers to the Middle East, there is a shift from individual and family initiated migrations to the more organized, highly commercial variety. While profit-taking intermediaries have played some role in the past, the increase in the number and influence of these intermediaries has altered the story of migration decision-making. In 1975, the signing of the bilateral labor agreement between the governments of Iran and the Philippines signalled the rising demand for Filipino contract workers. From 1970 to 1975, the number of Asian migrant workers in the Gulf countries rose from about 120,000 to 370,000. These figures rose dramatically to 3.3 million in 1985. The growing share of organized and commercialized migration has altered migration decision making. Primarily, intermediaries are able to broaden access to foreign job and high wage opportunities. Commercialization effectively raises the transaction costs for contract migration. Studies on recruitment costs and fees show that self-solicited foreign employment costs less than employment obtained through recruitment agents and intermediaries. The difference in the 2 prices is due, not only to overhead costs of intermediation, but more importantly to the rent exacted by agents from having job information and placement rights. In the Philippines in October 1987 the average placement fee was P8000, greatly exceeding the mandated maximum fee level of P5000. This average is understated because the computation includes the 17% who do not pay any fees. The widespread and popular view of recruitment intermediaries is negative, dominated by images of abuses and victims. Private intermediaries and the government bureaucracy need each other. Intermediaries need government; their consistent demand for incentives and protection is indicative. On the other hand, government expands its supervision of control of overseas employment via the

  6. Youth Labor Migration in Nepal

    OpenAIRE

    Bossavie, Laurent; Denisova, Anastasiya

    2018-01-01

    This descriptive study investigates internal and external labor migration by Nepalese youth. External labor migration is separated into the flow to India, which is unregulated, and the flow to other countries, which typically takes the form of temporary contract migration to countries with bilateral labor agreements with Nepal (referred to in Nepal as foreign employment). The study finds t...

  7. Musei del migration heritage / Migration heritage museums

    Directory of Open Access Journals (Sweden)

    Patrizia Dragoni

    2015-01-01

    Since the second half of the 1960s of the 20th century, a profound cultural innovation was accompanied to the radical change in the social, political and economic climate. The anthropological notion of culture as opposed to idealistic vision, the unusual and strong interest in material culture, the enunciation of the concept of cultural property by the Franceschini Commission, the luck of the Public History bring a change of the disciplinary statutes of historical sciences, which begin to attend to social history, focusing on the spontaneous sources of information and initiating experiences of oral history. To all this a remarkable transformation of the themes and of the social function of museums is added. This paper illustrates, in relation to this more general context, the foundation and the dissemination of museums dedicated to the history of migration in Italy and in the world, enunciates their possible social utility for the integration of present migrants in Italy and illustrates, by way of example, the museum recently opened in Recanati.

  8. Religion, migration og integration

    DEFF Research Database (Denmark)

    Borup, Jørn

    2010-01-01

    Sammenhængen mellem religion og integration har de sidste år været genstand for debat. Artiklen kommer ind på begreber og sammenhænge relateret til området (migration, diaspora, assimilation, etnicitet, kultur) og ser på religionens mulige rolle som negativ eller positiv ressource i integrationss......Sammenhængen mellem religion og integration har de sidste år været genstand for debat. Artiklen kommer ind på begreber og sammenhænge relateret til området (migration, diaspora, assimilation, etnicitet, kultur) og ser på religionens mulige rolle som negativ eller positiv ressource i...

  9. Grain boundary migration

    International Nuclear Information System (INIS)

    Dimitrov, O.

    1975-01-01

    Well-established aspects of grain-boundary migration are first briefly reviewed (influences of driving force, temperature, orientation and foreign atoms). Recent developments of the experimental methods and results are then examined, by considering the various driving of resistive forces acting on grain boundaries. Finally, the evolution in the theoretical models of grain-boundary motion is described, on the one hand for ideally pure metals and, on the other hand, in the presence of solute impurity atoms [fr

  10. Ventriculoperitoneal Shunt Migration

    Directory of Open Access Journals (Sweden)

    Justin P Puller

    2017-01-01

    Full Text Available History of present illness: A 40-year-old female presented to our ED with left upper abdominal pain and flank pain. The pain had begun suddenly 2 hours prior when she was reaching into a freezer to get a bag of frozen vegetables. She described the pain as sharp, constant, severe, and worse with movements and breathing. The pain radiated to the left shoulder. On review of systems, the patient had mild dyspnea and nausea. She denied fever, chills, headache, vision changes, vomiting, or urinary symptoms. Her medical history was notable for obstructive sleep apnea, gastroesophageal reflux disease, arthritis, fibromyalgia, depression, obesity, and idiopathic intracranial hypertension. For the latter, she had a VP (ventriculoperitoneal shunt placed 14 years prior to this visit. She had a history of 2 shunt revisions, the most recent 30 days before this ED visit. Significant findings: An immediate post-op abdominal x-ray performed after the patient’s VP shunt revision 30 days prior to this ED visit reveals the VP shunt tip in the mid abdomen. A CT of the abdomen performed on the day of the ED visit reveals the VP shunt tip interposed between the spleen and the diaphragm. Discussion: VP shunts have been reported to migrate to varied locations in the thorax and abdomen. Incidence of abdominal complications of VP shunt placement ranges from 10%-30%, and can include pseudocyst formation, migration, peritonitis, CSF ascites, infection, and viscus perforation. Incidence of distal shunt migration is reported as 10%, and most previously reported cases occurred in pediatric patients.1 A recent retrospective review cited BMI greater than thirty and previous shunt procedure as risk factors for distal shunt migration.2 The patient in the case presented had a BMI of 59 and 3 previous shunt procedures.

  11. Conservation physiology of animal migration

    Science.gov (United States)

    Lennox, Robert J.; Chapman, Jacqueline M.; Souliere, Christopher M.; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D.; Cooke, Steven J.

    2016-01-01

    Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains

  12. Insulin promotes cell migration by regulating PSA-NCAM

    Energy Technology Data Exchange (ETDEWEB)

    Monzo, Hector J.; Coppieters, Natacha [Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Park, Thomas I.H. [Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Department of Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Dieriks, Birger V.; Faull, Richard L.M. [Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Dragunow, Mike [Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Department of Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Curtis, Maurice A., E-mail: m.curtis@auckland.ac.nz [Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand); Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland (New Zealand)

    2017-06-01

    Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration. Insulin enhanced the phosphorylation of the focal adhesion kinase leading to dissociation of αv-integrin/PSA-NCAM clusters, and promoted cell migration. Our results show that αv-integrin plays a key role in the PSA-NCAM turnover process. αv-integrin knockdown stopped PSA-NCAM from being endocytosed, and αv-integrin/PSA-NCAM clusters co-labelled intracellularly with Rab5, altogether indicating a role for αv-integrin as a carrier for PSA-NCAM during internalisation. Furthermore, inhibition of p-FAK caused dissociation of αv-integrin/PSA-NCAM clusters and counteracted the insulin-induced accumulation of PSA at the cell surface and cell migration was impaired. Our data reveal a functional association between the insulin/p-FAK-dependent regulation of PSA-NCAM turnover and cell migration through the extracellular matrix. Most importantly, they identify a novel mechanism for insulin-stimulated cell migration. - Highlights: • Insulin modulates PSA-NCAM turnover through upregulation of p-FAK. • P-FAK modulates αv-integrin/PSA-NCAM clustering. • αv-integrin acts as a carrier for PSA-NCAM endocytosis. • Cell migration is promoted by cell surface PSA. • Insulin promotes PSA-dependent migration in vitro.

  13. Insulin promotes cell migration by regulating PSA-NCAM

    International Nuclear Information System (INIS)

    Monzo, Hector J.; Coppieters, Natacha; Park, Thomas I.H.; Dieriks, Birger V.; Faull, Richard L.M.; Dragunow, Mike; Curtis, Maurice A.

    2017-01-01

    Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration. Insulin enhanced the phosphorylation of the focal adhesion kinase leading to dissociation of αv-integrin/PSA-NCAM clusters, and promoted cell migration. Our results show that αv-integrin plays a key role in the PSA-NCAM turnover process. αv-integrin knockdown stopped PSA-NCAM from being endocytosed, and αv-integrin/PSA-NCAM clusters co-labelled intracellularly with Rab5, altogether indicating a role for αv-integrin as a carrier for PSA-NCAM during internalisation. Furthermore, inhibition of p-FAK caused dissociation of αv-integrin/PSA-NCAM clusters and counteracted the insulin-induced accumulation of PSA at the cell surface and cell migration was impaired. Our data reveal a functional association between the insulin/p-FAK-dependent regulation of PSA-NCAM turnover and cell migration through the extracellular matrix. Most importantly, they identify a novel mechanism for insulin-stimulated cell migration. - Highlights: • Insulin modulates PSA-NCAM turnover through upregulation of p-FAK. • P-FAK modulates αv-integrin/PSA-NCAM clustering. • αv-integrin acts as a carrier for PSA-NCAM endocytosis. • Cell migration is promoted by cell surface PSA. • Insulin promotes PSA-dependent migration in vitro.

  14. Genomic signatures of near-extinction and rebirth of the crested ibis and other endangered bird species

    DEFF Research Database (Denmark)

    Li, Shengbin; Li, Bo; Cheng, Cheng

    2014-01-01

    sequences of multiple crested ibis individuals, its thriving co-habitant, the little egret, Egretta garzetta, and the recently sequenced genomes of 41 other avian species that are under various degrees of survival threats, including the bald eagle, we carry out comparative analyses for genomic signatures...

  15. [Comparison of the Latissimus dorsi insertions on the iliac crest in chimpanzee (Pan troglodytes) and in man].

    Science.gov (United States)

    Vacher, C; Ben Hadj Yahia, S; Braun, M; Journeau, P

    2014-03-01

    Comparing to other primates, one of the most important specificities of the human anatomy are consequences of bipedalism. Although bone consequences are well known (lumbar lordosis, horizontal position of the foramen magnum, lengthening of the lower limbs, reduction of the pelvis, specialization of the foot), consequences of our locomotion on the Latissimus dorsi are still unclear. One dissection of a chimpanzee Latissimus dorsi (Pan troglodytes) has been performed and compared to 30 human Latissimus dorsi dissections (10 fresh cadavers and 20 formoled cadavers). In each dissection, the existence of direct muscular insertions on the iliac crest has been investigated and the constitution of the thoracolumbar fascia has been described. In chimpanzee dissection, a muscular direct insertion of the Latissimus dorsi was present on the iliac crest of 9 cm long. The TLF was made of the superficial and the deep fascias of the Latissimus dorsi and the superficial fascia of the erector spinae muscles which was deeper. In man, there was no direct muscular insertion of the Latissimus dorsi in 90 % of cases, the TLF was constituted the same way. This study suggests that the Latissimus dorsi has been separated from the iliac crest in man during the evolution because of the permanent bipedalism and that it stayed inserted on the iliac crest in chimpanzee because of the brachiation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. CREST biorepository for translational studies on malignant mesothelioma, lung cancer and other respiratory tract diseases: Informatics infrastructure and standardized annotation.

    Science.gov (United States)

    Ugolini, Donatella; Neri, Monica; Bennati, Luca; Canessa, Pier Aldo; Casanova, Georgia; Lando, Cecilia; Leoncini, Giacomo; Marroni, Paola; Parodi, Barbara; Simonassi, Claudio; Bonassi, Stefano

    2012-03-01

    Advances in molecular epidemiology and translational research have led to the need for biospecimen collection. The Cancer of the Respiratory Tract (CREST) biorepository is concerned with pleural malignant mesothelioma (MM) and lung cancer (LC). The biorepository staff has collected demographic and epidemiological data directly from consenting subjects using a structured questionnaire, in agreement with The Public Population Project in Genomics (P(3)G). Clinical and follow-up data were collected. Sample data were also recorded. The architecture is based on a database designed with Microsoft Access. Data standardization was carried out to conform with established conventions or procedures. As from January 31, 2011, the overall number of recruited subjects was 1,857 (454 LC, 245 MM, 130 other cancers and 1,028 controls). Due to its infrastructure, CREST was able to join international projects, sharing samples and/or data with other research groups in the field. The data management system allows CREST to be involved, through a minimum data set, in the national project for the construction of the Italian network of Oncologic BioBanks (RIBBO), and in the infrastructure of a pan-European biobank network (BBMRI). The CREST biorepository is a valuable tool for translational studies on respiratory tract diseases, because of its simple and efficient infrastructure.

  17. Prenuptial perfume: Alloanointing in the social rituals of the crested auklet ( Aethia cristatella) and the transfer of arthropod deterrents

    Science.gov (United States)

    Douglas, Hector D.

    2008-01-01

    Alloanointing, the transfer of chemicals between conspecifics, is known among mammals, but hitherto, the behavior has not been documented for birds. The crested auklet ( Aethia cristatella), a colonial seabird of Alaskan and Siberian waters, alloanoints during courtship with fragrant aldehydes that are released from specialized wick-like feathers located in the interscapular region. Crested auklets solicit anointment at the colony, and prospective mates rub bill, breast, head, and neck over wick feathers of their partners. This distributes aldehydes over the head, neck, and face where the birds cannot self-preen. The resulting chemical concentrations are sufficient to deter ectoparasites. Auklets that emit more odorant can transfer more defensive chemicals to mates and are thus more sexually attractive. Behavioral studies showed that crested auklets are attracted to their scent. Wild birds searched for dispensers that emitted their scent and rubbed their bills on the dispensers and engaged in vigorous anointment behaviors. In captive experiments, naïve crested auklets responded more strongly to synthetic auklet scent than controls, and the greatest behavioral response occurred during early courtship. This study extends scientific knowledge regarding functions of alloanointing. Alloanointing had previously been attributed to scent marking and individual recognition in vertebrates. Alloanointing is described here in the context of an adaptive social cue — the transfer of arthropod deterrents between prospective mates.

  18. OP-1 compared with iliac crest autograft in instrumented posterolateral fusion a randomized, multicenter non-inferiority trial

    NARCIS (Netherlands)

    Delawi, Diyar; Jacobs, Wilco; Van Susante, Job L C; Rillardon, Ludovic; Prestamburgo, Domenico; Specchia, Nicola; Gay, Emmanuel; Verschoor, Nico; Garcia-Fernandez, Carlos; Guerado, Enrique; Van Ufford, Henriette Quarles; Kruyt, Moyo C.; Dhert, Wouter J A; Cumhur Oner, F.

    2016-01-01

    Background: Spinal fusion with the use of autograft is a commonly performed procedure. However, harvesting of bone from the iliac crest is associated with complications. Bone morphogenetic proteins (BMPs) are extensively used as alternatives, often without sufficient evidence of safety and efficacy.

  19. The status of whitebark pine along the Pacific Crest National Scenic Trail on the Umpqua National Forest.

    Science.gov (United States)

    Ellen Michaels Goheen; Donald J. Goheen; Katy Marshall; Robert S. Danchok; John A. Petrick; Diane E. White

    2002-01-01

    Because of concern over widespread population declines, the distribution, stand conditions, and health of whitebark pine (Pinus albicaulis Englem.) were evaluated along the Pacific Crest National Scenic Trail on the Umpqua National Forest. Whitebark pine occurred on 76 percent of the survey transects. In general, whitebark pine was found in stands...

  20. Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

    NARCIS (Netherlands)

    Kasalak, Omer; Glaudemans, Andor W. J. M.; Overbosch, Jelle; Jutte, Paul C.; Kwee, Thomas C.

    OBJECTIVE: To determine and compare the value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. MATERIALS AND

  1. Many Faces of Migrations

    Directory of Open Access Journals (Sweden)

    Milica Antić Gaber

    2013-12-01

    We believe that in the present thematic issue we have succeeded in capturing an important part of the modern European research dynamic in the field of migration. In addition to well-known scholars in this field several young authors at the beginning their research careers have been shortlisted for the publication. We are glad of their success as it bodes a vibrancy of this research area in the future. At the same time, we were pleased to receive responses to the invitation from representatives of so many disciplines, and that the number of papers received significantly exceeded the maximum volume of the journal. Recognising and understanding of the many faces of migration are important steps towards the comprehensive knowledge needed to successfully meet the challenges of migration issues today and even more so in the future. It is therefore of utmost importance that researchers find ways of transferring their academic knowledge into practice – to all levels of education, the media, the wider public and, of course, the decision makers in local, national and international institutions. The call also applies to all authors in this issue of the journal.

  2. Searching for TeV cosmic electrons with the CREST experiment

    International Nuclear Information System (INIS)

    Coutu, S.; Anderson, T.; Bower, C.; Gennaro, J.; Geske, M.; Mueller, D.; Musser, J.; Nutter, S.; Park, N.H.; Schubnell, M.; Tarle, G.; Wakely, S.; Yagi, A.

    2011-01-01

    The Cosmic Ray Electron Synchrotron Telescope (CREST) high-altitude balloon experiment is a pathfinding effort to detect for the first time multi-TeV cosmic-ray electrons. Such would be the markers of nearby cosmic accelerators, as energetic electrons from distant Galactic sources are expected to be depleted by radiative losses during interstellar transport. Electrons will be detected indirectly by the characteristic signature of their geomagnetic synchrotron losses, in the form of a burst of coaligned x-ray photons intersecting the plane of the instrument. Since the primary electron itself need not traverse the payload, an effective detection area is achieved that is several times the nominal 6.4 m 2 instrument. The payload is composed of an array of 1024 BaF2 crystals surrounded by a set of veto scintillator detectors. A long-duration balloon flight in Antarctica is planned for the 2011-12 season.

  3. Searching for TeV cosmic electrons with the CREST experiment

    Energy Technology Data Exchange (ETDEWEB)

    Coutu, S., E-mail: coutu@phys.psu.edu [Department of Physics, Pennsylvania State University, 104 Davey Laboratory, University Park, PA 16802 (United States); Anderson, T. [Department of Physics, Pennsylvania State University, 104 Davey Laboratory, University Park, PA 16802 (United States); Bower, C. [Physics Department, Indiana University, 117 Swain Hall West, Bloomington, IN 47405 (United States); Gennaro, J. [Department of Physics, University of Michigan, Randall Physics Laboratory, 500 E. University Ave, Ann Arbor, MI 48109 (United States); Geske, M. [Department of Physics, Pennsylvania State University, 104 Davey Laboratory, University Park, PA 16802 (United States); Mueller, D. [Enrico Fermi Institute and Department of Physics, University of Chicago, 933 E. 56th St., Chicago, IL 60637 (United States); Musser, J. [Physics Department, Indiana University, 117 Swain Hall West, Bloomington, IN 47405 (United States); Nutter, S. [Department of Physics and Geology, Northern Kentucky University, Highland Heights, KY 41099 (United States); Park, N.H. [Enrico Fermi Institute and Department of Physics, University of Chicago, 933 E. 56th St., Chicago, IL 60637 (United States); Schubnell, M.; Tarle, G. [Department of Physics, University of Michigan, Randall Physics Laboratory, 500 E. University Ave, Ann Arbor, MI 48109 (United States); Wakely, S. [Enrico Fermi Institute and Department of Physics, University of Chicago, 933 E. 56th St., Chicago, IL 60637 (United States); Yagi, A. [Department of Physics, University of Michigan, Randall Physics Laboratory, 500 E. University Ave, Ann Arbor, MI 48109 (United States)

    2011-06-15

    The Cosmic Ray Electron Synchrotron Telescope (CREST) high-altitude balloon experiment is a pathfinding effort to detect for the first time multi-TeV cosmic-ray electrons. Such would be the markers of nearby cosmic accelerators, as energetic electrons from distant Galactic sources are expected to be depleted by radiative losses during interstellar transport. Electrons will be detected indirectly by the characteristic signature of their geomagnetic synchrotron losses, in the form of a burst of coaligned x-ray photons intersecting the plane of the instrument. Since the primary electron itself need not traverse the payload, an effective detection area is achieved that is several times the nominal 6.4 m{sup 2} instrument. The payload is composed of an array of 1024 BaF2 crystals surrounded by a set of veto scintillator detectors. A long-duration balloon flight in Antarctica is planned for the 2011-12 season.

  4. Coastal defence through low crested breakwater structures: jumping out of the frying pan into the fire?

    Science.gov (United States)

    Munari, Cristina; Corbau, Corinne; Simeoni, Umberto; Mistri, Michele

    2011-08-01

    The Adriatic coast of Punta Marina (Ravenna) is protected by 3-km long low crested breakwater structures (LCSs). Through a 3-years long multidisciplinar study, we assessed the impact of such defensive structures on environmental and biological condition. LCSs create pools where conditions are very different from the surrounding nearshore system. Mechanical disturbance by currents and waves varied greatly in intensity and frequency between seaward and landward sides of the structures. Sedimentary budget was positive at the landward side, but it was due to a gain on the seafloor and not on the emerged beach. The budget at seaward was negative. LCSs determine differences in benthic assemblages, alter the seasonal pattern of communities, and modify seasonal fluctuations of animal assemblages. Landward sheltered areas can be seen as "lagoonal island" surrounded by a "sea of marine habitat". Differences in ecological quality status, obtained through M-AMBI, are due to the sum of these factors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Crest Factor Reduction in MC-CDMA Employing Carrier Interferometry Codes

    Directory of Open Access Journals (Sweden)

    Natarajan Balasubramaniam

    2004-01-01

    Full Text Available This paper addresses signal compactness issues in MC-CDMA employing carrier interferometry codes using the measure of crest factor (CF. Carrier interferometry codes, applied to N -carrier MC-CDMA systems, enable 2N users to simultaneously share the system bandwidth with minimal degradation in performance (relative to the N -orthogonal-user case. First, for a fully loaded ( K=N and K=2N users MC-CDMA system with practical values of N , it is shown that the CF in downlink transmission demonstrates desirable properties of low mean and low variance. The downlink CF degrades when the number of users in the system decreases. Next, the high CF observed in the uplink is characterized and the poor CF in a partially loaded downlink as well as uplink is effectively combated using Schroeder's analytical CF reduction techniques.

  6. Numerical simulation of lowest-order short-crested wave instabilities

    DEFF Research Database (Denmark)

    Fuhrman, David R.; Madsen, Per A.; Bingham, Harry

    2006-01-01

    instabilities. These correctly lead to well-known (nearly symmetric) recurrence cycles below a previously established breaking threshold steepness, and to an asymmetric evolution (characterized by a permanent transfer of energy to the lower side-band) above this threshold, with dissipation from a smoothing...... that the unstable evolution of these initially three-dimensional waves leads to an asymmetric evolution, even for weakly nonlinear cases presumably well below breaking. This is characterized by an energy transfer to the lower side-band, which is also accompanied by a similar transfer to more distant upper side......-bands. At larger steepness, the evolution leads to a permanent downshift of both the mean and peak frequencies, driven in part by dissipation, effectively breaking the quasi-recurrence cycle. A single case involving a class Ib short-crested wave instability at relatively large steepness is also considered, which...

  7. Nymphal Linguatulosis in Indian Crested Porcupines (Histrix Indica in Southwest of Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Rajabloo

    2015-10-01

    Full Text Available Linguatula serrata is one of the important zoonotic parasites. Carnivores serve as definitive host. The larvae existed in mesenteric lymph nodes (MLNs, liver, lungs, etc of intermediate herbivores. The definitive host becomes infected by ingesting viscera containing the infective nymphal stage. Humans may be infected with Linguatula either by ingestion of nymphs resulting in a condition called nasopharyngeal linguatulosis or Halzoun syndrome or by ingestionof infective eggs which develop in internal organs resulting in visceral linguatulosis. Indian crested porcupine (Hystrix indica is a common rodent in Middle East. Based on some tradition, consumption of Histrix meat andviscera is common in some parts of Iran. The present study reports the occurrence of Linguatula serrata nymph in H. indica as a new intermediate host from southwest of Iran.

  8. Discharge coefficient of a rectangular sharp-edged broad-crested weir

    Directory of Open Access Journals (Sweden)

    Zachoval Zbyněk

    2014-06-01

    Full Text Available This paper is concerned with the determination of the relationship for the calculation of the discharge coefficient at free overflow over a rectangular sharp-edged broad-crested weir without lateral contraction. The determination was made on the basis of new measurement in a range of the relative thickness of the weir from 0.12 to 0.30 and newly in a large range of relative height of the weir extremely from 0.24 to 6.8 which greatly expands the application possibilities of low weirs. In addition, the effects of friction and surface tension on the value of the discharge coefficient were evaluated as well as the effect of the relative thickness of the weir. The new equation for discharge coefficient, expressed using the relative height of the weir, was subjected to verification made by an independent laboratory which confirmed its accuracy.

  9. Simultaneous occurrence of Salmonella arizonae in a sulfur crested cockatoo (Cacatua galerita galerita) and iguanas.

    Science.gov (United States)

    Orós, J; Rodríguez, J L; Fernández, A; Herráez, P; Espinosa de los Monteros, A; Jacobson, E R

    1998-01-01

    A case of fatal hepatitis in a captive sulfur crested cockatoo (Cacatua galerita galerita) in which Salmonella arizonae was microbiologically and immunohistochemically detected is described. The death of the cockatoo was closely related to the arrival of a group of 10 green iguanas (Iguana iguana) at a pet shop, and no previous clinical signs were observed in the cockatoo. The most important lesion observed at necropsy of the cockatoo was a multifocal necrotic hepatitis. Salmonella arizonae was isolated from the liver of the cockatoo and was detected immunohistochemically mainly around the edges of necrotic foci. Four iguanas died 3 days later showing a severe enteritis, and Salmonella arizonae was isolated from these lesions. The importance of quarantine and, because of pathogens such as Salmonella, the need to house reptiles at a distance from avian species, mainly psittacids, are reinforced. This is the first report of Salmonella arizonae infection in a cockatoo.

  10. Migration Process Evolution in Europe

    Directory of Open Access Journals (Sweden)

    Carmen Tudorache

    2006-08-01

    Full Text Available The migration phenomenon has always existed, fluctuating by the historic context, the economic, political, social and demographic disparities between the Central and East European countries and the EU Member States, the interdependencies between the origin and receiving countries and the European integration process evolutions. In the European Union, an integrated and inclusive approach of the migration issue is necessary. But a common policy on migration rests an ambitious objective. A common approach of the economic migration management and the harmonization of the migration policies of the Member States represented a challenge for the European Union and will become urgent in the future, especially due to the demographic ageing.

  11. Migrations in Slovenian geography textbooks

    Directory of Open Access Journals (Sweden)

    Jurij Senegačnik

    2013-12-01

    Full Text Available In Slovenia, the migrations are treated in almost all geographical textbooks for different levels of education. In the textbooks for the elementary school from the sixth to ninth grade, students acquire knowledge of the migrations by the inductive approach. Difficulty level of treatment and quantity of information are increasing by the age level. In the grammar school program a trail of gaining knowledge on migration is deductive. Most attention is dedicated to migrations in general geography textbooks. The textbooks for vocational and technical school programs deal with migrations to a lesser extent and with different approaches.

  12. Asymmetry of radial and symmetry of tangential neuronal migration pathways in developing human fetal brains

    Directory of Open Access Journals (Sweden)

    Yuta eMiyazaki

    2016-01-01

    Full Text Available AbstractThe radial and tangential neural migration pathways are two major neuronal migration streams in humans that are critical during corticogenesis. Corticogenesis is a complex process of neuronal proliferation that is followed by neuronal migration and the formation of axonal connections. Existing histological assessments of these two neuronal migration pathways have limitations inherent to microscopic studies and are confined to small anatomic regions of interest. Thus, little evidence is available about their three-dimensional fiber pathways and development throughout the entire brain. In this study, we imaged and analyzed radial and tangential migration pathways in the whole human brain using high-angular resolution diffusion MR imaging (HARDI tractography. We imaged ten fixed, postmortem fetal (17 gestational weeks (GW, 18 GW, 19 GW, three 20 GW, three 21 GW and 22 GW and eight in vivo newborn (two 30 GW, 34 GW, 35 GW and four 40 GW brains with no neurological/pathological conditions. We statistically compared the volume of the left and right radial and tangential migration pathways, and the volume of the radial migration pathways of the anterior and posterior regions of the brain. In specimens 22 GW or younger, the volume of radial migration pathways of the left hemisphere was significantly larger than that of the right hemisphere. The volume of posterior radial migration pathways was also larger when compared to the anterior pathways in specimens 22 GW or younger. In contrast, no significant differences were observed in the radial migration pathways of brains older than 22 GW. Moreover, our study did not identify any significant differences in volumetric laterality in the tangential migration pathways. These results suggest that these two neuronal migration pathways develop and regress differently, and radial neuronal migration varies regionally based on hemispheric and anterior-posterior laterality, potentially explaining regional

  13. Comparison of fracture site callus with iliac crest bone marrow as the source of plastic-adherent cells

    Directory of Open Access Journals (Sweden)

    Achmad Zaki

    2013-05-01

    Full Text Available Background: Red marrow has been described as the main source of mesenchymal stem cells although its aspiration and isolation from bone marrow was reported to have significant donor site morbidity. Since secondary bone healing occurs through formation of callus as the result of proliferation and differentiation of mesenchymal stem cells, callus may become alternative source for mesenchymal stem cells. In this study, we compared the number of plastic-adherent cells from fracture site callus and bone marrow of iliac crest after two and four weeks of culture.Methods: Sixteen New Zealand rabbits were fracturized at the femoral shaft. Then, these rabbits were taken care. After two weeks of fracturization, 3 mL iliac crest bone marrow aspiration and callus extraction of eight rabbits were cultured (group I. The other eight rabbits were treated equally after four weeks of fracturization (group II. Simultaneously, the cultures were observed after one and two weeks. Four weeks later, they were harvested. Cells were counted using Neubauer hemocytometer. The average number of cells between the sources and groups were statistically analyzed using the unpaired t-test. Results: In group I, there were 2.6 ± 0.1 x 104 cells in the culture of iliac crest bone marrow aspirate and 2.5 ± 0.1 x 104 cells in culture of callus extract from fracture site (p = 0.34. In group II, there were 2.7 ± 0.1 x 104 cells and 2.1 ± 0.1 x 104 cells, respectively (p < 0.001.Conclusion: Fracture site callus at the second week post-fracturization may be potential as source of plastic-adherent cells compared with iliac crest bone marrow. (Med J Indones. 2013;22:70-5Keywords: Bone marrow, fracture site callus, iliac crest, long bone, mesenchymal stem cell, plastic-adherent cells

  14. Morphological neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, G.X.; Sussner, P. [Univ. of Florida, Gainesville, FL (United States)

    1996-12-31

    The theory of artificial neural networks has been successfully applied to a wide variety of pattern recognition problems. In this theory, the first step in computing the next state of a neuron or in performing the next layer neural network computation involves the linear operation of multiplying neural values by their synaptic strengths and adding the results. Thresholding usually follows the linear operation in order to provide for nonlinearity of the network. In this paper we introduce a novel class of neural networks, called morphological neural networks, in which the operations of multiplication and addition are replaced by addition and maximum (or minimum), respectively. By taking the maximum (or minimum) of sums instead of the sum of products, morphological network computation is nonlinear before thresholding. As a consequence, the properties of morphological neural networks are drastically different than those of traditional neural network models. In this paper we consider some of these differences and provide some particular examples of morphological neural network.

  15. Neural Tube Defects

    Science.gov (United States)

    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 ...

  16. Neural tissue-spheres

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Johansen, Mathias; Blaabjerg, Morten

    2007-01-01

    By combining new and established protocols we have developed a procedure for isolation and propagation of neural precursor cells from the forebrain subventricular zone (SVZ) of newborn rats. Small tissue blocks of the SVZ were dissected and propagated en bloc as free-floating neural tissue...... content, thus allowing experimental studies of neural precursor cells and their niche...

  17. Matrix regulators in neural stem cell functions.

    Science.gov (United States)

    Wade, Anna; McKinney, Andrew; Phillips, Joanna J

    2014-08-01

    Neural stem/progenitor cells (NSPCs) reside within a complex and dynamic extracellular microenvironment, or niche. This niche regulates fundamental aspects of their behavior during normal neural development and repair. Precise yet dynamic regulation of NSPC self-renewal, migration, and differentiation is critical and must persist over the life of an organism. In this review, we summarize some of the major components of the NSPC niche and provide examples of how cues from the extracellular matrix regulate NSPC behaviors. We use proteoglycans to illustrate the many diverse roles of the niche in providing temporal and spatial regulation of cellular behavior. The NSPC niche is comprised of multiple components that include; soluble ligands, such as growth factors, morphogens, chemokines, and neurotransmitters, the extracellular matrix, and cellular components. As illustrated by proteoglycans, a major component of the extracellular matrix, the NSPC, niche provides temporal and spatial regulation of NSPC behaviors. The factors that control NSPC behavior are vital to understand as we attempt to modulate normal neural development and repair. Furthermore, an improved understanding of how these factors regulate cell proliferation, migration, and differentiation, crucial for malignancy, may reveal novel anti-tumor strategies. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Japanese migration in contemporary Japan: economic segmentation and interprefectural migration.

    Science.gov (United States)

    Fukurai, H

    1991-01-01

    This paper examines the economic segmentation model in explaining 1985-86 Japanese interregional migration. The analysis takes advantage of statistical graphic techniques to illustrate the following substantive issues of interregional migration: (1) to examine whether economic segmentation significantly influences Japanese regional migration and (2) to explain socioeconomic characteristics of prefectures for both in- and out-migration. Analytic techniques include a latent structural equation (LISREL) methodology and statistical residual mapping. The residual dispersion patterns, for instance, suggest the extent to which socioeconomic and geopolitical variables explain migration differences by showing unique clusters of unexplained residuals. The analysis further points out that extraneous factors such as high residential land values, significant commuting populations, and regional-specific cultures and traditions need to be incorporated in the economic segmentation model in order to assess the extent of the model's reliability in explaining the pattern of interprefectural migration.

  19. Labour migration from Turkey.

    Science.gov (United States)

    Uner, S

    1988-01-01

    This study is concerned with Turkish labor migration to Western Europe. Earlier and recent patterns of labor migration, characteristics of migrants by occupation, area of destination, and by geographical origins are discussed. Economic and demographic consequences of labor migration are also analyzed. It is estimated that Turkey's population will reach 73 million at the year 2000 with the present growth rate of 2.48% annually. Considering the efforts made to slow down the present high fertility rates and assuming that the decrease in labor force participation during 1970-1980 continues, the author concludes that the labor supply will increase with a growth rate of 2% annually for the next 13-15 years. Thus, the labor supply will reach 26.6 million people in the year 2000 from the 1980 level of 17.8 million. Assuming also that the income/employment elasticity of .25 which was observed throughout the period of 1960-1980 will not change until 2000, the annual growth rate of employment may be estimated as 1.5%. Thus, the number of people employed will reach 20 million in the year 1990 and 23.2 million in the year 2000. 8.8 million people will join the labor market as new entrants between 1980 and 2000. Only 6 million people out of 8.8 million will be employed. Thus, in the year 2000, it is estimated that 2.8 million new unemployed people will be added to the already open unemployment figure 1980 census data give the number of unemployed as .6 million people. Adding the 2.8 million new unemployed to this figure totals 3.4 million unemployed in 2000. The State Planning Organization's estimate of labor surplus for 1980 was 2.5 million people. When 2.8 million unemployed people are added to this figure, the labor surplus for the year 2000 reaches 5.3 million people.

  20. ILO - International Migration Programme.

    Science.gov (United States)

    Boudraa, Miriam

    2011-01-01

    In a wide International Context characterised not only by the economical development but also by the social, cultural, political and individual development, we witness more and more to a exchange between the developed and the developing countries, which can be translated especially in the migration of the work force. In theory, all countries are either countries of origin either countries of transit or destination, and they are all responsible for the rights of migrant workers by promoting the rights, by monitoring and by preventing the abusive conditions. The process of migration of the workforce can be divided into three stages: the first coincides with the period prior to departure, the second is represented by the aftermath of the departure and the period of stay in the country of destination, the third stage corresponds to the return in the country of origin. The workers must be protected throughout this process by the international organizations that perform the catalytic role of communication and exchange between countries, for the only purpose of protecting the rights of immigrant and/or immigrants workers. The responsibility for the protection of workers is divided among the various players in the International Labour Organisation. Every country has to apply measures according to the international standards regarding workers' rights, standards that guide the various countries in the formulation and implementation of their policies and legislation. These standards are suggested by International Conventions, the ILO Conventions and other international instruments such as the human rights instrument. There has been a big step forward once the ILO Fundamental Conventions and Conventions on Migrant Workers where implemented and this implementation represented the use of the Guidelines "ILO Multilateral Framework on Labour Migration".

  1. Urbanization, Migration, Information

    Directory of Open Access Journals (Sweden)

    Konstantin Lidin

    2016-05-01

    Full Text Available In the contemporary world urbanization becomes a large-scale process. Huge flows of people migrate from poorer districts to the cities with a higher level of consumption. It takes migrants about 15-25 years to give up their traditional ascetic way of life. In this period the ‘new citizens’ try to arrange compact settlements with an archaic way of life, insanitary conditions, high criminogenity and an authoritative local self-government. The processes of formation and decay of the ascetic enclave are viewed through the example of the ‘Shanghai’ trading neighborhood in Irkutsk.

  2. Exploration of molecular pathways mediating electric field-directed Schwann cell migration by RNA-Seq

    Science.gov (United States)

    Yao, Li; Li, Yongchao; Knapp, Jennifer; Smith, Peter

    2015-01-01

    In peripheral nervous systems, Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. Following spinal cord injury, Schwann cells regenerate and migrate to the lesion and are involved in the spinal cord regeneration process. Transplantation of Schwann cells into injured neural tissue results in enhanced spinal axonal regeneration. Effective directional migration of Schwann cells is critical in the neural regeneration process. In this study, we report that Schwann cells migrate anodally in an applied electric field (EF). The directedness and displacement of anodal migration increased significantly when the strength of the EF increased from 50 mV/mm to 200 mV/mm. The EF did not significantly affect the cell migration speed. To explore the genes and signaling pathways that regulate cell migration in EFs, we performed a comparative analysis of differential gene expression between cells stimulated with an EF (100 mV/mm) and those without using next-generation RNA sequencing, verified by RT-qPCR. Based on the cut-off criteria (FC > 1.2, q cells versus EF-stimulated cells. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found that compared to the control group, 21 pathways are down-regulated, while 10 pathways are up-regulated. Differentially expressed genes participate in multiple cellular signaling pathways involved in the regulation of cell migration, including pathways of regulation of actin cytoskeleton, focal adhesion, and PI3K-Akt. PMID:25557037

  3. Neuronal Migration and Neuronal Migration Disorder in Cerebral Cortex

    OpenAIRE

    SUN, Xue-Zhi; TAKAHASHI, Sentaro; GUI, Chun; ZHANG, Rui; KOGA, Kazuo; NOUYE, Minoru; MURATA, Yoshiharu

    2002-01-01

    Neuronal cell migration is one of the most significant features during cortical development. After final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. Neuronal migration is guided by radial glial fibers and also needs proper receptors, ligands, and other unknown extracellular factors, requests local signaling (e.g. some emitted by the Cajal-Retz...

  4. Electric Signals Regulate the Directional Migration of Oligodendrocyte Progenitor Cells (OPCs via β1 Integrin

    Directory of Open Access Journals (Sweden)

    Bangfu Zhu

    2016-11-01

    Full Text Available The guided migration of neural cells is essential for repair in the central nervous system (CNS. Oligodendrocyte progenitor cells (OPCs will normally migrate towards an injury site to re-sheath demyelinated axons; however the mechanisms underlying this process are not well understood. Endogenous electric fields (EFs are known to influence cell migration in vivo, and have been utilised in this study to direct the migration of OPCs isolated from neonatal Sprague-Dawley rats. The OPCs were exposed to physiological levels of electrical stimulation, and displayed a marked electrotactic response that was dependent on β1 integrin, one of the key subunits of integrin receptors. We also observed that F-actin, an important component of the cytoskeleton, was re-distributed towards the leading edge of the migrating cells, and that this asymmetric rearrangement was associated with β1 integrin function.

  5. Prolonged Expansion Induces Spontaneous Neural Progenitor Differentiation from Human Gingiva-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Rajan, Thangavelu Soundara; Scionti, Domenico; Diomede, Francesca; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana

    2017-12-01

    Neural crest-derived mesenchymal stem cells (MSCs) obtained from dental tissues received considerable interest in regenerative medicine, particularly in nerve regeneration owing to their embryonic origin and ease of harvest. Proliferation efficacy and differentiation capacity into diverse cell lineages propose dental MSCs as an in vitro tool for disease modeling. In this study, we investigated the spontaneous differentiation efficiency of dental MSCs obtained from human gingiva tissue (hGMSCs) into neural progenitor cells after extended passaging. At passage 41, the morphology of hGMSCs changed from typical fibroblast-like shape into sphere-shaped cells with extending processes. Next-generation transcriptomics sequencing showed increased expression of neural progenitor markers such as NES, MEIS2, and MEST. In addition, de novo expression of neural precursor genes, such as NRN1, PHOX2B, VANGL2, and NTRK3, was noticed in passage 41. Immunocytochemistry results showed suppression of neurogenesis repressors TP53 and p21, whereas Western blot results revealed the expression of neurotrophic factors BDNF and NT3 at passage 41. Our results showed the spontaneous efficacy of hGMSCs to differentiate into neural precursor cells over prolonged passages and that these cells may assist in producing novel in vitro disease models that are associated with neural development.

  6. Neural electrical activity and neural network growth.

    Science.gov (United States)

    Gafarov, F M

    2018-05-01

    The development of central and peripheral neural system depends in part on the emergence of the correct functional connectivity in its input and output pathways. Now it is generally accepted that molecular factors guide neurons to establish a primary scaffold that undergoes activity-dependent refinement for building a fully functional circuit. However, a number of experimental results obtained recently shows that the neuronal electrical activity plays an important role in the establishing of initial interneuronal connections. Nevertheless, these processes are rather difficult to study experimentally, due to the absence of theoretical description and quantitative parameters for estimation of the neuronal activity influence on growth in neural networks. In this work we propose a general framework for a theoretical description of the activity-dependent neural network growth. The theoretical description incorporates a closed-loop growth model in which the neural activity can affect neurite outgrowth, which in turn can affect neural activity. We carried out the detailed quantitative analysis of spatiotemporal activity patterns and studied the relationship between individual cells and the network as a whole to explore the relationship between developing connectivity and activity patterns. The model, developed in this work will allow us to develop new experimental techniques for studying and quantifying the influence of the neuronal activity on growth processes in neural networks and may lead to a novel techniques for constructing large-scale neural networks by self-organization. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Network migration for printers

    CERN Multimedia

    2016-01-01

    Further to the recent General Purpose (office) Network reorganisation (as announced in the Bulletin - see here), please note that the majority of print devices will be automatically migrated to the new network IP address range on Tuesday 27 September.   This change should be transparent for these devices and therefore end-users, provided you have installed the printers from the Print Service website. A small number of devices will require manual intervention from the Printer Support team in order to migrate correctly. These devices will not change their IP address until the manual intervention, which will be carried out before Monday 3rd October. However, if you have mistakenly connected directly to the printer’s IP address, then your printing will be affected – please uninstall the printer (for help, see: KB3785), and re-install it from the Print Service website (or follow instructions for visitor machines). Please do this as soon as possible in order to avoid printing issues, t...

  8. MIGRATION AND ITS ENVIROMENTAL EFFECTS

    OpenAIRE

    Rashid SAEED; Rana NADIR IDREES; Humna IJAZ; Marriam FURQANI; Raziya NADEEM

    2012-01-01

    Migration can be ongoing shifting of a particular person from one location to another. The reason of shifting depends on selected thought deficiency, shock, difficulties, hopes, enthusiasm. Case study ended up recognizing the extent to which in turn migration can be relying on the specifics especially natural environment. This particular document expects to research the actual linkages between the atmosphere as well as migration using secondary data. Lots of investigation may be completed wit...

  9. Nordic Migration and Integration Research

    OpenAIRE

    Pyrhönen, Niko; Martikainen, Tuomas; Leinonen, Johanna

    2017-01-01

    EXECUTIVE SUMMARY Migration and integration are currently highly contentious topics in political, public and scientific arenas, and will remain so in the near future. However, many common migration-related prejudices and inefficien¬cies in the integration of the migrant population are due to the lack of sound, tested and accessible scientific research. Therefore, the study of migration – by developing basic research and by properly resourcing novel methodological approaches and interventions ...

  10. The challenges of managing migration

    Energy Technology Data Exchange (ETDEWEB)

    Tacoli, Cecilia

    2005-10-15

    Migration and urbanisation are driven by economic growth and social change, but also by deepening inequalities. Managing migration should not be equated with curbing it, as this inevitably reduces migrants' rights. But managing population movement whilst respecting the rights of migrants and nonmigrants, supporting the contribution of migration to poverty reduction and economic growth in sending and receiving areas and reducing the human and material costs of movement means that fundamental challenges need to be addressed.

  11. Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A)

    DEFF Research Database (Denmark)

    Gane, Edward J; Pianko, Stephen; Roberts, Stuart K

    2017-01-01

    BACKGROUND: New hepatitis C virus (HCV) therapies with pan-genotypic efficacy are needed. The goals of part A of C-CREST-1 and C-CREST-2 were to compare the efficacies of two doses (300 mg or 450 mg once daily) of uprifosbuvir (MK-3682; NS5B inhibitor) in an 8-week regimen combined with grazoprev...

  12. Low-latitude scintillation occurrences around the equatorial anomaly crest over Indonesia

    Directory of Open Access Journals (Sweden)

    P. Abadi

    2014-01-01

    Full Text Available We investigated low-latitude ionospheric scintillation in Indonesia using two GPS receivers installed at Bandung (107.6° E, 6.9° S; magnetic latitude 17.5° S and Pontianak (109.3° E, 0.02° S; magnetic latitude 8.9° S. This study aimed to characterise climatological and directional ionospheric scintillation occurrences, which are useful not only for the physics of ionospheric irregularities but also for practical use in GNSS (global navigation satellite system-based navigation. We used the deployed instrument's amplitude scintillation (S4 index data from 2009, 2010, and 2011; the yearly SSN (sunspot-smoothed numbers were 3.1, 16.5, and 55.9, respectively. In summary, (1 scintillation occurrences in the post-sunset period (18:00–01:00 LT during equinox months (plasma bubble season at the two sites can be ascribed to the plasma bubble; (2 using directional analyses of the two sites, we found that the distribution of scintillation occurrences is generally concentrated between the two sites, indicating the average location of the EIA (equatorial ionisation anomaly crest; (3 scintillation occurrence enhancements for the two sites in field-aligned directions are herein reported for the first time by ground-based observation in a low-latitude region; (4 distribution of scintillation occurrences at Pontianak are concentrated in the southern sky, especially in the southwest direction, which is very likely associated with the plasma bubble tilted westward with increasing latitude; and (5 scintillation occurrence in the post-midnight period in the non-plasma-bubble season is the most intriguing variable occurring between the two sites (i.e. post-midnight scintillations are observed more at Bandung than Pontianak. Most of the post-midnight scintillations observed at Bandung are concentrated in the northern sky, with low elevation angles. This might be due to the amplitude of irregularities in certain directions, which may be effectively enhanced by

  13. Sexual signalling in female crested macaques and the evolution of primate fertility signals.

    Science.gov (United States)

    Higham, James P; Heistermann, Michael; Saggau, Carina; Agil, Muhammad; Perwitasari-Farajallah, Dyah; Engelhardt, Antje

    2012-06-18

    Female signals of fertility have evolved in diverse taxa. Among the most interesting study systems are those of multimale multifemale group-living primates, where females signal fertility to males through multiple signals, and in which there is substantial inter-specific variation in the composition and reliability of such signals. Among the macaques, some species display reliable behavioural and/or anogenital signals while others do not. One cause of this variation may be differences in male competitive regimes: some species show marked sexual dimorphism and reproductive skew, with males fighting for dominance, while others show low dimorphism and skew, with males queuing for dominance. As such, there is variation in the extent to which rank is a reliable proxy for male competitiveness, which may affect the extent to which it is in females' interest to signal ovulation reliably. However, data on ovulatory signals are absent from species at one end of the macaque continuum, where selection has led to high sexual dimorphism and male reproductive skew. Here we present data from 31 cycles of 19 wild female crested macaques, a highly sexually dimorphic species with strong mating skew. We collected measures of ovarian hormone data from faeces, sexual swelling size from digital images, and male and female behaviour. We show that both sexual swelling size and female proceptivity are graded-signals, but relatively reliable indicators of ovulation, with swelling size largest and female proceptive behaviours most frequent around ovulation. Sexual swelling size was also larger in conceptive cycles. Male mating behaviour was well timed to female ovulation, suggesting that males had accurate information about this. Though probabilistic, crested macaque ovulatory signals are relatively reliable. We argue that in species where males fight over dominance, male dominance rank is surrogate for competitiveness. Under these circumstances it is in the interest of females to increase

  14. Sexual signalling in female crested macaques and the evolution of primate fertility signals

    Directory of Open Access Journals (Sweden)

    Higham James P

    2012-06-01

    Full Text Available Abstract Background Female signals of fertility have evolved in diverse taxa. Among the most interesting study systems are those of multimale multifemale group-living primates, where females signal fertility to males through multiple signals, and in which there is substantial inter-specific variation in the composition and reliability of such signals. Among the macaques, some species display reliable behavioural and/or anogenital signals while others do not. One cause of this variation may be differences in male competitive regimes: some species show marked sexual dimorphism and reproductive skew, with males fighting for dominance, while others show low dimorphism and skew, with males queuing for dominance. As such, there is variation in the extent to which rank is a reliable proxy for male competitiveness, which may affect the extent to which it is in females’ interest to signal ovulation reliably. However, data on ovulatory signals are absent from species at one end of the macaque continuum, where selection has led to high sexual dimorphism and male reproductive skew. Here we present data from 31 cycles of 19 wild female crested macaques, a highly sexually dimorphic species with strong mating skew. We collected measures of ovarian hormone data from faeces, sexual swelling size from digital images, and male and female behaviour. Results We show that both sexual swelling size and female proceptivity are graded-signals, but relatively reliable indicators of ovulation, with swelling size largest and female proceptive behaviours most frequent around ovulation. Sexual swelling size was also larger in conceptive cycles. Male mating behaviour was well timed to female ovulation, suggesting that males had accurate information about this. Conclusion Though probabilistic, crested macaque ovulatory signals are relatively reliable. We argue that in species where males fight over dominance, male dominance rank is surrogate for competitiveness. Under these

  15. Chaotic diagonal recurrent neural network

    International Nuclear Information System (INIS)

    Wang Xing-Yuan; Zhang Yi

    2012-01-01

    We propose a novel neural network based on a diagonal recurrent neural network and chaos, and its structure and learning algorithm are designed. The multilayer feedforward neural network, diagonal recurrent neural network, and chaotic diagonal recurrent neural network are used to approach the cubic symmetry map. The simulation results show that the approximation capability of the chaotic diagonal recurrent neural network is better than the other two neural networks. (interdisciplinary physics and related areas of science and technology)

  16. The morphology and migration of transverse bars off the west-central Florida coast

    Science.gov (United States)

    Gelfenbaum, G.; Brooks, G.R.

    2003-01-01

    A series of migrating shore-normal sandbars with wavelengths of 75-120 m and heights up to 2 m have been identified off the northern tip of Anna Maria Island, a barrier island on the west-central Florida coast. Similar features have been described elsewhere since the 1930s and termed 'transverse bars'. The transverse bars identified off Anna Maria Island are found for about 3 km along the coast and extend 4 km offshore, well outside the normal surf-zone width. No cusps or any other associated beach expression is evident despite the fact that the bars come to within about 75 m of the beach. Sediments on the crests of the bars are a well-sorted fine quartz sand, whereas sediments in the troughs are a poorly sorted coarse carbonate shell hash. Historical aerial photographs and repeated high-resolution bathymetric surveys provide a means of quantifying the migration of the transverse bars. Analyses of orthorectified aerial photographs from the early 1940s through the mid 1990s clearly show movement or migration taking place in the bar field. In the 40-yr period from 1951 to 1991, the southern edge of the bar field moved 200-350 m to the south, with an average long-term migration rate of 8 m/yr. Repeated bathymetric surveys over an 8-month period give an average short-term migration rate of 21 m/yr to the south. Wave and current measurements suggest that southerly winds associated with the passage of cold fronts drive near-bed currents to the south that are strong enough to initiate sediment transport and cause the southerly migration of the transverse bars.

  17. Countering inbreeding with migration 1. Migration from unrelated ...

    African Journals Online (AJOL)

    Ret:ieved 6 Octoher 1991; ut:cepted I8 Mur- 1995. The eff'ect of migration on inbreeding is moclelled fbr small populations with immigrants from a large unrelated population. Different migration rates and numbers fbr the two sexes are assumed, and a general recursion equation for inbreeding progress derived, which can ...

  18. Evolvable Neural Software System

    Science.gov (United States)

    Curtis, Steven A.

    2009-01-01

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

  19. Theoretical Investigation of Peak-Delay Force Reduction for Caissons Exposed to Non-breaking Short-Crested Waves

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Liu, Z.

    In nature coastal structures are exposed to oblique short-crested waves. The effect of wave incident angle on total wave force on a long caisson are twofold. The one is the force reduction due to the reduction of instantaneous point pressure on the caisson, named point-pressure force reduction....... The other is the force reduction due to the fact that the peak pressures do not occur simultaneously along the caisson, named peak-delay force reduction. These two reduction effects can also be expected with short-crested waves, as the short-crestedness of waves means the spreading of wave energy over...... a range of incident angles. The peak-delay force reduction, i.e. no simultaneous peak along caisson, is of particular interest because the equipment improvement in construction enables the building of considerably long caissons. In Japan length of caissons exceeds often 100m. This paper will concentrate...

  20. Migration and regional inequality

    DEFF Research Database (Denmark)

    Peng, Lianqing; Swider, Sarah

    2017-01-01

    Scholars studying economic inequality in China have maintained that regional inequality and economic divergence across provinces have steadily increased over the past 30 years. New studies have shown that this trend is a statistical aberration; calculations show that instead of quickly and sharply...... rising, regional inequality has actually decreased, and most recently, remained stable. Our study suggests that China’s unique migratory regime is crucial to understanding these findings. We conduct a counterfactual simulation to demonstrate how migration and remittances have mitigated income inequality...... across provinces in order to show that without these processes, we would have seen more of a rise in interprovincial income inequality. We conclude by arguing that inequality in China is still increasing, but it is changing and becoming less place-based. As regional inequality decreases, there are signs...