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Sample records for neural crest nc

  1. The neural crest and neural crest cells: discovery and significance ...

    Indian Academy of Sciences (India)

    In this paper I provide a brief overview of the major phases of investigation into the neural crest and the major players involved, discuss how the origin of the neural crest relates to the origin of the nervous system in vertebrate embryos, discuss the impact on the germ-layer theory of the discovery of the neural crest and of ...

  2. CHARGEd with neural crest defects.

    Science.gov (United States)

    Pauli, Silke; Bajpai, Ruchi; Borchers, Annette

    2017-10-30

    Neural crest cells are highly migratory pluripotent cells that give rise to diverse derivatives including cartilage, bone, smooth muscle, pigment, and endocrine cells as well as neurons and glia. Abnormalities in neural crest-derived tissues contribute to the etiology of CHARGE syndrome, a complex malformation disorder that encompasses clinical symptoms like coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, ear anomalies, and deafness. Mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene are causative of CHARGE syndrome and loss-of-function data in different model systems have firmly established a role of CHD7 in neural crest development. Here, we will summarize our current understanding of the function of CHD7 in neural crest development and discuss possible links of CHARGE syndrome to other developmental disorders. © 2017 Wiley Periodicals, Inc.

  3. The neural crest and neural crest cells: discovery and significance ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    such as sea urchins, flies, fish and humans. (ii) Embryos (and so larvae and adults) form by differentiation from these germ layers. (iii) Homologous structures in different animals arise from the same germ layers. The germ-layer theory exerted a profound influence on those claiming a neural crest — that is, an ectodermal.

  4. 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

    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 re...

  5. The Neural Crest in Cardiac Congenital Anomalies

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    Keyte, Anna; Hutson, Mary Redmond

    2012-01-01

    This review discusses the function of neural crest as they relate to cardiovascular defects. The cardiac neural crest cells are a subpopulation of cranial neural crest discovered nearly 30 years ago by ablation of premigratory neural crest. The cardiac neural crest cells are necessary for normal cardiovascular development. We begin with a description of the crest cells in normal development, including their function in remodeling the pharyngeal arch arteries, outflow tract septation, valvulogenesis, and development of the cardiac conduction system. The cells are also responsible for modulating signaling in the caudal pharynx, including the second heart field. Many of the molecular pathways that are known to influence specification, migration, patterning and final targeting of the cardiac neural crest cells are reviewed. The cardiac neural crest cells play a critical role in the pathogenesis of various human cardiocraniofacial syndromes such as DiGeorge, Velocardiofacial, CHARGE, Fetal Alcohol, Alagille, LEOPARD, and Noonan syndromes, as well as Retinoic Acid Embryopathy. The loss of neural crest cells or their dysfunction may not always directly cause abnormal cardiovascular development, but are involved secondarily because crest cells represent a major component in the complex tissue interactions in the head, pharynx and outflow tract. Thus many of the human syndromes linking defects in the heart, face and brain can be better understood when considered within the context of a single cardiocraniofacial developmental module with the neural crest being a key cell type that interconnects the regions. PMID:22595346

  6. Neural crest specification by noncanonical Wnt signaling and PAR-1

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    Ossipova, Olga; Sokol, Sergei Y.

    2011-01-01

    Neural crest (NC) cells are multipotent progenitors that form at the neural plate border, undergo epithelial-mesenchymal transition and migrate to diverse locations in vertebrate embryos to give rise to many cell types. Multiple signaling factors, including Wnt proteins, operate during early embryonic development to induce the NC cell fate. Whereas the requirement for the Wnt/β-catenin pathway in NC specification has been well established, a similar role for Wnt proteins that do not stabilize β-catenin has remained unclear. Our gain- and loss-of-function experiments implicate Wnt11-like proteins in NC specification in Xenopus embryos. In support of this conclusion, modulation of β-catenin-independent signaling through Dishevelled and Ror2 causes predictable changes in premigratory NC. Morpholino-mediated depletion experiments suggest that Wnt11R, a Wnt protein that is expressed in neuroectoderm adjacent to the NC territory, is required for NC formation. Wnt11-like signals might specify NC by altering the localization and activity of the serine/threonine polarity kinase PAR-1 (also known as microtubule-associated regulatory kinase or MARK), which itself plays an essential role in NC formation. Consistent with this model, PAR-1 RNA rescues NC markers in embryos in which noncanonical Wnt signaling has been blocked. These experiments identify novel roles for Wnt11R and PAR-1 in NC specification and reveal an unexpected connection between morphogenesis and cell fate. PMID:22110058

  7. 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.

  8. Anterior Hox Genes Interact with Components of the Neural Crest Specification Network to Induce Neural Crest Fates

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    Gouti, Mina; Briscoe, James; Gavalas, Anthony

    2011-01-01

    Hox genes play a central role in neural crest (NC) patterning particularly in the cranial region of the body. Despite evidence that simultaneous loss of Hoxa1 and Hoxb1 function resulted in NC specification defects, the role of Hox genes in NC specification has remained unclear due to extended genetic redundancy among Hox genes. To circumvent this problem, we expressed anterior Hox genes in the trunk neural tube of the developing chick embryo. This demonstrated that anterior Hox genes play a central role in NC cell specification by rapidly inducing the key transcription factors Snail2 and Msx1/2 and a neural progenitor to NC cell fate switch characterized by cell adhesion changes and an epithelial-to-mesenchymal transition (EMT). Cells delaminated from dorsal and medial neural tube levels and generated ectopic neurons, glia progenitors, and melanocytes. The mobilization of the NC genetic cascade was dependent upon bone morphogenetic protein signaling and optimal levels of Notch signaling. Therefore, anterior Hox patterning genes participate in NC specification and EMT by interacting with NC-inducing signaling pathways and regulating the expression of key genes involved in these processes. Stem Cells 2011;29:858–870 PMID:21433221

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

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    Erika Kague

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

  10. Neural crest development in fetal alcohol syndrome.

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    Smith, Susan M; Garic, Ana; Flentke, George R; Berres, Mark E

    2014-09-01

    Fetal alcohol spectrum disorder (FASD) is a leading cause of neurodevelopmental disability. Some affected individuals possess distinctive craniofacial deficits, but many more lack overt facial changes. An understanding of the mechanisms underlying these deficits would inform their diagnostic utility. Our understanding of these mechanisms is challenged because ethanol lacks a single receptor when redirecting cellular activity. This review summarizes our current understanding of how ethanol alters neural crest development. Ample evidence shows that ethanol causes the "classic" fetal alcohol syndrome (FAS) face (short palpebral fissures, elongated upper lip, deficient philtrum) because it suppresses prechordal plate outgrowth, thereby reducing neuroectoderm and neural crest induction and causing holoprosencephaly. Prenatal alcohol exposure (PAE) at premigratory stages elicits a different facial appearance, indicating FASD may represent a spectrum of facial outcomes. PAE at this premigratory period initiates a calcium transient that activates CaMKII and destabilizes transcriptionally active β-catenin, thereby initiating apoptosis within neural crest populations. Contributing to neural crest vulnerability are their low antioxidant responses. Ethanol-treated neural crest produce reactive oxygen species and free radical scavengers attenuate their production and prevent apoptosis. Ethanol also significantly impairs neural crest migration, causing cytoskeletal rearrangements that destabilize focal adhesion formation; their directional migratory capacity is also lost. Genetic factors further modify vulnerability to ethanol-induced craniofacial dysmorphology and include genes important for neural crest development, including shh signaling, PDFGA, vangl2, and ribosomal biogenesis. Because facial and brain development are mechanistically and functionally linked, research into ethanol's effects on neural crest also informs our understanding of ethanol's CNS pathologies. © 2014

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

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    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.

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

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    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.

  13. Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage

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    Paige Snider

    2007-01-01

    Full Text Available Although it is well established that transgenic manipulation of mammalian neural crest-related gene expression and microsurgical removal of premigratory chicken and Xenopus embryonic cardiac neural crest progenitors results in a wide spectrum of both structural and functional congenital heart defects, the actual functional mechanism of the cardiac neural crest cells within the heart is poorly understood. Neural crest cell migration and appropriate colonization of the pharyngeal arches and outflow tract septum is thought to be highly dependent on genes that regulate cell-autonomous polarized movement (i.e., gap junctions, cadherins, and noncanonical Wnt1 pathway regulators. Once the migratory cardiac neural crest subpopulation finally reaches the heart, they have traditionally been thought to participate in septation of the common outflow tract into separate aortic and pulmonary arteries. However, several studies have suggested these colonizing neural crest cells may also play additional unexpected roles during cardiovascular development and may even contribute to a crest-derived stem cell population. Studies in both mice and chick suggest they can also enter the heart from the venous inflow as well as the usual arterial outflow region, and may contribute to the adult semilunar and atrioventricular valves as well as part of the cardiac conduction system. Furthermore, although they are not usually thought to give rise to the cardiomyocyte lineage, neural crest cells in the zebrafish (Danio rerio can contribute to the myocardium and may have different functions in a species-dependent context. Intriguingly, both ablation of chick and Xenopus premigratory neural crest cells, and a transgenic deletion of mouse neural crest cell migration or disruption of the normal mammalian neural crest gene expression profiles, disrupts ventral myocardial function and/or cardiomyocyte proliferation. Combined, this suggests that either the cardiac neural crest

  14. Pax7 lineage contributions to the mammalian neural crest.

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    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.

  15. DHODH modulates transcriptional elongation in the neural crest and melanoma.

    Science.gov (United States)

    White, Richard Mark; Cech, Jennifer; Ratanasirintrawoot, Sutheera; Lin, Charles Y; Rahl, Peter B; Burke, Christopher J; Langdon, Erin; Tomlinson, Matthew L; Mosher, Jack; Kaufman, Charles; Chen, Frank; Long, Hannah K; Kramer, Martin; Datta, Sumon; Neuberg, Donna; Granter, Scott; Young, Richard A; Morrison, Sean; Wheeler, Grant N; Zon, Leonard I

    2011-03-24

    Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation.

  16. Metabolic syndromes and neural crest development

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    A. Berio

    2011-01-01

    Full Text Available Aim of this study is to investigate for the possible connection between abnormal neural crest cell (NCC development and NCC-derived abnormal facial and cerebral structures in 3 children with pyruvate-dehydrogenase (PDH and in 10 cases with oxidative phosphorylation deficiency diagnosed from the Author by standard laboratory assays [i.e. 3 cases of Kearns-Sayre syndrome (KSS, 2 cases of Leigh syndrome, 1 case of KSS with De Toni-Debrè-Fanconi and rachitis (Berio disease, 1 case of KSS with aortic insuffiency and sub-aortic septum hyperthophy, 3 cases of chronic progressive external ophthalmoplegia]. There patients presented with hyperlactacidemia, hyperpyruvicemia and facial abnormalities, similar to those observed in the fetal alcohol syndrome (a typical neurocristopathy due to PDH deficiency, down-regulating NCC genes. The Author hypothesizes that the metabolic defect of scarce energy production is responsible of abnormal NCC proliferation/migration and consequent facial abnormalities.

  17. Neural crest delamination and migration: from epithelium-to-mesenchyme transition to collective cell migration.

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    Theveneau, Eric; Mayor, Roberto

    2012-06-01

    After induction and specification in the ectoderm, at the border of the neural plate, the neural crest (NC) population leaves its original territory through a delamination process. Soon afterwards, the NC cells migrate throughout the embryo and colonize a myriad of tissues and organs where they settle and differentiate. The delamination involves a partial or complete epithelium-to-mesenchyme transition (EMT) regulated by a complex network of transcription factors including several proto-oncogenes. Studying the relationship between these genes at the time of emigration, and their individual or collective impact on cell behavior, provides valuable information about their role in EMT in other contexts such as cancer metastasis. During migration, NC cells are exposed to large number of positive and negative regulators that control where they go by generating permissive and restricted areas and by modulating their motility and directionality. In addition, as most NC cells migrate collectively, cell-cell interactions play a crucial role in polarizing the cells and interpreting external cues. Cell cooperation eventually generates an overall polarity to the population, leading to directional collective cell migration. This review will summarize our current knowledge on delamination, EMT and migration of NC cells using key examples from chicken, Xenopus, zebrafish and mouse embryos. Given the similarities between neural crest migration and cancer invasion, these cells may represent a useful model for understanding the mechanisms of metastasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Neural crest specification: tissues, signals, and transcription factors.

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    Rogers, C D; Jayasena, C S; Nie, S; Bronner, M E

    2012-01-01

    The neural crest is a transient population of multipotent and migratory cells unique to vertebrate embryos. Initially derived from the borders of the neural plate, these cells undergo an epithelial to mesenchymal transition to leave the central nervous system, migrate extensively in the periphery, and differentiate into numerous diverse derivatives. These include but are not limited to craniofacial cartilage, pigment cells, and peripheral neurons and glia. Attractive for their similarities to stem cells and metastatic cancer cells, neural crest cells are a popular model system for studying cell/tissue interactions and signaling factors that influence cell fate decisions and lineage transitions. In this review, we discuss the mechanisms required for neural crest formation in various vertebrate species, focusing on the importance of signaling factors from adjacent tissues and conserved gene regulatory interactions, which are required for induction and specification of the ectodermal tissue that will become neural crest. Copyright © 2011 Wiley Periodicals, Inc.

  19. Neural Crest Migration and Survival Are Susceptible to Morpholino-Induced Artifacts.

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    Elena F Boer

    Full Text Available The neural crest (NC is a stem cell-like embryonic population that is essential for generating and patterning the vertebrate body, including the craniofacial skeleton and peripheral nervous system. Defects in NC development underlie many birth defects and contribute to formation of some of the most malignant cancers in humans, such as melanoma and neuroblastoma. For these reasons, significant research efforts have been expended to identify genes that control NC development, as it is expected to lead to a deeper understanding of the genetic mechanisms controlling vertebrate development and identify new treatments for NC-derived diseases and cancers. However, a number of inconsistencies regarding gene function during NC development have emerged from comparative analyses of gene function between mammalian and non-mammalian systems (chick, frog, zebrafish. This poses a significant barrier to identification of single genes and/or redundant pathways to target in NC diseases. Here, we determine whether technical differences, namely morpholino-based approaches used in non-mammalian systems, could contribute to these discrepancies, by examining the extent to which NC phenotypes in fascin1a (fscn1a morphant embryos are similar to or different from fscn1a null mutants in zebrafish. Analysis of fscn1a morphants showed that they mimicked early NC phenotypes observed in fscn1a null mutants; however, these embryos also displayed NC migration and derivative phenotypes not observed in null mutants, including accumulation of p53-independent cell death. These data demonstrate that morpholinos can cause seemingly specific NC migration and derivative phenotypes, and thus have likely contributed to the inconsistencies surrounding NC gene function between species. We suggest that comparison of genetic mutants between different species is the most rigorous method for identifying conserved genetic mechanisms controlling NC development and is critical to identify new

  20. Cardio-cephalic neural crest syndrome: A novel hypothesis of vascular neurocristopathy.

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    Komiyama, M

    2017-12-01

    A novel hypothesis proposes that "cardio-cephalic neural crest (NC) syndrome," i.e. cephalic NC including cardiac NC, contributes to the concurrent occurrence of vascular diseases in the cardio- and cerebrovascular regions. NC is a transient structure present in early embryogenesis. Cephalic NC provides mesenchymal cells to the vascular media in these regions. Concurrent cardio- and cerebrovascular lesions have been reported in PHACE syndrome, ACTA2 mutation syndrome, and less frequently in the spontaneous occlusion of the circle of Willis (so-called moyamoya disease). Cardiovascular lesions in these syndromes include coarctation of the aorta, persistent truncus arteriosus, patent ductus arteriosus, and coronary artery disease, and cerebrovascular lesions include agenesis and stenosis/occlusion of the internal carotid arteries, and moyamoya phenomenon. These concurrent vascular lesions both in the cardio- and cerebrovascular regions might be related to cephalic NC. This hypothesis, although not proven, may facilitate a better understanding of the above-mentioned NC-related vascular pathologies and lead to appropriate diagnostic and therapeutic approaches for clinicians and chart future direction for researchers.

  1. 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.

  2. A gene network that coordinates preplacodal competence and neural crest specification in zebrafish.

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    Bhat, Neha; Kwon, Hye-Joo; Riley, Bruce B

    2013-01-01

    Preplacodal ectoderm (PPE) and neural crest (NC) are specified at the interface of neural and nonneural ectoderm and together contribute to the peripheral nervous system in all vertebrates. Bmp activates early steps for both fates during late blastula stage. Low Bmp activates expression of transcription factors Tfap2a and Tfap2c in the lateral neural plate, thereby specifying neural crest fate. Elevated Bmp establishes preplacodal competence throughout the ventral ectoderm by coinducing Tfap2a, Tfap2c, Foxi1 and Gata3. PPE specification occurs later at the end of gastrulation and requires complete attenuation of Bmp, yet expression of PPE competence factors continues well past gastrulation. Here we show that competence factors positively regulate each other's expression during gastrulation, forming a self-sustaining network that operates independently of Bmp. Misexpression of Tfap2a in embryos blocked for Bmp from late blastula stage can restore development of both PPE and NC. However, Tfap2a alone is not sufficient to activate any other competence factors nor does it rescue individual placodes. On the other hand, misexpression of any two competence factors in Bmp-blocked embryos can activate the entire transcription factor network and support the development of NC, PPE and some individual placodes. We also show that while these factors are partially redundant with respect to PPE specification, they later provide non-redundant functions needed for development of specific placodes. Thus, we have identified a gene regulatory network that coordinates development of NC, PPE and individual placodes in zebrafish. Copyright © 2012 Elsevier Inc. All rights reserved.

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

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    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.

  4. 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.

  5. Compound developmental eye disorders following inactivation of TGFβ signaling in neural-crest stem cells

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    Suter Ueli

    2005-12-01

    Full Text Available Abstract Background Development of the eye depends partly on the periocular mesenchyme derived from the neural crest (NC, but the fate of NC cells in mammalian eye development and the signals coordinating the formation of ocular structures are poorly understood. Results Here we reveal distinct NC contributions to both anterior and posterior mesenchymal eye structures and show that TGFβ signaling in these cells is crucial for normal eye development. In the anterior eye, TGFβ2 released from the lens is required for the expression of transcription factors Pitx2 and Foxc1 in the NC-derived cornea and in the chamber-angle structures of the eye that control intraocular pressure. TGFβ enhances Foxc1 and induces Pitx2 expression in cell cultures. As in patients carrying mutations in PITX2 and FOXC1, TGFβ signal inactivation in NC cells leads to ocular defects characteristic of the human disorder Axenfeld-Rieger's anomaly. In the posterior eye, NC cell-specific inactivation of TGFβ signaling results in a condition reminiscent of the human disorder persistent hyperplastic primary vitreous. As a secondary effect, retinal patterning is also disturbed in mutant mice. Conclusion In the developing eye the lens acts as a TGFβ signaling center that controls the development of eye structures derived from the NC. Defective TGFβ signal transduction interferes with NC-cell differentiation and survival anterior to the lens and with normal tissue morphogenesis and patterning posterior to the lens. The similarity to developmental eye disorders in humans suggests that defective TGFβ signal modulation in ocular NC derivatives contributes to the pathophysiology of these diseases.

  6. The dual origin of the peripheral olfactory system: placode and neural crest

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    Katoh Hiroyuki

    2011-09-01

    Full Text Available Abstract Background The olfactory epithelium (OE has a unique capacity for continuous neurogenesis, extending axons to the olfactory bulb with the assistance of olfactory ensheathing cells (OECs. The OE and OECs have been believed to develop solely from the olfactory placode, while the neural crest (NC cells have been believed to contribute only the underlying structural elements of the olfactory system. In order to further elucidate the role of NC cells in olfactory development, we examined the olfactory system in the transgenic mice Wnt1-Cre/Floxed-EGFP and P0-Cre/Floxed-EGFP, in which migrating NC cells and its descendents permanently express GFP, and conducted transposon-mediated cell lineage tracing studies in chick embryos. Results Examination of these transgenic mice revealed GFP-positive cells in the OE, demonstrating that NC-derived cells give rise to OE cells with morphologic and antigenic properties identical to placode-derived cells. OECs were also positive for GFP, confirming their NC origin. Cell lineage tracing studies performed in chick embryos confirmed the migration of NC cells into the OE. Furthermore, spheres cultured from the dissociated cells of the olfactory mucosa demonstrated self-renewal and trilineage differentiation capacities (neurons, glial cells, and myofibroblasts, demonstrating the presence of NC progenitors in the olfactory mucosa. Conclusion Our data demonstrates that the NC plays a larger role in the development of the olfactory system than previously believed, and suggests that NC-derived cells may in part be responsible for the remarkable capacity of the OE for neurogenesis and regeneration.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Rabconnectin-3a regulates vesicle endocytosis and canonical Wnt signaling in zebrafish neural crest migration.

    Directory of Open Access Journals (Sweden)

    Adam M Tuttle

    2014-05-01

    Full Text Available Cell migration requires dynamic regulation of cell-cell signaling and cell adhesion. Both of these processes involve endocytosis, lysosomal degradation, and recycling of ligand-receptor complexes and cell adhesion molecules from the plasma membrane. Neural crest (NC cells in vertebrates are highly migratory cells, which undergo an epithelial-mesenchymal transition (EMT to leave the neural epithelium and migrate throughout the body to give rise to many different derivatives. Here we show that the v-ATPase interacting protein, Rabconnectin-3a (Rbc3a, controls intracellular trafficking events and Wnt signaling during NC migration. In zebrafish embryos deficient in Rbc3a, or its associated v-ATPase subunit Atp6v0a1, many NC cells fail to migrate and misregulate expression of cadherins. Surprisingly, endosomes in Rbc3a- and Atp6v0a1-deficient NC cells remain immature but still acidify. Rbc3a loss-of-function initially downregulates several canonical Wnt targets involved in EMT, but later Frizzled-7 accumulates at NC cell membranes, and nuclear B-catenin levels increase. Presumably due to this later Wnt signaling increase, Rbc3a-deficient NC cells that fail to migrate become pigment progenitors. We propose that Rbc3a and Atp6v0a1 promote endosomal maturation to coordinate Wnt signaling and intracellular trafficking of Wnt receptors and cadherins required for NC migration and cell fate determination. Our results suggest that different v-ATPases and associated proteins may play cell-type-specific functions in intracellular trafficking in many contexts.

  9. UTX-guided neural crest function underlies craniofacial features of Kabuki syndrome.

    Science.gov (United States)

    Shpargel, Karl B; Starmer, Joshua; Wang, Chaochen; Ge, Kai; Magnuson, Terry

    2017-10-24

    Kabuki syndrome, a congenital craniofacial disorder, manifests from mutations in an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A) or a H3 lysine 4 methylase (KMT2D). However, the cellular and molecular etiology of histone-modifying enzymes in craniofacial disorders is unknown. We now establish Kabuki syndrome as a neurocristopathy, whereby the majority of clinical features are modeled in mice carrying neural crest (NC) deletion of UTX, including craniofacial dysmorphism, cardiac defects, and postnatal growth retardation. Female UTX NC knockout (FKO) demonstrates enhanced phenotypic severity over males (MKOs), due to partial redundancy with UTY, a Y-chromosome demethylase-dead homolog. Thus, NC cells may require demethylase-independent UTX activity. Consistently, Kabuki causative point mutations upstream of the JmjC domain do not disrupt UTX demethylation. We have isolated primary NC cells at a phenocritical postmigratory timepoint in both FKO and MKO mice, and genome-wide expression and histone profiling have revealed UTX molecular function in establishing appropriate chromatin structure to regulate crucial NC stem-cell signaling pathways. However, the majority of UTX regulated genes do not experience aberrations in H3K27me3 or H3K4me3, implicating alternative roles for UTX in transcriptional control. These findings are substantiated through demethylase-dead knockin mutation of UTX, which supports appropriate facial development. Published under the PNAS license.

  10. Translocation of latex beads after laser ablation of the avian neural crest.

    Science.gov (United States)

    Coulombe, J N; Bronner-Fraser, M

    1984-11-01

    Previous studies from this laboratory (M.E. Bronner-Fraser, 1982, Dev. Biol. 91, 50-63) have demonstrated that latex beads translocate ventrally after injection into avian embryos during the phase of neural crest migration, to settle in the vicinity of neural-crest-derived structures. In order to examine the role of host neural crest cells in the ventral translocation of implanted beads, latex beads have been injected into regions of embryos from which the neural crest cells have been ablated using a laser microbeam. Prior to their migratory phase, neural crest cells reside in the dorsal portion of the neural tube. Laser irradiation of the dorsal neural tube was used to reproducibly achieve either partial or complete ablation of neural crest cells from the irradiated regions. The effectiveness of the ablation was assessed by the degree of reduction in dorsal root ganglia, a neural crest derivative. Because of the rapidity and precision of this technique, it was possible to selectively remove neural crest cells without significantly altering other embryonic structures. The results indicate that, after injection of latex beads into the somites of embryos whose neural crest cells were removed by laser irradiation, the beads translocate ventrally in the absence of the endogenous neural crest.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Signaling and transcriptional regulation in neural crest specification and migration: lessons from xenopus embryos.

    Science.gov (United States)

    Pegoraro, Caterina; Monsoro-Burq, Anne H

    2013-01-01

    The neural crest is a population of highly migratory and multipotent cells, which arises from the border of the neural plate in vertebrate embryos. In the last few years, the molecular actors of neural crest early development have been intensively studied, notably by using the frog embryo, as a prime model for the analysis of the earliest embryonic inductions. In addition, tremendous progress has been made in understanding the molecular and cellular basis of Xenopus cranial neural crest migration, by combining in vitro and in vivo analysis. In this review, we examine how the action of previously known neural crest-inducing signals [bone morphogenetic protein (BMP), wingless-int (Wnt), fibroblast growth factor (FGF)] is controlled by newly discovered modulators during early neural plate border patterning and neural crest specification. This regulation controls the induction of key transcription factors that cooperate to pattern the premigratory neural crest progenitors. These data are discussed in the perspective of the gene regulatory network that controls neural and neural crest patterning. We then address recent findings on noncanonical Wnt signaling regulation, cell polarization, and collective cell migration which highlight how cranial neural crest cells populate their target tissue, the branchial arches, in vivo. More than ever, the neural crest stands as a powerful and attractive model to decipher complex vertebrate regulatory circuits in vivo. Copyright © 2012 Wiley Periodicals, Inc.

  13. Gap Junction–mediated Cell–Cell Communication Modulates Mouse Neural Crest Migration

    OpenAIRE

    Huang, G.Y.; Cooper, E.S.; Waldo, K.; Kirby, M L; Gilula, N B; Lo, C.W.

    1998-01-01

    Previous studies showed that conotruncal heart malformations can arise with the increase or decrease in α1 connexin function in neural crest cells. To elucidate the possible basis for the quantitative requirement for α1 connexin gap junctions in cardiac development, a neural crest outgrowth culture system was used to examine migration of neural crest cells derived from CMV43 transgenic embryos overexpressing α1 connexins, and from α1 connexin knockout (KO) mice and FC transgenic mice expressi...

  14. Depletion of Neural Crest-Derived Cells Leads to Reduction in Plasma Noradrenaline and Alters B Lymphopoiesis.

    Science.gov (United States)

    Tsunokuma, Naoki; Yamane, Toshiyuki; Matsumoto, Chiaki; Tsuneto, Motokazu; Isono, Kana; Imanaka-Yoshida, Kyoko; Yamazaki, Hidetoshi

    2017-01-01

    Hematopoietic stem cells and their lymphoid progenitors are supported by the bone marrow (BM) microenvironmental niches composed of various stromal cells and Schwann cells and sympathetic nerve fibers. Although neural crest (NC) cells contribute to the development of all the three, their function in BM is not well understood. In this study, NC-derived cells were ablated with diphtheria toxin in double-transgenic mice expressing NC-specific Cre and Cre-driven diphtheria toxin receptor with yellow fluorescent protein reporter. We found that yellow fluorescent protein-expressing, NC-derived nonhematopoietic cells in BM expressed hematopoietic factors Cxcl12 and stem cell factor The ablation of NC-derived cells led to a significant decrease in B cell progenitors but not in hematopoietic stem cells or myeloid lineage cells in BM. Interestingly, plasma noradrenaline was markedly decreased in these mice. The i.p. administration of 6-hydroxydopamine, a known neurotoxin for noradrenergic neurons, led to a similar phenotype, whereas the administration of a noradrenaline precursor in NC-ablated mice partially rescued this phenotype. Additionally, the continuous administration of adrenergic receptor β antagonists partially decreased the number of B cell progenitors while preserving B lymphopoiesis in vitro. Taken together, our results indicate that NC-derived cell depletion leads to abnormal B lymphopoiesis partially through decreased plasma noradrenaline, suggesting this as a novel mechanism regulated by molecules released by the sympathetic neurons. Copyright © 2016 by The American Association of Immunologists, Inc.

  15. How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration

    Science.gov (United States)

    Chevalier, N. R.; Gazguez, E.; Bidault, L.; Guilbert, T.; Vias, C.; Vian, E.; Watanabe, Y.; Muller, L.; Germain, S.; Bondurand, N.; Dufour, S.; Fleury, V.

    2016-02-01

    Neural crest cells (NCCs) are a population of multipotent cells that migrate extensively during vertebrate development. Alterations to neural crest ontogenesis cause several diseases, including cancers and congenital defects, such as Hirschprung disease, which results from incomplete colonization of the colon by enteric NCCs (ENCCs). We investigated the influence of the stiffness and structure of the environment on ENCC migration in vitro and during colonization of the gastrointestinal tract in chicken and mouse embryos. We showed using tensile stretching and atomic force microscopy (AFM) that the mesenchyme of the gut was initially soft but gradually stiffened during the period of ENCC colonization. Second-harmonic generation (SHG) microscopy revealed that this stiffening was associated with a gradual organization and enrichment of collagen fibers in the developing gut. Ex-vivo 2D cell migration assays showed that ENCCs migrated on substrates with very low levels of stiffness. In 3D collagen gels, the speed of the ENCC migratory front decreased with increasing gel stiffness, whereas no correlation was found between porosity and ENCC migration behavior. Metalloprotease inhibition experiments showed that ENCCs actively degraded collagen in order to progress. These results shed light on the role of the mechanical properties of tissues in ENCC migration during development.

  16. Defective ALK5 signaling in the neural crest leads to increased postmigratory neural crest cell apoptosis and severe outflow tract defects

    Directory of Open Access Journals (Sweden)

    Sucov Henry M

    2006-11-01

    Full Text Available Abstract Background Congenital cardiovascular diseases are the most common form of birth defects in humans. A substantial portion of these defects has been associated with inappropriate induction, migration, differentiation and patterning of pluripotent cardiac neural crest stem cells. While TGF-β-superfamily signaling has been strongly implicated in neural crest cell development, the detailed molecular signaling mechanisms in vivo are still poorly understood. Results We deleted the TGF-β type I receptor Alk5 specifically in the mouse neural crest cell lineage. Failure in signaling via ALK5 leads to severe cardiovascular and pharyngeal defects, including inappropriate remodeling of pharyngeal arch arteries, abnormal aortic sac development, failure in pharyngeal organ migration and persistent truncus arteriosus. While ALK5 is not required for neural crest cell migration, our results demonstrate that it plays an important role in the survival of post-migratory cardiac neural crest cells. Conclusion Our results demonstrate that ALK5-mediated signaling in neural crest cells plays an essential cell-autonomous role in the pharyngeal and cardiac outflow tract development.

  17. Regulation of trunk neural crest delamination by δEF1 and Sip1 in the chicken embryo.

    Science.gov (United States)

    Yasumi, Takahiro; Inoue, Masashi; Maruhashi, Mitsuji; Kamachi, Yusuke; Higashi, Yujiro; Kondoh, Hisato; Uchikawa, Masanori

    2016-02-01

    The vertebrate Zfhx1 transcription factor family comprises δEF1 and Sip1, which bind to CACCT-containing sequences and act as transcriptional repressors. It has been a longstanding question whether these transcription factors share the same regulatory functions in vivo. It has been shown that neural crest (NC) delamination depends on the Sip1 activity at the cranial level in mouse and chicken embryos, and it remained unclear how NC delamination is regulated at the trunk level. We observed that the expression of δEF1 and Sip1 overlaps in many tissues in chicken embryos, including NC cells at the trunk level. To clarify the above questions, we separately knocked down δEF1 and Sip1 or in combination in NC cells by electroporation of vectors expressing short hairpin RNAs (shRNAs) against respective mRNAs on the dorsal side of neural tubes that generate NC cells. In all cases, the migrating NC cell population was significantly reduced, paralleled by the decreased expression of δEF1 or Sip1 targeted by shRNAs. Expression of Sox10, the major transcription factor that regulates NC development, was also decreased by the shRNAs against δEF1 or Sip1. We conclude that the trunk NC delamination is regulated by both δEF1 and Sip1 in an analogous manner, and that these transcription factors can share equivalent regulatory functions in embryonic tissues. © 2015 Japanese Society of Developmental Biologists.

  18. 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.

  19. Adenosine signaling promotes neuronal, catecholaminergic differentiation of primary neural crest cells and CNS-derived CAD cells.

    Science.gov (United States)

    Bilodeau, Matthew L; Ji, Ming; Paris, Maryline; Andrisani, Ourania M

    2005-07-01

    In neural crest (NC) cultures cAMP signaling is an instructive signal in catecholaminergic, sympathoadrenal cell development. However, the extracellular signals activating the cAMP pathway during NC cell development have not been identified. We demonstrate that in avian NC cultures, evidenced by tyrosine hydroxylase expression and catecholamine biosynthesis, adenosine and not adrenergic signaling, together with BMP2, promotes sympathoadrenal cell development. In NC cultures, addition of the adenosine receptor agonist NECA in the presence of BMP2 promotes sympathoadrenal cell development, whereas the antagonist CGS 15943 or the adenosine degrading enzyme adenosine deaminase (ADA) suppresses TH expression. Importantly, NC cells express A2A and A2B receptors which couple with Gsalpha increasing intracellular cAMP. Employing the CNS-derived catecholaminergic CAD cell line, we also demonstrate that neuronal differentiation mediated by serum withdrawal is further enhanced by treatment with IBMX, a cAMP-elevating agent, or the adenosine receptor agonist NECA, acting via cAMP. By contrast, the adenosine receptor antagonist CGS 15943 or the adenosine degrading enzyme ADA inhibits CAD cell neuronal differentiation mediated by serum withdrawal. These results support that adenosine is a physiological signal in neuronal differentiation of the CNS-derived catecholaminergic CAD cell line and suggest that adenosine signaling is involved in NC cell development in vivo.

  20. Dynamics of BMP and Hes1/Hairy1 signaling in the dorsal neural tube underlies the transition from neural crest to definitive roof plate.

    Science.gov (United States)

    Nitzan, Erez; Avraham, Oshri; Kahane, Nitza; Ofek, Shai; Kumar, Deepak; Kalcheim, Chaya

    2016-03-24

    The dorsal midline region of the neural tube that results from closure of the neural folds is generally termed the roof plate (RP). However, this domain is highly dynamic and complex, and is first transiently inhabited by prospective neural crest (NC) cells that sequentially emigrate from the neuroepithelium. It only later becomes the definitive RP, the dorsal midline cells of the spinal cord. We previously showed that at the trunk level of the axis, prospective RP progenitors originate ventral to the premigratory NC and progressively reach the dorsal midline following NC emigration. However, the molecular mechanisms underlying the end of NC production and formation of the definitive RP remain virtually unknown. Based on distinctive cellular and molecular traits, we have defined an initial NC and a subsequent RP stage, allowing us to investigate the mechanisms responsible for the transition between the two phases. We demonstrate that in spite of the constant production of BMP4 in the dorsal tube at both stages, RP progenitors only transiently respond to the ligand and lose competence shortly before they arrive at their final location. In addition, exposure of dorsal tube cells at the NC stage to high levels of BMP signaling induces premature RP traits, such as Hes1/Hairy1, while concomitantly inhibiting NC production. Reciprocally, early inhibition of BMP signaling prevents Hairy1 mRNA expression at the RP stage altogether, suggesting that BMP is both necessary and sufficient for the development of this RP-specific trait. Furthermore, when Hes1/Hairy1 is misexpressed at the NC stage, it inhibits BMP signaling and downregulates BMPR1A/Alk3 mRNA expression, transcription of BMP targets such as Foxd3, cell-cycle progression, and NC emigration. Reciprocally, Foxd3 inhibits Hairy1, suggesting that repressive cross-interactions at the level of, and downstream from, BMP ensure the temporal separation between both lineages. Together, our data suggest that BMP signaling is

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  10. File list: InP.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: Unc.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  14. File list: Pol.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Unc.PSC.50.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: InP.PSC.20.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. The connections between neural crest development and neuroblastoma.

    Science.gov (United States)

    Jiang, Manrong; Stanke, Jennifer; Lahti, Jill M

    2011-01-01

    Neuroblastoma (NB), the most common extracranial solid tumor in childhood, is an extremely heterogeneous disease both biologically and clinically. Although significant progress has been made in identifying molecular and genetic markers for NB, this disease remains an enigmatic challenge. Since NB is thought to be an embryonal tumor that is derived from precursor cells of the peripheral (sympathetic) nervous system, understanding the development of normal sympathetic nervous system may highlight abnormal events that contribute to NB initiation. Therefore, this review focuses on the development of the peripheral trunk neural crest, the current understanding of how developmental factors may contribute to NB and on recent advances in the identification of important genetic lesions and signaling pathways involved in NB tumorigenesis and metastasis. Finally, we discuss how future advances in identification of molecular alterations in NB may lead to more effective, less toxic therapies, and improve the prognosis for NB patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. 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.

  19. Asymmetric localization of DLC1 defines avian trunk neural crest polarity for directional delamination and migration.

    Science.gov (United States)

    Liu, Jessica Aijia; Rao, Yanxia; Cheung, May Pui Lai; Hui, Man-Ning; Wu, Ming-Hoi; Chan, Lo-Kong; Ng, Irene Oi-Lin; Niu, Ben; Cheah, Kathryn S E; Sharma, Rakesh; Hodgson, Louis; Cheung, Martin

    2017-10-30

    Following epithelial-mesenchymal transition, acquisition of avian trunk neural crest cell (NCC) polarity is prerequisite for directional delamination and migration, which in turn is essential for peripheral nervous system development. However, how this cell polarization is established and regulated remains unknown. Here we demonstrate that, using the RHOA biosensor in vivo and in vitro, the initiation of NCC polarization is accompanied by highly activated RHOA in the cytoplasm at the cell rear and its fluctuating activity at the front edge. This differential RHOA activity determines polarized NC morphology and motility, and is regulated by the asymmetrically localized RhoGAP Deleted in liver cancer (DLC1) in the cytoplasm at the cell front. Importantly, the association of DLC1 with NEDD9 is crucial for its asymmetric localization and differential RHOA activity. Moreover, NC specifiers, SOX9 and SOX10, regulate NEDD9 and DLC1 expression, respectively. These results present a SOX9/SOX10-NEDD9/DLC1-RHOA regulatory axis to govern NCC migratory polarization.

  20. Cadherin-6B undergoes macropinocytosis and clathrin-mediated endocytosis during cranial neural crest cell EMT.

    Science.gov (United States)

    Padmanabhan, Rangarajan; Taneyhill, Lisa A

    2015-05-01

    The epithelial-to-mesenchymal transition (EMT) is important for the formation of migratory neural crest cells during development and is co-opted in human diseases such as cancer metastasis. Chick premigratory cranial neural crest cells lose intercellular contacts, mediated in part by Cadherin-6B (Cad6B), migrate extensively, and later form a variety of adult derivatives. Importantly, modulation of Cad6B is crucial for proper neural crest cell EMT. Although Cad6B possesses a long half-life, it is rapidly lost from premigratory neural crest cell membranes, suggesting the existence of post-translational mechanisms during EMT. We have identified a motif in the Cad6B cytoplasmic tail that enhances Cad6B internalization and reduces the stability of Cad6B upon its mutation. Furthermore, we demonstrate for the first time that Cad6B is removed from premigratory neural crest cells through cell surface internalization events that include clathrin-mediated endocytosis and macropinocytosis. Both of these processes are dependent upon the function of dynamin, and inhibition of Cad6B internalization abrogates neural crest cell EMT and migration. Collectively, our findings reveal the significance of post-translational events in controlling cadherins during neural crest cell EMT and migration. © 2015. Published by The Company of Biologists Ltd.

  1. A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development

    NARCIS (Netherlands)

    Ciarlo, Christie; Kaufman, Charles K.; Kinikoglu, Beste; Michael, Jonathan; Yang, Song; D’Amato, Christopher; Blokzijl-Franke, Sasja; den Hertog, Jeroen|info:eu-repo/dai/nl/096717696; Schlaeger, Thorsten M.; Zhou, Yi; Liao, Eric C; Zon, Leonard I.

    2017-01-01

    The neural crest is a dynamic progenitor cell population that arises at the border of neural and non-neural ectoderm. The inductive roles of FGF, Wnt, and BMP at the neural plate border are well established, but the signals required for subsequent neural crest development remain poorly

  2. 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.

  3. 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.

  4. Cardiac, mandibular and thymic phenotypical association indicates that cranial neural crest underlies bicuspid aortic valve formation in hamsters.

    Directory of Open Access Journals (Sweden)

    Jessica Martínez-Vargas

    Full Text Available Bicuspid aortic valve (BAV is the most prevalent human congenital cardiac malformation. It may appear isolated, associated with other cardiovascular malformations, or forming part of syndromes. Cranial neural crest (NC defects are supposed to be the cause of the spectrum of disorders associated with syndromic BAV. Experimental studies with an inbred hamster model of isolated BAV showed that alterations in the migration or differentiation of the cardiac NC cells in the embryonic cardiac outflow tract are most probably responsible for the development of this congenital valvular defect. We hypothesize that isolated BAV is not the result of local, but of early alterations in the behavior of the NC cells, thus also affecting other cranial NC-derived structures. Therefore, we tested whether morphological variation of the aortic valve is linked to phenotypic variation of the mandible and the thymus in the hamster model of isolated BAV, compared to a control strain. Our results show significant differences in the size and shape of the mandible as well as in the cellular composition of the thymus between the two strains, and in mandible shape regarding the morphology of the aortic valve. Given that both the mandible and the thymus are cranial NC derivatives, and that the cardiac NC belongs to the cephalic domain, we propose that the causal defect leading to isolated BAV during embryonic development is not restricted to local alterations of the cardiac NC cells in the cardiac outflow tract, but it is of pleiotropic or polytopic nature. Our results suggest that isolated BAV may be the forme fruste of a polytopic syndrome involving the cranial NC in the hamster model and in a proportion of affected patients.

  5. Methods for Derivation of Multipotent Neural Crest Cells Derived from Human Pluripotent Stem Cells.

    Science.gov (United States)

    Avery, John; Dalton, Stephen

    2016-01-01

    Multipotent, neural crest cells (NCCs) produce a wide range of cell types during embryonic development. This includes melanocytes, peripheral neurons, smooth muscle cells, osteocytes, chondrocytes, and adipocytes. The protocol described here allows for highly efficient differentiation of human pluripotent stem cells to a neural crest fate within 15 days. This is accomplished under feeder-free conditions, using chemically defined medium supplemented with two small molecule inhibitors that block glycogen synthase kinase 3 (GSK3) and bone morphogenic protein (BMP) signaling. This technology is well suited as a platform to understand in greater detail the pathogenesis of human disease associated with impaired neural crest development/migration.

  6. Phenotypic chemical screening using a zebrafish neural crest EMT reporter identifies retinoic acid as an inhibitor of epithelial morphogenesis.

    Science.gov (United States)

    Jimenez, Laura; Wang, Jindong; Morrison, Monique A; Whatcott, Clifford; Soh, Katherine K; Warner, Steven; Bearss, David; Jette, Cicely A; Stewart, Rodney A

    2016-04-01

    The epithelial-to-mesenchymal transition (EMT) is a highly conserved morphogenetic program essential for embryogenesis, regeneration and cancer metastasis. In cancer cells, EMT also triggers cellular reprogramming and chemoresistance, which underlie disease relapse and decreased survival. Hence, identifying compounds that block EMT is essential to prevent or eradicate disseminated tumor cells. Here, we establish a whole-animal-based EMT reporter in zebrafish for rapid drug screening, calledTg(snai1b:GFP), which labels epithelial cells undergoing EMT to producesox10-positive neural crest (NC) cells. Time-lapse and lineage analysis ofTg(snai1b:GFP)embryos reveal that cranial NC cells delaminate from two regions: an early population delaminates adjacent to the neural plate, whereas a later population delaminates from within the dorsal neural tube. TreatingTg(snai1b:GFP)embryos with candidate small-molecule EMT-inhibiting compounds identified TP-0903, a multi-kinase inhibitor that blocked cranial NC cell delamination in both the lateral and medial populations. RNA sequencing (RNA-Seq) analysis and chemical rescue experiments show that TP-0903 acts through stimulating retinoic acid (RA) biosynthesis and RA-dependent transcription. These studies identify TP-0903 as a new therapeutic for activating RAin vivoand raise the possibility that RA-dependent inhibition of EMT contributes to its prior success in eliminating disseminated cancer cells. © 2016. Published by The Company of Biologists Ltd.

  7. The mych gene is required for neural crest survival during zebrafish development.

    Directory of Open Access Journals (Sweden)

    Sung-Kook Hong

    2008-04-01

    Full Text Available Among Myc family genes, c-Myc is known to have a role in neural crest specification in Xenopus and in craniofacial development in the mouse. There is no information on the function of other Myc genes in neural crest development, or about any developmental role of zebrafish Myc genes.We isolated the zebrafish mych (myc homologue gene. Knockdown of mych leads to severe defects in craniofacial development and in certain other tissues including the eye. These phenotypes appear to be caused by cell death in the neural crest and in the eye field in the anterior brain.Mych is a novel factor required for neural crest cell survival in zebrafish.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  9. Isolation and characterization of neural crest-derived stem cells from dental pulp of neonatal mice.

    Directory of Open Access Journals (Sweden)

    Kajohnkiart Janebodin

    Full Text Available Dental pulp stem cells (DPSCs are shown to reside within the tooth and play an important role in dentin regeneration. DPSCs were first isolated and characterized from human teeth and most studies have focused on using this adult stem cell for clinical applications. However, mouse DPSCs have not been well characterized and their origin(s have not yet been elucidated. Herein we examined if murine DPSCs are neural crest derived and determined their in vitro and in vivo capacity. DPSCs from neonatal murine tooth pulp expressed embryonic stem cell and neural crest related genes, but lacked expression of mesodermal genes. Cells isolated from the Wnt1-Cre/R26R-LacZ model, a reporter of neural crest-derived tissues, indicated that DPSCs were Wnt1-marked and therefore of neural crest origin. Clonal DPSCs showed multi-differentiation in neural crest lineage for odontoblasts, chondrocytes, adipocytes, neurons, and smooth muscles. Following in vivo subcutaneous transplantation with hydroxyapatite/tricalcium phosphate, based on tissue/cell morphology and specific antibody staining, the clones differentiated into odontoblast-like cells and produced dentin-like structure. Conversely, bone marrow stromal cells (BMSCs gave rise to osteoblast-like cells and generated bone-like structure. Interestingly, the capillary distribution in the DPSC transplants showed close proximity to odontoblasts whereas in the BMSC transplants bone condensations were distant to capillaries resembling dentinogenesis in the former vs. osteogenesis in the latter. Thus we demonstrate the existence of neural crest-derived DPSCs with differentiation capacity into cranial mesenchymal tissues and other neural crest-derived tissues. In turn, DPSCs hold promise as a source for regenerating cranial mesenchyme and other neural crest derived tissues.

  10. Isolation and Characterization of Neural Crest-Derived Stem Cells from Dental Pulp of Neonatal Mice

    Science.gov (United States)

    Janebodin, Kajohnkiart; Horst, Orapin V.; Ieronimakis, Nicholas; Balasundaram, Gayathri; Reesukumal, Kanit; Pratumvinit, Busadee; Reyes, Morayma

    2011-01-01

    Dental pulp stem cells (DPSCs) are shown to reside within the tooth and play an important role in dentin regeneration. DPSCs were first isolated and characterized from human teeth and most studies have focused on using this adult stem cell for clinical applications. However, mouse DPSCs have not been well characterized and their origin(s) have not yet been elucidated. Herein we examined if murine DPSCs are neural crest derived and determined their in vitro and in vivo capacity. DPSCs from neonatal murine tooth pulp expressed embryonic stem cell and neural crest related genes, but lacked expression of mesodermal genes. Cells isolated from the Wnt1-Cre/R26R-LacZ model, a reporter of neural crest-derived tissues, indicated that DPSCs were Wnt1-marked and therefore of neural crest origin. Clonal DPSCs showed multi-differentiation in neural crest lineage for odontoblasts, chondrocytes, adipocytes, neurons, and smooth muscles. Following in vivo subcutaneous transplantation with hydroxyapatite/tricalcium phosphate, based on tissue/cell morphology and specific antibody staining, the clones differentiated into odontoblast-like cells and produced dentin-like structure. Conversely, bone marrow stromal cells (BMSCs) gave rise to osteoblast-like cells and generated bone-like structure. Interestingly, the capillary distribution in the DPSC transplants showed close proximity to odontoblasts whereas in the BMSC transplants bone condensations were distant to capillaries resembling dentinogenesis in the former vs. osteogenesis in the latter. Thus we demonstrate the existence of neural crest-derived DPSCs with differentiation capacity into cranial mesenchymal tissues and other neural crest-derived tissues. In turn, DPSCs hold promise as a source for regenerating cranial mesenchyme and other neural crest derived tissues. PMID:22087335

  11. Caldesmon regulates actin dynamics to influence cranial neural crest migration in Xenopus

    OpenAIRE

    Nie, Shuyi; Kee, Yun; Bronner-Fraser, Marianne

    2011-01-01

    Caldesmon (CaD) is an important actin modulator that associates with actin filaments to regulate cell morphology and motility. Although extensively studied in cultured cells, there is little functional information regarding the role of CaD in migrating cells in vivo. Here we show that nonmuscle CaD is highly expressed in both premigratory and migrating cranial neural crest cells of Xenopus embryos. Depletion of CaD with antisense morpholino oligonucleotides causes cranial neural crest cells t...

  12. Ets-1 Confers Cranial Features on Neural Crest Delamination

    Science.gov (United States)

    Théveneau, Eric; Duband, Jean-Loup; Altabef, Muriel

    2007-01-01

    Neural crest cells (NCC) have the particularity to invade the environment where they differentiate after separation from the neuroepithelium. This process, called delamination, is strikingly different between cranial and trunk NCCs. If signalings controlling slow trunk delamination start being deciphered, mechanisms leading to massive and rapid cranial outflow are poorly documented. Here, we show that the chick cranial NCCs delamination is the result of two events: a substantial cell mobilization and an epithelium to mesenchyme transition (EMT). We demonstrate that ets-1, a transcription factor specifically expressed in cranial NCCs, is responsible for the former event by recruiting massively cranial premigratory NCCs independently of the S-phase of the cell cycle and by leading the gathered cells to straddle the basal lamina. However, it does not promote the EMT process alone but can cooperate with snail-2 (previously called slug) to this event. Altogether, these data lead us to propose that ets-1 plays a pivotal role in conferring specific cephalic characteristics on NCC delamination. PMID:17987123

  13. Ets-1 confers cranial features on neural crest delamination.

    Directory of Open Access Journals (Sweden)

    Eric Théveneau

    Full Text Available Neural crest cells (NCC have the particularity to invade the environment where they differentiate after separation from the neuroepithelium. This process, called delamination, is strikingly different between cranial and trunk NCCs. If signalings controlling slow trunk delamination start being deciphered, mechanisms leading to massive and rapid cranial outflow are poorly documented. Here, we show that the chick cranial NCCs delamination is the result of two events: a substantial cell mobilization and an epithelium to mesenchyme transition (EMT. We demonstrate that ets-1, a transcription factor specifically expressed in cranial NCCs, is responsible for the former event by recruiting massively cranial premigratory NCCs independently of the S-phase of the cell cycle and by leading the gathered cells to straddle the basal lamina. However, it does not promote the EMT process alone but can cooperate with snail-2 (previously called slug to this event. Altogether, these data lead us to propose that ets-1 plays a pivotal role in conferring specific cephalic characteristics on NCC delamination.

  14. Neural crest cell-derived VEGF promotes embryonic jaw extension

    Science.gov (United States)

    Wiszniak, Sophie; Mackenzie, Francesca E.; Anderson, Peter; Kabbara, Samuela; Ruhrberg, Christiana; Schwarz, Quenten

    2015-01-01

    Jaw morphogenesis depends on the growth of Meckel’s cartilage during embryogenesis. However, the cell types and signals that promote chondrocyte proliferation for Meckel’s cartilage growth are poorly defined. Here we show that neural crest cells (NCCs) and their derivatives provide an essential source of the vascular endothelial growth factor (VEGF) to enhance jaw vascularization and stabilize the major mandibular artery. We further show in two independent mouse models that blood vessels promote Meckel’s cartilage extension. Coculture experiments of arterial tissue with NCCs or chondrocytes demonstrated that NCC-derived VEGF promotes blood vessel growth and that blood vessels secrete factors to instruct chondrocyte proliferation. Computed tomography and X-ray scans of patients with hemifacial microsomia also showed that jaw hypoplasia correlates with mandibular artery dysgenesis. We conclude that cranial NCCs and their derivatives provide an essential source of VEGF to support blood vessel growth in the developing jaw, which in turn is essential for normal chondrocyte proliferation, and therefore jaw extension. PMID:25922531

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

    Science.gov (United States)

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

    2015-01-01

    A striking feature of neural crest development in vertebrates is that all the specification, delamination, migration, and differentiation steps occur consecutively in distinct areas of the embryo and at different timings of development. The significance and consequences of this partition into clearly separated events are not fully understood yet, but it ought to be related to the necessity of controlling precisely and independently each step, given the wide array of cell types and tissues derived from the neural crest and the long duration of their development spanning almost the entire embryonic life. In this chapter, using the examples of early neural crest induction and delamination, we discuss how time and space constraints influence their development and describe the molecular and cellular responses that are employed by cells to adapt. In the first example, we analyze how cell sorting and cell movements cooperate to allow nascent neural crest cells, which are initially mingled with other neurectodermal progenitors after induction, to segregate from the neural tube and ectoderm populations and settle at the apex of the neural tube prior to migration. In the second example, we examine how cadherins drive the entire process of neural crest segregation from the rest of the neurectoderm by their dual role in mediating first cell sorting and cohesion during specification and later in promoting their delamination. In the third example, we describe how the expression and activity of the transcription factors known to drive epithelium-to-mesenchyme transition (EMT) are regulated timely and spatially by the cellular machinery so that they can alternatively and successively regulate neural crest specification and delamination. In the last example, we briefly tackle the problem of how factors triggering EMT may elicit different cell responses in neural tube and neural crest progenitors. © 2015 Elsevier Inc. All rights reserved.

  16. Mir-29b Mediates the Neural Tube versus Neural Crest Fate Decision during Embryonic Stem Cell Neural Differentiation.

    Science.gov (United States)

    Xi, Jiajie; Wu, Yukang; Li, Guoping; Ma, Li; Feng, Ke; Guo, Xudong; Jia, Wenwen; Wang, Guiying; Yang, Guang; Li, Ping; Kang, Jiuhong

    2017-08-08

    During gastrulation, the neuroectoderm cells form the neural tube and neural crest. The nervous system contains significantly more microRNAs than other tissues, but the role of microRNAs in controlling the differentiation of neuroectodermal cells into neural tube epithelial (NTE) cells and neural crest cells (NCCs) remains unknown. Using embryonic stem cell (ESC) neural differentiation systems, we found that miR-29b was upregulated in NTE cells and downregulated in NCCs. MiR-29b promoted the differentiation of ESCs into NTE cells and inhibited their differentiation into NCCs. Accordingly, the inhibition of miR-29b significantly inhibited the differentiation of NTE cells. A mechanistic study revealed that miR-29b targets DNA methyltransferase 3a (Dnmt3a) to regulate neural differentiation. Moreover, miR-29b mediated the function of Pou3f1, a critical neural transcription factor. Therefore, our study showed that the Pou3f1-miR-29b-Dnmt3a regulatory axis was active at the initial stage of neural differentiation and regulated the determination of cell fate. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. 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.

  18. Evolutionarily conserved role for SoxC genes in neural crest specification and neuronal differentiation.

    Science.gov (United States)

    Uy, Benjamin R; Simoes-Costa, Marcos; Koo, Daniel E S; Sauka-Spengler, Tatjana; Bronner, Marianne E

    2015-01-15

    Members of the Sox family of transcription factors play a variety of critical developmental roles in both vertebrates and invertebrates. Whereas SoxBs and SoxEs are involved in neural and neural crest development, respectively, far less is known about members of the SoxC subfamily. To address this from an evolutionary perspective, we compare expression and function of SoxC genes in neural crest cells and their derivatives in lamprey (Petromyzon marinus), a basal vertebrate, to frog (Xenopus laevis). Analysis of transcript distribution reveals conservation of lamprey and X. laevis SoxC expression in premigratory neural crest, branchial arches, and cranial ganglia. Moreover, morpholino-mediated loss-of-function of selected SoxC family members demonstrates essential roles in aspects of neural crest development in both organisms. The results suggest important and conserved functions of SoxC genes during vertebrate evolution and a particularly critical, previously unrecognized role in early neural crest specification. Copyright © 2014 Elsevier Inc. All rights reserved.

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  10. Biphasic influence of Miz1 on neural crest development by regulating cell survival and apical adhesion complex formation in the developing neural tube

    Science.gov (United States)

    Kerosuo, Laura; Bronner, Marianne E.

    2014-01-01

    Myc interacting zinc finger protein-1 (Miz1) is a transcription factor known to regulate cell cycle– and cell adhesion–related genes in cancer. Here we show that Miz1 also plays a critical role in neural crest development. In the chick, Miz1 is expressed throughout the neural plate and closing neural tube. Its morpholino-mediated knockdown affects neural crest precursor survival, leading to reduction of neural plate border and neural crest specifier genes Msx-1, Pax7, FoxD3, and Sox10. Of interest, Miz1 loss also causes marked reduction of adhesion molecules (N-cadherin, cadherin6B, and α1-catenin) with a concomitant increase of E-cadherin in the neural folds, likely leading to delayed and decreased neural crest emigration. Conversely, Miz1 overexpression results in up-regulation of cadherin6B and FoxD3 expression in the neural folds/neural tube, leading to premature neural crest emigration and increased number of migratory crest cells. Although Miz1 loss effects cell survival and proliferation throughout the neural plate, the neural progenitor marker Sox2 was unaffected, suggesting a neural crest–selective effect. The results suggest that Miz1 is important not only for survival of neural crest precursors, but also for maintenance of integrity of the neural folds and tube, via correct formation of the apical adhesion complex therein. PMID:24307680

  11. 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.

  12. Williams Syndrome Transcription Factor is critical for neural crest cell function in Xenopus laevis.

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    Barnett, Chris; Yazgan, Oya; Kuo, Hui-Ching; Malakar, Sreepurna; Thomas, Trevor; Fitzgerald, Amanda; Harbour, William; Henry, Jonathan J; Krebs, Jocelyn E

    2012-01-01

    Williams Syndrome Transcription Factor (WSTF) is one of ∼25 haplodeficient genes in patients with the complex developmental disorder Williams Syndrome (WS). WS results in visual/spatial processing defects, cognitive impairment, unique behavioral phenotypes, characteristic "elfin" facial features, low muscle tone and heart defects. WSTF exists in several chromatin remodeling complexes and has roles in transcription, replication, and repair. Chromatin remodeling is essential during embryogenesis, but WSTF's role in vertebrate development is poorly characterized. To investigate the developmental role of WSTF, we knocked down WSTF in Xenopus laevis embryos using a morpholino that targets WSTF mRNA. BMP4 shows markedly increased and spatially aberrant expression in WSTF-deficient embryos, while SHH, MRF4, PAX2, EPHA4 and SOX2 expression are severely reduced, coupled with defects in a number of developing embryonic structures and organs. WSTF-deficient embryos display defects in anterior neural development. Induction of the neural crest, measured by expression of the neural crest-specific genes SNAIL and SLUG, is unaffected by WSTF depletion. However, at subsequent stages WSTF knockdown results in a severe defect in neural crest migration and/or maintenance. Consistent with a maintenance defect, WSTF knockdowns display a specific pattern of increased apoptosis at the tailbud stage in regions corresponding to the path of cranial neural crest migration. Our work is the first to describe a role for WSTF in proper neural crest function, and suggests that neural crest defects resulting from WSTF haploinsufficiency may be a major contributor to the pathoembryology of WS. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Evolutionary and Developmental Origins of the Cardiac Neural Crest: Building a Divided Outflow Tract

    Science.gov (United States)

    Keyte, Anna L.; Alonzo-Johnsen, Martha; Hutson, Mary R.

    2015-01-01

    The cardiac neural crest cells (CNCCs) have played an important role in the evolution and development of the vertebrate cardiovascular system: from reinforcement of the developing aortic arch arteries early in vertebrate evolution, to later orchestration of aortic arch artery remodeling into the great arteries of the heart, and finally outflow tract septation in amniotes. A critical element necessary for the evolutionary advent of outflow tract septation was the co-evolution of the cardiac neural crest cells with the second heart field. This review highlights the major transitions in vertebrate circulatory evolution, explores the evolutionary developmental origins of the CNCCs from the third stream cranial neural crest, and explores candidate signaling pathways in CNCC and outflow tract evolution drawn from our knowledge of DiGeorge Syndrome. PMID:25227322

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

    Science.gov (United States)

    Machon, Ondrej; Masek, Jan; Machonova, Olga; Krauss, Stefan; Kozmik, Zbynek

    2015-11-06

    TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging. We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities. Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.

  15. CHD7 cooperates with PBAF to control multipotent neural crest formation

    Science.gov (United States)

    Bajpai, Ruchi; Chen, Denise A.; Rada-Iglesias, Alvaro; Zhang, Junmei; Xiong, Yiqin; Helms, Jill; Chang, Ching-Pin; Zhao, Yingming; Swigut, Tomek; Wysocka, Joanna

    2010-01-01

    Summary Heterozygous mutations in the gene encoding CHD7, an ATP-dependent chromatin remodeler result in a complex constellation of congenital anomalies called CHARGE syndrome. Here we show that in humans and in Xenopus, CHD7 is essential for the formation of multipotent migratory neural crest cells, a transient cell population that is ectodermal in origin, but undergoes a major gene expression reprogramming to acquire a remarkably broad differentiation potential and ability to migrate throughout the body to give rise to bones, cartilages, nerves, and cardiac structures. We demonstrate that CHD7 function is essential for activation of core components of neural crest transcriptional circuitry, including Sox9, Twist and Slug. Moreover, the major features of CHARGE are recapitulated in Xenopus embryo by the downregulation of CHD7 levels or overexpression of its catalytically inactive ATP-ase mutant. We further show that in human multipotent neural crest cells, CHD7 associates with a BRG1-containing complex PBAF, and both factors co-occupy a neural crest-specific distal SOX9 enhancer, as well as a novel genomic element located upstream from TWIST1 gene and marked by H3K4me1. Furthermore, in the embryo CHD7 and PBAF act synergistically to promote neural crest gene expression and cell migration. Our work identifies an evolutionary conserved role for CHD7 in orchestrating neural crest gene expression programs, provides insights into the synergistic regulation of distal genomic elements by two distinct chromatin remodelers, and illuminates the patho-embryology of CHARGE syndrome. PMID:20130577

  16. Wave transmission at low-crested structures using neural networks

    NARCIS (Netherlands)

    Van Oosten, R.P.; Peixó Marco, J.; Van der Meer, J.W.; Van Gent, M.; Verhagen, H.J.

    2006-01-01

    The European Union funded project DELOS was focused on wave transmission and an extensive database on low-crested rubble mound structures was generated. During DELOS, new empirical wave transmission formulae were derived. These formulae still showed a considerable scatter due to a limited number of

  17. Neural Crest Stem Cells from Dental Tissues: A New Hope for Dental and Neural Regeneration

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    Gaskon Ibarretxe

    2012-01-01

    Full Text Available Several stem cell sources persist in the adult human body, which opens the doors to both allogeneic and autologous cell therapies. Tooth tissues have proven to be a surprisingly rich and accessible source of neural crest-derived ectomesenchymal stem cells (EMSCs, which may be employed to repair disease-affected oral tissues in advanced regenerative dentistry. Additionally, one area of medicine that demands intensive research on new sources of stem cells is nervous system regeneration, since this constitutes a therapeutic hope for patients affected by highly invalidating conditions such as spinal cord injury, stroke, or neurodegenerative diseases. However, endogenous adult sources of neural stem cells present major drawbacks, such as their scarcity and complicated obtention. In this context, EMSCs from dental tissues emerge as good alternative candidates, since they are preserved in adult human individuals, and retain both high proliferation ability and a neural-like phenotype in vitro. In this paper, we discuss some important aspects of tissue regeneration by cell therapy and point out some advantages that EMSCs provide for dental and neural regeneration. We will finally review some of the latest research featuring experimental approaches and benefits of dental stem cell therapy.

  18. Pax3 and Hippo Signaling Coordinate Melanocyte Gene Expression in Neural Crest

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    Lauren J. Manderfield

    2014-12-01

    Full Text Available Loss of Pax3, a developmentally regulated transcription factor expressed in premigratory neural crest, results in severe developmental defects and embryonic lethality. Although Pax3 mutations produce profound phenotypes, the intrinsic transcriptional activation exhibited by Pax3 is surprisingly modest. We postulated the existence of transcriptional coactivators that function with Pax3 to mediate developmental functions. A high-throughput screen identified the Hippo effector proteins Taz and Yap65 as Pax3 coactivators. Synergistic coactivation of target genes by Pax3-Taz/Yap65 requires DNA binding by Pax3, is Tead independent, and is regulated by Hippo kinases Mst1 and Lats2. In vivo, Pax3 and Yap65 colocalize in the nucleus of neural crest progenitors in the dorsal neural tube. Neural crest deletion of Taz and Yap65 results in embryo-lethal neural crest defects and decreased expression of the Pax3 target gene, Mitf. These results suggest that Pax3 activity is regulated by the Hippo pathway and that Pax factors are Hippo effectors.

  19. A population of caudally migrating cranial neural crest cells: functional and evolutionary implications.

    Science.gov (United States)

    McGonnell, I M; McKay, I J; Graham, A

    2001-08-15

    The deployment of the cranial neural crest is central to the patterning of the skeletomuscular elements of the vertebrate head, with cranial muscles invariably attaching to skeletal elements formed by crest from the same axial level. Here we demonstrate, through gene expression analysis, ablation studies and fate-mapping, the existence of a population of caudally migrating cranial crest that arise from the postotic neural tube. As with the rest of the postotic crest, these cells express the transcription factor Mafb, and this marker can be used to highlight their posterior migration. They pass out between the anterior somite and the otic vesicle, before turning caudally and running along the base of the somites. With long-term fate mapping, we show that these cells migrate to the clavicle and settle at the site of formation of the attachment point for the cleidohyoid muscle. As such, the influence of the cranial neural crest in organising skeletomuscular connectivity seems to extend beyond the head into the trunk. These results are of further importance as they help explain how, even though the pectoral girdle and the skull became physically dissociated during tetrapod evolution, skeletomuscular connectivity has been maintained. Copyright 2001 Academic Press.

  20. Multiple cranial organ defects after conditionally knocking out Fgf10 in the neural crest

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    Tathyane H.N. Teshima

    2016-10-01

    Full Text Available Fgf10 is necessary for the development of a number of organs that fail to develop or are reduced in size in the null mutant. Here we have knocked out Fgf10 specifically in the neural crest driven by Wnt1cre. The Wnt1creFgf10fl/fl mouse phenocopies many of the null mutant defects, including cleft palate, loss of salivary glands and ocular glands, highlighting the neural crest origin of the Fgf10 expressing mesenchyme surrounding these organs. In contrast tissues such as the limbs and lungs, where Fgf10 is expressed by the surrounding mesoderm, were unaffected, as was the pituitary gland where Fgf10 is expressed by the neuroepithelium. The circumvallate papilla of the tongue formed but was hypoplastic in the conditional and Fgf10 null embryos, suggesting that other sources of FGF can compensate in development of this structure. The tracheal cartilage rings showed normal patterning in the conditional knockout, indicating that the source of Fgf10 for this tissue is mesodermal, which was confirmed using Wnt1cre-dtTom to lineage trace the boundary of the neural crest in this region. The thyroid, thymus and parathyroid glands surrounding the trachea were present but hypoplastic in the conditional mutant, indicating that a neighbouring source of mesodermal Fgf10 might be able to partially compensate for loss of neural crest derived Fgf10.

  1. Caldesmon regulates actin dynamics to influence cranial neural crest migration in Xenopus.

    Science.gov (United States)

    Nie, Shuyi; Kee, Yun; Bronner-Fraser, Marianne

    2011-09-01

    Caldesmon (CaD) is an important actin modulator that associates with actin filaments to regulate cell morphology and motility. Although extensively studied in cultured cells, there is little functional information regarding the role of CaD in migrating cells in vivo. Here we show that nonmuscle CaD is highly expressed in both premigratory and migrating cranial neural crest cells of Xenopus embryos. Depletion of CaD with antisense morpholino oligonucleotides causes cranial neural crest cells to migrate a significantly shorter distance, prevents their segregation into distinct migratory streams, and later results in severe defects in cartilage formation. Demonstrating specificity, these effects are rescued by adding back exogenous CaD. Interestingly, CaD proteins with mutations in the Ca(2+)-calmodulin-binding sites or ErK/Cdk1 phosphorylation sites fail to rescue the knockdown phenotypes, whereas mutation of the PAK phosphorylation site is able to rescue them. Analysis of neural crest explants reveals that CaD is required for the dynamic arrangements of actin and, thus, for cell shape changes and process formation. Taken together, these results suggest that the actin-modulating activity of CaD may underlie its critical function and is regulated by distinct signaling pathways during normal neural crest migration.

  2. 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

  3. Dysregulation of Wnt-Signaling and a Candidate Set of miRNAs Underlie the Effect of Metformin on Neural Crest Cell Development.

    Science.gov (United States)

    Banerjee, Poulomi; Dutta, Sunit; Pal, Rajarshi

    2016-02-01

    Neural crest cells (NCC) are a population of epithelial cells that arise from the dorsal tube and undergo epithelial-mesenchymal transition (EMT) eventually generating tissues from peripheral nervous system, melanocytes, craniofacial cartilage, and bone. The antidiabetic drug metformin reportedly inhibits EMT in physiological conditions like cancer and fibrosis. We hypothesize that perturbation of EMT may also contribute to developmental disabilities associated with neural crest (NC) development. To understand the molecular network underlying metformin action during NC formation, we first differentiated murine embryonic stem (ES) cells into NCC and characterized them by demonstrating spatiotemporal regulation of key markers. Metformin treatment prompted a delay in delamination of NCC by inhibiting key markers like Sox-1, Sox-9, HNK-1, and p-75. We then revealed that metformin impedes Wnt axis, a major signaling pathway active during NC formation via DVL-3 inhibition and impairment in nuclear translocation of β-catenin. Concomitantly we identified and tested a candidate set of miRNAs that play a crucial role in NC cell fate determination. Further studies involving loss and gain of function confirmed that NCC specifiers like Sox-1 and Sox-9 are direct targets of miR-200 and miR-145, respectively and that they are essentially modulated by metformin. Our in vitro findings were strongly supported by in vivo studies in zebrafish. Given that metformin is a widely used drug, for the first time we demonstrate that it can induce a delayed onset of developmental EMT during NC formation by interfering with canonical Wnt signaling and mysregulation of miR-145 and miR-200. © 2015 AlphaMed Press.

  4. Embryonic requirements for ErbB signaling in neural crest development and adult pigment pattern formation

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    Budi, Erine H.; Patterson, Larissa B.; Parichy, David M.

    2009-01-01

    SUMMARY Vertebrate pigment cells are derived from neural crest cells and are a useful system for studying neural crest-derived traits during post-embryonic development. In zebrafish, neural crest-derived melanophores differentiate during embryogenesis to produce stripes in the early larva. Dramatic changes to the pigment pattern occur subsequently during the larva-to-adult transformation, or metamorphosis. At this time, embryonic melanophores are replaced by newly differentiating metamorphic melanophores that form the adult stripes. Mutants with normal embryonic/early larval pigment patterns but defective adult patterns identify factors required uniquely to establish, maintain, or recruit the latent precursors to metamorphic melanophores. We show that one such mutant, picasso, lacks most metamorphic melanophores and results from mutations in the ErbB gene erbb3b, encoding an EGFR-like receptor tyrosine kinase. To identify critical periods for ErbB activities, we treated fish with pharmacological ErbB inhibitors and also knocked-down erbb3b by morpholino injection. These analyses reveal an embryonic critical period for ErbB signaling in promoting later pigment pattern metamorphosis, despite the normal patterning of embryonic/early larval melanophores. We further demonstrate a peak requirement during neural crest migration that correlates with early defects in neural crest pathfinding and peripheral ganglion formation. Finally, we show that erbb3b activities are both autonomous and non-autonomous to the metamorphic melanophore lineage. These data identify a very early, embryonic, requirement for erbb3b in the development of much later metamorphic melanophores, and suggest complex modes by which ErbB signals promote adult pigment pattern development. PMID:18508863

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

    Science.gov (United States)

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

    2016-05-01

    During vertebrate axis extension, adjacent tissue layers undergo profound morphological changes: within the neuroepithelium, neural tube closure and neural crest formation are occurring, while within the paraxial mesoderm somites are segmenting from the presomitic mesoderm (PSM). Little is known about the signals between these tissues that regulate their coordinated morphogenesis. Here, we analyze the posterior axis truncation of mouse Fgf3 null homozygotes and demonstrate that the earliest role of PSM-derived FGF3 is to regulate BMP signals in the adjacent neuroepithelium. FGF3 loss causes elevated BMP signals leading to increased neuroepithelium proliferation, delay in neural tube closure and premature neural crest specification. We demonstrate that elevated BMP4 depletes PSM progenitors in vitro, phenocopying the Fgf3 mutant, suggesting that excessive BMP signals cause the Fgf3 axis defect. To test this in vivo we increased BMP signaling in Fgf3 mutants by removing one copy of Noggin, which encodes a BMP antagonist. In such mutants, all parameters of the Fgf3 phenotype were exacerbated: neural tube closure delay, premature neural crest specification, and premature axis termination. Conversely, genetically decreasing BMP signaling in Fgf3 mutants, via loss of BMP receptor activity, alleviates morphological defects. Aberrant apoptosis is observed in the Fgf3 mutant tailbud. However, we demonstrate that cell death does not cause the Fgf3 phenotype: blocking apoptosis via deletion of pro-apoptotic genes surprisingly increases all Fgf3 defects including causing spina bifida. We demonstrate that this counterintuitive consequence of blocking apoptosis is caused by the increased survival of BMP-producing cells in the neuroepithelium. Thus, we show that FGF3 in the caudal vertebrate embryo regulates BMP signaling in the neuroepithelium, which in turn regulates neural tube closure, neural crest specification and axis termination. Uncovering this FGF3-BMP signaling axis is

  6. Disruption of CXCR4 signaling in pharyngeal neural crest cells causes DiGeorge syndrome-like malformations.

    Science.gov (United States)

    Escot, Sophie; Blavet, Cédrine; Faure, Emilie; Zaffran, Stéphane; Duband, Jean-Loup; Fournier-Thibault, Claire

    2016-02-15

    DiGeorge syndrome (DGS) is a congenital disease causing cardiac outflow tract anomalies, craniofacial dysmorphogenesis, thymus hypoplasia, and mental disorders. It results from defective development of neural crest cells (NCs) that colonize the pharyngeal arches and contribute to lower jaw, neck and heart tissues. Although TBX1 has been identified as the main gene accounting for the defects observed in human patients and mouse models, the molecular mechanisms underlying DGS etiology are poorly identified. The recent demonstrations that the SDF1/CXCR4 axis is implicated in NC chemotactic guidance and impaired in cortical interneurons of mouse DGS models prompted us to search for genetic interactions between Tbx1, Sdf1 (Cxcl12) and Cxcr4 in pharyngeal NCs and to investigate the effect of altering CXCR4 signaling on the ontogeny of their derivatives, which are affected in DGS. Here, we provide evidence that Cxcr4 and Sdf1 are genetically downstream of Tbx1 during pharyngeal NC development and that reduction of CXCR4 signaling causes misrouting of pharyngeal NCs in chick and dramatic morphological alterations in the mandibular skeleton, thymus and cranial sensory ganglia. Our results therefore support the possibility of a pivotal role for the SDF1/CXCR4 axis in DGS etiology. © 2016. Published by The Company of Biologists Ltd.

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

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    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.

  8. CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance.

    Science.gov (United States)

    Schulz, Yvonne; Wehner, Peter; Opitz, Lennart; Salinas-Riester, Gabriela; Bongers, Ernie M H F; van Ravenswaaij-Arts, Conny M A; Wincent, Josephine; Schoumans, Jacqueline; Kohlhase, Jürgen; Borchers, Annette; Pauli, Silke

    2014-08-01

    Heterozygous loss of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex developmental disorder affecting craniofacial structures, cranial nerves and several organ systems. Recently, it was demonstrated that CHD7 is essential for the formation of multipotent migratory neural crest cells, which migrate from the neural tube to many regions of the embryo, where they differentiate into various tissues including craniofacial and heart structures. So far, only few CHD7 target genes involved in neural crest cell development have been identified and the role of CHD7 in neural crest cell guidance and the regulation of mesenchymal-epithelial transition are unknown. Therefore, we undertook a genome-wide microarray expression analysis on wild-type and CHD7 deficient (Chd7 (Whi/+) and Chd7 (Whi/Whi)) mouse embryos at day 9.5, a time point of neural crest cell migration. We identified 98 differentially expressed genes between wild-type and Chd7 (Whi/Whi) embryos. Interestingly, many misregulated genes are involved in neural crest cell and axon guidance such as semaphorins and ephrin receptors. By performing knockdown experiments for Chd7 in Xenopus laevis embryos, we found abnormalities in the expression pattern of Sema3a, a protein involved in the pathogenesis of Kallmann syndrome, in vivo. In addition, we detected non-synonymous SEMA3A variations in 3 out of 45 CHD7-negative CHARGE patients. In summary, we discovered for the first time that Chd7 regulates genes involved in neural crest cell guidance, demonstrating a new aspect in the pathogenesis of CHARGE syndrome. Furthermore, we showed for Sema3a a conserved regulatory mechanism across different species, highlighting its significance during development. Although we postulated that the non-synonymous SEMA3A variants which we found in CHD7-negative CHARGE patients alone are not sufficient to produce the phenotype, we suggest an important modifier role for SEMA3A in the

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

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    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

  10. 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.

  11. SNW1 is a critical regulator of spatial BMP activity, neural plate border formation, and neural crest specification in vertebrate embryos.

    Directory of Open Access Journals (Sweden)

    Mary Y Wu

    2011-02-01

    Full Text Available Bone morphogenetic protein (BMP gradients provide positional information to direct cell fate specification, such as patterning of the vertebrate ectoderm into neural, neural crest, and epidermal tissues, with precise borders segregating these domains. However, little is known about how BMP activity is regulated spatially and temporally during vertebrate development to contribute to embryonic patterning, and more specifically to neural crest formation. Through a large-scale in vivo functional screen in Xenopus for neural crest fate, we identified an essential regulator of BMP activity, SNW1. SNW1 is a nuclear protein known to regulate gene expression. Using antisense morpholinos to deplete SNW1 protein in both Xenopus and zebrafish embryos, we demonstrate that dorsally expressed SNW1 is required for neural crest specification, and this is independent of mesoderm formation and gastrulation morphogenetic movements. By exploiting a combination of immunostaining for phosphorylated Smad1 in Xenopus embryos and a BMP-dependent reporter transgenic zebrafish line, we show that SNW1 regulates a specific domain of BMP activity in the dorsal ectoderm at the neural plate border at post-gastrula stages. We use double in situ hybridizations and immunofluorescence to show how this domain of BMP activity is spatially positioned relative to the neural crest domain and that of SNW1 expression. Further in vivo and in vitro assays using cell culture and tissue explants allow us to conclude that SNW1 acts upstream of the BMP receptors. Finally, we show that the requirement of SNW1 for neural crest specification is through its ability to regulate BMP activity, as we demonstrate that targeted overexpression of BMP to the neural plate border is sufficient to restore neural crest formation in Xenopus SNW1 morphants. We conclude that through its ability to regulate a specific domain of BMP activity in the vertebrate embryo, SNW1 is a critical regulator of neural plate

  12. Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult Mammalian Carotid Body

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    Valentina Annese

    2017-04-01

    Full Text Available Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is hypoxia inducible factor (HIF dependent and sensitive to hypoxia-released vascular cytokines such as erythropoietin. Our data highlight a remarkable physiological plasticity in an adult population of tissue-specific stem cells and could have impact on the use of these cells for cell therapy.

  13. Making headway: the roles of Hox genes and neural crest cells in craniofacial development.

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    Trainor, Paul A

    2003-04-14

    Craniofacial development is an extraordinarily complex process requiring the orchestrated integration of multiple specialized tissues such as the surface ectoderm, neural crest, mesoderm, and pharyngeal endoderm in order to generate the central and peripheral nervous systems, axial skeleton, musculature, and connective tissues of the head and face. How do the characteristic facial structures develop in the appropriate locations with their correct shapes and sizes, given the widely divergent patterns of cell movements that occur during head development? The patterning information could depend upon localized interactions between the epithelial and mesenchymal tissues or alternatively, the developmental program for the characteristic facial structures could be intrinsic to each individual tissue precursor. Understanding the mechanisms that control vertebrate head development is an important issue since craniofacial anomalies constitute nearly one third of all human congenital defects. This review discusses recent advances in our understanding of neural crest cell patterning and the dynamic nature of the tissue interactions that are required for normal craniofacial development.

  14. Efficient genome editing of genes involved in neural crest development using the CRISPR/Cas9 system in Xenopus embryos.

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    Liu, Zhongzhen; Cheng, Tina Tsz Kwan; Shi, Zhaoying; Liu, Ziran; Lei, Yong; Wang, Chengdong; Shi, Weili; Chen, Xiongfeng; Qi, Xufeng; Cai, Dongqing; Feng, Bo; Deng, Yi; Chen, Yonglong; Zhao, Hui

    2016-01-01

    The RNA guided CRISPR/Cas9 nucleases have been proven to be effective for gene disruption in various animal models including Xenopus tropicalis. The neural crest (NC) is a transient cell population during embryonic development and contributes to a large variety of tissues. Currently, loss-of-function studies on NC development in X. tropicalis are largely based on morpholino antisense oligonucleotide. It is worthwhile establishing targeted gene knockout X. tropicails line using CRISPR/Cas9 system to study NC development. We utilized CRISPR/Cas9 to disrupt genes that are involved in NC formation in X. tropicalis embryos. A single sgRNA and Cas9 mRNA synthesized in vitro, were co-injected into X. tropicalis embryos at one-cell stage to induce single gene disruption. We also induced duplex mutations, large segmental deletions and inversions in X. tropicalis by injecting Cas9 and a pair of sgRNAs. The specificity of CRISPR/Cas9 was assessed in X. tropicalis embryos and the Cas9 nickase was used to reduce the off-target cleavages. Finally, we crossed the G0 mosaic frogs with targeted mutations to wild type frogs and obtained the germline transmission. Total 16 target sites in 15 genes were targeted by CRISPR/Cas9 and resulted in successful indel mutations at 14 loci with disruption efficiencies in a range from 9.3 to 57.8 %. Furthermore, we demonstrated the feasibility of generation of duplex mutations, large segmental deletions and inversions by using Cas9 and a pair of sgRNAs. We observed that CRISPR/Cas9 displays obvious off-target effects at some loci in X. tropicalis embryos. Such off-target cleavages was reduced by using the D10A Cas9 nickase. Finally, the Cas9 induced indel mutations were efficiently passed to G1 offspring. Our study proved that CRISPR/Cas9 could mediate targeted gene mutation in X. tropicalis with high efficiency. This study expands the application of CRISPR/Cas9 platform in X. tropicalis and set a basis for studying NC development using genetic

  15. CtBP2 downregulation during neural crest specification induces expression of Mitf and REST, resulting in melanocyte differentiation and sympathoadrenal lineage suppression.

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    Liang, Hongzi; Fekete, Donna M; Andrisani, Ourania M

    2011-03-01

    Trunk neural crest (NC) cells differentiate to neurons, melanocytes, and glia. In NC cultures, cyclic AMP (cAMP) induces melanocyte differentiation while suppressing the neuronal sympathoadrenal lineage, depending on the signal intensity. Melanocyte differentiation requires activation of CREB and cAMP-dependent protein kinase A (PKA), but the role of PKA is not understood. We have demonstrated, in NC cultures, cAMP-induced transcription of the microphthalmia-associated transcription factor gene (Mitf) and the RE-1 silencing transcription factor gene (REST), both Wnt-regulated genes. In NC cultures and zebrafish, knockdown of the corepressor of Wnt-mediated transcription C-terminal binding protein 2 (CtBP2) but not CtBP1 derepressed Mitf and REST expression and enhanced melanocyte differentiation. cAMP in NC and B16 melanoma cells decreased CtBP2 protein levels, while inhibition of PKA or proteasome rescued CtBP2 degradation. Interestingly, knockdown of homeodomain-interacting protein kinase 2 (HIPK2), a CtBP stability modulator, increased CtBP2 levels, suppressed expression of Mitf, REST, and melanocyte differentiation, and increased neuronal gene expression and sympathoadrenal lineage differentiation. We conclude that cAMP/PKA via HIPK2 promotes CtBP2 degradation, leading to Mitf and REST expression. Mitf induces melanocyte specification, and REST suppresses neuron-specific gene expression and the sympathoadrenal lineage. Our studies identify a novel role for REST in NC cell differentiation and suggest cross talk between cAMP and Wnt signaling in NC lineage specification.

  16. CtBP2 Downregulation during Neural Crest Specification Induces Expression of Mitf and REST, Resulting in Melanocyte Differentiation and Sympathoadrenal Lineage Suppression ▿

    Science.gov (United States)

    Liang, Hongzi; Fekete, Donna M.; Andrisani, Ourania M.

    2011-01-01

    Trunk neural crest (NC) cells differentiate to neurons, melanocytes, and glia. In NC cultures, cyclic AMP (cAMP) induces melanocyte differentiation while suppressing the neuronal sympathoadrenal lineage, depending on the signal intensity. Melanocyte differentiation requires activation of CREB and cAMP-dependent protein kinase A (PKA), but the role of PKA is not understood. We have demonstrated, in NC cultures, cAMP-induced transcription of the microphthalmia-associated transcription factor gene (Mitf) and the RE-1 silencing transcription factor gene (REST), both Wnt-regulated genes. In NC cultures and zebrafish, knockdown of the corepressor of Wnt-mediated transcription C-terminal binding protein 2 (CtBP2) but not CtBP1 derepressed Mitf and REST expression and enhanced melanocyte differentiation. cAMP in NC and B16 melanoma cells decreased CtBP2 protein levels, while inhibition of PKA or proteasome rescued CtBP2 degradation. Interestingly, knockdown of homeodomain-interacting protein kinase 2 (HIPK2), a CtBP stability modulator, increased CtBP2 levels, suppressed expression of Mitf, REST, and melanocyte differentiation, and increased neuronal gene expression and sympathoadrenal lineage differentiation. We conclude that cAMP/PKA via HIPK2 promotes CtBP2 degradation, leading to Mitf and REST expression. Mitf induces melanocyte specification, and REST suppresses neuron-specific gene expression and the sympathoadrenal lineage. Our studies identify a novel role for REST in NC cell differentiation and suggest cross talk between cAMP and Wnt signaling in NC lineage specification. PMID:21199918

  17. 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

  18. [Phenotypic plasticity of neural crest-derived melanocytes and Schwann cells].

    Science.gov (United States)

    Dupin, Elisabeth

    2011-01-01

    Melanocytes, the pigmented cells of the skin, and the glial Schwann cells lining peripheral nerves are developmentally derived from an early and transient ectodermal structure of the vertebrate embryo, the neural crest, which is also at the origin of multiple neural and non-neural cell types. Besides melanocytes and neural cells of the peripheral nervous system, the neural crest cells give rise to mesenchymal cell types in the head, which form most of the craniofacial skeleton, dermis, fat tissue and vascular musculo-connective components. How such a wide diversity of differentiation fates is established during embryogenesis and is later maintained in adult tissues are among key questions in developmental and stem cell biology. The analysis of the developmental potentials of single neural crest cells cultured in vitro led to characterizing multipotent stem/progenitor cells as well as more restricted precursors in the early neural crest of avian and mammalian embryos. Data support a hierarchical model of the diversification of neural crest lineages through progressive restrictions of multipotent stem cell potentials driven by local environmental factors. In particular, melanocytes and glial Schwann cells were shown to arise from a common bipotent progenitor, which depends upon the peptide endothelin-3 for proliferation and self-renewal ability. In vivo, signaling by endothelin-3 and its receptor is also required for the early development of melanocytes and proper pigmentation of the vertebrate body. It is generally assumed that, after lineage specification and terminal differentiation, specialized cell types, like the melanocytes and Schwann cells, do not change their identity. However, this classic notion that somatic cell differentiation is a stable and irreversible process has been challenged by emerging evidence that dedifferentiation can occur in different biological systems through nuclear transfer, cell fusion, epigenetic modifications and ectopic gene

  19. 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.

  20. Involvement of Neptune in induction of the hatching gland and neural crest in the Xenopus embryo.

    Science.gov (United States)

    Kurauchi, Takayuki; Izutsu, Yumi; Maéno, Mitsugu

    2010-01-01

    Neptune, a Krüppel-like transcription factor, is expressed in various regions of the developing Xenopus embryo and it has multiple functions in the process of development in various organs. In situ hybridization analysis showed that Neptune is expressed in the boundary region between neural and non-neural tissues at the neurula stage, but little is known about the function of Neptune in this region. Here, we examined the expression and function of Neptune in the neural plate border (NPB) in the Xenopus embryo. Depletion of Neptune protein in developing embryos by using antisense MO caused loss of the hatching gland and otic vesicle as well as malformation of neural crest-derived cranial cartilages and melanocytes. Neptune MO also suppressed the expression of hatching gland and neural crest markers such as he, snail2, sox9 and msx1 at the neurula stage. Subsequent experiments showed that Neptune is necessary and sufficient for the differentiation of hatching gland cells and that it is located downstream of pax3 in the signal regulating the differentiation of these cells. Thus, Neptune is a new member of hatching gland specifier and plays a physiological role in determination and specification of multiple lineages derived from the NPB region.

  1. Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs

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    Yvonne Mica

    2013-04-01

    Full Text Available Melanocytes are pigment-producing cells of neural crest (NC origin that are responsible for protecting the skin against UV irradiation. Pluripotent stem cell (PSC technology offers a promising approach for studying human melanocyte development and disease. Here, we report that timed exposure to activators of WNT, BMP, and EDN3 signaling triggers the sequential induction of NC and melanocyte precursor fates under dual-SMAD-inhibition conditions. Using a SOX10::GFP human embryonic stem cell (hESC reporter line, we demonstrate that the temporal onset of WNT activation is particularly critical for human NC induction. Subsequent maturation of hESC-derived melanocytes yields pure populations that match the molecular and functional properties of adult melanocytes. Melanocytes from Hermansky-Pudlak syndrome and Chediak-Higashi syndrome patient-specific induced PSCs (iPSCs faithfully reproduce the ultrastructural features of disease-associated pigmentation defects. Our data define a highly specific requirement for WNT signaling during NC induction and enable the generation of pure populations of human iPSC-derived melanocytes for faithful modeling of pigmentation disorders.

  2. 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

  3. Design of a high-throughput human neural crest cell migration assay to indicate potential developmental toxicants.

    Science.gov (United States)

    Nyffeler, Johanna; Karreman, Christiaan; Leisner, Heidrun; Kim, Yong Jun; Lee, Gabsang; Waldmann, Tanja; Leist, Marcel

    2017-01-01

    Migration of neural crest cells (NCCs) is one of the pivotal processes of human fetal development. Malformations arise if NCC migration and differentiation are impaired genetically or by toxicants. In the currently available test systems for migration inhibition of NCC (MINC), the manual generation of a cell-free space results in extreme operator dependencies, and limits throughput. Here a new test format was established. The assay avoids scratching by plating cells around a commercially available circular stopper. Removal of the stopper barrier after cell attachment initiates migration. This microwell-based circular migration zone NCC function assay (cMINC) was further optimized for toxicological testing of human pluripotent stem cell (hPSC)-derived NCCs. The challenge of obtaining data on viability and migration by automated image processing was addressed by developing a freeware. Data on cell proliferation were obtained by labelling replicating cells, and by careful assessment of cell viability for each experimental sample. The role of cell proliferation as an experimental confounder was tested experimentally by performing the cMINC in the presence of the proliferation-inhibiting drug cytosine arabinoside (AraC), and by a careful evaluation of mitotic events over time. Data from these studies led to an adaptation of the test protocol, so that toxicant exposure was limited to 24 h. Under these conditions, a prediction model was developed that allows classification of toxicants as either inactive, leading to unspecific cytotoxicity, or specifically inhibiting NC migration at non-cytotoxic concentrations.

  4. Sphere-Derived Multipotent Progenitor Cells Obtained From Human Oral Mucosa Are Enriched in Neural Crest Cells.

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    Abe, Shigehiro; Yamaguchi, Satoshi; Sato, Yutaka; Harada, Kiyoshi

    2016-01-01

    : Although isolation of oral mucosal stromal stem cells has been previously reported, complex isolation methods are not suitable for clinical application. The neurosphere culture technique is a convenient method for the isolation of neural stem cells and neural crest stem cells (NCSCs); neurosphere generation is a phenotype of NCSCs. However, the molecular details underlying the isolation and characterization of human oral mucosa stromal cells (OMSCs) by neurosphere culture are not understood. The purpose of the present study was to isolate NCSCs from oral mucosa using the neurosphere technique and to establish effective in vivo bone tissue regeneration methods. Human OMSCs were isolated from excised human oral mucosa; these cells formed spheres in neurosphere culture conditions. Oral mucosa sphere-forming cells (OMSFCs) were characterized by biological analyses of stem cells. Additionally, composites of OMSFCs and multiporous polylactic acid scaffolds were implanted subcutaneously into immunocompromised mice. OMSFCs had the capacity for self-renewal and expressed neural crest-related markers (e.g., nestin, CD44, slug, snail, and MSX1). Furthermore, upregulated expression of neural crest-related genes (EDNRA, Hes1, and Sox9) was observed in OMSFCs, which are thought to contain an enriched population of neural crest-derived cells. The expression pattern of α2-integrin (CD49b) in OMSFCs also differed from that in OMSCs. Finally, OMSFCs were capable of differentiating into neural crest lineages in vitro and generating ectopic bone tissues even in the subcutaneous region. The results of the present study suggest that OMSFCs are an ideal source of cells for the neural crest lineage and hard tissue regeneration. The sphere culture technique is a convenient method for isolating stem cells. However, the isolation and characterization of human oral mucosa stromal cells (OMSCs) using the sphere culture system are not fully understood. The present study describes the

  5. 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.

  6. 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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    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. Feasibility Study of Canine Epidermal Neural Crest Stem Cell Transplantation in the Spinal Cords of Dogs.

    Science.gov (United States)

    McMahill, Barbara G; Spriet, Mathieu; Sisó, Sílvia; Manzer, Michael D; Mitchell, Gaela; McGee, Jeannine; Garcia, Tanya C; Borjesson, Dori L; Sieber-Blum, Maya; Nolta, Jan A; Sturges, Beverly K

    2015-10-01

    This pilot feasibility study aimed to determine the outcome of canine epidermal neural crest stem cell (cEPI-NCSC) grafts in the normal spinal cords of healthy bred-for-research dogs. This included developing novel protocols for (a) the ex vivo expansion of cEPI-NCSCs, (b) the delivery of cEPI-NCSCs into the spinal cord, and (c) the labeling of the cells and subsequent tracing of the graft in the live animal by magnetic resonance imaging. A total of four million cEPI-NCSCs were injected into the spinal cord divided in two locations. Differences in locomotion at baseline and post-treatment were evaluated by gait analysis and compared with neurological outcome and behavioral exams. Histopathological analyses of the spinal cords and cEPI-NCSC grafts were performed at 3 weeks post-transplantation. Neurological and gait parameters were minimally affected by the stem cell injection. cEPI-NCSCs survived in the canine spinal cord for the entire period of investigation and did not migrate or proliferate. Subsets of cEPI-NCSCs expressed the neural crest stem cell marker Sox10. There was no detectable expression of markers for glial cells or neurons. The tissue reaction to the cell graft was predominantly vascular in addition to a degree of reactive astrogliosis and microglial activation. In the present study, we demonstrated that cEPI-NCSC grafts survive in the spinal cords of healthy dogs without major adverse effects. They persist locally in the normal spinal cord, may promote angiogenesis and tissue remodeling, and elicit a tissue response that may be beneficial in patients with spinal cord injury. It has been established that mouse and human epidermal neural crest stem cells are somatic multipotent stem cells with proved innovative potential in a mouse model of spinal cord injury (SCI) offering promise of a valid treatment for SCI. Traumatic SCI is a common neurological problem in dogs with marked similarities, clinically and pathologically, to the syndrome in people

  8. 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.

  9. Sox10-Venus mice: a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes.

    Science.gov (United States)

    Shibata, Shinsuke; Yasuda, Akimasa; Renault-Mihara, Francois; Suyama, Satoshi; Katoh, Hiroyuki; Inoue, Takayoshi; Inoue, Yukiko U; Nagoshi, Narihito; Sato, Momoka; Nakamura, Masaya; Akazawa, Chihiro; Okano, Hideyuki

    2010-10-31

    While several mouse strains have recently been developed for tracing neural crest or oligodendrocyte lineages, each strain has inherent limitations. The connection between human SOX10 mutations and neural crest cell pathogenesis led us to focus on the Sox10 gene, which is critical for neural crest development. We generated Sox10-Venus BAC transgenic mice to monitor Sox10 expression in both normal development and in pathological processes. Tissue fluorescence distinguished neural crest progeny cells and oligodendrocytes in the Sox10-Venus mouse embryo. Immunohistochemical analysis confirmed that Venus expression was restricted to cells expressing endogenous Sox10. Time-lapse imaging of various tissues in Sox10-Venus mice demonstrated that Venus expression could be visualized at the single-cell level in vivo due to the intense, focused Venus fluorescence. In the adult Sox10-Venus mouse, several types of mature and immature oligodendrocytes along with Schwann cells were clearly labeled with Venus, both before and after spinal cord injury. In the newly-developed Sox10-Venus transgenic mouse, Venus fluorescence faithfully mirrors endogenous Sox10 expression and allows for in vivo imaging of live cells at the single-cell level. This Sox10-Venus mouse will thus be a useful tool for studying neural crest cells or oligodendrocytes, both in development and in pathological processes.

  10. Sox10-Venus mice: a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes

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    Shibata Shinsuke

    2010-10-01

    Full Text Available Abstract Background While several mouse strains have recently been developed for tracing neural crest or oligodendrocyte lineages, each strain has inherent limitations. The connection between human SOX10 mutations and neural crest cell pathogenesis led us to focus on the Sox10 gene, which is critical for neural crest development. We generated Sox10-Venus BAC transgenic mice to monitor Sox10 expression in both normal development and in pathological processes. Results Tissue fluorescence distinguished neural crest progeny cells and oligodendrocytes in the Sox10-Venus mouse embryo. Immunohistochemical analysis confirmed that Venus expression was restricted to cells expressing endogenous Sox10. Time-lapse imaging of various tissues in Sox10-Venus mice demonstrated that Venus expression could be visualized at the single-cell level in vivo due to the intense, focused Venus fluorescence. In the adult Sox10-Venus mouse, several types of mature and immature oligodendrocytes along with Schwann cells were clearly labeled with Venus, both before and after spinal cord injury. Conclusions In the newly-developed Sox10-Venus transgenic mouse, Venus fluorescence faithfully mirrors endogenous Sox10 expression and allows for in vivo imaging of live cells at the single-cell level. This Sox10-Venus mouse will thus be a useful tool for studying neural crest cells or oligodendrocytes, both in development and in pathological processes.

  11. High-level activation of cyclic AMP signaling attenuates bone morphogenetic protein 2-induced sympathoadrenal lineage development and promotes melanogenesis in neural crest cultures.

    Science.gov (United States)

    Ji, Ming; Andrisani, Ourania M

    2005-06-01

    The intensity of cyclic AMP (cAMP) signaling is a differential instructive signal in neural crest (NC) cell specification. By an unknown mechanism, sympathoadrenal lineage specification is suppressed by high-level activation of cAMP signaling. In NC cultures, high-level activation of cAMP signaling mediates protein kinase A (PKA)-dependent Rap1-B-Raf-ERK1/2 activation, leading to cytoplasmic accumulation of phospho-Smad1, thus terminating bone morphogenetic protein 2 (BMP2)-induced sympathoadrenal cell development. Concurrently, cAMP signaling induces transcription of the melanocyte-determining transcription factor Mitf and melanogenesis. dnACREB and E1A inhibit Mitf expression and melanogenesis, supporting the notion that CREB activation is necessary for melanogenesis. However, constitutively active CREB(DIEDML) without PKA activation is insufficient for Mitf expression and melanogenesis, indicating PKA regulates additional aspects of Mitf transcription. Thus, high-level activation of cAMP signaling plays a dual role in NC cell differentiation: attenuation of BMP2-induced sympathoadrenal cell development and induction of melanogenesis. We conclude the intensity of activation of signal transduction cascades determines cell lineage segregation mechanisms.

  12. 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...... seen significantly more often in cleft palate. Combined cleft lip and palate: Number and type of dental deviations differed significantly from deviations in other cleft types, e.g. significantly more ageneses. CONCLUSIONS: Cleft lip seems to be caused by a disorder in neural crest migration...... to the frontonasal field and cleft palate by a disorder in neural crest migration to the maxillary and palatal fields. Combined cleft lip and palate seems to be caused by a primary early defect in the cranial course and function of the notochord. The dentition was significantly different in the different cleft types...

  13. High glucose environment inhibits cranial neural crest survival by activating excessive autophagy in the chick embryo

    Science.gov (United States)

    Wang, Xiao-Yu; Li, Shuai; Wang, Guang; Ma, Zheng-Lai; Chuai, Manli; Cao, Liu; Yang, Xuesong

    2015-01-01

    High glucose levels induced by maternal diabetes could lead to defects in neural crest development during embryogenesis, but the cellular mechanism is still not understood. In this study, we observed a defect in chick cranial skeleton, especially parietal bone development in the presence of high glucose levels, which is derived from cranial neural crest cells (CNCC). In early chick embryo, we found that inducing high glucose levels could inhibit the development of CNCC, however, cell proliferation was not significantly involved. Nevertheless, apoptotic CNCC increased in the presence of high levels of glucose. In addition, the expression of apoptosis and autophagy relevant genes were elevated by high glucose treatment. Next, the application of beads soaked in either an autophagy stimulator (Tunicamycin) or inhibitor (Hydroxychloroquine) functionally proved that autophagy was involved in regulating the production of CNCC in the presence of high glucose levels. Our observations suggest that the ERK pathway, rather than the mTOR pathway, most likely participates in mediating the autophagy induced by high glucose. Taken together, our observations indicated that exposure to high levels of glucose could inhibit the survival of CNCC by affecting cell apoptosis, which might result from the dysregulation of the autophagic process. PMID:26671447

  14. Neural crest cells pattern the surface cephalic ectoderm during FEZ formation.

    Science.gov (United States)

    Hu, Diane; Marcucio, Ralph S

    2012-04-01

    Multiple fibroblast growth factor (Fgf) ligands are expressed in the forebrain and facial ectoderm, and vascular endothelial growth factor (VEGF) is expressed in the facial ectoderm. Both pathways activate the MAP kinase cascade and can be suppressed by SU5402. We placed a bead soaked in SU5402 into the brain after emigration of neural crest cells was complete. Within 24 hr we observed reduced pMEK and pERK staining that persisted for at least 48 hr. This was accompanied by significant apoptosis in the face. By day 15, the upper beaks were truncated. Molecular changes in the FNP were also apparent. Normally, Shh is expressed in the frontonasal ectodermal zone and controls patterned growth of the upper jaw. In treated embryos, Shh expression was reduced. Both the structural and molecular deficits were mitigated after transplantation of FNP-derived mesenchymal cells. Thus, mesenchymal cells actively participate in signaling interactions of the face, and the absence of neural crest cells in neurocristopathies may not be merely structural. Copyright © 2012 Wiley Periodicals, Inc.

  15. Enrichment and Schwann Cell Differentiation of Neural Crest-derived Dental Pulp Stem Cells.

    Science.gov (United States)

    Al-Zer, Heba; Apel, Christian; Heiland, Max; Friedrich, Reinhard E; Jung, Ole; Kroeger, Nadja; Eichhorn, Wolfgang; Smeets, Ralf

    2015-01-01

    As already described in previous studies, neural crest stem cells (NCSCs) can be found in adult human dental pulp. The present study investigated the methodology for enrichment and differentiation-induction of the above mentioned cells. Dental pulp was extracted from human wisdom teeth of four patients and subsequently cultured as explants on fibronectin-coated plates in neurobasal medium supplemented with B27, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin, l-glutamine and neuregulin-β1. The cells were then characterized by immunofluorescence, while their differentiation-potential was tested by the attempt to induce cells into different lineages, i.e. osteogenic, melanocytic and glial. The enriched cell population expressed nestin, CD271 and SOX10, which are well-known markers for NCSCs. Consequently, the cells were successfully induced to differentiate into osteoblasts, melanocytes and Schwann cells, expressing the corresponding differentiation markers. Human adult dental pulp contains a population of stem cells with neural crest ontogeny, which can thus be recruited for multiple regenerative therapies. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis.

    Science.gov (United States)

    Sedykh, Irina; Yoon, Baul; Roberson, Laura; Moskvin, Oleg; Dewey, Colin N; Grinblat, Yevgenya

    2017-09-01

    The vertebrate retina develops in close proximity to the forebrain and neural crest-derived cartilages of the face and jaw. Coloboma, a congenital eye malformation, is associated with aberrant forebrain development (holoprosencephaly) and with craniofacial defects (frontonasal dysplasia) in humans, suggesting a critical role for cross-lineage interactions during retinal morphogenesis. ZIC2, a zinc-finger transcription factor, is linked to human holoprosencephaly. We have previously used morpholino assays to show zebrafish zic2 functions in the developing forebrain, retina and craniofacial cartilage. We now report that zebrafish with genetic lesions in zebrafish zic2 orthologs, zic2a and zic2b, develop with retinal coloboma and craniofacial anomalies. We demonstrate a requirement for zic2 in restricting pax2a expression and show evidence that zic2 function limits Hh signaling. RNA-seq transcriptome analysis identified an early requirement for zic2 in periocular neural crest as an activator of alx1, a transcription factor with essential roles in craniofacial and ocular morphogenesis in human and zebrafish. Collectively, these data establish zic2 mutant zebrafish as a powerful new genetic model for in-depth dissection of cell interactions and genetic controls during craniofacial complex development. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Neural crest cells pattern the surface cephalic ectoderm during FEZ formation

    Science.gov (United States)

    Hu, Diane; Marcucio, Ralph S.

    2012-01-01

    Multiple Fibroblast growth factor (Fgf) ligands are expressed in the forebrain and facial ectoderm, and Vascular Endothelial Growth Factor (VEGF) is expressed in the facial ectoderm. Both pathways activate the MAP kinase cascade and can be suppressed by SU5402. We placed a bead soaked in SU5402 into the brain after emigration of neural crest cells was complete. Within 24 hours we observed reduced pMEK and pERK staining that persisted for at least 48 hours. This was accompanied by significant apoptosis in the face. By day 15 the upper beaks were truncated. Molecular changes in the FNP were also apparent. Normally, Shh is expressed in the Frontonasal Ectodermal Zone and controls patterned growth of the upper jaw. In treated embryos Shh expression was reduced. Both the structural and molecular deficits were mitigated after transplantation of FNP-derived mesenchymal cells. Thus, mesenchymal cells actively participate in signaling interactions of the face, and the absence of neural crest cells in neurocristopathies may not be merely structural. PMID:22411554

  18. 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.

  19. Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult Mammalian Carotid Body.

    Science.gov (United States)

    Annese, Valentina; Navarro-Guerrero, Elena; Rodríguez-Prieto, Ismael; Pardal, Ricardo

    2017-04-18

    Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs) display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs) are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is hypoxia inducible factor (HIF) dependent and sensitive to hypoxia-released vascular cytokines such as erythropoietin. Our data highlight a remarkable physiological plasticity in an adult population of tissue-specific stem cells and could have impact on the use of these cells for cell therapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Making Headway: The Roles of Hox Genes and Neural Crest Cells in Craniofacial Development

    Directory of Open Access Journals (Sweden)

    Paul A. Trainor

    2003-01-01

    Full Text Available Craniofacial development is an extraordinarily complex process requiring the orchestrated integration of multiple specialized tissues such as the surface ectoderm, neural crest, mesoderm, and pharyngeal endoderm in order to generate the central and peripheral nervous systems, axial skeleton, musculature, and connective tissues of the head and face. How do the characteristic facial structures develop in the appropriate locations with their correct shapes and sizes, given the widely divergent patterns of cell movements that occur during head development? The patterning information could depend upon localized interactions between the epithelial and mesenchymal tissues or alternatively, the developmental program for the characteristic facial structures could be intrinsic to each individual tissue precursor. Understanding the mechanisms that control vertebrate head development is an important issue since craniofacial anomalies constitute nearly one third of all human congenital defects. This review discusses recent advances in our understanding of neural crest cell patterning and the dynamic nature of the tissue interactions that are required for normal craniofacial development.

  1. Stem cells from human exfoliated deciduous tooth exhibit stromal-derived inducing activity and lead to generation of neural crest cells from human embryonic stem cells.

    Science.gov (United States)

    Karbalaie, Khadijeh; Tanhaei, Somayyeh; Rabiei, Farzaneh; Kiani-Esfahani, Abbas; Masoudi, Najmeh Sadat; Nasr-Esfahani, Mohammad Hossein; Baharvand, Hossein

    2015-01-01

    The neural crest is a transient structure of early vertebrate embryos that generates neural crest cells (NCCs). These cells can migrate throughout the body and produce a diverse array of mature tissue types. Due to the ethical and technical problems surrounding the isolation of these early human embryo cells, researchers have focused on in vitro studies to produce NCCs and increase their knowledge of neural crest development. In this experimental study, we cultured human embryonic stem cells (hESCs) on stromal stem cells from human exfoliated deciduous teeth (SHED) for a two-week period. We used different approaches to characterize these differentiated cells as neural precursor cells (NPCs) and NCCs. In the first co-culture week, hESCs appeared as crater-like structures with marginal rosettes. NPCs derived from these structures expressed the early neural crest marker p75 in addition to numerous other genes associated with neural crest induction such as SNAIL, SLUG, PTX3 and SOX9. Flow cytometry analysis showed 70% of the cells were AP2/P75 positive. Moreover, the cells were able to self-renew, sustain multipotent differentiation potential, and readily form neurospheres in suspension culture. SHED, as an adult stem cell with a neural crest origin, has stromal-derived inducing activity (SDIA) and can be used as an NCC inducer from hESCs. These cells provide an invaluable resource to study neural crest differentiation in both normal and disordered human neural crest development.

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

    Science.gov (United States)

    Groysman, Maya; Shoval, Irit; Kalcheim, Chaya

    2008-01-01

    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. PMID:18945340

  3. In vivo transplantation of fetal human gut-derived enteric neural crest cells.

    Science.gov (United States)

    Cooper, J E; Natarajan, D; McCann, C J; Choudhury, S; Godwin, H; Burns, A J; Thapar, N

    2017-01-01

    The prospect of using neural cell replacement for the treatment of severe enteric neuropathies has seen significant progress in the last decade. The ability to harvest and transplant enteric neural crest cells (ENCCs) that functionally integrate within recipient intestine has recently been confirmed by in vivo murine studies. Although similar cells can be harvested from human fetal and postnatal gut, no studies have as yet verified their functional viability upon in vivo transplantation. We sought to determine whether ENCCs harvested from human fetal bowel are capable of engraftment and functional integration within recipient intestine following in vivo transplantation into postnatal murine colon. Enteric neural crest cells selected and harvested from fetal human gut using the neurotrophin receptor p75(NTR) were lentivirally labeled with either GFP or calcium-sensitive GCaMP and transplanted into the hindgut of Rag2(-) /γc(-) /C5(-) -immunodeficient mice at postnatal day 21. Transplanted intestines were assessed immunohistochemically for engraftment and differentiation of donor cells. Functional viability and integration with host neuromusculature was assessed using calcium imaging. Transplanted human fetal gut-derived ENCC showed engraftment within the recipient postnatal colon in 8/15 mice (53.3%). At 4 weeks posttransplantation, donor cells had spread from the site of transplantation and extended projections over distances of 1.2 ± 0.6 mm (n = 5), and differentiated into enteric nervous system (ENS) appropriate neurons and glia. These cells formed branching networks located with the myenteric plexus. Calcium transients (change in intensity F/F0 = 1.25 ± 0.03; 15 cells) were recorded in transplanted cells upon stimulation of the recipient endogenous ENS demonstrating their viability and establishment of functional connections. © 2016 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

  4. Calcium-mediated repression of β-catenin and its transcriptional signaling mediates neural crest cell death in an avian model of fetal alcohol syndrome.

    Science.gov (United States)

    Flentke, George R; Garic, Ana; Amberger, Ed; Hernandez, Marcos; Smith, Susan M

    2011-07-01

    Fetal alcohol syndrome (FAS) is a common birth defect in many societies. Affected individuals have neurodevelopmental disabilities and a distinctive craniofacial dysmorphology. These latter deficits originate during early development from the ethanol-mediated apoptotic depletion of cranial facial progenitors, a population known as the neural crest. We showed previously that this apoptosis is caused because acute ethanol exposure activates G-protein-dependent intracellular calcium within cranial neural crest progenitors, and this calcium transient initiates the cell death. The dysregulated signals that reside downstream of ethanol's calcium transient and effect neural crest death are unknown. Here we show that ethanol's repression of the transcriptional effector β-catenin causes the neural crest losses. Clinically relevant ethanol concentrations (22-78 mM) rapidly deplete nuclear β-catenin from neural crest progenitors, with accompanying losses of β-catenin transcriptional activity and downstream genes that govern neural crest induction, expansion, and survival. Using forced expression studies, we show that β-catenin loss of function (via dominant-negative T cell transcription factor [TCF]) recapitulates ethanol's effects on neural crest apoptosis, whereas β-catenin gain-of-function in ethanol's presence preserves neural crest survival. Blockade of ethanol's calcium transient using Bapta-AM normalizes β-catenin activity and prevents the neural crest losses, whereas ionomycin treatment is sufficient to destabilize β-catenin. We propose that ethanol's repression of β-catenin causes the neural crest losses in this model of FAS. β-Catenin is a novel target for ethanol's teratogenicity. β-Catenin/Wnt signals participate in many developmental events and its rapid and persistent dysregulation by ethanol may explain why the latter is such a potent teratogen. Copyright © 2011 Wiley-Liss, Inc.

  5. The Calcium-Mediated Repression of β-Catenin and Its Transcriptional Signaling Mediates Neural Crest Cell Death in an Avian Model of Fetal Alcohol Syndrome

    Science.gov (United States)

    Flentke, George R.; Garic, Ana; Amberger, Ed; Hernandez, Marcos; Smith, Susan M.

    2016-01-01

    Fetal Alcohol Syndrome (FAS) is a common birth defect in many societies. Affected individuals have neurodevelopmental disabilities and a distinctive craniofacial dysmorphology. These latter deficits originate during early development from the ethanol-mediated apoptotic depletion of cranial facial progenitors, a population known as the neural crest. We showed previously that this apoptosis is caused because acute ethanol exposure activates a G protein-dependent intracellular calcium within cranial neural crest progenitors, and this calcium transient initiates the cell death. The dysregulated signals that reside downstream of ethanol’s calcium transient and effect neural crest death are unknown. Here we show that ethanol’s repression of the transcriptional effector β-catenin causes the neural crest losses. Clinically-relevant ethanol concentrations (22–78 mM) rapidly deplete nuclear β-catenin from neural crest progenitors, with accompanying losses of β-catenin transcriptional activity and downstream genes that govern neural crest induction, expansion and survival. Using forced expression studies we show that β-catenin loss of function (via dominant-negative TCF) recapitulates ethanol’s effects on neural crest apoptosis, whereas β-catenin gain-of-function in ethanol’s presence preserves neural crest survival. Blockade of ethanol’s calcium transient using Bapta-AM normalizes β-catenin activity and prevents the neural crest losses, whereas ionomycin treatment is sufficient to destabilize β-catenin. We propose that ethanol’s repression of β-catenin causes the neural crest losses in this model of FAS. β-Catenin is a novel target for ethanol’s teratogenicity. β-Catenin/Wnt signals participate in many developmental events and its rapid and persistent dysregulation by ethanol may explain why the latter is such a potent teratogen. PMID:21630427

  6. 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

    Summary 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. PMID:24560767

  7. Neural crest-derived cells with stem cell features can be traced back to multiple lineages in the adult skin

    NARCIS (Netherlands)

    C.E. Wong (Christine); S. Paratore (Sabrina); M.T. Dours-Zimmermann (María); T. Rochat (Thierry); T. Pietri (Thomas); U. Suter (Ueli); D. Zimmermann (Dieter); S. Dufour (Sylvie); J.P. Thiery (Joachim); D.N. Meijer (Dies); C. Beermann (Christopher); Y. Barrandon (Yann); L. Sommer (Lukas)

    2006-01-01

    textabstractGiven their accessibility, multipotent skin-derived cells might be useful for future cell replacement therapies. We describe the isolation of multipotent stem cell-like cells from the adult trunk skin of mice and humans that express the neural crest stem cell markers p75 and Sox10 and

  8. CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations.

    Science.gov (United States)

    Okuno, Hironobu; Renault Mihara, Francois; Ohta, Shigeki; Fukuda, Kimiko; Kurosawa, Kenji; Akamatsu, Wado; Sanosaka, Tsukasa; Kohyama, Jun; Hayashi, Kanehiro; Nakajima, Kazunori; Takahashi, Takao; Wysocka, Joanna; Kosaki, Kenjiro; Okano, Hideyuki

    2017-11-28

    CHARGE syndrome is caused by heterozygous mutations in the chromatin remodeler, CHD7, and is characterized by a set of malformations that, on clinical grounds, were historically postulated to arise from defects in neural crest formation during embryogenesis. To better delineate neural crest defects in CHARGE syndrome, we generated induced pluripotent stem cells (iPSCs) from two patients with typical syndrome manifestations, and characterized neural crest cells differentiated in vitro from these iPSCs (iPSC-NCCs). We found that expression of genes associated with cell migration was altered in CHARGE iPSC-NCCs compared to control iPSC-NCCs. Consistently, CHARGE iPSC-NCCs showed defective delamination, migration and motility in vitro, and their transplantation in ovo revealed overall defective migratory activity in the chick embryo. These results support the historical inference that CHARGE syndrome patients exhibit defects in neural crest migration, and provide the first successful application of patient-derived iPSCs in modeling craniofacial disorders.

  9. Cranial muscles in amphibians: development, novelties and the role of cranial neural crest cells

    Science.gov (United States)

    Schmidt, Jennifer; Piekarski, Nadine; Olsson, Lennart

    2013-01-01

    Our research on the evolution of the vertebrate head focuses on understanding the developmental origins of morphological novelties. Using a broad comparative approach in amphibians, and comparisons with the well-studied quail-chicken system, we investigate how evolutionarily conserved or variable different aspects of head development are. Here we review research on the often overlooked development of cranial muscles, and on its dependence on cranial cartilage development. In general, cranial muscle cell migration and the spatiotemporal pattern of cranial muscle formation appears to be very conserved among the few species of vertebrates that have been studied. However, fate-mapping of somites in the Mexican axolotl revealed differences in the specific formation of hypobranchial muscles (tongue muscles) in comparison to the chicken. The proper development of cranial muscles has been shown to be strongly dependent on the mostly neural crest-derived cartilage elements in the larval head of amphibians. For example, a morpholino-based knock-down of the transcription factor FoxN3 in Xenopus laevis has drastic indirect effects on cranial muscle patterning, although the direct function of the gene is mostly connected to neural crest development. Furthermore, extirpation of single migratory streams of cranial neural crest cells in combination with fate-mapping in a frog shows that individual cranial muscles and their neural crest-derived connective tissue attachments originate from the same visceral arch, even when the muscles attach to skeletal components that are derived from a different arch. The same pattern has also been found in the chicken embryo, the only other species that has been thoroughly investigated, and thus might be a conserved pattern in vertebrates that reflects the fundamental nature of a mechanism that keeps the segmental order of the head in place despite drastic changes in adult anatomy. There is a need for detailed comparative fate-mapping of pre

  10. Cranial muscles in amphibians: development, novelties and the role of cranial neural crest cells.

    Science.gov (United States)

    Schmidt, Jennifer; Piekarski, Nadine; Olsson, Lennart

    2013-01-01

    Our research on the evolution of the vertebrate head focuses on understanding the developmental origins of morphological novelties. Using a broad comparative approach in amphibians, and comparisons with the well-studied quail-chicken system, we investigate how evolutionarily conserved or variable different aspects of head development are. Here we review research on the often overlooked development of cranial muscles, and on its dependence on cranial cartilage development. In general, cranial muscle cell migration and the spatiotemporal pattern of cranial muscle formation appears to be very conserved among the few species of vertebrates that have been studied. However, fate-mapping of somites in the Mexican axolotl revealed differences in the specific formation of hypobranchial muscles (tongue muscles) in comparison to the chicken. The proper development of cranial muscles has been shown to be strongly dependent on the mostly neural crest-derived cartilage elements in the larval head of amphibians. For example, a morpholino-based knock-down of the transcription factor FoxN3 in Xenopus laevis has drastic indirect effects on cranial muscle patterning, although the direct function of the gene is mostly connected to neural crest development. Furthermore, extirpation of single migratory streams of cranial neural crest cells in combination with fate-mapping in a frog shows that individual cranial muscles and their neural crest-derived connective tissue attachments originate from the same visceral arch, even when the muscles attach to skeletal components that are derived from a different arch. The same pattern has also been found in the chicken embryo, the only other species that has been thoroughly investigated, and thus might be a conserved pattern in vertebrates that reflects the fundamental nature of a mechanism that keeps the segmental order of the head in place despite drastic changes in adult anatomy. There is a need for detailed comparative fate-mapping of pre

  11. Genomic factors that shape craniofacial outcome and neural crest vulnerability in FASD

    Directory of Open Access Journals (Sweden)

    Susan M. Smith

    2014-08-01

    Full Text Available Prenatal alcohol exposure (PAE causes distinctive facial characteristics in some pregnancies and not others; genetic factors may contribute to this differential vulnerability. Ethanol disrupts multiple events of neural crest development including induction, survival, migration, and differentiation. Animal models and genomic approaches have substantially advanced our understanding of the mechanisms underlying these facial changes. PAE during gastrulation produces craniofacial changes corresponding with human fetal alcohol syndrome. These result because PAE reduces prechordal plate extension and suppresses sonic hedgehog, leading to holoprosencephaly and malpositioned facial primordia. Haploinsufficiency in sonic hedgehog signaling increases vulnerability to facial deficits and may influence some PAE pregnancies. In contrast, PAE during early neurogenesis produces facial hypoplasia, preceded by neural crest reductions due to significant apoptosis. Factors mediating this apoptosis include intracellular calcium mobilization, elevated reactive oxygen species, and loss of trophic support from β-catenin/calcium, sonic hedgehog, and mTOR signaling. Genomewide SNP analysis links PDGF receptor genes with facial outcomes in human PAE. Multiple genomic-level comparisons of ethanol-sensitive and –resistant early embryos, in both mouse and chick, independently identify common candidate genes that may potentially modify craniofacial vulnerability, including ribosomal proteins, proteosome, RNA splicing, and focal adhesion. In summary, research using animal models with genome-level differences in ethanol vulnerability, as well as targeted loss- and gain-of-function mutants, has clarified the mechanisms mediating craniofacial change in PAE. The findings additionally suggest that craniofacial deficits may represent a gene-ethanol interaction for some affected individuals. Genetic-level changes may prime individuals toward greater sensitivity or resistance to

  12. Oxidative stress during diabetic pregnancy disrupts cardiac neural crest migration and causes outflow tract defects.

    Science.gov (United States)

    Morgan, Sarah C; Relaix, Frédéric; Sandell, Lisa L; Loeken, Mary R

    2008-06-01

    Maternal diabetes increases risk for congenital malformations, particularly cardiac outflow tract defects. Maternal diabetes inhibits expression of Pax3 in neuroepithelium through hyperglycemia-induced oxidative stress. The neuroepithelium gives rise to the neural crest, and Pax3 expression in cardiac neural crest (CNC) is required for CNC migration to the heart and for outflow tract septation. Here we tested whether maternal diabetes, through hyperglycemia-induced oxidative stress, before the onset of CNC delamination, impairs CNC migration and cardiac outflow tract septation. CNC migration was mapped in mouse embryos whose mothers were diabetic, or transiently hyperglycemic, or in which oxidative stress was transiently induced, using reporters linked to Pax3 expression. CNC apoptosis was examined by TUNEL assay. Outflow tract septation was examined histologically and by gross inspection. Few, if any, migrating CNC cells were observed in embryos of diabetic mice, and this was associated with increased apoptosis along the path of CNC migration. Outflow tract defects were significantly increased in fetuses of diabetic mice. Notably, induction of hyperglycemia or oxidative stress on the day prior to the onset of Pax3 expression and CNC migration also impaired CNC migration, increased apoptosis, and caused outflow tract defects. However, antioxidants administered on the day prior to the onset of Pax3 expression and CNC migration prevented these effects of hyperglycemia or oxidative stress. In diabetic pregnancy, oxidative stress, which inhibits expression of genes required for CNC viability, causes subsequent CNC depletion by apoptosis during migration, which leads to outflow tract defects. Copyright 2008 Wiley-Liss, Inc.

  13. Impairment of human neural crest cell migration by prolonged exposure to interferon-beta.

    Science.gov (United States)

    Pallocca, Giorgia; Nyffeler, Johanna; Dolde, Xenia; Grinberg, Marianna; Gstraunthaler, Gerhard; Waldmann, Tanja; Rahnenführer, Jörg; Sachinidis, Agapios; Leist, Marcel

    2017-10-01

    Human cell-based toxicological assays have been used successfully to detect known toxicants, and to distinguish them from negative controls. However, there is at present little experience on how to deal with hits from screens of compounds with yet unknown hazard. As a case study to this issue, we characterized human interferon-beta (IFNβ) as potential developmental toxicant affecting neural crest cells (NCC). The protein was identified as a hit during a screen of clinically used drugs in the 'migration inhibition of neural crest' (MINC) assay. Concentration-response studies in the MINC combined with immunocytochemistry and mRNA quantification of cellular markers showed that IFNβ inhibited NCC migration at concentrations as low as 20 pM. The effective concentrations found here correspond to levels found in human plasma, and they were neither cytostatic nor cytotoxic nor did they did they affect the differentiation state and overall phenotype of NCC. Data from two other migration assays confirmed that picomolar concentration of IFNβ reduced the motility of NCC, while other interferons were less potent. The activation of JAK kinase by IFNβ, as suggested by bioinformatics analysis of the transcriptome changes, was confirmed by biochemical methods. The degree and duration of pathway activation correlated with the extent of migration inhibition, and pharmacological block of this signaling pathway before, or up to 6 h after exposure to the cytokine prevented the effects of IFNβ on migration. Thus, the reduction of vital functions of human NCC is a hitherto unknown potential hazard of endogenous or pharmacologically applied interferons.

  14. Phosphorylation of Sox9 is required for neural crest delamination and is regulated downstream of BMP and canonical Wnt signaling.

    Science.gov (United States)

    Liu, Jessica A J; Wu, Ming-Hoi; Yan, Carol H; Chau, Bolton K H; So, Henry; Ng, Alvis; Chan, Alan; Cheah, Kathryn S E; Briscoe, James; Cheung, Martin

    2013-02-19

    Coordination of neural crest cell (NCC) induction and delamination is orchestrated by several transcription factors. Among these, Sry-related HMG box-9 (Sox9) and Snail2 have been implicated in both the induction of NCC identity and, together with phoshorylation, NCC delamination. How phosphorylation effects this function has not been clear. Here we show, in the developing chick neural tube, that phosphorylation of Sox9 on S64 and S181 facilitates its SUMOylation, and the phosphorylated forms of Sox9 are essential for trunk neural crest delamination. Both phosphorylation and to a lesser extent SUMOylation, of Sox9 are required to cooperate with Snail2 to promote delamination. Moreover, bone morphogenetic protein and canonical Wnt signaling induce phosphorylation of Sox9, thereby connecting extracellular signals with the delamination of NCCs. Together the data suggest a model in which extracellular signals initiate phosphorylation of Sox9 and its cooperation with Snail2 to induce NCC delamination.

  15. 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,

  16. 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.

  17. A novel FoxD3 gene trap line reveals neural crest precursor movement and a role for FoxD3 in their specification.

    Science.gov (United States)

    Hochgreb-Hägele, Tatiana; Bronner, Marianne E

    2013-02-01

    Neural crest cells migrate extensively and contribute to diverse derivatives, including the craniofacial skeleton, peripheral neurons and glia, and pigment cells. Although several transgenic lines label neural crest subpopulations, few are suited for studying early events in neural crest development. Here, we present a zebrafish gene/protein trap line gt(foxd3-citrine)(ct110a) that expresses a Citrine fusion protein with FoxD3, a transcription factor expressed in premigratory and migrating neural crest cells. In this novel line, citrine expression exactly parallels endogenous foxd3 expression. High-resolution time-lapse imaging reveals the dynamic phases of precursor and migratory neural crest cell movements from the neural keel stage to times of active cell migration. In addition, Cre-recombination produces a variant line FoxD3-mCherry-pA whose homozygosis generates a FoxD3 mutant. Taking advantage of the endogenously regulated expression of FoxD3-mCherry fusion protein, we directly assess early effects of FoxD3 loss-of-function on specification and morphogenesis of dorsal root ganglia, craniofacial skeleton and melanophores. These novel lines provide new insights and useful new tools for studying specification, migration and differentiation of neural crest cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. [Retinoic acid signal pathway regulation of zebra fish tooth development through manipulation of the differentiation of neural crest].

    Science.gov (United States)

    Liu, Xin; Huang, Xing; Xu, Zhiyun; Yang, Deqin

    2016-04-01

    To investigate the mechanism of retinoic acid (RA) signal in dental evolution, RA is used to explore the influence of the mechanism on neural crest's migration during the early stage of zebra fish embryos. We divided embryos of wild type and transgenic line zebra fish into three groups. 1 x 10(-7) to 6 x 10(-7) mol x L(-1) RA and 1 x 10(-7) mo x L(-1) 4-diethylaminobenzaldehyde (DEAB) were added into egg water at 24 hpf for 9 h. Dimethyl sulfoxid (DMSO) with the concentration was used as control group. Then, antisense probes of dlx2a, dlx2b, and barxl were formulated to perform whole-mount in situ hybridization to check the expressions of the genes in 48 hpf to 72 hpf embryos. We observed fluorescence of transgenic line in 4 dpf embryos. We obtained three mRNA probes successfully. Compared with DMSO control group, a low concentration (1 x 10(-7) mol x L(-1)) of RA could up-regulate the expression of mRNA (barx1, dlx2a) in neural crest. Obvious migration trend was observed toward the pharyngeal arch in which teeth adhered. Transgenic fish had spreading fluorescence tendency in pharyngeal arch. However, a high concentration (4 x 10(-7) mol x L(-1)) of RA malformed the embryos and killed them after treatment. One third of the embryos of middle concentration (3 x 10(-7) mo x L(-1)) exhibited delayed development. DEAB resulted in neural crest dysplasia. The expression of barxl and dlx2a were suppressed, and the appearance of dlx2b in tooth was delayed. RA signal pathway can regulate the progenitors of tooth by controlling the growth of the neural crest and manipulating tooth development

  19. 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.

  20. Sox2 acts as a rheostat of epithelial to mesenchymal transition during neural crest development

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    Nikolaos eMandalos

    2014-09-01

    Full Text Available Precise control of self-renewal and differentiation of progenitor cells into the cranial neural crest (CNC pool ensures proper head development, guided by signaling pathways such as BMPs, FGFs, Shh and Notch. Here, we show that murine Sox2 plays an essential role in controlling progenitor cell behavior during craniofacial development. A Conditional by Inversion Sox2 allele (Sox2COIN has been employed to generate an epiblast ablation of Sox2 function (Sox2EpINV. Sox2EpINV/+(H haploinsufficient and conditional (Sox2EpINV/mosaic mutant embryos proceed beyond gastrulation and die around E11. These mutant embryos exhibit severe anterior malformations, with hydrocephaly and frontonasal truncations, which could be attributed to the deregulation of CNC progenitor cells during their epithelial to mesenchymal transition. This irregularity results in an exacerbated and aberrant migration of Sox10+ NCC in the branchial arches and frontonasal process of the Sox2 mutant embryos. These results suggest a novel role for Sox2 as a regulator of the epithelial to mesenchymal transitions that are important for the cell flow in the developing head.

  1. Prospect of Human Pluripotent Stem Cell-Derived Neural Crest Stem Cells in Clinical Application

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    Qian Zhu

    2016-01-01

    Full Text Available Neural crest stem cells (NCSCs represent a transient and multipotent cell population that contributes to numerous anatomical structures such as peripheral nervous system, teeth, and cornea. NCSC maldevelopment is related to various human diseases including pigmentation abnormalities, disorders affecting autonomic nervous system, and malformations of teeth, eyes, and hearts. As human pluripotent stem cells including human embryonic stem cells (hESCs and human induced pluripotent stem cells (hiPSCs can serve as an unlimited cell source to generate NCSCs, hESC/hiPSC-derived NCSCs can be a valuable tool to study the underlying mechanisms of NCSC-associated diseases, which paves the way for future therapies for these abnormalities. In addition, hESC/hiPSC-derived NCSCs with the capability of differentiating to various cell types are highly promising for clinical organ repair and regeneration. In this review, we first discuss NCSC generation methods from human pluripotent stem cells and differentiation mechanism of NCSCs. Then we focus on the clinical application potential of hESC/hiPSC-derived NCSCs on peripheral nerve injuries, corneal blindness, tooth regeneration, pathological melanogenesis, Hirschsprung disease, and cardiac repair and regeneration.

  2. SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis

    Science.gov (United States)

    Li, Jingyuan; Huang, Xiaofeng; Xu, Xun; Mayo, Julie; Bringas, Pablo; Jiang, Rulang; Wang, Songling; Chai, Yang

    2011-01-01

    TGFβ/BMP signaling regulates the fate of multipotential cranial neural crest (CNC) cells during tooth and jawbone formation as these cells differentiate into odontoblasts and osteoblasts, respectively. The functional significance of SMAD4, the common mediator of TGFβ/BMP signaling, in regulating the fate of CNC cells remains unclear. In this study, we investigated the mechanism of SMAD4 in regulating the fate of CNC-derived dental mesenchymal cells through tissue-specific inactivation of Smad4. Ablation of Smad4 results in defects in odontoblast differentiation and dentin formation. Moreover, ectopic bone-like structures replaced normal dentin in the teeth of Osr2-IresCre;Smad4fl/fl mice. Despite the lack of dentin, enamel formation appeared unaffected in Osr2-IresCre;Smad4fl/fl mice, challenging the paradigm that the initiation of enamel development depends on normal dentin formation. At the molecular level, loss of Smad4 results in downregulation of the WNT pathway inhibitors Dkk1 and Sfrp1 and in the upregulation of canonical WNT signaling, including increased β-catenin activity. More importantly, inhibition of the upregulated canonical WNT pathway in Osr2-IresCre;Smad4fl/fl dental mesenchyme in vitro partially rescued the CNC cell fate change. Taken together, our study demonstrates that SMAD4 plays a crucial role in regulating the interplay between TGFβ/BMP and WNT signaling to ensure the proper CNC cell fate decision during organogenesis. PMID:21490069

  3. Alcohol exposure induces chick craniofacial bone defects by negatively affecting cranial neural crest development.

    Science.gov (United States)

    Zhang, Ping; Wang, Guang; Lin, Zhuangling; Wu, Yushi; Zhang, Jing; Liu, Meng; Lee, Kenneth Ka Ho; Chuai, Manli; Yang, Xuesong

    2017-11-05

    Excess alcohol consumption during pregnancy could lead to fetal alcohol syndrome (FAS). However, the molecular mechanism leading to craniofacial abnormality, a feature of FAS, is still poorly understood. The cranial neural crest cells (NCCs) contribute to the formation of the craniofacial bones. Therefore, NCCs exposed to ethanol was investigated - using chick embryos and in vitro explant culture as experimental models. We demonstrated that exposure to 2% ethanol induced craniofacial defects, which includes parietal defect, in the developing chick fetus. Immunofluorescent staining revealed that ethanol treatment downregulated Ap-2ɑ, Pax7 and HNK-1 expressions by cranial NCCs. Using double-immunofluorescent stainings for Ap-2ɑ/pHIS3 and Ap-2ɑ/c-Caspase3, we showed that ethanol treatment inhibited cranial NCC proliferation and increased NCC apoptosis, respectively. Moreover, ethanol treatment of the dorsal neuroepithelium increased Laminin, N-Cadherin and Cadherin 6B expressions while Cadherin 7 expression was repressed. In situ hybridization also revealed that ethanol treatment up-regulated Cadherin 6B expression but down-regulated slug, Msx1, FoxD3 and BMP4 expressions. In summary, our experimental results demonstrated that ethanol treatment interferes with the production of cranial NCCs by affecting the proliferation and apoptosis of these cells. In addition, ethanol affected the delamination, epithelial-mesenchymal transition (EMT) and cell migration of cranial NCCs, which may have contributed to the etiology of the craniofacial defects. Copyright © 2017. Published by Elsevier B.V.

  4. The "domestication syndrome" in mammals: a unified explanation based on neural crest cell behavior and genetics.

    Science.gov (United States)

    Wilkins, Adam S; Wrangham, Richard W; Fitch, W Tecumseh

    2014-07-01

    Charles Darwin, while trying to devise a general theory of heredity from the observations of animal and plant breeders, discovered that domesticated mammals possess a distinctive and unusual suite of heritable traits not seen in their wild progenitors. Some of these traits also appear in domesticated birds and fish. The origin of Darwin's "domestication syndrome" has remained a conundrum for more than 140 years. Most explanations focus on particular traits, while neglecting others, or on the possible selective factors involved in domestication rather than the underlying developmental and genetic causes of these traits. Here, we propose that the domestication syndrome results predominantly from mild neural crest cell deficits during embryonic development. Most of the modified traits, both morphological and physiological, can be readily explained as direct consequences of such deficiencies, while other traits are explicable as indirect consequences. We first show how the hypothesis can account for the multiple, apparently unrelated traits of the syndrome and then explore its genetic dimensions and predictions, reviewing the available genetic evidence. The article concludes with a brief discussion of some genetic and developmental questions raised by the idea, along with specific predictions and experimental tests. Copyright © 2014 by the Genetics Society of America.

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

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    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.

  6. Regulators of gene expression in Enteric Neural Crest Cells are putative Hirschsprung disease genes.

    Science.gov (United States)

    Schriemer, Duco; Sribudiani, Yunia; IJpma, Arne; Natarajan, Dipa; MacKenzie, Katherine C; Metzger, Marco; Binder, Ellen; Burns, Alan J; Thapar, Nikhil; Hofstra, Robert M W; Eggen, Bart J L

    2016-08-01

    The enteric nervous system (ENS) is required for peristalsis of the gut and is derived from Enteric Neural Crest Cells (ENCCs). During ENS development, the RET receptor tyrosine kinase plays a critical role in the proliferation and survival of ENCCs, their migration along the developing gut, and differentiation into enteric neurons. Mutations in RET and its ligand GDNF cause Hirschsprung disease (HSCR), a complex genetic disorder in which ENCCs fail to colonize variable lengths of the distal bowel. To identify key regulators of ENCCs and the pathways underlying RET signaling, gene expression profiles of untreated and GDNF-treated ENCCs from E14.5 mouse embryos were generated. ENCCs express genes that are involved in both early and late neuronal development, whereas GDNF treatment induced neuronal maturation. Predicted regulators of gene expression in ENCCs include the known HSCR genes Ret and Sox10, as well as Bdnf, App and Mapk10. The regulatory overlap and functional interactions between these genes were used to construct a regulatory network that is underlying ENS development and connects to known HSCR genes. In addition, the adenosine receptor A2a (Adora2a) and neuropeptide Y receptor Y2 (Npy2r) were identified as possible regulators of terminal neuronal differentiation in GDNF-treated ENCCs. The human orthologue of Npy2r maps to the HSCR susceptibility locus 4q31.3-q32.3, suggesting a role for NPY2R both in ENS development and in HSCR. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. SiNC: Saliency-injected neural codes for representation and efficient retrieval of medical radiographs.

    Science.gov (United States)

    Ahmad, Jamil; Sajjad, Muhammad; Mehmood, Irfan; Baik, Sung Wook

    2017-01-01

    Medical image collections contain a wealth of information which can assist radiologists and medical experts in diagnosis and disease detection for making well-informed decisions. However, this objective can only be realized if efficient access is provided to semantically relevant cases from the ever-growing medical image repositories. In this paper, we present an efficient method for representing medical images by incorporating visual saliency and deep features obtained from a fine-tuned convolutional neural network (CNN) pre-trained on natural images. Saliency detector is employed to automatically identify regions of interest like tumors, fractures, and calcified spots in images prior to feature extraction. Neuronal activation features termed as neural codes from different CNN layers are comprehensively studied to identify most appropriate features for representing radiographs. This study revealed that neural codes from the last fully connected layer of the fine-tuned CNN are found to be the most suitable for representing medical images. The neural codes extracted from the entire image and salient part of the image are fused to obtain the saliency-injected neural codes (SiNC) descriptor which is used for indexing and retrieval. Finally, locality sensitive hashing techniques are applied on the SiNC descriptor to acquire short binary codes for allowing efficient retrieval in large scale image collections. Comprehensive experimental evaluations on the radiology images dataset reveal that the proposed framework achieves high retrieval accuracy and efficiency for scalable image retrieval applications and compares favorably with existing approaches.

  8. SiNC: Saliency-injected neural codes for representation and efficient retrieval of medical radiographs.

    Directory of Open Access Journals (Sweden)

    Jamil Ahmad

    Full Text Available Medical image collections contain a wealth of information which can assist radiologists and medical experts in diagnosis and disease detection for making well-informed decisions. However, this objective can only be realized if efficient access is provided to semantically relevant cases from the ever-growing medical image repositories. In this paper, we present an efficient method for representing medical images by incorporating visual saliency and deep features obtained from a fine-tuned convolutional neural network (CNN pre-trained on natural images. Saliency detector is employed to automatically identify regions of interest like tumors, fractures, and calcified spots in images prior to feature extraction. Neuronal activation features termed as neural codes from different CNN layers are comprehensively studied to identify most appropriate features for representing radiographs. This study revealed that neural codes from the last fully connected layer of the fine-tuned CNN are found to be the most suitable for representing medical images. The neural codes extracted from the entire image and salient part of the image are fused to obtain the saliency-injected neural codes (SiNC descriptor which is used for indexing and retrieval. Finally, locality sensitive hashing techniques are applied on the SiNC descriptor to acquire short binary codes for allowing efficient retrieval in large scale image collections. Comprehensive experimental evaluations on the radiology images dataset reveal that the proposed framework achieves high retrieval accuracy and efficiency for scalable image retrieval applications and compares favorably with existing approaches.

  9. Cranial neural crest contributes to the bony skull vault in adult Xenopus laevis: insights from cell labeling studies.

    Science.gov (United States)

    Gross, Joshua B; Hanken, James

    2005-03-15

    As a step toward resolving the developmental origin of the ossified skull in adult anurans, we performed a series of cell labeling and grafting studies of the cranial neural crest (CNC) in the clawed frog, Xenopus laevis. We employ an indelible, fixative-stable fluorescent dextran as a cell marker to follow migration of the three embryonic streams of cranial neural crest and to directly assess their contributions to the bony skull vault, which forms weeks after hatching. The three streams maintain distinct boundaries in the developing embryo. Their cells proliferate widely through subsequent larval (tadpole) development, albeit in regionally distinct portions of the head. At metamorphosis, each stream contributes to the large frontoparietal bone, which is the primary constituent of the skull vault in adult anurans. The streams give rise to regionally distinct portions of the bone, thereby preserving their earlier relative position anteroposteriorly within the embryonic neural ridge. These data, when combined with comparable experimental observations from other model species, provide insights into the ancestral pattern of cranial development in tetrapod vertebrates as well as the origin of differences reported between birds and mammals. Copyright 2005 Wiley-Liss, Inc.

  10. Epigenetic marks define the lineage and differentiation potential of two distinct neural crest-derived intermediate odontogenic progenitor populations.

    Science.gov (United States)

    Gopinathan, Gokul; Kolokythas, Antonia; Luan, Xianghong; Diekwisch, Thomas G H

    2013-06-15

    Epigenetic mechanisms, such as histone modifications, play an active role in the differentiation and lineage commitment of mesenchymal stem cells. In the present study, epigenetic states and differentiation profiles of two odontogenic neural crest-derived intermediate progenitor populations were compared: dental pulp (DP) and dental follicle (DF). ChIP on chip assays revealed substantial H3K27me3-mediated repression of odontoblast lineage genes DSPP and dentin matrix protein 1 (DMP1) in DF cells, but not in DP cells. Mineralization inductive conditions caused steep increases of mineralization and patterning gene expression levels in DP cells when compared to DF cells. In contrast, mineralization induction resulted in a highly dynamic histone modification response in DF cells, while there was only a subdued effect in DP cells. Both DF and DP progenitors featured H3K4me3-active marks on the promoters of early mineralization genes RUNX2, MSX2, and DLX5, while OSX, IBSP, and BGLAP promoters were enriched for H3K9me3 or H3K27me3. Compared to DF cells, DP cells expressed higher levels of three pluripotency-associated genes, OCT4, NANOG, and SOX2. Finally, gene ontology comparison of bivalent marks unique for DP and DF cells highlighted cell-cell attachment genes in DP cells and neurogenesis genes in DF cells. In conclusion, the present study indicates that the DF intermediate odontogenic neural crest lineage is distinguished from its DP counterpart by epigenetic repression of DSPP and DMP1 genes and through dynamic histone enrichment responses to mineralization induction. Findings presented here highlight the crucial role of epigenetic regulatory mechanisms in the terminal differentiation of odontogenic neural crest lineages.

  11. Conditional beta1-integrin gene deletion in neural crest cells causes severe developmental alterations of the peripheral nervous system

    DEFF Research Database (Denmark)

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

    2004-01-01

    Integrins are transmembrane receptors that are known to interact with the extracellular matrix and to be required for migration, proliferation, differentiation and apoptosis. We have generated mice with a neural crest cell-specific deletion of the beta1-integrin gene to analyse the role of beta1-....... There was an almost complete absence of Schwann cells and sensory axon segregation and defective maturation in neuromuscular synaptogenesis. Thus, beta1-integrins are important for the control of embryonic and postnatal peripheral nervous system development....

  12. Canonical Wnt/β-catenin signaling is required for maintenance but not activation of Pitx2 expression in neural crest during eye development.

    Science.gov (United States)

    Zacharias, Amanda L; Gage, Philip J

    2010-12-01

    Pitx2 is a paired-like homeodomain gene that acts as a key regulator of eye development. Despite its significance, upstream regulation of Pitx2 expression during eye development remains incompletely understood. We use neural crest-specific ablation of Ctnnb1 to demonstrate that canonical Wnt signaling is not required for initial activation of Pitx2 in neural crest. However, canonical Wnt signaling is subsequently required to maintain Pitx2 expression in the neural crest. Eye development in Ctnnb1-null mice appears grossly normal early but significant phenotypes emerge following loss of Pitx2 expression. LEF-1 and β-catenin bind Pitx2 promoter sequences in ocular neural crest, indicating a likely direct effect of canonical Wnt signaling on Pitx2 expression. Combining our data with previous reports, we propose a model wherein a sequential code of retinoic acid followed by canonical Wnt signaling are required for activation and maintenance of Pitx2 expression, respectively. Other key transcription factors in the neural crest, including Foxc1, do not require intact canonical Wnt signaling. Copyright © 2010 Wiley-Liss, Inc.

  13. 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.

  14. 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.

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

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    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.

  16. Deletion of integrin-linked kinase from neural crest cells in mice results in aortic aneurysms and embryonic lethality

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    Thomas D. Arnold

    2013-09-01

    Neural crest cells (NCCs participate in the remodeling of the cardiac outflow tract and pharyngeal arch arteries during cardiovascular development. Integrin-linked kinase (ILK is a serine/threonine kinase and a major regulator of integrin signaling. It links integrins to the actin cytoskeleton and recruits other adaptor molecules into a large complex to regulate actin dynamics and integrin function. Using the Cre-lox system, we deleted Ilk from NCCs of mice to investigate its role in NCC morphogenesis. The resulting mutants developed a severe aneurysmal arterial trunk that resulted in embryonic lethality during late gestation. Ilk mutants showed normal cardiac NCC migration but reduced differentiation into smooth muscle within the aortic arch arteries and the outflow tract. Within the conotruncal cushions, Ilk-deficient NCCs exhibited disorganization of F-actin stress fibers and a significantly rounder morphology, with shorter cellular projections. Additionally, absence of ILK resulted in reduced in vivo phosphorylation of Smad3 in NCCs, which correlated with reduced αSMA levels. Our findings resemble those seen in Pinch1 and β1 integrin conditional mutant mice, and therefore support that, in neural crest-derived cells, ILK and Pinch1 act as cytoplasmic effectors of β1 integrin in a pathway that protects against aneurysms. In addition, our conditional Ilk mutant mice might prove useful as a model to study aortic aneurysms caused by reduced Smad3 signaling, as occurs in the newly described aneurysms-osteoarthritis syndrome, for example.

  17. The taming of the neural crest: a developmental perspective on the origins of morphological covariation in domesticated mammals.

    Science.gov (United States)

    Sánchez-Villagra, Marcelo R; Geiger, Madeleine; Schneider, Richard A

    2016-06-01

    Studies on domestication are blooming, but the developmental bases for the generation of domestication traits and breed diversity remain largely unexplored. Some phenotypic patterns of human neurocristopathies are suggestive of those reported for domesticated mammals and disrupting neural crest developmental programmes have been argued to be the source of traits deemed the 'domestication syndrome'. These character changes span multiple organ systems and morphological structures. But an in-depth examination within the phylogenetic framework of mammals including domesticated forms reveals that the distribution of such traits is not universal, with canids being the only group showing a large set of predicted features. Modularity of traits tied to phylogeny characterizes domesticated mammals: through selective breeding, individual behavioural and morphological traits can be reordered, truncated, augmented or deleted. Similarly, mammalian evolution on islands has resulted in suites of phenotypic changes like those of some domesticated forms. Many domesticated mammals can serve as valuable models for conducting comparative studies on the evolutionary developmental biology of the neural crest, given that series of their embryos are readily available and that their phylogenetic histories and genomes are well characterized.

  18. SPECC1L deficiency results in increased adherens junction stability and reduced cranial neural crest cell delamination.

    Science.gov (United States)

    Wilson, Nathan R; Olm-Shipman, Adam J; Acevedo, Diana S; Palaniyandi, Kanagaraj; Hall, Everett G; Kosa, Edina; Stumpff, Kelly M; Smith, Guerin J; Pitstick, Lenore; Liao, Eric C; Bjork, Bryan C; Czirok, Andras; Saadi, Irfan

    2016-01-20

    Cranial neural crest cells (CNCCs) delaminate from embryonic neural folds and migrate to pharyngeal arches, which give rise to most mid-facial structures. CNCC dysfunction plays a prominent role in the etiology of orofacial clefts, a frequent birth malformation. Heterozygous mutations in SPECC1L have been identified in patients with atypical and syndromic clefts. Here, we report that in SPECC1L-knockdown cultured cells, staining of canonical adherens junction (AJ) components, β-catenin and E-cadherin, was increased, and electron micrographs revealed an apico-basal diffusion of AJs. To understand the role of SPECC1L in craniofacial morphogenesis, we generated a mouse model of Specc1l deficiency. Homozygous mutants were embryonic lethal and showed impaired neural tube closure and CNCC delamination. Staining of AJ proteins was increased in the mutant neural folds. This AJ defect is consistent with impaired CNCC delamination, which requires AJ dissolution. Further, PI3K-AKT signaling was reduced and apoptosis was increased in Specc1l mutants. In vitro, moderate inhibition of PI3K-AKT signaling in wildtype cells was sufficient to cause AJ alterations. Importantly, AJ changes induced by SPECC1L-knockdown were rescued by activating the PI3K-AKT pathway. Together, these data indicate SPECC1L as a novel modulator of PI3K-AKT signaling and AJ biology, required for neural tube closure and CNCC delamination.

  19. 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 (S...

  20. Pdgfrα functions in endothelial-derived cells to regulate neural crest cells and the development of the great arteries.

    Science.gov (United States)

    Aghajanian, Haig; Cho, Young Kuk; Rizer, Nicholas W; Wang, Qiaohong; Li, Li; Degenhardt, Karl; Jain, Rajan

    2017-09-01

    Originating as a single vessel emerging from the embryonic heart, the truncus arteriosus must septate and remodel into the aorta and pulmonary artery to support postnatal life. Defective remodeling or septation leads to abnormalities collectively known as conotruncal defects, which are associated with significant mortality and morbidity. Multiple populations of cells must interact to coordinate outflow tract remodeling, and the cardiac neural crest has emerged as particularly important during this process. Abnormalities in the cardiac neural crest have been implicated in the pathogenesis of multiple conotruncal defects, including persistent truncus arteriosus, double outlet right ventricle and tetralogy of Fallot. However, the role of the neural crest in the pathogenesis of another conotruncal abnormality, transposition of the great arteries, is less well understood. In this report, we demonstrate an unexpected role of Pdgfra in endothelial cells and their derivatives during outflow tract development. Loss of Pdgfra in endothelium and endothelial-derived cells results in double outlet right ventricle and transposition of the great arteries. Our data suggest that loss of Pdgfra in endothelial-derived mesenchyme in the outflow tract endocardial cushions leads to a secondary defect in neural crest migration during development. © 2017. Published by The Company of Biologists Ltd.

  1. 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...

  2. Exploring the developmental mechanisms underlying Wolf-Hirschhorn Syndrome: Evidence for defects in neural crest cell migration.

    Science.gov (United States)

    Rutherford, Erin L; Lowery, Laura Anne

    2016-12-01

    Wolf-Hirschhorn Syndrome (WHS) is a neurodevelopmental disorder characterized by mental retardation, craniofacial malformation, and defects in skeletal and heart development. The syndrome is associated with irregularities on the short arm of chromosome 4, including deletions of varying sizes and microduplications. Many of these genotypic aberrations in humans have been correlated with the classic WHS phenotype, and animal models have provided a context for mapping these genetic irregularities to specific phenotypes; however, there remains a significant knowledge gap concerning the cell biological mechanisms underlying these phenotypes. This review summarizes literature that has made recent contributions to this topic, drawing from the vast body of knowledge detailing the genetic particularities of the disorder and the more limited pool of information on its cell biology. Finally, we propose a novel characterization for WHS as a pathophysiology owing in part to defects in neural crest cell motility and migration during development. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

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    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.

  4. Melanoma Spheroids Grown Under Neural Crest Cell Conditions Are Highly Plastic Migratory/Invasive Tumor Cells Endowed with Immunomodulator Function

    Science.gov (United States)

    Lalou, Claude; Lauden, Laura; Michel, Laurence; de la Grange, Pierre; Khatib, Abdel-Majid; Aoudjit, Fawzi; Charron, Dominique; Alcaide-Loridan, Catherine; Al-Daccak, Reem

    2011-01-01

    Background The aggressiveness of melanoma tumors is likely to rely on their well-recognized heterogeneity and plasticity. Melanoma comprises multi-subpopulations of cancer cells some of which may possess stem cell-like properties. Although useful, the sphere-formation assay to identify stem cell-like or tumor initiating cell subpopulations in melanoma has been challenged, and it is unclear if this model can predict a functional phenotype associated with aggressive tumor cells. Methodology/Principal Findings We analyzed the molecular and functional phenotypes of melanoma spheroids formed in neural crest cell medium. Whether from metastatic or advanced primary tumors, spheroid cells expressed melanoma-associated markers. They displayed higher capacity to differentiate along mesenchymal lineages and enhanced expression of SOX2, NANOG, KLF4, and/or OCT4 transcription factors, but not enhanced self-renewal or tumorigenicity when compared to their adherent counterparts. Gene expression profiling attributed a neural crest cell signature to these spheroids and indicated that a migratory/invasive and immune-function modulating program could be associated with these cells. In vitro assays confirmed that spheroids display enhanced migratory/invasive capacities. In immune activation assays, spheroid cells elicited a poorer allogenic response from immune cells and inhibited mitogen-dependent T cells activation and proliferation more efficiently than their adherent counterparts. Our findings reveal a novel immune-modulator function of melanoma spheroids and suggest specific roles for spheroids in invasion and in evasion of antitumor immunity. Conclusion/Significance The association of a more plastic, invasive and evasive, thus a more aggressive tumor phenotype with melanoma spheroids reveals a previously unrecognized aspect of tumor cells expanded as spheroid cultures. While of limited efficiency for melanoma initiating cell identification, our melanoma spheroid model predicted

  5. LNGFR(+)THY-1(+) human pluripotent stem cell-derived neural crest-like cells have the potential to develop into mesenchymal stem cells.

    Science.gov (United States)

    Ouchi, Takehito; Morikawa, Satoru; Shibata, Shinsuke; Fukuda, Kimiko; Okuno, Hironobu; Fujimura, Takumi; Kuroda, Tatsuo; Ohyama, Manabu; Akamatsu, Wado; Nakagawa, Taneaki; Okano, Hideyuki

    2016-12-01

    Mesenchymal stem cells (MSCs) are defined as non-hematopoietic, plastic-adherent, self-renewing cells that are capable of tri-lineage differentiation into bone, cartilage or fat in vitro. Thus, MSCs are promising candidates for cell-based medicine. However, classifications of MSCs have been defined retrospectively; moreover, this conventional criterion may be inaccurate due to contamination with other hematopoietic lineage cells. Human MSCs can be enriched by selection for LNGFR and THY-1, and this population may be analogous to murine PDGFRα(+)Sca-1(+) cells, which are developmentally derived from neural crest cells (NCCs). Murine NCCs were labeled by fluorescence, which provided definitive proof of neural crest lineage, however, technical considerations prevent the use of a similar approach to determine the origin of human LNGFR(+)THY-1(+) MSCs. To further clarify the origin of human MSCs, human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs) were used in this study. Under culture conditions required for the induction of neural crest cells, human ESCs and iPSCs-derived cells highly expressed LNGFR and THY-1. These LNGFR(+)THY-1(+) neural crest-like cells, designated as LT-NCLCs, showed a strong potential to differentiate into both mesenchymal and neural crest lineages. LT-NCLCs proliferated to form colonies and actively migrated in response to serum concentration. Furthermore, we transplanted LT-NCLCs into chick embryos, and traced their potential for survival, migration and differentiation in the host environment. These results suggest that LNGFR(+)THY-1(+) cells identified following NCLC induction from ESCs/iPSCs shared similar potentials with multipotent MSCs. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

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

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    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.

  7. 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.

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

    NARCIS (Netherlands)

    Boot, M.J.; Steegers-Theunissen, R.P.M.; Poelmann, R.E.; Iperen, L. van; Lindemans, J.; Groot, A. de

    2003-01-01

    The beneficial effect of additional folic acid in the periconceptional period to prevent neural tube defects, orofacial clefts, and conotruncal heart defects in the offspring has been shown. Folate shortage results in homocysteine accumulation. Elevated levels of homocysteine have been related to

  9. 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.

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

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    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.

  11. Sonic hedgehog regulation of Foxf2 promotes cranial neural crest mesenchyme proliferation and is disrupted in cleft lip morphogenesis.

    Science.gov (United States)

    Everson, Joshua L; Fink, Dustin M; Yoon, Joon Won; Leslie, Elizabeth J; Kietzman, Henry W; Ansen-Wilson, Lydia J; Chung, Hannah M; Walterhouse, David O; Marazita, Mary L; Lipinski, Robert J

    2017-06-01

    Cleft lip is one of the most common human birth defects, yet our understanding of the mechanisms that regulate lip morphogenesis is limited. Here, we show in mice that sonic hedgehog (Shh)-induced proliferation of cranial neural crest cell (cNCC) mesenchyme is required for upper lip closure. Gene expression profiling revealed a subset of Forkhead box (Fox) genes that are regulated by Shh signaling during lip morphogenesis. During cleft pathogenesis, reduced proliferation in the medial nasal process mesenchyme paralleled the domain of reduced Foxf2 and Gli1 expression. SHH ligand induction of Foxf2 expression was dependent upon Shh pathway effectors in cNCCs, while a functional GLI-binding site was identified downstream of Foxf2 Consistent with the cellular mechanism demonstrated for cleft lip pathogenesis, we found that either SHH ligand addition or FOXF2 overexpression is sufficient to induce cNCC proliferation. Finally, analysis of a large multi-ethnic human population with cleft lip identified clusters of single-nucleotide polymorphisms in FOXF2 These data suggest that direct targeting of Foxf2 by Shh signaling drives cNCC mesenchyme proliferation during upper lip morphogenesis, and that disruption of this sequence results in cleft lip. © 2017. Published by The Company of Biologists Ltd.

  12. The Dlx5-FGF10 signaling cascade controls cranial neural crest and myoblast interaction during oropharyngeal patterning and development.

    Science.gov (United States)

    Sugii, Hideki; Grimaldi, Alexandre; Li, Jingyuan; Parada, Carolina; Vu-Ho, Thach; Feng, Jifan; Jing, Junjun; Yuan, Yuan; Guo, Yuxing; Maeda, Hidefumi; Chai, Yang

    2017-11-01

    Craniofacial development depends on cell-cell interactions, coordinated cellular movement and differentiation under the control of regulatory gene networks, which include the distal-less (Dlx) gene family. However, the functional significance of Dlx5 in patterning the oropharyngeal region has remained unknown. Here, we show that loss of Dlx5 leads to a shortened soft palate and an absence of the levator veli palatini, palatopharyngeus and palatoglossus muscles that are derived from the 4th pharyngeal arch (PA); however, the tensor veli palatini, derived from the 1st PA, is unaffected. Dlx5-positive cranial neural crest (CNC) cells are in direct contact with myoblasts derived from the pharyngeal mesoderm, and Dlx5 disruption leads to altered proliferation and apoptosis of CNC and muscle progenitor cells. Moreover, the FGF10 pathway is downregulated in Dlx5-/- mice, and activation of FGF10 signaling rescues CNC cell proliferation and myogenic differentiation in these mutant mice. Collectively, our results indicate that Dlx5 plays crucial roles in the patterning of the oropharyngeal region and development of muscles derived from the 4th PA mesoderm in the soft palate, likely via interactions between CNC-derived and myogenic progenitor cells. © 2017. Published by The Company of Biologists Ltd.

  13. Noncanonical transforming growth factor β (TGFβ) signaling in cranial neural crest cells causes tongue muscle developmental defects.

    Science.gov (United States)

    Iwata, Jun-ichi; Suzuki, Akiko; Pelikan, Richard C; Ho, Thach-Vu; Chai, Yang

    2013-10-11

    Microglossia is a congenital birth defect in humans and adversely impacts quality of life. In vertebrates, tongue muscle derives from the cranial mesoderm, whereas tendons and connective tissues in the craniofacial region originate from cranial neural crest (CNC) cells. Loss of transforming growth factor β (TGFβ) type II receptor in CNC cells in mice (Tgfbr2(fl/fl);Wnt1-Cre) causes microglossia due to a failure of cell-cell communication between cranial mesoderm and CNC cells during tongue development. However, it is still unclear how TGFβ signaling in CNC cells regulates the fate of mesoderm-derived myoblasts during tongue development. Here we show that activation of the cytoplasmic and nuclear tyrosine kinase 1 (ABL1) cascade in Tgfbr2(fl/fl);Wnt1-Cre mice results in a failure of CNC-derived cell differentiation followed by a disruption of TGFβ-mediated induction of growth factors and reduction of myogenic cell proliferation and differentiation activities. Among the affected growth factors, the addition of fibroblast growth factor 4 (FGF4) and neutralizing antibody for follistatin (FST; an antagonist of bone morphogenetic protein (BMP)) could most efficiently restore cell proliferation, differentiation, and organization of muscle cells in the tongue of Tgfbr2(fl/fl);Wnt1-Cre mice. Thus, our data indicate that CNC-derived fibroblasts regulate the fate of mesoderm-derived myoblasts through TGFβ-mediated regulation of FGF and BMP signaling during tongue development.

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

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    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.

  15. Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats.

    Science.gov (United States)

    Müller, Janine; Ossig, Christiana; Greiner, Johannes F W; Hauser, Stefan; Fauser, Mareike; Widera, Darius; Kaltschmidt, Christian; Storch, Alexander; Kaltschmidt, Barbara

    2015-01-01

    Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model. ©AlphaMed Press.

  16. A case of rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor: ROHHADNET syndrome.

    Science.gov (United States)

    Abaci, Ayhan; Catli, Gonul; Bayram, Erhan; Koroglu, Tolga; Olgun, Hatice Nur; Mutafoglu, Kamer; Hiz, Ayse Semra; Cakmakci, Handan; Bober, Ece

    2013-01-01

    Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare disorder that mimics both common obesity and genetic obesity syndromes along with several endocrine disorders during early childhood. We aim to present the clinical features, laboratory and imaging results, and treatment outcomes of a patient with ROHHAD syndrome. In this case report, we describe a 26-month-old boy who was admitted to our emergency department with dyspnea and cyanosis and was suspected to have ROHHAD syndrome due to his rapid-onset obesity and alveolar hypoventilation. A thoracal and abdominal magnetic resonance imaging was performed to demonstrate a possible accompanying neural crest tumor and it provided a yet asymptomatic retroperitoneal ganglioneuroblastoma. Based on these findings, the patient was diagnosed as ROHHADNET syndrome. Because of the high prevalence of cardiorespiratory arrest and probability of accompanying tumors, early recognition of ROHHAD syndrome is important. To prevent presumptive mortality and morbidity, ROHHAD syndrome should be considered in all cases of rapid and early-onset obesity associated with hypothalamic-pituitary endocrine dysfunctions.

  17. Histone deacetylase-4 is required during early cranial neural crest development for generation of the zebrafish palatal skeleton

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    DeLaurier April

    2012-06-01

    Full Text Available Abstract Background Histone deacetylase-4 (Hdac4 is a class II histone deacetylase that inhibits the activity of transcription factors. In humans, HDAC4 deficiency is associated with non-syndromic oral clefts and brachydactyly mental retardation syndrome (BDMR with craniofacial abnormalities. Results We identify hdac4 in zebrafish and characterize its function in craniofacial morphogenesis. The gene is present as a single copy, and the deduced Hdac4 protein sequence shares all known functional domains with human HDAC4. The zebrafish hdac4 transcript is widely present in migratory cranial neural crest (CNC cells of the embryo, including populations migrating around the eye, which previously have been shown to contribute to the formation of the palatal skeleton of the early larva. Embryos injected with hdac4 morpholinos (MO have reduced or absent CNC populations that normally migrate medial to the eye. CNC-derived palatal precursor cells do not recover at the post-migratory stage, and subsequently we found that defects in the developing cartilaginous palatal skeleton correlate with reduction or absence of early CNC cells. Palatal skeletal defects prominently include a shortened, clefted, or missing ethmoid plate, and are associated with a shortening of the face of young larvae. Conclusions Our results demonstrate that Hdac4 is a regulator of CNC-derived palatal skeletal precursors during early embryogenesis. Cleft palate resulting from HDAC4 mutations in human patients may result from defects in a homologous CNC progenitor cell population.

  18. The “Domestication Syndrome” in Mammals: A Unified Explanation Based on Neural Crest Cell Behavior and Genetics

    Science.gov (United States)

    Wilkins, Adam S.; Wrangham, Richard W.; Fitch, W. Tecumseh

    2014-01-01

    Charles Darwin, while trying to devise a general theory of heredity from the observations of animal and plant breeders, discovered that domesticated mammals possess a distinctive and unusual suite of heritable traits not seen in their wild progenitors. Some of these traits also appear in domesticated birds and fish. The origin of Darwin’s “domestication syndrome” has remained a conundrum for more than 140 years. Most explanations focus on particular traits, while neglecting others, or on the possible selective factors involved in domestication rather than the underlying developmental and genetic causes of these traits. Here, we propose that the domestication syndrome results predominantly from mild neural crest cell deficits during embryonic development. Most of the modified traits, both morphological and physiological, can be readily explained as direct consequences of such deficiencies, while other traits are explicable as indirect consequences. We first show how the hypothesis can account for the multiple, apparently unrelated traits of the syndrome and then explore its genetic dimensions and predictions, reviewing the available genetic evidence. The article concludes with a brief discussion of some genetic and developmental questions raised by the idea, along with specific predictions and experimental tests. PMID:25024034

  19. Abnormal neural crest innervation in Sox10-Venus mice with all-trans retinoic acid-induced anorectal malformations.

    Science.gov (United States)

    Suzuki, Ryota; Miyahara, Katsumi; Murakami, Hiroshi; Doi, Takashi; Lane, Geoffrey J; Mabuchi, Yo; Suzuki, Nobuharu; Yamataka, Atsuyuki; Akazawa, Chihiro

    2014-02-01

    Despite technical advances in the surgical/medical care of anorectal malformation (ARM), persistent unsatisfactory postoperative bowel habit has been attributed to histopathologic abnormalities of the distal rectum/pouch (DRP) and hypoplasia of anal sphincter muscles (ASM). We used Sox10-Venus mice with ARM induced by all-trans retinoic acid (ATRA) to investigate neural crest cell (NCC) innervation in the DRP and ASM. Pregnant Sox10-Venus mice were administered single doses of 50, 70, or 100 mg/kg of ATRA on embryonic day 8.5 (E8.5) then sacrificed on either E16.5 or E19.5. Bowel specimens comprising the anorectum were examined using fluorescence microscopy without immunohistochemical staining (FMIS). Anti-PGP9.5 was used to delineate ganglion cells and anti-SMA for smooth muscles. The appropriate dose of ATRA for inducing ARM was 50 mg/kg. Under FMIS, all ARM embryos (n = 5; all high type; 3 male:2 female) had less NCC innervation with thick Venus-positive nerve fibers in the DRP compared with normal embryos (n = 8); there was abnormal NCC innervation in the DRP and absent ASM in ARM mice. We are the first to delineate abnormal enteric nervous system innervation in the DRP of ARM mice without using immunohistochemical staining techniques thus allowing specimens to be examined without any distortion.

  20. Cranial neural crest-derived mesenchymal proliferation is regulated by Msx1-mediated p19(INK4d) expression during odontogenesis.

    Science.gov (United States)

    Han, Jun; Ito, Yoshihiro; Yeo, Jae Yong; Sucov, Henry M; Maas, Richard; Chai, Yang

    2003-09-01

    Neural crest cells are multipotential progenitors that contribute to various cell and tissue types during embryogenesis. Here, we have investigated the molecular and cellular mechanism by which the fate of neural crest cell is regulated during tooth development. Using a two- component genetic system for indelibly marking the progeny of neural crest cells, we provide in vivo evidence of a deficiency of CNC-derived dental mesenchyme in Msx1 null mutant mouse embryos. The deficiency of the CNC results from an elevated CDK inhibitor p19(INK4d) activity and the disruption of cell proliferation. Interestingly, in the absence of Msx1, the CNC-derived dental mesenchyme misdifferentiates and possesses properties consistent with a neuronal fate, possibly through a default mechanism. Attenuation of p19(INK4d) in Msx1 null mutant mandibular explants restores mitotic activity in the dental mesenchyme, demonstrating the functional significance of Msx1-mediated p19(INK4d) expression in regulating CNC cell proliferation during odontogenesis. Collectively, our results demonstrate that homeobox gene Msx1 regulates the fate of CNC cells by controlling the progression of the cell cycle. Genetic mutation of Msx1 may alternatively instruct the fate of these progenitor cells during craniofacial development.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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.

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

    Science.gov (United States)

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

    2014-06-15

    Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Its genetic basis is demonstrated by an increased recurrence risk in siblings and familial cases. However, the majority of TOF are sporadic, isolated cases of undefined origin and it had been postulated that rare and private autosomal variations in concert define its genetic basis. To elucidate this hypothesis, we performed a multilevel study using targeted re-sequencing and whole-transcriptome profiling. We developed a novel concept based on a gene's mutation frequency to unravel the polygenic origin of TOF. We show that isolated TOF is caused by a combination of deleterious private and rare mutations in genes essential for apoptosis and cell growth, the assembly of the sarcomere as well as for the neural crest and secondary heart field, the cellular basis of the right ventricle and its outflow tract. Affected genes coincide in an interaction network with significant disturbances in expression shared by cases with a mutually affected TOF gene. The majority of genes show continuous expression during adulthood, which opens a new route to understand the diversity in the long-term clinical outcome of TOF cases. Our findings demonstrate that TOF has a polygenic origin and that understanding the genetic basis can lead to novel diagnostic and therapeutic routes. Moreover, the novel concept of the gene mutation frequency is a versatile measure and can be applied to other open genetic disorders. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. [CREST syndrome].

    Science.gov (United States)

    Meyer, Olivier

    2002-05-01

    CREST syndrome has been described as a form of progressive systemic sclerosis in which there is relatively limited involvement of the skin, prominence of calcinosis, Raynaud's phenomenon, esophageal dysfunction and telangiectasia. The acronym CREST was coined in 1964 by Winterbauer in the USA but the very first case report was by French physicians Thibierge and Weissenbach in 1910. Antinuclear antibodies recognizing chromosomal centromere proteins are characteristic of CREST syndrome and are present in more than 50% of the cases. The prognosis of CREST syndrome is relatively good with a long lasting disease duration (>10 years). Two complications are seldom associated with CREST syndrome: digital gangrene with finger losses and pulmonary hypertension (3 to 14% of CREST syndrome). Pulmonary hypertension is a very late event and the prognosis is very severe (mortality rate of 50% after 2 years).

  5. 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....

  6. Boundary cap neural crest stem cells homotopically implanted to the injured dorsal root transitional zone give rise to different types of neurons and glia in adult rodents

    OpenAIRE

    Trolle, Carl; Abrahamsson, Ninnie; König, Niclas; Vasylovska, Svitlana; Kozlova, Elena

    2014-01-01

    The boundary cap is a transient group of neural crest-derived cells located at the presumptive dorsal root transitional zone (DRTZ) when sensory axons enter the spinal cord during development. Later, these cells migrate to dorsal root ganglia and differentiate into subtypes of sensory neurons and glia. After birth when the DRTZ is established, sensory axons are no longer able to enter the spinal cord. Here we explored the fate of mouse bNCSCs implanted to the uninjured DRTZ after dorsal root ...

  7. Adult bone marrow neural crest stem cells and mesenchymal stem cells are not able to replace lost neurons in acute MPTP-lesioned mice.

    Directory of Open Access Journals (Sweden)

    Virginie Neirinckx

    Full Text Available Adult bone marrow stroma contains multipotent stem cells (BMSC that are a mixed population of mesenchymal and neural-crest derived stem cells. Both cells are endowed with in vitro multi-lineage differentiation abilities, then constituting an attractive and easy-available source of material for cell therapy in neurological disorders. Whereas the in vivo integration and differentiation of BMSC in neurons into the central nervous system is currently matter of debate, we report here that once injected into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-treated mice, pure populations of either bone marrow neural crest stem cells (NCSC or mesenchymal stem cells (MSC survived only transiently into the lesioned brain. Moreover, they do not migrate through the brain tissue, neither modify their initial phenotype, while no recovery of the dopaminergic system integrity was observed. Consequently, we tend to conclude that MSC/NCSC are not able to replace lost neurons in acute MPTP-lesioned dopaminergic system through a suitable integration and/or differentiation process. Altogether with recent data, it appears that neuroprotective, neurotrophic and anti-inflammatory features characterizing BMSC are of greater interest as regards CNS lesions management.

  8. Modeling of genetic regulatory networks in the differentiation of neural crest stem cells to sensory neurons by means of boolean networks

    Directory of Open Access Journals (Sweden)

    Jorge Marcelo Aráus Patiño

    2011-01-01

    Full Text Available In the present study we have generated a GRN comprising the process by which neural crest stem cells develop to two types of sensory neurons (Propioceptors and Nocioceptors. We have also been able to fi nd patterns of regulation (motifs that act cooperatively to control such process. Surprisingly, these motifs take place in similar stages during the development of erythrocytes from hematopoietic stem cells. Regarding the complexity of the GRN found, we then used Random Boolean Networks (RBN for this purpose, which showed key components as well as the dynamics of the process through changes in initial conditions. Finally, the motifs were refl ected in the model, suggesting insights for further studies.

  9. 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

  10. CREST Syndrome

    Directory of Open Access Journals (Sweden)

    Tuğçe Köksüz

    2014-06-01

    Full Text Available We report a case of CREST syndrome (calsinosis cutis, Raynaud’s phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia with all of the five major symptoms. A 46-year-old woman was admitted to our clinic with the complaint of erythema, rigidity and pain on the plantar surface of the feet. She had had Raynaud’s phenomenon for 20 years and oesophageal reflux for five years. Her face had become masklike and there was prominent telangiectasies on her face and hands. Sclerosis were confined to the fingers (sclerodactyly. Direct X-ray graphy demonstrated calcinosis cutis on the left hand and suprapatellar region. She was treated with nifedipine 30 mg/day, acetylsalicylic acid 100 mg/day for Raynaud’s phenomenon and famotidine 40 mg/day, metoclopramide HCL 30 mg/day for oesophageal dysmotility. Her complaints were partially relieved after the treatment. This case had all of the five major symptoms of CREST syndrome, and we aimed to emphasize the major symptoms and complications of CREST syndrome. (Turk J Dermatol 2012; 6: 48-50

  11. CREST Syndrome

    Directory of Open Access Journals (Sweden)

    Tuğçe Köksüz

    2012-06-01

    Full Text Available We report a case of CREST syndrome (calsinosis cutis, Raynaud’s phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia with all of the five major symptoms. A 46-year-old woman was admitted to our clinic with the complaint of erythema, rigidity and pain on the plantar surface of the feet. She had had Raynaud’s phenomenon for 20 years and oesophageal reflux for five years. Her face had become masklike and there was prominent telangiectasies on her face and hands. Sclerosis were confined to the fingers (sclerodactyly. Direct X-ray graphy demonstrated calcinosis cutis on the left hand and suprapatellar region. She was treated with nifedipine 30 mg/day, acetylsalicylic acid 100 mg/day for Raynaud’s phenomenon and famotidine 40 mg/day, metoclopramide HCL 30 mg/day for oesophageal dysmotility. Her complaints were partially relieved after the treatment. This case had all of the five major symptoms of CREST syndrome, and we aimed to emphasize the major symptoms and complications of CREST syndrome.

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

    Science.gov (United States)

    Gosain, Ankush; Barlow-Anacker, Amanda J.; Erickson, Chris S.; Pierre, Joseph F.; Heneghan, Aaron F.; Epstein, Miles L.; Kudsk, Kenneth A.

    2015-01-01

    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 to

  13. Neural Crest Cell Implantation Restores Enteric Nervous System Function and Alters the Gastrointestinal Transcriptome in Human Tissue-Engineered Small Intestine.

    Science.gov (United States)

    Schlieve, Christopher R; Fowler, Kathryn L; Thornton, Matthew; Huang, Sha; Hajjali, Ibrahim; Hou, Xiaogang; Grubbs, Brendan; Spence, Jason R; Grikscheit, Tracy C

    2017-09-12

    Acquired or congenital disruption in enteric nervous system (ENS) development or function can lead to significant mechanical dysmotility. ENS restoration through cellular transplantation may provide a cure for enteric neuropathies. We have previously generated human pluripotent stem cell (hPSC)-derived tissue-engineered small intestine (TESI) from human intestinal organoids (HIOs). However, HIO-TESI fails to develop an ENS. The purpose of our study is to restore ENS components derived exclusively from hPSCs in HIO-TESI. hPSC-derived enteric neural crest cell (ENCC) supplementation of HIO-TESI establishes submucosal and myenteric ganglia, repopulates various subclasses of neurons, and restores neuroepithelial connections and neuron-dependent contractility and relaxation in ENCC-HIO-TESI. RNA sequencing identified differentially expressed genes involved in neurogenesis, gliogenesis, gastrointestinal tract development, and differentiated epithelial cell types when ENS elements are restored during in vivo development of HIO-TESI. Our findings validate an effective approach to restoring hPSC-derived ENS components in HIO-TESI and may implicate their potential for the treatment of enteric neuropathies. Published by Elsevier Inc.

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

    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); 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.

  15. Neural crest cell survival is dependent on Rho kinase and is required for development of the mid face in mouse embryos.

    Directory of Open Access Journals (Sweden)

    Helen M Phillips

    Full Text Available Neural crest cells (NCC give rise to much of the tissue that forms the vertebrate head and face, including cartilage and bone, cranial ganglia and teeth. In this study we show that conditional expression of a dominant-negative (DN form of Rho kinase (Rock in mouse NCC results in severe hypoplasia of the frontonasal processes and first pharyngeal arch, ultimately resulting in reduction of the maxilla and nasal bones and severe craniofacial clefting affecting the nose, palate and lip. These defects resemble frontonasal dysplasia in humans. Disruption of the actin cytoskeleton, which leads to abnormalities in cell-matrix attachment, is seen in the RockDN;Wnt1-cre mutant embryos. This leads to elevated cell death, resulting in NCC deficiency and hypoplastic NCC-derived craniofacial structures. Rock is thus essential for survival of NCC that form the craniofacial region. We propose that reduced NCC numbers in the frontonasal processes and first pharyngeal arch, resulting from exacerbated cell death, may be the common mechanism underlying frontonasal dysplasia.

  16. ALK5-mediated transforming growth factor β signaling in neural crest cells controls craniofacial muscle development via tissue-tissue interactions.

    Science.gov (United States)

    Han, Arum; Zhao, Hu; Li, Jingyuan; Pelikan, Richard; Chai, Yang

    2014-08-01

    The development of the craniofacial muscles requires reciprocal interactions with surrounding craniofacial tissues that originate from cranial neural crest cells (CNCCs). However, the molecular mechanism involved in the tissue-tissue interactions between CNCCs and muscle progenitors during craniofacial muscle development is largely unknown. In the current study, we address how CNCCs regulate the development of the tongue and other craniofacial muscles using Wnt1-Cre; Alk5(fl/fl) mice, in which loss of Alk5 in CNCCs results in severely disrupted muscle formation. We found that Bmp4 is responsible for reduced proliferation of the myogenic progenitor cells in Wnt1-Cre; Alk5(fl/fl) mice during early myogenesis. In addition, Fgf4 and Fgf6 ligands were reduced in Wnt1-Cre; Alk5(fl/fl) mice and are critical for differentiation of the myogenic cells. Addition of Bmp4 or Fgf ligands rescues the proliferation and differentiation defects in the craniofacial muscles of Alk5 mutant mice in vitro. Taken together, our results indicate that CNCCs play critical roles in controlling craniofacial myogenic proliferation and differentiation through tissue-tissue interactions. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  17. GMDH-type neural network approach for modeling the discharge coefficient of rectangular sharp-crested side weirs

    Directory of Open Access Journals (Sweden)

    Isa Ebtehaj

    2015-12-01

    Full Text Available Estimating the discharge coefficient using hydraulic and geometrical specifications is one of the influential factors in predicting the discharge passing over a side weir. Taking into account the fact that existing equations are incapable of estimating the discharge coefficient well, artificial intelligence methods are used to predict it. In this study, Group Method of Data Handling (GMDH was used for the purpose of predicting the discharge coefficient in a side weir. The Froude number (F1, weir dimensionless length (b/B, ratios of weir length to depth of upstream flow (b/y1 and weir height to its length (p/y1 were taken as input parameters to express a new model for predicting the discharge coefficient. Two different sets of laboratory data were used to train the artificial network and test the new model. Different statistical indexes were used to evaluate the performance of the GMDH model presented for two states, training and testing. The results indicate that the proposed model predicts the discharge coefficient precisely (MAPE = 5.263 & RMSE = 0.038 and this model is more accurate in predicting than the feed-forward neural network model and existing nonlinear regression equations.

  18. 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.

  19. Smooth Muscle Cells Derived From Second Heart Field and Cardiac Neural Crest Reside in Spatially Distinct Domains in the Media of the Ascending Aorta-Brief Report.

    Science.gov (United States)

    Sawada, Hisashi; Rateri, Debra L; Moorleghen, Jessica J; Majesky, Mark W; Daugherty, Alan

    2017-09-01

    Smooth muscle cells (SMCs) of the proximal thoracic aorta are embryonically derived from the second heart field (SHF) and cardiac neural crest (CNC). However, distributions of these embryonic origins are not fully defined. The regional distribution of SMCs of different origins is speculated to cause region-specific aortopathies. Therefore, the aim of this study was to determine the distribution of SMCs of SHF and CNC origins in the proximal thoracic aorta. Mice with repressed LacZ in the ROSA26 locus were bred to those expressing Cre controlled by either the Wnt1 or Mef2c (myocyte-specific enhancer factor 2c) promoter to trace CNC- and SHF-derived SMCs, respectively. Thoracic aortas were harvested, and activity of β-galactosidase was determined. Aortas from Wnt1- Cre mice had β-galactosidase-positive areas throughout the region from the proximal ascending aorta to just distal of the subclavian arterial branch. Unexpectedly, β-galactosidase-positive areas in Mef2c- Cre mice extended from the aortic root throughout the ascending aorta. This distribution occurred independent of sex and aging. Cross and sagittal aortic sections demonstrated that CNC-derived cells populated the inner medial aspect of the anterior region of the ascending aorta and transmurally in the media of the posterior region. Interestingly, outer medial cells throughout anterior and posterior ascending aortas were derived from the SHF. β-Galactosidase-positive medial cells of both origins colocalized with an SMC marker, α-actin. Both CNC- and SHF-derived SMCs populate the media throughout the ascending aorta. The outer medial cells of the ascending aorta form a sleeve populated by SHF-derived SMCs. © 2017 American Heart Association, Inc.

  20. A 3.7 kb fragment of the mouse Scn10a gene promoter directs neural crest but not placodal lineage EGFP expression in a transgenic animal.

    Science.gov (United States)

    Lu, Van B; Ikeda, Stephen R; Puhl, Henry L

    2015-05-20

    Under physiological conditions, the voltage-gated sodium channel Nav1.8 is expressed almost exclusively in primary sensory neurons. The mechanism restricting Nav1.8 expression is not entirely clear, but we have previously described a 3.7 kb fragment of the Scn10a promoter capable of recapitulating the tissue-specific expression of Nav1.8 in transfected neurons and cell lines (Puhl and Ikeda, 2008). To validate these studies in vivo, a transgenic mouse encoding EGFP under the control of this putative sensory neuron specific promoter was generated and characterized in this study. Approximately 45% of dorsal root ganglion neurons of transgenic mice were EGFP-positive (mean diameter = 26.5 μm). The majority of EGFP-positive neurons bound isolectin B4, although a small percentage (∼10%) colabeled with markers of A-fiber neurons. EGFP expression correlated well with the presence of Nav1.8 transcript (95%), Nav1.8-immunoreactivity (70%), and TTX-R INa (100%), although not all Nav1.8-expressing neurons expressed EGFP. Several cranial sensory ganglia originating from neurogenic placodes, such as the nodose ganglion, failed to express EGFP, suggesting that additional regulatory elements dictate Scn10a expression in placodal-derived sensory neurons. EGFP was also detected in discrete brain regions of transgenic mice. Quantitative PCR and Nav1.8-immunoreactivity confirmed Nav1.8 expression in the amygdala, brainstem, globus pallidus, lateral and paraventricular hypothalamus, and olfactory tubercle. TTX-R INa recorded from EGFP-positive hypothalamic neurons demonstrate the usefulness of this transgenic line to study novel roles of Nav1.8 beyond sensory neurons. Overall, Scn10a-EGFP transgenic mice recapitulate the majority of the Nav1.8 expression pattern in neural crest-derived sensory neurons. Copyright © 2015 the authors 0270-6474/15/358021-14$15.00/0.

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

    Directory of Open Access Journals (Sweden)

    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. EIF4A3 deficient human iPSCs and mouse models demonstrate neural crest defects that underlie Richieri-Costa-Pereira syndrome.

    Science.gov (United States)

    Miller, Emily E; Kobayashi, Gerson S; Musso, Camila M; Allen, Miranda; Ishiy, Felipe A A; de Caires, Luiz Carlos; Goulart, Ernesto; Griesi-Oliveira, Karina; Zechi-Ceide, Roseli M; Richieri-Costa, Antonio; Bertola, Debora R; Passos-Bueno, Maria Rita; Silver, Debra L

    2017-06-15

    Biallelic loss-of-function mutations in the RNA-binding protein EIF4A3 cause Richieri-Costa-Pereira syndrome (RCPS), an autosomal recessive condition mainly characterized by craniofacial and limb malformations. However, the pathogenic cellular mechanisms responsible for this syndrome are entirely unknown. Here, we used two complementary approaches, patient-derived induced pluripotent stem cells (iPSCs) and conditional Eif4a3 mouse models, to demonstrate that defective neural crest cell (NCC) development explains RCPS craniofacial abnormalities. RCPS iNCCs have decreased migratory capacity, a distinct phenotype relative to other craniofacial disorders. Eif4a3 haploinsufficient embryos presented altered mandibular process fusion and micrognathia, thus recapitulating the most penetrant phenotypes of the syndrome. These defects were evident in either ubiquitous or NCC-specific Eif4a3 haploinsufficient animals, demonstrating an autonomous requirement of Eif4a3 in NCCs. Notably, RCPS NCC-derived mesenchymal stem-like cells (nMSCs) showed premature bone differentiation, a phenotype paralleled by premature clavicle ossification in Eif4a3 haploinsufficient embryos. Likewise, nMSCs presented compromised in vitro chondrogenesis, and Meckel's cartilage was underdeveloped in vivo. These findings indicate novel and essential requirements of EIF4A3 for NCC migration and osteochondrogenic differentiation during craniofacial development. Altogether, complementary use of iPSCs and mouse models pinpoint unique cellular mechanisms by which EIF4A3 mutation causes RCPS, and provide a paradigm to study craniofacial disorders. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. 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.

  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. Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a

    Science.gov (United States)

    Khedgikar, Vikram; Abbruzzese, Genevieve; Mathavan, Ketan; Szydlo, Hannah; Cousin, Helene

    2017-01-01

    Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition, the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here, we show that adam13 interacts with the arid3a/dril1/Bright transcription factor. This interaction promotes a proteolytic cleavage of arid3a and its translocation to the nucleus where it regulates another transcription factor: tfap2α. Tfap2α in turn activates multiple genes including the protocadherin pcdh8l (PCNS). The proteolytic activity of adam13 is critical for the release of arid3a from the plasma membrane while the cytoplasmic domain appears critical for the cleavage of arid3a. In addition to this transcriptional control of pcdh8l, adam13 cleaves pcdh8l generating an extracellular fragment that also regulates cell migration. PMID:28829038

  7. 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.…

  8. 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

  9. 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

  10. Neural crest origin of olfactory ensheating glia.

    NARCIS (Netherlands)

    Barraud, P; Seferiadis, A.A.; Tyson, L.D.; Zwart, M.F.; Szabo-Rogers, H.L.; Ruhrberg, C; Liu, K.J.; Baker, C.V.

    2010-01-01

    Olfactory ensheathing cells (OECs) are a unique class of glial cells with exceptional translational potential because of their ability to support axon regeneration in the central nervous system. Although OECs are similar in many ways to immature and nonmyelinating Schwann cells, and can myelinate

  11. [Autoimmune hepatitis and CREST syndrome].

    Science.gov (United States)

    Ngo Mandag, N; Van Gossum, M; Rickaert, F; Golstein, M

    2007-01-01

    We report the case of an autoimmune hepatitis in a 59-year old woman who was referred for a progressive jaundice. The patient had an history of CREST syndrome. The particularity of this case report is the rare association between these two autoimmune diseases.

  12. Confinement at Large Nc

    NARCIS (Netherlands)

    Hooft, G. 't

    2004-01-01

    A discussion is given of the confinement mechanism in terms of the Abelian projection scheme, for a general number Nc of colors. There is a difficulty in the Nc to infinity limit that requires a careful treatment, as the charges of the condensing magnetic monopoles tend to infinity. We suggest that

  13. 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

  14. Juxtafoveolar telangiectasis associated with CREST syndrome.

    Science.gov (United States)

    Huerva, Valentin; Sánchez, M Carmen

    2008-01-01

    To report a case of CREST syndrome associated with juxtafoveolar telangiectasias (JT). Case report. Observational case report. A 64-year-old woman affected with CREST syndrome developed bilateral visual loss. Capillary dilatation and permeability changes in the outer retina were noticed during an angiographic study. Optical coherence tomography (OCT) showed thickening with loss of the foveal depression and inner lamellar cyst. The patient was diagnosed as stage 3, group 2A JT associated with CREST syndrome. Finding JT in association with CREST syndrome suggests a common pathophysiologic process.

  15. The Crest Wing Wave Energy Device

    DEFF Research Database (Denmark)

    Kofoed, Jens Peter; Antonishen, Michael Patrick

    This report presents the results of a continuation of an experimental study of the wave energy converting abilities of the Crest Wing wave energy converter (WEC), in the following referred to as ‘Phase 2'. The Crest Wing is a WEC that uses its movement in matching the shape of an oncoming wave...

  16. Morbidity from iliac crest bone harvesting

    NARCIS (Netherlands)

    Kalk, WWI; Raghoebar, GM; Jansma, J; Boering, G

    1996-01-01

    Purpose: The iliac crest is the most common donor site for autogenous bone grafting in maxillofacial surgery. The aim of this study was to evaluate retrospectively the morbidity of bone harvesting from the inner table of the anterior iliac crest. Patients and Methods: Sixty-five patients were

  17. Intracranial aneurysms in patients with CREST syndrome.

    Science.gov (United States)

    Nakae, Ryuta; Idei, Masaru; Kumano, Kiyoshi; Okita, Shinji; Yamane, Kanji

    2009-09-01

    CREST syndrome is a variant of scleroderma characterized by calcinosis, Raynaud's phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia, and is a collagen vascular disease characterized by inflammation and fibrosis of multiple organs/tissues. Neurological and cerebrovascular abnormalities are uncommon in CREST syndrome. Here, we report two patients with CREST syndrome harboring intracranial aneurysms. A 53-year-old woman with a 6-month history of CREST syndrome had multiple intracranial aneurysms that arose from the right middle cerebral artery, the left middle cerebral artery, the choroidal segment of the left internal carotid artery, and the left anterior cerebral artery. A 64-year-old woman with a 2-year history of CREST syndrome had a fusiform aneurysm located on the insular segment of the left middle cerebral artery. These patients were treated surgically and good outcome was achieved in both cases. The pathogenesis of cerebral aneurysms associated with collagen diseases, including CREST syndrome, remains unclear. Early treatment of CREST syndrome and other collagen diseases may prevent arteritis from progressing to affect the intracranial arteries and thus reduce the occurrence of aneurysms. The prognosis for patients with collagen diseases after rupture of cerebral aneurysm seems to be poor because the multiplicity, atypical morphology, and atypical location of their aneurysms make treatment difficult. Thus, early detection and treatment are important to improve the prognosis.

  18. Primary biliary cirrhosis accompanied by CREST syndrome.

    Science.gov (United States)

    Kouraklis, Gregory; Glinavou, Andromahi; Karatzas, Gabriel

    2002-09-01

    CREST syndrome, a relatively benign, slowly progressive variant of systemic scleroderma consists of calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia. Although the association of this syndrome with primary biliary cirrhosis (PBC) is recognized in women, it has never been described in a man. We report the rare case of a male patient with CREST syndrome accompanied by PBC, manifested by acute cholecystitis and mild jaundice. The association of the two conditions is clinically and etiologically important. Clinicians must be aware of this association, sincethe clinical features of CREST syndrome may be mild and may be thought to be complications of the underlying liver disease.

  19. Stability of Low-Crested Breakwaters in Shallow Water Short Crested Waves

    DEFF Research Database (Denmark)

    Kramer, Morten Mejlhede; Burcharth, Hans Falk

    2003-01-01

    The paper presents results of 3D laboratory experiments on low-crested breakwaters. Two typical structural layouts were tested at model scale in a wave basin at Aalborg University, Denmark, to identify and quantify the influence of various hydrodynamic conditions (obliquity of short crested waves......, wave hight and wave steepness) and structural geometries (crest width and freeboard) on the stability of low-crested breakwaters. Results are given in terms of recommendations for design guidelines for structure stability. Damage parameters for the trunk and the roundhead are proposed based on analysis...

  20. Design Guidelines for Low Crested Structures

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Lamberti, Alberto

    2004-01-01

    The European Union within the Fifth Framework Programme 1998-2002 Energy, Environment andmSustainable Development sponsored the research project: Enviromnental Design of Low Crested Coastal Defence Structures (DELOS), with participation of 18 European organisations.......The European Union within the Fifth Framework Programme 1998-2002 Energy, Environment andmSustainable Development sponsored the research project: Enviromnental Design of Low Crested Coastal Defence Structures (DELOS), with participation of 18 European organisations....

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

    Science.gov (United States)

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

    2017-04-08

    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 (5.8 cm on the right, 3.8 cm on the left) that projected into the foramina and into the spinal canal. The patient underwent minimally invasive bilateral surgical resection of the paraspinal masses, posterior decompressive laminectomy, posterior interbody, and posterolateral fusion. The specimen was consistent with the calcinosis of CREST syndrome. The patient's lumbar symptoms were relieved, however, two years later she presented with right radicular arm pain. A CT scan revealed a large lobulated benign tumor-like lesion on the left at C6-C7 encroaching upon the neural foramen and a large right lobulated lesion encroaching into the neural foramen with severe compression of the neural foramen at the C7-T1 level and extension into the canal, with anterior and posterior subluxation present throughout the cervical spine. Surgery was performed, which involved cervical mass resections, posterior spinal cord decompression, reconstruction, and fusion. The patient did well and has been symptom-free since her surgery. Calcinosis of the spine is a known entity that can cause morbidity in patients with CREST syndrome. Minimal invasive surgical approaches are effective and can be considered for some of these patients.

  2. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells.

    Science.gov (United States)

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-03-29

    The 'neural plate border' of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure.

  3. Homeodomain transcription factor Phox2a, via cyclic AMP-mediated activation, induces p27Kip1 transcription, coordinating neural progenitor cell cycle exit and differentiation.

    Science.gov (United States)

    Paris, Maryline; Wang, Wen-Horng; Shin, Min-Hwa; Franklin, David S; Andrisani, Ourania M

    2006-12-01

    Mechanisms coordinating neural progenitor cell cycle exit and differentiation are incompletely understood. The cyclin-dependent kinase inhibitor p27(Kip1) is transcriptionally induced, switching specific neural progenitors from proliferation to differentiation. However, neuronal differentiation-specific transcription factors mediating p27(Kip1) transcription have not been identified. We demonstrate the homeodomain transcription factor Phox2a, required for central nervous system (CNS)- and neural crest (NC)-derived noradrenergic neuron differentiation, coordinates cell cycle exit and differentiation by inducing p27(Kip1) transcription. Phox2a transcription and activation in the CNS-derived CAD cell line and primary NC cells is mediated by combined cyclic AMP (cAMP) and bone morphogenetic protein 2 (BMP2) signaling. In the CAD cellular model, cAMP and BMP2 signaling initially induces proliferation of the undifferentiated precursors, followed by p27(Kip1) transcription, G(1) arrest, and neuronal differentiation. Small interfering RNA silencing of either Phox2a or p27(Kip1) suppresses p27(Kip1) transcription and neuronal differentiation, suggesting a causal link between p27(Kip1) expression and differentiation. Conversely, ectopic Phox2a expression via the Tet-off expression system promotes accelerated CAD cell neuronal differentiation and p27(Kip1) transcription only in the presence of cAMP signaling. Importantly, endogenous or ectopically expressed Phox2a activated by cAMP signaling binds homeodomain cis-acting elements of the p27(Kip1) promoter in vivo and mediates p27(Kip1)-luciferase expression in CAD and NC cells. We conclude that developmental cues of cAMP signaling causally link Phox2a activation with p27(Kip1) transcription, thereby coordinating neural progenitor cell cycle exit and differentiation.

  4. Design Guidelines for Low Crested Structures

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Lamberti, Alberto

    2004-01-01

    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...... 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...

  5. Mandibular segmental reconstruction with iliac crest.

    Science.gov (United States)

    Obiechina, A E; Ogunlade, S O; Fasola, A O; Arotiba, J T

    2003-01-01

    Twenty patients consisting of 14 males and 6 females with benign destructive lesions of the mandible were reconstructed using free nonvascularised iliac crest. Harvested bone was contoured and secured with 0.5 mm stainless steel wire and reinforced with maxillo-mandibular fixation. Five patients has hemimandibulectomy with immediate reconstruction. The other 15 patients had 1 to 3 segments of the mandible reconstructed. There was only one failure. Mouth opening and closure were centric except in the patients that had hemimandibulectomy without condylar reconstruction. Mastication and facial appearance were satisfactory. In conclusion, the iliac crest is recommended for reconstruction of hemimandible as well as long contiguous segments of the mandible.

  6. Sporadic hemiplegic migraine and CREST syndrome.

    Science.gov (United States)

    Grecco, Martin Pablo; Pieroni, Miguel; Otero, Marcela; Ferreiro, Jorge Luis; Figuerola, María de Lourdes

    2010-04-01

    Hemiplegic migraines are characterised by attacks of migraine with aura accompanied by transient motor weakness. There are both familial and sporadic subtypes, which are now recognised as separate entities by the International Classification of Headache Disorders, edition II (ICHD-II). The sporadic subtype has been associated with other medical conditions, particularly rheumatological diseases. We report the case of a woman with sporadic hemiplegic migraine associated with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia). Since there is a close relationship between migraine and Raynaud's phenomenon, it could be speculated that the sporadic hemiplegic migraines in our patient might be secondary to CREST syndrome.

  7. Mandibular segmental reconstruction with iliac crest | Obiechina ...

    African Journals Online (AJOL)

    Twenty patients consisting of 14 males and 6 females with benign destructive lesions of the mandible were reconstructed using free nonvascularised iliac crest. Harvested bone was contoured and secured with 0.5mm stainless steel wire and reinforced with maxillo-mandibular fixation. Five patients has ...

  8. Structural Stability of Low-Crested Breakwaters

    DEFF Research Database (Denmark)

    Kramer, Morten

    A more and more widespread way to protect the coast against ongoing erosion is to build so called Low Crested Structures (LCS’s). Despite a large number of coast parallel LCS’s exist, the structural performance of these structures are not fully clarified. The LCS’s dealt with are coast parallel...

  9. Iliac crest histomorphometry and skeletal heterogeneity in men

    Directory of Open Access Journals (Sweden)

    Xiaoyu Tong

    2017-06-01

    Conclusions: This study reveals heterogeneity in cortical microarchitecture between the external and internal iliac crest cortices, as well as between the iliac crest, the femoral neck and the subtrochanteric femoral shaft. Standard iliac crest biopsy does not reflect accurately cortical microarchitecture of other skeletal sites.

  10. NC application to production site; Seisan genba eno NC oyo

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-01-10

    Fuji Electric Co., Ltd. built for and delivered to the Shinto plant of The Yokohama Rubber Co., Ltd., a manufacturing process management system with NC (network computer) used as an on-site client. This is a core system for manufacturing in the unified logistics plan of The Yokohama Rubber Co., Ltd., and constituted of five servers and about 200 NC client terminals. The on-site client terminals require (1) environmental resistance, (2) easiness of maintenance, and (3) reduction in maintenance control operations, for example. For these requirements, the system employed on-site client terminals by using the features of NC such as (1) it excels in the environmental resistance because of no magnetic disk device and (2) it reduces maintenance and maintenance control operations because of the unified management of software by the servers. Expected from now on are a number of NC applications to manufacturing sites having similar requirements. (translated by NEDO)

  11. Misexpression of BRE gene in the developing chick neural tube affects neurulation and somitogenesis.

    Science.gov (United States)

    Wang, Guang; Li, Yan; Wang, Xiao-Yu; Chuai, Manli; Yeuk-Hon Chan, John; Lei, Jian; Münsterberg, Andrea; Lee, Kenneth Ka Ho; Yang, Xuesong

    2015-03-01

    The brain and reproductive expression (BRE) gene is expressed in numerous adult tissues and especially in the nervous and reproductive systems. However, little is known about BRE expression in the developing embryo or about its role in embryonic development. In this study, we used in situ hybridization to reveal the spatiotemporal expression pattern for BRE in chick embryo during development. To determine the importance of BRE in neurogenesis, we overexpressed BRE and also silenced BRE expression specifically in the neural tube. We established that overexpressing BRE in the neural tube indirectly accelerated Pax7(+) somite development and directly increased HNK-1(+) neural crest cell (NCC) migration and TuJ-1(+) neurite outgrowth. These altered morphogenetic processes were associated with changes in the cell cycle of NCCs and neural tube cells. The inverse effect was obtained when BRE expression was silenced in the neural tube. We also determined that BMP4 and Shh expression in the neural tube was affected by misexpression of BRE. This provides a possible mechanism for how altering BRE expression was able to affect somitogenesis, neurogenesis, and NCC migration. In summary, our results demonstrate that BRE plays an important role in regulating neurogenesis and indirectly somite differentiation during early chick embryo development. © 2015 Wang, Li, Wang, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  12. Cell delamination in the mesencephalic neural fold and its implication for the origin of ectomesenchyme

    Science.gov (United States)

    Lee, Raymond Teck Ho; Nagai, Hiroki; Nakaya, Yukiko; Sheng, Guojun; Trainor, Paul A.; Weston, James A.; Thiery, Jean Paul

    2013-01-01

    The neural crest is a transient structure unique to vertebrate embryos that gives rise to multiple lineages along the rostrocaudal axis. In cranial regions, neural crest cells are thought to differentiate into chondrocytes, osteocytes, pericytes and stromal cells, which are collectively termed ectomesenchyme derivatives, as well as pigment and neuronal derivatives. There is still no consensus as to whether the neural crest can be classified as a homogenous multipotent population of cells. This unresolved controversy has important implications for the formation of ectomesenchyme and for confirmation of whether the neural fold is compartmentalized into distinct domains, each with a different repertoire of derivatives. Here we report in mouse and chicken that cells in the neural fold delaminate over an extended period from different regions of the cranial neural fold to give rise to cells with distinct fates. Importantly, cells that give rise to ectomesenchyme undergo epithelial-mesenchymal transition from a lateral neural fold domain that does not express definitive neural markers, such as Sox1 and N-cadherin. Additionally, the inference that cells originating from the cranial neural ectoderm have a common origin and cell fate with trunk neural crest cells prompted us to revisit the issue of what defines the neural crest and the origin of the ectomesenchyme. PMID:24198279

  13. The diagnostic quandary of hereditary haemorrhagic telangiectasia vs. CREST syndrome.

    Science.gov (United States)

    Lee, J B; Ben-Aviv, D; Covello, S P

    2001-10-01

    The distribution and clinical appearance of the telangiectasia in the CREST syndrome (calcinosis, Raynaud's phenomenon, oesophageal involvement, sclerodactyly, telangiectasia) and hereditary haemorrhagic telangiectasia (HHT) are very similar. Several previously reported cases of the CREST syndrome simulating HHT illustrate this diagnostic quandary. We report a patient who met the diagnostic criteria for both the CREST syndrome and HHT, and discuss the distinguishing features of the two diseases, including the distinctive histopathological findings of telangiectasia in HHT.

  14. 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...... 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....

  15. Short-crested waves in the surf zone

    Science.gov (United States)

    Wei, Zhangping; Dalrymple, Robert A.; Xu, Munan; Garnier, Roland; Derakhti, Morteza

    2017-05-01

    This study investigates short-crested waves in the surf zone by using the mesh-free Smoothed Particle Hydrodynamics model, GPUSPH. The short-crested waves are created by generating intersecting wave trains in a numerical wave basin with a beach. We first validate the numerical model for short-crested waves by comparison with large-scale laboratory measurements. Then short-crested wave breaking over a planar beach is studied comprehensively. We observe rip currents as discussed in Dalrymple (1975) and undertow created by synchronous intersecting waves. The wave breaking of the short-crested wavefield created by the nonlinear superposition of intersecting waves and wave-current interaction result in the formation of isolated breakers at the ends of breaking wave crests. Wave amplitude diffraction at these isolated breakers gives rise to an increase in the alongshore wave number in the inner surf zone. Moreover, 3-D vortices and multiple circulation cells with a rotation frequency much lower than the incident wave frequency are observed across the outer surf zone to the beach. Finally, we investigate vertical vorticity generation under short-crested wave breaking and find that breaking of short-crested waves generates vorticity as pointed out by Peregrine (1998). Vorticity generation is not only observed under short-crested waves with a limited number of wave components but also under directional wave spectra.

  16. A crested theropod dinosaur from antarctica.

    Science.gov (United States)

    Hammer, W R; Hickerson, W J

    1994-05-06

    Jurassic fossil vertebrates collected from the Falla Formation in the Central Transantarctic Mountains included a partial skull and postcranial elements of a crested theropod, Cryolophosaurus ellioti gen. nov. sp. nov. The theropod bears some resemblance to the large tetanurans of the Middle to Late Jurassic but also has primitive ceratosaurian features. Elements from a prosauropod, teeth from scavenging theropods, a pterosaur humerus, and a tritylodont molar were also recovered. The presence of this fauna suggests that a mild climate existed at high paleolatitude in this area of Gondwana during the Early Jurassic.

  17. Bronchiectasis in a patient with CREST syndrome.

    Science.gov (United States)

    Lavie, Frédéric; Rozenberg, Sylvie; Coutaux, Anne; Koeger, Anne-Claude; Bourgeois, Pierre; Fautrel, Bruno

    2002-10-01

    Bronchiectasis is an uncommon pulmonary manifestation of systemic sclerosis (SSc). We report the case of a 70-year-old woman with CREST syndrome and vasculitis who developed multifocal symptomatic bronchiectasis. The bronchiectasis and immunosuppressive therapy precipitated severe lower respiratory tract infection, which was fatal within a few months. The concomitant occurrence of bronchiectasis and SSc raises the possibility of a pathophysiological relationship. Several hypotheses can be put forward to explain the occurrence of bronchial wall damage leading to bronchiectasis. Whatever the mechanism, cases of bronchiectasis in patients with SSc should be reported to make physicians aware of the substantial risk associated with this combination.

  18. 36 CFR 212.21 - Pacific Crest National Scenic Trail.

    Science.gov (United States)

    2010-07-01

    ... AGRICULTURE TRAVEL MANAGEMENT Administration of the Forest Transportation System § 212.21 Pacific Crest National Scenic Trail. The Pacific Crest National Scenic Trail as defined by the National Trails Systems... necessary to meet emergencies or to enable landowners or land users to have reasonable access to their lands...

  19. 36 CFR 261.20 - Pacific Crest National Scenic Trail.

    Science.gov (United States)

    2010-07-01

    ... Trail. 261.20 Section 261.20 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE PROHIBITIONS General Prohibitions § 261.20 Pacific Crest National Scenic Trail. It is prohibited to use a motorized vehicle on the Pacific Crest National Scenic Trail without a special-use...

  20. Lumbar Herniation of Kidney following Iliac Crest Bone Harvest

    Directory of Open Access Journals (Sweden)

    Michael Justin Willcox

    2016-01-01

    Full Text Available The iliac crest is a popular source for autogenous bone harvesting, but the process is rife with complications. This case report presents a patient that experienced incisional lumbar herniation of her kidney following an iliac crest bone harvesting procedure. A discussion is included on the underappreciated complications of this procedure and recommendations for improving outcomes with more thorough evaluation and documentation.

  1. Comparison of cranial dysraphism in a breed of crested duck ...

    African Journals Online (AJOL)

    The dysraphic state in the Dutch crested duck is a breed specific autosomal trait with an incomplete penetrance. We have observed similarities between the lesions found in the head of the normal Dutch crested duck (Hollandse kuifeend) and cases of dysraphism found in calves that have continuously been brought to our ...

  2. Surveys of great crested grebes Podiceps cristatus and other ...

    African Journals Online (AJOL)

    Given the small size of this isolated population, the future of great crested grebes in Uganda is highly uncertain. We recorded 30 waterbird species on these lakes; in addition to Great Crested Grebes, other species of conservation interest included White-Backed Duck Thalassornis leuconotus and Giant Kingfisher Ceryle ...

  3. Clinical, serological and genetic study in patients with CREST syndrome.

    Science.gov (United States)

    Akiyama, Y; Tanaka, M; Takeishi, M; Adachi, D; Mimori, A; Suzuki, T

    2000-06-01

    To assess the clinical, serological and genetic features of Japanese patients with CREST syndrome. Clinical features, autoantibodies and human histocompatibility leukocyte antigen (HLA) typing were studied in thirty patients with CREST syndrome, including 29 females and one male, with a mean age of 59.0 years (ranging from 40 to 76 years). Interstitial pneumonia on chest X-ray and renal involvement were rare. Mitral regurgitation and tricuspid regurgitation were present in 56.7% and 76.7%, respectively. Sjören's syndrome (SS) and primary biliary cirrhosis (PBC) were highly associated, however the positivity of the marker antibodies to those syndromes, such as anti-SSA, anti-SSB, anti-mitochondrial (AMA) and anti-smooth muscle autoantibodies were less frequent than that of primary SS and PBC without the other autoimmune diseases. The histological findings of PBC were all early stages in Scheuer's classification. HLA-Cw6 were associated with CREST-PBC overlap syndrome (pCREST syndrome, and the frequency of HLA-DR2 between CREST syndrome with or without PBC was significantly different (pCREST syndrome alone and CREST-PBC overlap syndrome and there were differences (the positivity of AMA and the severity of bile duct lesion) between PBC and CREST-PBC overlap syndrome.

  4. Multiple cerebral aneurysms in a patient with CREST syndrome.

    Science.gov (United States)

    Masuoka, Jun; Murao, Kenichi; Nagata, Izumi; Iihara, Koji

    2010-08-01

    Systemic sclerosis (SSc) associated with cerebral aneurysm is rare. We describe a patient with multiple cerebral aneurysms with the calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia (CREST) variant of SSc. A 61-year-old woman with a 20-year history of CREST syndrome was incidentally found to have four cerebral aneurysms located at the C2, C3 and C5 segments of the right internal carotid artery (ICA) and the C2 segment of the left ICA. The bilateral C2 segment aneurysms were successfully clipped using 2-stage surgery. To date, intracranial aneurysms have been reported in only two other patients with CREST syndrome. We hypothesize that the pathogenesis of the aneurysm is related to CREST syndrome. Elucidating the true incidence of cerebral aneurysms associated with CREST syndrome would help to clarify the relationship between SSc-related autoantibodies and aneurysm formation. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. 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.

  6. Dungpat Microenvironmental Effects on Germination and Establishment of Crested Wheatgrass

    OpenAIRE

    Akbar, Ghulam

    1994-01-01

    Complementary greenhouse and field studies investigated the effects of ambient environmental conditions on cattle dungpat moisture, temperature, nutrient concentration, and crust formation dynamics, which in turn influence seed germination and seedling establishment in dungpats. 'Hycrest' crested wheatgrass [Agropyron desertorum (Fisch. ex Link) X A. cristatum (L.) Gaert.] was used as a representative revegetation species. After collecting feces from Holstein steers that had been fed crest...

  7. 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.

  8. 33 CFR 80.525 - Cape Lookout, NC to Cape Fear, NC.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Cape Lookout, NC to Cape Fear, NC... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Fifth District § 80.525 Cape Lookout, NC to Cape Fear... southeast side of the Inlet. (g) Except as provided elsewhere in this section from Cape Lookout to Cape Fear...

  9. 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.

  10. Microtubule-associated protein 1b is required for shaping the neural tube.

    Science.gov (United States)

    Jayachandran, Pradeepa; Olmo, Valerie N; Sanchez, Stephanie P; McFarland, Rebecca J; Vital, Eudorah; Werner, Jonathan M; Hong, Elim; Sanchez-Alberola, Neus; Molodstov, Aleksey; Brewster, Rachel M

    2016-01-18

    Shaping of the neural tube, the precursor of the brain and spinal cord, involves narrowing and elongation of the neural tissue, concomitantly with other morphogenetic changes that contribue to this process. In zebrafish, medial displacement of neural cells (neural convergence or NC), which drives the infolding and narrowing of the neural ectoderm, is mediated by polarized migration and cell elongation towards the dorsal midline. Failure to undergo proper NC results in severe neural tube defects, yet the molecular underpinnings of this process remain poorly understood. We investigated here the role of the microtubule (MT) cytoskeleton in mediating NC in zebrafish embryos using the MT destabilizing and hyperstabilizing drugs nocodazole and paclitaxel respectively. We found that MTs undergo major changes in organization and stability during neurulation and are required for the timely completion of NC by promoting cell elongation and polarity. We next examined the role of Microtubule-associated protein 1B (Map1b), previously shown to promote MT dynamicity in axons. map1b is expressed earlier than previously reported, in the developing neural tube and underlying mesoderm. Loss of Map1b function using morpholinos (MOs) or δMap1b (encoding a truncated Map1b protein product) resulted in delayed NC and duplication of the neural tube, a defect associated with impaired NC. We observed a loss of stable MTs in these embryos that is likely to contribute to the NC defect. Lastly, we found that Map1b mediates cell elongation in a cell autonomous manner and polarized protrusive activity, two cell behaviors that underlie NC and are MT-dependent. Together, these data highlight the importance of MTs in the early morphogenetic movements that shape the neural tube and reveal a novel role for the MT regulator Map1b in mediating cell elongation and polarized cell movement in neural progenitor cells.

  11. 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.

  12. [Granulomatous uveitis and CREST syndrome: a case study].

    Science.gov (United States)

    Courtade, M; Gicquel, J J; Mercie, M; Vabres, B; Dighiero, P

    2004-10-01

    To report a case of recurrent granulomatous panuveitis associated with CREST syndrome. A 74-year-old patient with CREST syndrome presented with unilateral granulomatous panuveitis in a pseudophakic eye. She had undergone cataract surgery 6 months before. The patient reported a vision loss that had been evolving for 1 month. Visual acuity was noted at 20/400. The initial clinical examination highlighted retrodescemetic precipitates and granulomatous precipitates on the IOL. A vitreous tyndall was noted. Funduscopic examination revealed papillary edema and cystoid macular edema, confirmed by fluorescein angiography. Topical treatment consisting in corticosteroid eye drops associated with mydriatics controlled uveitis in a few weeks. Visual recovery was 20/30. No granulomatous uveitis etiology could be highlighted. The diagnosis of chronic endophthalmitis was also ruled out. The diagnosis retained was uveitis associated with CREST syndrome. To our knowledge, this association has only been reported twice in the literature.

  13. Observations of highly localized oscillons with multiple crests and troughs

    CERN Document Server

    LI, Xiaochen; Liao, Shijun

    2014-01-01

    Stable, highly localized Faraday's resonant standing waves with multiple crests and troughs were observed in the alcoholic solution partly filled in a Hele-Shaw cell vertically oscillated with a single frequency. Two types of oscillons were observed. The influence of the experimental parameters (such as the concentration of alcoholic solution, the water depth, the frequency and acceleration amplitude of oscillation) on these oscillons were investigated in details. In the same experimental parameters, all of these oscillons have the almost same wave height but rather irregular crest-to-crest distances. Our experiments highly suggest that the complicated oscillons can be regarded as combination of the two elementary oscillons discovered by Rajchenbach et al. (Physical Review Letters, 107, 2011).

  14. CREST - a large and diverse superfamily of putative transmembrane hydrolases

    Directory of Open Access Journals (Sweden)

    Olson Eric N

    2011-07-01

    Full Text Available Abstract Background A number of membrane-spanning proteins possess enzymatic activity and catalyze important reactions involving proteins, lipids or other substrates located within or near lipid bilayers. Alkaline ceramidases are seven-transmembrane proteins that hydrolyze the amide bond in ceramide to form sphingosine. Recently, a group of putative transmembrane receptors called progestin and adipoQ receptors (PAQRs were found to be distantly related to alkaline ceramidases, raising the possibility that they may also function as membrane enzymes. Results Using sensitive similarity search methods, we identified statistically significant sequence similarities among several transmembrane protein families including alkaline ceramidases and PAQRs. They were unified into a large and diverse superfamily of putative membrane-bound hydrolases called CREST (alkaline ceramidase, PAQR receptor, Per1, SID-1 and TMEM8. The CREST superfamily embraces a plethora of cellular functions and biochemical activities, including putative lipid-modifying enzymes such as ceramidases and the Per1 family of putative phospholipases involved in lipid remodeling of GPI-anchored proteins, putative hormone receptors, bacterial hemolysins, the TMEM8 family of putative tumor suppressors, and the SID-1 family of putative double-stranded RNA transporters involved in RNA interference. Extensive similarity searches and clustering analysis also revealed several groups of proteins with unknown function in the CREST superfamily. Members of the CREST superfamily share seven predicted core transmembrane segments with several conserved sequence motifs. Conclusions Universal conservation of a set of histidine and aspartate residues across all groups in the CREST superfamily, coupled with independent discoveries of hydrolase activities in alkaline ceramidases and the Per1 family as well as results from previous mutational studies of Per1, suggests that the majority of CREST members are

  15. Small lymphocytic lymphoma in a patient with CREST syndrome.

    Science.gov (United States)

    William, Basem M; Harbert, Tracey; Ganti, Apar K; Bierman, Philip J

    2011-01-01

    We report a case of a 61-year-old man with a history of CREST syndrome (calcinosis cutis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) who presented for evaluation of thrombocytopenia. He had evident cervical adenopathy and lymph node biopsy showed small lymphocytic lymphoma (SLL) with evident systemic adenopathy and bone marrow involvement. The patient achieved a complete remission with FCR (fludarabine/cyclophosphamide/rituximab) chemotherapy. About 30 cases of lymphomas are reported in the literature in association with systemic sclerosis. To our knowledge, there are no reports of a small lymphocytic lymphoma (SLL) in association with limited cutaneous systemic sclerosis with classic features of the CREST syndrome.

  16. EnviroAtlas - Durham, NC - Block Groups

    Data.gov (United States)

    U.S. Environmental Protection Agency — This EnviroAtlas dataset is the base layer for the Durham, NC EnviroAtlas Area. The block groups are from the US Census Bureau and are included/excluded based on...

  17. A Comparative Experimental Study of Wave Forces on a Vertical Cylinder in Long-Crested and Short-Crested Seas

    DEFF Research Database (Denmark)

    Frigaard, Peter; Burcharth, Hans F.

    1988-01-01

    An experimental study is carried out to investigate the wave forces on a slender cylinder. Special attention is given to the wave forces in the surface zone and correlation of forces along the cylinder. The experiments consider the effects of both long and short-crested irregular waves.......An experimental study is carried out to investigate the wave forces on a slender cylinder. Special attention is given to the wave forces in the surface zone and correlation of forces along the cylinder. The experiments consider the effects of both long and short-crested irregular waves....

  18. Bare bone graft with vascularised iliac crest for mandibular reconstruction.

    Science.gov (United States)

    Sarukawa, Shunji; Noguchi, Tadahide; Oh-iwa, Ichiro; Sunaga, Ataru; Uda, Hirokazu; Kusama, Mikio; Sugawara, Yasushi

    2012-01-01

    "Bare bone graft" with a vascularised iliac crest is a procedure involving no soft tissue for intraoral lining, and the intraoral defect is covered with epithelial cells through secondary healing of the exposed bone. A vascularised iliac crest flap is transferred to a segmental mandibular defect intraorally in the position of the osteotomized stump upwardly. Granulation tissue is usually observed on the stump of the bone graft about 1 week after surgery. When sufficient granulation is observed after approximately 4 weeks, "resurfacing" is performed to prevent interference of hypergranulation tissue with epithelization. Resurfacing involves wiping the granulation tissue from the surface of the bone and covering with a plastic prosthesis fitted to the alveolus. A total of 11 patients underwent bare bone graft with a vascularised iliac crest. Resurfacing was performed at an average of 2.1 times for each patient. All wounds in the oral cavity were completely epithelialized from 2 weeks to 3 months after surgery. Complications with the recipient side occurred in four patients. Bare bone graft with the iliac crest is one favourable option for mandibular reconstruction utilising the particular shape of the bone without the attached soft tissue. Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  19. 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

  20. Genetic diversity and population structure of blue-crested lizard ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 96; Issue 2. Genetic diversity and population structure of blue-crested lizard, Calotes ... These two lineages are separated by mountain ranges, which play an important role as natural barriers blocking gene flow. Our finding reveal at least two cryptic lineages represented in C.

  1. 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, ...

  2. Genetic diversity and population structure of blue-crested lizard ...

    Indian Academy of Sciences (India)

    Weerachai Saijuntha

    2017-06-19

    Jun 19, 2017 ... Abstract. The blue-crested lizard, Calotes mystaceus Duméril & Bibron, 1837, is listed as a protected wild animal in Thailand. Its population is likely to be dramatically reduced due to massive hunting in several areas in this country. Basic information on its population genetics is therefore needed to facilitate ...

  3. Innovative concept overtopping dike : Crest Drainage Dike, Theoretical Study

    NARCIS (Netherlands)

    Verhagen, H.J.; Nieuwenhuis, O.E.

    2005-01-01

    The ComCoast concept involves measures in seaward and landward direction. One of the options in landward direction is an overtopping dike. In this concept the crest and/or inner slope of the dike is strengthened so that more overtopping of the dike can be allowed. Advantage is that heightening of

  4. 76 FR 15971 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Teleconference

    Science.gov (United States)

    2011-03-22

    ... Energy Regulatory Commission Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy... Eagle Crest Energy as part of its on-going Section 7 Endangered Species Act consultation efforts. e. All... Eagle Crest Energy, via e-mail at: [email protected] ; or via telephone at: 503-697-1478. All...

  5. 76 FR 22699 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Teleconference

    Science.gov (United States)

    2011-04-22

    ... Energy Regulatory Commission Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy... Eagle Crest Energy as part of its on-going Section 7 Endangered Species Act consultation efforts. e. All... Eagle Crest Energy, via e-mail at: [email protected] ; or via telephone at: 503-697-1478. All...

  6. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells

    Science.gov (United States)

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-01-01

    The ‘neural plate border’ of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure. DOI: http://dx.doi.org/10.7554/eLife.21620.001 PMID:28355135

  7. Mandibular defect reconstruction with nonvascularized iliac crest bone graft.

    Science.gov (United States)

    Okoje, V N; Obimakinde, O S; Arotiba, J T; Fasola, A O; Ogunlade, S O; Obiechina, A E

    2012-01-01

    Reconstruction of mandibular defect is a challenge to the head and neck surgeon because of associated functional and esthetic problems. Our experience with the use of nonvascularized iliac crest bone graft is hereby reported. The aim was to report our experience with the use of nonvascularized iliac crest bone for mandibular defect reconstruction at University College Hospital, Ibadan. Nigeria. A retrospective descriptive study was performed. Cases of mandibular reconstruction with iliac crest bone graft between January 2001 and December 2007 were included in this study. Grafts were secured with either a stainless steel wire or a titanium plate. Preoperative diagnosis, postoperative follow-up records including investigations, diagnosis of graft infection and subsequent treatment modalities were extracted from the available records. Descriptive variables were analyzed with SPSS version 14. A total of 47 patients had mandibular defect reconstruction with nonvascularized iliac crest block bone during the study period. Thirty-eight patients had graft secured with transosseous wire [NVIBw] while 9 had a titanium plate [NVIBp]. The male:female ratio was 26:21 while the mean age of the patients was 24.6±4.25 years. Ten patients (21.3%) developed persistent graft infection during the postoperative period. All cases of infection occurred in patients who had transosseous wiring and analysis showed that 60% of the infected grafts revealed mixed microbial isolates containing Klebsiela spp, Pseudomonas Aeurogenosa, and E coli. Six (60%) of the infected grafts were removed as a result of unabated infection while 4 (40%) were successfully treated by exploration and pus drainage. Nonvascularized iliac crest bone graft provides an affordable and less technical choice for mandibular reconstruction with minimal complications in a resource-limited economy.

  8. Flexibility of neural stem cells

    Directory of Open Access Journals (Sweden)

    Eumorphia eRemboutsika

    2011-04-01

    Full Text Available Embryonic cortical neural stem cells are self-renewing progenitors that can differentiate into neurons and glia. We generated neurospheres from the developing cerebral cortex using a mouse genetic model that allows for lineage selection and found that the self-renewing neural stem cells are restricted to Sox2 expressing cells. Under normal conditions, embryonic cortical neurospheres are heterogeneous with regard to Sox2 expression and contain astrocytes, neural stem cells and neural progenitor cells sufficiently plastic to give rise to neural crest cells when transplanted into the hindbrain of E1.5 chick and E8 mouse embryos. However, when neurospheres are maintained under lineage selection, such that all cells express Sox2, neural stem cells maintain their Pax6+ cortical radial glia identity and exhibit a more restricted fate in vitro and after transplantation. These data demonstrate that Sox2 preserves the cortical identity and regulates the plasticity of self-renewing Pax6+ radial glia cells.

  9. 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...... armour layer. Therefore, it was concluded that per used volume of concrete the Cubipods perform better than the cubes....

  10. 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....

  11. [CREST syndrome and pulmonary hypertension: a dark prognosis].

    Science.gov (United States)

    Carneiro, Ana C; Barbosa, Isabel P; Chaves, F Carneiro

    2004-01-01

    The CREST syndrome initially described as a limited, more indolent form of diffuse scleroderma, is characterized by calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasias. Subsequent studies showed that visceral abnormalities were not uncommon. Pulmonary abnormalities are frequent especially pulmonary hypertension, this one being a major cause of this syndrome's mortality. The authors present the case of white woman, 61 years old , with dyspnoea, cyanosis and peripheral edema with 12 months of evolution. She was admitted for pulmonary thromboembolism suspicion. After investigation the diagnosis of CREST syndrome was made, associated with severe pulmonary hypertension. The patient was treated with varfarina, nicorandil, nifedipine, furosemide and home oxygen. She died 3 months after. The authors discuss the diagnosis, treatment and follow-up.

  12. 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

  13. Scleroderma and CREST syndrome: a case report in dentistry.

    Science.gov (United States)

    Lauritano, D; Bussolati, A; Baldoni, M; Leonida, A

    2011-09-01

    CREST syndrome is part of the heterogeneous scleroderma group of autoimmune diseases that cause thickening, hardening and tightening of the connective tissue in different parts of the body, and it may lead to complex disorders. CREST syndrome is characterized by the coexistence of calcinosis, Raynaud's phenomenon, esophageal hypomotility, sclerodactily and telangectasia. A 72-year-old caucasian woman is referred to the S. Gerardo Hospital of Monza, with a chief complaint of oral pain and difficulties in deglutition and eating, associated with denture instability and difficulties to fit it. She had been previously diagnosed with Raynaud's phenomenon, and afterwards with CREST syndrome. Extra-oral examination underlined taut, thickened and rigid skin, pallid-red irregular maculae all over the face, telangiectasias and acrocyanosis. Intra-oral examination showed no alteration of the mucosa, but we can observe tongue rigidity and some speckled red alternating with white spots on the hard palate and in the vestibule. We undermitted the patient the dental treatment of Sjogren's syndrome. The management of the Sjogren's syndrome is symptomatic and empirical, and involves the use of saliva secretion stimulators, salivary substitutes and coadjuvants. Dental treatment and prophylaxis are important to prevent the consequences of xerostomia, such as rampant caries, based on the administration of topical fluoride in toothpastes and rinses, and supplemented by fluoride gels and varnishes. Instruction and reinforcement of oral hygiene, along with frequent dental assessment and management by the dentist are essential measures to preserve the oral health of those affected with CREST syndrome in progression to SS, complicated with Sjogren's syndrome.

  14. Pulmonary hypertension with limited cutaneous scleroderma (CREST syndrome).

    Science.gov (United States)

    Berends, J C; Dompeling, E C; van der Star, J G; Hoorntje, J C

    2000-12-01

    A patient is described with a typical manifestation of pulmonary hypertension associated with limited cutaneous scleroderma, also known as CREST syndrome. The patient was treated with a calcium antagonist, oral anticoagulation and, because of evidence for parenchymal inflammation of the lung, with low-dose prednisone and cyclophosphamide. This treatment resulted in initial improvement of diffusion capacity and exercise tolerance, however, 1 year after diagnosis the patient died of progressive pulmonary hypertension.

  15. Determinants of immigration strategies in male crested macaques (Macaca nigra).

    OpenAIRE

    Engelhardt, A.; Marty, PR; Hodges, JK

    2016-01-01

    Immigration into a new group can produce substantial costs due to resistance from residents, but also reproductive benefits. Whether or not individuals base their immigration strategy on prospective cost-benefit ratios remains unknown. We investigated individual immigration decisions in crested macaques, a primate species with a high reproductive skew in favour of high-ranking males. We found two different strategies. Males who achieved low rank in the new group usually immigrated after anoth...

  16. 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.

  17. Anti-myelin-associated glycoprotein polyneuropathy coexistent with CREST syndrome.

    Science.gov (United States)

    Andreadou, E; Zouvelou, V; Karandreas, N; Kilidireas, C

    2012-01-01

    Clinical involvement of the peripheral nervous system in the calcinosis cutis, raynaud's phenomenon, esophageal dismotility, sclerodactyly and telangiectasia (CREST) variant of systemic sclerosis occurs infrequently and is characterized by axonal degeneration due to necrotizing vasculitis. We report a female patient with a known history of CREST syndrome, which developed a slowly progressive, distal symmetric demyelinating sensorimotor polyneuropathy (PN), with tremor and ataxia as prominent features, compatible with anti-myelin associated glycoprotein (MAG) PN. The diagnosis of PN was established by the presence of monoclonal immunoglobulin M anti-MAG antibodies (Thin-Layer Chromatography, Western Blot and enzyme-linked immunoabsorbent assay). Given the evidence that in CREST activation of T-helper cells is observed and that anti-MAG antibodies, despite the fact that they are T-cell-independent, may be influenced by an increase in T-helper function, the coexistence of these two rare autoimmune disorders in the same patient may not be incidental but related to the underlying immunological mechanisms involved.

  18. Large vessel occlusive disease associated with CREST syndrome and scleroderma.

    Science.gov (United States)

    Youssef, P; Englert, H; Bertouch, J

    1993-01-01

    OBJECTIVES--To report the cases of three patients with CREST syndrome and one patient with diffuse scleroderma who had severe macrovascular disease and only minimal vascular risk factors. METHODS--The medical histories, physical examinations, and results of clinical investigations were reviewed in four patients. RESULTS--These four patients had severe morbidity from macrovascular disease of the arms and legs in the presence of minimal underlying vascular risk factors. These patients represent 11% of the women with scleroderma seen at our hospital since 1974. This is a greater than threefold increase above the expected proportion of symptomatic vascular disease seen in population studies. In the patients with CREST syndrome, large vessel disease was first seen more than 10 years after the onset of Raynaud's phenomenon, which was the first manifestation of the disease. A pathological specimen of the ulnar artery from one patient showed severe luminal narrowing by an acellular material with no evidence of atheroma. CONCLUSIONS--These cases suggest an association of both the CREST syndrome and scleroderma with macrovascular disease. PMID:8323401

  19. Anti-myelin-associated glycoprotein polyneuropathy coexistent with CREST syndrome

    Directory of Open Access Journals (Sweden)

    E Andreadou

    2012-01-01

    Full Text Available Clinical involvement of the peripheral nervous system in the calcinosis cutis, raynaud′s phenomenon, esophageal dismotility, sclerodactyly and telangiectasia (CREST variant of systemic sclerosis occurs infrequently and is characterized by axonal degeneration due to necrotizing vasculitis. We report a female patient with a known history of CREST syndrome, which developed a slowly progressive, distal symmetric demyelinating sensorimotor polyneuropathy (PN, with tremor and ataxia as prominent features, compatible with anti-myelin associated glycoprotein (MAG PN. The diagnosis of PN was established by the presence of monoclonal immunoglobulin M anti-MAG antibodies (Thin-Layer Chromatography, Western Blot and enzyme-linked immunoabsorbent assay. Given the evidence that in CREST activation of T-helper cells is observed and that anti-MAG antibodies, despite the fact that they are T-cell-independent, may be influenced by an increase in T-helper function, the coexistence of these two rare autoimmune disorders in the same patient may not be incidental but related to the underlying immunological mechanisms involved.

  20. Bupivacaine for pain reduction after iliac crest bone graft harvest.

    Science.gov (United States)

    O'Neill, Kevin R; Lockney, Dennis T; Bible, Jesse E; Crosby, Colin G; Devin, Clinton J

    2014-05-01

    Iliac crest bone graft remains the gold standard in achieving spinal arthrodesis, but chronic pain from graft harvest occurs in up to 39% of patients. Studies have shown that a single administration of local anesthetic reduces short-term pain, but they have not adequately investigated possible longer-term benefits. The goal of this study was to determine whether local administration of bupivacaine after iliac crest bone graft harvesting reduces pain and improves patient-reported outcomes. In this prospective, randomized, controlled, and blinded clinical study, 40 patients were identified who underwent posterior spine fusion with iliac crest bone graft and were randomized to receive either bupivacaine (treatment group, n=20) or saline (control group, n=20) at the iliac crest bone graft site. Pain at the harvest site was determined by a series of 12 visual and numeric pain scale assessments. Short Form-12 mental and physical component scores, EuroQol-5D, and Oswestry Disability Index assessments were made, along with determination of patient satisfaction and self-reported outcome of surgery. Baseline pain and outcome assessments were statistically similar (P>.05). Average pain scores were lower for all 12 assessments in the treatment group at mean follow-up of 5 weeks (significant differences in 6 assessments) and 20 weeks (significant differences in 2 assessments). No significant differences were found in Short Form-12 and EuroQol-5D scores. For patients who underwent lumbar fusion, the treatment group had significantly improved Oswestry Disability Index scores (mean±SD=10.8±7.1 vs 18.7±5.9, P=.012). Significantly more patients in the treatment group reported that surgery met all expectations (90% vs 50%, P=.016). This study is the 1st to show that a single administration of bupivacaine at the iliac crest bone graft harvest site during posterior spine fusion surgery can result in improved outcomes and reduced pain far beyond the anesthetic duration of activity

  1. 78 FR 72009 - Establishment of Class E Airspace; Star, NC

    Science.gov (United States)

    2013-12-02

    ... Federal Aviation Administration 14 CFR Part 71 Establishment of Class E Airspace; Star, NC AGENCY: Federal... at Star, NC, to accommodate a new Area Navigation (RNAV) Global Positioning System (GPS) Standard... Federal Register a notice of proposed rulemaking to establish Class E airspace at Star, NC (78 FR 54413...

  2. NC10 bacteria in marine oxygen minimum zones

    DEFF Research Database (Denmark)

    Padilla, Cory C; Bristow, Laura A; Sarode, Neha

    2016-01-01

    Bacteria of the NC10 phylum link anaerobic methane oxidation to nitrite denitrification through a unique O2-producing intra-aerobic methanotrophy pathway. A niche for NC10 in the pelagic ocean has not been confirmed. We show that NC10 bacteria are present and transcriptionally active in oceanic....... rRNA and mRNA transcripts assignable to NC10 peaked within the OMZ and included genes of the putative nitrite-dependent intra-aerobic pathway, with high representation of transcripts containing the unique motif structure of the nitric oxide (NO) reductase of NC10 bacteria, hypothesized...

  3. Concordance between vocal and genetic diversity in crested gibbons

    Directory of Open Access Journals (Sweden)

    Roos Christian

    2011-02-01

    Full Text Available Abstract Background Gibbons or small apes are, next to great apes, our closest living relatives, and form the most diverse group of contemporary hominoids. A characteristic trait of gibbons is their species-specific song structure, which, however, exhibits a certain amount of inter- and intra-individual variation. Although differences in gibbon song structure are routinely applied as taxonomic tool to identify subspecies and species, it remains unclear to which degree acoustic and phylogenetic differences are correlated. To trace this issue, we comparatively analyse song recordings and mitochondrial cytochrome b gene sequence data from 22 gibbon populations representing six of the seven crested gibbon species (genus Nomascus. In addition, we address whether song similarity and geographic distribution can support a recent hypothesis about the biogeographic history of crested gibbons. Results The acoustic analysis of 92 gibbon duets confirms the hypothesised concordance between song structure and phylogeny. Based on features of male and female songs, we can not only distinguish between N. nasutus, N. concolor and the four southern species (N. leucogenys, N. siki, N. annamensis, N. gabriellae, but also between the latter by applying more detailed analysis. In addition to the significant correlation between song structure and genetic similarity, we find a similar high correlation between song similarity and geographic distance. Conclusions The results show that the structure of crested gibbon songs is not only a reliable tool to verify phylogenetic relatedness, but also to unravel geographic origins. As vocal production in other nonhuman primate species appears to be evolutionarily based, it is likely that loud calls produced by other species can serve as characters to elucidate phylogenetic relationships.

  4. 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)

  5. Aerosolized iloprost in CREST syndrome related pulmonary hypertension.

    Science.gov (United States)

    Launay, D; Hachulla, E; Hatron, P Y; Goullard, L; Onimus, T; Robin, S; Fauchais, A L; Queyrel, V; Michon-Pasturel, U; Hebbar, M; Saulnier, F; Devulder, B

    2001-10-01

    To assess the outcome of patients with CREST syndrome associated severe pulmonary hypertension treated by aerosolized iloprost in a noncomparative study. Five patients with CREST syndrome associated severe pulmonary hypertension were treated with 100 microg/day of aerosolized iloprost. New York Heart Association functional class and exercise tolerance (6 min walk test) were assessed at baseline, after one month, and then every 6 months. A right heart catheterization was performed at baseline in all but one patient. Systolic pulmonary artery pressure (PAP) was measured with Doppler echocardiography after one month and every 6 months. The mean followup was 13.2 +/- 8.8 months (median 6, range 6-24). Subjective quality of life improved in all patients. NYHA functional class decreased from Class III to II in 3 patients, from Class III to I in one patient, and from Class IV to III in one patient. At 6 months, the distance walked in 6 min had increased from 352 +/- 48 to 437 +/- 56 m (p = 0.06). At one month the mean systolic PAP was 58 +/- 13 vs 81 +/- 9 mm Hg at baseline (p = 0.04). At 6 months the mean systolic PAP was 57 +/- 13 mm Hg (p = 0.06). The improvement of both clinical and hemodynamic status was maintained in the 2 patients treated for 2 years. Neither adverse effects nor need to increase the daily dose of iloprost were observed. One patient died of right heart failure and one patient did not experience any improvement of exercise tolerance and hemodynamics. Aerosolized iloprost might be potentially useful as treatment for CREST syndrome associated pulmonary hypertension. However, patients who could benefit from this treatment will probably have to undergo careful criteria selection.

  6. Clinical and histological characterization of hair coat and glandular tissue of Chinese crested dogs.

    Science.gov (United States)

    Wiener, Dominique J; Gurtner, Corinne; Panakova, Lucia; Mausberg, Theresa-Bernadette; Müller, Eliane J; Drögemüller, Cord; Leeb, Tosso; Welle, Monika M

    2013-04-01

    Two varieties exist in the Chinese crested dog breed, namely hairless Chinese crested dogs presenting with hypotrichosis and dentition abnormalities, and the coated powderpuffs. Hairless Chinese crested dogs are obligate heterozygotes for a FOXI3 mutation, and this phenotype is classified as a form of canine ectodermal dysplasia. We provide a detailed histological description of hair follicles and their density for the three subphenotypes (true hairless, semi-coated and powderpuffs) of Chinese crested dogs. Apocrine and exocrine glands of the skin and other tissues were compared with findings reported from dogs with X-linked ectodermal dysplasia. Skin biopsies were collected from 22 Chinese crested dogs. Additionally, the glands of the skin and other tissues were examined from another two dogs available for postmortem examination. Skin biopsies and tissues were processed, stained and evaluated in a blinded fashion. Hair follicular anomalies decreased with increasing number of hairs in the different phenotypes. The FOXI3 mutants had only simple primary hair follicles, whereas the nonmutant powderpuffs had compound follicles identical to other dog breeds. All Chinese crested dogs had an anagen-dominated hair cycle. Furthermore, apocrine glands in the skin and respiratory mucous glands of the mutant Chinese crested dogs were present and normal. We have identified striking histopathological differences between the three subphenotypes of Chinese crested dogs. We clearly demonstrated distinct differences between the canine ectodermal dysplasia in Chinese crested dogs and dogs with X-linked ectodermal dysplasia. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

  7. Coronary artery abnormalities in CREST syndrome revealed by cardiovascular magnetic resonance imaging.

    Science.gov (United States)

    Mavrogeni, Sophie; Bratis, Costas; Manoussakis, Menelaos

    2011-01-01

    CREST syndrome represents a subset of systemic sclerosis (SSc). Five patients with CREST syndrome and 5 with SSc without cardiac symptoms and with normal routine cardiac examination were investigated by cardiovascular magnetic resonance. All CREST patients had ectatic coronary arteries, and in 1 of them, an inferior, transmural myocardial infarction was identified. Furthermore, patchy fibrosis was identified in all the patients with SSc, although their coronary arteries were normal. Cardiovascular magnetic resonance can be a useful, noninvasive diagnostic tool in the evaluation of asymptomatic CREST and SSc patients. Copyright © 2011. Published by Elsevier Inc.

  8. 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.

  9. European Experience of Low Crested Structures for Coastal Management

    DEFF Research Database (Denmark)

    Kramer, Morten

    2005-01-01

    This paper aims to describe selected study sites monitored and analyzed during the DELOS project. All the selected sites are protected by Low Crested Structures (LCSs) under various environmental conditions. In the first part of the paper the characteristics of the European structures are presented...... parts, such as gaps and roundheads, where strong currents are responsible for erosion. Emergent LCSs show the formation of salients (Altafulla) or tombolos (Lønstrup) depending on the shoreline distances. In macro-tidal beaches (Elmer) tidal currents can control the salient development and the overall...

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

    Science.gov (United States)

    Bouchard, Susan M; Mohr, Melinda R; Pariser, Robert J

    2010-01-18

    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.

  11. Tinea Incognita in a Patient with Crest Syndrome: Case Report.

    Science.gov (United States)

    Gorgievska-Sukarovska, Biljana; Skerlev, Mihael; Žele-Starčević, Lidija

    2015-01-01

    Tinea incognita is a dermatophytic infection that is difficult to diagnose, usually modified by inappropriate topical or systemic corticosteroid therapy. We report an extensive case of tinea incognita caused by the zoophilic dermatophyte Trichophyton mentagrophytes (var. granulosa) in a 49-year-old female patient with CREST (Calcinosis; Raynaud phenomenon; Esophageal involvement; Sclerodactyly; Teleangiectasia) syndrome. Immunocompromised patients, as well as patients with keratinization disorders, seem to be especially susceptible to dermatophytic infections with atypical clinical presentation that is sometimes bizarre and difficult to recognize. Therefore, close monitoring and mycological skin examination is recommended in order to avoid misdiagnosis and to give the patient the best chance of recovery.

  12. Personality of Wild Male Crested Macaques (Macaca nigra)

    Science.gov (United States)

    Neumann, Christof; Agil, Muhammad; Widdig, Anja; Engelhardt, Antje

    2013-01-01

    Animal personalities, i.e. consistent differences in behavior across time and/or context, have received increased attention of behavioral biologists over the last years. Recent research shows that personalities represent traits on which natural and sexual selection work and which can have substantial fitness consequences. The aim of this study is to establish the personality structure of crested macaque (Macaca nigra) males as foundation for future studies on its adaptive value. We collected behavioral data through focal animal sampling and additionally conducted two sets of playback experiments. Results of a factor analysis on the behavioral data revealed a four factor structure with components we labeled Anxiety, Sociability, Connectedness and Aggressiveness. Results from the experiments revealed an additional and independent Boldness factor but the absence of Neophilia. Overall, this structure resembles other macaque and animal species with the exception of Connectedness, which might be a consequence of the species' tolerant social style. Our results thus not only form the basis for future studies on the adaptive value of personality in crested macaques but also contribute an important data point for investigating the evolution of personality structure from a comparative perspective by refining, for example, which personality factors characterized the last common ancestor of hominids and macaques. PMID:23940517

  13. Surgical management of digital calcinosis in CREST syndrome.

    Science.gov (United States)

    Merlino, Giorgio; Germano, Silvia; Carlucci, Salvatore

    2013-12-01

    As a limited form of sclerodermy, CREST syndrome is characterized by calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia, which determine the acronym CREST. Calcinosis is a particularly difficult entity to treat given the paucity of effective options described in the literature. Treatment of finger calcinosis has a wide range of possibilities depending on the extent of calcifications and the involvement of deep structures. From a surgical point of view, whereas simple removal is adequate in minor outpatient cases, a radical debridement in the major and more painful cases seems required. A cover flap is needed particularly in the thumb due to its great functional importance, also if the fingertip is not involved. The authors recommend the kite flap for the dimensions, the tissue quality, and the possibility of giving sensation to the reconstructed area. With this surgical option, the transferred skin is soft, sensate, and the right fit. Usually, no further operations are needed for flap remodeling. The time required for sensory integration is about 2 years, often related to the age of the patient. Debridement and flap reconstruction usually give total resolution of pain, with complete recovery of thumb motion and the thumb-index finger grip.

  14. Determinants of immigration strategies in male crested macaques (Macaca nigra).

    Science.gov (United States)

    Marty, Pascal R; Hodges, Keith; Agil, Muhammad; Engelhardt, Antje

    2016-08-18

    Immigration into a new group can produce substantial costs due to resistance from residents, but also reproductive benefits. Whether or not individuals base their immigration strategy on prospective cost-benefit ratios remains unknown. We investigated individual immigration decisions in crested macaques, a primate species with a high reproductive skew in favour of high-ranking males. We found two different strategies. Males who achieved low rank in the new group usually immigrated after another male had immigrated within the previous 25 days and achieved high rank. They never got injured but also had low prospective reproductive success. We assume that these males benefitted from immigrating into a destabilized male hierarchy. Males who achieved high rank in the new group usually immigrated independent of previous immigrations. They recieved injuries more frequently and therefore bore immigration costs. They, however, also had higher reproductive success prospects. We conclude that male crested macaques base their immigration strategy on relative fighting ability and thus potential rank in the new group i.e. potential reproductive benefits, as well as potential costs of injury.

  15. 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.

  16. Dual labeling of neural crest cells and blood vessels within chicken embryos using chick

    NARCIS (Netherlands)

    J.-M. Delalande (Jean-Marie); N. Thapar (Nikhil); A.J. Burns (Alan)

    2015-01-01

    textabstractAll developing organs need to be connected to both the nervous system (for sensory and motor control) as well as the vascular system (for gas exchange, fluid and nutrient supply). Consequently both the nervous and vascular systems develop alongside each other and share striking

  17. Neural crest-derived dental stem cells--where we are and where we are going.

    Science.gov (United States)

    Mayo, Vera; Sawatari, Yoh; Huang, C-Y Charles; Garcia-Godoy, Franklin

    2014-09-01

    There are five types of post-natal human dental stem cells that have been identified, isolated and characterized. Here, we review the information available on dental stem cells as well as their potential applications in dentistry, regenerative medicine and the development of other therapeutic approaches. Data pertinent to dental stem cells and their applications, published in peer-reviewed journals from 1982 to 2013 in English were reviewed. Sources were retrieved from PubMed databases as well as related references that the electronic search yielded. Manuscripts describing the origin, retrieval, characterization and application of dental stem cells were obtained and reviewed. Dental stem cell populations present properties similar to those of mesenchymal stem cells, such as the ability to self-renew and the potential for multilineage differentiation. While they have greater capacity to give rise to odontogenic cells and regenerate dental pulp and periodontal tissue, they have the capacity to differentiate into all three germ line cells, proving that a population of pluripotent stem cells exists in the dental tissues. Dental stem cells have the capacity to differentiate into endoderm, mesoderm and ectoderm tissues. Consequently they do not only have applications in dentistry, but also neurodegenerative and ischemic diseases, diabetes research, bone repair, and other applications in the field of tissue regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Kissing naevus arising from neural crest cells presenting as upper and the lower lid mass

    OpenAIRE

    Gian Chand Rajput; Deepti Mahajan; Kulbhushan Prakash Chaudhary; Deewana, V.

    2015-01-01

    A kissing nevus is a type of congenital compound nevus that affects equal portions of the upper and lower eyelid, and it extends to the lid margins. Congenital divided nevi of the eyelids are a rare melanocytic lesion. Only 30 patients are reported in the literature. We report a 40-year-old female of rural background who presented with a large painless enlarging pigmented mass, involving both upper and lower left eyelid since the past 20 years. Complete excision of the lesion was done, and th...

  19. The Development of a Primary Neural Crest Assay for Neuroblastoma Oncogenesis

    Science.gov (United States)

    2015-09-01

    CRISPR -­‐ CAS9  technology  we  are  going  introduced  silencing  mutations  in  the  various   gene...screening  for  oncogenic  drivers.    We  are  nearly  completed  on  generating   CRISPR -­‐ Cas9  guide  RNAs  that...determined  that  silencing  of  ARID1A  either  by  using  shRNA  (Figure  4A  and  B)  or  

  20. 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

  1. CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance

    NARCIS (Netherlands)

    Schulz, Yvonne; Wehner, Peter; Opitz, Lennart; Salinas-Riester, Gabriela; Bongers, Ernie M. H. F.; van Ravenswaaij-Arts, Conny M. A.; Wincent, Josephine; Schoumans, Jacqueline; Kohlhase, Juergen; Borchers, Annette; Pauli, Silke

    Heterozygous loss of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex developmental disorder affecting craniofacial structures, cranial nerves and several organ systems. Recently, it was demonstrated that CHD7 is essential for the formation

  2. 75 FR 3217 - Eagle Crest Energy Company; Notice of Application Ready for Environmental Analysis and Soliciting...

    Science.gov (United States)

    2010-01-20

    ... Energy Regulatory Commission Eagle Crest Energy Company; Notice of Application Ready for Environmental... filed: June 23, 2009. d. Applicant: Eagle Crest Energy Company. e. Name of Project: Eagle Mountain... Eagle Mountain Mine in Riverside County, California, near the Town of Desert Center, California, and...

  3. Conditional Second Order Short-crested Water Waves Applied to Extreme Wave Episodes

    DEFF Research Database (Denmark)

    Jensen, Jørgen Juncher

    2005-01-01

    A derivation of the mean second order short-crested wave pattern and associated wave kinematics, conditional on a given magnitude of the wave crest, is presented. The analysis is based on the second order Sharma and Dean finite water wave theory. A comparison with a measured extreme wave profile...

  4. 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...

  5. NC10 bacteria in marine oxygen minimum zones

    DEFF Research Database (Denmark)

    Padilla, Cory C; Bristow, Laura A; Sarode, Neha

    2016-01-01

    Bacteria of the NC10 phylum link anaerobic methane oxidation to nitrite denitrification through a unique O2-producing intra-aerobic methanotrophy pathway. A niche for NC10 in the pelagic ocean has not been confirmed. We show that NC10 bacteria are present and transcriptionally active in oceanic...... oxygen minimum zones (OMZs) off northern Mexico and Costa Rica. NC10 16S rRNA genes were detected at all sites, peaking in abundance in the anoxic zone with elevated nitrite and methane concentrations. Phylogenetic analysis of particulate methane monooxygenase genes further confirmed the presence of NC10...... to participate in O2-producing NO dismutation. These findings confirm pelagic OMZs as a niche for NC10, suggesting a role for this group in OMZ nitrogen, methane and oxygen cycling....

  6. 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.

  7. Environmental Design Guidelines for Low Crested Coastal Structures

    DEFF Research Database (Denmark)

    Burcharth, Hans F.; Hawkins, Stephen J.; Zanuttigh, Barbara

    The effect of human activities is primarily local but can extend far away from the location of intervention. This underlines the importance of establishing coastal zone management plans covering large stretches of coastlines. The interaction of wave climate, beach erosion, beach defence, habitat...... changes and beach value, which clearly exists based on EC research experiences and particularly on results obtained by DELOS Project (www.delos.unibo.it) for Low Crested Structures (LCSs), suggests the necessity of integrated approaches and thus the relevance of design guidelines covering: structure...... stability and construction problems, hydro and morphodynamic effects, environmental effects (colonisation of the structure and water quality), societal and economic impacts (recreational benefits, swimming safety, beach quality). The present guidelines are specifically dedicated to LCSs to provide...

  8. 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.

  9. Hycrest crested wheatgrass accelerates the degradation of pentachlorophenol in soil

    Science.gov (United States)

    Ferro, A. M.; Sims, R. C.; Bugbee, B.

    1994-01-01

    We investigated the effects of vegetation on the fate of pentachlorophenol (PCP) in soil using a novel high-flow sealed test system. Pentachlorophenol has been widely used as a wood preservative, and this highly toxic biocide contaminates soil and ground water at many sites. Although plants are known to accelerate the rates of degradation of certain soil contaminants, this approach has not been thoroughly investigated for PCP. The fate of [14C]PCP, added to soil at a concentration of 100 mg/kg, was compared in three unplanted and three planted systems. The plant used was Hycrest, a perennial, drought-tolerant cultivar of crested wheatgrass [Agropyron desertorum (Fischer ex Link) Schultes]. The flow-through test system allowed us to maintain a budget for 14C-label as well as monitor mineralization (breakdown to 14CO2) and volatilization of the test compound in a 155-d trial. In the unplanted systems, an average of 88% of the total radiolabel remained in the soil and leachate and only 6% was mineralized. In the planted system, 33% of the radiolabel remained in the soil plus leachate, 22% was mineralized, and 36% was associated with plant tissue (21% with the root fraction and 15% with shoots). Mineralization rates were 23.1 mg PCP mineralized kg-1 soil in 20 wk in the planted system, and for the unplanted system 6.6 mg PCP kg-1 soil for the same time period. Similar amounts of volatile organic material were generated in the two systems (1.5%). Results indicated that establishing crested wheatgrass on PCP-contaminated surface soils may accelerate the removal of the contaminant.

  10. ORF Sequence: NC_005296 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005296 gi|39933242 >gi|39933242|ref|NP_945518.1| possible nicotinate-nucleotide adn...WWLVSPGNPLKDISSLREIDARVAAAQAIADDPRIQVSRLEAVIGTRYTADTLRYLRRHCPGARFVWIMGADNLAQFHRWQQWQQIAAEIPIAVIDRPPTSFRALAAPAAQRLMRMRIPNNKAATLADREPPAWVYLTGLKSLVSSTALRNPDGSWKT

  11. ORF Sequence: NC_005814 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005814 gi|45476500 >gi|45476500|ref|NP_995415.1| putative RepA protein [Yersinia pestis biovar Mediev...VNEANKFGLEALCELMLAILDDLDLRDWQTIHNLETLADRAGLTTRSDAGHKSISRASRGCDRLSWLNAIISEKAPFNPYDARCACKHIEVTEDFFAILGIPLKQVYRERARLLKANPEEIISSGDVRLIAIKVENWTRKAAAGLARMKARRDAARQRKQEYYSPTFA

  12. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45440883 >gi|45440883|ref|NP_992422.1| heat shock protein GrpE [Yersinia pestis biovar Mediev...RRRTELDVEKAHKFALERFSSELLPVIDNLERALDTADKTNTELTSMIEGVELTLKSLLDAVGKFGIEVVGETHVPFNPEVHQAMTMLESADHEPNHVMMVMQKGYTLNGRLLRPAMVAVSKAKS

  13. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45439868 >gi|45439868|ref|NP_991407.1| aspartate-ammonia ligase [Yersinia pestis biovar Mediev...alis str. 91001] MKKQFIQKQQQISFVKSFFSRQLEQQLGLIEVQAPILSRVGDGTQDNLSGSEKAVQVKVKSLPDST

  14. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45440421 >gi|45440421|ref|NP_991960.1| malate dehydrogenase [Yersinia pestis biovar Mediev...DIVLISAGVARKPGMDRSDLFNVNAGIVRNLVEQIARTCPNALIGIITNPVNTTVAIAAEVLKKAGVYDKNKLFGITTLDTIRSNTFVAELKGKQPQDIEVPVIGGHS

  15. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45441614 >gi|45441614|ref|NP_993153.1| putative lipoprotein [Yersinia pestis biovar Mediev...VGTHFDYVLSSGADEFLTLLVTGQIDKKKIEVVRDGSFNLNKKKDGFTGKIALKYRYQTAEERGKIEPLIKGADWNCPSLTETTGICNINLNNLVGTIHRKGATPADIFRFEHPLQVKFYSKNTTSAKRALYPVAVAADVVMLPVYLLSAAAVAAFYGVVSLN

  16. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45443443 >gi|45443443|ref|NP_994982.1| chaperone protein DnaJ [Yersinia pestis biovar Mediev...IFEREGNNLYCEVPINFAMAALGGEIEVPTLDGRVKLKIPAETQTGKMFRMRGKGVKSVRGGSQGDLLCRVVVETPVSLSEKQKQLLRELEESFVGAAGEKNSPRAKSFLDGVKKFFDDLTR

  17. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available rsinia pestis biovar Medievalis str. 91001] MTTTTPIRLLVRPITAGDNLAIANVIREVSAEFGLTADKGYTVSDPNLDHLYELYSQPRSAYWVIEV... NC_005810 gi|45440492 >gi|45440492|ref|NP_992031.1| putative acetyltransferase [Ye

  18. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available PIVLEIGFGMGTSLVTMATNNPQQNFLGIEVHSPGVGACLSSAHDAGLSNLRIMCHDAVEVLENMIPEASLDMVQLFFPDPWHKARHNKRRIVQTPFVELVKSKLKVGGVFHMATDWQPYAEHMLEVMSGVSGYLNLSEQNDYVPRPDSRPLTKFELRGQRLGHGVWDLMFERKE ... NC_005810 gi|45443229 >gi|45443229|ref|NP_994768.1| Putative methyltransferase [Ye...rsinia pestis biovar Medievalis str. 91001] MINDVISPEFDENGRALRRIRSFVRRQGRLTKGQQLALDSYWPVMGVEYQAAPVDLNTLFGREA

  19. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45441658 >gi|45441658|ref|NP_993197.1| putative esterase [Yersinia pestis biovar Mediev...alis str. 91001] MNINTVPLATDFANLLAARRLFFGKGAQHETDYGRQRVARWIANVSAPLSGKIEVTGHVRRFIPEKLRSAEPI

  20. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45439934 >gi|45439934|ref|NP_991473.1| serine acetyltransferase [Yersinia pestis biovar Mediev...VSILQSVTLGGTGKTSGDRHPKIREGVMIGAGAKILGNIEVGRGAKIGAGSVVLQSVPAHTTAAGVPARIVGKPESDKPSLDMDQHFNGSIQGFEYGDGI

  1. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45442769 >gi|45442769|ref|NP_994308.1| putative membrane protein [Yer...NKTKGMENGIAIDSKSMSSKQRQKYSLNNVIPDMPILSIKTYSPEELSVKNNKNNKTEEYSLGYIEVIMKIQDLEFIHTVEKAGEVFLTPKSGDHKRIDLDDIIPTLQTIRELRG

  2. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45442616 >gi|45442616|ref|NP_994155.1| putative membrane protein [Yer...sinia pestis biovar Medievalis str. 91001] MSYVMFLQHLFSAKRRVLLLYLLVISIPIVYYITSRVIEVRNNKLLIKYSELSYHLQQHSIMAKK

  3. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45439885 >gi|45439885|ref|NP_991424.1| Predicted GTPases [Yersinia pestis biovar Mediev...alis str. 91001] MTIRNYNYHMTHFVISAPDIRHLPRDEGIEVAFAGRSNAGKSSALNTLTNQKGLARTSKTPGRTQLINLFEVV

  4. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45443717 >gi|45443717|ref|NP_995256.1| heat shock protein [Yersinia pestis biovar Mediev...alis str. 91001] MATYYLASKKELTYMRNYDLSPLLRQWIGFDKLASTMQGGQEPQGFPPYNIEKTDDNHYRISLALAGFKQSELDIEV

  5. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45440351 >gi|45440351|ref|NP_991890.1| 4Fe-4S ferrodoxin [Yersinia pestis biovar Mediev...AIITGSHGVQLLASRCIGCKTCMLVCPFGAMSIIERPADGQQAADSQPVMASGSGRAQAHKCDLCHQRESGPACIEVCPTNALKLVTPGVLEALQREKQLRAARGSAPGIAR

  6. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45442659 >gi|45442659|ref|NP_994198.1| putative membrane protein [Yer...sinia pestis biovar Medievalis str. 91001] MINFRGRFGRPLWHYLVLPVVLLLLAVILLTPMIVQTESTLKIRPNQQGLSLPDGFYLYQHLNGRGIHIKSIIPENDSLVVSLEFPEQQMQAIEVLQDVLPAGYAIVASESKKRHRLLPVFRSNQQNLG

  7. ORF Sequence: NC_006155 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available g protein (involved in environmental [Yersinia pseudotuberculosis IP 32953] MTKTDYLMRLRKCTTIDTLERVIEKNKYELSDDELELFYSAADHRLAELTMNKLYDKIPPTVWQHVK ... NC_006155 gi|51595328 >gi|51595328|ref|YP_069519.1| hemolysin expression modulatin

  8. ORF Sequence: NC_003078 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available etitiveness [Sinorhizobium meliloti 1021] MQLSACARRREAVRYRRRMARILILLFSLLSAFAFPVTPVP... NC_003078 gi|16264863 >gi|16264863|ref|NP_437655.1| probable membrane protein necessary for nodulation comp

  9. ORF Sequence: NC_002678 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_002678 gi|13471138 >gi|13471138|ref|NP_102707.1| transcriptional regulatory protein, nodulation competit...iveness determinant [Mesorhizobium loti MAFF303099] MTNESDTRSAELAELTADIVSAYVSNNPLPV

  10. ORF Sequence: NC_002607 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available MRRDDRDDPFDDIFREIERMMEDMMADGQRLDRGDQSGFASSTHVDVHETEDAIRVIADLPGVEKDDISIQCDGTSVTVSAQSGHREYDERVDLPGRVDAHSGAATYNNGILEVAFDRTESSTNIDVQ ... NC_002607 gi|15789422 >gi|15789422|ref|NP_279246.1| Hsp2 [Halobacterium sp. NRC-1

  11. ORF Sequence: NC_004088 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available rsinia pestis KIM] MVKQFTSGLIISTFFLAVPGYAASFDCDNAKGYVETSICTNPVLSKLDDTLLSVYAKAQAAAPDQEINIRNEQREWLKNSRNTLTSEDALILSYEARIAQLSKANVSIPASAASETPVSTPD ... NC_004088 gi|22125156 >gi|22125156|ref|NP_668579.1| hypothetical protein y1256 [Ye

  12. ORF Sequence: NC_004431 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_004431 gi|26249430 >gi|26249430|ref|NP_755470.1| Transposase [Escherichia coli ...CFT073] MPLLDKLREQYGVGPVCSELHIAPSTYYHCQQQRHHPDKRSARAQRDDWLKKEIQRVYDENHQVYGVRKVWRQLLREGIRVARCTVARLMAVMGLAGVLRGKKVRTTSAGKPLLQVTA

  13. ORF Sequence: NC_002128 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available O157:H7] MPLLDKLREQYGVGPVCSELHIAPSTYYHCQQQRHHPDKRSARAQRDDWLKREIQRVYDENHQVYGVRKVWRQLLREGIRVARCTVARLMAVMGLAGVL... NC_002128 gi|10955343 >gi|10955343|ref|NP_052684.1| transposase [Escherichia coli

  14. ORF Sequence: NC_003070 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003070 gi|18407972 >gi|18407972|ref|NP_564823.1| no apical meristem (NAM) famil...y protein [Arabidopsis thaliana] MQAEEIICRVSDEEIIENYLRPKINGETSSIPRYVVELAEELYTVEPWLLPRQTAPILNPGEWFYFGKRNRKYSN

  15. ORF Sequence: NC_003901 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available anosarcina mazei Go1] MMFATIGASFHKGWRAGPSIFMGHALVECILFMLILIGASSFLRQSIISYLSIVGGFVMVAFGLLMIKKAKEASTMDVSISASSLN... NC_003901 gi|21228124 >gi|21228124|ref|NP_634046.1| transporter, LysE family [Meth

  16. 76 FR 5580 - Eagle Crest Energy Company; Notice of Applicant-Proposed Water Pipeline Route for the Proposed...

    Science.gov (United States)

    2011-02-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Eagle Crest Energy Company; Notice of Applicant-Proposed Water Pipeline... January 21, 2011. On June 22, 2009, Eagle Crest Energy Company (Eagle Crest or applicant) filed an...

  17. Comparison between implants inserted into piezo split and unsplit alveolar crests.

    Science.gov (United States)

    Danza, Matteo; Guidi, Riccardo; Carinci, Francesco

    2009-11-01

    Piezoelectric surgery (PES) uses a modulated ultrasonic frequency that permits highly precise and safe hard tissue cutting. A retrospective study on a series of spiral family implants inserted with or without PES split crest was performed to verify if implants inserted into crests split using PES have a comparable outcome to those inserted into unsplit bone. In the period from May 2004 to November 2007, 86 patients (55 women and 31 men, median age 53 yrs) were operated on and 234 spiral family implants were inserted. Among these, 21 were inserted into PES split crest. Mean follow-up was 13 months (3 to 35 months). The Kaplan-Meier algorithm was used to compare the 2 groups in survival and clinical success (ie, decreased bone resorption around implant neck). Only 9 of 234 implants were lost (ie, survival rate 96.2%), all of which belonged to the unsplit group but no statistical difference was demonstrated. To detect if PES split crest produces a better clinical outcome in comparison with fixtures inserted into unsplit alveolar ridges, crestal bone loss was compared in the remaining loaded implants (234--9 lost--5 not prosthetized = 220). No statistical significant difference was detected by comparing implants inserted into PES split crests with untreated alveolar ridges, although a better trend was visible for fixtures inserted into PES split crests. PES split crests provide several advantages and clinical outcomes that are not worse in terms of bone remodeling, if compared with standard procedures.

  18. Mean alveolar bone crest height decrement in subjects with an osteoporosis risk

    Science.gov (United States)

    Effrianto, H. P. S.; Priminiarti, M.; Makes, B. N.

    2017-08-01

    People 40-75 years of age have an osteoporosis risk that may be signaled by a decrease in alveolar bone crest height. Thus, this measure can be used as an indicator of osteoporosis risk. This study was conducted to provide a database of decreased alveolar bone crest heights in ages at risk of osteoporosis by using intraoral radiographs. Forty periapical radiographs of the posterior region of tooth 36 (or 46) were measured twice at different times by two different observers. The interproximal decrease in alveolar bone crest height was measured from the alveolar bone crest to the cementoenamel junction (CEJ) for each tooth on the mesial and distal sides using a ruler (mm). The mean decrease in alveolar bone crest height in at-risk ages for osteoporosis was 3.50±1.085 mm, with a mean of 3.15±0.864 mm for those 45-59 years of age, and 3.90±1.156 mm for those aged 60-75 years. The mean decrease in alveolar bone crest height in people 60-75 years of age was larger than in people 45-59 years of age. There was a medium correlation between age and decreased alveolar bone crest height.

  19. Nodular regenerative hyperplasia of the liver, CREST syndrome and primary biliary cirrhosis: an overlap syndrome?

    Science.gov (United States)

    McMahon, R F; Babbs, C; Warnes, T W

    1989-01-01

    Nodular regenerative hyperplasia of the liver (NRHL) has been found in association with collagen vascular diseases, after drug therapy, with autoimmune disease, and with a variety of haematological disorders. The association of NRHL with the syndrome of Calcinosis cutis, Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly and telangiectasia (CREST syndrome) has only been reported on two previous occasions. The liver disease usually associated with CREST syndrome is primary biliary cirrhosis (PBC) and recently nodular hyperplasia of the liver has been reported in patients with early stage PBC. We present a case of NRHL with CREST syndrome and serological and biochemical features of PBC, a newly recognised overlap syndrome. Images Figure PMID:2583572

  20. Analysis of Overtopping Flow on Sea Dikes in Oblique and Short-Crested Waves

    DEFF Research Database (Denmark)

    Nørgaard, Jørgen Harck; Andersen, Thomas Lykke; Burcharth, Hans F.

    2013-01-01

    in a shallow water basin at Aalborg University to cover the so far unknown 3D effects from oblique long-crested and short-crested waves. Based on results from the laboratory tests, expansions are proposed to the existing 2D formulae so as to cover oblique and short-crested waves. The wave obliquity is seen......Dike resilience against wave overtopping has gained more and more attention in recent years due to the effect of expected future climate changes. The overtopping flow velocities and flow depths on dikes have recently been studied in 2D small-scale experiments. This has led to semi...

  1. ncRNA consensus secondary structure derivation using grammar strings.

    Science.gov (United States)

    Achawanantakun, Rujira; Sun, Yanni; Takyar, Seyedeh Shohreh

    2011-04-01

    Many noncoding RNAs (ncRNAs) function through both their sequences and secondary structures. Thus, secondary structure derivation is an important issue in today's RNA research. The state-of-the-art structure annotation tools are based on comparative analysis, which derives consensus structure of homologous ncRNAs. Despite promising results from existing ncRNA aligning and consensus structure derivation tools, there is a need for more efficient and accurate ncRNA secondary structure modeling and alignment methods. In this work, we introduce a consensus structure derivation approach based on grammar string, a novel ncRNA secondary structure representation that encodes an ncRNA's sequence and secondary structure in the parameter space of a context-free grammar (CFG) and a full RNA grammar including pseudoknots. Being a string defined on a special alphabet constructed from a grammar, grammar string converts ncRNA alignment into sequence alignment. We derive consensus secondary structures from hundreds of ncRNA families from BraliBase 2.1 and 25 families containing pseudoknots using grammar string alignment. Our experiments have shown that grammar string-based structure derivation competes favorably in consensus structure quality with Murlet and RNASampler. Source code and experimental data are available at http://www.cse.msu.edu/~yannisun/grammar-string.

  2. Inherent and antigen-induced airway hyperreactivity in NC mice

    Directory of Open Access Journals (Sweden)

    Tetsuto Kobayashi

    1999-01-01

    Full Text Available In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those strains in vivo. NC mice again showed comparable airway reactivity to that seen in A/J mice and a significantly greater reactivity than that seen in BALB/c and C57BL/6 mice. To investigate the effects of airway inflammation on airway reactivity to acetylcholine in vivo, NC and BALB/c mice were sensitized to and challenged with antigen. Sensitization to and challenge with antigen induced accumulation of inflammatory cells, especially eosinophils, in lung and increased airway reactivity in NC and BALB/c mice. These results indicate that NC mice exhibit inherent and antigen-induced airway hyperreactivity. Therefore, NC mice are a suitable strain to use in investigating the mechanisms underlying airway hyperreactivity and such studies will provide beneficial information for understanding the pathophysiology of asthma.

  3. 76 FR 49664 - Drawbridge Operation Regulation; Beaufort Channel, Beaufort, NC

    Science.gov (United States)

    2011-08-11

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Beaufort Channel, Beaufort, NC AGENCY... the Grayden Paul Bridge across the Beaufort (Gallants) Channel, mile 0.1 at Beaufort, NC. The... current operating regulations of the Grayden Paul Bridge, across the Beaufort (Gallants) Channel, mile 0.1...

  4. 33 CFR 117.822 - Beaufort Channel, NC.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Beaufort Channel, NC. 117.822 Section 117.822 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements North Carolina § 117.822 Beaufort Channel, NC. The...

  5. 77 FR 45247 - Drawbridge Operation Regulations; Gallants Channel, Beaufort, NC

    Science.gov (United States)

    2012-07-31

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulations; Gallants Channel, Beaufort, NC... operation of the US 70 (Grayden Paul) Bridge, at mile 0.1, over Gallants Channel, at Beaufort, NC. The... out in 33 CFR 117.823, the draw of the US 70 (Grayden Paul) Bridge, at mile 0.1, over Gallants Channel...

  6. Neural activity during interoceptive awareness and its associations with alexithymia – An fMRI study in major depressive disorder and non-psychiatric controls

    Directory of Open Access Journals (Sweden)

    Christine eWiebking

    2015-05-01

    Full Text Available Objective: Alexithymia relates to difficulties recognizing and describing emotions. It has been linked to subjectively increased interoceptive awareness (IA and to psychiatric illnesses such as major depressive disorder (MDD and somatization. MDD in turn is characterized by aberrant emotion processing and IA on the subjective as well as on the neural level. However, a link between neural activity in response to IA and alexithymic traits in health and depression remains unclear. Methods: A well-established fMRI task was used to investigate neural activity during IA (heartbeat counting and exteroceptive awareness (tone counting in non-psychiatric controls (NC and MDD. Firstly, comparing MDD and NC, a linear relationship between IA-related activity and scores of the Toronto Alexithymia Scale (TAS was investigated through whole-brain regression. Secondly, NC were divided by median-split of TAS scores into groups showing low (NC-low or high (NC-high alexithymia. MDD and NC-high showed equally high TAS scores. Finally, IA-related neural activity was compared on a whole-brain level between the three independent samples (MDD, NC-low, NC-high. Results: Whole-brain regressions between MDD and NC revealed neural differences during IA as a function of TAS-DD (subscale difficulty describing feelings in the supragenual anterior cingulate cortex (sACC; BA 24/32, which were due to negative associations between TAS-DD and IA-related activity in NC. Contrasting NC subgroups, high TAS scores were associated with decreased neural activity during IA in the sACC and increased insula activity. Though having equally high alexithymia scores, NC-high showed increased insula activity during IA compared to MDD, whilst both groups showed decreased activity in the sACC. Conclusions: Within the context of decreased sACC activity during IA in alexithymia (NC-high and MDD, increased insula activity might mirror a compensatory mechanism in NC-high, which is disrupted in MDD.

  7. NC CATCH: Advancing Public Health Analytics.

    Science.gov (United States)

    Studnicki, James; Fisher, John W; Eichelberger, Christopher; Bridger, Colleen; Angelon-Gaetz, Kim; Nelson, Debi

    2010-01-01

    The North Carolina Comprehensive Assessment for Tracking Community Health (NC CATCH) is a Web-based analytical system deployed to local public health units and their community partners. The system has the following characteristics: flexible, powerful online analytic processing (OLAP) interface; multiple sources of multidimensional, event-level data fully conformed to common definitions in a data warehouse structure; enabled utilization of available decision support software tools; analytic capabilities distributed and optimized locally with centralized technical infrastructure; two levels of access differentiated by the user (anonymous versus registered) and by the analytical flexibility (Community Profile versus Design Phase); and, an emphasis on user training and feedback. The ability of local public health units to engage in outcomes-based performance measurement will be influenced by continuing access to event-level data, developments in evidence-based practice for improving population health, and the application of information technology-based analytic tools and methods.

  8. A retrospective study of iliac crest bone grafting techniques with allograft reconstruction: do patients even know which iliac crest was harvested? Clinical article.

    Science.gov (United States)

    Pirris, Stephen M; Nottmeier, Eric W; Kimes, Sherri; O'Brien, Michael; Rahmathulla, Gazanfar

    2014-10-01

    Considerable biological research has been performed to aid bone healing in conjunction with lumbar fusion surgery. Iliac crest autograft is often considered the gold standard because it has the vital properties of being osteoconductive, osteoinductive, and osteogenic. However, graft site pain has been widely reported as the most common donor site morbidity. Autograft site pain has led many companies to develop an abundance of bone graft extenders, which have limited proof of efficacy. During the surgical consent process, many patients ask surgeons to avoid harvesting autograft because of the reported pain complications. The authors sought to study postoperative graft site pain by simply asking patients whether they knew which iliac crest was grafted when a single skin incision was made for the fusion operation. Twenty-five patients underwent iliac crest autografting with allograft reconstruction during instrumented lumbar fusion surgery. In all patients the autograft was harvested through the same skin incision but with a separate fascial incision. At various points postoperatively, the patients were asked if they could tell which iliac crest had been harvested, and if so, how much pain did it cause (10-point Numeric Rating Scale). Most patients (64%) could not correctly determine which iliac crest had been harvested. Of the 9 patients who correctly identified the side of the autograft, 7 were only able to guess. The 2 patients who confidently identified the side of grafting had no pain at rest and mild pain with activity. One patient who incorrectly guessed the side of autografting did have significant sacroiliac joint degenerative pain bilaterally. Results of this study indicate the inability of patients to clearly define their graft site after iliac crest autograft harvest with allograft reconstruction of the bony defect unless they have a separate skin incision. This simple, easily reproducible pilot study can be expanded into a larger, multiinstitutional

  9. 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.

  10. 76 FR 22393 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Cancellation...

    Science.gov (United States)

    2011-04-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy... and Wildlife Service for the proposed Eagle Mountain Pumped Storage Hydroelectric Project. This...

  11. Biology of nesting crested, least, and whiskered auklets at Buldir Island, Alaska

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — During avifaunal investigations at Buldir Island 1974-1976, some aspects of the biology of Crested, Least, and Whiskered Auklets were investigated in a colony where...

  12. Nodular regenerative hyperplasia of the liver, CREST syndrome and primary biliary cirrhosis: an overlap syndrome?

    OpenAIRE

    McMahon, R F; Babbs, C; Warnes, T. W.

    1989-01-01

    Nodular regenerative hyperplasia of the liver (NRHL) has been found in association with collagen vascular diseases, after drug therapy, with autoimmune disease, and with a variety of haematological disorders. The association of NRHL with the syndrome of Calcinosis cutis, Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly and telangiectasia (CREST syndrome) has only been reported on two previous occasions. The liver disease usually associated with CREST syndrome is primary biliary ci...

  13. Immediate implant placement: the fate of the buccal crest. A retrospective cone beam computed tomography study.

    Science.gov (United States)

    Groenendijk, E; Staas, T A; Graauwmans, F E J; Bronkhorst, E; Verhamme, L; Maal, T; Meijer, G J

    2017-12-01

    This retrospective study aimed to analyse the fate of the buccal crest after immediate implant placement (IIP) through the use of cone beam computed tomography (CBCT). In 16 consecutive patients, an implant was placed in a more palatal position after extraction, thereby creating a gap of at least 2mm between the implant and the buccal crest. Subsequently, this gap was filled with a bone substitute. Preoperatively, immediate postoperatively, and late postoperatively, a CBCT was made to measure the thickness of the buccal crest. After application of the bone substitute, the buccal crest increased in thickness from 0.9mm to 2.4mm (mean). At a mean of 103 weeks after IIP, late postoperative CBCT scans showed that the thickness of the buccal crest was compacted to 1.8mm. In the same period, the height of the buccal crest increased by 1.6mm (mean) to, on average, 1.2mm above the implant shoulder. The aesthetic outcome was analysed using the White and Pink Esthetic Score (WES and PES). Both scored high: 8.4 and 11.8, respectively. Within the limitations of this study, the results of this IIP protocol are promising. Long-term prospective research on this topic on a large number of patients is necessary. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  14. On pseudorandom generators in NC0

    DEFF Research Database (Denmark)

    Cryan, Mary; Miltersen, Peter Bro

    2001-01-01

    In this paper we consider the question of whether NC 0 circuits can generate pseudorandom distributions. While we leave the general question unanswered, we show – • Generators computed by NC 0 circuits where each output bit depends on at most 3 input bits (i.e, DNC 3 0 circuits) and with stretch....... – • There is an NC 4 0 generator with a super-linear stretch that passes the linear dependency test as well as k-wise independence tests, for any constant k....

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Development of NC1 and NC2 domains of type VII collagen ELISA for the diagnosis and analysis of the time course of epidermolysis bullosa acquisita patients.

    Science.gov (United States)

    Saleh, Marwah Adly; Ishii, Ken; Kim, Yool-Ja; Murakami, Akihiro; Ishii, Norito; Hashimoto, Takashi; Schmidt, Enno; Zillikens, Detlef; Shirakata, Yuji; Hashimoto, Koji; Kitajima, Yasuo; Amagai, Masayuki

    2011-06-01

    Epidermolysis bullosa acquisita (EBA) is an acquired autoimmune mechanobullous disease. EBA patients possess autoantibodies against type VII collagen which is composed of a collagenous domain flanked by non-collagenous NC1 and NC2 domains. It was reported that major epitopes reside within the NC1 domain and minor epitopes reside within NC2 domain. The aim of this study is to develop a sensitive and specific ELISA to facilitate the diagnosis of EBA. We developed ELISAs using recombinant NC1 domain produced by mammalian expression system and recombinant NC2 domain produced by mammalian or bacterial expression system to characterize autoantibodies in EBA. Next, we developed an ELISA using a combination of the NC1 (mammalian expression) and NC2 (bacterial expression). We tested the ELISAs with 49 EBA sera, 55 normal control sera, 20 pemphigus vulgaris and 20 bullous pemphigoid sera. When we evaluated the 49 EBA sera using the NC1 and NC2 ELISAs, 38 (77.5%) reacted with NC1 domain only, 7 sera (14.2%) reacted with both NC1 and NC2 domains, and one serum (2%) reacted with NC2 domain only. Therefore, to increase the sensitivity of the assay, we developed an ELISA coated with a mixture of recombinant NC1 and NC2 domains, resulting in 93.8% sensitivity and 98.1% specificity. By analyzing the time course of two EBA patients, ELISA scores fluctuated in parallel with their disease activity. We conclude that the NC1+NC2 ELISA can be a practical assay for the diagnosis and follow up of the antibody titers of EBA patients. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. ORF Sequence: NC_006513 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006513 gi|56476405 >gi|56476405|ref|YP_157994.1| outer membrane protein, ortholog involved in agglutinat...ion in some bacteria [Azoarcus sp. EbN1] MKNLRTVICVAALAALPRFAAAEVPEALRDAARKAVVANPEV

  18. ORF Alignment: NC_006138 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006138 gi|51244364 >1ek9A 2 411 56 457 3e-44 ... ref|YP_064248.1| similar to outer membrane (agglutination...ter ... membrane (agglutination) protein [Desulfotalea ... psychrophila LSv54] ... Lengt

  19. ORF Alignment: NC_006371 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006371 gi|54302263 >1ek9A 1 410 26 423 9e-60 ... ref|YP_132256.1| putative agglutination... protein [Photobacterium profundum SS9] ... emb|CAG22456.1| putative agglutination protein ...

  20. ORF Alignment: NC_005085 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005085 gi|34495763 >1ek9A 2 407 6 404 7e-54 ... gb|AAQ57987.2| probable agglutination... protein [Chromobacterium violaceum ATCC ... 12472] ref|NP_899978.1| probable agglutination protei

  1. ORF Sequence: NC_001144 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available efective in mating and agglutination, expression is downregulated by alpha-factor; Ccw12p [Saccharomyces cer... NC_001144 gi|6323139 >gi|6323139|ref|NP_013211.1| Cell wall protein, mutants are d

  2. ORF Sequence: NC_001139 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Spo12p; overexpression bypasses need for Spo12p, but not required for meiosis; Bns1p [Saccharomyces cerevisi... NC_001139 gi|6321669 >gi|6321669|ref|NP_011746.1| Protein with some similarity to

  3. ORF Alignment: NC_006086 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006086 gi|50914876 >1edt0 6 248 223 459 1e-24 ... emb|CAE84954.1| chitin binding protein [Debaryomyces robe...rtsiae] ... Length = 237 ... Query: 138 WHDKTSDPTEKDKVNSMGELPKEVDLAFIFHDWTKDYSL

  4. ORF Sequence: NC_006270 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006270 gi|52079925 >gi|52079925|ref|YP_078716.1| Hypothetical Lambda integrase-like, N-terminal,DNA brea...king-rejoining enzyme, catalytic core [Bacillus licheniformis ATCC 14580] MYMRGRRRP

  5. ORF Alignment: NC_003295 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003295 gi|17546126 >1wqgA 1 184 3 186 8e-57 ... emb|CAD15109.1| PROBABLE RIBOSOME RECYCLING... ... PROBABLE RIBOSOME RECYCLING FACTOR (RIBOSOME RELEASING ... FACTOR) PROTEIN [Ralstonia solana

  6. ORF Sequence: NC_001137 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_001137 gi|6320997 >gi|6320997|ref|NP_011076.1| Coiled-coil polarisome protein r...equired for polarized morphogenesis, cell fusion, and low affinity Ca2+ influx; forms polarisome complex wit

  7. ORF Sequence: NC_003995 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available vities [Bacillus anthracis str. A2012] MKEVLEVLPKTMKQLVESCKQYDALEEIRVRIGRPLECIAHGEV... NC_003995 gi|21402245 >gi|21402245|ref|NP_658230.1| AAA, ATPases associated with a variety of cellular acti

  8. ORF Alignment: NC_005125 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005125 gi|37520491 >1vp6A 12 129 11 134 4e-08 ... ref|NP_923868.1| nitrogen assimilation... regulatory protein [Gloeobacter violaceus PCC ... 7421] dbj|BAC88863.1| nitrogen assimilation

  9. ORF Sequence: NC_001135 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_001135 gi|10383790 >gi|10383790|ref|NP_009956.2| Putative Rheb-related GTPase involved in regulating can...avanine resistance and arginine uptake; member of the Ras superfamily of G-proteins

  10. ORF Sequence: NC_003281 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003281 gi|17557043 >gi|17557043|ref|NP_498707.1| copper (CU) Chaperonin, functi...onal, complements yeast atx1 mutant (7.6 kD) (cuc-1) [Caenorhabditis elegans] MTQYVFEMGMTCNGCANAARKVLGKLGEDKIKIDDINVETKKITVTTDLPASDVLEALKKTGKEIKQLQ

  11. ORF Sequence: NC_001133 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_001133 gi|6319307 >gi|6319307|ref|NP_009390.1| Cystathionine gamma-lyase, catalyzes one of the two react...ions involved in the transsulfuration pathway that yields cysteine from homocystein

  12. ORF Sequence: NC_003281 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003281 gi|25151987 >gi|25151987|ref|NP_499440.2| TRAnsformer : XX animals trans...formed into males TRA-1, HERmaphrodization of XO animals HER-2, sex determination zinc-finger protein, alter

  13. ORF Sequence: NC_003282 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available inization of XX and XO animals FEM-3 (46.2 kD) (fem-3) [Caenorhabditis elegans] MEVDPGSDDVEADRETRAQKLKLKRNVK... NC_003282 gi|17540880 >gi|17540880|ref|NP_501587.1| sex determination protein, FEM

  14. ORF Alignment: NC_006274 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006274 gi|52140937 >1y0yA 3 348 7 355 e-103 ... ref|YP_085892.1| glucanase/ deblocking... aminopeptidase [Bacillus cereus ZK] ... gb|AAU15956.1| glucanase/ deblocking aminopeptidase ...

  15. ORF Sequence: NC_001136 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_001136 gi|6320315 >gi|6320315|ref|NP_010395.1| Nucleolar protein required for DNA replication fork block...ing and recombinational hotspot activities; binds to the replication fork barrier s

  16. ORF Alignment: NC_004307 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_004307 gi|23465117 >1g5aA 80 628 2 589 5e-59 ... gb|AAL05573.1| alpha-glucosidase [Bifidobacterium adolesce...ntis] ... Length = 588 ... Query: 1 ... MTANNLNDDWWKQAVVYQIYPRSFKDVNGDGLGDIAGVTEK

  17. ORF Sequence: NC_001146 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available factor, as suggested by computational analysis of large-scale protein-protein interaction data; Ist1p [Sacch... NC_001146 gi|6324064 >gi|6324064|ref|NP_014134.1| Putative translation initiation

  18. Observations of NC stop nets for bottlenose dolphin takes

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — To observe the NC stop net fishery to document the entanglement of bottlenose dolphins and movement of dolphins around the nets.

  19. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45442575 >gi|45442575|ref|NP_994114.1| 30S ribosomal protein S2 [Yersinia pestis biovar Mediev...alis str. 91001] MIVINRLWGRCYGTRGGITPTDTIEVLIMATVSMRDMLQAGVHFGHQTRYWNPKMKPFIFGARNKV

  20. ORF Sequence: NC_003030 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003030 gi|15895978 >gi|15895978|ref|NP_349327.1| Response regulator (CheY-like reciev...er domain and HTH-type DNA-binding domain) [Clostridium acetobutylicum ATCC 824] MDNRVVVAEDEPITRMDICEMLTGAGYSVVGQVPNGLEAIEV

  1. ORF Sequence: NC_005813 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available rsinia pestis biovar Medievalis str. 91001] MIMTQPKQTKRRFSPEFKLEAIEQVVKYQRSTIEVARALELDPSQLRKWIRQYKEEVSGVTPDNPALTPEQREIQSLRAQIKRLEMEKEILKQAAVLMSEFPIKSLR ... NC_005813 gi|45478586 >gi|45478587|ref|NP_995414.1| hypothetical protein pCD98 [Ye

  2. ORF Sequence: NC_005810 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005810 gi|45441608 >gi|45441608|ref|NP_993147.1| YjgF-family lipoprotein [Yersinia pestis biovar Mediev...alis str. 91001] MPQHHNRNRRMIIKTQNAPAAIGPYSQGVVAGNLLFISGCCPFSEKDGSVVGIDITEQTIQAMKNLKAIVEATGSYMNDVVKTTCFISDMNNFQSFNTIYAGYFPSGTFPARSCVEVARLPKDVLIEVEAIVSLK

  3. ORF Sequence: NC_005813 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available rsinia pestis biovar Medievalis str. 91001] MIMTQPKQTKRRFSPEFKLEAIEQVVKYQRSTIEVARALELDPSQLRKWIRQYKEEVSGMTPDNPALTPEQREIQSLRAQIKRLEMEKEILKQAAVLMSEFPIKSLR ... NC_005813 gi|45478566 >gi|45478566|ref|NP_995393.1| hypothetical protein pCD71 [Ye

  4. ORF Sequence: NC_001145 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_001145 gi|6323710 >gi|6323710|ref|NP_013781.1| Protein required for nuclear mem...brane fusion during karyogamy, localizes to the membrane with a soluble portion in the endoplasmic reticulum

  5. ORF Sequence: NC_003070 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003070 gi|15219789 >gi|15219789|ref|NP_176868.1| lupeol synthase, putative / 2,3-oxidosqualene-triterpen...oid cyclase, putative [Arabidopsis thaliana] MWRLKVGEGKGKDPYLFSSNNFVGRQTWEFDPKAGTRE

  6. ORF Sequence: NC_003070 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003070 gi|30699377 >gi|30699377|ref|NP_178017.2| lupeol synthase, putative / 2,3-oxidosqualene-triterpen...oid cyclase, putative [Arabidopsis thaliana] MWKLKIGEGNGEDPYLFSSNNFVGRQTWEFDPKAGTPE

  7. ORF Sequence: NC_000964 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_000964 gi|16079850 >gi|16079850|ref|NP_390676.1| inhibition of SpoIVFB (negative regulation) and hypothe...sised to stabilize the thermolabile spoIVFB product (positive regulation) (stage IV

  8. ORF Sequence: NC_006905 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available of cations and cationic drugs [Salmonella enterica subsp. enterica serovar Choleraesuis str. SC-B67] MFYWILL... NC_006905 gi|62180070 >gi|62180070|ref|YP_216487.1| putative membrane transporter

  9. ORF Sequence: NC_006905 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available of cations and cationic drugs [Salmonella enterica subsp. enterica serovar Choleraesuis str. SC-B67] MQQFEWI... NC_006905 gi|62180071 >gi|62180071|ref|YP_216488.1| putative membrane transporter

  10. ORF Alignment: NC_005296 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005296 gi|39936399 >1qr0A 1 183 5 186 1e-25 ... emb|CAE28777.1| possible lipopeptide antibiotics... ... possible lipopeptide antibiotics iturin a biosynthesis ... protein [Rhodopseudomonas palu

  11. Large-Nc Gauge Theory and Chiral Random Matrix Theory

    Science.gov (United States)

    Hanada, Masanori; Lee, Jong-Wan; Yamada, Norikazu

    Effective theory approaches and the large-Nc limit are useful for studying the strongly coupled gauge theories. In this talk we consider how the chiral random matrix theory (χRMT) can be used in the study of large-Nc gauge theories. It turns out the parameter regions, in which each of these two approaches are valid, are different. Still, however, we show that the breakdown of chiral symmetry can be detected by combining the large-Nc argument and the χRMT with some cares. As a demonstration, we numerically study the four dimensional SU(Nc) gauge theory with Nf = 2 heavy adjoint fermions on a 24 lattice by using Monte-Carlo simulations, which is related to the infinite volume lattice through the Eguchi-Kawai equivalence.

  12. ORF Sequence: NC_003282 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003282 gi|17540144 >gi|17540144|ref|NP_500824.1| feminization 1 homolog a, FEMinization of XX and XO ani...mals FEM-1 (fem-1) [Caenorhabditis elegans] MTPNGHHFRTVIYNAAAVGNLQRIKVFTINSRNDRQWII

  13. ORF Sequence: NC_001137 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ull mutation has global effects on transcription; Yer064cp [Saccharomyces cerevisiae] MIDDTENSKIHLEGSHKTGKYT... NC_001137 gi|6320907 >gi|6320907|ref|NP_010986.1| Non-essential nuclear protein; n

  14. ORF Sequence: NC_003423 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available e nuclear protein with effects on N-glycosylation of proteins in the secretory pathway by similarity to yeas... NC_003423 gi|19113351 >gi|19113351|ref|NP_596559.1| bystin-family protein; putativ

  15. ORF Sequence: NC_006905 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available g protein (involved in environmental regulation of virulence factors) [Salmonella enterica subsp. enterica s... NC_006905 gi|62179085 >gi|62179085|ref|YP_215502.1| hemolysin expression modulatin

  16. ORF Sequence: NC_004307 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available se/invertase); possible inulinase [Bifidobacterium longum NCC2705] MTDFTPETPVLTPIHDHAAELAKAEAGVAEMAANRNNRWYP... NC_004307 gi|23464731 >gi|23464731|ref|NP_695334.1| beta-fructofuranosidase (sucra

  17. ORF Alignment: NC_001145 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_001145 gi|6323724 >1lv7A 48 256 339 536 1e-04 ... gb|AAW44927.1| sister chromatid cohesion...1| ... sister chromatid cohesion-related protein, putative ... [Cryptococcus neoformans var. n

  18. ORF Alignment: NC_003070 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003070 gi|15219798 >1lv7A 48 256 339 536 1e-04 ... gb|AAW44927.1| sister chromatid cohesion....1| ... sister chromatid cohesion-related protein, putative ... [Cryptococcus neoformans var.

  19. ORF Alignment: NC_003423 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003423 gi|19111992 >1lv7A 48 256 339 536 1e-04 ... gb|AAW44927.1| sister chromatid cohesion....1| ... sister chromatid cohesion-related protein, putative ... [Cryptococcus neoformans var.

  20. ORF Alignment: NC_005783 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005783 gi|45185248 >1lv7A 48 256 339 536 1e-04 ... gb|AAW44927.1| sister chromatid cohesion....1| ... sister chromatid cohesion-related protein, putative ... [Cryptococcus neoformans var.

  1. ORF Alignment: NC_003282 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003282 gi|17541368 >1lv7A 48 256 339 536 1e-04 ... gb|AAW44927.1| sister chromatid cohesion....1| ... sister chromatid cohesion-related protein, putative ... [Cryptococcus neoformans var.

  2. ORF Sequence: NC_001148 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_001148 gi|6325264 >gi|6325264|ref|NP_015332.1| Meiosis-specific component of sister chromatid cohesion... complex; maintains cohesion between sister chromatids during meiosis I; maintains cohesion

  3. ORF Alignment: NC_006371 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006371 gi|54302237 >1r690 2 63 15 79 7e-05 ... ref|YP_132230.1| hypotethical trans...criptional regulator [Photobacterium profundum ... SS9] emb|CAG22430.1| hypotethical transcriptional ...

  4. ORF Sequence: NC_006905 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006905 gi|62182728 >gi|62182728|ref|YP_219145.1| putative nitrite reductase; formate-dependent, Fe-S cen...ters [Salmonella enterica subsp. enterica serovar Choleraesuis str. SC-B67] MSCTRRQ

  5. ORF Sequence: NC_006824 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006824 gi|58616603 >gi|58616603|ref|YP_195734.1| thiolase, related to ditF possibly involved in diterpen...oid metabolism [Azoarcus sp. EbN1] MTIRDKTAIVGLGSTPYYKRGQSAPQTLIELVGKSVLAALDDAGLSVR

  6. ORF Alignment: NC_003295 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003295 gi|17546028 >1fjgR 2 71 22 91 5e-16 ... emb|CAD15011.1| PROBABLE PRIMOSOMAL REPLICATION... PROTEIN [Ralstonia solanacearum] ... ref|NP_519430.1| PROBABLE PRIMOSOMAL REPLICATION ...

  7. ORF Alignment: NC_003295 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003295 gi|17545851 >1xjhA 4 62 266 325 7e-15 ... emb|CAD14834.1| PUTATIVE REDOX REGULATED MOLECULA... ... PUTATIVE REDOX REGULATED MOLECULAR CHAPERONE ... HEAT-SHOCK-LIKE PROTEIN [Ralstonia solanacea

  8. ORF Sequence: NC_000962 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_000962 gi|15608520 >gi|15608520|ref|NP_215896.1| PROBABLE ASPARTATE CARBAMOYLTR...ANSFERASE PYRB (ATCase) (Aspartate transcarbamylase) [Mycobacterium tuberculosis H37Rv] MTPRHLLTAADLSRDDATAI

  9. ORF Sequence: NC_002945 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_002945 gi|31792574 >gi|31792574|ref|NP_855067.1| PROBABLE ASPARTATE CARBAMOYLTR...ANSFERASE PYRB (ATCase) (Aspartate transcarbamylase) [Mycobacterium bovis AF2122/97] MTPRHLLTAADLSRDDATAILDD

  10. ORF Sequence: NC_000962 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_000962 gi|15608523 >gi|15608523|ref|NP_215899.1| PROBABLE CARBAMOYL-PHOSPHATE S...YNTHASE SMALL CHAIN CARA (Carbamoyl-phosphate synthetase glutamine chain) [Mycobacterium tuberculosis H37Rv

  11. The Investigation of EM Scattering from the Time-Varying Overturning Wave Crest Model by the IEM

    Directory of Open Access Journals (Sweden)

    Xiao Meng

    2016-01-01

    Full Text Available Investigation of the electromagnetic (EM scattering of time-varying overturning wave crests is a worthwhile endeavor. Overturning wave crest is one of the reasons of sea spike generation, which increases the probability of false radar alarms and reduces the performance of multitarget detection in the environment. A three-dimensional (3D time-varying overturning wave crest model is presented in this paper; this 3D model is an improvement of the traditional two-dimensional (2D time-varying overturning wave crest model. The integral equation method (IEM was employed to investigate backward scattering radar cross sections (RCS at various incident angles of the 3D overturning wave crest model. The super phenomenon, where the intensity of horizontal polarization scattering is greater than that of vertical polarization scattering, is an important feature of sea spikes. Simulation results demonstrate that super phenomena may occur in some time samples as variations in the overturning wave crest.

  12. 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.

  13. Quantification of Dune Response over the Course of a 6-Day Nor'Easter, Outer Banks, NC

    Science.gov (United States)

    Brodie, K. L.; Spore, N.; Swann, C.

    2014-12-01

    The amount and type of foredune morphologic change during a storm event primarily scales with the level of inundation during that event. Specifically, external hydrodynamic forcing (total water level) can be compared with antecedent beach and foredune morphology to predict an impact regime that relates to the type of expected morphologic evolution of the system. For example, when total water levels are above the dune toe, but below the dune crest, the impact regime is classified as "collision" and the expected morphology response is slumping or scarping of the dune face. While the amount of dune retreat scales largely with the duration of wave attack to the dune face, characteristics of the dune other than its crest or toe elevation may also enhance or impede rates of morphologic change. The aftermath of Hurricane Sandy provided a unique opportunity to observe alongshore variations in dune response to a 6-day Nor'Easter (Hs >4 m in 6 m depth), as a variety of dunes were constructed (or not) by individual home owners in preparation for the winter storm season. Daily terrestrial lidar scans were conducted along 20 km of coastline in Duck, NC using Coastal Lidar And Radar Imaging System (CLARIS) during the first dune collision event following Sandy. Foredunes were grouped by their pre-storm form (e.g. vegetated, pushed, scarped, etc) using automated feature extraction tools based on surface curvature and slope, and daily rates of morphologic volume change were calculated. The highest dune retreat rates were focused along a 1.5 km region where cross-shore erosion of recently pushed, un-vegetated dunes reached 2 m/day. Variations in dune response were analyzed in relation to their pre-storm morphology, with care taken to normalize for alongshore variations in hydrodynamic forcing. Ongoing research is focused on identifying specific metrics that can be easily extracted from topographic DEMs to aid in dune retreat predictions.

  14. SU(3) Clebsch-Gordan coefficients at large Nc

    Science.gov (United States)

    Stancu, Fl.

    2016-01-01

    It is argued that several papers where SU (3) Clebsch-Gordan coefficients were calculated in order to describe properties of hadronic systems are, up to a phase convention, particular cases of analytic formulae derived by Hecht in 1965 in the context of nuclear physics. This is valid for irreducible representations with multiplicity one in the corresponding Clebsch-Gordan series. For multiplicity two, Hecht has proposed an alternative which can provide correct 1 /Nc sub-leading orders in large Nc studies.

  15. precision deburring using NC and robot equipment. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Gillespie, L.K.

    1980-05-01

    Deburring precision miniature components is often time consuming and inconsistent. Although robots are available for deburring parts, they are not precise enough for precision miniature parts. Numerical control (NC) machining can provide edge break consistencies to meet requirements such as 76.2-..mu..m maximum edge break (chamfer). Although NC machining has a number of technical limitations which prohibits its use on many geometries, it can be an effective approach to features that are particularly difficult to deburr.

  16. What lies beneath? An evaluation of lower molar trigonid crest patterns based on both dentine and enamel expression.

    Science.gov (United States)

    Bailey, Shara E; Skinner, Matthew M; Hublin, Jean-Jacques

    2011-08-01

    The nearly ubiquitous presence of a continuous crest connecting the protoconid and metaconid of the lower molars (often referred to as the middle trigonid crest), is one of several dental traits that distinguish Homo neanderthalensis from Homo sapiens. This study examined variation in trigonid crest patterns on the enamel and dentine surfaces to (1) evaluate the concordance between the morphology of trigonid crests at the inner dentine and the outer enamel surfaces; (2) examine their developmental origin(s); and (3) examine trait polarity through comparison with Australopithecus africanus and Pan. The sample included 73 H. neanderthalensis, 67 contemporary H. sapiens, 5 A. africanus, and 24 Pan lower molars. Results indicate general agreement in the morphology observed on the dentine and enamel surfaces. All but one H. neanderthalensis molar shows some trigonid crest development, whereas trigonid crests occur in low frequency in contemporary humans. Pan and A. africanus both also show high frequencies of a continuous trigonid crest. However, the origin of the trigonid crest differs among groups. H. neanderthalensis uniquely possesses a 'middle' trigonid crest that originates from the mesial accessory ridge of one or both cusps. Based on our results we suggest that presence of a continuous middle trigonid crest at the dentine surface is primitive and the lack of any trigonid crest is derived. Genetic drift may explain the high frequency of trigonid crests in H.neanderthalensis. However, H. neanderthalensis still appears to be derived relative to Pan and A. africanus in its high frequency of the mesial-mesial trigonid crestconfiguration. Copyright © 2011 Wiley-Liss, Inc.

  17. 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.

  18. Assessing bone thickness in the infrazygomatic crest area aiming the orthodontic miniplates positioning: a tomographic study.

    Science.gov (United States)

    Santos, Aline Rode; Castellucci, Marcelo; Crusoé-Rebello, Iêda Margarida; Sobral, Márcio Costa

    2017-01-01

    Due to the increasing use of miniplates for anchorage purposes in orthodontics, it is very important to know more about infrazigomatic crest anatomy (thickness), in adult patients. Evaluate the infrazygomatic crest region thickness, in adult (male and female) patients. Cone-beam computerized tomography (CBCT) images from 40 patients were used to assess cross-sectional measurements of the infrazygomatic crest region. Measurement 1 considered thickness 2 mm above the distobuccal root of the permanent maxillary first molar, while measurement 2 was taken 2 mm above the first measurement. The mean thickness of the infrazygomatic crest in males was 3.55 mm for measurement 1 and 2.84 mm for measurement 2, while in females these were 2.37 mm and 2.24 mm, respectively. The authors concluded that the overall mean thickness of the infrazygomatic crest was 2.49 mm with respect to measurement 1, and 2.29 mm for measurement 2, with no statistically significant differences between gender.

  19. Assessing bone thickness in the infrazygomatic crest area aiming the orthodontic miniplates positioning: a tomographic study

    Directory of Open Access Journals (Sweden)

    Aline Rode Santos

    Full Text Available ABSTRACT Introduction: Due to the increasing use of miniplates for anchorage purposes in orthodontics, it is very important to know more about infrazigomatic crest anatomy (thickness, in adult patients. Objectives: Evaluate the infrazygomatic crest region thickness, in adult (male and female patients. Methods: Cone-beam computerized tomography (CBCT images from 40 patients were used to assess cross-sectional measurements of the infrazygomatic crest region. Measurement 1 considered thickness 2 mm above the distobuccal root of the permanent maxillary first molar, while measurement 2 was taken 2 mm above the first measurement. Results: The mean thickness of the infrazygomatic crest in males was 3.55 mm for measurement 1 and 2.84 mm for measurement 2, while in females these were 2.37 mm and 2.24 mm, respectively. Conclusion: The authors concluded that the overall mean thickness of the infrazygomatic crest was 2.49 mm with respect to measurement 1, and 2.29 mm for measurement 2, with no statistically significant differences between gender.

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

    Science.gov (United States)

    Anastasopoulos, Georgios; Marinis, Athanasios; Konstantinidis, Christos; Theodosopoulos, Theodosios; Fragulidis, Georgios; Vassiliou, Ioannis

    2008-10-01

    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. 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. 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.

  1. 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.

  2. Corresponding mitochondrial DNA and niche divergence for crested newt candidate species.

    Directory of Open Access Journals (Sweden)

    Ben Wielstra

    Full Text Available Genetic divergence of mitochondrial DNA does not necessarily correspond to reproductive isolation. However, if mitochondrial DNA lineages occupy separate segments of environmental space, this supports the notion of their evolutionary independence. We explore niche differentiation among three candidate species of crested newt (characterized by distinct mitochondrial DNA lineages and interpret the results in the light of differences observed for recognized crested newt species. We quantify niche differences among all crested newt (candidate species and test hypotheses regarding niche evolution, employing two ordination techniques (PCA-env and ENFA. Niche equivalency is rejected: all (candidate species are found to occupy significantly different segments of environmental space. Furthermore, niche overlap values for the three candidate species are not significantly higher than those for the recognized species. As the three candidate crested newt species are, not only in terms of mitochondrial DNA genetic divergence, but also ecologically speaking, as diverged as the recognized crested newt species, our findings are in line with the hypothesis that they represent cryptic species. We address potential pitfalls of our methodology.

  3. Structural studies of n-type nc-Si-QD thin films for nc-Si solar cells

    Science.gov (United States)

    Das, Debajyoti; Kar, Debjit

    2017-12-01

    A wide optical gap nanocrystalline silicon (nc-Si) dielectric material is a basic requirement at the n-type window layer of nc-Si solar cells in thin film n-i-p structure on glass substrates. Taking advantage of the high atomic-H density inherent to the planar inductively coupled low-pressure (SiH4 + CH4)-plasma, development of an analogous material in P-doped nc-Si-QD/a-SiC:H network has been tried. Incorporation of C in the Si-network extracted from the CH4 widens the optical band gap; however, at enhanced PH3-dilution of the plasma spontaneous miniaturization of the nc-Si-QDs below the dimension of Bohr radius (∼4.5 nm) further enhances the band gap by virtue of the quantum size effect. At increased flow rate of PH3, dopant induced continuous amorphization of the intrinsic crystalline network is counterbalanced by the further crystallization promoted by the supplementary atomic-H extracted from PH3 (1% in H2) in the plasma, eventually holding a moderately high degree of crystallinity. The n-type wide band gap (∼1.93 eV) window layer with nc-Si-QDs in adequate volume fraction (∼52%) could furthermore be instrumental as an effective seed layer for advancing sequential crystallization in the i-layer of nc-Si solar cells with n-i-p structure in superstrate configuration.

  4. 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.

  5. Space-time system architecture for the neural optical computing

    Science.gov (United States)

    Lo, Yee-Man V.

    1991-02-01

    The brain can perform the tasks of associative recall detection recognition and optimization. In this paper space-time system field models of the brain are introduced. They are called the space-time maximum likelihood associative memory system (ST-ML-AMS) and the space-time adaptive learning system (ST-ALS). Performance of the system is analyzed using the probability of error in memory recall (PEMR) and the space-time neural capacity (ST-NC). 1.

  6. Hydraulics of flow over broad-crested weirs; Abfluss ueber breitkronige Wehre

    Energy Technology Data Exchange (ETDEWEB)

    Castro-Orgaz, Oscar [Consejo Superior de Investigaciones Cientificas, Cordoba (Spain). Inst. de Agricultura Sostenible; Pfister, Michael [ETH Zuerich (CH). Versuchsanstalt fuer Wasserbau, Hydrologie und Glaziologie (VAW)

    2010-07-01

    Weir flow is known to be subject to streamline curvature effects since the 18{sup th} century, when Boussinesq conducted his pioneer developments. A number of investigations have focused on the development of related theoretical models. However, hydraulic practice is often based on model test research, e.g. for weir flow features where the standard hydraulic theory based on the specific energy equation fails. In this paper, a hydraulic theory is presented describing flows over broad-crested weirs allowing both for streamline curvature effects and the so-called scale effect, originated by the boundary layer development on the weir crest. The theoretical results are compared to model test data, resulting in an excellent agreement. Further, it is shown that based on the hydraulic theory the features of broad-crested weir flow may be explained, and the contradictions coming from a standard hydraulic approach are overcome. (orig.)

  7. Solar Simulation for the CREST Preflight Thermal-Vacuum Test at B-2

    Science.gov (United States)

    Ziemke, Robert A.

    2013-01-01

    In June 2011, the multi-university sponsored Cosmic Ray Electron Synchrotron Telescope (CREST) has undergone thermal-vacuum qualification testing at the NASA Glenn Research Center (GRC), Plum Brook Station, Sandusky, Ohio. The testing was performed in the B- 2 Space Propulsion Facility vacuum chamber. The CREST was later flown over the Antarctic region as the payload of a stratospheric balloon. Solar simulation was provided by a system of planar infrared lamp arrays specifically designed for CREST. The lamp arrays, in conjunction with a liquid-nitrogen-cooled cryoshroud, achieved the required thermal conditions for the qualification tests. This report focuses on the design and analysis of the planar arrays based on first principles. Computational spreadsheets are included in the report.

  8. A case of porphyria cutanea tarda in association with idiopathic myelofibrosis and CREST syndrome.

    Science.gov (United States)

    Lee, S C; Yun, S J; Lee, J B; Lee, S S; Won, Y H

    2001-01-01

    We report a 56-year-old Korean woman with porphyria cutanea tarda (PCT), showing multiple scarring bullae and hypertrichosis on sun-exposed areas of skin with postinflammatory hyperpigmentation. Sclerodermoid changes were also found on both hands, the face and neck. The patient had suffered from CREST syndrome, manifesting with Raynaud's phenomenon and sclerodactyly, for more than 15 years. Anticentromere antibody was positive. She had presented with splenomegaly 3 years before the development of PCT, and was diagnosed as having idiopathic myelofibrosis, based on bone marrow biopsy. In summary, she had had CREST syndrome for 15 years and later developed idiopathic myelofibrosis and PCT. This is the first reported case of PCT in association with idiopathic myelofibrosis and CREST syndrome.

  9. Reduced dependence of Crested Ibis on winter-flooded rice fields: implications for their conservation.

    Directory of Open Access Journals (Sweden)

    Yiwen Sun

    Full Text Available The Crested Ibis Nipponia nippon was once thought to be extinct in the wild until seven birds were discovered in a remote mountain village in China in 1981. Studies suggested that winter-flooded rice fields play an essential role in nest site selection by the Crested Ibis and hence in their survival. Considerable efforts were therefore made to conserve the winter-flooded rice fields, but these have caused conflicts between the agricultural and conservation communities. The population and geographical range of the wild Crested Ibis has expanded greatly since 1981, but there is no spatial information on the winter-flooded rice fields, nor on the current association of nest sites and winter-flooded rice fields. We mapped winter-flooded rice fields across the entire current range of Crested Ibis using innovative remote sensing and geographical information systems (GIS techniques. The spatial relationships between the nest site clusters and winter-flooded rice fields were quantified using Ward's hierarchical clustering method and Ripley's K-function. We show that both have significantly clumped distribution patterns and that they are positively associated. However, the dependence of Crested Ibis on the winter-flooded rice fields varied significantly among the nest site clusters and has decreased over the years, indicating the absence of winter-flooded rice fields is not constraining their recovery and population expansion. We therefore recommend that efforts should be made to protect the existing winter-flooded rice fields and to restore the functionality of natural and semi-natural wetlands, to encourage both in-situ conservation and the re-introduction of the Crested Ibis. In addition, we recommend that caution should be exercised when interpreting the habitat requirements of species with a narrow distribution, particularly when that interpretation is based only on their current habitat.

  10. Density of bunches of native bluebunch wheatgrass and alien crested wheatgrass

    Energy Technology Data Exchange (ETDEWEB)

    Rickard, W.H.

    1985-10-01

    The density of bunches of bluebunch wheatgrass in a natural undisturbed stand averaged 3.28 per m/sup 2/ as compared to 2.96 per m/sup 2/ for a nearby stand of crested wheatgrass that was planted 30 years ago. Bunch density was similar in both stands indicating that spacing is a response to an environment deficient in soil water. Bunches of crested wheatgrass on the average weighed 3.5 times more than bunches of bluebunch wheatgrass and they also produced a greater weight of seedheads.

  11. Disproportionately severe calcinosis cutis in an 88-year-old patient with CREST syndrome.

    Science.gov (United States)

    Buchowski, J M; Ahn, N U; Ahn, U M; McCarthy, E F; Mehta, M B

    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.

  12. Complications in Placement of a Glaucoma Drainage Device in a Patient With CREST Syndrome.

    Science.gov (United States)

    Husain, Maria Q; Alsheikh, Oday

    2017-02-01

    This case describes difficulty with conjunctival closure in an 80-year-old woman with CREST syndrome, a subset of systemic scleroderma. The patient underwent uneventful glaucoma drainage device implantation, but friability of the conjunctiva was noted during closure. Amniotic membrane was used to ensure secure closure, and the patient had a successful outcome. There is a paucity of existing studies on patients with CREST syndrome and their ocular findings. This report sheds light on ocular findings in this autoimmune disease and the necessity for alternative closure methods in special cases.

  13. Acute central retinal artery occlusion presenting as CREST syndrome: a case report.

    Science.gov (United States)

    Raja, Muhammad Sa; Marshall, Tarnya; Burton, Ben Jl

    2009-01-05

    A 75 year old lady presented with acute central retinal artery occlusion and contralateral cotton wool spots. General physical examination and investigations led to a diagnosis of CREST syndrome; however, association of central retinal artery occlusion with CREST syndrome is not well known. While diabetes, systemic hypertension, carotid atherosclerosis and cardiac pathology are common causes of CRAO it is always important to rule out giant cell arteritis. This case highlights that inflammatory causes of central retinal artery occlusion other than giant cell arteritis should also be considered as a possibility to spare unnecessary use of excessive systemic corticosteroids.

  14. [Pulmonary hypertension in patients with systemic scleroderma with CREST-syndrome and without it].

    Science.gov (United States)

    Karoli, N A; Rebrov, A P; Orlova, E E

    2004-01-01

    To study incidence rate and characteristics of pulmonary hypertension development in patients with systemic sclerosis (SS). The study included 31 SS patients (30 females, 1 male, age 33-75 years, mean age 47.7 +/- 1.7 years). Pulmonary hypertension occurred more frequently in SS patients with CREST-syndrome than in SS patients free of this syndrome. SS patients with CREST-syndrome had also more severe ventricular hypertrophy than ventricular dilation. Echocardiography proved to be a highly informative method for detection of pulmonary hypertension in patients with SS. The necessity of hemodynamical study in SS patients is emphasized.

  15. T-CREST: Time-predictable multi-core architecture for embedded systems

    DEFF Research Database (Denmark)

    Schoeberl, Martin; Abbaspourseyedi, Sahar; Jordan, Alexander

    2015-01-01

    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...... of a collaborative research and development project executed by eight partners from academia and industry. The European Commission funded T-CREST....

  16. The in vivo developmental potential of porcine skin-derived progenitors and neural stem cells.

    Science.gov (United States)

    Zhao, Ming-Tao; Yang, Xiaoyu; Lee, Kiho; Mao, Jiude; Teson, Jennifer M; Whitworth, Kristin M; Samuel, Melissa S; Spate, Lee D; Murphy, Clifton N; Prather, Randall S

    2012-09-20

    Multipotent skin-derived progenitors (SKPs) can be traced back to embryonic neural crest cells and are able to differentiate into both neural and mesodermal progeny in vitro. Neural stem cells (NSCs) are capable of self-renewing and can contribute to neuron and glia in the nervous system. Recently, we derived porcine SKPs and NSCs from the same enhanced green fluorescent protein (EGFP) transgenic fetuses and demonstrated that SKPs could contribute to neural and mesodermal lineages in vivo. However, it remains unclear whether porcine SKPs and NSCs can generate ectoderm and mesoderm lineages or other germ layers in vivo. Embryonic chimeras are a well-established tool for investigating cell lineage determination and cell potency through normal embryonic development. Thus, the purpose of this study was to investigate the in vivo developmental potential of porcine SKPs and fetal brain-derived NSCs by chimera production. Porcine SKPs, NSCs, and fibroblasts were injected into precompact in vitro fertilized embryos (IVF) and then transferred into corresponding surrogates 24 h postinjection. We found that porcine SKPs could incorporate into the early embryos and contribute to various somatic tissues of the 3 germ layers in postnatal chimera, and especially have an endodermal potency. However, this developmental potential is compromised when they differentiate into fibroblasts. In addition, porcine NSCs fail to incorporate into host embryos and contribute to chimeric piglets. Therefore, neural crest-derived SKPs may represent a more primitive state than their counterpart neural stem cells in terms of their contributions to multiple cell lineages.

  17. Volume independence in large Nc QCD-like gauge theories

    Science.gov (United States)

    Kovtun, Pavel; Ünsal, Mithat; Yaffe, Laurence G.

    2007-06-01

    Volume independence in large Nc gauge theories may be viewed as a generalized orbifold equivalence. The reduction to zero volume (or Eguchi-Kawai reduction) is a special case of this equivalence. So is temperature independence in confining phases. A natural generalization concerns volume independence in ``theory space'' of quiver gauge theories. In pure Yang-Mills theory, the failure of volume independence for sufficiently small volumes (at weak coupling) due to spontaneous breaking of center symmetry, together with its validity above a critical size, nicely illustrate the symmetry realization conditions which are both necessary and sufficient for large Nc orbifold equivalence. The existence of a minimal size below which volume independence fails also applies to Yang-Mills theory with antisymmetric representation fermions [QCD(AS)]. However, in Yang-Mills theory with adjoint representation fermions [QCD(Adj)], endowed with periodic boundary conditions, volume independence remains valid down to arbitrarily small size. In sufficiently large volumes, QCD(Adj) and QCD(AS) have a large Nc ``orientifold'' equivalence, provided charge conjugation symmetry is unbroken in the latter theory. Therefore, via a combined orbifold-orientifold mapping, a well-defined large Nc equivalence exists between QCD(AS) in large, or infinite, volume and QCD(Adj) in arbitrarily small volume. Since asymptotically free gauge theories, such as QCD(Adj), are much easier to study (analytically or numerically) in small volume, this equivalence should allow greater understanding of large Nc QCD in infinite volume.

  18. An overview on STEP-NC compliant controller development

    Science.gov (United States)

    Othman, M. A.; Minhat, M.; Jamaludin, Z.

    2017-10-01

    The capabilities of conventional Computer Numerical Control (CNC) machine tools as termination organiser to fabricate high-quality parts promptly, economically and precisely are undeniable. To date, most CNCs follow the programming standard of ISO 6983, also called G & M code. However, in fluctuating shop floor environment, flexibility and interoperability of current CNC system to react dynamically and adaptively are believed still limited. This outdated programming language does not explicitly relate to each other to have control of arbitrary locations other than the motion of the block-by-block. To address this limitation, new standard known as STEP-NC was developed in late 1990s and is formalized as an ISO 14649. It adds intelligence to the CNC in term of interoperability, flexibility, adaptability and openness. This paper presents an overview of the research work that have been done in developing a STEP-NC controller standard and the capabilities of STEP-NC to overcome modern manufacturing demands. Reviews stated that most existing STEP-NC controller prototypes are based on type 1 and type 2 implementation levels. There are still lack of effort being done to develop type 3 and type 4 STEP-NC compliant controller.

  19. Telangiectasis in CREST syndrome and systemic sclerosis: correlation of clinical and pathological features with response to pulsed dye laser treatment.

    Science.gov (United States)

    Halachmi, Shlomit; Gabari, Osama; Cohen, Sarit; Koren, Romelia; Amitai, Dan Ben; Lapidoth, Moshe

    2014-01-01

    Telangiectasia are cardinal features of systemic sclerosis (SS) and calcinosis, Raynaud's syndrome, esophageal motility, sclerodactyly, telangiectasias (CREST) syndrome. The etiology of telangiectasia in these syndromes is unknown, but vascular dysfunction has been proposed. However, the telangiectasia of CREST have anecdotally been considered relatively resistant to pulse dye laser (PDL), the treatment of choice for classic telangiectasia. The study was designed to test whether SS/CREST telangiectasia require more treatments than sporadic telangiectasia and to identify clinical and histological features that could explain such an effect. Nineteen skin biopsies from patients with SS or CREST and 10 control biopsies were examined and compared for features that may predict a differential response to PDL. Sixteen cases of SS or CREST treated with PDL between 1997 and 2007 were evaluated and response to treatment was compared with 20 patients with sporadic telangiectasis. Relative to normal skin, CREST/scleroderma telangiectasia exhibited thickened vessels in 17 out of 19 sections and thickened collagen fibers in the reticular or deep dermis in all sections. The number of treatments required to clear SS/CREST telangiectasia was approximately twofold higher. SS/CREST telangiectasia are more resistant to PDL but can be effectively cleared with more treatments.

  20. Comparison of mechanical behavior of TiN, TiNC, CrN/TiNC, TiN/TiNC films on 9Cr18 steel by PVD

    Science.gov (United States)

    Feng, Xingguo; Zhang, Yanshuai; Hu, Hanjun; Zheng, Yugang; Zhang, Kaifeng; Zhou, Hui

    2017-11-01

    TiN, TiNC, CrN/TiNC and TiN/TiNC films were deposited on 9Cr18 steel using magnetron sputtering technique. The morphology, composition, chemical state and crystalline structure of the films were observed and analyzed by X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Hardness and adhesion force were tested by nanoindentation and scratch tester, respectively. The friction and wear behavior of TiN, TiNC, CrN/TiNC and TiN/TiNC films sliding against GCr15 balls were investigated and compared synthetically using ball-on-disk tribometer. It was found that Tisbnd N, Tisbnd C, Tisbnd Nsbnd C and Csbnd C bonds were formed. The TiN/TiNC film was composed of TiN, TiC and TiNC phases. Hardness and adhesion force results indicated that although the TiN film possessed the highest hardness, its adhesion force was lowest among all the films. Tribological test results showed that the friction coefficient of TiN/TiNC was much lower than that of TiN and the wear rate decreases remarkably from 2.3 × 10-15 m3/Nm to 7.1 × 10-16 m3/Nm, which indicated the TiN/TiNC film has better wear resistance.

  1. A multimarker phylogeography of crested newts, Triturus cristatus superspecies, reveals cryptic species

    NARCIS (Netherlands)

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

    2013-01-01

    The crested newt Triturus cristatus superspecies is composed of five recognized species. One of these, T. karelinii sensu lato, comprises three geographically structured mitochondrial DNA lineages: ‘eastern’, ‘central’ and ‘western T. karelinii’. Genetic divergence among these lineages is comparable

  2. CSUB CREST Research on Climate Change and the San Joaquin Valley, CA

    Science.gov (United States)

    Krugh, W. C.; Negrini, R. M.; Baron, D.; Gillespie, J.; Horton, R. A.; Montoya, E.; Cruz-Boone, C.; Andrews, G. D.; Guo, J.

    2015-12-01

    As part of the NSF-supported Centers for Excellence in Science and Technology (CREST), student and faculty researchers at California State University, Bakersfield (CSUB) have been investigating the regional impacts of climate change as well as evaluating the potential of local contributions to its abatement. Highlights of this research include; 1) the development of a high-resolution climate record from Tulare Lake sediments that spans the past 20,000 years, 2) the quantitative analysis and prediction of climate change impacts on Sierra Nevada snowpack, 3) the detailed subsurface characterization of San Joaquin Valley oilfields targeted for CO2 sequestration, and 4) the evaluation of proposed host rock suitability under simulated CO2 injection conditions. To date, CSUB CREST supported research has resulted in 26 contributions to peer-reviewed journals (currently published or in-review). A primary goal of CSUB CREST is to improve the recruitment, retention, and success of students from the local community, the majority of whom are from backgrounds under-represented in STEM disciplines. More than 28 students have been directly involved in the basic and applied research projects supported by this program. The majority of these students have received, or are on track to receive, an M.S. degree and have ultimately gained employment in a STEM field or been accepted into a Ph.D. program. This presentation, and others in this session, will focus on the accomplishments, challenges, and strategies for success gleaned from CSUB CREST Phase 1.

  3. Decline of traditional rice farming constrains the recovery of the endangered Asian crested ibis (Nipponia nippon).

    Science.gov (United States)

    Sun, Yiwen; Wang, Tiejun; Skidmore, Andrew K; Wang, Qi; Ding, Changqing

    2015-12-01

    Traditional agriculture benefits a rich diversity of plants and animals. The winter-flooded rice fields in the Qinling Mountains, China, are the last refuge for the endangered Asian crested ibis (Nipponia nippon), and intensive efforts have been made to protect this anthropogenic habitat. Analyses of multi-temporal satellite data indicate that winter-flooded rice fields have been continuously reduced across the current range of crested ibis during the past two decades. The rate of loss of these fields in the core-protected areas has unexpectedly increased to a higher level than that in non-protected areas in the past decade. The best fit (R (2) = 0.87) numerical response model of the crested ibis population shows that a reduction of winter-flooded rice fields decreases population growth and predicts that the population growth will be constrained by the decline of traditional winter-flooded rice fields in the coming decades. Our findings suggest that the decline of traditional rice farming is likely to continue to pose a threat to the long-term survival and recovery of the crested ibis population in China.

  4. 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.

  5. 77 FR 4274 - Migratory Bird Permits; Double-Crested Cormorant Management in the United States

    Science.gov (United States)

    2012-01-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE INTERIOR Fish and Wildlife Service 50 CFR Part 21 RIN 1018-AX82 Migratory Bird Permits; Double-Crested Cormorant Management in the United States AGENCY: Fish and Wildlife Service, Interior. ACTION: Request for comments...

  6. 77 FR 5505 - Eagle Crest Energy Company; Notice of Availability of the Final Environmental Impact Statement...

    Science.gov (United States)

    2012-02-03

    ... Energy Regulatory Commission Eagle Crest Energy Company; Notice of Availability of the Final Environmental Impact Statement for the Eagle Mountain Pumped Storage Hydroelectric Project In accordance with... of Energy Projects has reviewed the application for license for the Eagle Mountain Pumped Storage...

  7. 77 FR 47628 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting...

    Science.gov (United States)

    2012-08-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy... Management Act and the Federal Power Act), on the Eagle Mountain Pumped Storage Hydroelectric Project...

  8. 77 FR 43280 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2012-07-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy... Management Act and the Federal Power Act), on the Eagle Mountain Pumped Storage Hydroelectric Project. e. All...

  9. 78 FR 26358 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2013-05-06

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy...), on the Eagle Mountain Pumped Storage Hydroelectric Project. e. All local, state, and federal agencies...

  10. 78 FR 25263 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2013-04-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy... Power Act), on the Eagle Mountain Pumped Storage Hydroelectric Project. e. All local, state, and federal...

  11. 76 FR 1149 - Eagle Crest Energy Company; Notice of Availability of the Draft Environmental Impact Statement...

    Science.gov (United States)

    2011-01-07

    ... Federal Energy Regulatory Commission Eagle Crest Energy Company; Notice of Availability of the Draft Environmental Impact Statement for the Eagle Mountain Pumped Storage Hydroelectric Project and Notice of Public... for the Eagle Mountain Pumped Storage Hydroelectric Project (FERC No. 13123), located on the site of...

  12. Static histomorphometry of human iliac crest and vertebral trabecular bone: a comparative study

    DEFF Research Database (Denmark)

    Thomsen, Jesper Skovhus; Ebbesen, Ebbe Nils; Mosekilde, Lis

    2002-01-01

    We recently developed a new, rapid method for conducting static histomorphometry on large histologic sections. This method has now been applied on both iliac crest and lumbar vertebral bone to compare the age-related changes at these two skeletal sites and to investigate the correlation between...

  13. 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

  14. 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...

  15. 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...

  16. 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...

  17. Numerical simulation of lowest-order short-crested wave instabilities

    DEFF Research Database (Denmark)

    Fuhrman, David R.; Madsen, Per A.; Bingham, Harry

    2006-01-01

    A numerical study of doubly periodic deep-water short-crested wave instabilities, arising from various quartet resonant interactions, is conducted using a high-order Boussinesq-type model. The model is first verified through a series of simulations involving classical class I plane wave instabili......A numerical study of doubly periodic deep-water short-crested wave instabilities, arising from various quartet resonant interactions, is conducted using a high-order Boussinesq-type model. The model is first verified through a series of simulations involving classical class I plane wave...... filter promoting this behaviour in these cases. A series of class Ia short-crested wave instabilities, near the plane wave limit, are then considered, covering a wide range of incident wave steepness. A close match with theoretical growth rates is demonstrated near the inception. It is shown......-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...

  18. Association of an irregularly shaped anterior choroidal aneurysm with CREST syndrome. Case report.

    Science.gov (United States)

    Zoumalan, Richard A; Bendok, Bernard R; Parkinson, Richard J; Sorin, John; Burke, Allan M; Batjer, H Hunt

    2004-11-01

    The authors present the case of a 50-year-old woman with a history of CREST syndrome (calcinosis, Raynaud phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia), a variant of scleroderma, who was incidentally found to have an irregular intracranial aneurysm. The patient presented with migraine headaches. A magnetic resonance image of the brain obtained during the headache workup revealed a right posterior carotid artery wall aneurysm in the region of the anterior choroidal artery (AChA). On digital subtraction angiograms, the lesion measured 3.5 mm at its largest diameter. Because of the irregular shape of the aneurysm, the patient's relatively young age, and the potential for further aneurysm growth due to collagen disease, surgical clip application was recommended following a discussion of available treatment options. At surgery, the aneurysm was identified as bilobed and broad based, and the AChA was found to be associated with the aneurysm neck. Satisfactory clipping of the aneurysm was achieved with preservation of the parent vessels. An association of CREST syndrome with intracranial aneurysms has only been reported once before. This case is presented to draw attention to the possibility of a pathophysiological connection between CREST syndrome and intracranial aneurysms and to postulate a possible mechanism whereby this condition may result in aneurysm formation. The association of aneurysms with other pathological collagen-related conditions is well known, and literature relevant to a possible connection between CREST syndrome and aneurysms is reviewed and discussed.

  19. Gastric telangiectasis: a rare cause of severe blood loss in CREST syndrome.

    Science.gov (United States)

    el-Omar, M. M.; Jenkins, A. P.; Hollowood, K.; Banerjee, A. K.; Thompson, R. P.

    1994-01-01

    A 46 year old woman presented with the CREST variety of systemic sclerosis and occult gastrointestinal bleeding due to vascular malformations of her stomach. Partial gastrectomy cured her anaemia. In systemic sclerosis, visceral angiography should be performed early when initial investigations have been negative. Images Figure 1 Figure 2 PMID:8183780

  20. Treatment of cutaneous calcinosis in CREST syndrome by extracorporeal shock wave lithotripsy.

    Science.gov (United States)

    Sparsa, Agnès; Lesaux, Nicolas; Kessler, Emmanuel; Bonnetblanc, Jean-Marie; Blaise, Sophie; Lebrun-Ly, Valérie; Colombeau, Pierre; Vidal, Elisabeth; Bédane, Christophe

    2005-11-01

    We describe the unusual case of a 78-year-old woman consulting for extensive and painful wound leg ulcerations and calcifications secondary to CREST syndrome that was treated by extracorporeal shock wave lithotripsy. This treatment was considered because of the severity of our patient's symptoms and her failure to respond to various medical and surgical treatment.

  1. Crew Escape Technologies (CREST) Mission Area Requirements Study Current and Future Crew Escape Requirements

    Science.gov (United States)

    1992-02-01

    anthropometry and the type and location of the equipment worn by the test suboect. Based upon the data taken In the early nineteen sixties it was...3.1.1 of the CREST Specification describes the system as having -Flow stagnation fence to reduce windblast Induced loads on the head, torso and upper

  2. Piezosurgery-assisted, flapless split crest surgery for implant site preparation.

    Science.gov (United States)

    Brugnami, Federico; Caiazzo, Alfonso; Mehra, Pushkar

    2014-03-01

    Bucco-lingual resorption of the alveolar ridge can, at times, be predictably corrected at the time of implant placement. Among the different options available to achieve this are a group of surgical techniques described as split crest or split ridge procedures. Most of these procedures require the use of a mallet and some type of chisels and/or osteotomes; they are very technique-sensitive and can be uncomfortable for patients. Recently, alternative tools to split the crest have been presented, and these include the newer bone expanders and the piezoelectric scalpel. A flapless approach to implant dentistry has become popular with the aim to alleviate post treatment side effects, accelerate healing and avoid bone resorption caused by flap elevation. We present a technique combining the use of a piezoelectric scalpel and a tapered bone expander in a flapless fashion as a novel way to perform split crest procedures with an aim to optimize outcomes and acceptability by patients. All implants were successfully placed and the resorbed ridge expanded in the same setting. Findings were confirmed by postoperative cone beam cat scan (CBCT) evaluation. This new technique is a predictable approach for split crest procedures and has high acceptability by patients and is technically simple for surgeons.

  3. 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.

  4. 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

  5. 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.

  6. Oral crest lengthening for increasing removable denture retention by means of CO2 laser.

    Science.gov (United States)

    Nammour, Samir; Gerges, Elie; Bou Tayeh, Rima; Zeinoun, Toni

    2014-01-01

    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/cm(2), 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.

  7. ORF Alignment: NC_005296 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005296 gi|39936401 >1xktA 8 266 465 736 4e-19 ... emb|CAE28779.1| possible Condensation... domain, peptide synthetase [Rhodopseudomonas ... palustris CGA009] ref|NP_948677.1| possible Condensation

  8. ORF Alignment: NC_005296 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_005296 gi|39936401 >1l5aA 5 413 24 449 2e-42 ... emb|CAE28779.1| possible Condensation... domain, peptide synthetase [Rhodopseudomonas ... palustris CGA009] ref|NP_948677.1| possible Condensation

  9. ORF Alignment: NC_003911 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003911 gi|56696929 >1vkmA 3 282 10 299 3e-80 ... gb|AAV95332.1| indigoidine syntha...se A family protein [Silicibacter pomeroyi DSS-3] ... ref|YP_167291.1| indigoidine synthase A family

  10. ORF Alignment: NC_004461 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_004461 gi|27467261 >1swvA 2 252 3 215 2e-17 ... ref|NP_763898.1| indigoidine systh...esis protein [Staphylococcus epidermidis ATCC ... 12228] gb|AAO03940.1| indigoidine systhesis protein

  11. ORF Alignment: NC_006138 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006138 gi|51246320 >1swvA 5 256 3 215 9e-25 ... ref|YP_066204.1| similar to indigo...idine systhesis protein [Desulfotalea psychrophila ... LSv54] emb|CAG37197.1| related to indigoidine

  12. ORF Alignment: NC_002942 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_002942 gi|52842146 >1vkmA 3 284 12 301 3e-86 ... ref|YP_095945.1| indigoidine synt...ila ... subsp. pneumophila str. Philadelphia 1] gb|AAU27998.1| ... indigoidine synthase A-like

  13. ORF Alignment: NC_006461 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006461 gi|55981146 >1vkmA 10 271 2 266 5e-61 ... ref|YP_144443.1| indigoidine synt...hase A like protein [Thermus thermophilus HB8] ... dbj|BAD71000.1| indigoidine synthase A like protei

  14. ORF Alignment: NC_006834 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_006834 gi|58583037 >1o08A 5 191 6 187 1e-21 ... ref|YP_202053.1| indigoidine synth...esis-like protein [Xanthomonas oryzae pv. oryzae ... KACC10331] gb|AAW76668.1| indigoidine synthesis-

  15. ORF Alignment: NC_003919 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003919 gi|21244071 >1swvA 4 253 5 214 5e-24 ... gb|AAM38189.1| indigoidine synthes...is-like protein [Xanthomonas axonopodis pv. ... citri str. 306] ref|NP_643653.1| indigoidine ...

  16. ORF Alignment: NC_002973 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_002973 gi|46908510 >1vkmA 3 283 11 301 6e-86 ... ref|YP_014899.1| indigoidine synt...hase A-like protein [Listeria monocytogenes str. 4b ... F2365] gb|AAT05076.1| indigoidine synthase A-

  17. ORF Alignment: NC_003902 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003902 gi|21232616 >1o08A 5 215 6 212 5e-21 ... ref|NP_638533.1| indigoidine synth...esis like protein [Xanthomonas campestris pv. ... campestris str. ATCC 33913] gb|AAM42457.1| indigoid

  18. ORF Alignment: NC_003098 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003098 gi|15902282 >1in4A 3 311 20 328 5e-98 ... ref|NP_357832.1| Branch migration of Holliday structures... [Streptococcus pneumoniae ... R6] gb|AAK99042.1| Branch migration of Holliday ... structures... [Streptococcus pneumoniae R6] pir||F97901 ... branch migration of Holliday structures

  19. ORF Alignment: NC_004605 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_004605 gi|28900809 >1ek9A 1 415 22 427 8e-60 ... ref|NP_800464.1| agglutination pr...otein [Vibrio parahaemolyticus RIMD 2210633] ... dbj|BAC62297.1| agglutination protein [Vibrio ...

  20. ORF Alignment: NC_004603 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_004603 gi|28898408 >1yc9A 8 414 18 416 1e-11 ... ref|NP_798013.1| agglutination pr...otein [Vibrio parahaemolyticus RIMD 2210633] ... dbj|BAC59897.1| agglutination protein [Vibrio ...